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 TABLE OF CONTENTS

CHAPTER 1
ANATOMICAL SCIENCES

Muscles
Joints
Bone (Hard Tissue)
Tissues
PDL & Gingiva
Tooth Histology & Life Cycle
Tooth Tissues (Pulp, Cementum, Dentin, Enamel)
Reproductive System
Gastrointestinal System
Respiratory System
Endocrine System
Urinary System
Lymphatic System
Nervous System
Cranial Nerves
Foramen
Heart
Arteries
Veins
Blood
Embryology

CHAPTER 2
BIOCHEMISTRY & PHYSIOLOGY

The Cell & Cell Division

Cell Membrane
Central Nervous System (CNS)
PNS & ANS
Nerve Transmission
Hormones
Gastrointestinal Hormones
Blood
Heart Physiology
Vitamins, Minerals, & Deficiencies
Physiologic Disorders
Metabolism
Oral Cavity Physiology
Muscle Physiology
Respiration
Reproduction
Sensory Organs
Renal (Kidney)
Liver
Gastrointestinal System
DNA & RNA
Compounds & Substances
Chemistry
Carbohydrates
Lipids
Proteins & Amino Acids
Enzymes

CHAPTER 3
MICROBIOLOGY & PATHOLOGY

Bone Disorders
Hormonal & Endocrine Disorders
Gastrointestinal Disorders
Skin Disorders
Neurological Disorders
Cardiac & Cerebral Disorders
Renal Disorders
Ocular Disorders
Autoimmune Disorders
Immunology
Cellular Disorders
Genetic Disorders & Mutations
Respiratory Disorders
Blood & Hemodynamic Disorders
Liver Disorders
Inflammation & Necrosis
Neoplasms (Tumors)
Infections
Plaque, Caries, Calculus
Cells & Organelles
Pathogen Sterilization & Disinfection
Wound Healing, Grafts, & Teratology
Bacteria
Antibiotics
Viruses
Vaccines
Fungi
Parasites

CHAPTER 4
DENTAL ANATOMY & OCCLUSION

Tooth Anatomy
Eruption Sequence
Deciduous (Primary) Teeth
Succedaneous (Permenant) Anterior Teeth
Succedaneous (Permenant) Posterior Teeth
Periodontium Anatomy
Tooth Histology & Development
Enamel, Dentin, Cementum, Pulp
Parafunction & Erosion
Muscles of Mastication & Mandibular Movement
Temperomandibular Joint (TMJ)
Mandibular Movements & Positions
Posterior & Anterior Contacts in Ideal MICP
Malocclusion & Curves of Spee & Wilson
Centric Occlusion, Centric Relation, & Rest
Articulation, Occlusal Balance & VDO
DENTIN “HIGH-SPEED DRILL” PREVIEW

 MUSCLES
SOFT PALATE-mobile fold attached to the hard palate that separates the oral cavity from the
nasopharynx. Attached laterally to the tongue by glossopalatine arches, and to the lateral wall of the
pharynx by pharyngopalatine arches.
• Palate salivary glands are in the posterolateral zone, derived from ectoderm and are separated
by C.T. septa.

TWO ARCHES FORMED BY THE FAUCES ANTERIOR & POSTERIOR PILLARS:

1. Glossopalatine arch (palatoglossal arch)-formed by anterior pillars. Palatoglossus muscle is
below this arch and elevates the tongue and narrows the fauces. It’s the posterior boundary of the
oral cavity, and anterior boundary of the fauces.

2. Pharyngopalatine arch (palatopharyngeus arch)-formed by posterior pillars.

• Palatopharyngeus muscle-located below this arch, it elevates the pharynx, shuts the
nasopharynx, narrows the fauces, and aids in swallowing. During swallowing, muscular
contraction causes movements that seal off the oropharynx from the nasopharynx.
Palatopharyngeus muscle CAUSES MOVEMENTS THAT FORM A FOLD IN THE
POSTERIOR WALL OF THE PHARYNX.

PALATINE TONSILS-consist mostly of lymphoid tissue, found between the two arches in the “fauces
area”= passageway from the oral cavity to the oral pharynx.

SOFT PALATE-consists of 5 paired skeletal muscles:

1. Tensor veli palatini-TENSES the soft palate & opens mouth of auditory tube during
swallowing/yawning. Its tendon curves or loops around the pterygoid hamulus to insert into the
side of the soft palate. *Nerve supply comes from V3 of trigeminal.

2. Levator veli palatini-RAISES the soft palate.

3. Palatoglossus-a pharynx muscle that ELEVATES POSTERIOR TONGUE, closes the

oropharyngeal isthmus and initiates swallowing. Nerve supply is from the Pharyngeal Plexus.

4. Palatopharyngeus-ELEVATES THE PHARYNX, pulls the palatopharyngeal arches toward the

midline, and closes the nasopharynx.

5. Muscularis uvulae-ELEVATES and RETRACTS the uvula.

Pharyngeal plexus INNERVATES all soft palate muscles EXCEPT Tensor veli palatini (innervated by
nerve to the medial pterygoid) = branch of mandibular division of trigeminal nerve (V3).

SOFT PALATE BLOOD SUPPLY:

1. Greater and lesser palatine arteries (descending palatine artery branches of maxillary artery).
 2. Ascending palatine artery (facial artery branch).
3. Palatine artery (ascending pharyngeal artery branch).

Anterior zone of the palatal submucosa contains fat, and posterior zone contains mucous glands.

Soft palate ends posteriorly in the midline as a conical projection = UVULA

• Bifid uvula-results from failure of complete fusion of the palatine shelves.

TONGUE-all tongue muscles (intrinsic & extrinsic) are innervated by Hypoglossal nerve (CN XII)
EXCEPT palatoglossus muscle (innervated by pharyngeal plexus of CNX).

• Paired Extrinsic Tongue Muscles: originate on structures away from the tongue and insert onto it
causing tongue movements during speaking, food manipulation, cleaning teeth, and swallowing:
1. Genioglossus-protrudes tongue apex through mouth (sticks out tongue). Origin is
superior genial spine of mandible. Insertion: dorsum of tongue. Innervation:
hypoglossal nerve.

2. Hyoglossus-depresses side of tongue. Origin: hyoid bone. Inserts on side of tongue.

CN XII.

3. Styloglossus-elevates and retracts tongue. Origin is styloid process of temporal bone.

Insertion: lateral side and dorsum of tongue. Innervation: hypoglossal nerve.

4. Palatoglossus-pulls tongue root up and back (elevates the tongue). Origin: palatine
aponeurosis. Insertion: side of tongue. Innervation: PHARYNGEAL PLEXUS of
Vagus.

• Intrinsic Tongue Muscles: longitudinal, transverse, and vertical muscles alter tongue shape, and
are confined to the tongue and NOT attached to bone. All are innervated by HYPOGLOSSAL
NERVE. Intrinsic muscles are named based on the 3 spatial planes that they run.

• Tongue develops from: copula, tuberculum impar, 2nd & 3rd brachial arches, & lateral lingual
swellings.

Tongue Blood Supply:

1. lingual artery (from tonsilar branch of facial artery)
2. ascending pharyngeal artery
3. veins drain into the internal jugular vein.

Tongue Lymph Drainage:

1. tip of tongue-drains into submental lymph nodes.
2. remaining anterior 2/3-drains bilaterally into submandibular and deep cervical lymph nodes.
3. posterior 1/3-drains into deep cervical lymph nodes on both sides.

LINGUAL PAPILLAE-small, nipple-shaped projections on anterior 2/3 of tongue dorsum. Consists of:
1. Filiform papillae-most numerous, small cones arranged in “V-shaped” rows paralleling sulcus
terminalis. Characterized by absence of taste buds (NO TASTE BUDS), and increased
 keratinization.

2. Fungiform papillae-scattered among filiform papillae; flattened, mushroom-shaped, found

mainly at the tip and lateral margins.

3. Foliate papillae-found on lateral margins as 3-4 vertical folds.

4. Circumvallate (vallate) papillae-largest, but lease numerous and circular shaped. Arranged in an
inverted “V-shaped” row toward the back of tongue. Associated with ducts of Von Ebner’s
glands.
• Von Ebner’s glands-located around circumvallate papilla of the tongue. Their main
function is to rinse food away from the papilla after it has been tasted by the taste buds.
PURELY SEROUS.

Fungiform, circumvallate, & foliate papillae contain taste buds that respond to 4 taste sensations:
sweet, sour, bitter, and salty.

TONGUE INNERVATION:
• Posterior 1/3 of tongue & circumvallate papillae receive general and taste sensation from
glossopharyngeal nerve (CN IX).

• Anterior 2/3 of tongue receives general sensory innervation from LINGUAL NERVE (CN V3)
and taste sensation from CHORDA TYMPANI (CN VII).

• Extrinsic and intrinsic tongue muscles are innervated by HYPOGLOSSAL NERVE (CN XII)
except palatoglossus (innervated by vagus nerve-CN X).

CARDIAC MUSCLE FIBERS-make up the myocardium (thick, middle layer of the heart). It is striated
muscle that contains transverse tubules, a slow rate of calcium sequestration, and is inhibited by
acetylcholine.
• Have MORE mitochondria b/t myofibrils and richer in myoglobin than most skeletal muscle.

• Like skeletal muscle, contain mylofilaments (contractile units) and are STRIATED with actin &
myosin.

• Have LARGER t-tubules and LESS DEVELOPED sarcoplasmic reticulums than skeletal
muscle fibers.

• Cardiac muscle fibers are short, branched, and single or binucleated in contrast to skeletal muscle
fibers.

• Contain large, oval centrally placed nuclei, and strong, thin unions b/t fibers =
INTERCALATED DISCS (junctions between cardiac muscle cells that provide low resistance to
current flow). Intercalated discs contain desmosomes that are within the discs to attach cells, and
gap junctions to communicate electrical impulse from cell-to-cell.

• Cardiac muscle fibers CONTRACT SPONTANEOUSLY WITHOUT NERVE SUPPLY.

 Cardiac fibers respond to increased demand by increasing its fiber size = Compensatory
hypertrophy.

• Cardiac and skeletal muscle fibers cannot mitotically divide. Certain smooth muscle fibers can
under hormonal influences (e.g. during pregnancy myometrium smooth muscle fibers of the uterus
increase in length and form new cells).

SKELETAL MUSCLE FIBERS-attaches to the skeleton, responsible for voluntary body movement.
Consists of BUNDLES of very long, narrow, cylindrical, multinucleated cells with regularly ordered
myofibrils = STRIATED (distinct transverse striations) that span a joint attached at either end by a
tendon. Comprises ~40% of a person’s body weight.
• Slender ovoid or elongated nuclei, and are situated peripherally.

• CONTAIN transverse tubules (t-tubules) & WELL-DEVELOPED sarcoplasmic reticulum.

• FAST, FORCEFUL VOLUNTARY CONSCIOUS CONTRACTION caused by myofibrils

(ACTIN & MYOSIN) = contractile element proteins of skeletal muscle that reduces
sarcomere length.

ACTIN FILAMENTS (thin myofilaments 5-8nm diameter) are composed of:

1. Actin-globular actin (G-actin) molecules arranged in double spherical chains = fibrous actin (F-
actin).
2. Tropomyosin-long threadlike molecules that lie on the surface of F-actin strands and physically
cover actin binding sites during the resting state.
3. Troponin-small oval molecule attached to each tropomyosin.

MYOSIN FILAMENTS (thick myofilaments 12-18nm diameter) composed of myosin which has two
components:
1. Light meromyosin (LMM)-makes up the rod-like backbone of myosin filaments.

2. Heavy meromyosin (HMM)-forms shorter globular lateral cross-bridges that link to actin
binding sites during contraction.

SKELETAL MUSCLE contracts when a stimuli from the nervous system excites individual muscle
fibers. This starts as a series of events leading to interactions b/t myosin (thick filaments) and actin (thin
filaments) of the sarcomeres of the fibers.
• Skeletal muscle fiber origin is the stationary attachment, and their insertion is the movable
attachment.

• Skeletal muscle fibers are classified by their fiber arrangement (parallel, convergent, circular, or
pinnate).

• Each skeletal muscle fiber is innervated by an axon of a motor neuron terminal at a motor
end plate (a large complex terminal formation by which an axon of a motor neuron establishes
synaptic contact with a skeletal muscle).

• The axon of a motor neuron is highly branched, thus one motor neuron innervates many muscle
 fibers. When a motor neuron transmits an impulse, ALL fibers it innervates contract
simultaneously.

Skeletal muscle fibers are enclosed and covered by sheets of fibrous C.T. (fascia):
1. Endomysium-fine C.T. sheath surrounding an individual skeletal muscle fiber.
2. Perimysium-fibrous sheath surrounding a bundle of muscle fibers.
3. Epimysium-external C.T. sheath surrounding an entire muscle.

SARCOPLASMIC RETICULUM-organelle that releases & stores calcium ions during contraction and
relaxation of skeletal muscle. It’s a network membranous channels of tubules and sacs in skeletal
muscles that extends throughout the sarcoplasm. Similar to the endoplasmic reticulum of other cells.
Sarcoplasm-muscle cell cytoplasm. Sarcoplasm of each muscle fiber contains many parallel, thread-like
myofibrils.
• Myofibril-composed of smaller strands of myofilaments that contain actin and myosin contractile
proteins whose regular spatial organization within the myofibril forms cross banding. Myofibrils
are arranged in compartments = SARCOMERES.

• Skeletal muscle enlarges with prolonged activity from an increase in sarcoplasm and in the
number of myofibrils within each existing skeletal muscle fiber.

The arrangement of thick (myosin) and thin (actin) filaments creates dark and light striations of a
sarcomere.
• A BANDS (Anisotropic)-dark bands that contain THIN ACTIN & THICK MYOSIN
FILAMENTS. Outer regions of A bands contain actin and myosin, but lighter central regions (H
bands) of A bands contain only myosin. The thick myofilaments observed in transmission
electron microscope preparations of skeletal muscle are present only in the A band.

• I BANDS (Isotropic)-lighter bands bisected by dark Z lines where actin filaments of adjacent
sarcomeres join. It’s the zone of THIN filaments not superimposed by thick filaments.

SMOOTH MUSCLE FIBERS-composed of uninucleate (single nucleus), elongated spindle-shaped

FUSIFORM CELLS. Located throughout the body in tunica (walls) of hollow internal organs.
• Much smaller than skeletal muscle fibers with 1 nuclei located in the widest part of each fiber.

• No transverse (t-tubules) with poorly developed sarcoplasmic reticulum.

• No regularly ordered myofibrils = NOT STRIATED. The myofibrils lack transverse striations.

• SLOW, INVOLUNTARY CONTRACTION OF INTERNAL ORGANS (e.g. peristalsis).

2 Types of Smooth Muscle:

1. Single-unit: have numerous gap junctions (electrical synapses) b/t adjacent smooth fibers.
Single-unit fibers contract spontaneously (i.e. inside muscular tunica of GI tract, uterus,
ureters, and arterioles).

2. Multi-unit: no gap junctions. Individual fibers are autonomically innervated (i.e. ciliary
muscle, smooth muscle of iris, ductus deferens, and arteries).
MUSCLES OF MASTICATION-4 pairs of muscles responsible for biting and grinding movement of the
mandible during mastication. All muscles of mastication are innervated by TRIGEMINAL NERVE
(V3-mandibular division)

1. TEMPORALIS-fan-shaped, originates from bony floor of the temporal fossa and deep surface of
the temporal fascia. It passes medially (downward and deep) to the zygomatic arch as a thick
tendon before inserting on coronoid process of mandible.
• Its anterior & superior fibers ELEVATE MANDIBLE. Its posterior fibers RETRACT
MANDIBLE and maintain resting position of closure of the mouth.

• temporalis inserts into the mandible’s coronoid process and anterior border of the
ramus of the mandible.

• innervated by deep temporal nerves (branches of mandibular division of trigeminal

nerve-V3).

2. MASSETER-originates at zygomatic arch & inserts on lateral ramus of mandible. ELEVATES

MANDIBLE to occlude teeth. Forms a sling around the angle of the mandible. The stretch
reflex maintains masseter muscle tone. MASSETER IS THE MOST POWERFUL
MASTICATORY MUSCLE.

3. MEDIAL PTERYGOID-origin is the lateral pterygoid plate and tuberosity of maxilla. Inserts
on medial surface of angle of mandible. ELEVATES MANDIBLE & MOVES IT
LATERALLY. Forms a sling around the angle of the mandible.
• During an inferior alveolar block injection, the needle passes through the mucous
membrane and buccinator muscle, and lies LATERAL to the medial pterygoid.

4. LATERAL PTERYGOID (2 Heads)-origin is lateral pterygoid plate (inferior head) and

greater wing of sphenoid bone infratemporal crest (superior head). BOTH HEADS INSERT into
the neck of mandible (condyle), articular disc of TMJ, & capsule to OPEN & PROTRUDE
MANDIBLE & MOVE IT LATERALLY (SIDE-TO-SIDE).
• Lateral pterygoids (right and left) acting together are PRIME MANDIBLE PROTRACTORS.
For right lateral excursive movements, the left lateral pterygoid muscle is the primary mover,
while for left lateral movements the right lateral pterygoid is the primary mover.

• With lateral pterygoid injury, the mandible deviates toward the side of injury.

• With unilateral condylar fracture, the mandible also deviates to the injured side upon opening.

• Damage to the TMJ’s articular disc can cause paralysis of the lateral pterygoid muscle
(unable to open mouth).

All 4 muscles of mastication receive blood from the PTERYGOID BRANCH OF THE MAXILLARY
ARTERY (the larger terminal branch of the external carotid artery).

ANGLE OF THE MANDIBLE rests in a SLING formed by the masseter muscle & medial pterygoid
that exert similar forces on the mandible. Both are the PRIMARY CLOSING MUSCLES that provide
LATERAL STABILIZATION of the mandible.
• Masseter inserts on the external (lateral) surface of the angle.
• Medial pterygoid inserts on the internal (medial) surface of the angle.

PHARYNX-consists of 3 circular and 3 longitudinal muscles:

1. CIRCULAR MUSCLES (ALL innervated by vagus nerve via pharyngeal plexus):
• Superior constrictor: constricts UPPER pharynx. Origin: medial pterygoid plate,
pterygoid hamulus; pterygomandibular raphe; mylohyoid line of mandible; side of tongue.
Insertion: median raphe and pharyngeal tubercle of skull.
• Middle constrictor: constricts LOWER pharynx. Origin: greater & lesser horns of
hyoid; stylohyoid ligament. Insertion: median raphe.
• Inferior constrictor: constricts LOWER pharynx. Origin: arch of cricoid and oblique
line of thyroid cartilages. Insertion: median raphe of pharynx.

2. LONGITUDINAL MUSCLES:
• Stylopharyngeus: elevates pharynx & larynx. Origin: styloid process. Insertion: thyroid
cartilage and pharynx muscles. Innervation: GLOSSOPHARYNGEAL NERVE.
• Palatopharyngeus: elevates pharynx & closes nasopharynx. Origin: hard palate;
aponeurosis of soft palate. Insertion: thyroid cartilage and pharynx muscles. Innervation:
pharyngeal branch of vagus nerve (CN X) with motor fibers originating in the
accessory nerve (CN XI).
• Salpingopharyngeus: elevates nasopharynx, opens auditory tube. Origin: cartilage of
auditory tube. Insertion: pharynx muscles. Innervation: vagus nerve via pharyngeal
plexus.

LARYNX: Cricothyroid muscle-the only larynx muscle innervated by EXTERNAL LARYNGEAL

BRANCH OF VAGUS NERVE. All other larynx muscles are innervated by RECURRENT
LARYNGEAL BRANCH OF VAGUS NERVE.
1. Cricothyroid muscle-tenses vocal cords.
2. Posterior cricoarytenoid-abducts vocal cords.
3. Lateral cricoarytenoid-adducts vocal cords.
4. Transverse arytenoid-adducts vocal cords; closes laryngeal inlet.
5. Oblique arytenoids-adducts vocal cords; closes laryngeal inlet.
6. Aryepiglottic-adducts vocal cords.
7. Thyroarytenoid-adducts and relaxes vocal cords.
8. Thyroepiglottic-adducts vocal cords.
9. Vocalis-adducts and tenses vocal cords.
NECK MUSCLES:
1. Sternocleidomastoid-separates the anterior & posterior triangles of neck. Innervated by
accessory nerve. Innervated by CN XI.
• Origin: sternum; clavicle. Insertion: mastoid process of temporal bone.
• Action: turns head to side; flexes head and neck.

2. Digastric-opens jaw; elevates hyoid bone. Innervation: anterior belly (trigeminal-V3);

posterior belly (facial). Origin: inferior border of mandible; mastoid groove. Insertion: hyoid
bone.
 3. Mylohyoid-elevates hyoid bone & floor of mouth. Innervation: trigeminal nerve-V3. Origin:
inferior border of mandible. Insertion: body of hyoid bone and median raphe.

4. Stylohyoid-elevates and retracts tongue. Innervation: facial nerve. Origin: styloid process of
temporal bone. Insertion: body of hyoid bone.

5. Hyoglossus-depresses side of tongue. Innervation: hypoglossal nerve. Origin: body of hyoid

bone. Insertion: side of tongue.

6. Sternohyoid-depresses hyoid. Innervation: Ansa cervicalis. Origin: manubrium. Insertion:

body of hyoid bone.

7. Thyrohyoid-depresses hyoid & elevates thyroid. Innervation: C1 via hypoglossal nerve.

Origin: thyroid cartilage. Insertion: greater cornu of hyoid bone.

8. Omohyoid-depresses hyoid. Innervation: Ansa cervicalis. Origin: superior border of scapula.

Insertion: clavicle; body of hyoid bone.

TRIANGLES OF NECK:
1. Triangle of auscultation-site where BREATHING SOUNDS are heard most clearly, bound by
the upper border of latissimus dorsi, lower border of trapezius, and medial margin of the
scapula. Its floor is formed by rhomboid major.

2. ANTERIOR TRIANGLE-boundaries are sternocleidomastoid, medial line of neck, & inferior

border of mandible. It contains 4 lesser triangles, salivary glands, larynx, trachea, thyroid glands,
vessels and nerves.
1. Carotid triangle-formed by the anterior border of sternocleidomastoid muscle, posterior
belly of the digastric muscle, and superior belly of the omohyoid muscles. Contains
carotid arteries, internal jugular vein, and vagus nerve.
2. Submandibular triangle-formed by digastric muscle (both heads), inferior border of
mandible. Contains salivary glands.
3. Submental triangle-bound by digastric muscle, hyoid bone (only unpaired triangle of
the neck). Contains muscles of mouth floor, salivary glands, and ducts.
4. Omotracheal triangle-bound by sternocleidomastoid and omohyoid muscles, midline of
neck. Contains larynx, trachea, thyroid gland, and carotid sheath.

3. POSTERIOR TRIANGLE-boundaries are sternocleidomastoid, trapezius muscles, & clavicle.

Contains nerves and vessels, and 2 lesser triangles:
1. Occipital triangle-bound by sternocleidomastoid, trapezius, and omohyoid muscles.
Contains cervical plexus and accessory nerve.
2. Omoclavicular triangle-bound by sternocleidomastoid and omohyoid muscles; clavicle.
Contains brachial plexus and subclavian artery.

DIAPHRAGM-PRIMARY RESPIRATION/BREATHING MUSCLE (quiet breathing); is dome-

shaped and separates thoracic and abdominal cavities. The diaphragm’s upper surface contacts the
heart and lungs; its lower surface contacts liver, stomach, and spleen. Diaphragm is innervated by
PHRENIC NERVE, which lies close to the lateral surfaces of the pericardial sac. Diaphragm has 3
openings:
1. Aortic opening-transmits the aorta, thoracic duct, and azygos vein.
2. Esophageal opening-transmits the esophagus, right & left vagus nerves.
3. Caval opening-transmits the inferior vena cava and right phrenic nerve.

MNEMONIC: “I 8 10 EGGS AT 12” which tells the structures that pierce the diaphragm at which
thoracic level (inferior vena cava, esophagus, and aorta).

During inspiration: diaphragm MOVES DOWN, increasing thoracic cavity volume.

During expiration: diaphragm MOVES UP, decreasing thoracic cavity volume.

Other Respiratory Muscles: internal & external intercostals, subcostal, and transverses thoracis (all
innervated by the intercostal nerve).

DIAPHRAGM divides the anterior body cavity into an UPPER thoracic cavity and LOWER
abdominopelvic cavity. THERE ARE 2 PRINCIPAL BODY CAVITIES:

1. Posterior (dorsal) cavity-is subdivided into two cavities:

• Cranial cavity-contains the brain.
• Spinal cavity-contains the spinal cord.
• Cranial and spinal cavities communicate through the FORAMEN MAGNUM and are
both lined by meninges. These cavities contain cerebrospinal fluid (CSF).

2. Anterior (ventral) cavity-is subdivided into two cavities:

• Thoracic cavity-is divided into the pericardial cavity (surrounds the heart) and pleural
cavities (right and left) that surround each lung. Mediastinum-is the portion between the
two pleural cavities that contains the heart and pericardial cavity.
• Abdominopelvic cavity-is divided into the abdominal cavity (contains the stomach,
spleen, liver, gallbladder, pancreas, and both intestines). Also contains the pelvic cavity
(contains the rectum bladder, and female internal reproductive organs).

THORAX-intrinsic muscles of the thorax are involved in BREATHING by drawing the ribs together or
by elevating or depressing the rib cage. 3 muscles sets originate from the lower border of ribs and
insert on the upper border of rib. All are innervated by the intercostals nerves derived from anterior
rami of thoracic spinal nerves:
1. External Intercostals-pass from rib-to-rib running at right angles to the fibers of the internal and
innermost muscles. ELEVATE RIBS DURING INSPIRATION.

2. Internal Intercostals-11 on both sides of ribs. Fibers pass obliquely down and laterally to
DEPRESS RIBS.

3. Innermost Intercostals-run obliquely down and laterally (like internals), but the two layers are
separated by nerves and vessels. ELEVATE RIBS.

 MUSCLES OF FACIAL EXPRESSION
Most of the 10 muscles of facial expression are motor innervated by the FACIAL NERVE (CN VII) and
blood supply comes from the FACIAL ARTERY (external carotid artery branch).

3 Smile Muscles: Zygotamicus (major & minor), Levator anguli oris, and Risorius.
1. Levator Anguli Oris-elevates (lifts) the corners of the mouth.
2. Zygomatic Major & Minor-smiles and laughs.
3. Risorius-retracts the angle of the mouth to produce a SMILE. Arises in the parotid gland fascia.

• If the facial expression muscle inserts into the mouth, an origin above the mouth contributes to
smiling, while an origin below the mouth causes frowning.

6 Additional Muscles of Facial Expression:

1. Depressor Labii Inferioris-pulls down the lower lip.

2. Depressor Anguli Oris-pulls down the corners of mouth.

3. Mentalis-lower lip muscle that pulls chin skin upward to raise the central portion of the lips
(allows the lips to POUT). Hyperactivity can make lower lip retraction difficult.

4. Platsyma-lower lip, tenses neck skin (overlaps SCM). Gives expression of GRIMACE.

5. Orbicularis Oris-contracts and protrudes the lips. KISSING or PUCKER MUSCLE.

6. Orbiularis Oculi-closes the eyelids. THE ONLY MUSCLE THAT CLOSES THE EYE.

7. Levator labii superioris alaeque nasi (Elvis Muscle)-lifts upper lip and wing of nose). Enables a
SNARL expression (ELVIS PRESLEY used this muscle a lot in his facial expressions).

8. BUCCINATOR MUSCLE (muscle of facial expression) innervated by buccal branch of facial

nerve (CN VII). Originates from ALVEOLAR PROCESS of maxilla and mandible and
PTERYGOMANDIBULAR RAPHE. Buccinator muscle compresses the cheeks and lips
against the teeth, and hypertrophies with bruxism.
• Blood supply from facial and maxillary arteries.

• ORIGIN: outer surface of alveolar processes of maxilla and mandible opposite the
molar teeth and from the pterygomandibular raphe (thin, fibrous band from the hamulus of
the medial pterygoid plate down to the mandible).

• INSERTION: at orbicularis oris muscle and skin at angle of the mouth and lips.

• Pierced by the PAROTID DUCT.

During an inferior alveolar block injection, the needle passes through the mucous membrane and
buccinator muscle, and lies LATERAL to the medial pterygoid. However, if the needle passes
posteriorly at the level of the mandibular foramen, it penetrates the PAROTID GLAND causing
cheek numbness and possible paralysis of muscles of facial expression due to CN VII damage
(BELLS PALSY). If the needle tip rests well BELOW the mandibular foramen, you will penetrate
the medial pterygoid muscle.

THIGH MUSCLES:
1. Posterior Group-FLEX LEG and EXTEND THIGH. All innervated by tibial nerve.
• Biceps femoris, Semitendinosus, and Semimembranosus.

2. Anterior Group: FLEX LEG & THIGH; ABDUCTS THIGH. Innervated by femoral nerve.
Sartorius.

QUADRICEPS FEMORIS GROUP:

• Rectus femoris-flexes thigh and extends leg at knee because it crosses the hip and knee joints.
• Vastus lateralis, intermedius, and medialis extend the leg at the knee.

FOREARM MUSCLES:
 1. Triceps brachii-extends the forearm. Innervation: radial nerve. Origin: scapula and humerus.
Insertion: ulna (olecranon process).
2. Brachialis-flexes forearm. Innervation: Musculocutaneous nerve. Origin: humerus. Insertion:
ulna (coronoid process).
3. Brachioradialis-flexes forearm. Innervation: radial nerve. Origin: humerus. Insertion: radius
(styloid process).
4. Biceps-flexes & supinates forearm; flexes arm. Innervation: Musculocutaneous nerve. Origin:
scapula (coracoid process and supraglenoid tubercle). Insertion: radius (tuberosity).

RADIAL NERVE: MOST COMMONLY INJURED IN A MID-HUMORAL SHAFT FRACTURE.

AXILLA (ARMPIT)-contains axillary vessels, braches of brachial plexus, biceps brachii heads, &
coracobrachialis. Axilla boundaries are formed by:
1. medial wall-formed by the upper 4 or 5 ribs and their intercostals muscles and the serratus
anterior muscle.
2. lateral wall-formed by the HUMERUS (specifically, by coracobrachialis and biceps muscles in
the bicipital groove (intertubercular groove) of the humerus).
3. posterior wall-formed by subscapularis, teres major, and latissimus dorsi muscles.
4. anterior wall-formed by pectoralis major, minor, and subclavius muscles.
5. base-formed by axillary fascia or skin.

• BICEPS BRACHII-primary SUPINATOR OF THE RADIO-ULNAR JOINT.

1. Pectoralis major-flexes, adducts, and medially rotates arm. Innervation: medial & lateral pectoral
nerves from brachial plexus.

2. Pectoralis minor-depresses scapula (forward & downward). Innervation: medial pectoral nerve.

3. Latissimus dorsi-extends, adducts and medially rotates arm. Innervation: Thoracodorsal nerve
from brachial plexus.

4. Deltoids-abducts & laterally rotates arm. Innervation: Axillary nerve (C5 & C6).

5. Teres major-adducts, extends, and medially rotates the arm. Innervation: lower subscapular nerve
from brachial plexus.

6. Teres minor-rotates arm laterally. Innervation: branch of axillary nerve.

PECTORAL GIRDLE MUSCLES (6):

1. Serratus anterior-pulls scapula forward & downward. Innervation: long thoracic nerve.
2. Pectoralis minor-pulls scapula forward & downward. Innervation: medial pectoral nerve.
3. Subclavius-draws clavicle downward. Innervation: C5 & C6.
4. Trapezius-elevates & adducts scapula, draws head back, & braces shoulder. Innervation:
accessory nerve (CN XI).
5. Levator scapulae-elevates scapula. Innervation: dorsal scapular nerve.
6. Rhomboideus major & minor-elevate and retract scapula. Innervation: dorsal scapular nerve.
ABDOMINAL WALL MUSCLES:
• Anterior Abdominal Muscles:
1. internal oblique-helps form CREMASTER MUSCLE. As the spermatic cord (round
ligament of uterus) passes under the lower border of internal oblique, it carries some
muscle fibers of the cremaster muscle. Action: compresses abdomen & lateral
rotation. Innervation: intercostals, iliohypogastric, and ilioinguinal nerves.
2. external oblique-compresses abdomen & lateral rotation. Innervation: intercostals,
iliohypogastric, and ilioinguinal nerves.
3. transverse abdominis-compresses abdomen. Innervation: intercostals, iliohypogastric,
and ilioinguinal nerves.
4. rectus abdominis-flexes vertebral column. Innervation: intercostal nerves.

• Posterior Abdominal Muscles: psoas major & minor, and quadratus lumborum (innervated by
lumbar plexus), and iliacus (innervated by femoral nerve).

 JOINTS
Most body joints are SYNOVIAL JOINTS. Synovial joints-freely movable joints (diarthrodial) with
movement limited only by joint surfaces, ligaments, muscles, or tendons. Some synovial joints have
articular discs (TMJ and sternoclavicular joint) that consist of fibrocartilage and divide the cavity
into two separate cavities. Synovial joint have 5 distinguishing features:
1. Articular cartilage-thin layer of hyaline cartilage that covers smooth articular bone surfaces.
This layer contains no vessels or nerves. Note: TMJ contains fibrocartilage, NOT hyaline
cartilage.
2. Articular capsule-double-layered, outer layer of fibrous C.T. enclosing the joint. The inner layer
is a vascular synovial membrane.
3. Synovial cavity-small fluid-filled space separating the ends of adjoining bones.
4. Synovial fluid-clear, thick secretion of synovial membrane that lubricates and nourishes.
5. Supporting ligaments-has capsular, extracapsular, and intracapsular ligaments that maintain the
normal position of the bones.

Joints are classified by structure (fibrous, cartilaginous, or synovial) or by function:

1. Synarthroses-immovable joints articulating bones in close contact, binding fibrous tissue or
cartilage.
2. Amphiarthroses-slightly movable joints articulating bones separated by a fibrocartilaginous disc
or binding interosseous ligament.
3. Diarthroses-freely movable joints (synovial joints); joint capsule containing synovial membrane
and fluid (i.e. TMJ).

Joint Structural Classification:

1. Fibrous joint-lacks a joint cavity; fibrous C.T. binding articulating bones. 3 types:
▪ sutures-found only within the skull. Skull joints between flat bones of skull.
▪ syndesmoses-articulating ends of tibia and fibula.
▪ gomphoses-a tooth root is attached to the PDL of dental alveolus (socket) of the bone.

2. Cartilaginous joint-lacks a joint cavity; cartilage binding articulating bones. 2 types:

▪ symphyses-symphysis pubis and intervertebral joints.
▪ synchondroses-form epiphyseal plates in long bones.

3. Synovial joint-contains a joint cavity; ligaments help support articulating bones. 6 types:
▪ gliding-intercarpal joints
▪ condyloid-radiocarpal joint
▪ saddle-carpometacarpal joint of thumb
▪ ball and socket-shoulder and hip joints
▪ hinge-knee, elbow
▪ pivot-atlantoaxial joint

PRINCIPAL ARTICULATIONS IN THE BODY: Each joint is named by its location and classified by
the amount of movement permitted:
1. Skull joints-are fibrous (suture) and immovable.
2. TMJ-a snynovial joint (hinge; gliding). Elevation, depression, protraction, retraction.
3. Atlanto-occipital joint-a synovial (condyloid) joint. Flexion, extension, circumduction.
4. Atlanto-axial joint-a synovial (pivot) joint. Rotation.
5. Intervertebral joints: bodies of vertebrae (cartilaginous; symphysis). Slight movement.
Articular processes (synovial; gliding). Flexion, extension, slight rotation.
6. Sacroiliac joint-cartilaginous (symphysis); synovial (gliding). Slight gliding movement; may fuse
in adults.
7. Sternoclavicular joint-synovial (gliding). Slight movement when shrugging shoulders.
8. Elbow-synovial (hinge). Flexion, extension.
9. Symphysis pubis-cartilaginous (symphysis). Slight movement.
10. Coxal (hip)-synovial (ball-and-socket). Flexion, extension, adduction, abduction, rotation,
circumduction.

Atlanto-axial joint-synovial (pivot) articulation between the inferior articulating facets of the atlas (C1)
and superior articulating facets of the axis (C2). CAUSES “NO” MOVEMENTS OF HEAD. Allows
movement of the head about its VERTICAL AXIS (rotation to the right or left). Allows
ROTATION.

Atlanto-occipital joint-synovial (condyloid) articulation between the superior articulating facets of the
atlas (C1) & occipital condyles of the skull. Allows rocking or nodding head movements “YES”
MOVEMENTS. Allows flexion, extension, circumduction.


TEMPOROMANDIBULAR JOINT (TMJ)

TMJ-articulation between the condyle of the mandible and squamous portion of the temporal bone.
• condyle-elliptically shaped with its long axis oriented mediolaterally.
• articular surface of the temporal bone-composed of the concave articular fossa (glenoid fossa)
and convex articular eminence (tubercle).

ARTICULAR DISC (MENISCUS)-a fibrocartilaginous, saddle-shaped tissue associated with the TMJ
that resembles dense, irregular C.T. IT SEPARATES THE CONDYLE & TEMPORAL BONE, and
provides a smooth articulating surface.

MENISCUS-a biconcave oval plate that divides the TMJ into superior and inferior joint spaces.
• superior joint space-bound by the articular fossa and articular eminence.
• inferior joint space-bound below the condyle.

MENISCUS varies in thickness. Its thinner, central intermediate zone separates the thicker portions =
anterior and posterior bands. Posteriorly, the meniscus is contiguous with the posterior attachment
tissues = bilaminar zone (a vascular, innervated posterior attachment tissue important in allowing the
condyle to move forward).

ARTICULAR CAPSULE-surrounds the TMJ and is attached above to the articular eminence (tubercle)
and to the margins of the mandibular fossa and below to the neck of the mandible.
• Synovial membrane-lines the articular capsule in the superior and inferior spaces of the joint. It
does not cover the articular surfaces or articular disc.

ARTICULAR SURFACES of the TMJ are lined/covered with dense, fibrocartilaginous tissue that
resembles hyaline cartilage (but it is not!).
• Articular surfaces of most diarthrodial joints are covered by hyaline cartilage, but the TMJ is an
atypical diarthrodial joint because TMJ’s articular surfaces are covered by
FIBROCARTILAGE. The non-articular TMJ surfaces are covered with periosteum.

3 TMJ LIGAMENTS:
1. Stylomandibular ligament-separates the infratemporal region anteriorly from the parotid region
behind. This ligament runs from the styloid process of sphenoid bone to the angle of the
mandible.

2. Sphenomandibular ligament-attaches to the spine of sphenoid bone & lingula of the mandible.

3. Temporomandibular ligament (lateral ligament)-runs from the articular eminence (tubercle) to

the neck of the mandibular condyle. It provides lateral reinforcement for the capsule &
PREVENTS POSTERIOR & INFERIOR DISPLACEMENT OF THE CONDYLE. Resists
posterior movement of the mandibular condyle, and is found on the lateral surfaces of the TMJ.
Best way to PALPATE the POSTERIOR ASPECT of the MANDIBULAR CONDYLE is through the
external auditory meatus. Posterior aspect of the condyle is rounded and convex, and the anteroinferior
aspect is concave.

TMJ should be evaluated for tenderness and noise. TMJ is palpated laterally (in front of the external
auditory meatus) with the mandible in a closed and open position, and palpated through the external
auditory meatus with the mandible in a closed and open position.
• tenderness, sensitivity, joint noises (clicking and crepitus), and mandibular range of motion
should be examined. The normal range of movement of an adult mandible is ~50mm (opening)
and 10mm protrusively and laterally.

TMJ is the only normal joint that can be dislocated (luxated) without any external force. This may
be manifested by true luxation that requires assistance for reduction, or may be an overextended
excursion anteriorly that is self-reducing (subluxation).
• DISLOCATION of TMJ is almost always ANTERIORLY, BILATERAL, and OCCURS WHILE
LAUGHING OR YAWNING.

• REDUCING DISLOCATION is done by standing behind the patient with the thumbs inside the
mouth and index fingers below the chin. The thumbs depress the back of the jaw, and the chin is
elevated by the index fingers. The head of the condyle of the mandible will then slide into the articular
fossa.


BONE (HARD TISSUE)

Bone exists in 2 forms: Compact bone (appears as a solid mass) and Spongy bone (cancellous) that
consists of a branching network of trabeculae. BONE IS VASCULAR!

ENDOCHONDRIAL OSSIFICATION-method of bone development or FORMATION that involves a

cartilaginous model (hyaline cartilage) being laid down first. FORMS SHORT & LONG BONES.
• Bone replaces cartilage (osteocytes replace chondrocytes). Ex: ethmoid, sphenoid, and occipital
bones. The cartilage degenerates, leaving cavities that coalesce forming the marrow cavity.

• Osteoblasts secrete bone matrix and endochondrial ossification occurs along the diaphysis wall
and within the epiphysis, BUT NOT at the epiphyseal growth plates. Linear growth occurs at
epiphyseal plates until adult height is reached, then there is ossification at the growth plates.

• growth rate in the cartilage of the epiphyseal plate of a long bone is markedly retarded when there
is a lack of hormone from the HYPOPHYSIS.

• diametric (width) bone growth occurs by the addition of new bone tissue around the outer surface
of bone.

• HYALINE CARTILAGE PROVIDES A REGION WHERE LONG BONE CAN GROW IN

LENGTH.

INTRAMEMBRANOUS OSSIFICATION-takes place within fibrous membranes of C.T. FORMS

FLAT BONES (MAXILLA & MANDIBLE, clavicles, patellae, & skull flat bones---except sphenoid,
ethmoid, and occipital bones). The maxilla and mandible are formed primarily by intramembranous
ossification.
• intramembranous ossification contributes to growth of short bones and thickening of long bones
that involves transformation of osteoblasts into osteocytes.

• After bone is formed, it GROWS by APPOSITIONAL GROWTH (growth by adding new

layers on top of previously formed layers). Due to its rigid structure, BONE CAN ONLY GROW
BY APPOSITIONAL GROWTH.

• Appositional growth-occurs by proliferation and differentiation of osteoprogenitor cells

(mesenchymal cells that differentiate into osteoblasts) in the inner layer of the periosteum and
deposition of new ossified tissue one the outer bone surface. Periosteum-consists of a fibrous
outer layer and a cellular inner layer of osteoblasts. Interstitial growth of bone is NOT
POSSIBLE because of bone’s rigid structure.

• Resting lines-the result of appositional growth. Bone apposition-is the deposition of successive
layers of bone upon those already present. Apposition occurs by proliferation and differentiation of
osteoprogenitor cells (mesenchymal cells that differentiate into osteoblasts) in the inner layer of
 the periosteum.

BONE STRUCTURES: A typical long bone has a diaphysis containing a medullary cavity filled with
marrow, an epiphysis, epiphyseal plates for linear growth (length), a periosteum covering for diametric
growth (width), and attachments of ligaments and tendons.

1. Diaphysis-bone shaft consisting of a cylindrical tube of durable compact bone.

2. Epiphysis-caps the diaphysis; consists of spongy bone surrounded by compact bone. Contains
red bone marrow for RBC, WBC, and platelet production.

3. Epiphyseal plate-located between the epiphysis and diaphysis; region of miotic activity
responsible for elongation of bone.

4. Medullary cavity-centrally positioned tube within diaphysis that contains fatty yellow bone
marrow.

5. Nutrient foramen-opening into diaphysis that provides a site for nutrient vessels to enter and
exit the medullary cavity.

6. Articular cartilage-caps each epiphysis; composed of hyaline cartilage to facilitate joint

movement.

7. Endosteum-lines the medullary cavity. Consists of supportive dense regular C.T.

8. Periosteum-COVERS SURFACE OF BONES. Consists of dense regular C.T. and is a site for
ligament and tendon muscle attachment. Responsible for diametric (width) bone growth.

9. Compact bone-hard, outer layer of bone tissue covered by periosteum. Serves as an

attachment for muscles, provides protection, & gives durable strength to bone. Its basic structural
unit is the osteon. Compact bone functions as a supportive tissue of the body.

10. Cancellous (spongy) bone-porous, high vascular, inner layer of bone tissue. Makes bone lighter
and provides spaces for red bone marrow where blood cells are produced.

OSTEOBLAST-a bone-forming cell derived from mesenchyme (fibroblast) and forms an osseous
matrix where it becomes enclosed as an osteocyte. Osteoblasts synthesize the organic components of
bone matrix (collagen and glycoproteins). Osteoblasts have high RNA content and stain intensely.
Bone is hard because of calcification of its extracellular matrix and possesses some elasticity due to
the presence of organic fibers.

OSTEOCLAST-a large multinucleated cell associated with bone absorption and removal.

OSTEON (Haversian System)-basic structural unit of adult compact bone. Consists of lacunae,
canaliculi, concentric lamellae, and haversian canal. Osteon is a highly organized system of
interconnecting canals. Each osteon contains:
• Haversian canal (blood vessels, nerve fibers, and lymphatics pass through). Haversian canals are
 surrounded by concentrically arranged lamellae or layers of bone (4-20 lamellae). The oldest
lamella of an osteon is the most peripheral one.

• Lacunae-small cavities located b/t adjacent lamellae that contain osteocytes (mature bone
cells). Most osteons run with the long axis of the bone.

• Nutrients and oxygen reach osteocytes through canaliculi, capillaries, and Volkmann’s canals
(small canals that provide a system of communication between the periosteal bone, Haversian
canals, and bone marrow spaces).
HAVERSIAN SYSTMES (Osteons) usually found only in the diaphysis (shaft of long bones), but
small haversian systems may be found elsewhere. Spongy bone does not have Haversian System
characteristics of compact bone (lamellae are not arranged in concentric layers).

SKELETAL SYSTEM FUNCTIONS:

1. Support-skeleton forms a rigid framework for softer tissues and organs to attach.

2. Protection-skull and vertebral column enclose the CNS; the rib cage protects heart, lungs, great
vessels, liver, and spleen; the pelvic cavity supports pelvic viscera.

3. Body Movement-bones are anchoring attachments for most skeletal muscles acting as levers with
the joints, and functioning as pivots when muscles contract to cause body movement.

4. Hemopoiesis-red bone marrow of an adult produces RBC, WBC, and platelets.

5. Mineral Storage-bone’s inorganic matrix is composed mostly of calcium and phosphorus. These
minerals give bone rigidity and are 2/3 of bone weight. About 95% of calcium and 90% of
phosphorus in the body is deposited in bones and teeth.

Collagenous fibrils of bone matrix give bone tensile strength. When bone mineralizes, its inorganic
material increases, water content decreases, with little change in the collagen.

AGE, RACE, and GENDER affect bone mass, structural integrity, and bone loss. Blacks commonly
have denser bones than whites, and men have denser bones than women. Bone density and structural
integrity (ability to withstand stress) decreases after age 30 in women and age 45 in men. Thereafter,
a relatively steady quantitative loss of bone matrix occurs.

THE INTERCELLULAR MATRIX OF BONE contains both organic components

(glycosaminoglycans in the ground substance and collagen fibers) and inorganic salts that consist of
calcium phosphate (present in the form of highly insoluble hydroxyapatite crystals). Collagen fibers
provide bone with great tensile strength, while inorganic salts allow bone to withstand compression.
Bone is an important reservoir.

OSTEOBLASTS-secrete the organic components of the intercellular matrix of bone, including

glycosaminoglycans (5%) and collagen (makes up 95% of intercellular matrix). Within a period of days,
the intercellular matrix becomes calcified by the deposition of insoluble calcium salts within it.

SOME COMMON GLYCOSAMINOGLYCANS in the intercellular matrix of bone are hyaluronic

acid and chondroitin sulfate. The intercellular matrix also contains a calcium-binding protein
(OSTEOCALCIN) and a calcium and collagen-binding protein (OSTEONECTIN).

NASAL CAVITY-opens on the face through nostrils (nares) and communicates with nasopharynx
through a posterior opening (choanae). Meatus-the area below each concha (superior, middle, and
inferior).
1. roof-formed by nasal, frontal, sphenoid (body), and ethmoid (cribiform plate) bones.
2. floor-formed by palatine processes of maxilla and horizontal plate of palatine bone.
3. lateral walls-formed by superior, middle, and inferior conchae.
4. medial wall (nasal septum)-formed by the perpendicular plate of ethmoid bone, vomer, and
septal cartilage.
5. nose bridge-formed by the two nasal bones.

The remaining nose framework consists of cartilage plates (lateral nasal cartilage and greater and
lesser alar cartilage) held together by fibrous C.T.

NASAL CAVITY FLOOR-formed by the MAXILLA PALATINE PROCESSES and horizontal plates
of the two PALATINE bones.
• Nasal Cavity Innervation: OLFACTORY NERVE (CN I).

• Nasal Cavity Blood Supply: MAINLY sphenopalatine branch of maxillary artery, but some
blood from anterior ethmoidal branch of the ophthalmic artery and septal branch of the
superior labial branch of facial artery.

HARD PALATE-horizontal bony plate formed by the PALATINE PROCESSES and PALATINE BONE
(formed by this union). Forms the nasal cavity floor and roof of the mouth.
• Anterior 2/3 of hard palate-formed by palatine processes of maxilla

• Posterior 1/3 of hard palate-formed by horizontal plates of palatine bones.

• Soft palate-also forms the floor of nasal cavity, but contains no bones.

• Care must be taken when placing implants in the maxillary incisor region not to perforate the nasal
cavity. CT scan (cone-beam) technology is critical when planning implant placement.

NASAL CONCHAE-3 pairs of scroll-like, delicate shelves (projections) that hang into the nasal cavity
from the lateral walls of the nasal cavity. Conchae help increase surface area in the nasal cavity,
better exposing the brachiating olfactory nerve to inhale odors.
1. superior & middle conchae-part of the ETHMOID BONE and form the medial surfaces of the
lateral masses.

2. inferior conchae-are separate bones (called inferior turbinated bones).

MEATUS-space below each concha (3):

1. Superior meatus-lies below and lateral to the superior concha. It receives openings of the
posterior ethmoidal sinuses.
 2. Middle meatus-lies below and lateral to the middle concha. It receives the following openings:
▪ frontal sinus which drains into the infundibulum (funnel-like structure of the middle
meatus)
▪ middle ethmoidal sinuses which drain onto the ethmoidal bulla (a rounded prominence on
the middle meatus lateral wall).
▪ anterior ethmoidal sinuses and maxillary sinus which drain into the middle meatus via
the hiatus semilunaris (a groove on the middle meatus lateral wall leading into the
infundibulum).

3. Inferior meatus-lies below and lateral to the inferior conchae. It receives the nasolacrimal duct
opening which drains the inferior aspect of the lacrimal gland (located in the lacrimal fossa-a
depression on the orbital plate of the frontal bone).

ETHMOID BONE-sieve-like bone at the base of the skull, behind the root of the nose that runs through
the mid-sagittal plane and aids to connect the cranial skeleton to the facial skeleton. Ethmoid is 1 of 4
paired cranium bones (ethmoid, frontal, occipital, sphenoid bones) and consists of these plates and paired
projections:
1. horizontal plate (cribiform plate)-a perforated plate on either side of the crista galli that
transmits the olfactory nerve. It contains many olfactory foramina for olfactory nerves to pass
through.

2. crista galli-a midline projection from the horizontal plate located on the upper surface of the
ethmoid bone. It is attachment for the falx cerebri.

3. lateral masses (right & left)-project downward from the horizontal plate and contain the
ethmoid sinuses and lamina orbitalis (lamina papyracea). The thin plates of bone that form the
medial surfaces of the lateral masses of the ethmoid bone are the superior and middle conchae.

4. perpendicular plate-downward projection from the midline of the undersurface of the horizontal
plate that forms the upper portion of the nasal septum.

SPHENOID BONE-a single bone that runs through the mid-sagittal plane that aids in connecting the
cranial skeleton to the facial skeleton. It consists of a hollow body and 3 pairs of projections:
1. Hollow body (body of sphenoid bone)-contains sella turcica (houses pituitary gland) and
sphenoid sinus.
2. Greater wings-helps form the lateral wall of the orbit and roof of infratemporal fossa. Contain 3
foramina that provide access to the pterygopalatine and infratemporal fossa:
• Foramen Rotundum (transmits maxillary nerve-V2).
• Foramen Ovale (transmits mandibular nerve-V3).
• Foramen Spinosum (transmits middle meningeal vessels and nerves to tissues covering
the brain).

LEFT & RIGHT PTYERGOID PROCESSES project downward from near the junction of each of the
greater wings within the body of the SPHENOID BONE. Pterygoid processes run along the posterior
portion of the nasal passage toward the palate. EACH PTERYGOID PROCESS FORMS FROM A
MEDIAL & LATERAL PTERYGOID PLATE.
 1. Lateral Pterygoid Plate-the origin for both lateral and medial pterygoid muscles, and forms
the medial wall of the infratemporal fossa.

2. Medial Pterygoid Plate-forms the posterior limit of the lateral wall of the nasal cavity, and
ends inferiorly as the HAMULUS (a small, slender hook).

LESSER WINGS-help form roof of the orbit and superior orbital fissure. Contains the optic canal (optic
foramen) which transmits the optic nerve (CN II).

ZYGOMATIC BONE (a.k.a. cheekbone, malar bone, or zygoma)-forms the cheek prominence and
part of the lateral wall & floor of the orbital cavity.
• MEDIALLY, zygomatic bone articulates with the maxilla, and LATERALLY it articulates with the
zygomatic process of the temporal bone to form the zygomatic arch (cheek).
• temporal fossa-a shallow depression above the zygomatic arch filled with the temporalis muscle
which passes medial to the zygomatic arch before it inserts into the coronoid process of the
mandible.
• masseter muscle-attached to the lower margin of the zygomatic arch

TEMPORAL FOSSA-a shallow depression on the side of the cranium bound by the temporal lines and
terminating below the level of the zygomatic arch. The infratemporal crest of the greater wing of the
sphenoid bone separates the temporal fossa from the infratemporal fossa below it.
• Temporal and infratemporal fossae communicate with each other deep to the zygomatic arch.

• Infratemporal fossa communicates laterally with the pterygopalatine fossa via the
pterygomaxillary fissure.

INFRATEMPORAL FOSSA-an irregular-shaped space lying posterior to the maxilla, between the
PHARYNX & RAMUS OF THE MANDIBLE. Boundaries of the infratemporal fossa:
1. anterior wall-formed by posterior surface of maxilla.
2. posterior wall-formed by styloid process of the temporal bone.
3. medial wall-formed by lateral pterygoid plate of sphenoid bone.
4. lateral wall-formed by ramus of mandible.
5. superior margin-formed by infratemporal surface of the greater wing of sphenoid bone (separated
from the temporal fossa by the infratemporal crest). Foramen ovale in the roof of this fossa
transmits mandibular nerve (V3).
6. inferior margin-the point where the medial pterygoid muscle inserts into the medial aspect of the
mandible near the angle.

Infratemporal Fossa Contents: lower portion of temporalis muscle, medial and lateral pterygoid
muscles, maxillary artery and its branches, pterygoid plexus of veins, mandibular nerve-V3, chorda
tympani (facial nerve branch), otic ganglion (parasympathetic ganglion associated with
glossopharyngeal nerve).

PTERYGOPALATINE FOSSA-a small space behind and below the orbital cavity that lies between the
pterygoid plates of the sphenoid and palatine bone below the apex of the orbit. Pterygopalatine fossa
communicates as follows:
 • medially with the nasal cavity through the sphenopalatine foramen.
• posteriorly with foramen lacerum through the pterygoid canal.
• superiorly with the skull through the foramen rotundum.
• anteriorly with the orbit through the inferior orbital fissure.

Openings into Pterygopalatine Fossa: pterygomaxillary fissure, inferior orbital fissure, sphenopalatine
foramen, pterygoid canal, pharyngeal canal, and foramen rotundum.

PTERYGOPALATINE GANGLION-lies in the pterygopalatine fossa just below maxillary nerve (V2).
This ganglion receives preganglionic parasympathetic fibers from the facial nerve via the greater
petrosal nerve. It sends postganglionic parasympathetic fibers to the lacrimal gland and glands in
the palate and nose.
• Maxillary nerve (V2) and maxillary artery both pass through the pterygopalatine fossa.

MANDIBULAR FOSSA (GLENOID FOSSA OR ARTICULAR FOSSA)-a deep hollow in the

squamous portion of the TEMPORAL BONE at the base of the zygomatic process where the condyle of
the mandible rests. The mandibular fossa articulates with the condyle of the mandible to form the
TMJ.

• Anterior Part of Mandibular Fossa-formed by the articular eminence (a rounded bar of bone).
The anterior part is the functional area and articular portion of the TMJ. Posterior slope of the
eminence is lined by fibrous C.T.

• squamotympanic fissure-SEPARATES MANDIBULAR FOSSA from the tympanic plate,

through the medial end of which (petrotympanic fissure) and chorda tympani exits the tympanic
cavity.

• Tympanic plate-bony plate between the anterior wall of the external acoustic meatus and posterior
wall of the mandibular fossa.

• Chorda tympani-a facial nerve branch that conveys preganglionic parasympathetic

(secretomotor) fibers to the submandibular ganglion and taste fibers from the anterior 2/3 of
tongue.

ANTERIOR CRANIAL FOSSA-formed by frontal & ethmoid bones. Contains: frontal lobes of
cerebrum, cribiform plate, foramen cecum, and anterior & posterior ethmoidal foramina.

MIDDLE CRANIAL FOSSA-formed by sphenoid, temporal, and parietal bones. It’s a thin layer of
bone that separates the middle ear cavity and sphenoid sinus. Contains: temporal lobes of cerebrum,
hypophysis cerebri (pituitary gland), optic & carotid canals, superior orbital fissure, foramen rotundum,
ovale, spinosum, and lacerum.

POSTERIOR CRANIAL FOSSA-formed by occipital and temporal bones. Contains: occipital lobes
of cerebrum, cerebellum, pons, and medulla oblongata; internal auditory meatus, jugular, condyloid, and
mastoid foramens, foramen magnum, and hypoglossal canal.

PETROUS PORTION OF THE TEMPORAL BONE forms the floor of the middle cranial fossa, and
separates the middle and posterior cranial fossae.

HIPBONE (OS COXA)-formed by fusion of the ILIUM, ISCHIUM, PUBIS on each side of the pelvis.
Os Coxa articulates with the sacrum at the sacroiliac joint to form the pelvic girdle. The two hipbones
articulate with each other anteriorly at the symphysis pubis.
• Ilium-upper flattened part of the hipbone that possesses the iliac crest which ends in front at the
anterior superior iliac spine and behind at the posterior superior iliac spine. The ilium possesses
the greater sciatic notch (a large notch).

• Ischium-L-shaped with an upper thicker part (body) and lower thinner part (ramus). Ischium bears
a person’s body weight when upright or seated. Features include ischial spine and ischial
tuberosity. The obturator foramen is formed by the ramus of the ischium together with the
pubis.

• Pubis-is divided into a body, superior ramus, and inferior ramus. The bodies of the two pubic
bones articulate with each other in the midline anteriorly at the symphysis pubis. Medial to
symphysis is the pubic tubercle. The inguinal ligament connects the pubic tubercle to the anterior
superior iliac spine.

ACETABULUM-a cup-shaped cavity on the lateral side of the hipbone that RECEIVES THE
HEAD OF FEMUR. Acetabulum is formed superiorly by the ilium, postero-inferiorly by the ischium,
and antero-medially by the pubis.

ALVEOLAR PROCESS-part of the maxilla and mandible that forms teeth sockets and supports the
teeth. It consists of 2 main parts:
1. Alveolar Bone Proper (cribiform plate or lamina dura)-part of the alveolar process that
immediately surrounds the tooth root and to which the PDL fibers are attached. It has
numerous tiny openings that provide passage for vascular and nerve components. Consists of 2
bone layers: compact lamellar bone & bundle bone (layer that the periodontal fibers insert into).
• Alveolar bone proper is the only essential part of the bone socket. Supporting alveolar bone
is not always present. Reversal lines on the alveolar bone proper indicate the cessation of
osteoclastic activity.

• Alveolar bone proper of a tooth socket resorbs when subjected to pressure, and contains
numerous openings through which vessels pass.

• ALVEOLAR BONE IS COMPOSED of cells (osteoblasts, osteocytes, & osteoclasts), a

fibrous matrix (collagen fibers, hydroxyapatite), and ground substance (proteoglycans).

2. Supporting Alveolar Bone-surrounds alveolar bone proper and supports the socket. It consists of:
a. cortical plate (compact lamellar bone)-forms the outer and inner plates of the alveolar
processes.
b. spongy bone (cancellated bone)-fills in the area between cortical plates of bone.

If a tooth fails to erupt, the alveolar bone never forms in that area, and if a tooth is extracted, the alveolus
resorbs after the extraction until finally the alveolar ridge completely atrophies. TOOTH POSITION
(not functional load) DETERMINES SHAPE OF THE ALVEOLAR RIDGE.

In a young child, the ALVEOLAR PROCESS is the area of the maxilla that grows in HEIGHT and
LENGTH to accommodate the developing dentition.

The alveolar mucous membrane APPEARS RED due to high vascularity and thinness of epithelium.

THE SPACE BETWEEN THE JAWS into which the teeth erupt is provided by growth at the
mandibular condyles (especially the molars). The condyle is a major site of growth. Soft-tissue
development carries the mandible forward and downward, while condylar growth fills the resultant
space to maintain contact with the base of the skull.

• Long axes of the mandibular condyles intersect at foramen magnum. This indicates long axes
are directed posteromedially.


BONE SURFACE FEATURES

Bone Depressions:
1. Fissure (sharp, deep groove)-sharp, narrow cleft-like opening b/t the parts of a bone that allows
for the passage of blood vessels and nerves. Ex: superior orbital fissure of sphenoid bone.

2. Sulcus-groove that is shallower and less abrupt cleft than a fissure. It’s a shallow, wide groove on
the bone surface that allows passage of vessels, nerves, and tendons. Ex: intertubercular sulcus of
the humerus (a.k.a. bicepital groove).

3. Incisure (notch)-deep indentation on a bone border. Ex: Greater sciatic incisure/notch of os coxa.

4. Fovea-small, very shallow pit depression in bone. Ex: fovea capitus on the head of femur
accepts a tendon from the hip socket or acetabulum.

5. Fossa-shallow depression that may or may not be an articulating surface. Ex: (articulating
surface): glenoid fossa of scapula or mandibular fossa of temporal bone. Ex: (non-articulating
surface): subscapular fossa.

Bone Openings:
1. Foramen-opening through which vessels, nerves, or ligaments pass. Ex: foramen magnum of
occipital bone, mental foramen of mandible.

2. Meatus (canal)-tube-like passage running through a bone. Ex: acoustic meatus of temporal bone.

Enlargements & Processes:

1. Process-generic term for a bone projection that serves as an attachment point for other structures.
Ex: Acromion process of scapula, transverse process of vertebrae.

2. Epicondyle-projection or swelling to the side of a condyle (or above in some cases). Ex: medial
& lateral epicondyles of femur.

3. Spine-a sharp, slender projecting process. Ex: spinous process of vertebrae, spine of scapula.

4. Tubercle-small, rounded process. Ex: greater and lesser tubercles of humerus.

5. Tuberosity-large, rounded, roughened process. Ex: ischial tuberosity of the ischium.

6. Trochanter-large, blunt projection for muscle attachments on the femur. Ex: greater & lesser
trochanters of the femur (a tuberosity taken to an extreme).

7. Crest-prominent elevated ridge or border of a bone. Ex: iliac crest of the ilium (os coxa).

8. Linea (line)-small crest that is straighter than a crest. Ex: linea aspera of femur.
9. Ramus-a major branch off of the main body of a bone that may have its own articulation or
processes. Ex: coronoid and condylar processes of the mandible are subdivisions of the major
ramus that angles off the main body of the bone.

10. Neck-a slight narrowing of the body of the bone that supports the head. Ex: necks of the humerus
and femur.

11. Lamina-very thin layer of bone. Ex: neural arch of the cervical vertebrae.

 TISSUES
MESENCHYMAL CELLS (mesoblastic cells)-present in mesenchyme capable of differentiating into
any of the special types of connective tissue or supporting tissue, smooth muscle, vascular endothelium, or
blood cells. Mesenchymal cells have the potential to proliferate and differentiate into diverse types
of cells (fibroblasts, chondroblasts, odontoblasts, and osteoblasts). Mesenchymal cells form a loosely
woven tissue (mesenchyme) or embryonic connective tissue.
• mesenchymal cells in the dental papilla adjacent to the inner enamel epithelium differentiate into
odontoblasts which produce predentin that calcifies to become dentin.

MESECTODERM (Ectomesenchyme)-mesenchyme derived from ectoderm (especially from the neural

crest) in the very young embryo. From this area (neural crest), neural crest cells give rise to spinal
ganglia (dorsal root ganglia), and the ganglia of the autonomic nervous system. Neuralcrest cells also
give rise to neurolemma cells (Schwann cells), cells of the meninges that line the brain & spinal cord
(ependymal cells), pigment cells (melanocytes), chromaffin cells of adrenal medulla, and several
skeletal and muscular components of the head.

CARTILAGE-specialized C.T. that has cells and fibers embedded in a gel-like matrix (amorphous
ground substance). Cartilage is a specialized type of supportive and protective C.T. that is
nonvascular, lacks nerves, and has firm consistency. 3 types of cartilage in the body: hyaline
cartilage, fibrocartilage, & elastic cartilage.

Cartilage has 3 components:

1. Cells-chondroblasts & chondrocytes
2. Fibrous matrix-collagen and elastic fibers
3. Ground substance-sulfated proteoglycans and glycosaminoglycans. Ground substance of
hyaline cartilage is BASOPHILIC since it contains SULFATED PROTEOGLYCANS. Ground
substance also contains hyaluronic acid and sulfated proteoglycans which are
glycosaminoglycans.
• chemical nature and organization of glycosaminoglycans allows ground substance to bind
and hold water to allow tissue to assume a gelatinous nature that resists compression
and permits some diffusion through the matrix.

Except on exposed surfaces of joints, cartilage is covered by a PERICHONDRIUM = FIBROUS

MEMBRANE that has a fibrous outer layer and chondroblastic inner layer.
• cartilage is a PRECURSOR TO ENDOCHNODRIAL BONE.
• Located in lacunae, chondrocytes receive nutrients through diffusion from vessels within the
surrounding perichondrium.
• No calcium salts are present in cartilage, which is why cartilage is radiolucent on x-rays.

HYALINE CARTILAGE-MOST ABUNDANT CARTILAGE IN BODY. Hyaline cartilage has a high

proportion of intercellular matrix with extremely FINE COLLAGENOUS FIBERS. Found where strong
support, but flexibility is needed. Has great wear resistance and COVERS ARTICULAR SURFACES
OF ALL SYNOVIAL JOINTS. It cannot be repaired if fractured, and the defect is filled with fibrous
tissue. Ex: articular surfaces of bones, nose, walls or respiratory passage, and fetal skeleton.

• During endochondrial ossification in a long bone of an extremity, hyaline cartilage provides a

region where a long bone can grow in length.

• THROUGHOUT CHILDHOOD & ADOLESCENCE hyaline cartilage is important in growth

in the length of long bones.

• Epiphyseal Plate-composed of hyaline cartilage and persists b/t primary and secondary ossification
centers. Hyaline cartilage proliferates at epiphyseal plates, and an increase in length of the entire
long bone occurs (interstitial growth).

• Hyaline cartilage has a capsule around the chondrocytes (the youngest layer of intercellular
substance).

• Hyaline Cartilage FORMS THE FETAL SKELETON. In adults, its remnants are:
1. articular cartilage-smooth and slippery (lines movable joints).
2. costal cartilages-at sternal ends of the ribs.
3. respiratory cartilages-moveable external nose and septum, larynx, trachea, and bronchus walls.
4. auditory cartilages-external auditory meatus and pharyngotympanic tube.

Long Bone Ossification Centers:

1. primary ossification center-ossification occurs NEAR THE MIDDLE OF THE DIAPHYSIS.
2. secondary ossification center-forms later in the epiphyses.

METAPHYSIS-REGION BETWEEN a primary & secondary ossification center. The ossification

centers enlarge until all that is left between them is a thin plate with hyaline cartilage at its center =
epiphyseal plate.

FIBROCARTILAGE-contains many collagen fibers embedded in a small amount of matrix. It resembles

dense, irregular C.T. (consists of a dense matrix of collagenous fibers). Fibrocartilage HAS THE
GREATEST TENSILE STRENGTH of the three types of cartilage in the body. If damaged, it repairs
itself slowly. Ex: TMJ, sternoclavicular joint, knee joint, articular surfaces of the clavicle and
mandible.

ELASTIC CARTILAGE-contains large numbers of elastic fibers embedded in matrix; highly flexible,
and repairs itself with fibrous tissue if damaged. Ex: auricle of ear, external auditory meatus, auditory
tube, and epiglottis.

GROWTH OF CARTILAGE (2 PROCESSES): Cartilage grows by appositional & interstitial

growth.
1. Interstitial growth-involves the division of existing chondrocytes within the cartilage.
Interstitial growth is important in forming the FETAL SKELETON and continues in the epiphyseal
plates and articular cartilages. Ex: hyaline cartilage growth.

2. Appositional growth-involves differentiation of chrondroblasts and stem cells into

 chondrocytes on the inner surface of the perichondrium. Appositional growth is important for
continued increase in girth of cartilage masses. Bone also grows via appositional growth!

Important: Do not confuse bone growth with bone formation. Bone forms by either endochondrial or
intramembranous ossification. Hyaline cartilage differs from bone in that hyaline cartilage grows by
interstitial growth (bone cannot as it only grows by appositional growth).

CONNECTIVE TISSUE-derived from mesenchyme (mesoderm) and contains more intracellular

material than cells. Fibroblasts and macrophages are the MOST COMMON C.T. cells.
CONNECTIVE TISSUE FORMS: BONE, CARTILAGE, & ADIPOSE TISSUE. C.T. binds and
supports other body tissues and provides metabolic need to all body organs. 2 types of C.T:
1. Loose (areolar) C.T.-has large spaces separating the fibers and cells and contains much
intracellular fluid.

2. Dense C.T.-provides structural support with greater fiber concentration.

2 Types of Dense C.T:

1. Dense regular C.T. (tendon, ligaments, & aponeuroses)-consists of tightly packed fibers
arranged in a CONSISTENT PATTERN. Provides strong, flexible support.

2. Dense irregular C.T. (dermis, submucosa, GI tract, fibrous capsules, and fascia)-tightly
packed fibers arranged in an INCONSISTENT PATTERN.

TENDON-band or cord of dense, regular collagenous C.T. bundles that ATTACHES MUSCLE TO
BONE. Functions: allows individual muscles to control the movement of a given bone more efficiently.
Aponeuroses-tendons that are broad, thin sheets composed of dense regular C.T.

LIGAMENTS-tough, fibrous tissues that CONNECT BONE TO BONE. Main Function: support &
strengthen joints. Ligaments are like giant rubber bands. It is most susceptible to injury when
stretched across its fibers. Ligaments have POOR BLOOD SUPPLY so they HEAL SLOWLY.

SHARPEY’S FIBERS-attaching fibers when a tendon or ligament is attached to bone; periosteal

collagen fibers that penetrate the bone matrix, binding the periosteum to bone.
• Periodontal ligament-contains collagen fibers that insert on one side in the cementum, and into
alveolar bone on the other side. The terminal ends of PDL fibers are Sharpey’s fibers.

4 TYPES OF TISSUES:
1. Connective Tissue-highly vascular (except cartilage), contains an intracellular matrix, mitotically
active tissues. Connective Tissue SUPPORTS OR BINDS OTHER TISSUES & PROVIDES
METABOLIC NEEDS TO ALL BODY ORGANS. Ex: tendons, ligaments, cartilage, bone,
adipose, blood.

2. Muscle Tissue-limited mitotic activity. Fibers contract in response to stimuli; involves

movement of materials through the body, movement of one part of the body with respect to another,
and locomotion. Ex: smooth, cardiac, and skeletal muscles.

3. Nervous Tissue-limited mitotic activity; respond to stimuli and conduct impulses to and from all
 body organs. Ex: Neurons and neuroglia.

4. Epithelial Tissue-classified by shape of the cell at the free surface of the tissue and by
number and arrangement of cell layers. May be 1 layer (simple) or several layers (stratified)
thick. Its lower surface is bound to a supportive basement glycoprotein membrane.
▪ Mitotically active tissues that line ALL body surfaces, cavities, & lumina. Function:
protection, absorption, excretion, and secretion depending on its location.

▪ Composed of closely joined cells with minimum of intracellular material between them.
Epithelial tissue either covers a body surface, or lines a body cavity.

▪ Ex: outer skin layer, GI tract linings, urinary bladder, ducts, and vessels; lung alveoli,
and covering of viscera and body cavities.

EPITHELIAL TISSUES-classified by cell shape and number and arrangement of cell layers.

1. SIMPLE-one layer of epithelial cells ALL CELLS CONTACT THE BASAL LAMINA:
a. Squamous epithelium (flat)-single layer of flat cells that line areas where gases need to
cross readily (diffusion and filtration). Ex: endothelium lining blood vessels, mesothelium
that lines body cavities and coats organs of these cavities, and epithelium lines air sacs
(alveoli) of lungs.

b. Cuboidal epithelium (square)-single layer of square cells of equal height and width; line
secretion and absorption areas (secretion, excretion, absorption). Ex: collecting ducts,
proximal and distal tubules of kidney, thyroid follicles.

c. Columnar epithelium (rectangular)-single layer of cells taller than wide, lining absorption
areas (absorption, secretion, protection). Ex: lining of stomach and intestines, gallbladder,
uterine, salivary gland striated ducts. Lines the GI tract except the esophagus and anus.

2. STRATIFIED-epithelium with two or more cell layers with only the deepest layer in contact
with the basal lamina (basement membrane). Contains hemidesmosomes.

• Squamous epithelium-lines areas needing protection (protection, prevents water loss).

Usually contains cuboidal cells in deeper layers and squamous cells in the surface layer.
Well adapted for abrasion and protection. Ex: skin epidermis (keratinized), linings of
mouth (oral cavity), oropharynx, laryngopharynx, esophagus (not keratinized), anus, and
vagina

Stratified Squamous epithelium acts as a MECHANICAL BARRIER that protects underlying

tissues. 3 types found in the oral cavity:
1. Keratinized-least frequently present; effective mechanical protector. Cells filled with keratin.
Ex: Gingiva & hard palate.

2. Non-keratinized-selective barrier that acts as a cushion. Cells do not contain keratin. Ex: soft
palate, cheeks.
• Some medications can be absorbed through the mucosa of the tongue’s ventral surface
 and through the mucosa of the mouth floor because the mucosa in these areas is covered by
thin, non-keratinized stratified squamous epithelium with a thin lamina propria.

3. Parakaratinized-intermediate form that gradually becomes keratinized.

• Cuboidal epithelium-lines mid-sized sweat gland ducts (protection and secretion).
• Columnar epithelium-lines large ducts of salivary glands & male urethra (protection).

SPECIALIZED EPITHELIUM:
• Pseudostratified columnar epithelium-specialized for secretion & movement along luminal
surfaces. Appears multilayered, but is only a single layer with ALL CELLS TOUCHING THE
BASAL LAMINA.
▪ Pseudostratified ciliated columnar epithelium-lines mucous membrane of nasopharynx.
Lines upper respiratory tract: nasal cavity, paranasal sinuses, nasopharynx, trachea,
and bronchial tree (not the respiratory bronchioles lining which loses its cilia and
changes to cuboidal, and then squamous ). Also lines parts of male reproductive tract.

• Transitional epithelium-lines areas that accommodate an increase in luminal area by changing cell
shape (has low permeability). Varies between cuboidal and squamous (permits lumen expansion).
Lines the URINARY BLADDER, ureter, and upper urethra. It does NOT have a basement
membrane. It makes up specialized tissue that allows organ expansion with minimal resistance
from the tissue. Contains dome-shaped superficial cells (globular cells) that change form
depending on if the bladder is empty of full (expanded).

BASEMENT MEMBRANE-thin, delicate non-cellular structure consisting of two protein-

polysaccharide layers that ANCHOR EPITHELIUM TO UNDERLYING CONNECTIVE TISSUE:
Separates the dermis from epidermis.
1. basal lamina-develops from epithelial cells; composed of collagen and glycoproteins.
2. reticular lamina-develops from C.T.; much thicker, composed of reticular fibers.

Hemidesmosomes-half desmosomes (spot-like junction) that ANCHOR EPITHELIUM TO BASAL

LAMINA, thus underlying C.T. Common in stratified epithelium of skin, and junctional epithelium of
the epithelium attachment (epithelial cuff).
• Bullous pemphigoid-clinical condition involves disruption of hemidesmosomes and consequent
separation of the epithelium from the basal lamina.

• Hemidesmosomes are spot-like adhering junctions that connect or anchor the plasma membrane of
an epithelial cell to underlying basal lamina. Found between basal cells of epithelium and basal
lamina.

Desmosomes (macula adherens)-a spot-like junction that connects two neighboring (adjacent) cells.
Functions by serving as a means for attachment of adjacent cells.

Intermediate junction-a belt-like adhering junction that connects two neighboring (adjacent) cells.

Focal Contacts (adhesion plaques)-spot-like junction that connects the plasma membrane of a fibroblast
to surrounding connective tissue.
 • Focal contacts represent points where stress fibers are attached to the plasma membrane.
FOUND IN FIBROBLASTS and form in response to cell tension.

• An active fibroblast is characterized by abundant endoplasmic reticulum.

ORAL EPITHELIUM CELLS: cells found in the oral epithelium:

1. Stratified squamous epithelium (keratinized, non-keratinized, and parakaratinized).
2. Melanocytes-derived from the NEURAL CREST and produce melanin.
3. Langerhans cells-antigen presenting cells (APC); part of immune system.
4. Merkel cells-associated with nerve endings.
5. Inflammatory cells-lymphocytes, monocytes, and neutrophils.

Connective Tissue of the Oral Cavity: referred to as lamina propria-connective tissue that provides
mechanical support to the epithelium, and carries nerves and blood vessels. Lamina Propria (dermis)
has 2 layers in the oral cavity:
1. Papillary layer-lies directly under the oral epithelial layer.
2. Reticular layer-dense, fibrous C.T. layer lies directly below the papillary layer.

ORAL MUCOSA-INNERMOST LAYER of mucous membrane that covers all oral structures
EXCEPT clinical crowns of teeth. Composed of two layers:
1. Stratified squamous epithelium-outermost layer of (may be keratinized, parakaratinized, or non-
keratinized) depending on its location.

2. Lamina propria-C.T. below the stratified squamous epithelium. It is a basement membrane that
supports the epithelium. It can be attached to the periosteum of the alveolar bone, or interposed
over the submucosa.

SUBMUCOSA-innermost layer below the lamina propria, found only in areas requiring a high
degree of compressibility and flexibility (ex: CHEEKS, SOFT PALATE). Located between
connective tissue and muscle tissue. Contains glands, vessels, and nerves.
▪ mucosa in areas subject to mechanical stress (gingiva & hard palate) is KERATINIZED.
▪ mucosa of soft palate, sublingual, and buccal regions is NON-KERATINIZED.

Oral Mucosa Permeabilities: decrease in the order of sublingual > buccal > palatal. This rank is based
on the relative thickness and degree of keratinization of these tissues as follows:
▪ sublingual mucosa thin and non-keratinized
▪ buccal thicker and non-keratinized
▪ palatal mucosa is intermediate in thickness but keratinized.

3 MAJOR FUNCTIONAL TYPES OF ORAL MUCOSA:

1. Masticatory Mucosa-composed of free & attached gingiva, and hard palate mucosa. The
epithelium of these tissues is keratinized, and the lamina propria is a dense, thick, firm C.T.
containing collagenous fibers. Note: the surface epithelium of the gingiva is highly
impermeable making it resistant to bacterial invasion.

2. Lining (Reflective) Mucosa-covers inside of lips, cheek, vestibule, lateral surfaces of the
 alveolar process (except the mucosa of the palate), floor of mouth, soft palate, and inferior
surface of the tongue. Lining mucosa is a thin, movable tissue with a thin, nonkeratinized
epithelium and thin lamina propria. Mucogingival junction- junction of the lining mucosa with
masticatory mucosa.

3. Specialized Mucosa-covers the tongue dorsum and taste buds. Its epithelium is non-
keratinized.

Important: the oral cavity is highly acceptable to systemic drug delivery as the oral mucosa is
permeable with a rich blood supply. The lack of Langerhans cells makes the oral mucosa tolerant to
potential allergens. This route also bypasses the first pass effect and avoids pre-systemic elimination in
the GI tract.
• Ex: Nitroglycerin tablets are given sublingually for rapid absorption. Note: Alveolar mucosa is
similar to sublingual mucosa as it too is red due to numerous blood vessels and its thin epithelial
covering.

SKIN-consists of two layers:

EPIDERMIS-outer skin layer that develops from ectoderm. Epidermis has 5 sub-layers (strata):
1. Stratum basale (stratum germinativum or basal layer)-INNERMOST LAYER 3-5 cells thick.
It’s the LEAST cytodifferentiated, contains columnar cells that exhibit high mitosis held
together by desmosomes. Melanocytes-produce melanin pigment located in stratum basale.

2. Stratum spinosum (prickle cell layer)-2nd layer 8-10 cells thick, cells appear spiny. Contains
Langerhans cells (involved in immune response). Less cell mitosis than stratum basal layer.
Malpighian layer denotes the stratum basale and stratum spinosum.

3. Stratum granulosum (grainy layer)-layer 3-5 cells thick. It’s the layer where keratin is
produced by KERATINOCYTES = “the most common cell found in the epidermis”.

4. Stratum lucidum (clear layer)-a compact, thin layer 3-4 cells thick. It’s a clear band whose cells
contain ELEIDIN-a clear intracellular protein transformed into keratin as this layer becomes
part of stratum corneum. Most prominent in thick skin, absent in thin skin.

5. Stratum corneum (horny layer)-THICKEST OUTERMOST LAYER 25-30 cells thick,

composed of closely packed dead squamous cells filled with keratin. Every 2 weeks the entire
layer sloughs off to reveal new skin.
EPIDERMIS CHARACTERISTICS: composed of stratified squamous keratinized epithelium
separated from the dermis by a basement membrane. NO BLOOD VESSELS and is thinner than the
dermis. Contains: keratinocytes (most common cell), melanocytes (produce melanin), and Langerhans
cells (immune function).

• Nourishment: the epidermis of the skin obtains nourishment by the diffusion of tissue fluid
(interstitial fluid) from capillary beds in the papillary layer of the dermis. This tissue fluid
contains a small % of plasma proteins of low MW that pass through the capillary walls due to the
blood’s hydrostatic pressure.
FLUIDS ACCOUNT FOR 40 LITERS (55-60%) of adult body weight. There are 2 types of fluids:
1. Intracellular Fluids (within body cells)-account for 40% of body weight.
2. Extracellular Fluids (outside cells)-account for 20% of body weight. 3 extracellular fluids:
1. interstitial fluid-surrounds cells; 12% of body weight.
2. blood plasma-fluid within blood vessels; 5% of body weight.
3. lymph, serous, synovial, cerebrospinal, and intraocular fluids; 3% of body weight.

Each cell in the body exists in a fluid environment. Intracellular fluid provides cells with turgidity
and a medium of transport. Extracellular fluid provides the cell with a medium of support and
homeostasis. Note: extracellular fluid pH must be maintained in the alkaline pH range of 7.0-7.8 to be
compatible with life.

DERMIS-deeper, thicker dense, irregular collagenous C.T. layer of skin below the epidermis that
connects the skin to the hypodermal layer. It is not composed of entirely of cells, but of dense,
irregular collagenous C.T. with interwoven collagen (main component of collagen fibers), and elastin
(main component of elastic fibers) that allow the skin to stretch and recoil. Dermis has 5 types of nerve
endings that sense pain, heat, cold, touch, and pressure.

DERMIS-develops from mesoderm and is made of two layers:

1. Papillary layer-thin & less fibrous layer with papillae projections that extend up toward the
epidermis. Papillary layer contains more blood vessels than the reticular layer, and supplies the
overlying epidermis. Contains fibroblasts, mast cells, and macrophages.

2. Reticular layer-thick, fibrous layer continuous with the hypodermis. Blood vessels from the
hypodermis pass through the reticular layer which contains more fibers, but fewer cells than the
papillary layer.

▪ HYPODERMAL LAYER- layer of loose C. T. that connects the dermis to the underlying fascia of
muscles. THE MAJOR SITE OF FAT DEPOSITION (50% of body fat). Has good blood supply.

▪ Dermis contains: BLOOD, LYMPH VESSELS, NERVE FIBERS, HAIR FOLLICLES, SEBACEOUS
GLANDS (secrete oil), SWEAT GLANDS, collagen, elastic, and reticular fibers; fibroblasts &
macrophages.

SIX MAJOR CELLULAR JUNCTIONS IN HUMAN CELLS:

1. Tight Junctions (zonula occludens)-occluding junctions & belt-like
2. Intermediate junctions (zonula adherens)-anchoring/adhering junctions
3. Desmosomes (macula adherens)- anchoring/adhering junctions
4. Hemidesmosomes- anchoring/adhering junctions
5. Focal Contacts- anchoring/adhering junctions
6. Gap Junctions-communicating junctions

JUNCTIONAL COMPLEXES-specialized cell junctions found in many tissues, but highly abundant in
epithelial tissues. Junctional complexes make epithelial tissues so well suited to cover the body surfaces
and line body cavities. Junctional complexes have 3 distinct components:
 1. Tight junctions (zonula occludens)-a belt-like junction that completely encircles the epithelial
cell, binding it to all its neighboring cells. Tight junctions are always found on the lateral
surface of the plasma membrane, very close to the apical end of the cell.

2. Intermediate junctions (zonula adherens)-form continuous belt-like junction around the entire
cell. They are located just below the tight junction on the lateral surface of the plasma membrane.

3. Desmosomes (macula adherens)-differs from tight and intermediate junctions because each
desmosome is a point of cell attachment (not a zone or belt of attachment).
• desmosome is a strong adhesion on the lateral surface of the plasma membrane; the strength
is created by an intermediate filament.

• in a junctional complex, the desmosome is always below the intermediate junction, and
found in cardiac muscle and uterus muscles.

• Pemphigus-affected individual makes antibodies against their own desmosome protein

(desmogleins) that bind and disrupt desmosomes between epithelial cells in skin.

GAP JUNCTIONS-specialized areas (communicating junctions) of cell membranes that connect

neighboring cells. Gap junctions are organized collections of protein channels that allow passage of
IONS & SMALL MOLECULES to passively traverse between connected cells.

• GAP JUNCTIONS ARE NOT COMPONENTS OF JUNCTIONAL COMPLEXES, but exist in

all multi-cellular organisms and in nearly all cell types EXCEPT skeletal muscle, RBC, and
freestanding cells (e.g. circulating lymphocytes.


PERIODONTAL LIGAMENT (PDL) & GINGIVA

PERIODONTAL LIGAMENT-a complex, specialized soft C.T. derived from the dental sac
containing numerous cells, blood vessels, nerves, and extracellular substances consisting mostly of
collagen fibers (gingival and principal) and ground substance (composed of proteins and
polysaccharides). PDL contains these specialized cells:
▪ cementoclasts or cementoblasts-resorb and replace cementum.
▪ fibroclasts or fibroblasts-resorb and replace periodontal ligament.
▪ osteoclasts or osteoblasts-resorb and replace alveolar bone.
▪ Macrophages-phagocytic cell found stationary in tissues or as a mobile WBC.

PERIODONTAL LIGAMENT (PDL)-a complex, highly cellular and vascular, soft, fibrous connective
tissue (TYPE 1 COLLAGEN) that contains numerous cells, blood vessels, nerves, & extracellular
substances. PDL collagen fibers are arranged into GINGIVAL FIBERS and PRINICIPAL FIBERS that
surround teeth roots to connect root cementum to surrounding alveolar bone (bony socket).

1. PDL GINGIVAL FIBERS-have no bony attachment. Found in the free gingiva, but are
continuous with the PDL to SUPPORT the gingival margin and interdental papillae. Gingival
 Fibers: circular, dentogingival, dentoperiosteal, alveologingival, and transpetal.

2. PDL PRINCIPAL FIBERS-PDL collagen fibers that CONNECT ROOT CEMENTUM TO

ALVEOLAR BONE (tooth-to-bone fibers). Distinguished by the location and direction that
they extend from cementum to alveolar bone. Each principal fiber has a terminal end called
SHARPEY’S FIBERS.

SHARPEY’S FIBERS-the TERMINAL END PORTIONS of the PDL PRINCIPAL COLLAGEN

FIBERS collage EMBEDDED in CEMENTUM & ALVEOLAR BONE attaching fibers when a tendon or
ligament is attached to bone; periosteal collagen fibers that penetrate the bone matrix, binding the
periosteum to bone. Oblique fibers are most numerous and resist intrusive and rotational forces.
Sharpey’s fibers anchor the PDL fibers into cementum and bone. The diameter of Sharpey’s fibers is
MUCH GREATER on the bone side than on the cementum side.

1. Transeptal Fibers-keep teeth aligned. Extend interproximally OVER the alveolar bone crest
and insert into cementum of adjacent teeth to form an interdental ligament. May be classified
as a gingival fiber since it has no bony attachment. Have the ability to regenerate after damaged by
disease.

2. Horizontal Fibers-attach to root cementum below the alveolar crest fibers and run
perpendicular (at right angles to the tooth’s long axis) from cementum to alveolar bone. RESIST
LATERAL FORCES.

3. Alveolar Crest Fibers-extends from the cervical root cementum (apical to the junctional
epithelium) to the alveolar bone crest. Function to counterbalance occlusal forces on the more
apical fibers and resist lateral movements. Prevent tooth extrusion.

4. Oblique Fibers-the LARGEST & MOST NUMEROUS FIBERS, running from root cementum’s
middle third in an oblique direction to insert CORONALLY into alveolar bone. RESIST
MASTICATORY FORCES ALONG THE TOOTH’S LONG AXIS (VERTICALLY). 1/3 of
all fibers.

5. Apical Fibers-radiate from cementum around the ROOT APEX to bone to form the base of the
socket or alveolus. Provide INITIAL RESISTANCE to tooth movement in an OCCLUSAL
DIRECTION. Do not occur in incompletely formed roots.

6. Interradicular Fibers-found ONLY BETWEEN ROOTS OF MULTI-ROOTED TEETH

(premolars or molars). Attach from cementum on the root furcation into cementum of the other
roots. HAS NO BONY ATTACHMENT but assists in minor tooth movement.

When the tooth loses its function, the PDL becomes very thin and loses its regular arrangement of fibers.
• PDL is shaped like an HOUR-GLASS, with the narrowest part at the middle of the root.

• PDL occupies the space between cementum and the periodontal surface of alveolar bone.

• Cementum and alveolar bone are the tissues immediately adjacent to the PDL.
 • Epithelial Rests of Malassez-remnants of Hertwig’s epithelial root sheath, found as groups of
epithelial cells in the PDL.

GINGIVAL FIBERS (supracrestal gingival fibers)- C.T. collagen fibers found in the FREE GINGIVA
and are continuous with C.T. fibers of the PDL. Gingival fibers support the marginal gingiva &
interdental papilla, by attaching the gingiva to the teeth and alveolar bone. Gingival fibers (5):
1. Circumferential (circular) fibers-encircle the tooth around the most cervical part of the root and
insert into cementum and lamina propria of the free gingiva and alveolar crest. Resist rotational
forces.

2. Transseptal fibers-extend from tooth-to-tooth, coronal to the alveolar crest and are embedded in
the cementum of adjacent teeth. Not found on the facial aspect, and have no attachment to alveolar
crestal bone. Connects all teeth and maintain integrity of the dental arches. Transseptal fibers
are sometimes classified in principal fibers of PDL.

3. Dentogingival fibers-extend from cementum apical to the epithelial attachment and course
laterally and coronally into the lamina propria of the gingiva.

4. Dentoperiosteal fibers-extend from the cervical cementum over the alveolar crest to the
periosteum of the cortical plates of bone.

5. Alveologingival fibers-insert in crest of alveolar process and spread through the lamina propria
into the free gingiva.

• Gingival Apparatus-describes the gingival fibers and epithelial attachment.

PDL CONTAINS 2 TYPES OF NERVE ENDINGS:

1. free, unmyelinated nerve endings convey pain.
2. encapsulated (myelinated) nerve endings; convey pressure.

PERIODONTAL LIGAMENT: a specialized C.T. that is soft, fibrous, cellular, and vascular. PDL’s
main function is to support the tooth in its socket (alveolar bone). PDL occupies the space between
cementum & alveolar bone.
• PDL becomes very thin and loses the regular arrangement of its fibers when a tooth loses its
function.
• Cementicles-calcified bodies sometimes found lying free within the PDL or fused with cementum.

WIDTH OF PDL relates to the degree of function. PDL normally appears as an unbroken radiolucent line
around the tooth root (it is actually less than 0.25mm thick). PDL is THINNEST about the roots of
embedded teeth and teeth that lost their antagonists (disuse atrophy). PDL is wider during occlusal
trauma. PDL Functions:
1. Physical (support)-attaches tooth to bone via principal fibers and absorbs occlusal forces.
2. Formative-formation of C.T. components by fibroblasts, osteoblasts, and cementoblasts.
3. Resorptive-occurs by C.T. cells (fibroblasts, osteoclasts, and cementoclasts).
4. Nutritive-through blood vessels to supply cementum, bone, and gingiva.
5. Sensory-carried by trigeminal nerve (CN V), proprioceptive and tactile sensitivity (sensation of
 contact between teeth) is imparted through PDL.

Orthodontic Treatment is possible because the PDL continuously responds and changes due to
functional requirements imposed on it by externally applied forces.

DENTOJUNCTIONAL EPITHELIUM-the gingival epithelium facing the tooth, composed of non-

keratinized stratified squamous epithelium. There are 2 types:
1. Sulcular epithelium-line the sulcus. It connect directly with the junctional epithelium.

2. Junctional epithelium-a specialized epithelium surrounding each tooth that starts at the base of
the sulcus. It’s a collar-like band of stratified squamous epithelium firmly attached to the tooth by
hemidesmosomes.
• at its beginning, it is 15-30 cell layers thick, but only a few cell layers thick at its apical
end.
• Junctional epithelium has a basal layer and suprabasal layer.
• In ideal gingival health, the junctional epithelium is located entirely on enamel above the
CEJ.

EPITHELIAL ATTACHMENT-inner layer of cells (specifically the basal lamina and

hemidesmosomes) of the junctional epithelium that forms the actual attachment to the tooth surface.
Formed by reduced enamel epithelium.
Histologically, the best way to distinguish free gingiva vs. epithelial attachment is there are no rete pegs
in the epithelium attachment. FREE GINGIVA HAS RETE PEGS.
• Rete pegs-epithelial projections extending into the gingival C.T.

• Connective tissue papillae-C.T. projections that extend into the overlying epithelium.


TOOTH HISTOLOGY & LIFE CYCLE

FIRST sign of tooth development is seen during the 6th week in the embryo.
1. TOOTH DEVELOPMENT IS INITIATED BY mesenchyme’s inductive influence on the
overlying ectoderm. Early in the 6th week oral epithelium thickenings (U-shaped) DENTAL
LAMINA appear (a derivative of the surface ectoderm). DENTAL LAMINA follow the curves of
the primitive jaws.

2. At certain points on the dental lamina, ectodermal cells proliferate and produce swellings that
become the enamel organ. Inside the depression of the enamel organ, an area of condensed
mesenchyme becomes the dental papilla. Dental sac-capsule-like structure of mesenchyme that
surrounds both the enamel organ and dental papilla Note: enamel organ separates from the
dental lamina AFTER the first layer of dentin is deposited.

REMEMBER: Each tooth is the product of oral epithelium and underlying ectomesenchyme which
interact during tooth development. The oral epithelium grows down into the underlying
ectomesenchyme and forms small areas of condensed mesenchyme that become tooth germs.

TOOTH GERM-composed of the ENAMEL ORGAN, DENTAL SAC, & DENTAL PAPILLA:

ENAMEL ORGAN-formed from oral epithelium and derived from ectoderm. It gives rise to enamel
(ameloblasts) and forms Hertwig’s epithelial root sheath. Enamel organ has 4 distinct layers:
1. outer enamel epithelium (OEE)-outer cellular layer of the enamel organ (very thin) that outlines
the shape of the future developing enamel organ. Helps form Hertwig’s root sheath.

2. inner enamel epithelium (IEE)-innermost cellular layer of the enamel organ (very thin). IEE
cells differentiate into ameloblasts to produce enamel. IEE is essential to initiate dentin
formation after enamel is formed. Helps form Hertwig’s root sheath.

3. stratum intermedium-area lies immediately lateral to the IEE (it is thicker than OEE & IEE).
This layer is essential for enamel formation b/c it prepares nutrients for IEE ameloblasts.

4. stellate reticulum-”central core” area that fills the bulk of the enamel organ. It contains a lot of
intercellular fluid (mucous type fluid rich in albumin) that is lost just before enamel deposition.

AFTER ENAMEL FORMATION is complete, all 4 enamel organ layers unite and form REDUCED
ENAMEL EPITHELIUM which is important in forming the dentogingival junction and attachment
epithelium.
• Dentogingival junction-an area where the enamel and oral epithelium unite as the tooth erupts into
the mouth. This forms the initial junctional epithelium (epithelium attachment), which later
migrates down the tooth to assume its normal position.

• Attachment epithelium-formed by reduced enamel epithelium; joins the gingiva to the tooth.
 When a tooth first erupts into the oral cavity, the attachment epithelium is derived from reduced
enamel epithelium.

INNER & OUTER ENAMEL EPITHELIUM of the enamel organ join in the neck region to form
Hertwig’s epithelial root sheath.

DENTAL SAC-formed from mesenchyme (ectomesenchyme) derived from neural crest cells. It
surrounds developing tooth germ and FORMS cementum (cementoblasts), PDL, & alveolar bone
proper.
• Cementoblasts-cells that form cementum; formed by the inner cells of the dental sac.

DENTAL PAPILLA-formed from mesenchyme (ectomesenchyme) derived from neural crest cells.
Forms dentin and dental pulp. The outer layers of cells (peripheral cells) differentiate into odontoblasts
(dentin-forming cells).
• Peripheral cells-dental papilla cells that form odontoblasts (produce predentin which calcifies
and becomes dentin). The center of the dental papilla forms the dental pulp.

HERTWIG’S EPITHELIAL ROOT SHEATH-molds the shape of the root and stimulates the
differentiation of odontoblasts which produce root dentin. After root dentin is deposited, the cervical
portion of the root sheath breaks down and this new dentin contacts the dental sac. This contact stimulates
dental sac cells to differentiate into cells that produce cementum, PDL, and alveolar bone proper.
• Continuity of Hertwig’s root epithelial root sheath must be broken for cementum to be deposited
during tooth development (cementogenesis).

• Hertwig’s characteristics: forms cells rests (Epithelial Rests of Malassez) in the PDL once
Hertwig’s functions are complete. Contains no stellate reticulum or stratum intermedium.

• INNER & OUTER ENAMEL EPITHELIUM JOIN to form Hertwig’s epithelial root sheath.

HERTIWIGS SHEATH is an epithelial diaphragm derived from inner and outer enamel epithelium
of the enamel organ. After crown formation, the root sheath grown down and shapes the tooth root and
induces the formation of root dentin.
• Uniform growth of Hertwig’s sheath forms a single-rooted tooth, while medial outgrowths or
evaginations of Hertwig’s sheath form multi-rooted teeth. Accessory root canals form by a break
or perforation in the root sheath BEFORE root dentin is deposited.
• After the first root dentin is deposited, cervical portions of Hertwig’s epithelial root sheath
break down, and this new dentin now contacts the dental sac. This communication stimulates
cells to differentiate into cementoblasts (produce cementum) via cementogenesis.

EPITHELIAL RESTS OF MALASSEZ-the structural remnants of Hertwig’s epithelial root sheath.

Found as groups of epithelial cells in the PDL. Some degenerate, other become calcified to form
cementicles. The fate of the epithelial rests of Malassez is that they may undergo calcification and form
into cementicles.

GNARLED ENAMEL-MOST often found IN CUSPS.

REDUCED ENAMEL EPITHELIUM (REE): the thin multi-layered epithelium that covers enamel after
formation but that is mainly lost after tooth eruption (four layers of condensed enamel after enamel
formation). Derived mainly from reduced AMELOBLASTS and STRATUM INTERMEDIUM layers
of the enamel organ, but may include cellular remnants of the stellate reticulum and outer enamel
epithelium. The major remnant of the REE is the JUNCTIONAL EPITHELIUM.

EVENTS IN HISTOGENESIS OF A TOOTH: Tooth Development depends on a series of sequential

cellular interactions between epithelial and mesenchymal components of the tooth germ. Once
ectomesenchyme influences the oral epithelium to grow down into the ectomesenchyme to become a
tooth germ, 5 events occur:

1. Elongation of Inner Enamel Epithelium Cells of the enamel organ. This causes mesenchymal
cells on the periphery of the dental papilla to differentiate into odontoblasts.
2. Differentiation of Odontoblasts (derived from ectomesenchyme)
3. Deposition of the FIRST LAYER OF DENTIN
4. Deposition of the FIRST LAYER OF ENAMEL
5. Deposition of ROOT DENTIN & CEMENTUM

Korff’s Fibers-rope-like grouping of fibers in the periphery of the pulp that help form the dentin matrix.

Tooth Histogenesis-the formation and development of tooth tissues.



TOOTH LIFE CYCLE

1. Initiation (Bud Stage)-initial interaction between oral epithelium and mesenchyme

(ectomesenchyme) forming the dental lamina.

2. Proliferation (Cap Stage)-shape of tooth becomes evident, and the enamel organ is formed.

3. Differentiation (Bell Stage)-final shaping of the tooth. Cells differentiate into specific tissue-
forming cells (ameloblasts, odontoblasts, cementoblasts, and fibroblasts) in the enamel organ.

4. Apposition-cells that were differentiated into specific tissue-forming cells begin to deposit the
specific dental tissues (enamel, dentin, cementum, and pulp).

5. Calcification-mineralization of tissues.

6. Eruption-emergence of the tooth through the gingiva.

7. Attrition-loss of tooth structure due to tooth-to-tooth contact.

TOMES GRANULAR LAYER (Granular Layer of Tomes)-organic matrix produced by
odontoblasts found in the radicular dentin which lies just below cementum. Interglobular dentin differs
from Tomes Granular Layer because it occurs a short distance inside the DEJ and represents uncalcified
areas. Histologically, root dentin is distinguished from crown dentin by Tomes Granular Layer.

 TOOTH TISSUES
PULP FUNCTIONS: MAIN FUNCTION of dental pulp is to FORM DENTIN (FORMATIVE).
1. Formative (main function)-peripheral layer of pulp cells gives rise to the odontoblasts that form
dentin.

2. Nutritive-pulp keeps organic components of the surrounding mineralized tissue supplied with
moisture and nutrients. Very rich blood supply that surrounds the odontoblasts.

3. Sensory-free nerve endings that contact the odontoblasts to sense extremes in temp, pressure, or
trauma to dentin or pulp which are perceived as pain.

4. Protective-responds to external stimuli that may trigger formation of reparative or secondary

dentin.

PULP CAPPING is more successful in PRIMARY TEETH because the apical foramen is larger AND
young pulp contains more odontoblastic cells, is very vascular, less fibrous, and has more tissue fluid
than adult pulp. YOUNG PULP LACKS COLLATERAL CIRCULATION.

As pulp ages, PULP SIZE & NUMBER OF RETICULIN FIBERS DECREASES.

• As pulp ages reticulin fibers decrease (the pulp becomes less cellular and more fibrous). The
size of the pulp also decreases because of continued deposition of dentin.

• As pulp ages, the number of collagen fibers and calcification (pulp stones or denticles) within
the pulp increases.

PULP contains MYELINATED & UNMEYLINATED NERVE FIBERS (afferent and sympathetic).
Sympathetic and afferent fibers are the primary nerves in dental pulp.
1. Myelinated fibers are sensory.
2. Unmyelinated fibers are motor and regulate lumen size of blood vessels.
3. Free nerve ending-the only type of nerve ending found in pulp. It’s a specific pain receptor.
Regardless of the source of stimulation (heat, cold, pressure) the only response is PAIN.
4. Proprioceptors-respond to stimuli regarding movement (found in gingiva, skeletal muscle, PDL,
TMJ) BUT NOT FOUND IN PULP!

Anatomically, PULP is divided into two portions (CORONAL & RADICULAR PULP):
1. Coronal Pulp-located in the pulp chamber and pulp horns (CROWN portion of tooth).

2. Radicular Pulp-located in pulp canals (ROOT portion of tooth). Accessory canals extend from
pulp canals through the root dentin to the PDL.

CENTRAL ZONE (PULP PROPER)-area that contains large nerves and blood vessels, lined
peripherally by a specialized odontogenic area that has 3 layers:
1. Cell-rich zone-contains fibroblasts = the most numerous cell type found in dental pulp.
 2. Cell-free zone (zone of Weil)-rich in capillaries and nerve networks.
3. Odontoblastic layer-contains odontoblasts and lies next to predentin and mature dentin.
Odontoblasts are derived from ectomesenchyme.

DENTAL PULP CELLS: fibroblasts, odontoblasts, histiocytes (macrophages), and lymphocytes.

Diseased pulp contains: plasma cells, PMN’s, monocytes, and eosinophils.


CEMENTUM

CEMENTUM-hard avascular dental tissue covering anatomical roots of teeth formed by

CEMENTOBLASTS of the periodontal ligament. Cementum is formed from the dental sac.

1. ATTACH “PDL PRINCIPAL FIBERS” TO THE TOOTH ROOT (MAIN FUNCTION)

2. Compensates for loss of tooth surface due to occlusal wear by apical deposition of cementum
through life.
3. Protects the root surface from resorption during vertical eruption and tooth movement.
4. Reparative function that allows reattachment of C.T. after periodontal treatment.

2 Types of Cementum:
1. Acellular Cementum (no cells)-predominates on the coronal 2/3 of root, and is thinnest at the
CEJ.

2. Cellular Cementum (cementoblasts, inactive cementocytes, PDL fibroblasts, &

cementoclasts). Occurs more frequently on the apical 1/3 of root. THICKEST to compensate for
attritional wear of occlusal/incisal surfaces and passive tooth eruption.
• On a comparative basis, bone and cellular cementum are similar as both contain cells
in lacunae with canaliculi that extend primarily toward the nutritional source.

Cementum contains 2 types of Collagen Fibers:

1. Sharpey’s Fibers-TERMINAL PORTIONS of the PDL principal fibers embedded in cementum
(run perpendicular to cementum) on one end, and alveolar bone on the other end.

2. Collagen Fibers-within cementum itself running parallel to the cementum surface.

Cementum Characteristics:
• Slightly softer and lighter in color (yellow) than dentin, and is formed by cementoblasts from the
PDL.

• MOST CLOSELY RESEMBLES BONE, except no haversian system or blood vessels

(avascular).

• 45-50% inorganic (hydroxyapatite), 50-55% organic (collagen & protein), 10% water.
Important: Cementum is more organic, has no nerve innervation, and is avascular.

• Cementum is important in orthodontics. It is more resistant to resorption than alveolar bone,

permitting orthodontic movement of teeth without root resorption.

• Histologically, cementum differs from enamel in that it has collagen fibers and cellular
components in the mature tissue. CEMENTOID-peripheral layer of developing, uncalcified
cementum.
• Cementum differs from dentin because it is produced by PDL cells, while dentin is produced by
pulp cells.


DENTIN

DENTIN-specialized avascular and calcified C.T. makes up the bulk of the tooth, extending nearly
the entire tooth length. Dentin is hard, elastic (20% organic collagen, 75% inorganic, 5%
water/minerals). The 20% organic substance is primarily collagen. Dentin is formed by pulp
odontoblasts.

• Dentin is more mineralized than cementum or bone, but less mineralized than enamel. The
mineral phase (inorganic matter) of dentin is composed primarily of hydroxyapatite (calcium &
phosphate) and makes up the bulk of the tooth. Morphologically and chemically, dentin has many
characteristics common with bone.

• Dentin is much softer than enamel, but harder than bone. It is more flexible (lower modulus of
elasticity) than enamel. Its compressive strength is much higher than its tensile strength. It
supports enamel (acts as a cushion for enamel to withstand mastication forces).

• Odontoblast is the main cell type in dentin derived from ectomesenchyme. Unlike enamel which
is acellular, dentin has a cellular component (retained after its formation) by pulp odontoblasts.

• Dentin and pulp are FORMED BY THE DENTAL PAPILLA. Pulp tissue is a loose, highly
vascular, and non-calcified C.T. while dentin is avascular and calcified tissue.

MATURE DENTIN IS PRIMARILY TYPE 1 COLLAGEN!

4 TYPES OF DENTIN:
1. Mantle dentin-dentin right next to the DEJ (most peripheral layer of dentin). FIRST LAYER
OF DENTIN FORMED. The remaining dentin is circumpulpal dentin.

2. Intratubular (Peritubular dentin)-lines each dentinal tubule, and is THE MOST HIGHLY
MINERALIZED PORTION OF DENTIN (greater content of inorganic salts than intertubular
dentin).

3. Intertubular dentin-surrounds peritubular dentin, less mineralized (has lower content of

inorganic salts).

4. Interglobular dentin-imperfectly calcified matrix of dentin situated between the calcified

globules; located near the dentin periphery.

TOMES’ FIBERS (Tomes’ Processes)-odontoblastic processes that occupy dentinal tubules (1 per
odontoblast). A long, slender cytoplasmic extension (Tomes Fiber) formed by each odontoblast of dentin.
• Tomes’ fibers mediate dentin sensitivity in the live tooth. Tomes’ fibers makes dentin a living
tissue with the ability to react to different stimuli and produce secondary, sclerotic, and/or
reparative dentin.
 • Each dentinal tubule contains a TOMES’ FIBER = a long, slender cytoplasmic process of an
odontoblast.

• In the life cycle of an ameloblast, there are cells that contain Tomes’ processes. These cells
are in the SECRETORY STAGE of the ameloblast life cycle.

ODONTOBLASTS-begin dentin formation (dentinogenesis) immediately BEFORE ENAMEL

FORMATION by ameloblasts. Dentinogenesis-begins with odontoblasts start laying down a collagen
matrix (forming dentin) at the DEJ and moving inwards toward the pulp.
• Most recently formed layer of dentin is always adjacent to the pulpal surface. Cells of the inner
enamel epithelium adjacent to this newly formed dentin differentiate into ameloblasts (produce
enamel prisms or rods over the dentin).

• Dentinoenamel junction (DEJ)-interface b/t dentin & enamel; a remnant of the onset of enamel
formation. DEJ is the structure first formed by a tooth germ bud that remains in evidence in
the formed tooth. DEJ is also the area where tooth calcification begins, and DEJ morphology is
determined during the BELL STAGE.

• Odontoblast cell body lies in the pulp cavity.

• Dentinal tubules are s-shaped in the crown due to overcrowding of odontoblasts.

• Ameloblasts-form enamel and have short extensions towards the DEJ = Tomes’ processes.
Ameloblasts are in the secretory stage.

DEAD TRACTS-groups of dead, coagulated cytoplasmic processes of dentinal tubules caused by the
aging process of dentinal tissue and caused by caries, erosion, cavity preparation, or odontoblastic
crowding. DENTIN RESPONSES (4):
1. PRIMARY DENTIN-dentin that forms the initial shape of the tooth, deposited BEFORE
completion of the apical foramen.

2. SECONDARY DENTIN-dentin formed AFTER completion of the apical foramen. Formed at a

slower rate than primary dentin as functional stresses are placed on the tooth. Secondary dentin
is regular, and uniform layer of dentin around the pulp cavity.

3. REPARATIVE DENTIN (TERTIARY)-formed very rapidly in response to irritants (attrition,

abrasion, erosion, moderately advancing caries, and trauma).

4. SCLEROTIC DENTIN-results from AGING & SLOWLY ADVANCING CARIES. Dentin

tubules become calcified and obliterated, which blocks access of irritants to the pulp via the
dentin tubules.

The junction between primary and secondary dentin is characterized by a sharp change in the direction
of dentinal tubules. Dentin tubules are S-shaped in the crown of the tooth due to CROWDING OF
ODONTOBLASTS.


ENAMEL

ENAMEL-(Substantia Adamantina) HARDEST SUBSTANCE IN BODY & RICHEST IN

CALCIUM. Enamel has no nerve supply, but is a good thermal insulator. Enamel is derived from
ECTODERM and is composed of:
• 95% inorganic hydroxyapatite made of calcium & phosphate (fluoride and zinc are minor
inorganic constituents). Due to its high inorganic content, enamel appears optically clear on
histologic section of a tooth.

• Organic protein matrix (1-2%) and 4% water. The organic matrix and water content decrease as
enamel matures, while the inorganic content increases (up to 96% mineral in its mature state).

• Enamel’s organic matrix consists mainly of protein (rich in proline) composed of enamel rods,
or prism sheaths (organic matrix), bound together by a cementing interred substance
(interprismatic substance).

• Cross striations are indicative of an incremental growth pattern. Each rod extends through the
entire thickness of the enamel layer. The oldest enamel in a fully erupted tooth is at the DEJ
underlying a cusp or cingulum.

• DEJ-interface between dentin and enamel; DEJ is the remnant of the onset of enamel
formation.

• Enamel forms more evenly before birth than after birth. Deciduous (primary) teeth, thus are
almost always uniform in appearance, while permanent teeth vary in color and degree of
calcification. Enamel is produced in a rhythmical fashion.


ENAMEL STRUCTURES

ENAMEL ROD (enamel prisms)- fundamental morphological unit of enamel. Formed in increments
by the ameloblast (enamel-forming cell). Each enamel rod traverses uninterrupted through the entire
thickness of enamel.
• 5-12 million rods per crown. Rods increase in diameter (4 up to 8 microns) as they flare out from
the DEJ.

• Enamel rods are aligned perpendicularly to the DEJ (except in cervical regions of permanent
teeth, where they are oriented apically).

• Hunter-Schreger bands-alternating light and dark lines in dental enamel that start at the DEJ
and end before the reach the enamel surface. Hunter-Schreger bands represent areas of enamel
rods cut in cross-section dispersed between areas of rods cut longitudinally.

ENAMEL TUFTS-fan-shaped, hypocalcified structures of enamel rods that originate at the DEJ and
extend into the enamel proper (unknown function) for part of its thickness.

ENAMEL SPINDLES-elongated odontoblastic processes (hair-like) that traverse the DEJ from the
underlying odontoblast. May serve as PAIN RECEPTORS. Enamel spindles are formed by
ODONTOBLASTS.

ENAMEL LAMELLAE-enamel DEFECTS resembling CRACKS or FRACTURES that traverse the

entire crown length from the enamel surface to the DEJ. Lamellae contain mostly organic material and
may provide an area for bacteria decay to enter.
AMELOBLASTS-form enamel and enter their first formative state AFTER the first layer of dentin
forms. Ameloblasts secrete enamel matrix as they retreat away from the DEJ, which then mineralizes.
• Primary Enamel Cuticle (NASMYTH’S MEMBRANE)-a delicate membrane covering the
crown of a newly erupted tooth produced by ameloblasts after enamel rods are formed. The
cuticle membrane is worn away by mastication and cleaning, and replaced by an organic
deposit (PELLICLE) formed by salivary glycoproteins. The enamel pellicle is invaded by
bacteria that form bacterial plaque, which can cause dental caries and periodontal disease if not
removed.

• Unlike dentin, enamel cannot repair itself once destroyed. Ameloblasts degenerates after
forming the primary enamel cuticle (Nasmyth’s membrane).

• ENAMEL CONTAINS INCREMENTAL LINES OF RETZIUS.

ENAMEL FORMATION begins at the future cusp and spreads down the cusp slope. As ameloblasts
retreat in incremental steps, they create an artifact (growth rings) in the enamel (LINES OF
RETZIUS). Lines of Retzius have increased organic content and represent the rhythmic variation in the
calcification of the enamel matrix. Lines of Retzius follow the appositional growth pattern.
 • Neonatal Line-a Line of Retzius in ENAMAL more accentuated and obvious line than others,
marking the transition between ENAMEL formed before birth vs. after birth.

• Lines of Von Ebner (contour lines of Owen)-incremental lines IN DENTIN similar to Lines of
Retzius in enamel. A dentin neonatal line marks the transition between dentin formed before vs.
after birth.

• Imbrication lines of Pickerill- depressions or grooves formed when the growth rings (lines of
Retzius) are incomplete at the enamel surface.

PERIKYMATA-tiny valleys on the TOOTH (CROWN) SURFACE created by the termination of the
lines of Retzius, and travel circumferentially around the crown.

MATURATION OF ENAMEL is characterized by a percentage INCREASE in inorganic content and a

percentage DECREASE in water and organic content.

ORTHODONTIC MOVEMENT OF TEETH: always causes remodeling of alveolar bone proper to

accommodate teeth movement.
• If a tooth is tilted MESIALLY during orthodontics, the CORONAL HALF of the mesial wall
shows resorption due to osteoclastic activity, while the CORONAL HALF of the distal wall
shows deposition due to osteoblastic activity.
 • A similar situation is the alternate loosening and tightening of a deciduous tooth before it is lost
caused by the alternate resorption (cementoclasts, osteoclasts) and apposition (cementoblasts,
osteoblasts) of cementum and bone.

• During active tooth eruption, there is apposition of bone on all alveolar crest surfaces and on all
walls of the bony socket. Permanent teeth move OCCLUSALLY & BUCALLY when erupting.

• In a newly erupted tooth, the junction between tooth surface and the crevicular epithelium
consists of a basal lamina-like structure between enamel and epithelium.

Apical abscesses of MANDIBULAR SECOND & THIRD MOLARS have a marked tendency to
produce cervical spread of infection MOST RAPIDLY.

Attachment of muscles may determine the direction/route that an infection will take, channeling the
infection into certain tissue spaces.

• INFECTIONS OF MANDIBULAR TEETH (Especially 2nd & 3rd molars) perforate the bone
below the buccinator causing swelling of the lower half of the face. The infection spreads
medially from the mandible into the submandibular and masticatory spaces. It pushes the tongue
forward and upward. Further spread cervically may involve the visceral space and lead to edema
of the vocal cords and airway obstruction.

• INFECTIONS OF MAXILLARY TEETH that perforate the bone above the buccinator
attachment causes swelling of the upper half of the face (which eventually spreads to the entire
face).

• LINGUAL SPREAD FROM INFECTED MANDIBULAR BICUSPIDS OR MOLARS is into

the floor of the mouth when the perforation is superior (above) the level of attachment of the
mylohyoid muscle. Below (inferior) to the mylohyoid, infection would drain into the
submandibular space.


REPRODUCTIVE SYSTEM

GONADS-consist of OVARIES in females & TESTIS in males.

1. Ovaries-paired, oval (almond-shaped) organs (glands) located on each side of the uterus in
the lower abdomen. Main Function of Ovaries: produce mature ova (eggs) & female steroid
hormones (estrogen and progesterone).
• Estrogen-stimulates development of female sex organs, breasts, and secondary sexual
characteristics.

• Progesterone-simulates secretion of “uterine milk” by the uterine endometrial glands, and

promotes development of the secretory apparatus of the breasts.

CORPUS LUTEUM-an endocrine body that secretes progesterone; formed in the ovary at the site of
a ruptured ovarian (Graafian) follicle immediately after ovulation. If pregnancy does not occur, corpus
luteum degenerates into a mass of scar tissue (corpus albicans) that eventually disappears. If pregnancy
occurs, the corpus luteum does not degenerate, but persists for several months.

SIZE, SHAPE, & POSITION OF THE OVARIES VARY WITH AGE. Round, smooth, and pink at
birth, ovaries grow larger, flatten, and turn grayish by puberty. During the childbearing years, ovaries are
almond-shape and a rough, pitted surface. After menopause, they shrink and turn white.

Oogonium-cells that form most of the ovarian tissue and serve as a source of oocytes.

Oocyte-a cell in the ovary derived from an oogonium that upon undergoing meiosis, produces an ovum
(a primitive egg in the ovary.

During maturation of an egg, 4 daughter cells are produced; one is the large, fertilizable ovum, the
other 3 are polar bodies (polocytes) = small, rudimentary ova

TESTIS-paired structures suspended from the body of the scrotum in the male. Testis produce
spermatozoa (sperm) and secrete sex hormone testosterone which stimulates growth of the male sex
organs, and promotes development of male secondary sex characteristics.

Interstitial cells of Leydig-lie in the space b/t the seminiferous tubules (in testis) and SECRETES
TESTOSTERONE.
• Testis is a FIRM, MOBILE ORGAN lying within the scrotum. Each testis (right & left)
develops retroperitoneally and descends into the scrotum retroperitoneally.
• Seminiferous tubules of the testis contain SERTOLI CELLS (maintain the blood-testis
barrier).

ROUND LIGAMENT OF UTERUS-a fibromuscular band attached to the uterus on either side in front
of and below the fallopian tube opening. It is found in the INGUINAL CANAL where it passes through
to reach the labia majora.
INGUINAL CANAL-transmits the spermatic cord in males, round ligament of the uterus in females,
& ilioinguinal nerve in both sexes. Its is much smaller in females than males.
• Inguinal canal begins at the deep inguinal ring and extends to the superficial inguinal ring.
• Anterior wall is formed by aponeuroses of the external and internal oblique muscles.

SPERMATIC CORD-a collection of male structures that traverse the inguinal canal and pass to and
from the testes.
• Testis-are suspended from the spermatic cord inside the scrotum and covered with 3 concentric
layers of fascia derived from the layers of the anterior abdominal wall: the internal and
external spermatic fascia, and cremasteric fascia (cremaster muscle and fascia).
SPERMATIC CORD CONTENTS (are associated with the testes): “SEVEN-UP”
1. Ductus (vas) deferens-a cordlike structure that conveys sperm from the epididymis to the
ejaculatory duct. Lined with stereocilia and pseudostratified columnar epithelium (stereocilia).
• ejaculatory duct-a canal formed by the union of the deferent duct (vas deferens) and
excretory of the seminal vesicle. The ejaculatory duct opens into the prostatic urethra.

2. Testicular artery-branch of abdominal aorta that supplies testes and each epididymis.

3. Testicular veins-pampiniform plexus forms testicular veins; drains into the left renal vein on the
left side, and into the inferior vena cava on the right side.

4. Nerves (sympathetic fibers from the renal or aortic sympathetic plexuses) and lymphatic vessels
which empty into the lumbar lymph nodes.

EPIDIDYMIS-tortuous C-shaped, cordlike tube located in the male scrotum lined with
STEREOCILIA. The tube emerges from the tail as the vas deferens, which enters the spermatic cord. It
provides a storage space for spermatozoa and allows them to mature. Epididymis CARRIES SPERM
from the seminiferous tubules of the testis to the vas deferens.
• STEREOCILIA-long, non-motile microvilli that cover free surfaces of some pseudostratified
columnar epithelium which lines the inside of the epididymis. Stereocilia facilitate the passage
of nutrients from the epithelium to the sperm. Stereocilia are also present in ductus (vas)
deferens which is also lined with pseudostratified columnar epithelium.

MALE URETHRA-is longer in males (~8inch long) extending from the neck of the bladder to the
external meatus on the glans penis. The urethra is a passageway for semen and urine.
• Male urethra begins at the bladder, passes through the prostate gland, between the two sheets of
tissue that connect the pubic bones and, finally passes through the urinary meatus of the penis.
• Male urethra is divided into 3 parts (prostatic, membranous, and penile (spongy urethra)-which
receives the ducts of the bulbourethral glands (Cowper’s glands).

ACCESSORY GLANDS produce most semen and include:

1. Seminal vesicles-paired sacs at the base of the bladder.
2. Bulbourethral glands (Cowper’s glands)-paired glands located inferior to the prostate gland.
3. Prostate gland-lies under the bladder and surrounds the urethra. It continually secretes prostatic
fluid called SEMEN-thin, milky alkaline fluid. Corpora amylacea-located in the alveoli of the
prostate gland.
FEMALE URETHRA-1.5inch long extending from the neck of the bladder to an external opening
(urethral meatus) located anterior to the vaginal opening. Female urethra lies directly behind the
symphysis pubis ANTERIOR to the vagina.

MAMMARY GLANDS-lie in the superficial fascia and are MODIFIED SWEAT GLANDS. Most
lymph from the mammary glands goes to lymph nodes in the axilla (armpit).

BREAST-receives arterial blood through branches of the lateral thoracic artery (axillary artery branch)
& internal thoracic arteries. Breasts are supported by suspensory ligaments = Fibrous Cooper’s
ligaments.
• Cooper’s ligaments-strong suspensory ligaments/fibrous processes that run from the dermis of the
skin to the deep layer of superficial fascia through the breast.

• Nipple lies at the level of the 4th intercostals space.

• Breast cancer causes dimpling of the overlying skin and nipple retraction.

Mammary, sweat, lacrimal, and salivary glands contain MYOEPITHELIAL CELLS (STAR-
SHAPED) which are special smooth muscle cells with processes that spiral around the epithelial cells of
these glands. Contraction of myoepithelial cells forces secretion of the glands toward the ducts.


GASTROINTESTINAL SYSTEM

ESOPHAGUS-MUSCULAR TUBE that extends from the pharynx through the mediastinum of the
stomach. Located POSTERIOR to the trachea and starts at C6 vertebrae.
• Pathway: in the thorax, its passes down to the left through the superior and then posterior
mediastinum where it passes through the diaphragm and empties into the CARDIAC STOMACH
through the CARDIAC ORIFICE-opening into the stomach that connects the esophagus to the
stomach.

• Esophagus is divided into 2 parts based on changes in its tunica muscularis (double layer of muscle
tissue):
1. UPPER PORTION contains SKELETAL MUSCLE (voluntary).
2. LOWER PORTION contains SMOOTH MUSCLE (involuntary).

• Esophagus Blood Supply: inferior thyroid and phrenic arteries, descending thoracic aorta
branches, left gastric artery branches.

• Nerve Innervation: receives parasympathetic fibers from esophageal branches of VAGUS

NERVE, and MOTOR FIBERS from RECURRENT LAYRNGEAL BRANCHES OF VAGUS
NERVE.

STOMACH-situated in the upper part of the abdomen, extending from beneath the left coastal margin
region into the epigastric and umbilical regions. Much of the stomach is covered by the lower ribs.
Stomach is connected to the esophagus by the CARDIAC ORIFICE. PYLORIC SPHINCTER-guards
the exit point from the stomach and connects the stomach to join the small intestine.
• 4 MAIN STOMACH REGIONS:
1. Cardia-lies near the junction of the stomach and esophagus.
2. Fundus-enlarged portion above and left of the esophageal opening into the stomach.
3. Body-middle or main portion of stomach.
4. Pyloris-lower portion near the junction of the stomach and duodenum (small intestine).

ABDOMEN (Divided into 9 regions by four imaginary planes):

1. Umbilical-located centrally and surrounds the umbilicus.
2. Lumbar-areas to the right and left of the umbilical region.
3. Epigastric-middle region above the umbilical region (contains most of the stomach).
4. Hypochondriac-regions right and left of the epigastric region. Located below cartilage of the rib
cage.
5. Hypogastric (pubic)-midline region directly below the umbilical region.
6. Iliac (inguinal)-regions on right and left of the hypogastric region,

LESSER & GREATER OMENTA-MESENTARY that connect the stomach to other viscera (liver and
small intestine, respectively)
WINSLOW’S FORAMEN-the epiploic foramen the permits free communication between the lesser
and greater omentum (lesser and greater peritoneal sacs).

PERITONEAL CAVITY-the space between parietal and visceral layers of the peritoneum which is
divided into two parts:

1. GREATER OMENTUM (greater sac)-the MAIN COMPARTMENT of the PERITONEAL

CAVITY that extends from the diaphragm down to the pelvis. It is divided into 3 separate
portions:
1. gastrocolic ligament-connects the stomach to the transverse colon.
2. gastrolienal ligament-connects the stomach to the spleen.
3. gastrophrenic ligament-connects the stomach to the diaphragm. The greater omentum
generally contains lymph nodes and large deposits of fat.

2. LESSER OMENTUM (lesser sac)-smaller and lies BEHIND THE STOMACH. It’s a
periotoneal fold connecting the lesser curvature and first part of the duodenum to the liver. It
covers most of the liver and has two parts:
1. hepatogastric ligament-connects the liver to the stomach.
2. hepatoduodenal ligament-connects the liver to the duodenum.

▪ Common bile duct, hepatic artery, and portal vein pass through the lesser
omentum.

The average capacity of the stomach is 1.0 LITER. Stomach receives blood from all 3 branches of celiac
artery (left & right gastric artery, short gastric, right & left gastroepiploic arteries).

STOMACH MUCOSA-contains many GASTRIC GLANDS in the lamina propria:

1. Parietal (oxyntic) cells-located in stomach fundus and body; SECRETES HCL.
2. Zymogenic (chief) cells-located in stomach fundus and body; SECRETES PEPSIN.
3. Enteroendocrine (argentaffin) cells-present throughout the entire stomach; PRODUCE
GASTRIN & SEROTONIN.

SMALL INTESTINE-the LONGEST ORGAN of the GI tract (6m-20m long) that extends from the
pyloric opening to the ileocecal junction, and is where MOST food digestion and absorption occurs
(it completes food digestion). Small intestine has 3 major regions:
1. DUODENUM-FIRST PART of small intestine (1 foot long), horseshoe-shaped, curves around
the head of the pancreas. Contains Brunner’s Glands in its submucosal that secretes mucus.
• Duodenum is a C-shaped tube surrounding the head of the pancreas and connects the
stomach to jejunum. DUODENUM IS THE SHORTEST BUT WIDEST PART.

• Submucosal glands are usually only located in the duodenum. It is possible to distinguish
histologically between the stomach and the duodenum because of the presence of
submucosal glands in the duodenum only.

• Duodenum is retroperitoneal; receives the common bile duct and pancreatic duct at the
duodenal papilla (a small, rounded elevation in the duodenum wall).
 • Blood Supply: superior pancreaticoduodenal artery (gastroduodenal artery branch) &
inferior pancreaticoduodenal artery (superior mesenteric artery).

• Innervation: preganglionic parasympathetic neurons to the duodenum are in the dorsal

motor nucleus of VAGUS NERVE.

BRUNNER’S GLANDS (duodenal glands)-small, branched, coiled tubular glands deep in the
duodenum submucosa that SECRETE ALKALINE MUCUS TO NEUTRALIZE GASTRIC ACID IN
CHYME. Histologically, one can distinguish the duodenum from the stomach by the presence of
Brunner’s glands.

2. JEJUNUM-middle portion of the small intestine (~8 feet long) that contains valves of Kerckring
(plicae circulares) and more villi for greater absorption.
• thicker muscular wall for more active peristalsis, and a mucosal lining of greater
diameter for absorption.
• Suspended by mesentary

3. ILEUM-terminal portion (12 feet long). It’s the distal portion of the small intestine that extends
from the jejunum to cecum. It contains more mesenteric fat and lymphoid tissue (Peyer’s
patches) to handle waste materials. PREFERRED SITE FOR VITAMIN B12 ABSORPTION.
• Goblet Cells-secrete mucus; abundant in the Ileum.
• Peyer’s patches-groups of lymph nodes that intercept and destroy bacteria before they
are absorbed by the digestive tract.
• complex blood supply & more goblet cells.
• suspended by mesentary

INTESTINAL MUCOSA-secretes food digestion ENZYMES essential that complete the digestion
started by the pancreatic enzymes. Intestinal Mucosa Enzymes:
1. maltase, sucrase, lactase-breaks down disaccharides into monosaccharides.
2. aminopeptidase & dipeptidase-breakdown polypeptides into amino acids.
3. enterokinase-acts on trypsinogen to produce trypsin.

SMALL INTESTINE MUCOSA: contains the following:

1. Plicae circulares (valves of Kerckring)-transverse folds of mucous membrane that increase
surface area of the small intestine. Found in the JEJUNUM.

2. Villi-finger-like projections of mucosa that project into the small intestine lumen. FOUND
THROUGHOUT ENTIRE INTESTINE. Villi are covered by 3 types of epithelial cells:
1. goblet cells-secrete mucus; abundant in ileum.
2. absorptive cells-participate in absorption, simple columnar cells w/ microvilli on their
surface.
3. enteroendocrine cells (argentaffin cells)-secrete enterogastrones (secretin &
cholecystokinin). Abundant in the duodenum.
4. crypts of Lieberkuhn- tubular intestinal glands between the bases of villi that contain
PANETH CELLS that secrete digestive enzymes.
Small intestine joins the large intestine at the ileocecal valve.

LARGE INTESTINE-major function: REMOVES WATER from the material (chyme) entering it by
absorption. Unlike the small intestine, the large intestine DOES NOT SECRETE ENZYMES INTO
ITS LUMEN. Histologically, the LARGE INTESTINE contains:
• Absorptive cells-participate in absorption, simple columnar cells w/ microvilli on their surface.
• Goblet cells-very abundant; secrete mucus.

• Intestinal glands (crypts of Lieberkuhn); contain PANETH CELLS.

• tunica mucosa & submucosa lack villi.

• TENIAE COLI- 3 thick longitudinal bands of fibers that make up the tunica muscularis and run the
entire length of the colon. Teniae are shorter than the large intestine, causing the colon to form
small pouches of HAUSTRA.
Innervation: VAGUS NERVE-supplies parasympathetic (sensory) fibers to ascending and transverse
colons. PELVIC SPLANCHNIC NERVES-innervates descending & sigmoid colon, rectum, and anus.

LARGE INTESTINE extends from the ileocecal valve to the anus. Converts liquid contents of the
ileum into semisolid feces by absorbing fluid and electrolytes. Contains many GOBLET CELLS
(mucous) and some absorptive cells with microvilli. 3 PARTS OF LARGE INTESTINE:
1. Cecum-beginning of large intestine, bag-like structure that receives the ileum. Contains a
vermiform appendix-a narrow, blind tube extending downward from the cecum. It contains a lot of
lymphoid tissue.

2. Colon-consists of ascending colon-shortest part of large intestine that extends upward from the
cecum on the right posterior abdominal wall. Transverse colon-extends across upper abdomen
where it bends downward along the left posterior abdominal wall as the descending colon. Low
in the abdomen, it curves toward the midline as the S-shaped sigmoid colon. Contains
HAUSTRA POUCHES.

3. Rectum-extends from the sigmoid colon to the anus. It is straight without teniae coli which are
present in the rest of the large intestine. Rectum ends as the anal canal (3-4 cm) which opens to the
exterior through the anus. Anal canal is surrounded by the internal and external sphincter muscles
which control expulsion of contents (bowel movements).

LARGE INTESTINE is ¼ the size of the small intestine, but its lumen is wider in diameter than the
small intestine.
• The smooth muscle coat of the large intestine consists of 3 bands = teniae coli that cause the colon
to form pouches (Haustra). The large intestine walls (tunics) LACK VILLI.
• The external surface of the large intestine has small areas of fat-filled peritoneum = epiploic
appendages (not found in small intestine).

LIVER-largest and most active gland in the body. Many liver functions are vital for life. It lies under
the right side of the diaphragm, and is divided into 2 lobes (large right lobe & small left lobe) by the
attachment of the peritoneum of the falciform ligament.
• Falciform ligament-separates the 2 liver lobes and attaches the liver to the anterior
 abdominal wall.

• Coronary ligament-attaches the liver to the undersurface of the diaphragm.

• LOBULE-LIVER’S FUNCTIONAL UNIT that consists of a plate of hepatic cells

(hepatocytes) that encircle a central vein and radiate outward. Separating the hepatocyte
plates from each other are SINUSOIDS (the liver’s capillary system). Liver is the
LEAST likely site of an infarct.

• Liver’s right lobe is further divided into a quadrate lobe & caudate lobe by the
gallbladder, fissure for the ligamentum teres, inferior vena cava, and fissure for the
ligamentum venosum.

• Blood Supply: liver receives blood from HEPATIC ARTERY (supplies liver with
oxygenated blood from the aorta), and HEPATIC PORTAL VEIN (carries digestion
products to the liver for processing). Portal vein blood eventually drains via the 3
hepatic veins into the inferior vena cava, which transports blood to the heart.

• Liver receives autonomic nerve fibers from the CELIAC PLEXUS.

BILE-produces and excreted by LIVER HEPATOCYTES (CELLS)-the most versatile cells in the
body.
1. Bile is secreted by the liver into the common hepatic duct which is attached to the gall bladder
(stores bile). A short cystic duct joins the common hepatic duct to form the common bile duct
which transports bile inferiorly to the duodenum to HELP DIGEST FAT.

2. Kupffer cells-reticuloendothelial macrophages that line liver sinusoids to filter bacteria and small
foreign particles out of the blood. Kupffer cells remove bacteria and toxins that have entered the
blood through the intestinal capillaries. Kupffer cells have definite cytological characteristics such as
clear vacuoles, lysosomes, and granular endoplasmic reticulum (RER). Kupffer cells line liver
sinusoids.

HEPATOCYTES-PRODUCE & EXCRETE BILE, which functions to emulsify fats. IT’S THE MOST
VERSATILE CELL IN THE BODY! Hepatocytes also EXCRETE BILIRUBIN (major end product of
hemoglobin decomposition). Hepatocytes contain many mitochondria and smooth ER, responsible for
conjugation process.

GALL BLADDER-small, pear-shaped muscular sac that lies on ventral (undersurface) of the liver.
It is connected to the ventral surface of the LIVER by the CYSTIC DUCT. It STORES ~30ml of BILE.
Gall bladder receives BILE formed in the liver, concentrates it by absorbing water and salts, and stores
it until delivered to the duodenum to help emulsify fat.
• Blood Supply: receives blood from the CYSTIC ARTERY (right hepatic artery branch).
• Innervation: vagal fibers from the CELIAC PLEXUS.
• Lymph drains into a cystic lymph node, then into the hepatic nodes, and finally into the celiac
nodes.
• NO SUBMUCOSA (unlike the stomach, large, and small intestines).
CHOLECYSTOKININ (CCK)SECRETION-a hormone produced by duodenal mucosa when food
arrives in the duodenum, it stimulates gallbladder contraction and relaxation of ODDI’S SPHINCTER.
CCK is secreted by I-CELLS, while gastrin is secreted by G-CELLS.

• Oddi’s sphincter-a circular muscle that surrounds the ampulla of Vater causing release of bile
into the common bile duct for delivery to the duodenum. Oddi Sphincter remains taut & bile
accumulates in the gallbladder, when digestion is not taking place.


RESPIRATORY SYSTEM

MEDIASTINUM-SPACE between the lungs (interpleural space) in the THORAX. Consists of the
superior mediastinum above the pericardium (heart sac) and three lower divisions: anterior, middle, and
posterior. The mediastinum consists of:
• heart, trachea, esophagus, thymus gland, thoracic duct, thoracic aorta, pulmonary artery & veins,
vena cavae, azygos veins, vagus and phrenic nerves. LUNGS DO NOT LIE IN THE
MEDIASTINUM.

MEDIASTINUM is the region between the pleural sacs, containing the heart and all thoracic viscera
EXECEPT THE LUNGS. The mediastinum is DIVIDED INTO the superior and inferior mediastina.
The inferior mediastinum is further subdivided into the anterior, middle, and posterior mediastina.
1. SUPERIOR MEDIASTINUM-contains the aortic arch with its branches, right and left
brachiocephalic veins, upper half of the superior vena cava, trachea, esophagus, thoracic duct,
thymus gland, phrenic nerves, vagus nerve, cardiac nerve, and left recurrent laryngeal nerve.

2. INFERIOR MEDIASTINUM-region directly below the superior mediastinum, subdivided into

three regions (anterior, middle, and posterior).
• Anterior mediastinum-part of the thymus gland, some lymph nodes, branches of the
internal thoracic artery.
• Middle mediastinum-pericardium and heart, phrenic nerve and its accompanying vessels.
• Posterior mediastinum-descending (thoracic) aorta, thoracic duct, esophagus, azygos
veins, vagus nerves, splanchnic nerves, and many lymph nodes.

RESPIRATORY SYSTEM-consists of nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles,

and lung alveoli. LUNGS ARE THE ESSENTIAL ORGANS OF RESPIRATION. The respiratory
system brings air (oxygen) into the body and removes wastes (carbon dioxide) through BREATHING
(RESPIRATION). The respiratory system also makes vocalization possible.

• Respiratory system has 2 major parts: conducting airways (a branching, tree-like set of hollow
tubes) and alveoli (very thin-walled pouches at the ends of the conducting airways).

NASAL CAVITY-extends from the nostrils (nares) in the front to the choanae (posterior nares) behind. It
is divided into right and left halves by the nasal septum. Each half with a floor, roof, lateral & medial
wall. Nasal Cavity Functions:
• Allows passage of air in and out of the respiratory system.
• Nasal epithelium covering the conchae warms, moistens, and cleanses inhaled air.
• Olfactory epithelium in the upper medial portion of the cavity responds to volatile chemical
particles in reception of odors.
• Voice phonetics as a resonating chamber.
• Receives secretions from paranasal sinuses and lacrimal glands (found in the lacrimal fossa of
frontal bone).
 • Goblet Cells (mucus secreting cells)-form the mucous layer of the respiratory mucous
membrane. Inspired dust particles are removed from the air by the moist, sticky surface of the
mucous membrane. The contaminated mucus is continually being moved backward by the
ciliary action of the columnar epithelium that covers the surface. On reaching the pharynx,
the mucus is swallowed. NASAL CAVITIES ARE LINED BY PSEUDOSTRATIFIED
CILIATED COLUMNAR EPITHELIUM.

• A dentist will use screw-type implants to replace maxillary incisors (teeth 7, 8, 9, 10). If
these implants pass through the bone in this region, the implants will enter the nasal cavity.
PHARYNX (THROAT)-a TUBE that serves as a passageway for the respiratory & digestive tracts
that extends from the mouth and nasal cavities to the larynx. Pharynx has 3 regions (subdivisions):
1. Nasopharynx-lies above the soft palate and is continuous with the nasal passages. It
communicates with the nasal cavities through the nasal choanae. The auditory (Eustachian tubes)
connect the nasopharynx with the middle ear. The soft palate and uvula form the anterior wall
of the nasopharynx.
• tensor veli palatini & levator veli palatini muscles prevent food from entering the
nasopharynx during swallowing.

• Nasopharynx contains pharyngeal tonsils in its posterior wall; also contains eustachian
canal, salpingopharyngeal cord, and pharyngeal recess.

2. Oropharynx-extends from the soft palate to the beginning of the laryngopharynx. It is a food and
air passageway that communicates with the oral cavity through the fauces. Oropharynx receives
food from the mouth and air from the nasopharynx. CONTAINS PALATINE & LINGUAL
TONSILS.

3. Laryngopharynx-extends from the oropharynx above to the larynx and esophagus below. It is a
passageway for food and air. Air entering the laryngopharynx goes to the larynx, while food goes
to the esophagus. Note: Food entering the larynx would be expelled by violent coughing.

LUNGS-pair of respiratory organs that LIE IN THE THORACIC CAVITY & SEPARATED BY THE
MEDIASTINUM. Lungs contain pulmonary vessels and bronchial trees for gaseous exchange.
1. RIGHT LUNG: (3 LOBES-superior, middle, inferior) and 3 secondary (lobar) bronchi.
Contains 10 bronchial segments (tertiary bronchi). Right lung receives one bronchial artery, and
has a slightly LARGER capacity than the left lung.

2. LEFT LUNG: (2 LOBES-superior & inferior) and 2 secondary (lobar) bronchi. Contains 8
bronchial segments (tertiary bronchi). Left lung has a SMALLER VOLUME than the right lung.
• CARDIAC NOTCH-a deep indentation on the SUPERIOR LOBE of left lung. Left
lung receives 2 bronchial arteries.

• Contains a LINGULA-tongue-shaped portion of the left lung’s superior lobe that

corresponds to the middle lobe of the right lung.

• PLEURA (double-layered sac)-ENCLOSES EACH LUNG. One layer is the visceral

pleura, the other layer is the parietal pleura. Between the two layers is the pleural cavity
 (space filled with pleural fluid).

• Bronchial Arteries-descending aorta branches that supply oxygenated blood TO THE

LUNGS and to the capillary plexus of tissues surrounding the secondary bronchus.

EACH LUNG is shaped like a cone, blunt apex, concave base (sits on the diaphragm), convex costal
surface, and a concave mediastinal surface. Hilum-a depression at the middle of the mediastinal surface
in which the bronchi, vessels, and nerves that form the lung root enter and leave the lung. 3 Structures
Form the Lung Root:

1. Bronchus- right and left bronchi arise from the midline trachea and carry air to the lung hilus
during inspiration, and carry air from the lung during expiration.
• Hyaline cartilage is the main support of the wall of the bronchus.

2. Pulmonary arteries (2)-one per lung; they enter the hilus of each lung carrying deoxygenated
blood.

3. Pulmonary veins (4)-a superior & inferior vein for each lung; they leave the hilus of each lung
carrying oxygenated blood to the left atrium.

4. lymph vessels, nerves, and bronchial vessels also form the root of the lung.

RIGHT PRIMARY BRONCHUS (mainstem) is straighter, shorter, and larger than the LEFT primary
bronchus and is in a more direct line with the trachea (important in dental chair if a patient swallows an
object).

CRICOTHYROID SPACE-space below the thyroid eminence (Adam’s apple) of the thyroid cartilage,
and above the arch of the cricoid cartilage. AN EMERGENCY TRACHEOTOMY involves entering the
cricothyroid space. It is most easily made by an incision through the median cricothyroid ligament
which runs from the cricoid cartilage to the thyroid cartilage.
• From an anatomic standpoint, an emergency airway may be established most readily by opening
into the trachea through the median cricothyroid ligament.

TRACHEA-a tube that begins below the cricoid cartilage (C6) of the larynx and ends at the LEVEL OF
STERNAL ANGLE (T5) where it divides at the carina into PRIMARY BRONCHI (right and left
primary or mainstem bronchi).
• Trachea contacts posteriorly with the isthmus of the thyroid gland.

EXCHANGE of oxygen and carbon dioxide between the air and the blood occurs in the lungs.
1. Air enters the mouth or nose and passes into the pharynx, larynx, and trachea.
2. As the trachea passes behind the arch of the aorta, it bifurcates into a right and left primary
(mainstem) bronchus, which leads to each lung.
3. After entering each lung, the two main bronchi branch into the five lobar bronchi (secondary
bronchi). Note: the right main bronchus divides into 3 lobar bronchi, and left main bronchus
divides into 2 lobar bronchi. Each secondary (lobar) bronchus serves one of the 5 lobes of the
two lungs.
EACH LOBAR BRONCHUS enters a lobe in each lung (2 lobes on the left, 3 lobes on the right.
Within its lobe, each of the secondary bronchi (lobar bronchi) branch into tertiary bronchi (segmental
bronchi) that continue to divide deeper in the lungs into tiny bronchioles. Bronchioles subdivide many
times, forming terminal bronchioles. Each terminal bronchioles gives rise to several respiratory
bronchioles. Cartilaginous rings are found in main bronchi.

EACH RESPIRATORY BRONCHIOLE subdivides into several alveolar ducts that end in ALVEOLI
clusters of small, thin-walled air sacs that open into a common chamber = alveolar sacs-forms the
functional unit of the lung.

BRONCHIOLES-tube-like extensions of a bronchus. 2 main divisions of the bronchioles:

1. Terminal bronchioles-pass inspired air from bronchioles to the respiratory bronchioles. Contain
Clara cells.

2. Respiratory bronchioles-allow the exchange of air and waste gases between alveolar ducts and
terminal bronchioles. Respiratory bronchioles are the LAST BRONCHIOLES of the bronchial
tree.

TUBES OF THE BRONCHIAL TREE are lined with a pseudostratified ciliated columnar epithelium
that contains goblet cells that secrete mucus. Toward the end of the bronchial tree (respiratory
bronchioles) the epithelial lining loses its cilia and goblet cells, and changes to cuboidal, finally to
squamous in the narrowest bronchioles.

THIS EPITHELIAL LINING is supported by C.T. and surrounding smooth muscle, and hyaline
cartilage. As the bronchial tree continues to divide, this supportive cartilage is gradually replaced by
smooth muscle. The bronchioles and alveoli both completely lack cartilage. Bronchioles have a lot of
smooth muscle, but alveoli do not have much smooth muscle. The variation of the lumen size of the
bronchioles, which occurs during inspiration and expiration, is primarily due to the presence of smooth
muscle and elastic fibers. Smooth muscle of bronchi & bronchioles are controlled by VAGUS &
SYMPATHETIC NERVOUS SYSTEM.

RESPIRATORY ANATOMY
 ENDOCRINE SYSTEM

The body contains two types of glands (EXOCRINE & ENDOCRINE):

1. EXOCRINE GLANDS-have a DUCT through which their product (sweat, saliva, digestive
enzymes, etc.) is secreted or released. Exocrine glands secrete their products into ducts which
are then carried to target sites. Examples: sweat, salivary, sebaceous, and Von Ebner’s glands.
EXOCRINE GLANDS ARE CLASSIFIED BY:
• Type of Secretion:
1. mucous-secrete water + mucin (e.g. buccal glands, esophagus glands, cardiac and
pyloric glands of stomach).
2. serous-(enzymes): parotid gland, Von Ebner’s gland, pancreas, and uterine glands.
3. mixed (mucous and serous): submandibular and sublingual salivary glands, nasal cavity
glands, paranasal sinuses, nasopharynx, larynx, trachea, and bronchi.

• Mode of Secretion:
1. merocrine-only cell secretory product in membrane secretory granules (e.g. pancreatic
acinar cells).

2. apocrine-secretion of product plus small portion of cytoplasm (e.g. fat droplet

secretion by mammary glands).

3. holocrine-entire cell with secretory product (e.g. sebaceous glands of skin and nose).

• Structure of Duct System:

1. unbranched-simple glands (sweat glands).
2. branched-compound glands (pancreas).

• Shape of Secretory Unit:

1. tubular-cylindrical lumen surrounded by secretory cells (e.g. sweat glands).
2. acinar (alveolar)-dilated sac-like secretory unit (sebaceous and mammary glands).
3. tubuloacinar (tubuloalveolar)-intermediate in shape or having both tubular and alveolar
secretory units (e.g. 3 major salivary glands).

2. ENDOCRINE GLANDS-secrete their products (hormones) into interstitial fluid surrounding the
secretory cells from which they diffuse into capillaries to be carried away by blood. Endocrine
glands constitute the endocrine system and include:
• Pituitary gland, Thyroid gland, Parathyroid gland, Adrenal gland, and Pineal glands.

MAJOR SALIVARY GLANDS (parotid, submandibular, & sublingual) are compound tubuloalveolar
glands that deliver salivary secretions into the mouth by way of large excretory ducts (Stenson’s,
Wharton’s, and numerous small Rivian ducts).
• Parasympathetic innervation controlling salivation originates in cranial nerves VII and IX.
Major Salivary Glands: Parotid (purely serous), Submandibular (submaxillary-mixed with serous
demilunes), & Sublingual Glands (mixed with serous demilunes).
• All major salivary glands are compound tubuloalveolar glands (their ducts branch repeatedly
(compound) and their secretory portions are tubular and composed of small sacs (alveoli or
acini).

• Salivary gland striated ducts are composed of SIMPLE LOW COLUMNAR

EPITHELIUM.

PAROTID GLANDS-LARGEST salivary gland, and is PURELY SEROUS. The parotid glands are
below and just anterior to the ear. It divides into deep and superficial lobes with the stylomandibular
tunnel (encloses facial nerve) being the dividing line. Thus, part of the parotid lies superficial to the
mandibular ramus, and another portion lies deep.
• STENSON’S DUCT-drains the parotid gland. Stenson’s duct pierces the buccinator muscle and
crosses the masseter muscle where it drains into the vestibule of the mouth opposite the
maxillary second molar.

• Innervation: receives parasympathetic secretomotor innervation from glossopharyngeal nerve

(via lesser petrosal nerve), otic ganglion, and auriculotemporal nerve (V3 branch).

• Facial nerve (CN7), retromandibular vein, & external carotid artery LIE INSIDE the parotid
gland. EXTERNAL CAROTID ARTERY and its terminal branches (superficial temporal and
maxillary arteries) within the parotid, supply the parotid.

• If a needle is advanced to far posteriorly during an inferior alveolar block injection, anesthesia
of the mandibular teeth will NOT OCCUR because the needle has entered the PAROTID GLAND.

• As a result of a mandibular block injection, a patient can develop paralysis of the muscles of
 facial expression due to depositing anesthetic solution into the parotid gland.

• Lymphatic drainage of parotid gland is through parotid nodes into deep cervical lymph nodes.

• PAROTID GLAND & GLANDS OF VON EBNER are the only entirely PURE SEROUS
adult salivary glands with no mucous secreting acini or alveoli.

SUBMANDIBULAR GLANDS (submaxillary glands)- large salivary glands located in the space
bound by the two bellies of the digastric muscle and angle of the mandible. A MIXED GLAND of serous
and mucous acini (secretory units are mostly serous, but a few mucous acini with serous demilunes are
present).
• WHARTON’S DUCT (submandibular duct)-passes forward along side of the tongue, below the
mucous membrane of the floor of the mouth. It is crossed by the LINGUAL NERVE and then
lies between the sublingual gland and genioglossus muscle. It opens at the base of the frenulum
of the tongue.

• To expose the submandibular duct by an intraoral approach, one must cut through MUCOUS
MEMBRANE ONLY.

• During its course, Wharton’s duct is closely related to the lingual nerve which eventually
crosses over the duct. This is important b/c if you cut/incise the mucous membranes of the
mouth floor, depending on where the cut is made, one may expose the lingual nerve, Wharton’s
duct, and the sublingual gland.

• Innervation: parasympathetic secretomotor fibers from FACIAL NERVE, which runs in the
chroda tympani and in the lingual nerve (V3 branch), and synapses in the submandibular
ganglion. Note: this is the same as the sublingual glands. Postganglionic sympathetic fibers to
the vessels of the submandibular salivary gland arise from cells in the superior cervical ganglion.

• Blood supply: facial artery (branch of external carotid artery).

SUBLINGUAL GLANDS- SMALLEST SALIVERY GLAND located in the floor of the mouth under
the tongue close to the midline. Mylohyoid muscle supports the individual sublingual glands inferiorly.
Sublingual glands have numerous small ducts (Rivian ducts) that open onto the floor of the mouth.
MIXED GLAND secreting MUCOUS and SEROUS ACINI with SEROUS DEMILUNES.
• Innervation: parasympathetic secretomotor fibers from FACIAL NERVE which runs in the
chorda tympani and in the LINGUAL NERVE (V3 branch), and synapse in the submandibular
ganglion.
• Blood supply: sublingual artery (a lingual artery branch, a branch of the external carotid).

• lymphatic drainage from the sublingual & submandibular glands drain into the submandibular and
deep cervical lymph nodes.
• Bartholin’s ducts-the major sublingual gland duct that drains the sublingual salivary gland and
opens in the sublingual papilla in the floor of the mouth. It also joins the submandibular duct.

SEROUS DEMILUNES (half-moon or crescent shape)-serous cells at the distal end of a mucous
tubuloalveolar secretory unit of the submandibular & sublingual glands. (NOT IN PAROTID GLAND).
 • Serous Demilunes secrete mucus that contain the enzyme lysozyme that degrades bacteria cell
walls. Lysozyme confers antimicrobial activity to mucus.

• The crescents or demilunes of the mucous alveoli of the sublingual gland are composed of
SEROUS CELLS.
MUCOUS CELLS-secrete thin mucus that coats each gland’s respective mucosa with a mucous gel layer
(of mucin) that provides a major shell of protection and lubrication for food transport. Mucous cells
contain large, clear secretory granules that occupy most of the cell, with a flattened, nucleus-
containing, condensed chromatin at the cell base.
• Mucous-secreting cells are found in: submandibular, sublingual, and buccal glands, esophagus
glands, and trachea mucosa.

• Palatine Gland-is a PURE MUCOUS GLAND.

SEROUS CELLS-have a rounded euchromatic nucleus surrounded by rough ER (RER) in the basal third
of the cell, and clearly visible and easily stained secretory granules (ZYMOGEN GRANULES) at the
cell apex. Serous secretions contain ptyalin (an -amylase)-an enzyme for digesting starches.
• PAROTID & VON EBNER GLANDS THE ONLY ADULT PURE SEROUS SALIVARY
GLANDS.

Minor Salivary Glands: located on lips, cheek (purely mucous), tongue (Von Ebner’s glands-pure
serous), and hard palate (in the posterolateral zone).

ADENOMERE-functional unit of SALIVARY GLANDS composed of:

2. intercalated ducts-transport saliva to larger ducts.
3. striated ducts-contain lots of mitochondria, responsible for electrolyte and water transport
during secretion. Simple, low columnar line these ducts.
4. glandular cells-synthesize glycoproteins.

THYMUS GLAND-MAJOR IMMUNE SYSTEM GLAND composed of two soft, pinkish-gray lobes
lying in a bib-like fashion just below the thyroid gland and above the heart.
• Thymus gland is a PRIMARY LYMPHOID ORGAN. The spleen, tonsils, lymph nodes, and
Peyer’s patches are secondary lymphoid organs with 2 lobes surrounded by a thin C.T. layer.

• Thymus is located deep to the sternum in the superior mediastinum.

• Thymus consists of an outer cortex of primarily lymphocytes. Its inner medulla contains
lymphocytes and Hassall’s corpuscles (vestiges of epithelium with unknown function). Thymus is
the master organ in immunogenesis in the young, and monitors the total lymphoid system
throughout life.

• Many NUTRIENTS function as important cofactors in the manufacture, secretion, and function of
thymic hormones (Zinc, vitamin B6, vitamin C) are the most critical cofactors. ZINC is the
most critical mineral involved in thymus gland function and thymus hormone action. Zinc is
involved in every aspect of immunity.

• Thymus has NO afferent lymphatics or lymphatic nodules.

 • Other lymphoid organs originate exclusively from mesenchyme, but the thymus has a double
embryologic origin. The lymphocytes are derived from hematopoietic stem cells (mesenchyme),
while Hassall’s corpuscles (epithelium) are derived from endoderm of the 3rd pharyngeal pouch.

• Thymus blood supply: internal thoracic & inferior thyroid arteries. Innervated by the VAGUS
NERVE (CN X).

Thymus Gland Hormones: Thymopoietin, Thymosin, Thymic Humor Factor (THF), & Thymic
Factor. These hormones are important in normal development of the immune system, and promote
proliferation & maturation of T lymphocytes (WBC responsible for “cell-mediated immunity”).

PITUITARY GLAND (hypophysis cerebri)-”MASTER ENDORINE GLAND VITAL FOR LIFE”

located in the hypophyseal fossa of the SELLA TURCICA (houses the pituitary gland) = “Turkish
Saddle” of the sphenoid bone which lies immediately posterior and superior to the sphenoid sinus and
medial to the cavernous sinus. The hypophysis is situated in the hypophyseal fossa of the SPHENOID
BONE.

Pituitary gland is the master gland because it controls many other glands through the action of tropic
hormones-hormones that affect activity of another endocrine gland. Releasing or inhibiting hormones
produced by the hypothalamus control these hormones of the anterior pituitary.

• Pituitary develops from two sources: an upgrowth from ectoderm of the stomodeum (from the
roof of the mouth) and from a downgrowth from the neuroectoderm of the diencephalons (floor
of brain). THIS DOUBLE ORIGIN is why the pituitary gland is composed of two completely
different tissues. The adenohypophysis (glandular portion) arises from oral ectoderm, and
neurohypophysis (nervous portion) originates from neuroectoderm.

• RATHKE’S POUCH-a diverticulum that arises from the roof of the stomodeum (primitive mouth)
and grows toward the brain during the developmental stage (3 weeks). As this pouch approaches
the developing neurohypophysis, its attachment with the mouth is lost. Rathke’s pouch then forms
the adenohypophysis (anterior) portion of the pituitary.

• Pituitary Gland Blood Supply: superior and inferior hypophyseal arteries (internal carotid
branches). These arteries form the rich vascular portal system. The veins drain into the
intercavernous sinuses.

• Pituitary gland is suspended from or attached to the hypothalamus by the infundibulum-a thin stalk
of tissue divided into the anterior & posterior pituitary; it is where nerve tracts and substances that
act on the pituitary pass. Pituitary Gland has 2 lobes (anterior and posterior):

ANTERIOR PITUITARY (adenohypophysis = glandular lobe)-derived from ORAL ECTODERM

(from roof of stomodeum) formed by pars distalis, pars tuberalis, & pars intermedia (an avascular zone
b/t the anterior and posterior pituitary lobes, but is considered part of the anterior pituitary. Pars
intermedia & pars tuberalis have NO PROVEN FUNCTION in mammals. Pars distalis contains the
Alpha & Beta cells:
 • Alpha Cells (acidophils that stain strong with acid dyes)-composed of somatotropes (secrete
GH) and lactotropes (secrete prolactin).

• Beta Cells (basophils stain strongly with basic dyes)-composed of corticotropes (secrete ACTH),
gonadotropes (secretes FSH & LH), and thyrotropes (secrete TSH).

• HYPOTHALAMO-HYPOPHYSEAL PORTAL TRACT-refers to the way that anterior pituitary

secretions are controlled by hormones = hypothalamic releasing & inhibiting factors secreted
within the hypothalamus, and then conducted to the anterior pituitary through tiny blood vessels
(hypothalamic-hypophyseal portal vessels).

ANTERIOR PITUITARY HORMONES: anterior pituitary gland makes 4 TROPIC HORMONES

(F.L.A.T.) (FSH, LH, ACTH, TSH) and makes 2 “regular hormones” (GH & prolactin):
1. Follicle-Stimulating Hormone (FSH)-initiates ovarian follicle development and secretion of
estrogens in the ovaries of females. In males, FSH stimulates sperm production in the testes
(spermatogenesis).

2. Luteinizing Hormone (LH)-stimulates estrogen secretion by ovarian cells causing ovulation,

and stimulates formation of corpus luteum and progesterone secretion in females. In males, LH
stimulates interstitial cells of the testes to secrete testosterone.

3. Adrenocorticotropic Hormone (ACTH)-controls production & secretion of glucocorticoids by

the adrenal cortex of the adrenal gland.

4. Thyroid-Stimulating Hormone (TSH)-regulates thyroid gland activities, iodine uptake, and

synthesis and release of thyroid hormones.

5. Growth Hormone (somatotropin)-MOST PLENTIFUL anterior pituitary hormone that targets

most body cells (especially BONES & MUSCLES). GH accelerates body growth, stimulates
cellular uptake of amino acids and protein synthesis, and stimulates carbohydrate and fat
breakdown. It is not a tropic hormone. The amount of growth hormone secreted by the anterior
pituitary gland can dramatically effect bone development:

• Acromegaly (gigantism)-tumor AFTER adolescence, excess GH secreted after epiphyseal

cartilages have been replaced by bone (fusion of epiphyses). Whether or not the epiphyses of
the long bones have fused with the shaft determines if gigantism will occur when over-
secretion of GH occurs.

• Pituitary giant-tumor PRIOR to adolescence, excessive GH delays ossification of epiphyseal

cartilage (non-fusion of epiphyses).

• Pituitary dwarf-GH deficiency resulting in early replacement of epiphyseal cartilage by

bone.

6. Prolactin-promotes breast and milk development. Prolactin release is triggered by rising

estrogen levels.
POSTERIOR PITUITARY (neurophypophysis=nervous lobe)-derived from NEUROECTODERM
(from floor of diencephalons) formed by pars nervosa & infundibulum. Consists of 100,000
UNMYELINATE NERVE FIBERS (axons) of secretory nerve cells.
• Hypothalamo-Hypophyseal Nerve Tract-nerve fibers that control posterior pituitary hormone
secretions originating (formed) in the hypothalamus and terminate in the posterior pituitary.

• Pituicytes-the main cell in the POSTERIOR PITUITARY, are found in the Pars Nervosa.

Posterior Pituitary Hormones: 2 hormones are secreted by the posterior pituitary, but made in the
hypothalamus, and then transported to the posterior pituitary through the infundibulum.
1. Antidiuretic Hormone (Vasopressin or ADH)-major hormone that regulates WATER
BALANCE in the body. ADH causes cells in the kidney tubules to RETAIN WATER rather than
adding it to produced urine.
• Diuresis (urine production) so ADH reduces urine volume, increasing water content of
body tissues.

• Hypothalamus osmoreceptors monitor blood volume and concentration of water.

When blood volume is low, the hypothalamus makes ADH and sends it to the posterior
pituitary, where it is released into the blood. ADH production stops when the
hypothalamus senses appropriate blood volume. ADH increases blood volume and water
retention.

2. Oxytocin-stimulates uterus contraction during labor, and EJECTION of breast milk during
suckling.

DIAPHRAGMA SELLAE-small, circular fold of dura mater that forms the roof of the sella turcica
and separates the anterior pituitary from the optic chiasma. Has a small opening in its center that
allows passage of the pituitary gland’s infundibulum.

ADRENAL GLANDS (2 “suprarenal” glands)-flattened, triangular-shaped, ENDOCRINE GLANDS

that rest on the superior poles of each KIDNEY. Adrenal glands have 2 parts:

1. ADRENAL CORTEX (outer portion)-develops from mesoderm. Cortex produces STERIOD

HORMONES (mineralocorticoids, glucocorticoids, and androgenic-like & estrogenic-like
substances). Makes up 80% of the total weight of each adrenal gland. It’s the outer region
surrounded by C.T. capsule. Adrenal cortex has endocrine glands organized into 3 areas:
1. Zona glomerulosa-thin layer of cell clusters under the C.T. capsule. Its cells secrete
mineralocorticoids (primarily ALDOSTERONE) involved with maintenance of electrolyte
and water balance.

2. Zona fasciculate-thick, middle layer with cells arranged in parallel columns that run at right
angles to the surface of the gland. Its cells secrete glucocorticoids (CORTISOL) when
stimulated by ACTH. It also produces small amounts of estrogenic and androgenic-like
substances called gonadocorticoids).

3. Zona reticularis-inner layer of cortex with cells are arranged in a network of interconnecting
 cords. Helps secrete small amounts of cortisol and is responsible for ANDROGEN
PRODUCTION (ex: testosterone, DHEA).

2. ADRENAL MEDULLA-ENDOCRINE GLAND that develops from neuroectoderm (neural

crest cells) that differentiate into medullary cells = chromaffin cells. Adrenal Medulla secretes
hormones NOT ESSENTIAL TO LIFE. ONLY ORGAN THAT RECEIVES
PREGANGLIONIC SYMPATHETIC FIBERS.
• Chromaffin cells-when stimulated produce & release large quantities of EPINEPHRINE
& NOREPINEPHRINE. Sympathetic nerves also stimulate the release of these
hormones, but their effects last longer when the adrenal medulla secretes them. With or
without one or the other (medulla or sympathetic nerves), the adrenal medulla would still
be stimulated (in other words, adrenal medulla functions similar to postganglionic
sympathetic cells).

• Adrenal medulla behaves like neural tissue rather than as a typical endocrine gland.
Adrenal medulla is composed of chromaffin cells arranged around blood vessels that is
modified nervous tissue and functions similar to postganglionic sympathetic cells. It
really does not do anything different than the sympathetic nervous system, but it reinforces
and prolongs its effects.

PANCREAS-a triangular organ that lies across the posterior abdominal wall. It’s a retroperitoneal
organ (except a small part of its tail which lies in the lienorenal ligament). The pancreas head and neck
rests in the curve of the duodenum, and its body stretches horizontally behind the stomach, and its tail
extends to the spleen. PANCREAS IS BOTH AN ENDOCRINE & EXOCRINE GLAND with groups
of special cell scattered among glandular alveoli.
1. Islets of Langerhans (Endocrine Portion)-3 types:
• Alpha cells-secrete glucagon which counters the action of insulin. Increase blood sugar.
• Beta cells-secrete insulin that helps carbohydrate metabolism. Decrease blood sugar.
• Delta cells-secrete somatostatin which inhibits growth hormone.
• *degeneration of the Islets of Langerhans cells lead to DIABETES MELLITUS.

2. Acinar Cells (Exocrine Portion)-produce pancreatic juice that contains trypsinogen and other
digestive enzymes. Trypsinogen is then converted to trypsin in the small intestine.

The primary histologic characteristic of the pancreas is groups of special cell scattered among glandular
alveoli.
PANCREAS DUCTS (2):
1. Duct of Wirsung-MAIN EXCRETORY DUCT OF PANCREAS that begins at the tail, joins the
common bile duct from the gallbladder to form the hepatopancreatic ampulla (ampulla of Vater)
before opening into the duodenum. Ampulla of Vater discharges bile and pancreatic enzymes
into the duodenum.

2. Santorini’s duct-an accessory pancreatic duct that begins in the lower portion of the pancreas
head and opens into the duodenum.

THYROID GLAND-located in the neck, just below the larynx (Adam’s apple). Its two lateral lobes (one
on each side of the trachea) join with the isthmus-a narrow tissue bridge that contracts the trachea to
give the gland its butterfly shape.
• Thyroid gland is a very vascular organ that receives its blood supply from superior and inferior
thyroid arteries. It is innervated from glandular branches of the three cervical ganglia of the
sympathetic trunk. Lymph from the thyroid gland drains laterally into the deep cervical lymph
nodes.

• Thyroid gland consists of FOLLICLES-hollow balls of cells that synthesize thyroglobulin-a

 tyrosine-containing protein stored in the basophilic stained colloid of each thyroid gland follicle
that is the PRECURSOR to hormones triiodothyronine (T3) and thyroxine (T4). Thyroid
hormones T3 & T4 control basal metabolic rate. Metabolically active follicular colloid in the
thyroid follicle stains basophilic (stains strongly with basic stains).

• Thyroid gland is composed of lobules separated by trabeculae and intralobular C.T. Inside each
lobule are numerous thyroid follicles filled with colloid. COLLOID-a protein substance that
stores thyroglobulin, that is produced by the follicular cells. When the PITUITARY GLAND
secretes thyrotropin, colloid becomes active and thyroglobulin is released and taken back into
the follicular cells where they are broken down into thyroid hormone = thyroxine (T4) and
triiodothyronine (T3). This hormone then passes out of the follicular cells and enters the
bloodstream.

• T3 and T4 are produced in the thyroid gland by the combination of iodine + tyrosine. T4 (80%)
and T3 (20%), but T3 (the active form) produces about 4x the hormone strength as T4.

• FOLLICULAR CELLS remain inactive at times of low thyroid hormone need and is activated
when necessary to mobilize colloid found in the thyroid follicle. Metabolically INACTIVE
follicular colloid stains acidophillic (stains strongly with acid stains).

• Thyroid gland produces, stores, and releases CALCITONIN-hormone (secretory product)

produced by thyroid parafollicular cells to maintain blood calcium levels by INHIBITING
calcium release from bone.

Thyroglossal Duct-a narrow canal that connects the thyroid gland to the tongue during development,
but disappears soon after development of the thyroid gland. In adults, the proximal end of the ducts
persists as the foramen cecum of the tongue. In adults, the thyroid glands point of origin is seen as the
foramen cecum.

PARATHYROID GLANDS-there are 4 (superior & inferior pairs) each the size of a pea embedded in
the dorsum behind the thyroid gland. PRODUCE PARATHYROID HORMONE (PTH = parathormone)
which REGULATES CALCIUM & PHOSPHATE METABOLISM. PARATHYROID GLANDS
ARE ESSENTIAL FOR LIFE and contain Oxyphil cells.
• Innervation: postganglionic sympathetic fibers of superior cervical ganglion.

• Blood supply: superior pair receives blood from superior thyroid artery (from external carotid)
and the inferior pair from the inferior thyroid artery (from thyrocervical trunk).

PARATHYROID HORMONE (PTH)-regulates homeostasis of calcium & phosphate by

INCREASING blood calcium level and DECREASING blood phosphate.
• PTH increases the number and activity of OSTEOCLASTS, promotes CALCITROL FORMATION
(active form of vitamin B3), which increases absorption of calcium, magnesium, and phosphorus
from the GI tract.

• Blood calcium level directly controls calcitonin secretion (by thyroid gland) and parathyroid
hormone via negative feedback loops.
 • Parathyroid glands develop from the THIRD & FOURTH PHARYNGEAL POUCHES.

PINEAL GLAND-located in epithalamus of the brain and releases MELATONIN hormone which
regulates sleep-wake cycles, body temperature, and appetite.

MOST ORGANS of the abdominopelvic cavity are suspended from the posterior wall of the cavity
by a double-layered membrane of peritoneum (MESENTERIES). Mesenteries hold the organs in
place and provide a pathway for blood vessels and nerves to reach abdominopelvic cavity organs.
Some structures (kidney, aorta, pancreas, ureters, and adrenal glands) do not hang into the cavity on
mesenteries, but are located OUTSIDE THE CAVITY between the posterior body wall and parietal
peritoneum. Thus, they are retroperitoneal viscera (located BEHIND THE PERITONEUM).

PERITONEUM-the serous membrane lining of the interior of the abdominopelvic cavity consisting of
mesothelium and a thin layer of irregular C.T. Peritoneum organs are covered with visceral
peritoneum, and the outer walls of the cavity are lined with parietal peritoneum. The space between
these two membranes is filled with peritoneal fluid.

RETROPERITONEAL ORGANS/VISCERA: KIDNEYS, AORTA, andrenal glands, pancreas,

ureters, bladder, and ascending and descending colon ARE RETROPERITONEAL (located BEHIND
THE PERITONEUM).

NON-RETROPERITONEAL ORGANS/VISCERA: LIVER, SPLEEN, and STOMACH.



URINARY SYSTEM

URINARY SYSTEM-removes urea waste from the blood by filtration and consists of kidneys (2),
ureters (2) urinary bladder, and urethra. Urinary system filters the blood and maintains the volume
and chemical composition of blood.
• kidneys, ureters, & urinary bladder are located retroperitoneally (behind the peritoneum).
Peritoneum-serous membrane lining abdomen walls and pelvic cavities and enclosing the viscera.
• urinary system is lined with transitional epithelium.
• genital & urinary systems are supplied with parasympathetic fibers from the pelvic splanchnic
nerve.
• Urea is produced when food containing protein (i.e. meat) are broken down in the body.

KIDNEYS-paired organs with extensive vascularity and millions of nephrons in the renal cortex and
renal medulla. Kidneys filter blood & regulate the volume & composition of body fluids during urine
formation.
• Each kidney is divided into an outer dark-brown renal cortex & inner light-brown renal
medulla.
• Kidneys are located retroperitoneally, the right kidney lies slightly lower than the left kidney
due to the large size of the right lobe of the liver.
• Each kidney is surrounded by a fibrous renal capsule and supported by the adipose capsule.
• Renal medulla is composed of renal pyramids separated by renal columns.
• Each kidney has an indentation (HILUS) on its medial border through which ureters, renal vessels,
and nerves enter of leave the kidney.
• Kidneys receive blood supply from the RENAL ARTERY (aorta branch).
• Kidneys remove urea from the blood through nephrons-tiny filtering units. Urea, water, and other
waste substances, form urine as it passes through nephrons and down renal tubules of the kidney.

NEPHRONS-the kidney’s anatomical and functional units. Each nephron consists of a renal corpuscle,
proximal convoluted tubule, a nephron loop (Loop of Henle), and distal convoluted tubule. Nephrons
filter blood to form urine. EACH NEPHRON HAS 2 PARTS:
1. Renal Corpuscle:
• Glomerulus-filters water and dissolved substances from blood plasma.
• Glomerular (Bowman’s capsule)-receives glomerular filtrate from the glomerulus.

2. Collecting Duct (Renal Duct):

• Proximal convoluted tubule-reabsorption of glucose, amino acids, lactic acid, uric acid,
ascorbic acid, phosphate ions, sulfate ions, calcium ions, potassium ions, and sodium ions
by active transport. Most absorption occurs here.
• Descending limb of nephron loop (of Henle)-reabsorption of water by osmosis.
• Ascending limb of nephron loop (of Henle)-reabsorption of chloride ions by active
transport and passive reabsorption of sodium ions. Reabsorption of Cl- & Na+.
• Distal convoluted tubule-reabsorption of sodium ions by active transport, reabsorption of
 water by osmosis; active secretion of hydrogen ions, passive secretion of potassium ions
by electrochemical attraction.

INTERNAL KIDNEY FEATURES:

1. Cortex-outer layer consists of renal tubules.
2. Medulla-inner layer, consists of renal pyramids.
3. Renal columns-found between pyramids. Cortical tissue
4. Renal papilla-apex of pyramids, here the collecting tubules pour into minor calyces (cup-like
structure).
5. Minor calyces-unite to form major calyces, which then unite to form the renal pelvis.

Pressure from blood in the glomerulus causes fluid to filter into Bowman’s capsule. From there, it
flows to the proximal convoluted tubule, loop of Henle, and then to the distal convoluted tubule.
Within this system, water, glucose, and sodium are reabsorbed into the blood. Waste products are
retained and emptied into a collecting tubule, which is discharged to the ureters.

URETERS-long, slender muscular tubes that transport urine from pelvis of the kidney to the base of
the urinary bladder.

URETHRA-muscular tube that carries urine from the renal pelvis to the urinary bladder then to outside
the body. In males the urethra carries spermatic fluid and urine.

URINARY BLADDER-a distensible sac situated in the pelvic cavity posterior to the symphysis pubis.
The bladder is slightly lower in females than males, and serves as a reservoir for urine, which it
receives from the kidneys through the ureters and later discharges through the urethra.

URINE: adults pass 1-½ quarts of urine each day depending on the fluids and foods consumed. The
volume of urine at night is half that formed during the day.
• Normal urine is sterile. It contains fluids, salts, and waste products, but is free of bacteria,
viruses, and fungi.

• Tissues of the bladder are isolated from urine and toxic substances by a coating that discourages
bacteria from attaching and growing on the bladder wall.


LYMPHATIC SYSTEM

LYMPHATIC SYSTEM- MAIN FUNCTION is to COLLECT & TRANSPORT TISSUE FLUIDS from
intracellular spaces in all body tissues back to vein in the blood system. Lymphatic system consists of:
• bone marrow, spleen, thymus gland, lymph nodes, tonsils, appendix, Peyer’s patches, lymph,
and lymphatic vessels. ALL LYMPHATIC ORGANS CONTAIN LYMPHOCYTES.

• Unlike the circulatory system, the lymphatic system DOES NOT HAVE A PUMP to propel
lymph throughout lymph vessels. Instead lymphatic system depends on SKELETAL MUSCLE
CONTRACTIONS, valves in lymphatic vessels (like in veins), breathing, and simple gravity
to move fluid throughout the body.

LYMPHATIC SYSTEM is a part (subset) of the circulatory system comprised of a network of tiny
channels and nodes (lymphatic vessels) that carry clear lymph fluid (filled with lymphocytes and WBCs)
towards the heart (LYMPH FLOWS ONLY IN A SINGLE UPWARD DIRECTION TOWARD THE
HEART). It consists of lymphatic organs, lymphatic vessels, and circulating lymph.

LYMPHATIC SYSTEM FUNCTIONS: helps the venous circulation remove interstitial fluid from
tissues into the blood, absorbs and transports fatty acids and fats from the digestive system, transports
white blood cells (WBCs), to and from lymph nodes into bones, and activates the body’s immune
response by transporting antigen-presenting cells (APCs) like dendritic cells, macrophages, and B-cells.
Lymphatic system plays a major defense in the IMMUNE system.

• Returns tissue fluid to the bloodstream; when this fluid enters lymph capillaries it is called
lymph. Lymph is returned to the venous system via the Thoracic Duct & Right Lymphatic Duct.

• Transports absorbed fats; within small intestine villi, lymph capillaries (Lacteals) transport fat
absorption products away from the GI tract and into the circulatory system.

• Provides immunological defenses against disease; causing agents; lymph filters through lymph
nodes that filter out microorganisms (bacteria) and foreign substances (toxins).

• Lymphatic system consists of lymph nodes, spleen, thymus gland, bone marrow, lymph nodes,
tonsils, appendix, Peyer’s Patches, lymph, and lymphatic vessels. ALL LYMPHATIC ORGANS
CONTAIN LYMPHOCYTES.

• LYMPHATIC CAPILLARIES are MORE PERMEABLE than BLOOD CAPILLARIES (but are
lined by endothelium like blood capillaries). They are present in BONES, TEETH, BONE
MARROW, and the CNS, but NOT in the digestive system.

LYMPH-a transparent, slightly yellow, often opalescent liquid found in the lymphatic vessels. Lymph
contains a liquid portion that resembles blood plasma, WBC (mostly lymphocytes), and a few RBC.
Lymph is absorbed from tissue spaces by lymphatic capillaries (a system of closed tubes) and eventually
returned to the venous circulation by the lymphatic vessels, after it flows through the filtering system
(lymph nodes). Most lymph is returned to the blood at the junction of left internal jugular and
subclavian veins.

LYMPH NODES-small, round specialized dilations (structures) of lymphatic tissue permeated by

lymphatic channels and found periodically along lymph vessels. FUNCTION AS FILTERS by removing
and destroying antigens that circulate in the blood and lymph. Lymph nodes thus contain a lot of
macrophages. Lymphoid tissue in the nodes also produces antibodies and stores lymphocytes. Lymph
nodes occur in clusters (especially in the armpits, groin, lower abdomen, and sides of the neck). Each
lymph node is enclosed in a fibrous capsule with internal trabeculae (C.T.) supporting lymphoid tissue
and lymph sinuses. Lymph node consists of:

1. Outer cortical region-contains separate masses of lymphoid tissue (germinal centers = nodules)
which are source of lymphocytes. Also contains subscapular and cortical sinuses.

2. Inner medullary region-lymphoid tissue is arranged in medullary cords (a source of plasma

cells that secrete antibodies). Also contains medullary sinuses.

LYMPH ENTERS NODES through numerous afferent lymphatic vessels and filters slowly through
the sinuses (first through the cortical, then the medullary sinuses). In the sinuses, lymph is cleansed by
macrophages, lymphocytes, & plasma cells.
1. From medullary sinuses, lymph leaves the node via afferent lymphatic vessels which transport
lymph into efferent collecting vessels which converge into larger vessels = lymph trunks (there
are 5 major lymph trunks in the body).

2. Lymph trunks, in turn, empty into either the thoracic duct or right lymphatic duct. The
thoracic duct drains most of the body and empties its lymph into the junction of the left internal
jugular and left subclavian veins. The right lymphatic duct drains the right upper portion of the
body and empties its lymph into the junction of the right internal jugular and right subclavian
veins.

EFFERENT LYMPHATIC VESSELS- transport lymph out of nodes at a small concave indentation on
the HILUS (node). Afferent lymphatic vessels enter on the convex surface of the node. There are less
efferent vessels than afferent vessels associated with a node.

Note: spleen, thymus, palatine and pharyngeal tonsils do not have numerous afferent vessels entering
them as do lymph nodes.

DEEP CERVICAL LYMPH NODES: form a chain along the course of the internal jugular vein, from
the SKULL TO THE ROOT OF THE NECK. Deep cervical lymph nodes receive lymph from neighboring
structures and from all other regional lymph nodes in the HEAD & NECK. In the HEAD & NECK, ALL
LYMPH ultimately drains into deep cervical lymph nodes. Efferent lymph vessels joint to form the
jugular lymph trunk-vessel that drains into the thoracic duct or right lymphatic duct.

REGIONAL LYMPH NODES:

1. Parotid lymph nodes-receive lymph from a strip of scalp above the parotid salivary gland, from
 the anterior wall of the external auditory meatus, and from lateral parts of the eyelids and middle
ear. Efferent lymph vessels drain into the deep cervical lymph nodes.

2. Submandibular lymph nodes-receive lymph from the front of the scalp, nose, and adjacent
cheek; upper and lower lips (except the center part); paranasal sinuses; maxillary and
mandibular teeth (except mandibular incisors); anterior 2/3 of tongue (except tip); floor of mouth
and vestibule; and gingiva. Efferent lymph vessels drain into the deep cervical lymph nodes.
• Infections or neoplasms that spread by lymphatics from the skin of the angle of the mouth
MOST likely pass to the submandibular lymph nodes.
• Submandibular lymph nodes are the major drainage of the head and neck.
• lymph vessels that drain BOTH DENTAL ARCHES connect directly with the
submandibular lymph nodes.
• THE MAIN DRAINAGE OF THE HEAD & NECK!

3. Submental lymph nodes-receive lymph from the tip of tongue, floor of mouth beneath the tip
of tongue, mandibular incisor teeth and associated gingiva, center part of lower lip, and chin
skin. Efferent lymph vessels drain into the submandibular and deep cervical lymph nodes.
• Submental lymph nodes receive lymphatic vessels from: tip of tongue, middle lower lip,
mandibular lateral and central incisors. Submental lymph nodes DO NOT receive
lymphatic vessels from mandibular molars.

THORACIC DUCT-begins below in the abdomen as a dilated sac (cisterna chili). It drains most of the
body and empties lymph into the junction of the left internal jugular & left subclavian veins (the
beginning of the left brachiocephalic vein).
• Thoracic duct ascends through the aortic opening in the diaphragm, on the right side of the
descending aorta.
• In the posterior mediastinum, the thoracic duct lies POSTERIOR TO THE ESOPHAGUS.
• Thoracic duct contains valves and ascends between the aorta & azygos vein in the thorax.
• Thoracic duct conveys to the blood all lymph from the lower limbs, pelvic cavity, abdominal
cavity, left side of the thorax, and left side of the head, neck, and left arm.

RIGHT LYMPHATIC DUCT-drains the right side of the head and neck, right upper limb, and right side
of the thorax. It empties into the junction of the right internal jugular and right subclavian veins
(which is the beginning of the right brachiocephalic vein).

PHARYNGEAL TONSIL-(non-encapsulated) collection of sub-epithelial lymphatic tissue in the

posterior wall and roof of the nasopharynx. It has no lymph, sinuses, or crypts. It is surrounded partly
by C.T. and epithelium. It is called the ADENOID when enlarged, and are lymphoid aggregations most
associated with pseudostratified columnar ciliated epithelium.

PALATINE TONSILS-two masses of lymphoid tissue, one on each side of the oropharynx. They reach
their maximum size during early childhood, but after puberty diminish considerably in size. Palatine
tonsils contain many crypts, lymphoid follicles, but NO SINUSES, and are partly surrounded by C.T.
and epithelium.

LINGUAL TONSILS-smaller and most numerous; collections of lymphoid follicles on the posterior
portion of the dorsum of the tongue. Each has a single crypt.

PEYER’S PATCHES-similar in structure and function to the TONSILS (they form “intestinal
tonsils”). Located in the small intestine (ileum) to destroy abundant bacteria that would otherwise thrive
in the moist intestines. Peyer’s patches and tonsils are sub-epithelial & non-encapsulated lymphoid
tissues.

SPLEEN-reddish in color and is the LARGEST SINGLE MASS OF LYMPHOID TISSUE IN THE
BODY. It is oval-shaped and LIES IN THE UPPER LEFT HYPOCHONDRIUM of the abdominal
cavity between the stomach and diaphragm. It is composed of white pulp (consists of lymphatic
nodules and lymphocytes) and red pulp (consists of lymphocytes, macrophages, plasma cells, monocytes,
and RBC). Spleen is a site of erythropoiesis (blood formation) in a fetus and infant.
• Spleen is a lymphatic system component that is an important blood reservoir, phagocytosis of
undesirable blood particles, and manufacture of mononuclear leukocytes.

SPLEEN is an oval structure the size of a fist. It is the LARGEST LYMPHOID ORGAN.
• Splenic pulp-the interior of the spleen that contains white and red pulp.
▪ white pulp-contains compact masses of lymphocytes surrounding branches of the splenic
artery.

▪ red pulp-consists of a network of blood-filled sinusoids, lymphocytes, macrophages,

plasma cells, and monocytes (phagocytic WBC).

• SPLEEN FUNCTIONS include acting as a blood reservoir, phagocytosis of undesirable blood

particles, and production of mononuclear leukocytes and initiating an immune response.

• BLOOD ENTERS THE SPLEEN AT THE HILUM through the splenic artery (the largest
branch of the celiac artery). Blood is drained by the splenic vein, which joins the superior
mesenteric vein to form the hepatic portal vein to the liver. NERVES TO THE SPLEEN
accompany the splenic artery and are derived from the CELIAC PLEXUS.

• Spleen DOES NOT DEVELOP from the primitive gut tube like the lungs, liver, pancreas,
gallbladder, stomach, esophagus, & intestines. SPLEEN DEVELOPS FROM
MESENCHYMAL CELLS of the mesentery attached to the primitive stomach.

BONE MARROW-contains stem cells that develop into any of several different cell types
(pluripotent). Some stem cells destined to produce immune system cells are sources for lymphocytes,
whereas others develop into phagocytes. Stem cells that become lymphocytes differentiate to become B
cells (which mature in bone marrow) or T cells (travel to the thymus where they mature).

THYMUS-a bi-lobed lymphoid organ positioned in the superior mediastinum that has no lymphatics. Its
main function is to develop immature T-cells into immunocompetent T-cells. The thymus is large in
newborns, grows until puberty, and regresses in adults. In the adult thymus, blood supply is isolated
from thymus parenchyma (functioning part of the gland as distinguished from the C.T. or stroma). In the
child thymus, the blood supply is not as isolated from the parenchyma.


NERVOUS SYSTEM

NEURAL CREST-a band of neuroectodermal cells that lie dorsolateral to the developing spinal cord,
where they separate into clusters of cells (neural crest cells) that develop into dorsal root ganglion
cells, autonomic ganglion cells, chromaffin cells of adrenal medulla, neurolemma cells (Schwann
cells), integumentary pigment cells (melanocytes), and the meningeal covering of the brain and
spinal cord.

NEURAL TISSUE FORMATION: causes the folding of the embryo during the 4th week of development.
This folding gives the embryo the characteristic C-shaped curvature.
• AT ABOUT THE 18th DAY the neural plate invaginates along its central axis to form the
neural groove with neural folds on each side. During the 4th week the neural fold move together
and fuse, converting the neural plate into a neural tube. Ectoderm of the neuroplate
(neuroectoderm) gives rise to CNS (brain and spinal cord).

• During 4th week of Embryonic Development the neural tube is closed, 4 pairs of brachial arches
are visible externally, characteristic C-shaped curvature of embryo is present due to folding, and
upper and lower limb buds appear.

NERVOUS TISSUE is composed of two classes of cells:

1. NEURONS-the basic structural and functional component of the nervous system that transmits
nerve impulses, and are specialized for reception, integration, and transmission of information.
• Cell body (perikaryon)-located mostly in the CNS as clusters (nucleus); some found in the
peripheral nervous system as groups of ganglion.

• Dendrites-neuronal processes that conduct electrical signals TOWARD cell body from
other cells.

• Axon (nerve fiber)-neuronal processes that conducts electrical signals AWAY from the
cell body toward other cells. If the axon is covered with a fatty substance (myelin), it is a
myelinated fiber. If there is no cover, it is an unmyelinated fiber.

• NEURONS ARE CLASSIFED by structure/shape (by the number of processes extending

from the cell body): unipolar (sensory neurons of the PNS), bipolar (neurons in olfactory
epithelium, retina, and inner ear), or multipolar (most common in CNS). Classified by
function: motor (efferent), sensory (afferent), or mixed (sensory + motor).

2. NERUOGLIA-non-neuronal specialized CNS tissue that performs supportive and other ancillary
functions. Neuroglia are composed of neuroglial cells (glial cells = astrocytes,
oligodendrocytes, microglia, and ependymal cells) found only in CNS and derived from
ectoderm (except microglia, come from mesoderm).
1. Astrocytes-stellate structure with numerous processes that form structural support
between capillaries and CNS neurons.
 2. Oligodendrocytes-similar to astrocytes, but with shorter and fewer processes that form
the myelin sheath in CNS, and guide development of CNS neurons.

3. Microglia-minute cells with few short processes that phagocytize pathogens and
cellular debris within CNS.

4. Ependymal-columnar cells with ciliated free surfaces; they line ventricles and central
canal within the CNS where cerebrospinal fluid (CSF) is circulated by ciliary motion.
NERVOUS SYSTEM is present throughout the body and functions with the endocrine system to
control and integrate the activities of the different parts of the body. FUNCTIONALLY, the nervous system
is divided into:
1. SOMATIC NERVOUS SYSTEM (SNS)- controls voluntary activities
2. AUTONOMIC NERVOUS SYSTEM (ANS)- controls involuntary activities (cardiovascular
system).

NERVOUS SYSTEM’S 2 MAIN STRUCTURAL PARTS:

1. Central Nervous System (CNS)-consists of the brain and spinal cord. It is the control center
that receives SENSORY input from PNS and formulates responses to this input. CNS is
composed of nerve cells and their processes, supported by specialized tissue (NEUROGLIA). A
neuron-is the nerve cell and all of its processes. The interior of the CNS is organized into:

o Gray matter-consists of nerve cells embedded in neuroglia.

o White matter-consists of nerve fibers (axons) embedded in neuroglia.

ENTIRE CNS (brain & spinal cord) is covered by 3 MENINGES:

1. DURA MATER-outermost fused double-layer of dense, strong, fibrous sheet surrounding the
brain composed of a periosteal layer that adheres lightly to the cranium, and meningeal layer
follows the contour of the brain, and contains folds or extensions:
• 2 Vertical folds: Falx cerebri-separates cerebral hemispheres, and contains inferior and
superior sagittal sinuses. Falx cerebelli-separates cerebellar hemispheres (lateral lobes
of cerebellum), and contains the occipital sinus.

• 2 Horizontal folds: Tentorium cerebelli-separates cerebrum and cerebellum. Contains

the straight, transverse, and superior petrosal sinuses. Diaphragma sellae-forms roof
of the sella turcica. Small opening in the center that allows passage of the infundibulum
(stalk) of the pituitary gland.

• Single layer dural sheath surrounds the spinal cord, and is separated in the spinal cord
from the walls of the vertebral canal by the epidural space (contains loose areolar tissue).
It is separated from the arachnoid matter in the brain and spinal cord by subdural space
(contains a thin film of tissue fluid).

2. ARACHNOID MATTER-a delicate, impermeable membrane separated from the pia mater by
subarachnoid space, which is filled with cerebrospinal fluid (CSF), and is the location entered
when performing a spinal tap.
 o SPINAL CORD ENDS in the adult around L1-L2. Dura mater and arachnoid mater
however, continue down to S2 where the arachnoid fuses with filum terminale. Thus a
needle inserted between the spines at L2 and L3 enters the subarachnoid space filled
with CSF, without injuring the spinal cord.

3. PIA MATER-innermost vascular membrane of loose C.T. that closely covers the brain &
spinal cord (CNS). In the brain, pia mater forms the tela choroidea of the roof of the third and
fourth ventricles, and fuses with the ependyma (the epithelial membrane of the ventricles) to form
the choroid plexuses.

PERIPHERAL NERVOUS SYSTEM (PNS)-consists of 12 pairs of cranial nerves and 31 pairs of

spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal). PNS has two divisions:
sensory (afferent) and motor (efferent) components. It also contains ganglia, and sensory receptors.

Functionally, fiber components of peripheral nerves are somatic or visceral, and either sensory (afferent)
or motor (efferent). 4 types of PNS fibers:
1. somatic sensory (afferent) fibers-carry impulses from cutaneous and proprioceptive receptors.
2. visceral sensory (afferent) fibers-carry impulses from the viscera.
3. somatic motor (efferent) fibers-carry impulses to skeletal muscle.
4. visceral motor (efferent) fibers-carry impulses to smooth and cardiac muscle, and glands.
Autonomic nervous system-part of the PNS that controls visceral motor activity.

AUTONOMIC NERVOUS SYSTEM-innervates organs that function under involuntary control.

Effectors that respond to autonomic regulation are: cardiac muscle, smooth muscle, and visceral organs
and glands. Autonomic outflow has two divisions (SYMPATHETIC & PARASYMPATHETIC). Both
divisions have afferent (sensory) and efferent (motor) nerve fibers:

1. SYMPATHETIC DIVISION-prepares the body for intense physical activity in emergencies

(“fight or flight”) through adrenergic effects. Heart rate increases, blood glucose rises, blood
flows to skeletal muscles, pupils dilate, bronchioles dilate, and adrenal medulla releases
EPINEPHRINE & NOREPINEPHRINE into blood.
• Preganglionic sympathetic neurons release ACETYLCHOLINE. Postganglionic
sympathetic neurons release NE (except vessels in skeletal muscles and sweat glands).

2. PARASYMPATHETIC DIVISION-restores and conserves energy (“rest and digest”) to the

sympathetic system. Effects include decreased heart rate accomplished by papillary and
bronchiolar constriction. It does not effect the adrenal medulla. MAINTAINS NORMALITY
OF BODY FUNCTIONS.

PNS Cells that support neurons: Schwann & Satellite cells.

• Satellite cells-small, flattened cells that support PNS ganglia.

• Schwann cells (neurolemmocytes or neurolemma cells)-flattened cells arranged in series around

axons or dendrites that form myelin sheath (fat-like substance) in PNS. Schwann cells form the
myelin sheath around axons of peripheral nerve (PNS) fibers. The point of junction between
two Schwann cells = NODE OF RANVIER. There are no Schwann cells in the CNS
AUTONOMIC NERVOUS SYSTEM ORGANIZATION (ANS): synapses between neurons are made
in the autonomic ganglia. Parasympathetic ganglia are in or near the effector organs. Sympathetic
ganglia are in the paravertebral chain.
• Preganglionic neurons-have their cell bodies in the CNS and synapse in autonomic ganglia.
Preganglionic neurons of the sympathetic system originate in the thoracolumbar region (T1-
L3). Preganglionic neurons of parasympathetic system originate in cranial nerves and in the
craniosacral region (S2-S4).

• Postganglionic neurons of both divisions have cell bodies in the autonomic ganglia and synapse
on effector organs (e.g. heart, blood vessels, sweat glands).

• All preganglionic & postganglionic neurons of the Parasympathetic Nervous System

RELEASE ACETYLCHOLINE.

EACH PART OF THE BRAIN HAS 3 AREAS:

1. Gray matter-cortex, outer surface of cerebral hemispheres, composed primarily of nerve cell
bodies of UNMYELINATED FIBERS.

2. White matter-medulla, inner part composed of MYELINATED NERVE FIBERS (axons).

3. Ventricles (chambers = hollow spaces)-filled with cerebrospinal fluid (CSF). CSF is produced
by ependymal cells that line the ventricles and choroid plexuses. CSF protects the spinal cord
from injury.

CERBREOSPINAL FLUID (CSF)-a clear, colorless fluid formed mainly by the CHOROID
PLEXUSES in the lateral, third, & fourth ventricles of the brain. CSF enters the SUBARACHNOID
SPACE through 3 foramina of the 4th ventricle. These choroids plexuses regulate intraventricular
pressure by secretion and absorption of CSF.
• CSF and bony ligamentous walls of the vertebral canal protect the spinal cord from injury.

BRAIN FORMATION begins with differentiation of the cephalic end of the hollow neural tube. Hollow
spaces persist as ventricles within the brain. There are 4 ventricles that all interconnect:
1. Two lateral ventricles-2 hollow “C”-shaped spaces within the right and left cerebral
hemispheres.

2. Third ventricle-forms a median cavity within the diencephalons (forebrain). Interventricular

foramina (Foramen of Monro)-are oval openings that provide communication b/t third and
lateral ventricles.
• Cerebral Aqueduct-located in the floor of third ventricle; it connects the 3rd and 4th
ventricles. Obstruction of the cerebral aqueduct causes enlargement of LATERALS
and THIRD VENTRICLE (not the 4th ventricle).

3. Fourth ventricle-located in the metencephalon (hindbrain). It contains two openings in its walls
= lateral apertures (foramina of Luschka) and a single opening in its roof (foramen of
Magendie).

HINDBRAIN STRUCTURES:
 1. Metencephalon:
• Cerebellum-small, trilobed, spherical mass of brain tissue connected to the pons,
midbrain, and medulla. Responsible for regulation and coordination of complex
voluntary muscular movement, and maintenance of posture and balance.

• Pons-connects the mesencephalon and medulla oblongata.

• 4th ventricle-a pyramidal cavity located in the hindbrain just ventral to the cerebellum.

2. Myelencephalon:

• Medulla Oblongata-the lowermost portion of the brain that connects pons above to the
spinal cord below. It is continuous with the spinal cord inside foramen magnum.
Responsible for control of respiration, circulation, and other bodily functions. CN
9,10,11, and 12 originate here.

3. Mesencephalon (Midbrain)-a short section of the brain stem between the diencephalons
(forebrain) and pons. It contains the tectum with superior and inferior colliculi, cerebral
aqueduct, substantia nigra, & cerebral peduncles. Initiates body responses to visual and
auditory stimuli.

MNEMONIC: (tel, di, mes, met, my = CN 1,2, 3-4, 5-8, 9-12). Structures cerebrum, thalamus,
midbrain, pons/cerebellum, and medulla are associated with this mnemonic and respective cranial nerves.

FOREBRAIN STRUCTURES:
1. CEREBRUM (telencephalon)-LARGEST PART OF THE BRAIN that controls CONSCIOUS
activities. It consists of two bilaterally symmetrical cerebral hemispheres joined by corpus
callosum (a mass of white matter).

• CEREBRAL CORTEX-extensive outer layer of gray matter of each cerebral

hemispheres responsible for higher brain functions (sensation, thought, reasoning,
memory, and voluntary muscle movement). Sulci (fissures) subdivide the cerebral
cortex (gray matter) into lobes. Cerebral Cortex Lobes include:
1. precentral gyrus of frontal lobe-the primary motor area that controls voluntary
skeletal muscle contractions. Its the cortical area of the brain hemisphere that
controls highly skilled, discrete motor activity of the hand.
2. precentral gyrus of parietal lobe-the primary sensory area that receives sensory
information on temperature, touch, pain, and proprioception. Sensations from the
left face and teeth are interpreted in the right parietal lobe.
3. posterior occipital lobe-primary visual area.
4. temporal lobe (medial surface)-primary olfactory (smell) area.
5. parietal lobe (near bottom of post-central gyrus)-primary taste area. The post-
central gyrus is located in the parietal lobe.
6. temporal lobe (upper margin)-primary auditory (hearing) area.
7. frontal lobe-frontal association area (higher intellectual functions).
8. parietal lobe-somatic association area (integration and interpretation center).
 • Basal nuclei-specialized masses of gray matter in each cerebral hemisphere that help control
skeletal muscle activity.

• Cerebellar cortex is characterized histologically by PURKINJE CELLS.

• Broca Area-frontal brain region (left hemisphere) that contains neurons involved in SPEECH
FUNCTION/ARTICULATION. Connected to Wernicke Area via the arcuate fasciculus.

• Wernicke Area-postrior third of uppter temoporal region (left hemisphere) that contains motor
neurons involved in SPEECH AND LANGUAGE COMPREHENSION CENTER.

2. DIENCEPHALON (Forebrain)-wedge-shaped area between cerebral hemispheres that contains

the THALAMUS (sensory relay station), optic chiasm, infundibulum, hypothalamus
(homeostasis), and 3rd ventricle.

SPINAL CORD- cylindrical, occupies upper 2/3 of the vertebral canal, enveloped by the meninges.
1. Substantia Gelatinosa-the apical part of the posterior horn of the GRAY MATTER of the
spinal cord composed of very small nerve cells. Its gelatinous appearance is due to its very low
content of myelinated nerve fibers. It integrates sensory stimuli that give rise to SENSATIONS
OF HEAT & PAIN.
• It is the GATE CONTROLLER IN THE PAIN GATE THEORY-states a controller
system (substantia gelatinosa) modulates sensory input so there is a selective and
integrative action occurring before impulses reach their first synapse for onward
transmission

2. Substantia Nigra-a pigmented band of gray matter (composed of motor nuclei) in the
mesencephalon (midbrain) that produces DOPAMINE and whose destruction is associated with
PARKINSON’S DISEASE.

3. Substantia Grisea-gray matter of the spinal cord and brain. Composed of nerve cell bodies.

SPINAL CORD (3 MAIN AREAS):

1. Gray matter- “H” shaped, centrally located area consisting of nerve cell bodies & unmyelinated
nerve fibers. Gray commissure-the center of the “H” that connects the two-paired posterior or
dorsal (sensory) horns and anterior or ventral (motor) horns.

2. Central canal-within the gray commissure, filled with cerebrospinal fluid (CSF).

3. White matter-surrounds the gray matter, composed of primarily myelinated axons.

Cell bodies of the somatic MOTOR system lie within the anterior (VENTRAL) horn. Cell bodies of
the somatic SENSORY system lie within the posterior (DORSAL) horn.

SPINAL CORD is cylindrical, occupies the upper 2/3 of the vertebral canal, enveloped by the
meninges. It has a centrally located gray matter and peripherally located white matter (in contrast to
the cerebral hemispheres (brain). The spinal cord ends at L1 (in adult) and L3 (in young child) which is
called the CONUS MEDULLARIS.
At each intervertebral foramen, SPINAL NERVES are formed by the UNION of anterior (ventral)
roots and posterior (dorsal) roots. Thus each spinal nerve has 2 roots that connect them to the spinal
cord (CNS).
• Anterior root-contain axons (fibers) of motor (efferent) neurons (nerve fibers that go to skeletal
muscles); the cell bodies lie in the anterior gray horn of the spinal cord. Consists of efferent nerve
fibers carrying impulses AWAY from the CNS (efferent fibers).

• Posterior root-contain axons of sensory (afferent) neurons whose cell bodies are located
outside the spinal cord in a swelling on the posterior root (posterior ganglion). Consists of
afferent nerve fibers carrying impulses TO the CNS (afferent fibers). Since they convey
information about sensations (pain, touch, temperature), they are sensory fibers.

AFTER the anterior and posterior ROOTS UNITE at each intervertebral foramen, motor and
sensory fibers become MIXED, so a spinal nerve is a mixture of motor and sensory fibers (mixed
nerves).

AFTER EMERGING FROM THE INTERVERTEBRAL FORAMEN each spinal nerve (31) divide
into two branches (rami) that are also mixed nerves:
1. Anterior (ventral) ramus-large, continues anteriorly to supply the muscles and skin over the
anterolateral body wall and all muscles and skin of limbs.
2. Posterior (dorsal) ramus-small, passes posteriorly to supply the skin and muscles of the back.

IN THE CERVICAL BRACHIAL, LUMBAR, & SACRAL REGIONS, the anterior rami of the spinal
nerves unite to form complicated nerve plexuses which then give rise to many other nerves that supply
many structures.

DERMATOME-area/region of skin supplied by a single spinal nerve. Each spinal nerve consists of
afferent (sensory) and efferent (motor) neurons that carry messages to and from particular body regions.

SPINAL CORD TRACTS-columns of WHITE MATTER in the spinal cord that conduct impulses to the
CNS (ascending tracts) and away from the CNS (descending tracts). White matter of the spinal cord
consists mainly of MYELINATED AXONS.

ASCENDING TRACTS (Sensory impulses):

1. Anterior spinothalamic-conducts sensory impulses for TOUCH & PRESSURE.
2. Lateral spinothalamic-conducts PAIN & TEMP impulses.
3. Fasciculus gracillis & fasciculus cuneatus-conducts sensory impulses from skin, muscles,
tendons, and joints; also fine touch localization.
4. Posterior spinocerebellar-conducts sensory impulses from one side of body to same side of
cerebellum for subconscious proprioception.

DESCENDING TRACTS (Motor impulses):

1. Anterior corticospinal-conducts motor impulses from cerebrum to spinal nerves and outward
through anterior horns for coordinated movements.

2. Lateral corticospinal-conducts motor impulses from cerebrum to spinal nerves through anterior
 horns for coordinated movements.

3. Tectospinal-conducts motor impulses to cells of anterior horns and eventually to muscles that
move the head.

4. Rubrospinal tract-conducts motor impulses concerned with muscle tone and posture.

5. Vestibulospinal-conducts motor impulses that regulate body tone and posture (equilibrium) in
response to head movements.

6. Anterior and medial reticulospinal-conducts motor impulses that control muscle tone and sweat
gland activity.

7. Lateral reticulospinal- conducts motor impulses that control muscle tone and sweat gland
activity.


CRANIAL NERVES

OLFACTORY NERVE (CN I)-exits skull through cribiform plate of the ethmoid bone to enter the
olfactory bulb where synapses are made. Provides SENSORY innervation for SMELL.

OPTIC NERVE (CN II)-arises from axons of ganglion cells of the retina that converge at the optic
disk. Optic nerve enters the cranial cavity (exits skull) through the optic foramen (optic canal) of the
sphenoid bone. After forming the optic chiasma, the nerve fibers that arise from the medial (nasal) half of
each retina cross the midline and enter the optic tract of the opposite side; fibers from the lateral
(temporal) half of each retina pass posteriorly in the optic tract of the same side. Optic nerve travels
with the ophthalmic artery through the OPTIC CANAL (FORAMEN).

• OPTIC DISC (OPTIC PAPILLA)-the small BLIND SPOT on the surface of the retina located
3mm to the nasal side of the macula where the optic nerve exits the eye. It’s the only part of the
retina that CONTAINS NO PHOTORECEPTORS (rods or cones). The optic disc consists of
optic nerve fibers and central artery of the retina (the ophthalmic artery branch that pierces
the optic nerve).

• OPTIC CHIASMA-formed when the two optic nerves (one from each eye) exit the eye at the
optic disc and unite in the floor of the diencephalons (meet at the optic chiasma). Here, the
axons from the medial (nasal) half of each retina cross to the opposite side, while axons from the
lateral half of each retina remain on the same side. From the optic chiasma, the axons continue
as the optic tracts. Most ganglion cell axons within the optic tracts then travel to the lateral
geniculate bodies/nucleus (LGN) of the thalamus.
• Optic nerve fibers from the nasal half of the retina cross the midline and enter the optic
tract of the opposite side by way of the optic chiasm.

• OPTIC TRACT-a continuation of the optic nerve that emerges from the optic chiasma and
passes backward to reach the thalamus where most of its fibers terminate and synapse within
the lateral geniculate nuclei (LGN) of the lateral geniculate body. Most of its axons are from
ganglion cells.

OPTIC NERVE (CN II) innervates the RETINA with sensory fibers; conducts impulses of vision to
the thalamus from where the visual pathway terminates in the visual cortex in the occipital lobe of
the brain.

OCULOMOTOR NERVE (CN III)-cranial nerve that exits the skull through superior orbital fissure.
Provides MOTOR FIBERS to most extra-ocular (extrinsic) muscles: medial, superior, and inferior
recti; inferior oblique, & LEVATOR PALPEBRAE SUPERIORIS.
• CN III sends preganglionic parasympathetic fibers to ciliary ganglion. Its postganglionic fibers
leave the ciliary ganglion in the short ciliary nerves to supply sphincter pupillae & ciliary muscle
of lens.
SO4LR6:
• TROCHLEAR NERVE (CN IV)-the SMALLEST and only CRAINIAL NERVE, that emerges
from dorsal (back) aspect of the brainstem, exiting the skull through superior orbital fissure.
It supplies MOTOR function to SUPERIOR OBLIQUE MUSCLE of the eye.

• ABDUCENS NERVE (CN VI)-passes through the cavernous sinus, enters the orbit (exits skull)
through superior orbital fissure, and supplies MOTOR function to LATERAL RECTUS which
abducts the eyeball. A lesion to abducens nerve results in medial strabismus and diplopia
(double vision).

CN III, IV, V1, VI all exit the cranium through SUPERIOR ORBITAL FISSURE and innervate extrinsic
ocular muscles causing movements of the eyeball.

TRIGEMINAL NERVE (CN V)-LARGEST CRANIAL NERVE that is the principal general sensory
nerve to the head (face). It originates on the inferior surface of the pons. CN V has 2 roots (small
motor and large sensory). Emerges from the PONS.
• trigeminal ganglion (semilunar ganglion or gasserian ganglion)-formed when the large
trigeminal sensors expand. It’s a large flattened sensory ganglion lying close to the cavernous
sinus along the median part of the middle cranial fossa, that occupies the trigeminal impression
on the petrous portion of the temporal bone. Cell bodies of sensory neurons are found in the
trigeminal ganglion.
• Trigeminal nerve supplies derivatives of the FIRST BRACHIAL ARCH.

3 DIVISIONS: (ophthalmic, maxillary, & mandibular) ARISE FROM THE TRIGEMINAL

GANGLION and ALL exit the skull through openings in the SPHENOID BONE:

1. Ophthalmic Division (V-1)-enters the orbit (exits skull) through superior orbital fissure
(sphenoid bone) to provide SENSORY innervation to eyeball (cornea), tip of nose, skin of
face above the eye (forehead, scalp). Has 3 branches: lacrimal, frontal, & nasocilliary
nerves.

2. Maxillary Division (V-2)-exits the skull through FORAMEN ROTUNDUM (sphenoid bone)
and provides SENSORY innervation to the midface (below the eye, but above the upper lip),
nasal cavity, palate, paranasal sinuses, and maxillary teeth, skin of cheek and upper lip.

3. Mandibular Division (V-3)-exits the skull through FORAMEN OVALE (sphenoid bone) and
supplies MOTOR innervation to tensor veli palatini, tensor tympani, MUSCLES OF
MASTICATION (temporalis, masseter, medial & lateral pterygoids), and anterior belly of
digastric and mylohyoid muscles.
o Provides SENSORY innervation to skin of the cheek, skin of mandible, lower lip, and
side of the head, TMJ, mandibular teeth, mucous membranes of cheek, floor of
mouth, and anterior part of the tongue.

o LINGUAL NERVE-branch of mandibular division (V3) that supplies (carries) general

sensation from the anterior 2/3 of tongue, mouth floor, & mandibular lingual gingiva.
Submandibular duct has an intimate relationship with the lingual nerve (which crosses the
 duct twice).
▪ Lingual Nerve descends deep to the lateral pterygoid muscle, where it joins
chorda tympani (branch of facial nerve), which conveys preganglionic
parasympathetic fibers to the submandibular ganglion & taste fibers from
the anterior 2/3 of tongue. Important: CUTTING the lingual nerve AFTER
ITS JUNCTION with the chord tympani, results in loss of taste and tactile
sense on the anterior 2/3 of the tongue.

o Nerve to mylohyoid muscle-a branch of mandibular nerve (V3) innervates the

ANTERIOR BELLY OF DIGASTRIC MUSCLE.

TRIGEMINAL NERVE CONTAINS NO PARASYMPATHETIC COMPONENT AT ITS ORIGIN.

TMJ INNERVATION: derived from branches of MANDIBULAR DIVISION (V3) OF
TRIGEMINAL NERVE. The mandibular division is the largest division and only division that carries
MOTOR FIBERS. The main V3 trunk divides into a small anterior division (mainly motor except the
buccal nerve) and a large posterior division (mainly sensory except mylohyoid nerve). The
mandibular division (V3) and its branches lie within the infratemporal fossa:

1. Auriculotemporal Nerve-arises from the posterior division of V3. Provides MAJOR

SENSORY INNERVATION OF TMJ (especially to posterior portion). PAIN is transmitted in
the capsule and periphery of the disk. Auriculotemporal nerve RECIEVES postganglionic
parasympathetic secretomotor fibers from the otic ganglion, which it conveys to the parotid
gland.
• A patient’s pain from the TMJ was referred to the skin over the parotid region and side of
the head. This referral pattern is based on the distribution of the Auriculotemporal nerve.
• Pain, touch, temperature, and proprioceptive modalities for the TMJ are carried by
way of the Auriculotemporal nerve.
• The TMJ capsule is supplied by the auriculotemporal nerve and masseteric nerve.

2. Masseteric Nerve-arises from the anterior division of V3 to innervate the masseter muscle
and carries a few sensory fibers to the anterior portion of the TMJ.

3. Deep Temporal Nerves (anterior, middle, posterior branches)-innervate the temporal muscle
and carry a few fibers to the anterior portion of the TMJ.

Two nuclei (mass of nerve cells) are associated with the TRIGEMINAL NERVE (CN-5):
1. Mesencephalic nucleus of V-a nucleus from which fibers run laterally with the mandibular
 nerve (V3) to innervate muscles of mastication. Cell bodies of proprioceptive nerve fibers of
cranial nerve V carrying information from the periodontal ligament are located here.

2. Spinal nucleus-receives fibers that mediate pain and temperature for the head and neck.

If trigeminal nerve is CUT or DAMAGED, it results in complete loss of sensation in the facial area
on the same side (“ipsilateral”). There would also be difficulty chewing and speaking.

FACIAL NERVE (CN VII)-exits skull through stylomastoid foramen contains SENSORY neurons that
originates in the pons, traverses the facial canal of the temporal bone, and exits the skull through
stylomastoid foramen.

Cell bodies of facial sensory neurons are located in the geniculate ganglia-located in facial canal
(petrous portion of temporal bones). Geniculate Ganglia-contains cell bodies of taste sensory neurons
that innervate taste buds on anterior 2/3 of tongue. Facial nerve also contains parasympathetic
fibers to the sublingual and submandibular salivary glands (via submandibular ganglion) and
lacrimal glands (via pterygopalatine ganglion).

• FACIAL NERVE: provides MOTOR innervation to MUSCLES OF FACIAL EXPRESSION,

SENSORY (taste) to taste buds in anterior 2/3 of tongue, & PARASYMPATHETIC fiber
innervation to salivary glands (sublingual, submandibular), & lacrimal glands.

• FACIAL NERVE is most likely damaged during an operation that involves a right side radical
mastoid operation causing facial distortion where the mouth is drawn upward to the left, the
patient is unable to close his right eye, and saliva tends to accumulate in his right cheek and dribble
out of the corner of the patient’s mouth.

• FACIAL NERVE supplies the mimetic muscles.

• Chorda tympani-branch of the facial nerve that provides taste to anterior 2/3 of tongue. It
emerges from a small canal in the posterior wall of the tympanic cavity (petrotympanic fissure)
and crosses the medial surface of the tympanic membrane. It joins the lingual nerve in the
infratemporal fossa.

• GREATER PETROSAL NERVE-a parasympathetic secretory BRANCH OF FACIAL NERVE

that arises from facial nerve’s geniculate ganglion. Greater Petrosal then passes through the
foramen lacerum, then anteriorly through the pterygoid canal, and synapses with the
pterygopalatine ganglion. Greater Petrosal nerve is the parasympathetic root of the
pterygopalatine ganglion (largest of the 4 parasympathetic ganglion associated with the
cranial nerves). It sends preganglionic parasympathetic fibers to the lacrimal glands, nose, oral
cavity (palate), and uppermost part of the pharynx.

• Facial Nerve (CN VII) muscular branches innervate the DIGASTRIC MUSCLE (POSTERIOR
BELLY digastric muscle) and stylohyoid muscle.

• Cutting the facial nerve just after it exits the stylomastoid foramen causes loss of innervation
to all MUSCLES OF FACIAL EXPRESSION (e.g. Orbicularis oculi).
 • Peripheral (LMN) lesions of CN VII cause IPSILATERAL FLACCID PARALYSIS of ALL
facial musculature (BELLS PALSY).

FACIAL NERVE (CN VII) FUNCTIONS:

1. Motor innervation-muscles of facial expression, posterior belly of digastric muscle, styohyoid
muscle, and stapedius muscle in the middle ear. LMN lesions of the facial nerve cause
ipsilateral (same side) flaccid paralysis of the facial musculature (muscles of facial
expression).

2. Motor parasympathetic-innervation to lacrimal gland for secretion of tears, and salivation

from sublingual and submandibular glands. Note: parasympathetic innervation controlling
salivation also originates in the glossopharyngeal nerve (CN IX).

3. Sensory-proprioception innervation to the same muscles listed for motor innervation.

4. Sensory-taste (sweet sensation) from taste buds on the anterior 2/3 of tongue, floor of mouth, and
palate.

SUPRAHYOID MUSCLES (origin above hyoid bone):

1. Digastric Muscle (posterior belly-innervated by facial nerve VII). Anterior belly innervated by
V3 (nerve to mylohyoid).

2. Mylohyoid muscle (innervated by V3 branch (nerve to mylohyoid). When placing film for a
periapical view of the mandibular molars, the mylohyoid muscle gets in the way if not relaxed.
Function: elevates hyoid bone, base of tongue, and floor of mouth. Sublingual gland is located
superior to mylohyoid muscle.

3. Geniohyoid muscle (innervated by C1 fibers carried by the hypoglossal nerve).

4. Stylohyoid muscle- innervated by facial nerve VII.

INFRAHYOID MUSCLES (origin below hyoid bone): include sternohyoid, sternothyroid, thyrohyoid
& omohyoid all innervated by ANSA CERVICALIS (loop formed by cervical plexus branches C1,C2,
and C3).

VESTIBULOCOCHLEAR NERVE (CN VIII)-exits skull through internal auditory meatus. Provides
SENSORY function to the ear for equilibrium and hearing.

GLOSSOPHARYNGEAL NERVE (IX)-controls contraction of pharynx muscles used in

SWALLOWING (stylopharyngeus) and saliva secretion from the PAROTID GLAND.
• supplies sensory innervation from the posterior 1/3 of the tongue where the taste buds are
located that respond to bitter sensations. It innervates carotid sinus & carotid body to help
regulate blood pressure and respiration.

• Glossopharyngeal nerve innervates STYLOPHARYNGEAL MUSCLE. It is the only muscle

supplied by this nerve. Stylopharyngeus is a landmark for locating the glossopharyngeal nerve
in the neck because as CN IX enters the pharyngeal wall, it curves posteriorly around the lateral
 margin of stylopharyngeus.

Glossopharyngeal Nerve Branches:

1. Tympanic nerve-contributes to tympanic plexus, giving rise to the lesser petrosal nerve which
synapses in the otic ganglion. LESSER PETROSAL NERVE-a parasympathetic secretory
branch of glossopharyngeal nerve that contains secretomotor fibers for the parotid gland. Its
origin is the tympanic nerve (IX branch)
• Important: tympanic nerve and lesser petrosal nerve supply preganglionic
parasympathetic secretomotor fibers to OTIC GANGLION. Here the fibers synapse,
and postganglionic fibers leave the otic ganglion and join auriculotemporal nerve (to
innervate PAROTID GLAND).

2. Carotid nerve-contains sensory fibers from the carotid sinus and carotid body.
3. Nerve to stylopharyngeus muscle.
4. Pharyngeal branches-help form pharyngeal plexus-supplies all palate muscles (except tensor
veli palatini) and all pharynx muscles (except stylopharyngeus muscle).
5. Lingual branch-supplies general sensation and special taste to posterior 1/3 of tongue and
vallate papilla.

GLOSSOPHARYNGEAL NERVE (IX)-a mixed nerve (motor and sensory), that originates from the
anterior surface of the medulla oblongata along with the vagus nerve (CN X) and spinal accessory
nerve (CN XI). It passes laterally in the posterior cranial fossa and exits the skull through jugular
foramen to supply sensory to the pharynx and taste to posterior 1/3 of tongue. Cell bodies of these
sensory neurons are in the superior and inferior ganglia of IX. Glossopharyngeal nerve then descends
through the upper part of the neck along with the internal jugular vein and internal carotid artery to
reach the posterior border of the stylopharyngeus muscle of the pharynx to which it supplies somatic
motor fibers.

• Glossopharyngeal nerve carries primary afferent (sensory) neurons in the GAG RELFEX (it
innervates mucous membranes of the fauces).

• glossopharyngeal nerve provides preganglionic parasympathetic fibers through the otic ganglion to the
parotid gland.

• Superior ganglion of cranial nerve IX-the location of cell bodies of pain fibers in the
glossopharyngeal nerve.

• Functions: motor to STYLOPHARYNGEUS MUSCLE; sensory to POSTERIOR 1/3 TONGUE,

pharynx, middle ear, and carotid sinuses; parasympathetics to PAROTID GLAND.

• Glossopharyngeal is the cranial nerve that supplies derivatives of the THIRD BRANCHIAL
ARCH.

OTIC GANGLION-a small parasympathetic ganglion functionally associated with the

glossopharyngeal nerve. It is situated below the foramen ovale medial to the mandibular nerve (V3).
The tympanic and lesser petrosal branches of the glossopharyngeal nerve supply preganglionic
parasympathetic secretomotor fibers to the otic ganglion. Here the fibers synapse, and the
postganglionic fibers leave the ganglion and join the auriculotemporal nerve which innervates the parotid
gland.

Cranial nerves that also contain preganglionic parasympathetic fibers: occulomotor (ciliary
ganglion), facial (pterygopalatine and submandibular ganglions), and vagus (small terminal ganglia).

CAROTID SHEATH-fibrous C.T. that surrounds the vascular part of the neck, located at the lateral
boundary of the retropharyngeal space at the level of the oropharynx on each side of the neck, deep to the
SCM. It extends from the base of the skull to the first rib and sternum. 4 Major Contents: common
carotid artery, internal carotid artery, internal jugular vein, vagus nerve, and deep cervical lymph
nodes.

VAGUS NERVE (CN X)-the only cranial nerve NOT RESTRICTED TO THE HEAD & NECK
regions. It is THE DOMINANT NERVE TO THE HEART. It originates in the medulla oblongata and
passes through the JUGULAR FORAMEN of the temporal bone. Vagus nerve then descends through
the neck with the carotid arteries and internal jugular vein within the carotid sheath. It passes
through the mediastinum of the thorax, pierces the diaphragm with the esophagus, and terminates in the
abdomen. VAGUS HAS THE MOST EXTENSIVE DISTRIBUTION OF ALL THE CRANIAL
NERVES.
• Vagus nerve is a mixed nerve (sensory and motor) that supplies the pharynx, larynx, trachea,
lungs, heart, and GI tract as far as the left colic flexure (including ascending & transverse
colon). The pelvic splanchnic nerves innervate the descending and sigmoid colons and other
pelvic viscera.
• Vagus nerve contains sensory fibers associated with reflexes, it does not contain pain fibers.
• Vagus nerve mediates TASTE & GENERAL SENSATION FROM THE ROOT OF THE
TONGUE.
• Vagus nerve carries preganglionic fibers to the thoracic and abdominal viscera.
• Vagus nerve supplies parasympathetic fibers to the ASCENDING COLON.
• A few cardiac nerve branches arise from the vagus nerve as it descends through the neck. They end
in the cardiac plexus in the thorax, and innervate the cardiac muscle and great vessels.

VAGUS NERVES lose their identity in the esophageal plexus. At the lower end of the esophagus,
branches of the plexus reunite to form an anterior vagal trunk (anterior gastric nerve), which can be cut
(vagotomy) to reduce gastric secretion.

LEFT VAGUS NERVE-enters the thorax in front of the left subclavian artery and behind the left
brachiocephalic vein. It then crosses the left side of the aortic arch and is itself crossed by the left
phrenic nerve. It passes behind the left lung, forms the pulmonary plexus, and continues to form the
esophageal plexus. It enters the abdomen in front of the esophagus through the esophageal hiatus of the
diaphragm as the anterior vagal trunk (reaches the anterior surface of the stomach).
• Left vagus nerve can be cut on the lower part of the esophagus to reduce gastric secretion
(vagotomy).
• Left vagus forms the anterior vagal trunk at the lower part of the esophagus.
• Left vagus passes in front of the left subclavian artery as it enters the thorax.
• Left vagus contributes to the anterior esophageal plexus.
LEFT VAGUS NERVE gives rise to the LEFT RECURRENT LARYNGEAL NERVE that innervates
the same muscles and mucous membranes as the right recurrent laryngeal, except on the left side. It
crosses the arch of the aorta, hooks around the ligamentum ateriosum, and ascends in the groove between
the trachea and esophagus.

RIGHT VAGUS NERVE crosses the anterior surface of the right subclavian artery and enters the
thorax posterolateral to the brachiocephalic trunk, lateral to the trachea, and medial to the azygos vein. It
passes posterior to the root of the right lung and arch of the azygos vein, contributing to the
pulmonary plexus and esophageal plexus. It enters the abdomen behind the esophagus through the
esophageal hiatus of the diaphragm as the posterior vagal trunk (reaches the posterior surface of the
stomach).

RIGHT VAGUS forms the RIGHT RECURRENT LARYNGEAL NERVE in the neck which hooks
around the first part of the subclavian artery and passes backwards and upwards behind the artery
ascending in the groove between the trachea and esophagus. Right Recurrent Laryngeal Nerve
Innervates:
1. all larynx muscles (except cricothyroid-supplied by external laryngeal branch of superior
laryngeal nerve).
2. mucous membrane of larynx below the vocal folds, and mucous membrane of upper trachea.

Right Recurrent Laryngeal Nerve contacts the thyroid gland, and runs closely with the inferior thyroid
artery.

ACCESSORY NERVE (CN XI)-exits the skull through jugular foramen to supply MOTOR function &
innervation to the TRAPEZIUS & STERNOCLEIDOMASTIOD muscles.

HYPOGLOSSAL NERVE (CN XII)-exits skull through hypoglossal canal medial to the carotid canal
and jugular foramen. It supplies MOTOR function to all INTRINSIC & EXTRINSIC TONGUE
muscles (except palatoglossus = supplied by vagus).
• Hypoglossal nerve passes above the hyoid bone on the lateral surface of the hyoglossus
muscle deep to the mylohyoid muscle. It loops around the occipital artery and passes between the
external carotid artery and internal jugular vein. In the upper part of its course, it is joined by C1
fibers from the cervical plexus.

• Hypoglossal Nerve Lesions: unilateral lesions cause deviation of the protruded tongue
towards the affected side due to lack of genioglossus muscle function on the diseased side.
Injury to hypoglossal nerve eventually produces paralysis & atrophy of the tongue on the
affected side with the tongue deviated to the affected side (ex: a patient who damages the right
hypoglossal nerve will protrude the tongue toward the right side). Dysarthria (inability to
articulate) may also occur. If the genioglossus muscle is paralyzed, the tongue may fall back and
obstruct the oropharyngeal airway risking suffocation.

VAGUS NERVE has two SENSORY GANGLIA:

1. Superior ganglia-lies on vagus nerve within the jugular foramen. Gives off 2 branches:
• Meningeal branch-supplies DURA MATER.
• Auricular branch-supplies auricle, external auditory meatus.
 2. Inferior ganglia-lies on the vagus nerve just below the jugular foramen.
• Pharyngeal nerve-forms pharyngeal plexus, supplies all muscles of the pharynx (except
stylopharyngeus muscle (innervated by glossopharyngeal nerve) and all soft palate
muscles (except tensor veli palatini which is innervated by mandibular branch V3).

• Superior laryngeal nerve-divides at the cricoid cartilage into the internal laryngeal
branch-travels with superior laryngeal artery and pierces the thyrohyoid membrane.
Supplies mucous membranes of the larynx above the vocal folds. External laryngeal
branch-travels with superior thyroid artery and innervates the CRICOTHYROID
MUSCLE.

Important: if both vagus nerves are damaged, DEATH ensues rapidly because vital autonomic
functions stop. But injury to just one vagus nerve causes vocal impairment, difficulty in swallowing,
and other visceral disturbances.

PARASYMPATHETIC GANGLIA:
1. CILIARY GANGLION-located lateral to the optic nerve. Parasympathetic fibers from
occulomotor nerve and its inferior division. Sympathetic fibers from internal carotid plexus.
Chief Distribution is to ciliary muscle and sphincter pupillae (parasympathetic); dilator
pupillae, & tarsal (sympathetic).

2. PTERYGOPALATINE GANGLION-located in the pterygopalatine fossa. Parasympathetic

fibers from facial nerve, greater petrosal nerve, and nerve of pterygoid canal. Sympathetic fibers
from internal carotid plexus. Chief distribution is to lacrimal gland and glands in the palate and
nose.

3. SUBMANDIBULAR GANGLION-located on hyoglossus muscle. Parasympathetic fibers from

facial nerve, chorda tympani, and lingual nerve. Sympathetic fibers from plexus on facial artery.
Chief distribution to submandibular and sublingual salivary glands.

4. OTIC GANGLION-lies in the infratemporal fossa just below foramen ovale between the
mandibular nerve and tensor veli palatini muscle. Parasympathetic fibers from glossopharyngeal
nerve, its tympanic branch, and lesser petrosal nerve. Sympathetic fibers from plexus on the
middle meningeal artery. Chief distribution to PAROTID GLAND.

SYMPATHETIC TRUNKS-two long chains of sympathetic ganglia on either side of the vertebral
column that extend from the base of the skull to the coccyx. The two trunks lie close to the vertebral
column and end below by joining together to form a single ganglion (ganglion impar).

EACH SYMPATHETIC TRUNK CONTAINS SYMPATHETIC GANGLIA located at intervals

alongside the vertebral column. These nerves arise from the 12 thoracic ganglia (T5-T12) and all pass
through the diaphragm. There are 3 cervical, 12 thoracic, 4 lumbar, and 4 sacral sympathetic
ganglia.

3 CERVICAL GANGLIA:
• Superior cervical ganglion-uppermost and largest ganglion that lies between internal carotid
 artery & internal jugular vein. Most fibers that go to the head region have their cell bodies here.

• Middle cervical ganglion-small ganglion located at the level of the cricoid cartilage. It is
related to the loop of the inferior thyroid artery.

• Inferior cervical ganglion-occurs at C-7 vertebral level. Usually fused to the first thoracic
sympathetic ganglion to form a stellate ganglion.

GRAY RAMI-connect the sympathetic trunk to every spinal nerve. White rami-connect sympathetic trunk
only to spinal cord segments (T1-L2). The cell bodies of the visceral efferent fibers in visceral branches
of the sympathetic trunk are located in the interomediolateral cell column (or lateral horn) of the spinal
cord; the cell bodies of visceral afferent fibers are located in the dorsal root ganglia (DRG).

PREGANGLIONIC SYMPATHETIC FIBERS may pass through the sympathetic ganglia on the
thoracic part of the sympathetic trunk without synapsing. These myelinated fibers form 3
SPLANCHNIC NERVES that arise from the THORACIC REGION OF THE SYMPATHETIC
TRUNK:

1. Greater splanchnic nerve-sympathetic fibers from T5-T9 pierce the diaphragm and synapse
with excitor cells in the ganglia of the celiac plexus.

2. Lesser splanchnic nerve- sympathetic fibers from T10-T11 pierce the diaphragm and synapse
with excitor cells in the ganglia of the lower part of the celiac plexus.

3. Least splanchnic nerve- sympathetic fibers from T12 pierce the diaphragm and synapse with
excitor cells in the ganglia of the renal plexus.

Important: Thoracic splanchnic nerves (specifically the greater splanchnic nerve) to the celiac plexus
consist primarily of preganglionic visceral efferent fibers. Postganglionic fibers arise from the
excitor cells in the celiac plexus and are distributed to smooth muscle and glands of viscera.
BRANCHIAL ARCHES (pharyngeal pouches):
1. 1st Branchial Arch: gives rise to muscles of mastication, mylohyoid and anterior belly of
digastric, tensor tympani, and tensor veli palatini. Innervated by TRIGEMINAL NERVE (CN
V).

2. 2nd Branchial Arch: gives rise to muscles of facial expression, stapedius, stylohyoid, and
posterior belly of digastric. Innervated by FACIAL NERVE (CN VII).
 3. 3rd Branchial Arch: gives rise to stylopharyngeus. Innervated by GLOSSOPHARYNGEAL
NERVE (IX).

4. 4th & 6th Branchial Arches: gives rise to cricothyroid, levator veli palatini, constrictors of
pharynx, and intrinsic muscles of larynx. Innervated by EXTERNAL & RECURRENT
LARYNGEAL BRANCHES OF VAGUS (X).

Trigeminal, Facial, Glossopharyngeal, & Vagus nerves are BRANCHIOMERIC (NONSOMITIC) IN

ORIGIN because they originate from BRANCHIAL ARCHES.

4 MAIN NERVE PLEXUSES-formed by intermixing of the ventral rami of the spinal nerves:
1. Cervical Plexus (C1-C4)-positioned deep on the side of the neck, lateral to the first 4 cervical
vertebrae. Cervical Plexus sends out numerous cutaneous, muscular, and communication
branches to the neck, shoulder, and chest.
• motor nerves that supply most of the infrahyoid muscles are branches of ansa cervicalis
(loop formed by C1,C2,C3). Cervical nerves C1-C4 contribute motor fibers to the
cervical plexus.
• Phrenic nerve-an important branch of each cervical plexus that supplies the DIAPHRAGM.
• Supraclavicular nerve branches of the cervical plexus innervate skin over the shoulder.
• Transverse cervical nerve branch provides sensory innervation to the anterior and lateral
parts of the neck.

2. Brachial Plexus (C5-C8, T1)-formed in the posterior triangle of the neck, it extends into the
axilla (armpit), supplying nerves to the upper limbs. Has 3 cords (trunks):
• Posterior cord-gives rise to axillary and radial nerve branches.
• Lateral cord-forms musculocutaneous nerve.
• Medial cord-forms the ulnar nerve
• Median nerve forms its two roots (medial and lateral) from the medial and lateral cords.
RADIAL NERVE is MOST often injured when the humerus is fractured.

• Brachial plexus roots are derived from the ventral rami of spinal nerves C5 –T1.

3. Lumbar Plexus (L1-L4)-formed in the psoas muscle, it supplies lower abdomen and parts of
lower limbs. Main branches: femoral and obturator nerves.

4. Sacral plexus (L4, L5, S1-S4)-lies in the posterior pelvic wall in front of the piriformis muscle.
It supplies the lower back, pelvis, parts of the thigh, leg, and foot. Main branches: SCIATIC
(LARGEST NERVE IN BODY), gluteal, and pelvic splanchnic nerves.

DENTAL PULP INNERVATION: pulp contains BOTH myelinated & unmyelinated nerve fibers.
Pulp consists of a loose C.T. Its main components are thin collagen fibers arranged asymmetrically
plus a ground substance containing glycosaminoglycans.
• Pulp is highly innervated & vascularized tissue, with numerous fibroblasts.
• Odontoblasts-surround pulp and separate it from the dentin.
• Pain originates in the pulp due to free nerve endings contacting odontoblastic cells.
FREE NERVE ENDING-THE ONLY NERVE ENDING FOUND IN PULP. It’s a specific receptor
of pain. Regardless of the source of stimulation (heat, cold, pressure), THE ONLY RESPONSE IS
PAIN.

PRINCIPAL NERVES FOUND IN PULP: SYMPATHETIC & SENSORY (AFFERENT) FIBERS:

Sensory (afferent) fibers transmit pain, temperature, touch, and proprioception from the body to CNS.

 FORAMEN
SUPERIOR ORBITAL FISSURE-located between lesser and greater wings of the sphenoid bone, and
transmits the following nerves and vessels: (CN 3, 4, V1, 6)
1. Ophthalmic nerve (V1) and ophthalmic veins
2. Abducens nerve (CN VI)
3. Occulomotor nerve (CN III)
4. Trochlear nerve (CN IV)

FORAMEN:
1. Mandibular Foramen-located on the mandible. Contains inferior alveolar nerve, artery, and vein.
2. Petrotympanic Foramen-located on the temporal bone. Contains chorda tympani, anterior
tympanic artery.
3. Lacerum-located on temporal & sphenoid bones. Contains internal carotid artery, greater & deep
petrosal nerves.
4. Supraorbital foramen-located on the frontal bone. Contains the supraorbital nerve, artery, and
vein.
5. Infraorbital foramen-located on sphenoid & maxilla. Contains infraorbital nerve, artery, and
vein.
6. Stylomastoid foramen-located on the temporal bone. Contains the facial nerve (CN VII).
7. Incisive foramen-located on the maxilla. Contains the nasopalatine nerve.

MANDIBULAR FORAMEN-in relation to the occlusal plane of the mandibular molars, the mandibular
foramen is above the occlusal plane and posterior to the molars. It is located on the medial surface
of the ramus of the mandible just below the LINGULA, midway between the anterior and posterior
borders of the ramus. The foramen leads into the mandibular canal, which opens on the lateral surface
of the body of the mandible at the mental foramen. The incisive canal is a continuation forward of the
mandibular canal beyond the mental foramen and below the incisor teeth.
• LINGULA-a protection of bone on the mandible that serves as an attachment for the
Sphenomandibular ligament. The sphenomandibular ligament is MOST often damaged when
giving an inferior alveolar nerve block.

• INFERIOR ALVEOLAR nerve (branch of V3), artery, and vein all travel through the
mandibular foramen.

A severe blow to the head that fractures the optic canal would injure the optic nerve (CN II) and
ophthalmic artery as these structures travel through the optic canal.

• Cribiform plate (alveolar bone proper) perforations-openings the ETHMOID BONE of the skull
that contain olfactory nerves (CN I). Cribiform plate usually consists of bundle bone and lamellar
bone, and the openings allow the passage of vascular and nerve elements.

• Hypoglossal canal-an opening in the OCCIPITAL BONE of the skull that contains the hypoglossal
 nerve (CN XII) and meningeal artery.

• Carotid canal-an opening in the TEMPORAL BONE of the skull that contains the internal carotid
artery, and sympathetic nerves (carotid plexus).

• Nasolacrimal canal-and opening in the LACRIMAL BONE of the skull that contains the
nasolacrimal (tear) duct.

JUGULAR FORAMEN-located in the temporal and occipital bones, it transmits the internal jugular
vein, glossopharyngeal, vagus, and spinal accessory nerves. A lesion in the jugular foramen may
damage the spinal accessory nerve (CN XI), vagus nerve (CN X), glossopharyngeal nerve (CN IX), and
internal jugular vein.

STYLOMASTOID FORAMEN-transmits the FACIAL NERVE (CN VII).

Internal Acoustic Meatus-a canal running through the petrous portion of the temporal bone, that transmits
the Vestibulocochlear nerve (CN VIII) and Facial nerve (CN VII).
• Vestibulocochlear nerve enters the internal acoustic meatus and remains within the temporal bone.
• Facial nerve-enters the internal acoustic meatus, the facial canal in the temporal bone, and
emerges from the stylomastoid foramen. The stylomastoid foramen lies between the styloid and
mastoid processes of the temporal bone.

AFTER THE MAIN TRUNK OF THE FACIAL NERVE exits the stylomastoid foramen, it enters
into the substance of the parotid gland where it gives off 5 main branches that supply motor movements
of the superficial musculature of the face (muscles of facial expression).
• Inadvertently depositing anesthetic solution into the parotid gland when giving a mandibular
block, causes paralysis of the muscles of facial expression.

CAVERNOUS SINUS-cranial nerves that pass through the cavernous sinus include: abducens (CN6),
trochlear (CN4), trigeminal (CN5), and oculomotor (CN3).


THE HEART

ADULT HEART-a hollow, cone-shaped organ the size of a closed fist located between the lungs inside
the pericardium, close to the midline of the body (MIDDLE MEDIASTINUM). The heart is connected
at its base to the great vessels, but otherwise lies free within the pericardium.

HEART IS ENCLOSED in a fibroserous sac =PERICARDIUM that consists of the serous

pericardium (thin, smooth inner portion) and fibrous pericardium (tough, fibrous outer layer).
• Serous pericardium-has an inner parietal layer & outer visceral layer. Between these two
layers is the pericardial space (contains pericardial fluid that minimizes friction as the heart
beats).

HEART-is composed of three major types of cardiac muscle (Atrial muscle, Ventricular muscle, and
Specialized Excitatory and Conductive muscle fibers). The specialized excitatory and conductive fibers
contract very weakly because they contain few contractile fibrils. Instead, they provide an excitatory
system for the heart and a transmission system for rapid conduction of impulses throughout the heart.
• Cardiac muscle (heart) contracts INVOLUNTARILY, and is innervated by the autonomic
nervous system, but contracts spontaneously without any nerve supply.

• Cardiac muscle cells are faintly striated, branching cells that are connected by intercalated
disks that form a functional network.

• Cardiac heart fibers are separate cellular units which unlike other striated muscle fibers, DO NOT
CONTAIN NUCELI.

• The heart (cardiac muscle) responds to increased demands by increasing the size of its fiber =
COMPENSATORY HYPERTROPHY.

• Heart’s IMPULSE-CONDUCTING SYSTEM consists of specialized cardiac muscle that

contains modified cardiac muscle fibers present in the SA node, AV node, and bundle of His
(includes its Purkinje Fibers).
Cardiac muscle is similar in FUNCTION to smooth muscle. It is INVOLUNTARY controlled by the
autonomic nervous system, and is FOUND ONLY IN THE HEART. Cardiac muscle’s main function is
to expel the blood to the various 4 chambers. Unlike smooth muscle, cardiac muscle appears striated
due to its INTERCALATED DISKS.

HEART CONSISTS OF 4 CHAMBERS & FUNCTIONS AS A DOUBLE PUMP (each pump has a
receiving chamber (atrium) and a propulsion chamber (ventricles):
• right and left atria are small, and located toward the superior region of the heart and are separated
by the interatrial septum.
• right and left ventricles are larger, are located at the apex of the heart, and are separated by the
interventricular septum.

THE ATRIAL PORTION of the heart has thin walls and is divided by the ATRIAL (interatrial)
SEPTUM into right and left atriums. FOSSA OVALIS & ANULIS OVALIS lie on the ATRIAL
(interatrial) SEPTUM.
• Foramen Ovale-permits blood flow from the right to left atrium in the FETAL HEART. The
blood than passes to the left ventricle and aorta. Foramen ovale eventually is permanently
closed with fibrous C.T. and BECOMES FOSSA OVALIS IN THE ADULT.

• Fossa Ovalis-a shallow depression that was the site for the foramen ovale in the fetus. Anulis
ovalis forms the upper margin of the fossa. Lies on the interatrial septum.

RIGHT SIDE (RIGHT ATRIUM) receives deoxygenated blood from the systemic venous circuit via
the superior and inferior venae cavae, and coronary sinus. Blood then goes from the right atrium to the
right ventricle via the right AV valve. The right ventricle then pumps blood into the pulmonary circuit (via
the pulmonary semilunar valve which allows blood to flow into the pulmonary arteries). Resistance to
pulmonary blood flow in the lungs would cause strain on the right ventricle.
• Right atrium receives deoxygenated blood from the superior and inferior venae cavae &
anterior cardiac veins, and coronary sinus.

• PECTINATE MUSCLES-prominent ridges of atrial myocardium located on the inner surfaces

of the right atrium and of both auricles (small, conical pouches projecting from the upper
anterior portion of each atrium).

• CRISTA TERMINALIS-a vertical muscular ridge that runs along the right atrial wall from the
opening of the superior vena cava to the inferior vena cava. It is the origin for the pectinate
muscles. Crista terminalis-the junction between the sinus venosus and the heart in the
developing embryo. It is represented externally on the outside of the heart by a vertical groove
(sulcus terminalis).
o SA node is located in crista terminalis (in right atrium) near the opening of the superior vena
cava.

CARDIAC VEINS lie superficial to the arteries. The largest vein (coronary sinus) opens into the right
atrium. Most cardiac veins empty into the coronary sinus, except the anterior cardiac veins which empty
directly into the right atrium.
o anterior cardiac veins drain DIRECTLY INTO RIGHT ATRIUM, while all other cardiac veins
drain into the coronary sinus. Coronary sinus-is a continuation of the great cardiac vein, and
drains most of the blood from the heart wall, opens into the right atrium between the inferior
vena cava and atrioventricular orifice. The anterior interventricular artery accompanies the
great cardiac vein.

o Small and middle cardiac veins are tributaries of the coronary sinus.
 o Thrombosis of CORONARY SINUS may cause dilation of the small, great, oblique and middle
cardiac veins. Thrombosis DOES NOT cause dilation of the ANTERIOR cardiac veins, b/c it
drains directly into the right atrium.

SUPERIOR VENA CAVA-opens into the UPPER part of the RIGHT ATRIUM. It returns venous
blood from the upper half of the body.

INFERIOR VENA CAVA-is larger than the superior vena cava, and opens into the LOWER part of the
RIGHT ATRIUM.

LEFT SIDE (LEFT ATRIUM)-receives oxygenated blood from the lungs via the pulmonary veins.
This blood then flows through the left AV mitral valve into the left ventricle. From the left ventricle, blood
passes through the aortic valve and enters the arch of the aorta, which delivers blood to the systemic
circuit.

VENTRICLES are larger and thicker walled than the ATRIA, are divided by the ventricular septum
into right and left ventricles which each receive blood from the atria:
• Right ventricle- pumps blood to and from the lungs. Receives deoxygenated blood from the
right atrium via the AV valve. Right ventricle then pumps blood into the pulmonary circuit (via the
pulmonary semilunar valve which allows blood to flow into the pulmonary arteries).

• Left ventricle-is larger and thicker-walled than the right, pumps blood through all other vessels of
the body, and enlarges briefly in response to coarctation (constriction) of the aorta. Receives
oxygenated blood from the left atrium via the left AV.
o APEX OF THE HEART-is formed by the tip of the LEFT VENTRICLE and lies at the level
of the left fifth intercostals space medial to the nipple line (9 cm from the midline). This
location is useful to determine the left border of the heart and for auscultation of the MITRAL
VALVE (Bicuspid valve) which is best heard over the apex of the heart.

CORONARY ARTERIES (RIGHT & LEFT)-provide ARTERIAL BLOOD SUPPLY to the heart.
Coronary arteries arise from the aorta immediately above the aortic valve; they are the first braches
off of the aorta. Most blood from the heart wall drains into the right atrium through the coronary sinus
(via cardiac veins).
1. RIGHT CORONARY ARTERY-supplies blood to the RIGHT ATRIUM (including SA & AV
nodes, and atrioventricular bundle), part of the left atrium, most of the right ventricle, and the
inferior part of the left ventricle.

2. LEFT CORONARY ARTERY-splits into the anterior interventricular and circumflex artery,
supplies blood to the left atrium, most of the left ventricle, and most of the interventricular
septum.

Obstruction of either coronary artery can lead to ANOXIA of the heart area supplied, causing spasmatic
contractions (heart attack), and eventually death.

CARDIAC SHUNTS-pattern of blood flow that deviates from normal circulation. Can be right-left,
left-right, bidirectional, or pulmonary-to-systemic. Blood flow direction is controlled by left and/or right
heart pressure, or biological/artificial heart valve. The most common congenital heart defect that causes
shunting is an ATRIAL and VETRICULAR SEPTAL DEFECTS.
• Ductus Arteriosus-a blood vessel in the developing fetus connecting the pulmonary artery to
the proximal descending aorta, allowing most blood from the right ventricle to “bypass” the
fetus’s fluid-filled, non-funtioning lungs. Becomes the ligamentum arteriosum when it closes at
birth. Two other fetal shunts are ductus venous and foramen ovale.

HEART BLOOD FLOW:

1. Entering the right atrium are the coronary sinus and superior and inferior venae cavae
carrying deoxygenated blood from the systemic circuit.
2. Upon contraction of the right atrium, blood passes through the right AV valve to the right
ventricle.
3. Upon contraction of the right ventricle, blood leaves to pass to the right and left lungs via the
pulmonary arteries.
4. Blood gases are exchanged in the lung and oxygenated blood returns via pulmonary veins to the
left atrium.
5. Upon contraction of the left atrium, blood passes through the left AV valve to the left
ventricle.
6. Upon contraction of the left ventricle, oxygenated blood passes through the aortic valve to
the systemic circuit via the aorta and its branches.
HEART HAS 4 VALVES (2 atrioventricular & 2 semilunar) that keep blood flowing in one
direction:
1. RIGHT & LEFT ATRIOVENTRICULAR VALVES separate the atria from ventricles:
• Tricuspid Valve (right AV valve)-guards the right atrioventricular orifice. It consists of 3
cusps, and controls blood flow through the right AV opening. Thin, but strong chordae
tendinae attach the cusps of the valve to the papillary muscles of the right ventricle.
Tricuspid valve controls blood flow between the right atrium and right ventricle.
o Tricuspid valve is best heard over the RIGHT HALF of the lower end of the BODY
OF THE STERNUM.

• Mitral Valve (bicuspid) (left AV valve)-guards the left atrioventricular orifice. It consists of 2
cusps. Chordae tendinae attach these cusps to papillary muscles in the left ventricle. Mitral
(bicuspid) valve controls blood flow between the left atrium and left ventricle.

2. SEMILUNAR VALVES (DO NOT CONTAIN chordae tendinae or papillary muscles):

• Pulmonary Valve-guards the pulmonary orifice (between the right ventricle and pulmonary
 artery); consists of 3 semilunar cusps. Pulmonary valve is best heard over the second
left intercostal space.

• Aortic Valve-a left semilunar valve that guards the aortic orifice; consists of 3 semilunar
cusps. When closed, the aortic valve prevents backflow of blood into the left ventricle.
Aortic valve is best heard over the second right intercostal space.

WALL OF THE HEART CONSISTS OF 3 LAYERS (TUNICS):

1. Epicardium-the serous membrane of the heart made of simple squamous epithelial cells overlying
C.T. Adipose tissue that surrounds the heart accumulates in this layer; it’s the visceral layer of
pericardium.

2. Myocardium-the thick MIDDLE MUSCULAR LAYER that forms the bulk of the heart wall.
It consists of cardiac muscle cells arranged in a spiral manner with intercalated disks.
Myocardium contains cone-shaped papillary muscles and fibrous strands (chordae tendineae).
• PAPILLARY MUSCLES-cone-shaped muscles that terminate in the tendinous cords
(chordae tendinae) that attach to the cusps of the atrioventricular valves (tricuspid and
mitral valve). Papillary muscles do not help the valves close, but prevent the cusps from being
everted (blown out) back into the atrium during ventricular contraction. ONLY FOUND IN
THE VENTRICLES and are NOT associated with semilunar valves.

3. Endocardium-heart’s INNER LAYER that consists of endothelial tissue with small blood
vessels and bundles of smooth muscle. It is homologous with the intima of the veins.
SINOATRIAL NODE (SA)-structure located in the wall of the RIGHT ATRIUM near the superior
vena cava and acts as a heart “PACEMAKER”. SA node is a small mass of specialized cardiac
muscle fibers that lies in the right atrium wall. SA node produces a spontaneous rhythm of electrical
discharge that causes excitation of the two atria.

• The rate of discharge of the SA node sets the rhythm of the entire heart. This heart rate is
increased by sympathetic stimulation (sympathetic trunk fibers) or decreased (slowed down)
by parasympathetic stimulation (vagus nerve) of the autonomic nervous system. Drugs that
mimic this stimulation also effects heart rate.

• A STIMULATORY IMPULSE FROM SA NODE spreads throughout the MYOCARDIUM of

the atria and stimulates atria contraction. This stimulatory impulse cannot pass directly to the
myocardium of the ventricles. It reaches the ventricles via the heart’s conducting system. The
impulse reaches another mass of specialized myocardial cells located in the part of the atrial
septum called the ATRIOVENTRICULAR NODE (AV NODE). From the AV node, a
specialized muscle tissue (bundle of His or atrioventricular bundle) which contains PURKINJE
FIBERS, carries the impulse to the ventricles, causing the ventricles to contract.


ARTERIES

SMOOTH MUSCLE CELLS-the MOST PROMINENT FUNCTIONAL COMPONENT in the

tunica media of small arteries, while ELASTIC FIBERS are the MOST PROMINENT FUNCTIONAL
COMPONENT is large arteries.

BLOOD VESSEL WALLS HAVE 3 LAYERS (TUNICS):

1. Tunica intima-the INNERMOST LAYER that consists of a layer of simple squamous epithelium
(endothelium) surrounded by elastic fibers and C.T. Tunica intima is the only layer common to
ALL blood vessels.

2. Tunica media- thick MIDDLE LAYER usually very thick in arteries, and consists of transverse
elastic fibers and smooth muscle fibers.

3. Tunica externa (adventitia)-the thin OUTMOST LAYER that consists of elastic and
collagenous fibers. Attaches the vessel to surrounding tissue. Tunica externa contains vasa
vasorum (small nutrient vessels that supply the large vessels (arteries and veins) with
nourishment since their walls are too thick to be nourished by diffusion from the blood in the
vessel.

• ARTERIES & ARTERIOLES-carry blood to the heart.

• CAPILLARIES-allow exchange of molecules between the blood and tissue.
• VENULES & VEINS-return blood to the heart.

ARTERIOLES-play a significant role in peripheral vascular resistance and in regulating blood

pressure. Arterioles are one of the blood vessels of the smallest branch of arterial circulation. Blood
flowing from the heart is pumped by the left ventricle to the aorta (largest artery), which then branches
into smaller arteries, and finally arterioles. The blood continues to flow through these arterioles into
capillaries, venules, and finally veins which return blood back to the heart.

ARTERIOLES have a VERY SMALL DIAMETER (< 0.5mm), a SMALL LUMEN, and THICK
TUNICA MEDIA composed almost entirely of smooth muscle, with little elastic tissue. This smooth
muscle constricts and dilates in response to neurochemical stimuli, which then changes the diameter of the
arterioles. This causes profound and rapid changes in peripheral resistance. This change in diameter
of the arterioles regulates the flow of blood into capillaries. By affecting peripheral resistance,
arterioles directly affect arterial blood pressure.

BLOOD PRESSURE IS HIGHEST IN ARTERIES, and gradually drops as blood flows through the
arterioles, capillaries, venules, and veins (where BP is LOWEST). The greatest drop in blood
pressure occurs at the transition from arteries to arterioles.

AORTA-the MAJOR ARTERY and is the LARGEST ARTERY and carries oxygenated blood from
the LEFT VENTRICLE to all parts of the body. The Aorta branches into vessels that supply specific
organs and areas of the body. The characteristic feature is it contains a lot of ELASTIC FIBERS in its
tunica media (middle layer of blood vessel wall). In the fetus, blood enters the common carotid arteries
via the aorta.


AORTA (4 PARTS)

1. ASCENDING AORTA-a short vessel that starts at the aortic opening of the left ventricle. Its only
branches are the right and left coronary arteries, which supply the heart muscle.

2. ARCH OF AORTA-gives rise to three arterial branches (brachiocephalic, left common carotid,
and left subclavian arteries). These arteries supply all blood to the head, neck, and upper
limbs.
o Brachiocephalic Artery (innominate artery)-one of three arteries that branch from the
ARCH OF THE AORTA. Brachiocephalic artery is an extremely SHORT artery and is
the first artery to stem directly from the aortic arch. AT THE NECK, brachiocephalic
artery divides into the RIGHT COMMON CAROTID ARTERY & RIGHT
SUBCLAVIAN ARTERY.

o Left Common Carotid Artery & Left Subclavian Artery are the other two branches off the
arch of aorta.

o HEAD & NECK are supplied by the RIGHT & LEFT COMMON CAROTID
ARTERIES.

o UPPER LIMBS are supplied by the RIGHT & LEFT SUBCLAVIAN ARTERIES.

3. THORACIC PORTION OF DESCENDING AORTA-extends from T4-T12 (lies in the

posterior mediastinum). All of the arterial branches (posterior intercostals, subcostal arteries)
from this part are small and supply the THORAX and DIAPHRAGM.
• Thoracic duct is found in the posterior mediastinum. The thoracic duct empties directly
into the junction of the left internal jugular and subclavian veins.

4. ABDOMINAL PORTION OF DESCENDING AORTA-extends from T12-L4 where it

terminates by dividing into the right and left common iliac arteries and a small middle sacral
artery. Arteries from this area supply the ABDOMEN, PELVIC REGION, & LOWER
LIMBS.
• Abdominal Aorta Branches include three unpaired branches: CELIAC TRUNK,
SUPERIOR MESENTERIC, & INFERIOR MESENTERIC ARTERIES. Also
included are the paired branches (renal, suprarenal, gonadal, and lumbar arteries).

VERTEBRAL ARTERY-a branch of the SUBCLAVIAN ARTERY that provides circulation to the
BRAIN. On its way to the brain, it passes through the foramen magnum. Vertebral artery is the first
branch of the subclavian artery.
• PICA-largest branch of the vertebral artery that supplies the cerebellum, choroids plexus, and
medulla oblongata.

INTERNAL THORACIC ARTERY-usually arises from the first part of the SUBLCAVIAN
ARTERY and descends directly behind the first 6 costal cartilages, just lateral to the sternum. Internal
Thoracic Artery
• 12 smaller anterior intercostals arteries which anastomose with the posterior intercostals
arteries, which arise from the thoracic aorta. This network provides muscular branches to the
intercostals, serratus anterior, and pectoral muscles.

• Superior epigastric & musculophrenic arteries-the two terminal branches of the internal
thoracic artery. Superior Epigastric Artery enters the rectus sheath and supplies the rectus
muscle as far as the umbilicus. Musculophrenic Artery-supplies diaphragm and lower intercostals
spaces.

• Inferior Epigastric Artery-a branch of the external iliac artery.

STOMACH ARTERIES-supply blood to the STOMACH are from the CELIAC TRUNK (Celiac
Artery): CELIAC ARTERY originates in the ABDOMINAL AORTA just below the diaphragm at
about the level of the 12th thoracic vertebra (T12).

CELIAC ARTERY (TRUNK) is very short and almost immediately divides into 3 BRANCHES:
1. Left Gastric Artery-supplies the lesser curvature of the stomach and lower part of the
esophagus.

2. Splenic Artery-supplies the SPLEEN, and gives off the left gastroepiploic artery branch
(supplies the greater curvature of the stomach). Splenic artery is the largest branch of the
Celiac Artery.

3. Common Hepatic Artery-gives rise to:

• gastroduodenal, which gives rise to the right gastroepiploic artery that supplies the greater
curvature of the stomach. The right gastric artery supplies the lesser curvature of the stomach.
After dividing into these branches, the common hepatic artery divides into the right and left
hepatic arteries that supply the LIVER & GALLBLADDER.

HEPATIC ARTERY & HEPATIC PORTAL VEIN-are responsible for the DUAL BLOOD SUPPLY
to the LIVER & LUNGS (the only two organs that receive dual blood supply).

LIVER-receives most of its blood (70%) via the HEPATIC PORTAL VEIN which drains nearly all
blood from the intestines. This ensures that all absorbed food goes directly to the liver where it is
packaged and stored for use until needed. The liver receives the other 30% of its blood supply from the
HEPATIC ARTERIES which is also important because the arterial blood is well oxygenated, unlike
the deoxygenated venous blood arriving through the portal vein.
• Hepatic Veins (3)-drains blood from the liver into the inferior vena cava.
• Hepatic Artery-arises from the common hepatic artery (a branch of the celiac artery).
• Hepatic Portal Vein-formed by the union of the superior mesenteric vein and splenic vein.

The most unusual aspect of hepatic circulation is that all blood supplied to the liver from the hepatic
arteries and portal vein EMPTIES INTO THE SAME SINUSOIDS, which thus is a mixture of arterial
and venous blood. The sinusoids of each lobule empty into a common central vein. The common central
vein of each lobule then empties into one of three hepatic veins which all empty into the inferior
vena cava, which transports blood to the heart.
• Common bile duct, hepatic artery, and portal vein are found grouped in the LESSER
OMENTUM.

SUPERIOR MESENTERIC ARTERY-supplies the ASCENDING COLON.

INFERIOR MESENTERIC ARTERY-supplies sigmoid colon, descending colon, transverse colon,

and rectum.

COMMON CAROTID ARTERY divides into its external and internal branches at the level of the
superior border of the THYROID CARTILAGE.

• RIGHT & LEFT COMMON CAROTID ARTERIES ascend in the neck, and bifurcate at the
level of the superior border of the thyroid cartilage to form the EXTERNAL & INTERNAL
CAROTID ARTERIES.

CAROTID SINUS-located at the junction of the internal and external carotid arteries. It contains
baroreceptors to monitor blood pressure, & chemoreceptors within the carotid body that respond to
chemical changes in blood. CAROTID BODY is innervated by the glossopharyngeal nerve.

• Carotid sinus is stimulated by CHANGES IN BLOOD PRESSURE. Carotid sinus is a spindle-

shaped dilation of the common carotid artery at its bifurcation into the internal and external
carotids. This bifurcation occurs at the level of the superior border of the thyroid cartilage. It
contains baroreceptors that slow the heart, cause vasodilation, and drop in blood pressure when
 stimulated.

• Carotid sinus is innervated by carotid sinus branch of the glossopharyngeal nerve and by a
branch of the vagus nerve.

• Carotid sheath-an investment of the internal & common carotid arteries, internal jugular vein, and
vagus nerve.

• CAROTID SINUS SYNDROME-a temporary loss of consciousness that sometimes

accompanies convulsive seizures because of the intensity of the carotid sinus reflex when pressure
builds in one or both carotid sinuses.

• Carotid Body-a chemoreceptor that lies posterior to the point of bifurcation of the common carotid
artery, and is innervated by the glossopharyngeal nerve. It is sensitive to excess CARBON
DIOXIDE and REDUCED OXYGEN TENSION in the blood (this produces a rise in blood
pressure and heart rate).
INTERNAL CAROTID ARTERY-supplies the BRAIN and all surrounding structures. It also gives of a
large branch OPHTHALMIC ARTERY that supplies blood to the eye and surrounding structures. The
ophthalmic artery also gives off two small branches (posterior communicating and choroidal
arteries), and ends in two terminal branches (anterior cerebral artery & middle cerebral artery
(largest branch of internal carotid).
• Ophthalmic artery (branch of internal carotid) gives off branches in the orbital cavity:
(central artery of retina, muscular branches, ciliary arteries, lacrimal artery, supratrochlear
and supraorbital arteries (terminal branches).

• Ophthalmic artery arises from the internal carotid artery and follows the optic nerve through the
optic foramen to enter the orbit.

• Ophthalmic artery is a branch of the internal carotid artery.

INTERNAL CAROTID ARTERY TERMINAL BRANCHES (anterior & middle cerebral arteries)
supply blood to the BRAIN. COMMON CAROTIDS branch into the two internal carotids which further
divide in the middle cranial fossa into anterior & middle cerebral arteries to supply the anterior and
middle brain.

• 4 major arteries (2 vertebral & 2 carotid) supply the brain with oxygenated blood. The two
vertebral arteries (branches of subclavians) converge to become the BASILAR ARTERY
(supplies posterior brain, pons, roots of CNV, and cerebellar peduncles).

MIDDLE CEREBRAL ARTERY- LARGEST BRANCH of the INTERNAL CAROTID ARTERY.

The small, deep, penetrating arteries of the basal ganglia called “Lenticulostriate arteries” are middle
cerebral artery branches.
• Lenticulostriate Arteries- “ARTERIES OF STROKE” because they are often involved in
stroke (cerebrovascular accident). These vessels are thin-walled and often rupture and cause
hemorrhage. Blood from the damaged brain flows directly into the ventricles, increasing
intracranial pressure, edema, and herniation of brain tissue.
 • Stroke Warning Signs: sudden weakness, paralysis or numbness of face, arm, or leg on one or
both sides. Loss of speech of difficulty speaking or understanding speech. Dimness or loss of
vision (especially in one eye). Unexplained dizziness (especially when associated with other
neurologic symptoms), unsteadiness, and sudden falls. Sudden severe headache and loss of
consciousness.

CIRCLE OF WILLS (cerebral arterial circle)-formed by the posterior cerebral (branch of basilar
artery), posterior communicating (branch of internal carotid), internal carotid, anterior cerebral, and
anterior communicating (branch of internal carotid) arteries.
• CIRCLE OF WILLS FORMS AN IMPORTANT MEANS OF COLLATERAL
CIRCULATION IN THE EVENT OF OBSTRUCTION.

EXTERNAL CAROTID ARTERY- main blood supply to the facial region, supplying blood to
muscles of the neck, face, thyroid gland, salivary glands, scalp, tongue, jaws, and teeth.
• External carotid artery lies within the substance of the PAROTID GLAND. The external
carotid extends from the level of the upper border of the thyroid cartilage to the neck of the
mandible, where it ends in the substance of the parotid gland by dividing into its terminal
branches (MAXILLARY & SUPERFICIAL TEMPORAL ARTERIES). At its origin, where
pulsations are felt, the external carotid artery lies within the carotid triangle.

• External carotid artery supplies most of the HEAD & NECK (except the brain which gets its
blood supply from the internal carotid and vertebral arteries). The external carotid passes
through the parotid salivary gland and terminates as the maxillary and superficial temporal
arteries (supplies the scalp).

• External carotid artery contributes to the blood supply of the NASAL CAVITY by way of the
maxillary artery, sphenopalatine artery, and posterior lateral nasal arteries.

EXTERNAL CAROTID BRANCHES (Some Ladies Find All Old Poor Men Sexy)
1. Superior thyroid artery-supplies thyroid gland, and gives off a branch to the sternocleidomastoid
muscle and superior laryngeal artery.
2. Lingual artery-supplies the anterior 2/3 of the tongue.
3. Facial artery-supplies the face and submandibular gland.
4. Ascending pharyngeal artery-supplies the pharynx.
5. Occipital artery-supplies the pharynx.
6. Posterior auricular artery-supplies back of the scalp.
7. Maxillary artery-the TERMINAL BRANCH of the external carotid.
8. Superficial temporal artery-the TERMINAL BRANCH of the external carotid.

Maxillary Artery & Superficial Temporal Arteries are terminal branches of the external carotid
artery.

LINGUAL ARTERY-supplies blood to the tongue and floor of the mouth, and receives blood from the
tonsillar branch of the facial artery and ascending pharyngeal artery. Lingual artery arises from the
EXTERNAL CAROTID ARTERY at the level of the tip of the greater horn of the hyoid bone in the
carotid triangle, and passes deep to the hyoglossus muscle to supply the TONGUE.
 • Lingual artery DOES NOT ACCOMPANY ITS CORRESPONDING NERVE throughout its
course.

• Lingual artery supplies blood to the tongue, floor of mouth, suprahyoid region, sublingual
gland, and palatine tonsils.

Lingual Artery Branches: suprahyoid artery, dorsal lingual artery, sublingual artery (supplies the
sublingual gland). It terminates as the deep lingual artery, which ascends between the genioglossus and
inferior longitudinal muscles.
1. Suprahyoid artery-supplies the suprahyoid region.
2. Dorsal lingual artery-dorsum of the tongue is the top part of the tongue seen easily.
3. Sublingual artery-supplies the floor of mouth, and sublingual gland.
4. Deep lingual artery-supplies blood to anterior 2/3 of the tongue

Inferior alveolar nerve and artery, and LINGUAL NERVE are found in the space between the
medial pterygoid muscle and ramus of the mandible.

FAST FACT REVIEW: TONGUE INNERVATION:

• Motor is from the HYPOGLOSSAL NERVE (CN XII).
• Sensory to anterior 2/3 is from the LINGUAL NERVE (V3 branch).
• Glossopharyngeal Nerve (CN IX) supplies posterior 1/3 of tongue (including vallate papillae).
Pain fibers from the posterior 1/3 of the tongue travel with the Glossopharyngeal nerve.
• Vagus Nerve (CN X) through the internal laryngeal nerve supplies area near the epiglottis.
• Taste: Facial Nerve (CN VII) via chorda tympani supplies anterior 2/3; Glossopharyngeal (CN
IX) supplies posterior 1/3.

FACIAL ARTERY-branch of EXTERNAL CAROTID ARTERY that supplies the

SUBMANDIBULAR GLAND. The facial artery arises from the external carotid just above the upper
border of the hyoid bone. It hooks around the lower border of the mandible at the anterior margin of the
masseter to enter the face. Facial artery has CERVICAL & FACIAL PORTIONS:
1. Cervical portion-gives rise to the ascending palatine, tonsillar, glandular (to submandibular
gland), and submental branches in the neck.

2. Facial portion-gives rise to the inferior labial, superior labial, and lateral nasal branches on the
face. It terminates as the angular artery at the medial angle of the eye.

FACIAL ARTERY supplies blood to the face, tonsils, palate, labial glands, and muscles of the lips. It
also supplies the submandibular gland, ala and dorsum of the nose, and MUSCLES OF FACIAL
EXPRESSION.

MAXILLARY ARTERY-branches of the maxillary artery supply BLOOD TO BOTH DENTAL

ARCHES (maxillary and mandibular teeth). Maxillary Artery supplies MUSCLES OF
MASTICATION, ALL TEETH, palate, and almost the entire NASAL CAVITY.

Maxillary teeth are supplied by branches of Part 3 (Pterygopalatine part):

• Posterior Teeth (molars and premolars) from the posterior superior alveolar arteries.
 • Anterior Teeth (canines and incisors) from the anterior and middle superior alveolar arteries.

DESCENDING PALATINE ARTERY-gives rise to greater and lesser palatine arteries which pass
through the greater and lesser palatine foramina, to supply HARD & SOFT PALATES. In addition to the
soft palate, the lesser palatine artery also supplies the TONSILS (along with the tonsillary artery-a
branch of the facial artery).
• Lesser Palatine Artery-supplies the soft palate and tonsils.

• Greater Palatine Artery-a branch of descending palatine artery that supplies hard palate
mucosa posterior to the maxillary canine.
o Greater Palatine Artery also sends a branch to anastomose with the nasopalatine branch of
the sphenopalatine artery in the incisive foramen to supply mucosa of the hard palate
anterior to the maxillary canine.

Mandibular teeth are supplied by the INFERIOR ALVEOLAR ARTERY (branch of Mandibular V1).

Venous return of both dental arches is to the PTERYGOID PLEXUS OF VEINS.

MAXILLARY ARTERY arises from the external carotid artery at the posterior border of the ramus
of the mandible. LATERAL PTERYGOID muscle divides MAXILLARY ARTERY into 3 PARTS:
1. Mandibular Part (portion before muscle)-its branches include
o Deep auricular artery to external auditory meatus.
o Anterior tympanic artery to eardrum.
o Middle meningeal artery to cranial cavity (damage causes EPIDURAL HEMATOMA).
o Accessory meningeal artery supplies cranial cavity.
o Inferior alveolar artery supplies tissues on the chin and lower teeth.

2. Pterygoid Part (passes over lateral pterygoid)-all of these branches supply muscles: Anterior
and posterior deep temporal arteries, pterygoid artery, masseteric artery, and buccal artery.

3. Pterygopalatine Part (portion after crossing lateral pterygoid)-its branches are:

1. Posterior-superior alveolar supplies maxillary molars & premolars (posteriors).
2. Infraorbital artery-its branches supply maxillary canine and incisors teeth (anteriors).
3. Descending palatine-gives rise to greater and lesser palatine arteries.
4. Artery of the pterygoid canal.
5. Pharyngeal artery

SPHENOPALATINE ARTERY-principal artery supplying the NASAL CAVITY (conchae, meatus,

and paranasal sinuses). Sphenopalatine artery is the TERMINAL BRANCH of the maxillary artery
that enters the nasal cavity through the sphenopalatine foramen along with the nasopalatine branch of the
maxillary nerve. Damage to sphenopalatine artery causes EPISTAXIS.
• A patient bleeds from the anterior septal region of his nose due to a break in the walls of vessels
that originate from the Sphenopalatine artery.

• Anterior Ethmoidal Artery-a branch of the ophthalmic artery that also supplies the NASAL
CAVITY.
 • Small arteries that supply blood to the NASAL CAVITY are the descending palatine branch of
the maxillary artery, superior labial branch of the facial artery, and lateral nasal branch of
the facial artery.

CAPILLARIES-site for exchange of nutrients and wastes between blood and tissue takes place across
capillary walls. Unlike ARTERIES & VEINS, capillaries are VERY THIN & FRAGILE.

• CAPILLARY WALLS are only one epithelial layer thick and CONSIST OF ENDOTHELIUM
ONLY, NO TUNICA MEDIA OR ADVENTITIA. The exchange of oxygen and carbon dioxide
takes place through the thin capillary wall. RBCs inside the capillary release their oxygen,
which passes through the capillary wall into surrounding tissue. The tissue then releases its waste
products (carbon dioxide) which passes through the wall into the RBC.

• CAPILLARIES CARRY BLOOD between the smallest arteries (arterioles), and smallest
veins (venules). RBC carrying oxygen and other nutrients must pass through capillaries in single
file due to the small capillary diameter (0.008mm).

• VELOCITY of blood flow is SLOWEST IN CAPILLARIES because a decrease in vessel

diameter increases in resistance to blood flow.

SINUSOIDS-are a substitute for capillaries in the liver, spleen, bone marrow, pituitary gland, adrenal
gland, carotid body, pancreas, and parathyroid glands. These organs and glands have a “sinusoidal
arrangement of blood vessels”. In the arrangement, arterioles, rather than connecting with capillaries,
empty directly into large vascular channels (SINUSOIDS).
• Sinusoids have very, very thin walls that conform to the space where they are located (from
irregular tortuous tubes). Sinusoid walls consist largely of PHAGOCYTIC CELLS.

• Sinusoids are WIDER and MORE IRREGULAR than capillaries. Sinusoids form part of the
RETICULOENDOTHELIAL SYSTEM (RES is mainly concerned with phagocytosis and
antibody formation).

• The difference between capillaries and sinusoids is capillaries have a constant lumen and
complete endothelial lining whereas sinusoids are irregular, tortuous tubes.

 VEINS
VEINS structure is similar to its companion arteries. However, blood pressure in veins is lower, veins
have less muscle, larger diameter, much less elastic tissue, and a more prominent tunica adventitia.
• Veins have THINNER WALLS than arteries but LARGER DIAMETERS because of the low
blood pressures required for venous return to the heart.
• VALVES-are found in veins of the neck, arms, and legs to prevent venous backflow. Valves are
also found in lymphatic vessels.
• Except for pulmonary vessels and certain fetal vessels, arteries transport oxygenated blood, and
veins transport deoxygenated blood.
• VENULES-continue FROM CAPILLARIES and MERGE TO FORM VEINS.

VEINS:
• Have a thick tunica media with few muscle fibers
• Have a thick tunica adventitia with little elastic tissue.
• Have a larger lumen and thinner walls than the arteries they accompany.
• Some contain valves and vasa vasorum.
• Veins receive blood from venules and carry deoxygenated blood from the body (except the
lungs) to the RIGHT ATRIUM of the heart.

DURAL SINUSES (cerebral sinuses or sinuses of dura mater)-VEINS OF THE BRAIN are direct
tributaries of dural venous sinuses. Dural sinuses are channels located in dura mater and are lined with
epithelial cells.

VENOUS SINUSES-endothelium channels only found in the cranium between layers of dura mater.

CAVERNOUS SINUSES-are paired, irregularly shaped, venous dural sinuses located on either side of
the SELLA TURCICA of the sphenoid bone in the middle cranial fossa. Cavernous sinuses empty via
the parietal sinuses into the transverse sinus, which then empties into the INTERNAL JUGULAR
VEIN.
• Structures EMBEDDED in the LATERAL WALL of the cavernous sinuses:
o Ophthalmic nerves (V1 branch of Trigeminal)
o Oculomotor nerves (CN 3)
o Maxillary nerves (V2 branch of Trigeminal)—exits sinus via foramen rotundum.
o Trochlear nerves (CN 4)
o Trigeminal ganglion (CN 5)

• Abducens nerve (CN 6) and Internal Carotid Artery run through the MEDIAL (middle) wall of
the cavernous sinuses.

• Structures that EMPTY (DRAIN) into the CAVERNOUS SINUS:

o Superior ophthalmic vein
o Inferior ophthalmic vein (divides into two terminal branches: one runs to the pterygoid
 plexus, and the other either joins the superior ophthalmic vein or empties directly into the
cavernous sinus.
o Cerebral veins
o Sphenoparietal veins
o Central vein of the retina

EMISSARY VEINS-are valveless, and connect the dural venous sinuses to the veins of the scalp. An
emissary vein found in the foramen ovale is a means of communication between the pterygoid plexus
and cavernous sinus.

DIPLOIC VEINS-lie in channels in the diploe of the skull and communicates with the dural sinuses,
veins of the scalp, and meningeal veins. Located within the bones of the calvarium.

PORTAL VEIN (Hepatic Portal Vein)-formed by UNION of SUPERIOR MESENTERIC &

SPLENIC VEINS. Portal vein is a wide, short vein formed by the union of the superior mesenteric
and splenic veins behind the pancreas, ascends in front of the inferior vena cava, and divides into right
and left branches before entering the liver. Portal vein drains the stomach, intestines, spleen, pancreas,
and gallbladder.

PORTAL VEIN drains this blood into the hepatic (liver) sinusoids, which then drain into the central
vein. Here, the blood travels through the hepatic portal system and makes it possible for the liver to
perform many functions. It can remove substances from the blood and store them, metabolize them, or if
they are harmful, detoxify them. After leaving the liver, blood travels through the hepatic veins to enter the
inferior vena cava.

PORTAL VEIN-ascends POSTERIOR to the bile duct and proper hepatic artery and passes anterior
to the epiploic foramen in the free edge of the lesser omentum.
• POTRAL VEIN is formed posterior to the neck of the pancreas by the union of the splenic,
and superior mesenteric veins.
• PORTAL VEIN TRIBUTARIES are the left and right gastric veins, and cystic veins.
• PORTAL VEIN CARRIES TWICE AS MUCH BLOOD AS THE HEPATIC ARTERY.
• portal vein and splenic vein are involved in drainage of the stomach.

SPLENIC VEIN-drains the spleen and receives tributaries from the stomach (right and left
gastroepiploic veins, right and left gastric veins), pancreas (pancreatic vein), and gallbladder (cystic
vein).

Superior Mesenteric Vein-drains the small intestine, cecum, and ascending and transverse colon of
the large intestine.

Inferior Mesenteric Vein-drains the rectum and descending colon of the large intestine. It joins the
splenic vein behind the neck of the pancreas.

MAXILLARY VEIN-forms the pterygoid plexus of veins. It joins the superficial temporal vein within
the parotid gland to form the retromandibular vein.

• PTERYGOID PLEXUS OF VEINS-surrounds the MAXILLARY ARTERY. Pterygoid plexus

 occupies the infratemporal fossa, and is a venous network associated with the pterygoid muscles.
It receives veins that correspond to the maxillary artery branches. It terminates posteriorly in
the maxillary vein, and anteriorly the pterygoid plexus drains via the deep facial vein into the
facial vein. Drains the teeth.

FACIAL VEIN-joins the RETROMANDIBULAR VEIN below the border of the mandible, and
empties into the main venous structure of the neck (internal jugular vein).
• FACIAL VEIN communicates with the superior ophthalmic vein and thus, with the cavernous
sinus allowing a route of infection from the face to the cranial dural sinus.

• FACIAL VEIN begins as the angular vein by the confluence of the supraorbital and
supratrochlear veins. The angular vein is continued at the lower border of the orbital margin into
the facial vein. It receives the infraorbital and deep facial veins. The facial vein drains either
directly into the internal jugular vein, or by joining the anterior branch of the retromandibular
vein to form the common facial vein which then enters the internal jugular vein.

DANGER TRIANGLE OF THE FACE-a triangle exists that covers the nose and maxilla and goes up to
the region between the eyes. This is an area in which superficial veins communicate with the dural
sinuses. The FACIAL VEIN HAS NO VALVES & backflow can cause an infection to get into the
dural sinuses, through the deep facial vein (via pterygoid plexus) and superior ophthalmic vein (via
cavernous sinus).

IMPORTANT:
• Deep facial vein is a communication between the FACIAL VEIN & PTERYGOID PLEXUS.
• Superior ophthalmic vein is a communication between FACIAL VEIN & CAVERNOUS SINUS.

SUPERFICIAL TEMPORAL VEIN-drains the scalp and side of the head. It descends anterior to the ear
and plunges into the substance of the parotid gland.

RETROMANDIBULAR VEIN-formed by the union of the superficial temporal and maxillary veins
within the parotid gland. Retromandibular vein divides at the angle of the mandible into
1. anterior branch-joins the facial vein to form the common facial vein.
2. posterior branch-joins the posterior auricular vein from behind the ear to form the external
jugular vein.

EXTERNAL JUGULAR VEIN-is formed by the union of the posterior auricular and posterior
branch of the retromandibular vein. It crosses the sternocleidomastoid muscle obliquely, under the
platysma, and ends in the subclavian vein.

INTERNAL JUGULAR VEIN-begins in the jugular foramen as a continuation of the SIGMOID

SINUS. It descends in the carotid sheath and ends in the brachiocephalic vein. It receives blood from the
brain, face, and neck.
• Internal jugular vein DESCENDS through the neck within the carotid sheath and unites behind
the sternoclavicular joint with the subclavian vein to form the brachiocephalic vein.
Brachiocephalic veins (right and left) unite in the superior mediastinum to form the SUPERIOR
VENA CAVA, which returns blood to the right atrium of the heart.
RIGHT & LEFT BRACHIOCEPHALIC VEINS-unite in the superior mediastinum to FORM THE
SUPERIOR VENA CAVA. Formed by the union of the internal jugular and subclavian veins.
• At the root of the neck, the internal jugular vein joins the subclavian vein to form the large
brachiocephalic vein. This occurs on both sides of the neck and the two brachiocephalic veins
unite in the superior mediastinum to form the superior vena cava (azygos vein also joins the
posterior aspect of the superior vena cava just before it enters the pericardium.

• An infection of the lower lip enters the bloodstream via the brachiocephalic vein.

SUBCLAVIAN VEIN-a continuation of the axillary vein at the inferior margin of the first rib, passing
medially to join the internal jugular vein and forming the brachiocephalic vein on each side. As
subclavian vein crosses the first rib it lies anterior to the anterior scalene muscle.
• Subclavian vein receives two venous tributaries in the root of the neck: external jugular vein and
transverse cervical chain.
• axillary vein begins at the lower border of the teres major muscle as the continuation of the basilic
vein. As it ascends to the inferior margin of the first rib, it forms the SUBLCAVIAN VEIN

CERVICAL TRIANGLE-is composed of the RETROMANDIBULAR VEIN & EXTERNAL &

INTERNAL JUGULAR VEINS.

AZYGOS VEIN-drains venous blood from structures of the posterior abdominal and thoracic body
wall. THE ORIGIN OF THE AZYGOS VEIN IS VARIABLE. It is often formed by the union of the
right ascending lumbar vein and right subcostal vein, or solely by the inferior vena cava.

• AZYGOS VEIN ascends through the aortic orifice of the diaphragm, lies in the posterior
mediastinum, and empties into the superior vena cava. Azygos vein leaves an impression on
the right lung as it arches over the root.

• Azygos vein ends in the superior vena cava.

• Right superior intercostals vein drains into the azygos vein

• Left superior intercostals vein drain into the left brachiocephalic vein.

• AZYGOS VEIN LEAVES AN IMPRESSION ON THE RIGHT LUNG.

• Second, third, & fourth right posterior intercostals veins drain from the right superior intercostals
vein into the AZYGOS VEIN.

OTHER THORAX VEINS:

1. Inferior hemiazygos vein-formed by the union of the left ascending lumbar vein and left subcostal
vein, and empties into the azygos vein.
2. Superior hemiazygos vein-formed by the union of the fourth to eighth intercostals veins, and
empties into the azygos vein.

External jugular vein drain venous blood from the skin, parotid gland, facial and neck muscles;
converges with the subclavian vein to form the brachiocephalic vein.
Internal jugular vein drains venous blood from the venous sinuses within the cranial cavity and empties
into the brachiocephalic vein.

INTERNAL JUGULAR VEINS (right and left), External jugular vein (right and left), and Vertebral
vein (right and left) RETURNS MOST VENOUS BLOOD FROM THE HEAD & NECK TO THE
HEART.

DUCTUS VENOSUS-the venous shunt within the liver to connect with the inferior vena cava. It
transports oxygenated blood directly from the umbilical vein to the inferior vena cava. DUCTUS
VENOSUS is present in the FETUS and BECOMES the LIGAMENTUM VENOSUM (a fibrous cord in
the liver) in the newborn. Ligamentum venosum-is a fibrous remnant of a fetal channel connecting the
left pulmonary artery to the aorta. Ductus Venosus allows blood returning from the placenta to reach
the heart without passing through liver sinusoids.

UMBILICAL VEIN- connects the placenta to the liver, and forms a major portion of the umbilical cord.
Transports nutrient-rich oxygenated blood from the placenta to the fetus. It forms the round ligament of
the liver in the newborn.
• BLOOD LEAVES THE PLACENTA and enters the fetus through the umbilical vein. It is the only
fetal vessel to carry blood rich in oxygen and nutrients. All other vessels that carry a mixture of
arterial and venous blood. After circulating in the fetus, the blood returns to the placenta through
the umbilical arteries.

UMBILICAL ARTERIES-arise from internal iliac arteries, and is associated with the umbilical cord.
These arteries transport blood from the fetus to the placenta. Upon birth, it atrophies and becomes the
lateral umbilical ligaments. Only present before birth, not after.

FORAMEN OVALE-located at the opening between the right and left atria. It functions as a shunt to
bypass the pulmonary circuitry. In the newborn, it closes at birth and becomes fossa ovalis (a depression
in the interatrial septum). Foramen ovale is located in the interatrial septum of the embryo and fetus,
that allows blood to pass from the right atrium to the left atrium directly. Its an embryological
opening between the right and left atria.

DUCTUS ARTERIOSUM-located between the pulmonary trunk and aortic arch. It functions as a shunt to
bypass the pulmonary circuitry. In the newborn, it closes shortly after birth, atrophies, and becomes the
ligamentum arteriosum.
• Brachial vein-drains venous blood from deep antebrachial regions and brachial regions into
axillary vein.

• Cephalic vein-drains venous blood from the radial side to the antebrachium and brachium into the
subclavian vein.

• Brachiocephalic vein (right or left)-is formed by the union of the internal jugular vein and
subclavian veins.

• Superior vena cava-a large vein formed by the union of the two brachiocephalic veins; it has no
valves. It receives blood from the head, neck, upper limbs, and chest, and empties into the right
 atrium of the heart.

• Inferior vena cava-(larger than the superior vena cava)-opens into the lower part of the right
atrium; it is guarded by a rudimentary, non-functioning valve. It returns blood to the heart from the
lower half of the body.

 BLOOD
HEMATOPOIESIS-the formation of blood or blood cells in ADULTS that occurs in TWO TISSUES:

1. MYELOID TISSUE-red bone marrow present only in certain bones (humeri, femurs, ribs,
sternum, osa coxae, and portions of the skull). This red bone marrow manufactures
erythrocytes, granular leukocytes (neutrophils, eosinophils, and basophils), and platelets
from HEMOCYTOBLASTS.
• Hemocytoblast (pluripotent stem cells)-a precursor cell in red bone marrow that gives
rise to all formed element of the blood.

2. LYMPHOID TISSUE-present in the lymph nodes, tonsils, spleen, and thymus. Lymphoid tissue
produces agranular leukocytes (monocytes and lymphocytes).

DURING EMBRYONIC DEVELOPMENT, the yolk sac, liver, spleen, thymus, and forming bone
marrow all participates at various times in producing blood cells.

IN ADULTS, most bones contain YELLOW BONE MARROW which functions primarily as a SITE
FOR FAT STORAGE and is found in the center of long bones. Red bone marrow (MYELOID
TISSUE) is only present in certain bones (flat bones of skull, ribs, sternum, vertebrae, pelvis, and the
proximal epiphyses of the humerus and femur).

ERYTHROPOIESIS-process of erythrocyte (RBC) production stimulated by ERYTHROPOIETIN

hormone produced in the KIDNEY. Average RBC life span is 120 days.

ERYTHROCYTES (RBC)-appear as biconcave discs without nuclei & mitochondria. Erythrocytes are
the MOST NUMEROUS of the formed elements contained in the blood. RBC’s primary function is to
TRANSPORT OXYGEN & CARBON DIOXIDE.
▪ The hemoglobin molecules in erythrocytes combine with oxygen in the lungs to form
oxyhemoglobin. Oxyhemoglobin is transported in this state to body tissues where it is released
to diffuse into the interstitial fluid. Within the tissues, carbon dioxide is combined with
hemoglobin to form carbaminohemoglobin, which is transported to the lungs. ~70% of carbon
dioxide, however, is transported by blood plasma as bicarbonate ions (HCO3-).

▪ 4.3-5.8 million erythrocytes per cubic mm.

HEMATOCRIT-proportion of erythrocytes in a blood sample (~ 46% for males and ~40% for females).

PLATELETS-minute, irregularly shaped, disk-like CYTOPLASMIC FRAGMENTS OF CELLS found

in blood plasma that PROMOTE BLOOD CLOTTING. Platelets have no definite nucleus, no DNA,
and no hemoglobin.
• Normal blood contains 250,000-400,000 platelets per cubic mm with a life span 5-9 days.
Platelets are removed in the SPLEEN & LIVER.
• Thrombopoietin-stimulates MEGAKARYOCYTES to form platelets
PLATELETS STOP BLOOD LOSS BY FORMING A PLATELET PLUG. Platelets contain many
secretory vesicles (granules) that contain chemicals and promote clotting. When platelets adhere to
collagen, they release ADP and other chemicals from their secretory vesicles. Many of these chemicals,
including ADP, induce changes in the platelet surfaces that cause the surfaces to become “STICKY”. As a
result, additional platelets adhere to the original platelets and form a “plug”. Thromboxane A-directly
promotes platelet aggregation.

BLOOD is 8% of total body weight (4-6 liters), its temperature is 38 C, and pH (7.35-7.45). Blood
consists of:
• 55% PLASMA-the LIQUID PORTION of blood that is 91% water, 7% protein, and 2% solutes
▪ 7% plasma proteins are Albumins (55%), Globulins (38%), and Fibrinogen (7%).
▪ 2% solutes are metabolic end products, food materials, respiratory gases, hormones, and
ions.
▪ SERUM = blood plasma without fibrinogen (after coagulation).

• 45% FORMED ELEMENTS (Leukocytes (WBC), Platelets, and Erythrocytes).

LEUKOCYTES (White Blood Cells):

1. Neutrophils –most numerous leukocytes (make up 60-70% of all leukocytes). Are granulocytes.
2. Lymphocytes-make up 20-30% of all leukocytes. Lymphocytes are agranulocytes.
3. Monocytes-make up 2-6% of all leukocytes. Monocytes are agranulocytes.
4. Eosinophils-make up 1-4% of all leukocytes. Eosinophils are granulocytes.
5. Basophils-the LEAST ABUNDANT leukocytes (0-1%). Basophils are granulocytes.

FORMED ELEMENTS:-are all derived from Hemoctyoblasts in red bone marrow.

1. Erythrocytes-are 7.5microns in diameter. Function to transport oxygen and aid in the CO2
transport.

2. Platelets-are 2.5microns in diameter; involved in hemostasis and blood coagulation.

3. Leukocytes (Granulocytes or Agranulocytes):

▪ Neutrophils-are 12-14 microns; are phagocytic cells that function to ingest bacteria and
other foreign substances.
▪ Eosinophils-are 9 microns; participate in destruction of parasites (parasitic worms) and
play a role in certain allergic inflammatory responses.
▪ Basophils-12 microns; release chemicals like HISTAMINE & HEPARIN.
▪ Monocytes-20-25 microns; develop into large phagocytic cells (macrophages) within
the tissues.
▪ Lymphocytes-9-14 microns; involved in specific immune responses including antibody
production.

HEMOCYTOBLASTS form committed progenitor cells, which then form formed elements and give
rise to:
1. Proerythroblast>ErythroblastENormoblastNReticulocyteRErythrocyte

2. Myeloblast (a unipotent stem cell in the stroma of marrow)→ProgranulocyteP(Neutrophilic,

 Eosinophilic, & Basophilic myelocyte)((Neutrophilic, Eosinophilic, & Basophilic band cell)(
Neutrophil Eosinophil, & Basophil.

3. Monoblast→Monocyte

4. Lymphoblast→→Lymphocyte

5. Megakaryoblast→MegakaryocyteMPlatelet

 EMBRYOLOGY
BRANCHIAL ARCHES (pharyngeal arches)-a series of rounded, mesodermal ridges on each side of
the future head and neck region that begin to develop around the 4th week of embryonic life. The
first three arches help form the face and oral cavity. The first arch develops into the mandible and a
large part of the maxilla. 1st, 2nd and 3rd arches play a part in the development of the tongue.

• A TYPICAL BRANCHIAL ARCH contains an artery, cartilaginous bar (Meckel’s cartilage), a

muscular component, and nerve.

• Most oral cavity structures develop from the FRONTAL PROCESS and FIRST
BRANCHIAL ARCH.

• Facial development begins to form during the 4th week of embryonic development, with the
STOMODEUM marking the earliest sign of facial development.

• The external face is completed by the 6th week. Between 6th and 8th weeks palate develops and
divides into the nasal and oral cavities. Development continues into the 12th week when soft palate
development is complete (FACIAL DEVELOPMENT IS COMPLETE BY THE 12th WEEK).

BRANCHIAL ARCHES begin to develop early in the 4th week as neural crest cells migrate into the
future head and neck region. By the end of the 4th week, four well-defined pairs of branchial arches
are visible externally; 5th and 6th arches are small and cannot be seen on the embryo surface. It is the
proliferative activity of neural crest cells that produce the discrete swellings or branchial arches.

PHARYNGEAL POUCHES-paired evaginations of pharyngeal endoderm that line inner aspects of

branchial arches, which give rise to epithelial tissues and organs (e.g. thymus, thyroid).
1. 1st pharyngeal pouch-forms tympanic membrane, auditory tube, & cavities of middle ear.
2. 2nd pharyngeal pouch-lymphatic nodules and palatine tonsil.
3. 3rd pharyngeal pouch-gives rise to inferior parathyroid gland, thymus gland.
4. 4th pharyngeal pouch-forms superior parathyroid gland, ultimobranchial body which gives rise to
parafollicular cells (C cells) of the thyroid gland (produce calcitonin).
5. 5th pharyngeal pouch-a rudimentary structure that becomes part of the fourth pouch.

De-George Syndrome-deletion defect in chromosome 22 with underdevelopment of the 3rd and 4th
branchial pouches. The most common microdeletion syndrome causing heart and palatal defects.

FIRST BRANCHIAL ARCH during the 4th week of embryonic development, it divides to form two
prominences or processes: larger mandibular process forms the mandible, and a smaller maxillary
process forms the maxilla, zygomatic bone, and squamous part of the temporal bone.
• 1st branchial arch also gives rise to the tuberculum impar (median tongue bud) and two lateral
lingual swellings (distal tongue buds) that help form the tongue. 2nd and 3rd branchial arches also
contribute to tongue formation.
• As demonstrated by the pattern of sensory innervation, 1st, 2nd, and 3rd branchial arches are
 involved in tongue development.
• corner of the mouth is formed by the fusion of the maxillary and mandibular processes.

Embryologic structures derived from the first branchial arch: tuberculum impar, maxillary process,
mandibular process, and lateral lingual swellings. Intermaxillary process IS NOT derived from the first
branchial arch.
MANDIBLE: THE FIRST PART OF THE FACE TO FORM IN THE EMBRYO. Mandible forms
from the merging of the medial ends of the two large mandibular processes (prominences) of the 1st
branchial arch during the fourth week of embryonic development. The mandible (except the condyles)
and maxilla are mostly formed by intramembranous ossification.

MAXILLA: formed by merging of the two smaller maxillary processes of the 1st branchial arch. These
maxillary processes also form upper cheek regions and most of the upper lip.

3 FACIAL PROMINENCES (processes) contribute directly to formation of the lips:

1. Maxillary processes-merge to form most of the upper lip.
2. Frontal nasal processes (2 medial nasal processes)-merge to form the philtrum of upper lip.
3. Mandibular processes-merge to form the lower lip.

CLEFT LIP-results from failure of maxillary and medial NASAL PROCESSES to fuse. Can be
unilateral or bilateral.

CLEFT PALATE-occurs when the PALATINE SHELVES fail to fuse. Affects 1:700 births worldwide.

FRONTAL NASAL PROCESS (prominence)-produced by the growth of the forebrain; it develops the
forehead and nose. Nasal placodes-thickened areas of specialized ectoderm that form on each side of
the frontal nasal process. Elevations form at the margin of nasal placodes.
• Two lateral nasal processes (prominences)-form the sides (alae) of the nose.
• Two medial nasal processes (prominences)-form bridge of the nose, nostrils, and philtrum of
upper lip.

Merger of the two MEDIAL NASAL PROCESSES (prominences) FORM THE PRIMARY
PALATE. These elevations are proliferations of mesenchyme at the margins of the nasal placodes that
develop on each side of the lower part of the frontal nasal process.
• PRIMARY PALATE-becomes the pre-maxillary part of the maxilla, which contains the central
and lateral incisors. The primary palate gives rise only to a small part of the adult hard palate
(anterior to the incisive foramen).

• SECONDARY PALATE-forms hard and soft palates, extending from the region of the incisive
foramen posteriorly. Secondary palate develops from elevations of the two maxillary processes
= lateral palatine processes.

VESTIBULAR LAMINA-the outer lamina that separates the lips and cheeks externally, and jaw
structures internally in the developing embryo. In the developing embryo, the palate is separated from
the lip by a shallow sulcus in the depths where two epithelial laminae arise. The vestibular lamina is
the outer lamina.
TUBERCULUM IMPAR (median tongue bud)-a structure that gives the first indication of TONGUE
DEVELOPMENT in the embryo at the 4th week of embryonic life.. It’s a median, triangular elevation
that appears in the floor of the pharynx just rostral to the foramen cecum.
• Soon, two distal tongue buds (lateral lingual swellings) develop on each side of the median tongue
bud. These elevations result from the proliferation of mesenchyme of the first, second, and third
branchial arches. These swellings fuse to form the anterior 2/3 of the tongue.
• Posterior 1/3 of tongue is formed by two elevations: copula (from 2nd arch) & hypobranchial
eminence (3rd arch).
• Bifid tongue-result of lack of fusion of distal tongue buds (lateral swellings). Common in South
American infants.

Tongue Development is from Branchial arches 1-4, lingual buds (bilateral lingual swellings),
tuberculum impar, and copula.
STOMODEUM (primitive mouth)-a slight depression of the surface ectoderm the forms the mouth
(oral cavity) in the embryo. Stomodeum is between the first branchial arch and forebrain.
• Initially, stomodeum is separated from the primitive embryonic pharynx by a bilaminar
membrane (buccopharyngeal membrane a.k.a. oropharyngeal membrane) composed of
ectoderm externally and endoderm internally. The membrane ruptures at about 3 ½ weeks (24
days), bringing the primitive mouth in contact with the primitive pharynx.

DERIVATIVES OF BRANCHIAL ARCH CARTILAGES:

• First arch cartilage (Meckel’s cartilage)-the cartilaginous bar (rod) of the first branchial arch,
closely related to the developing middle ear, and becomes ossified to form the malleus & incus of
the middle ear. Meckel’s cartilage is a model for the mandible, but does not participate in the
formation of any part of the mandible. Its fate is said to be dissolution with minor contributions
to ossification.

• Second arch cartilage (Reichert’s cartilage)-also closely related to the developing middle ear,
and becomes ossified to form the stapes of the middle ear and styloid process of the temporal
bone.

• Third arch cartilage-ossifies to form part of the hyoid bone.

• Fourth & sixth arch cartilages-fuse to form the laryngeal cartilages (except for epiglottis). Fifth
and sixth arches are rudimentary.

Wolffian duct (Mesonephric duct)-an embryonic duct that forms the male internal genitalia (epididymis,
vas deferens, and seminal vesicles). Develops in males and females, but is obliterated in the female.

Lung, liver, pancreas, and gallbladder each develops as an outpocketing of the gut tube. THE SPLEEN
DOES NOT DEVELOP FROM THE GUT TUBE.


THE CELL

PROTOPLASM-a viscous, translucent, watery material that is the primary component of plant and
animal cells. It contains a large percentage of water, inorganic ions (potassium, calcium, magnesium, and
sodium), and naturally occurring organic compounds (proteins, lipids, and carbohydrates). Types of
protoplasms:
1. Nucleoplasm-the protoplasm of the cell nucleus that plays a role in reproduction.

2. Cytoplasm-the protoplasm of the cell body that surrounds the nucleus and converts raw materials
into energy. A clear, thin film of protoplasm (cell membrane) always surrounds the cytoplasm.
Ectoplasm-the outer part of the cytoplasm.

3. Cytoplasm is the site of most synthesizing activities and contains:

• Cytosol-viscous, semitransparent fluid that is 70-90% water.

• Organelles: mitochondria, ribosomes, vacuoles, lysosomes, centrosomes, peroxisomes.

• Metaplasm (cytoplasmic inclusions)-lifeless substances (yolk, fat, starch) that may be

stored in various parts of the cytoplasm. Examples: glycogen (carbohydrate deposits in
liver cells), fat deposits, pigment granules (deposits of colored substances). Two types
of pigment granules:

1. Lipofuscin-yellowish-brown substance that increases in quantity as cells age.

2. Melanin-abundant in epidermis of the skin and retina.

ORGANELLES:
1. Centrosomes-organelle that contains centrioles (short cylinders adjacent to the nucleus that take
part in cell division).

2. Peroxisomes-contain oxidases, enzymes capable of reducing oxygen to hydrogen peroxide and

hydrogen peroxide to water. Beta-oxidation of very long chain fatty acids begins in peroxisomes.

3. Ribosomes-sites of most protein synthesis (translation). Bind messenger RNA and transfer RNA
to synthesize polypeptides and proteins.

4. Mitochondria-threadlike structures within the cytoplasm that provide most of body’s ATP (fuels
cellular activities). Involved in cellular respiration and metabolic energy production in
eukaryotes.

5. Vacuoles-store and excrete various substances within the cytoplasm.

6. Lysosomes-digestive bodies formed in the golgi apparatus that break down foreign or damaged
materials in cells. Contain hydrolytic enzymes.
 7. Cytoskeletal elements-form a network of protein structures.

8. Endoplasmic Reticulum (ER)-organelle & extensive network of membrane-enclosed tubules in

the cell cytoplasm involved in protein and lipid synthesis, and transport these metabolites
within the cell. N-linked glycoproteins are the most commonly found in the ER.
• Granular (rough-surfaced ER)-has ribosomes attached to the membrane surface.
• Agranular (smooth-surfaced ER)-no ribosomes, but enzymes that synthesize lipids.

CELLULAR COMPONENTS:
1. Golgi Apparatus-synthesizes COMPLEX CARBOHYDRATES that combine with protein
produced by RER to form secretory products (e.g. lipoproteins). The “manufacturing and
shipping center” where modification and assembly of o-linked glycoproteins occurs. Pro-collagen
filaments are produced by the golgi apparatus.

2. Endoplasmic Reticulum-extensive network of internal membrane-enclosed tubules. RER is covered

with ribosomes and produces certain proteins. Smooth ER contains enzymes that synthesize lipids.
Involved in coordinating protein synthesis. SYNTHESIZES STEROIDS. Two types of ER:
• Smooth ER (contains ribosomes)-where fatty acids and phospholipids are synthesized and
metabolized. Primary function is lipid and carbohydrate synthesis.

• Rough (granular) ER-where ribosomes synthesize certain membrane and secreted proteins.

• Active cells (fibroblasts, osteoblasts, etc.) contain an abundance of Rough ER.

3. Ribosomes-cellular structures composed of rRNA & protein. The site of protein synthesis in cells.

4. Cell (plasma or cytoplasmic) Membrane-a semi-permeable membrane that serves as the cell’s
external boundary. It consists of a double layer of phospholipids with protein molecules. Cell
membrane is a basic component of a typical cell that serves as the cell’s external boundary,
separating it from other cells and from the external environment.
• cell membrane controls the exchange of materials between the cell and its environment by
various processes (i.e. osmosis, phagocytosis, pinocytosis, and secretion).

• cell membrane is a selectively permeable membrane that forms the protoplasmic boundary
of all cells. In bacteria, the cell wall surrounds the cell membrane.

• cell membrane can only be observed with an ELECTRON MICROSCOPE.

5. Nucleus-cell’s control center that plays a role in cell growth, metabolism, and reproduction. Nucleus
is surrounded by two membranes (inner and outer) and contains DNA. Has a double-unit membrane.
RNA and DNA are distinguished by the FEULGEN STAIN REACTION.

6. Nucleolus-a dark-staining NON-MEMBRANE BOUND structure that lies inside the nucleus that
controls protein synthesis. Nucleolus synthesizes, ribosomal (rRNA). It’s an RNA-rich intranuclear
body SITE OF rRNA SYNTHESIS. NOT BOUND BY A LIMITING MEMBRANE!

7. Nuclear membrane-supports the nucleus, and controls passage of materials between the nucleus and
 cytoplasm.

8. Mitochondria-an organelle of the cell cytoplasm that consists of an inner membrane and outer
membrane (like the nucleus) and principal energy source of the cell (major site of ATP production).
Involved in ALL oxidative processes, is MATERNALLY transmitted, and CONTAIN CYCLIC
DNA.

9. Fibrils & microtubules-support cytoplasm and transports materials within the cytoplasm.

10. Cilia & flagella-move particles along the surface of a cell, or moves the entire cell itself.


CELL MEMBRANE

CELL MEMBRANE (Plasma Membrane)-a fluid-mosaic composed mainly of lipids and proteins. Its
a “fluid-mosaic” since its lipids and proteins can diffuse laterally within the plane of the membrane.
Hydrophobic interaction is the primary force stabilizing the lipid-protein complex in cell membranes.
Cell membrane is present in both prokaryotic and eukaryotic cells.
• Lipids-form a bilayer with their hydrophilic heads interacting with water on both the extracellular
and intracellular surfaces; the lipids hydrophobic fatty acyl tails are in the center of the cell
membrane.

• Cell membranes lipids: Phospholipids (sphingomyelin, phosphatidyl choline), Gangliosides, and

Cholesterol.

• Peripheral proteins-embedded at the periphery and can be removed by detergents.

• Integral proteins-span from one side of the membrane to the other side. Integral proteins are
associated with the hydrophobic phase of the bilayer.

• Carbohydrates-are attached to proteins and lipids on the exterior side of the cell membrane.

• CHOLESTEROL-the most abundant non-phospholipid component of the cell membrane.

FUNCTION OF CELL MEMBRANE is primarily to regulate the flow of material in and out of the
cell. The cytoplasmic membrane is a selectively permeable barrier (movement of molecules across the
membrane is selectively restricted).
• Polar (hydrophilic “water loving”)-molecules or groups soluble in water (ions, glucose, urea).
Molecules and ions LARGE & POLAR move across the membrane via TRANSPORT
SYSTEMS.

• Nonpolar (hydrophobic)-molecules or groups poorly soluble in water (oxygen, carbon dioxide,

alcohol). SMALL, NONPOLAR molecules easily penetrate the biologic membrane quiet readily.

When Active Transport is involved in moving a solute across a biologic membrane expenditure of
metabolic energy occurs, the system gains free energy, solutes rapidly move across the biological
membrane AGAINST THE CONCENTRATION GRADIENT in one direction, and PROTEINS are
the specific binding molecules used for active transport. Active transport systems generally involve
specific binding molecules (PROTEINS).

Biological Cell Membranes (6 common features):

1. SHEET-LIKE STRUCTURES only a few molecules thick (60 to 100 A thick).

2. CONSIST MAINLY OF LIPIDS & PROTEINS (carbohydrates are attached to exterior).

 3. MEMBRANE LIPIDS are small molecules that form bimolecular sheets (lipid bilayers) in
aqueous media. Lipid regions are BARRIERS to the flow of POLAR MOLECULES.

4. PROTEINS that make up the cell membrane function as:

1. Transporters-proteins that transport substances across the cell membrane.
2. Enzymes-proteins that catalyze biochemical reactions.
3. Receptors-proteins that bind hormones or growth factors.
4. Mediators-proteins that aid in triggering a sequence of events.

5. MEMBRANES ARE NONCOVALENT ASSEMBLIES. The protein and lipid molecules are
held together by many non-covalent interactions.

6. MEMBRANES ARE ASYMMETRIC. The inside and outside faces are different. One side
contains the N-terminal residues of proteins, the other side has polar heads of phospholipids
oriented towards it.

LIPID BILAYER (bimolecular sheets) is the basic structure of cell membranes formed by
phospholipid molecules in an aqueous environment (water). Consists of two regions:
• polar regions (negative charged phosphate group) are located at the surfaces of the lipid bilayer
to interact with water (hydrophilic).
• non-polar regions (fatty acid tail portion) are oriented toward the interior of the bilayer away
from the water (hydrophobic).
• In the lipid bilayer, globular proteins (peripheral and integral) are embedded at irregular
intervals, held by hydrophobic interactions between the membrane lipids and hydrophobic
domains in the proteins.
• When suspended in water, lipids spontaneously form bilayer structures stabilized by hydrophobic
interactions.
• lipid bilayer serves as a permeability barrier, yet it is quite fluid. The membrane mosaic is fluid
because of non-covalent interactions among lipids, and between lipids and proteins, leaving
individual lipid and protein molecules free to move laterally in the membrane plane.

CILIA & FLAGELLA-cell motile projections made of microtubules designed to either move the cell
itself, or move substances over or around the cell. They have the same internal structure; but FLAGELLA
ARE MUCH LONGER THAN CILIA.

1. CILIA-the primary purpose of cilia in mammalian cells is to move fluid, mucous, or cells over
their surface. CILIARY MOVEMENT is a whip-like movement on the cell surface. This
movement occurs in only two places in the human body; on the inside of surface of the
respiratory airways, and inside surfaces of uterine tubes (fallopian tubes) of the female
reproductive tract. Cilia are found in the trachea, bronchioles, primary bronchi but not in
alveolar ducts of the respiratory system.

2. FLAGELLA-present in the human body ONLY IN SPERMATOZOA. In contrast to cilia,

flagella move in quasi-sinusoidal waves (not whip-like movements).

AXONEME-distinctive array of MICROTUBULES in the core of cilia and flagella comprised of a

central pair surrounded by a sheath of nine doublet microtubules (characteristic 9+2 pattern).
• The 9 peripheral pairs of DOUBLETS share a common wall of 2-3 protofilaments. The central pair
of tubules are separated from one another and enclosed in a CENTRAL (SINGLE) SHEATH.
The doublets and central sheaths are linked by NEXINS (proteins).

• Dynein-family of cytoskeletal MOTOR PROTEINS the move along microtubules to convert ATP
stored chemical energy into mechanical work. Dynein drives the beat of cilia and flagella and is
involved in cellular transport.

MICROVILLI-finger-like evaginations that greatly increase the efficiency of absorption and the surface
area of the cell. Found mostly on the mucosa of the small intestine. Microvilli also form the brush
border of NEPHRONS IN THE KIDNEY. The core of a microvillus consists of microfilaments.

MICROTUBULES-a special type of filament composed of polymerized TUBULIN (protein)

molecules. Microtubules are cylindrical, hollow structures distributed throughout the cytoplasm of
eukaryotic cells. Microtubules provide structural support and assist in cellular locomotion and
transport. Microtubules make up the core of cilia.

BARR BODY-sex chromatin body found IN FEMALES, the genetic activity of both X chromosomes is
essential only during the first few weeks after conception. Later, development requires just one
functional X chromosome. The other X chromosome is inactivated and appears as a dense chromatin
mass = BARR BODY which is attached to the nuclear membrane in the cells of a normal female. In
cells of a normal male, who has only one functional X chromosome BARR BODY IS ABSENT IN
MALES. Barr body’s presence is the basis of sex determination tests (e.g. amniocentesis).

• Barr body found in certain epithelial cells is significant because it assists in differentiating
between sexes. EMBRYO’S SEX CAN BE DETERMINED BY WEEK 8 OF
DEVELOPMENT.

CELL CYCLE consists of GROWTH, SYNTHESIS, & MITOSIS:

1. Growth-the increase in cellular mass as the result of metabolism.
2. Synthesis-the production of DNA and RNA to regulate cellular activity.
3. Mitosis-splitting of the nucleus and cytoplasm to form TWO DIPLOID CELLS.

MITOSIS (M phase)-equal division of material in the nucleus (karyokinesis) followed by division of

the cell body or cytoplasm (cytokinesis). Mitosis results in two exact duplicates of the original cell
(DIPLOID DAUGHTER CELLS).
• All human body cells (somatic cells) EXCEPT GAMETES (sex cells) undergo mitosis. Mitosis
results in two daughter cells, each containing 23 pairs of chromosomes (46) = DIPLOID
NUMBER.
• The diploid number of chromosomes is maintained in proliferating somatic cells by MITOSIS.

MITOSIS Occurs in 5 Phases (1 inactive and 4 active phases): PROTEIN PRODUCTION STOPS!
1. Interphase (the only INACTIVE phase)-it’s the period of time between one mitosis and the next.
It’s the interval between successive cell divisions during which the cell is metabolizing and the
chromosomes are directing RNA synthesis. Interphase has 3 phases: G1 (first gap or growth
 phase), S (DNA synthesis), and G2 (second gap or growth phase).

2. Prophase-chromosomes become distinct and start dividing into chromatids, centrioles move to
opposite sides of cytoplasm, nuclear membrane and nucleolus disappear, microtubules appear.

3. Metaphase-chromosomes become arranged midway between centrioles; spindle is complete.

Chromosomes align at the EQUITORIAL PLATE.

4. Anaphase-centromeres separate and duplicated parts of chromosomes become separated.

Beginning of cell division.

5. Telophase-chromosomes elongate and form chromatin threads, nuclear membranes appear around
each chromosome set, nucleoli appear, microtubules disappear. End of cell division.

MEIOSIS-involves only GAMETES (ova and spermatozoa). Meiosis is cell division where genetic
material between homologous chromosomes is intermixed, and the number of chromosomes in the 4
daughter cells diminishes by half. Meiosis occurs in Seminiferous Tubules. Meiosis has two divisions
separated by a resting phase.

CELL TURNOVER RATE varies greatly from one tissue to another (i.e. there is rapid turnover in
the epithelium of the alimentary canal and epidermis, and slow turnover in the pancreas and thyroid.

CHROMOSOMES-composed of DNA and PROTEIN. Chromosomes appear as a network of

chromatin granules (chromatids) in the non-dividing cell. Except in gametes (germ cells), chromosomes
appear in pairs. One chromosome from each pair comes from the male germ cell (sperm), the other from
the female germ cell (ovum).
• NORMAL HUMAN CELLS contain 23 pairs of chromosomes (46 chromosomes). In these
cells, 22 pairs are homologous chromosomes (autosomes) that contain genetic information that
controls the same characteristics or functions. The 23rd pair contains sex (X and Y)
chromosomes. The composition of these chromosomes determine gender: XX produces a genetic
female; XY a genetic male.

• Chromatin-consists of fine strands of DNA and a protein base (histones). Chromatin has two
forms: Euchromatin (active loose fibrils) and Heterochromatin (inactive dense fibrils).

• Chromatids-are attached at the centrally located and constricted centromere, to which the
spindle fiber is attached during mitosis.

B CELLS (B-Lymphocytes)-a principal type of white blood cell that completes maturation in bone
marrow and migrates to lymphoid organs (lymph nodes, spleen, etc.) B-lymphocytes ARE
COMMITTED TO DIFFERENTIATE INTO ANTIBODY-PRODUCING PLASMA CELLS
involved in antibody-mediated immunity.
• PLASMA CELLS are further differentiated B cells that are very important in the production
of antibody. Plasma cells are found in bone marrow, C.T., and in blood. Plasma cells have a
short life span (5-10 days).

T CELLS (T-Lymphocytes)-a principal type of white blood cell that completes maturation in the
THYMUS. T cells are important in cell-mediated immunity and in the modulation of antibody-
mediated immunity. Account for 70-80% of circulating lymphoctyes and are more numerous than B-
cells. HIV infects CD4 helper T-cells. Two Major Classes: Helper T cells and Cytotoxic T cells.

STEM CELLS-a formative cell present in red bone marrow that gives rise to a specific specialized cell
such as a blood cell (erythrocyte or leukocyte), B cells, T cells, or macrophages.

MACROPHAGES-any phagocytic cell of the reticuloendothelial system concerned with defense

against bacterial invasion. Macrophages include Kupffer cell in the liver, splenocyte in the spleen, &
histiocytes in the loose C.T.

MAST CELLS-large cells with coarse cytoplasmic granules containing HEPARIN (anticoagulant),
HISTAMINE (vasodilator), and other substances. Mast cells (resemble basophils) are found in most
loose C.T. especially along the path of blood vessels. Act as mediators of inflammation on contact
with an antigen.
• Mast cells & basophils liberate heparin into the blood. Heparin can prevent blood coagulation
and speed the removal of fat particles from the blood after a fatty meal. Mast cells and basophils
both release histamine and smaller quantities of bradykinin, and serotonin. It is mainly the mast
cells in inflamed tissues that release these substances during inflammation.

• Mast cells & basophils play an exceedingly important role in allergic reactions because the
type of antibody that causes allergic reactions (IgE) has a special propensity to become attached
to mast cells & basophils. The reaction between antigen and antibody causes the mast cell or
basophil to rupture and RELEASE exceedingly large quantities of HISTAMINE,
BRADYKININ, HEPARIN, SRS-A (slow-reacting substance of anaphylaxis), and
LYSOSOMAL ENZYMES. This causes local vascular and tissue reactions that cause most
allergic reactions.


CENTRAL NERVOUS SYSTEM (CNS)

CEREBRUM-divided into right and left hemispheres connected by nerve fibers = CORPUS
CALLOSUM. Each hemisphere has 4 lobes:
1. Frontal Lobes-control skilled motor behavior (speech, mood, thought, and planning for the
future). In most people, the control of language is situated predominantly in the left frontal lobe.
2. Parietal Lobes-interpret sensory input for the rest of the body and control body movement.
3. Occipital Lobes-interpret vision.
4. Temporal Lobes-generate memory and emotions (contains the limbic system).

CEREBELLUM-functions to maintain muscle tone, coordinate voluntary muscle movement, and control
balance. Cerebellum lies below and posterior to the cerebrum just above the brainstem (pons,
midbrain, & medulla). It is morphologically divided into two lateral hemispheres and a middle portion.
Its function is to coordinate voluntary muscular activity, maintaining equilibrium, and coordination.

BRAINSTEM-lies immediately inferior to the cerebrum, anterior to the cerebellum. 3 Parts:

1. Midbrain-connects dorsally with cerebellum, and contains large voluntary motor nerve tracts.

2. Pons-connects the cerebellum with the cerebrum, and links the midbrain to the medulla
oblongata; serves as the exit point for cranial nerves V, VI, and VII. Pons is the primary link
between the nervous and endocrine systems.

3. Medulla Oblongata-is the lowermost portion of the vertebrate brain, continuous with the
spinal cord. It joins the spinal cord at the level of the foramen magnum. It contains the cardiac,
vasomotor, and respiratory centers of the brain, serving as an autonomic reflex center to
maintain homeostasis, regulating respiratory, vasomotor, and cardiac functions. Mediates
reflexes like blinking, coughing, vomiting, swallowing. It’s the origin of the VAGUS NERVE.

LIMIBIC SYSTEM-the PRIMITIVE BRAIN area deep within the TEMPORAL LOBE of the brain.
Limbic system initiates basic drives: hunger, aggression, EMOTIONAL feelings, sexual arousal, and
screens all sensory messages traveling to the cerebral cortex.

HYPOTHALAMUS-a collection of nerve cells at the base of the cerebrum (CNS) that REGULATES
HOMEOSTASIS, or affects body temperature, water balance, appetite, sleep, pituitary secretions,
emotions, carbohydrate metabolism & autonomic nervous system functions (e.g. sleep and wakeful
cycles). Hypothalamus is a collating center for information concerned with good body health and in
turn, much of this information controls secretions by the pituitary gland.

• Hypothalamus controls many vital processes associated with the autonomic nervous system
(ANS). Hypothalamus is involved in regulating body temperature, water balance, appetite, GI
activity, sexual activity, sleep, and emotions of fear and rage. Hypothalamus also regulates the
release of pituitary gland hormones, thus, it greatly affects the ENDOCRINE SYSTEM.
 • Hypophyseal Portal Vessels-carry hypothalamic releasing factors to anterior lobe of pituitary
gland (adenohypophysis).

THALAMUS-a large ovoid mass of gray matter that RELAYS ALL SENSORY STIMULI (except
olfactory) as they ascend to the cerebral cortex. Thalamus is a collection of nerve cells at the base of the
cerebrum.

BASAL GANGLIA-a large collection of nerve cells (nuclei) at the base of the cerebrum. It consists of
the caudate nucleus, putamen, globus pallidus, substantia nigra, and subthalamic nucleus. The major
masses of the basal ganglia are the caudate nucleus and putamen. FUNCTIONS TO HELP
SMOOTH OUT MOVEMENTS.

BASAL GANGLIA & cerebellum are large collections of nuclei that modify movement on a minute-to-
minute basis. The cerebral (motor) cortex sends information to both, and both structures send information
right back to the cortex via the thalamus. The basal ganglia are located deep to the white matter of the
cerebral cortex.
• Basal ganglia output is INHIBITORY (uses GABA as neurotransmitter), while the cerebellum
output is excitatory. This balance between the two systems allows for SMOOTH
COORDIANTED MOVEMENT, and a disturbance in either system will manifest as
movement disorders:
▪ Parkinson’s disease, Huntington’s disease, Dysmetria, and Ataxia.

• GABA (gamma-amino butyric acid)-an inhibitory neurotransmitter used by the basal ganglia,
and synthesized by the decarboxylation of glutamate by the nervous tissue enzyme glutamate
decarboxylase. GABA is secreted by nerve terminals in the spinal cord, basal ganglia, and cortex.
GABA increases the permeability of postsynaptic membranes to Cl- ions.

• Within the spinal cord, the H-shaped mass of gray matter is divided into horns (roots) that
consist mainly of neuron cell bodies. Cell bodies in the posterior (dorsal) horn (dorsal root
ganglia) relay SENSORY IMPULSES. Cell bodies in the anterior (ventral) horn (root)
transmit MOTOR IMPULSES.

• White matter-surrounds the horns and consists of myelinated nerve fibers that form the
ascending and descending tracts. Sensory pathways are ascending systems (i.e. spinothalmic and
DC-ML systems). Motor pathways are descending systems (i.e. pyramidal and extrapyramidal
systems)

TRACT-a group of axons within the CNS with the same origin, termination, and function; tracts are often
named for its origin and termination (i.e. spinothalmic tract).

• Descending (motor) spinal tracts-carry motor impulses FROM THE BRAIN to lower motor
neurons (LMN) that regulate the activity of skeletal muscles. Upper motor neurons (UMN)
originate in the brain and form the PYRAMIDAL SYSTEM (corticospinal tract) and
EXTRAPYRAMIDAL SYSTEM.

Motor impulses travel FROM THE BRAIN TO MUSCLES via the motor (efferent or descending)
pathways. Originating in the motor cortex of the frontal lobe, motor impulses reach LMN of the
peripheral nervous system via the upper motor neurons (UMN). UMN originate in the brain and form 2
major systems:

1. PYRAMIDAL SYSTEM (corticospinal tract)-is composed of lateral (70-90%) and anterior

(ventral) 10-30% corticospinal tracts. Impulses in the pyramidal system travel from the motor
cortex through the internal capsule of the medulla where they cross to the opposite side and
continue down the spinal cord. Pyramidal System is responsible for FINE, SKILLED,
MOVEMENTS OF SKELTAL MUSCLE.

2. EXTRAPYRAMIDAL SYSTEM-impulses originate in the premotor area of the frontal lobe and
travel to the pons where they cross to the opposite side. The impulses then travel down the spinal
cord to the anterior horn, where they are relayed to the lower motor neurons (LMN). LMN then
carry the impulses to the muscles. CONTROLS GROSS MOTOR MOVEMENTS FOR
POSTURE & BALANCE. Extrapyramidal system tracts include:
• Rubrospinal, reticulospinal, olivospinal, vestibulospinal, and tectospinal tracts.
• Cerebral nuclei of the extrapyramidal system are specifically responsible for
coordination of limb movements.

SPINOTHALAMIC TRACTS (anterolateral system)-a pathway in the somatosensory system that

processes sensations of temperature, pain, and light touch. Its anterior and lateral tracts travel in the
anterolateral quadrant of the spinal cord.

Pain, temperature, and light touch sensations originate in the posterior dorsal horns of the spinal
gray matter, cross to the opposite side of the cord, and ascend via the spinothalamic tracts through
the anterior and lateral white columns of the cord to terminate at the levels of the brain stem and in
the thalamus.
• lateral spinothalamic tracts-convey impulses of pain and temperature.
• anterior (ventral) spinothalamic tracts-carry impulses from receptors sensitive to light touch.

DORSAL COLUMN (Medial Lemniscal System)-carries sensations mainly in the posterior (dorsal)
columns of the cord and then, after synapsing and crossing to the opposite side in the medulla, upward
through the brain stem to the thalamus via the medial lemniscus. Conveys well-localized sensations of
touch, pressure, and vibration.
• Fasciculus gracilis and fasciculus cuneatus are the two tracts that carry the sensory information
in the dorsal columns of the spinal cord. In the medulla, nerve fibers from fasciculus gracilis
synapse in the nucleus gracilis and nerve fibers from the fasciculus cuneatus synapse in the
nucleus cuneatus. Processes from the two nuclei cross to the other side of the medulla and give
rise to the medial lemniscus tract. Nerve fibers from the medial lemniscus tract synapse in the
thalamus.

Ipsilateral-axons of cells that run on the same side as their cell bodies of origin. Right-sided lesions of
the spinal cord result in loss of motor activity on the SAME SIDE.

Contralateral-axons of cells that run on the opposite side as their cell bodies of origin. Right-sided
lesions of the spinal cord result in loss of pain and temperature sensations on the OPPOSITE SIDE.
CNS EXCITATORY NEUROTRANSMITTERS: excitatory neurotransmitters in the CNS
DEPOLARIZE the postsynaptic membrane, bringing it closer to threshold and closer to firing an
action potential. Excitatory neurotransmitters increase the postsynaptic membrane’s permeability to
SODIUM IONS (Na+). The altered membrane potential is the excitatory post-synaptic potential
(EPSP). CNS excitatory neurotransmitters include:
• Acetylcholine (ACh); Catecholamines (Norepinephrine, Epinephrine, Dopamine); glutamate &
serotonin

CNS INHIBITORY NEUROTRANSMITTERS (GLYCINE and GABA) hyperpolarize the

postsynaptic membrane moving it away from threshold and farther from firing an action potential.
Inhibitory neurotransmitters increase the postsynaptic membrane’s permeability to CHLORIDE &
POTASSIUM (Cl & K). The altered membrane potential = inhibitory postsynaptic potential (IPSP).

RECEPTORS-structures generally activated by changes (stimuli) in the internal or external environment

of the body. As a result of the activity of receptors, nerve impulses are initiated within sensory nerve
cells. The generator potential of a receptor is characterized as being graded according to the strength of
the stimulus.

2 Receptor Classes based on the stimuli location in which the receptors respond:
1. Interoreceptors (visceroceptors)-sensitive to pressure, pain, and chemical changes in the body’s
internal environment.
• Proprioceptors-a type of interoceptor that provides information concerning position of
body parts, without the necessity of visually observing the parts. Proprioceptors are
located in muscles, tendons, joints, and the vestibular apparatus. Ex: sensory receptors of
the stretch reflex.

2. Exteroreceptors-receptors that respond to stimuli from the body surface (stimuli like touch,
pressure, pain, temperature, light, and sound).

ADAPTATION-a property of certain receptors where the receptor becomes LESS RESPONSIVE or
stops responding to repeated or continued stimuli of constant intensity. Adaptation is a decrease in the
frequency of action potentials in an afferent neuron despite constant stimulus intensity.

RECEPTORS-also classified based on the type of stimulus to which they are sensitive:
1. Photoreceptors-specialized receptors sensitive to light energy, located only in the RETINAS of
the eyes (rods and cones of the retina).

2. Mechanoreceptors-sensitive to touch, pressure or stretch. Ex: Pacinian corpuscles, muscle

spindles, neurotendinous organs (golgi tendons), & Meissner’s corpuscles.

3. Thermoreceptors-sensitive to changes in temperature (cold and warm). Connected by AC and

C fibers. Ex: Ruffini’s corpuscles, end-bulbs of Krause, and some free nerve endings.

4. Chemoreceptors-stimulated by various chemicals (in food, air, or blood). Ex: taste receptors,
smell (olfactory) receptors, and receptors that monitor pH and gas levels in blood
(osmoreceptors and carotid body O2 receptors).
 5. Nocioceptors and free nerve endings are sensitive to pain.

ADRENERGIC RECEPTORS-membrane receptor proteins located on autonomic effector organs that

are regulated by catecholamines (epinephrine, norepinephrine, dopamine, isoproterenol). Two main
types of adrenergic receptors in the ANS:
1. Alpha Receptors:
• Alpha 1-located on smooth muscle; produce excitation (contraction or constriction)
• Alpha 2-located in presynaptic nerve terminals, platelets, fat cells, and walls of GI
tract; produce inhibition (relaxation or dilation).

2. Beta Receptors:
• Beta 1-located in the heart; produces excitation (increased heart rate and contractility).
• Beta 2-located on smooth muscle; produces relaxation (dilation).

Norepinephrine (NE) stimulates mainly ALPHA receptors. EPI stimulates alpha & beta receptors.

Monoamine oxidase (MAO)-an enzyme that catalyzes oxidative deamination of monoamines like
(norepinephrine, serotonin, and EPI). This deamination process aids in metabolizing excess
neurotransmitters that may build up at post-synaptic terminals.

CHOLINERGIC RECEPTORS (nicotinic & muscarinic)-membrane receptor proteins located on

autonomic postganglionic neurons or on effector organs regulated by ACETYLCHOLINE (ACh).
Cholinergic neurons release acetylcholine neurotransmitter in the sympathetic and parasympathetic
nervous system.

1. Muscarinic receptors-located on all effector organs innervated by postganglionic cholinergic

neurons of the parasympathetic & sympathetic divisions (sweat glands). Muscarinic receptors
are inhibitory or excitatory (mimics the effects of ACh and are blocked by atropine). Found at
salivary glands, heart muscle, and smooth muscle.

2. Nicotinic receptors-located at the ganglia (synapses) between pre and postganglionic

sympathetic and parasympathetic fibers, and at neuromuscular junctions. Nicotinic mimics
the effects of ACh. They are always excitatory and can be blocked by curare and hexamethonium,
but not blocked by atropine. Only found at neuromuscular junctions.

All preganglionic autonomic neurons (sympathetic & parasympathetic) and postganglionic

parasympathetic neurons are CHOLINERGIC (USE ACETYLCHOLINE as its neurotransmitter).
• Cholinergic effects of preganglionic autonomic neurons (sympathetic and parasympathetic) are
EXCITATORY.
• All preganglionic autonomic nerve fibers are exclusively cholinergic (release ACh)
• Cholinergic effects of POSTGANGLIONIC PARASYMPATHETIC fibers are usually
excitatory, with exceptions (i.e. parasympathetic fibers innervating the heart that cause
slowing of the heart).

ACETYLCHOLINE (ACh)-neurotransmitter of the preganglionic sympathetic neurons. ACh

stimulates the action potentials in postganglionic neurons (used by blood vessels of skeletal muscles and
sweat glands). Acetylcholine is the neurotransmitter of both preganglionic and postganglionic
parasympathetic neurons.
• Acetylcholine (ACh)-is the neurotransmitter released from the presynaptic terminal, and the
postsynaptic membrane contains a nicotinic receptor. ACh is synthesized in the neurons from
which it is released.
• Acetylcholine is not released at the terminal sympathetic fibers to the heart because
norepinephrine is released. Cardiac muscle is inhibited by acetylcholine.

• Choline acetyltransferase-catalyzes ACh formation from acetyl CoA & choline in the
presynaptic terminal. ACh is stored in synaptic vesicles.

• Acetylcholinesterase (AChE)-an enzyme that rapidly breaks down ACh into acetate and
choline after its release from the presynaptic terminal onto the muscle end-plate. If
acetylcholinesterase is inhibited, there is prolongation of the end-plate potential (EPP).

ADRENAL MEDULLA-a specialized ganglion of the sympathetic nervous system. Preganglionic fibers
synapse directly on Chromaffin cells in the adrenal medulla that secrete epinephrine (80%) and
norepinephrine (20%) into circulation. Both epinephrine and norepinephrine are direct-acting
adrenergic agonists biosynthesized from the polar amino acid TYROSINE.
• Adrenal Medulla’s main function is to secrete EPI & NE.

1. EPINEPHRINE (ADRENALIN) effects: EPI is most closely related in structure to tyrosine.

• Stimulates glycogenolysis and gluconeogenesis which both raise blood glucose levels
(when injected epinephrine raises blood sugar).
• Stimulates lipolysis in adipose tissue (breakdown of triglycerides into glycerol and fatty
acids).
• Increases rate, force, and amplitude of the heartbeat.
• Constricts blood vessels in skin, mucous membranes, and kidneys.
• Dilates bronchioles in the lungs, and relaxes bronchiolar smooth muscle.
• Activates muscle glycogen phosphorylase and adenyl cyclase.

2. NOREPINEPHRINE (NORADRENALIN)-neurotransmitter stored & released by

postganglionic sympathetic neurons (nerve endings) of the autonomic nervous system
(sympathetic nervous system). Exceptions: sympathetic cholinergics which innervate blood
vessels in skeletal muscle & sweat glands). Norepinephrine is released at the terminal
sympathetic fibers to the heart. Norepinephrine is released 2 ways:
1. by the adrenal medulla into the bloodstream (has widespread effects).
2. directly onto an organ by a postganglionic sympathetic (adrenergic) neuron that stores
norepinephrine.

• Norepinephrine Effects: increases heart rate and force of contraction of heart muscle (but NE
does not affect cardiac output); promotes lipolysis in adipose tissue; and constricts blood
vessels in all areas of the body.

• NE effects are more widespread when it is released into the bloodstream by the adrenal
medulla, rather than directly onto an organ by a postganglionic sympathetic neuron.
 • Tyrosine Derivatives: Dopamine, EPI, NE, and Thyroxine

ADRENAL MEDULLA is supplied by cholinergic preganglionic sympathetic neurons that release

acetylcholine. In response to this, adrenal medulla releases norepinephrine & epinephrine into the
bloodstream which carries the hormones to effector organs.

Outside the nervous system, norepinephrine and its methylated derivative epinephrine act as
regulators of carbohydrate and lipid metabolism. NE and E increase degradation of triacylglycerol and
glycogen, and increase the heart’s output (specifically, epinephrine) and blood pressure. These effects are
part of a coordinated response to prepare the individual for emergency “fight or flight” reactions. The
release of norepinephrine and epinephrine from storage vesicles in the adrenal medulla is caused by:
• Response to fright, exercise, cold, low blood glucose levels.


PERIPHERAL NERVOUS SYSTEM (PNS) &

AUTONOMIC NERVOUS SYSTEM (ANS)

PERIPHERAL NERVOUS SYSTEM (PNS)- sensory neurons running from stimulus receptors that
inform the CNS of the stimuli + motor neurons (effectors) running from the CNS to the muscles, organs,
and glands that take action. PNS is divided into 2 systems:

1. SENSORY SOMATIC NERVOUS SYSTEM-consists of 12 pairs of cranial nerves and 31 pairs

of spinal nerves. Consists of sensory and motor neurons, and INNERVATES SKELETAL
MUSCLES and includes sensations of touch, movement, temperature, and pain. INITIATES
VOLUNTARY ACTION using two groups of motor neurons to stimulate the effectors instead of
one motor neuron.

2. AUTONOMIC NERVOUS SYSTEM (ANS)-a set of efferent (motor) pathways from the CNS
(spinal cord and brain) that innervates and regulates glands (exocrine and endocrine), cardiac
muscle, smooth muscle, and visceral organs.
• ANS synapses between neurons are made in AUTONOMIC GANGLIA. Sympathetic
ganglia-located in the paravertebral chain. Parasympathetic ganglia-located in or near
effector organs.

• ANS CONTROLS INVOLUNTARY MOVEMENT. ANS does not innervate skeletal

muscle (skeletal muscle is innervated by the sensory-somatic nervous system).

AUTONOMIC NERVOUS SYSTEM has two subdivisions:

1. SYMPATHETIC NERVOUS SYSTEM (originates in spinal cord T1-L2) contains two groups of
neurons:
• Preganlionic neurons-arise in the thoracolumbar region of the spinal cord, and pass into
sympathetic ganglia organized into two paravertebral chains that run parallel to and on
each side of the spinal cord.
▪ Each sympathetic preganglionic neuron branches extensively and synapses with
numerous postganglionic neurons. This HIGH RATIO of postganglionic to
preganglionic fibers results in stimulation of the sympathetic nervous system
leading to widespread effects throughout the body.

• Postganglionic neurons-synapse with preganglionic neurons, that reenter the spinal nerve
and ultimately pass out to the various effectors (muscles, organs, and glands).

2. PARASYMPATHETIC NERVOUS SYSTEM-main nerve of the PNS is the VAGUS NERVE

which originates in the medulla oblongata (brain stem). Each preganglionic parasympathetic
neuron synapses with only a few postganglionic parasympathetic neurons located near or in
effector organs (organs, muscles, glands).
Preganglionic neurons (first group) arise in the CNS and run to autonomic ganglia in the body where
they synapse with Postganglionic neurons (second group) that run to the effector organ (cardiac
muscle, smooth muscle, visceral organs, or glands).

MOTOR NEURONS (2 TYPES):

1. Preganglionic neurons-have their cell bodies in the CNS and synapse in autonomic ganglia.
• preganglionic neuron cell bodies of the sympathetic nervous system originate in spinal cord
segments T1-L3 (thoracolumbar region).

• preganglionic neurons of the parasympathetic nervous system originate in the nuclei of

cranial nerves in spinal cord segments S2-S4 (craniosacral region).

• preganglionic neurons of both sympathetic and parasympathetic systems are

cholinergic (parasympathomimetic-they release acetylcholine neurotransmitter).

2. Postganglionic neurons of both the sympathetic and parasympathetic systems have their cell
bodies in autonomic ganglia and synapse on effector organs.
• Parasympathetic postganglionic neurons are cholinergic (release ACh).

• Sympathetic postganglionic neurons are adrenergic (release norepinephrine).



NERVE TRANSMISSION

SYNAPSE-an anatomical junction between two neurons where the electrical impulse in one neuron
initiates a series of events influencing the excitability of the second neuron. Synapses are polarized. A
synapse consists of:
1. Axon terminal (synaptic knob or presynaptic terminal)-synaptic vesicles within the axon
terminal contain a neurotransmitter. Synaptic vesicle contents are released at the
neuromuscular junction when CALCIUM ENTERS the nerve terminal
2. Synaptic cleft-space between the presynaptic and postsynaptic neurons.
3. Postsynaptic membrane-membrane of postsynaptic neuron that contains specific receptors for the
neurotransmitter.

Presynaptic neurons-transmit information TOWARD a synapse. Postsynaptic neurons-transmit

information AWAY from a synapse. Nerve impulses can only travel in one direction because synapses
are polarized.

CHEMICAL SYNAPSE-is the MOST COMMON type of synapse.

1. An axon terminal of a presynaptic neuron closely approaches a dendrite or cell body of a
postsynaptic neuron. However, the two neurons are separated by a small synaptic cleft. Chemical
signaling substances (neurotransmitters) are stored inside the axon terminal of a presynaptic
neuron in synaptic vesicles.

2. The neurotransmitters are released when a nerve impulse arrives at this axon terminal, and then
diffuse across the synaptic cleft and bind to receptors on the membrane of the postsynaptic neuron
= SYNAPTIC TRANSMISSION PROCESS. Synaptic delay-time required to cross a chemical
synapse due to the time required to release the neurotransmitter.

ELECTRICAL SYNAPSE-are RARE; occur in the brain and cardiac and smooth muscle. Connected by
gap junctions that allow local electrical currents resulting from action potentials in the presynaptic
neuron to pass directly to the postsynaptic neuron = EPHAPTIC TRANSMISSION process.

NEUROMUSCULAR JUNCTION (NMJ)-the synapse between axons of motor neurons & skeletal
muscle. Once the end plate region is depolarized by ACh (production of an end plate potential EPP),
local currents cause depolarization and action potentials in the adjacent muscle tissue. These action
potentials in the muscle are followed by muscle contraction. After its release from the pre-synaptic
terminal, ACh is rapidly broken down into acetate and choline by the enzyme acetylcholinesterase
(AChE) on the muscle end-plate. If acetylcholinesterase is inhibited at the neuromuscular junction,
prolongation of the endplate potential (EPP) occurs. Acetylcholine esterase is involved in the
TERMINATION of neuromuscular transmission.

• EPP (End-Plate Potential)-is NOT an action potential, but depolarization of the specialized
muscle end plate.
 • MEEPs (miniature end-plate potentials)-due to the release of sub-threshold (lower)) amounts of
acetylcholine.

• Acetylcholine is not released at the terminal sympathetic fibers to the heart because
norepinephrine is released. Cardiac muscle is inhibited by acetylcholine.

ABSOLUTE REFRACTORY PERIOD-the duration of this period determines the maximal number of
impulses that a nerve fiber can carry. The absolute refractory period of a nerve action potential is
determined by the duration of sodium inactivation gate closure.

RESTING MEMBRANE POTENTIAL-the difference in electrical charge between the inside and
outside of the cell membrane in an UNSTIMULATED (non-conducting) neuron. The difference in
electrical charge across the membrane of an unstimulated neuron is due to an imbalance of charged
particles (ions and proteins) between the extracellular and intracellular fluids. As a result, there are
more positive ions (cations) outside the cell membrane, and more negative ions (anions) on the
inside. This causes the membrane to be POLARIZED (a voltage exists across the membrane; this
“voltage” is the resting membrane potential).

• Visceral smooth muscle and cardiac pacemaker cells LACK A TRUE RESTING MEMBRANE
POTENTIAL.

• Size of the resting membrane potential varies, but in excitable cells is between –70 to –85
millivolts. This means the inside of the neuron is 70mV less than the outside. Resting membrane
potential is created by two activities:

1. Sodium/Potassium Pump-pumps only 2 potassium (K+) ions INTO the cell for every 3 sodium
(Na+) ions it pumps OUT of the cell so it actively results in a net loss of positive charges inside
the cell.

2. Some potassium channels in the plasma membrane are “leaky” allowing a slow facilitated
diffusion of potassium out of the cell.

AMPLITUDE of an action potential is directly proportional to CONCENTRATION OF

EXTRACELLULAR SODIUM (Na+). Increasing [Na+] causes and increases the amplitude of action
potential.

ACTION POTENTIAL-an explosion of electrical activity created by a depolarization current. This

means that some event (a stimulus) causes the resting potential to move from -70mv toward 0mv. When
the depolarization reaches (-55mv), a neuron fires an action potential (in neurons, the action potential is
called the nerve impulse). This is the threshold. If the neuron does not reach this critical threshold level,
then no action potential will fire.

• Action potential is all-or-none response = action potential strength is an intrinsic property of the
cell. As long as they can reach the threshold of the cell, strong stimuli produce no stronger action
potentials than weak stimuli. This action potential is unique to nerve and muscle cells.

• Depolarization-makes the membrane potential LESS NEGATIVE (inside of the cell becomes less
 negative) due to the influx of sodium (Na+) ions across the membrane from the extracellular
fluid into the intracellular fluid.

• After depolarization, the membrane potential starts to go back toward –70mV (a

repolarization) when a rapid decrease in membrane permeability to sodium (Na+) ions occurs,
and a net outward movement of potassium ions (K+) out of the nerve membrane.

• If membrane potential goes past –70mv (hyperpolarization) occurs since potassium (K+)
channels remained open too long (“positive afterpotential”). Gradually, the ion concentrations
return to resting levels, and the cell returns to –70mv.

POSITIVE AFTER POTENTIAL-occurs for a few milliseconds after the action potential is over
CAUSED when many potassium channels remain open for several milliseconds AFTER repolarization
of the membrane is complete. Positive afterpotential allows excess potassium (K+) ions to diffuse out
of the nerve fiber, leaving an extra deficit of positive ions inside the cell, which means a more
negative resting membrane potential.
• After the action potential is over, for a few milliseconds the membrane potential becomes EVEN
MORE NEGATIVE than the original resting membrane potential = Positive Afterpotential.
Gradually, the ion concentrations return to resting levels, and the cell membrane returns to –70mV.

• positive afterpotential is and important indication of the rate at which the nerve fiber is begin
recharged. During positive after-potential, nerve fibers are in a “HYPOEXCITABLE STATE”.

In a myelinated neuron, the myelin sheath provides insulation to the axon, preventing movement of
sodium and potassium through the membrane. If the myelin sheath were continuous, action potentials could
not be produced. However, myelin insulation does not cover the entire axon, since there are breaks in the
myelin sheath = NODES OF RANVIER. Distance between nodes of Ranvier is 0.2-2.0mm. Action
potentials traveling down the axon “jump” or “leap” from node-to-node = SALTATORY
CONDUCTION.

SALTATORY CONDUCTION-increases the conduction velocity of nerve transmission along

myelinated fibers; conserves energy for the axon because only the node depolarizes since sodium
(Na+) and potassium (K+) pumps have to reestablish concentration differences only at the nodes of
Ranvier; allow repolarization to occur with litter transfer of ions. Saltatory conduction depends
largely on the presence of nodes of Ranvier.
• Conduction velocity depends on: DIAMETER of nerve fiber & PRESENCE of myelin sheath.
• Saltatory conduction is a FASTER WAY to travel down an axon than traveling in an
unmyelinated axon. Saltatory conduction allows a faster rate of conduction (up to 100m/sec).

In an unmyelinated neuron the impulse travels along the entire membrane surface = continuous
conduction. Continuous conduction is relatively slow (1.0 m/sec).

NEURILEMMA (sheath of Schwann, Schwann’s membrane)-thin membrane spirally enwrapping the

myelin layers of certain PNS fibers (peripheral nerve fibers), or axons of unmyelinated nerve fibers.
• CNS (brain and spinal cord) nerve fibers ARE NOT ENCLOSED BY A NEURILEMMA. This
is why regeneration of severed axons does not occur in the CNS (brain and spinal cord).
 • Peripheral nerve fibers can regenerate if the soma (cell body) is not damaged and some
neurilemma remains intact. Neurilemma forms a regeneration tube through which the growing axon
reestablishes its original connection. If the nerve originally led to a skeletal muscle, the muscle
atrophies in the absence of innervation, but regrows when the connection is reestablished.

• All axons of PNS have a sheath of Schwann cells (neurilemma) made of the outer layer of
Schwann cells around them. When a Schwann cell is wrapped successively around an axon, it
becomes a myelin sheath.

LOCAL ANESTHETICS effect the nerve membrane by DECREASING MEMBRANE

PERMABILITY to SODIUM (Na+) ions and REDUCING membrane excitability.
• Most local anesthetics act directly on the activation gates of the sodium channels, making it much
more difficult for the sodium gates to open. This decreases sodium membrane permeability, thus
reducing membrane excitability. When the excitability has been reduced below a critical level, a
nerve impulse fails to pass through the anesthetized area.

• Local anesthetics REVERSIBLY BLOCK NERVE IMPULSE CONDUCTION and produce

reversible loss of sensation at their administration site.

• Local anesthetics FIRST AFFECT SMALL NONMYELINATED nerve fibers that conduct pain
and temperature sensations. Local anesthetics then affect touch, proprioception, and skeletal muscle
tone.

• K+ FLUX REMAINS UNCHANGED.

Neurotransmitters are excitatory (causes the postsynaptic neuron to become active) or inhibitory
(preventing the postsynaptic neuron from becoming active). Excitatory neurotransmitters
(acetylcholine, norepinephrine, epinephrine, dopamine, glutamate, serotonin) increase the
postsynaptic membrane’s permeability to sodium (Na+) ions. The altered membrane potential is EPSP
(excitatory postsynaptic potential) and the membrane is hypopolarized. There are 2 ways EPSPs
combine to reach threshold and initiate an action potential:

1. Spatial Summation-results from the convergence of several afferent (sensory) impulses on

the same postsynaptic nerve soma (cell body). Occurs when two excitatory inputs arrive at a
postsynaptic neuron SIMULTANEOUSLY.
• In spatial summation, there is an increase in the number of fibers stimulated. It is the
result of a converging circuit dependent on the simultaneous arrival of impulses from a
large number of receptors.
• Spatial summation in spinal reflexes depends on the simultaneous arrival of impulses from
a large number of receptors.

2. Temporal Summation-occurs when two excitatory inputs arrive at a postsynaptic neuron in

RAPID SUCCESSION. Thus, increasing the frequency of nerve impulses in each fiber.

RECRUITMENT-very similar to spatial summation in that there is a progressive increase in the number
of motor units. Recruitment is the gradual increase in response to a stimulus that has a constant
intensity, but prolonged duration.


HORMONES

OXYTOCIN-hormone secreted by the posterior pituitary (pars nervosa) in response to dilation of the
cervix and to suckling (breast feeding). Oxytocin stimulates smooth muscle of the uterus, and promotes
contraction of myoepithelial cells surrounding the saclike alveoli of the mammary glands, resulting in
the ejection of milk during breast-feeding.
• Although both ADH and oxytocin are stored and released from the posterior pituitary (pars
nervosa), neither hormone is produced there. ADH & Oxytocin are PRODUCED by the
HYPOTHALAMUS (supraoptic and paraventricular nuclei).

ANTIDIURETIC HORMONE ADH (vasopressin)-decreases urine production by increasing water

reabsorption by the renal tubules (INCREASES H2O PERMEABILITY of collecting ducts & distal
tubules to water). Without ADH, extreme loss of water into the urine would occur. At high
concentrations, ADH causes arterioles to constrict (increases blood pressure). It retains body water.

ADH release occurs in response to a decrease of water in the blood; increased sodium
concentration; by pain, stress, or action of certain drugs (epinephrine or norepinephrine).
▪ Sweating (water loss) increases ADH secretion, while drinking large amounts of water
decreases ADH.

▪ ADH Hyposecretion Effects: Diabetes insipidus (polyuria, polydipsia, & polyphagia).

HYPOACTIVITY of the posterior pituitary gland leads to diabetes insipidus.

▪ Nephrogenic diabetes insipidus-”end-organ resistance” to Antidiuretic hormone

(ADH) that results in the inability to concentrate urine (polyuria), & increased serum
osmolarity (resulting from the loss of free water in the urine).

• ADH (vasopressin) is unique because it is produced in the hypothalamus (supraoptic nuclei),

but stored and released into the bloodstream by the posterior pituitary.

• ADH decreases urine production by increasing water reabsorption by the renal tubules (increases
water permeability of the collecting ducts and distal tubules). ADH receptors are located on the
membranes of these ducts and distal tubules.

HYPOTHALAMUS-transmits signals that control almost all pituitary gland secretions. Posterior
pituitary hormones (ADH and Oxytocin) are synthesized in hypothalamic nuclei (supraoptic &
paraventricular nuclei) of the brain, which contain the cell bodies of neurosecretory cells. ADH and
Oxytocin hormones are then transported along the axons of neurosecretory cells to pars nervosa
(posterior pituitary). Neural inputs to the brain influence their release.

ANTERIOR PITUITARY-secretions are controlled by hypothalamic releasing and inhibitory factors

(hormones secreted within the hypothalamus itself) and conducted to the anterior pituitary through minute
blood vessels (hypothalamic-hypophyseal portal system). The major releasing hormones are:
 1. Gonadotropin-releasing hormone (Gn-RH)-stimulates release of FSH and LH.

2. Thyrotropin-releasing hormone (TRH)-produced by the hypothalamus to stimulate TSH release.

3. Corticotropin-releasing hormone (CRH)-stimulate release of ACTH.

4. Growth-hormone-releasing hormone (GH-RH)-stimulates GH release.

5. Prolactin-releasing hormone (PRH)-stimulates release of prolactin.

THYROID-STIMULATING HORMONE (TSH Thyrotropin)-a glycoprotein hormone secreted by

basophils of the pars distalis of the anterior pituitary gland. TSH controls the synthesis and secretion
rate of thyroid hormones (thyroxine & triiodothyronine). Thyroxine, in turn, controls the rates of many
metabolic processes and metabolic rate. Humans moving to arctic regions have been known to develop
basal metabolic rates 15-20% above normal.
o TSH is regulated by TRH which is released in the median eminence of the hypothalamus.

o TSH secretion is inhibited by STRESS by neural influences that inhibit the secretion of
thyrotopin-releasing hormone (TRH) from the hypothalamus.

o EXPOSURE TO COLD is the best know stimuli to increase the rate of thyroid-stimulating
hormone (TSH) secretion by the anterior pituitary gland.
• Grave’s Disease-caused by hypersecretion of TSH (hyperthyroidism).
• Cretinism (young people) or Myxedema (adult hypothyroidism) is caused by TSH
hyposecretion.

THYROGLOBULIN-a glycoprotein hormone (10% carbohydrate) synthesized by the thyroid

follicular cell and iodinated once it has been synthesized. Thyroglobulin contains iodine attached to
tyrosine molecules. The follicle cells of the thyroid gland synthesize thyroglobulin and secrete it into the
colloid-containing regions of the follicles. Here thyroglobulin undergoes iodination and coupling
processes to produce thyroid hormones (thyroxine (T4) and triiodothyronine (T3). The thyroglobulin
molecules containing T3 and T4 are then stored in the colloid-containing regions of the follicles.

WHEN THE THYROID IS ACTIVELY SECRETING, the thyroglobulin molecules are taken back into
the follicle cells and broken down into the thyroid hormones (T3 & T4) that enter the bloodstream
(mostly T4) and produce the following actions:
▪ Normal growth and development (especially the brain).
▪ Affects many metabolic processes and metabolic rate by maintaining normal body temperature.
▪ Increases oxygen consumption and heat production.

THYROID GLAND-composed of follicles filled with a colloid secretory substance. The major
constituent of colloid is thyroglobulin-the large tyrosine-containing glycoprotein that contains the thyroid
hormones.

▪ Thyroid gland secretes two iodine containing amine hormones that are structurally different by 1
iodine atom. Most T4 (thyroxine) is converted peripherally by target cells into T3
(triiodothyronine) which is the more potent thyroid hormone. This T4 conversion into T3
occurs by enzymatic removal of 1 iodine atom. T4 acts primarily as a pro-hormone for T3.
Thyroid Hormones (T3 & T4) ARE THE BODY’S MAJOR METABOLIC HORMONES:
• Thyroid hormones increase glycogenolysis, gluconeogenesis, lipolysis, protein synthesis degradation,
and regulate metabolism by speeding up cellular respiration.

• T3 (triiodothyronine) has several times the biologic activity of T4 (thyroxine), but the ratio of T4:T3 is
20:1. There is more T4, but T3 is more potent and biologically active.

• Thyroid hormone stimulates bone maturation due to ossification and fusion of growth plates.

• Iodine is primarily component important in the biochemical synthesis of thyroid hormones, and
regulating energy metabolism.

CALCITONIN-a linear polypeptide of 32 amino acids produced by parafollicular cells (C cells) of the
THYROID GLAND. When the blood concentration of calcium ions in the plasma rises, calcitonin
secretion increases, lowering the blood-calcium and blood-phosphate levels. Calcitonin acts on bone
cells to SUPPRESS/INHIBIT BONE RESORPTION, and ENHANCE bone formation (the opposite
action of PTH).
• Calcitonin secretion is stimulated by an increase in serum calcium. It acts primarily to
INHIBIT bone resorption (destruction) by inhibiting osteoclast activity.

• Calcitonin promotes excretion in the urine of phosphate, sodium, and calcium by decreasing
their reabsorption in the kidney tubules.

• Parathyroid hormone (PTH), 1,25-DHC, and calcitonin are major regulators of calcium
metabolism.

• CALCITONIN secretion is increased by GASTRIN-released by enteroendocrine cells (G

cells) of the GI tract (stomach) in response to a meal. In calcium regulation, the greatest
elimination of calcium occurs in the GI tract.

PARATHYROID HORMONE (PTH)-secreted by CHIEF CELLS in the parathyroid gland in response

to decreased plasma-calcium levels. Blood plasma-calcium level is the major controller of parathyroid
hormone secretion. PTH is a principal controller of calcium and phosphate metabolism, and is
involved in remodeling of bone. PTH increases plasma-calcium concentration, and decreases plasma-
phosphate concentration.
• PTH production and bone resorption are caused by a diet low in calcium.
• PTH stimulates 1-alpha hydroxylase in the kidney, and stimulates osteoclast activity in bone,
and calcium reabsorption in the kidney.
• PTH inhibits PO4- reabsorption by the kidney.

PTH’s 3 Modes of Action:

1. Osteoclast bone cells increase bone resorption causing release of calcium & phosphate into
blood plasma.
2. PTH acts on kidneys to decrease calcium excretion, but increases phosphate excretion, and
stimulates 1-alpha-hydroxylase in the kidneys.
3. Increases calcium absorption in the GI tract.
Hyperparathyroidism (von Recklinghausen’s disease)-causes extensive bone decalcification marked
by extremely high blood calcium levels and low blood phosphate levels leading to muscular weakness.

Hypoparathyroidism (tetany)-causes decreased bone resorption, decreased renal Ca2+ reabsorption,

increased renal phosphate reabsorption, and decreased production of the active form of vitamin D (1,25-
dihydroxycholecalciferol). Together, these effects decrease serum calcium and increase serum
phosphate.

A deficiency in parathyroid hormone (PTH) causes hypocalcemia (low calcium) and

hyperphosphatemia. A CALCIUM DEFICIENT DIET RESULTS IN PTH PRODUCTION & BONE
RESORPTION.

CALCIUM LEVELS are regulated by parathyroid hormone (PTH) (increased hormone causes bone
resorption) which increases serum calcium levels. Calcium is also regulated by the kidney tubules and GI
mucosa (lowering pH causes increased calcium absorption). The greatest elimination of calcium occurs
in the GI tract. Note: low serum calcium levels result in hyperirritability of nerves and muscles.
• Normal plasma concentration of calcium varies between 8.5 – 10.5 mg/dl.
• Calcium is important in bone and tooth formation, blood clotting, nerve transmission, and muscle
contraction.
• Most bound calcium is transported in BLOOD as an albumin complex.

Phosphorus concentration (normal is 3.0-4.5 mg/dl) is also regulated by parathyroid hormone (PTH).
Increased PTH causes the kidneys to increase the rate of phosphate excretion causing a decrease in
plasma phosphate concentration. Phosphorus is involved in bone & tooth formation, acid-base balance,
release of energy (ADP, ATP).

ADRENOCORTICOTROPIC HORMONE (ACTH)-”STRESS HORMONE” whose secretion is

controlled by the hypothalamus, to which the pituitary gland is attached. When the body is stressed,
corticotropin-releasing factor (CRF) produced by the hypothalamus travels through a network of
capillaries to the anterior lobe of the pituitary, where it induces production and secretion of ACTH by
basophils of the pars distalis. ACTH then stimulates the adrenal cortex to synthesize and secrete
glucocorticoids (cortisol is the major glucocorticoid). ACTH controls release of glucocorticoids
(cortisol).

• Corticosteroids-includes mineralocorticoid (aldosterone), and glucocorticoids (cortisol).

CORTISOL (Hydrocortisone)-the main glucocorticoid produced and secreted by cells of the zona
fasiculata in the adrenal cortex. Cortisol allows insulin, glucagon, and epinephrine to work more
effectively at their target tissues. Cortisol influences carbohydrate, lipid, & protein metabolism.
Glucocorticoids possess anti-inflammatory, metabolic, and immunosuppressive effects. A patient taking
cortisol medication for a long period may experience atrophy of the adrenal cortex due to inhibition
of ACTH production.
• Cortisol is released by the zona fasciculate and exerts permissive actions to allow insulin,
glucagon, and epinephrine to work more effectively at their target tissues.
CORTISOL RELEASE is controlled by ACTH secreted by basophils in the pars distalis of the anterior
pituitary gland. ACTH release is influenced by corticotropin-releasing hormone (CRH) from the
hypothalamus. Cortisol exerts an inhibitory influence on ACTH and CRH release by negative
feedback. Cortisol has a direct INHIBITORY effect on the hypothalamus and anterior pituitary
gland.

CORTISOL ACTIONS:
1. stimulates gluconeogenesis and inhibits glucose uptake by cells (increases blood glucose).
2. anti-inflammatory effects.
3. promotes mobilization of fatty acids into blood from adipose tissue by stimulating lipolysis.
4. suppresses the immune response.
5. maintenance of vascular responsiveness to catecholamines (NE, E, dopamine).
6. increases blood amino acids by stimulating protein breakdown.
7. increases blood fat, sugar, and amino acids.

CUSHING’S SYNDROME-a metabolic disorder resulting from chronic and excessive production of
CORTISOL. The most common cause of Cushing’s syndrome is a PITUITARY TUMOR causing
increased ACTH secretion.

ALDOSTERONE-principal mineralocorticoid secreted by cells in the zona glomerulosa of the

adrenal cortex. Aldosterone promotes reabsorption of sodium into the blood from glomerular
filtrate. Potassium is lost (excreted) in the urine because of the electronegativity created by the
reabsorption of sodium in the kidney tubules. Note: increased blood aldosterone levels result in high
sodium and low potassium levels in the plasma.

• ALDOSTERONE secretion from the adrenal cortex is induced by the sodium-potassium ratio of the
body and by angiotensin (not induced by ACTH). Aldosterone’s primary effect is on the kidney
tubules, where it stimulates sodium retention and potassium excretion. Aldosterone facilitates
reabsorption of sodium in the renal tubules. Aldosterone partially regulates sodium (Na+) balance.

• ALDOSTERONE-primary effect is on KIDNEY (kidney tubules) where it stimulates sodium

retention and potassium excretion to restore extracellular fluid blood volumes to normal.

• Important: Decreased sodium concentration causes kidney juxtaglomerular cells to secrete RENIN
which converts angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II,
which stimulates the adrenal cortex to release aldosterone.

• ADDISON’S DISEASE-caused by hyposecretion (undersecretion) of ALDOSTERONE &

CORTISOL.

PROLACTIN (lactogenic or luteotropic hormone)-major hormone responsible for lactogenesis

(production of milk by the mammary glands).
• PROLACTIN is produced by acidophils in the pars distalis of the anterior pituitary gland.
Prolactin stimulates milk production by mammary glands (during pregnancy for breast
development and after child delivery for lactation). Release of small amounts of prolactin is
caused by the secretion of prolactin-releasing hormone (PRH) by the hypothalamus.
 • HYPOTHALAMUS SYNTHESIZES prolactin inhibitory factor (PIF). Under normal
conditions, large amounts of PIF are continually transmitted to the anterior pituitary gland so that
the normal rate of prolactin secretion is slight. This is why Prolactin is under predominant control
of the hypothalamus. However, during pregnancy and lactation, PIF formation is suppressed,
allowing the anterior pituitary gland to secrete an uninhibited amount of prolactin.

• Blocking the hypothalamic-hypophyseal venous portal system increases prolactin secretion

Important: Most anterior pituitary hormones are enhanced by neurosecretory releasing factors
transmitted from the hypothalamus.

GRANULOSA CELLS in the corpus luteum produces PROGESTERONE & ESTROGEN (it
produces more progesterone than estrogen).
• Corpus luteum-a yellowish mass of cells that forms from an ovarian follicle after the release of a
mature egg (ovulation). If the mature egg is not fertilized and pregnancy does not occur, the
corpus luteum retrogresses to a mass of scar tissue (corpus albicans) which eventually disappears.
If the mature egg is fertilized and pregnancy occurs, the corpus luteum does not degenerate,
but persists for several months.
• Human chorionic gonadotropin (HCG)-produced by the PLACENTA and stimulates corpus
luteum to produce estradiol and progesterone.

FEMALE OVARIES produce ova, female sex hormones (progesterone and estrogen), and follicles.

Two Gonadotropins Produced by ANTERIOR PITUITARY:

1. Follicle stimulating hormone (FSH)-stimulates Graafian follicle development and induces
secretion of estrogens. Stimulates development of the ovarian follicles to the point of ovulation.
FSH exerts its action on germinal epithelium.

2. Luteinizing hormone (LH)-stimulates ovulation and development of the corpus luteum. In

increase in LH triggers ovulation. Ovulation is caused by a shift in the anterior pituitary
gonadotropin secretion with LH predominating in the mixture. Oral contraceptives decrease LH.

GONADOTROPIN-RELEASING HORMONE-produced by the hypothalamus to stimulate the

release of FSH & LH. Once produced, FSH & LH work together to cause ovulation and form the
corpus luteum.

ORAL CONTRACEPTIVES (“the pill”)-contain a combination of synthetic estrogen-like (ethynyl

estradiol and mestranol) and progesterone-like (norethindrone, norgestrel) substances to INHIBIT
OVULATION. Oral contraceptives may weaken the effectiveness of some antibiotics.

• SYNTHETIC HORMONES prevent the rise of luteinizing hormone (LH) which prevents
ovulation. Oral Contraceptive Mechanism: in the presence of estrogen or progesterone (or
synthetic substitute), the hypothalamus fails to secrete the normal surge of LH-releasing factor
(Gonadotropin Releasing Factor). This inhibits release of luteinizing hormone from the anterior
pituitary gland basophils which STOPS OVULATION.

• Ovulation occurs as a result of the estrogen-induced LH surge.

 • Unlike other steroid hormones, ALL ESTROGENS HAVE AN AROMATIC “A” RING.

HORMONES & SITE PRODUCTION:

1. Aldosterone-produced in ADRENAL CORTEX. Helps regulate salt and water balance by
retaining salt and water and excreting potassium.
2. Corticosteroid-produced in ADNREAL CORTEX. Widespread effects throughout the body;
especially has anti-inflammatory action; maintains blood sugar level, blood pressure, and muscle
strength; helps control salt and water balance.
3. Antidiuretic hormone (vasopressin)-produced in POSTERIOR PITUITARY GLAND. Causes
kidneys to retain water and along with aldosterone, helps control blood pressure.
4. Oxytocin- produced in POSTERIOR PITUITARY GLAND. Causes uterus muscles and milk
ducts in the breast to contract.
5. Corticotropin- produced in PITUITARY GLAND. Controls production and secretion of
hormones by the adrenal cortex.
6. Growth Hormone-produced in PITUITARY GLAND. Controls growth and development;
promotes protein production.
7. Luteinizing Hormone-produced in PITUITARY GLAND. Controls reproductive functions
(production of sperm and semen), egg maturation, & menstrual cycles; controls male & female sex
characteristics.
8. Prolactin- produced in PITUITARY GLAND. Starts and maintains milk production in mammary
glands.
9. Thyroid-Stimulating Hormone-produced in PITUITARY GLAND. Stimulates production and
secretion of thyroid gland hormones (T3 and T4).
10. Erythropoietin-produced in KIDNEYS. Stimulates RBC (red blood cell) production.
11. Renin & Angiotensin- produced in KIDNEYS. Controls blood pressure.
12. Estrogen-produced in OVARIES.
13. Progesterone- produced in OVARIES. Prepares the lining of the uterus for implantation of a
fertilized egg and readies the mammary glands to secrete milk.
14. Glucagon-produced in PANCREAS. Raises blood sugar level.
15. Insulin-produced in PANCREAS. Lowers blood sugar level, affects metabolism of glucose,
protein, and fat throughout the body.
16. Parathyroid Hormone-produced by PARATHYROID GLANDS. Controls bone formation and
secretion of calcium and phosphorus.
17. Thyroid Hormone-produced in the THYROID GLAND. Regulates growth, maturation, and the
speed of metabolism.

SOMATOSTATIN-a peptide hormone formed primarily by the median eminence of the hypothalamus
and by delta cells of the pancreatic islets. Somatostatin inhibits secretion of GH, TSH, ACTH,
insulin, glucagons, gastrin, secretin, and renin:
1. inhibits growth hormone (somatotropin), thyrotropin (TSH), and corticotropin (ACTH)
release by the anterior pituitary.

2. inhibits insulin release from pancreatic beta cells, and glucagon release from pancreatic alpha
cells.
 3. inhibits gastrin secretion by the gastric mucosa, and secretion of secretin by the intestinal
mucosa.

4. inhibits renin secretion by juxtaglomerular cells of the kidney.

GROWTH HORMONE (SOMATOTROPIN = GH)-produced by acidophils in the pars distalis of the

anterior pituitary gland.
• Increase GH: sleep, stress, starvation, exercise, hypoglycemia, and puberty hormones
• Decrease GH: somatostatin, somatomedins, obesity, hyperglycemia, and pregnancy.

• GH secretion rate increases or decreases within minutes. Most of the time, GH secretion is related
to the person’s state of nutrition or stress. GH is released in a pulsatile fashion.

• GH is also released in response to a decline in blood glucose concentration and an elevated blood
level of certain amino acids (especially arginine).

• SOMATOTROPIN (Growth hormone) undersecretion produces pituitary dwarfism.

oversecretion causes gigantism (Acromegaly in adults).

• Patients taking growth hormone are likely to exhibit a Positive nitrogen balance-means
nitrogen intake exceeds nitrogen output. May occur after taking growth hormone. Negative
nitrogen balance-means nitrogen output exceeds nitrogen intake.

Growth hormone (somatotropin) in contrast to other hormones, DOES NOT FUNCTION THROUGH
A TARGET GLAND, but directly exerts its effects on all or almost all tissues of they body. GH is
produced by acidophils in the pars distalis of the anterior pituitary gland. GH causes the liver (and
other tissues) to form small proteins SOMATOMEDINS (insulin-like growth factors) that increase
all aspects of bone growth.

Basic Metabolic Effects of Growth Hormone:

• Increased rate of protein synthesis in all cells of the body.
• Decreased rate of carbohydrate utilization throughout the body.
• Increased mobilization of fats and the use of fat for energy.
• GH causes cells to shift from using carbohydrates to using fat for energy (during prolonged
exercise).


GASTROINTESTINAL HORMONES

ENTEROGASTRONE-peptide hormone principally involved in DIGESTION OF LIPIDS, released

by the SMALL INTESTINE in response to the acidity of the duodenal chyme and the presence of fat and
certain amino acids and fatty acids in the chyme.

• Enterogastrone enters the blood and is carried to the stomach, where it depresses the
“pyloric pump” (pumping action of the stomach), thus inhibiting gastric motility which slows
down gastric emptying. Enterogastrone is sometimes considered a hormone itself, or as a group of
hormones (secretin, cholecystokinin, gastrin, and gastric inhibitory peptide).

ENTEROGASTRIC REFLEX-initiated when the duodenum fills with chyme, and also inhibits the
“pyloric pump” thus inhibiting gastric motility and emptying. Function: decreases motility of the
stomach.

GASTRIC INHIBITORY PEPTIDE (GIP)-hormone that enhances insulin release in response to

infusions of glucose. Like secretin, GIP inhibits gastric acid secretion (HCL) and motility, and
potentiates insulin release from beta cells in response to elevated blood glucose concentration. GIP
release is stimulated by presence of fat and glucose in the small intestine.

GASTRIN-GI hormone that stimulates gastric acid secretion (HCL) and stomach motility. Gastrin release
is caused by peptides and amino acids in the gastric lumen, and distention of the stomach.

SECRETIN-functions as a “fireman” released in response to acid (HCL) in the small intestine, and
stimulates the pancreas and bile ducts to release a flood of bicarbonate base and water to neutralize
the acid. Low pH in the duodenum (small intestine) stimulates secretin secretion.

SECRETIN is released when gastric contents (H+ and fatty acids) are delivered to the duodenum.
Low pH (acidic) in the duodenum causes secretin secretion. In turn, secretin causes the secretion of
pancreatic fluid that is high in bicarbonate (HCO3-), which neutralizes H+ in the duodenum. Secretin
Functions:
• Inhibits gastric acid secretion and stomach motility.

• Stimulates pancreas to release a watery fluid (pancreatic juice) that contains lots of
bicarbonate ions, but is low in enzymes (pancreatic juice contains lipase, amylase, trypsinogen,
chymotrypsinogen). Secretin functions in protein digestion by increasing flow of pancreatic
juice.

• Stimulates secretion of bile from the gallbladder.

CHOLECYSTOKININ (CCK)-produced by the small intestine in response to the presence of amino

acids and fatty acids in the small intestine. Cholecystokinin Functions:
• Stimulates release/secretion of pancreatic enzymes (trypsin, chymotrypsin, and
 carboxypeptidase).

• Stimulates GALL BLADDER CONTRACTION and EMPTYING OF BILE.

• Cholecystokinin is secreted from mucosal cells in the first part of the small intestine (duodenum),
and stimulates delivery of digestive enzymes into the small intestine from the pancreas, and
bile from the gallbladder by causing the gall bladder to contract.

BLOOD GLUCOSE concentration (normal is 80-100 mg/dl) is regulated by INSULIN (lowers blood
glucose) and GLUCAGON (increases blood glucose levels). Glucose normally does not appear in
urine although it is freely filtered because it is reabsorbed in the proximal convoluted tubule of the
kidney.
INSULIN-secreted by beta-cells in Islets of Langerhans of the PANCREAS in response to high blood
glucose levels and causes glycogenesis in the liver (conversion of glucose to glycogen). Insulin lowers
blood glucose by stimulating and facilitating glucose uptake and the utilization of glucose as an energy
source by cells. Insulin also promotes the synthesis of glycogen, triglycerides, and proteins (it decreases
blood amino acid concentration). Insulin’s primary action ENHANCES CELL PERMEABILITY TO
GLUCOSE.
• Insulin causes a low concentration of glucose in the blood and high concentration of liver glycogen.
• Insulin is secreted more during the absorptive state than during the post-absorptive state.
• Insulin decreases cAMP, gluconeogenesis, and glycolysis.

INSULIN RELEASE by pancreas beta-cells is increased by:

• increased blood glucose levels (hyperglycemia)-MAJOR FACTOR controlling insulin release.
• increased level of amino acids (arginine, lysine, and leucine) in blood plasma.
• Secretion of glucagon, GH, and cortisol.
• Parasympathetic stimulation.

INHIBITS INSULIN RELEASE: sympathetic stimulation, secretion of epinephrine, norepinephrine, &

somatostatin.

Insulin inhibits lipolysis (it enhances triglyceride synthesis) and stimulates protein synthesis (inhibits
protein breakdown). INSULIN CONSERVES body proteins, carbohydrates, and fat in the body.
Removing the anterior lobe of the pituitary gland results in increased sensitivity to insulin.

GLUCAGON-secreted by alpha-cells in the Islets of Langerhans of the PANCREAS in response to a

drop in BLOOD GLUCOSE. Glucagon is called the “hyperglycemic factor”, and has the opposite effect of
insulin.

Glucagon Release by alpha-cells is promoted by:

o A fall in blood glucose level (hypoglycemia); MAJOR FACTOR OF GLUCAGON
RELEASE.
o Sympathetic stimulation, and secretion of epinephrine and norepinephrine.
o Elevated level of amino acids (especially arginine) in the blood plasma.
o Cholecystokinin secretion.
Factors that DECREASE Glucagon Secretion: rise in blood glucose level, insulin, somatostatin, fatty
acids & ketoacids.

GLUCAGON ACTIONS: the most important function of glucagon is its ability to cause
glycogenolysis (conversion of glycogen to glucose) in the liver. This increases the blood glucose
concentration. Glucagon does not stimulate glycogen degradation in muscle. Other Glucagon Actions:
• Increases blood glucose concentration, blood fatty acid and ketoacid concentration.
• Increases urea production

STEROID HORMONES-derivatives of cholesterol (non water-soluble) that bind to intracellular

receptors, forming complexes that activate or inactivate genes. Steroid Hormones:
• Cortisol, Progesterone, Testosterone (directly controls growth and development of male
secondary sex organs), Estrogen, and Aldosterone.

AMINE HORMONES-derived from TYROSINE (an essential amino acid found in most proteins).
Amine hormones include the thyroid hormones (T3 and T4), and catecholamines (epinephrine,
norepinephrine, and dopamine).

POLYPEPTIDE HORMONES-proteins with a defined, genetically coded structure. Polypeptide

hormones include: anterior pituitary hormones (GH, TSH, FSH, LH, and prolactin); posterior
pituitary hormones (ADH and Oxytocin); pancreatic hormones (insulin and glucagon); and PTH.

• Polypeptide Hormones Characteristics:

1. Synthesized in precursor form by a pre-prohormone.
2. Transported unbound in plasma.
3. Stored in secretory vesicles, and act by generating a second messenger (cAMP).

A PARTICULAR HORMONE does not necessarily affect all cells; only its target cells. Target cells
of a hormone possess receptors to which molecules of a hormone can attach. These receptors can be
located on the plasma membrane or within the cell itself. All major anterior pituitary hormones (except
GH = somatotropin) exert their effects by stimulating “target glands”.

cGMP & cAMP-are SECOND MESSENGERS (cyclic nucleotides) that carry signals from many
peptide and polypeptide hormones from the cell surface to proteins inside the cell. These “second
messenger” molecules intervene between the original message (neurotransmitter or hormone) and the
ultimate effect on the cell. Second messengers act to simulate protein kinases, and they are rapidly
broken down in cells (to terminate response) by phosphodiesterases (enzymes).

• In the contraction process of cardiac and smooth muscle, cAMP relaxes smooth muscle and
contracts cardiac muscle.

• cAMP is formed from ATP in a reaction catalyzed by Adenylate cyclase-an integral protein of
the plasma membrane induced by hormones like glucagon, epinephrine, and parathyroid hormone.

Hormones that use cAMP as a second messenger: glucagon, EPI, ACTH, PTH, TSH, FSH, & LH.
• GLUCAGON, EPINEPHRINE, & PARATHYROID HORMONE induce activation of cyclic
AMP, which increases the rate of glycolysis and gluconeogenesis.
• INSULIN decreases activation of cyclic AMP, while reducing the rate of glycolysis and
gluconeogenesis.


BLOOD

SERUM-the clear, thin and sticky fluid portion of the blood obtained after removing the fibrin clot and
blood cells. Serum contains albumin and globulin, but NO blood cells, platelets, or fibrinogen. Serum =
Plasma - Fibrinogen

PLASMA-pale, yellow liquid portion of blood (makes up 55% of the body’s total blood volume).
Plasma is the intravascular fluid part of extracellular fluid (all body fluid outside of cells). Plasma plays
a critical role in an intravascular osmotic effect that keeps electrolytes balanced, and protects the body
from infection and other blood disorders. Plasma is acellular and is composed of:

1. Dissolved proteins (7%)-consists of albumins, globulins, and fibrinogen.

2. Water (92%).
3. Solutes (2%)-consists of metabolic end products, food materials, respiratory gases, hormones,
ions, clotting factors, and carbon dioxide.

45% of blood consists of formed elements (erythrocytes, leukocytes, & cell fragments (platelets).
The function of platelets in hemostasis is they agglutinate and plug small, ruptured vessels.

ALBUMIN-major SIMPLE protein in plasma that functions to provide colloid osmotic pressure in
plasma. Albumin is formed in the liver, and is the major contributor to colloid osmotic pressure.
• Albumin is often associated with free fatty acid transport in human blood.

• Free fatty acids are transported in blood plasma as a complex with Albumin.

COLLOID OSMOTIC PRESSURE (oncotic pressure)-pressure in plasma that draws water into the
capillaries by osmosis (the capillary membrane is highly permeable to water and other substances
dissolved in plasma and tissue fluids, except plasma proteins (mainly albumin). Colloid osmotic
pressure of the blood is important because it prevents excess loss of plasma fluid from the
capillaries.
• colloid osmotic pressure in the plasma is opposed by the colloid osmotic pressure in the
interstitial fluid, caused by non-diffusible proteins in the interstitial fluid. This pressure draws
water out of the capillaries by osmosis.

• If forces that move fluid out of a capillary are greater than forces moving fluid in, the fluid will
leave, and vice versa.

• Decreased blood colloidal osmotic pressure causes fluid to shift from blood into interstitial
space.

Plasma colloid osmotic pressure (oncotic pressure) acts in the same direction as tissue pressure in
regards to its effect upon the movement of water between the vascular and extravascular space.
KIDNEY is the organ mainly responsible for regulating osmotic pressure in the body fluids (the total
body water contained in blood plasma and in the intracellular and interstitial fluids).

Colloid Osmotic Pressure of the interstitial fluid and Capillary Pressure are two forces that move
fluid out of a capillary membrane:
1. Capillary Pressure-the blood pressure within the capillaries that tends to force fluid out of the
capillaries and into the tissue spaces by filtration through the capillary walls. The colloid osmotic
pressure of the interstitial fluid tends to draw water out of the capillaries by osmosis.

2. Interstitial Fluid Pressure-the pressure of interstitial fluid and it opposes the capillary pressure.
The pressure tends to move fluid out of the tissue spaces into the capillaries. The colloid osmotic
pressure of the plasma (oncotic pressure) opposes the colloid osmotic pressure of the
interstitial fluid. This oncotic pressure tends to draw water into the capillaries by osmosis.
• Intracellular and interstitial body fluids have similar total osmotic pressures.

KEY POINT: if forces tending to move fluid out of a capillary are greater than the forces tending to move
fluid into the capillary, fluid will leave, and vice versa.

HEMOGLOBIN-the oxygen-bearing protein of RBC that constitutes 33% of RBC weight. Under
normal conditions, oxygen is carried to the tissues almost entirely by hemoglobin. Oxygen is picked up in
blood (from the lungs) and forms oxyhemoglobin (HbO2); blood leaving the lungs is saturated with
oxygen and carries oxygen to the tissues with decreased oxygen pressure. Oxygen splits away from the Hb
and creates reduced hemoglobin (HHb).
• Combination of Hb with oxygen (O2) is REVERSIBLE, and whether Hb binds with or releases
O2 depends largely on the oxygen partial pressure (PO2).

• When PO2 is relatively high (as in pulmonary capillaries), Hb binds with a lot of O2, and Hb is
completely saturated.

• At lower PO2 (as in tissue capillaries), Hb binds with less O2 and is only partially saturated.

• Hb molecule components: iron, copper, protein, histidine, & Pyrrole ring.

Factors that Release Oxygen from Oxyhemoglobin (RIGHT SHIFT):

• ↑ arterial PCO2, ↑ body temperature, ↑H+ concentration
• ↓ arterial PO2, ↓ pH (increased H+)

The influences of pH, PCO2, and temperature on binding of oxygen by Hb operate to ensure adequate
delivery of oxygen to active tissues. Active tissues have these characteristics:
• Lower pH: acidic conditions cause decrease in the amount of O2 that binds to Hb. The higher the
H+ concentration ( pH), the less O2 is bound to Hb. This happens for the same reason as carbon
dioxide (H+ bind to Hb, altering the Hb molecule and reducing its affinity for O2).

• Increased arterial PCO2: the partial pressure of carbon dioxide (PCO2) effects the binding of O2
to Hb because carbon dioxide molecules bind with Hb and alter the Hb molecule, thus reducing
their O2 affinity. Thus, the higher the PCO2, the less O2 is bound to Hb. An increase in PCO2 also
 tends to increase the H+ ion concentration, and thus lowers the pH.

• Increased temperature: the higher the body temperature, the less O2 is bound to Hb at any given
PO2.

HEMOGLOBIN-the production of hemoglobin requires IRON, and the body normally contains 4g of
iron. 66% of iron in the body is in the form of hemoglobin. Besides hemoglobin, 15-30% of iron is stored
in the liver, spleen, and bone marrow as intracellular iron-protein complexes = FERRITIN &
HEMOSIDERIN.

IRON IS ABSORBED entirely in the upper part of the small intestine (duodenum) where it
immediately combines in blood plasma with a beta globulin apotransferrin, to form transferrin, which
is then transported in plasma. Iron is bound loosely with transferrin, and can be released to any tissue
cells at any point in the body. The MOST ABUNDANT FORM OF IRON in blood plasma is found
associated with transferrin. Iron is a component of hemoglobin and enzymes involved in energy
metabolism.

Iron transport (ferrous iron) in plasma is almost entirely in the form of the plasma protein
TRANSFERRIN. 60% of excess iron is STORED in the liver where it combines with apoferritin (a
protein) to form FERRITIN. The iron stored in ferritin = storage iron.
• IRON is a mineral very important is FORMATION OF HEMOGLOBIN.
• The dominant factor controlling absorption of iron from the GI tract is the saturation of mucosal
cells with iron.
• COPPER is also involved in hemoglobin synthesis.

HEMOGLOBIN STRUCTURE:
1. Globin (protein) portion-consists of 4 polypeptide chains (2 alpha & 2 beta chains). Globin
proteins incorporate the globin fold (series of 8 alpha helical segments). Globins are involved in
the binding and/or transporting of oxygen.

2. Four disc-shaped heme molecules (non-protein groups)-each heme is a nitrogen-containing

organic pigment molecule that has a single atom of iron in the reduced state (Fe2+ or ferrous
iron) in its center, which combines with one molecule of oxygen. These heme groups are attached
to the polypeptide chains. Dietary components specifically involved in hemoglobin synthesis
are IRON & COPPER.
EACH IRON ATOM reversibly binds with 1 oxygen molecule. Thus, a hemoglobin molecule can
potentially bind with 4 oxygen molecules. When Hb combines with oxygen = oxyhemoglobin. When Hb
is not combined with oxygen = reduced hemoglobin (deoxyhemoglobin).
• Hemoglobin combines reversibly with carbon dioxide at the protein (globin) portion of the
hemoglobin molecule.

• Carbon monoxide decreases the amount of oxygen that can be transported by Hb by competing
with oxygen for hemoglobin binding sites.

• Methemoglobin (Hb-M) contains iron in the ferric state and cannot function as an oxygen carrier.

HEMOGLOBIN TYPES:
1. Hemoglobin A-the NORMAL hemoglobin.

2. Hemoglobin C-abnormal hemoglobin where lysine replaced glutamic acid, causing reduced
plasticity of red blood cells (RBCs).

3. Hemoglobin H-an abnormal hemoglobin that cannot effectively transport oxygen; it is usually
associated with a thalassemia-like syndrome.

4. Hemoglobin M-a group of abnormal hemoglobins where a single amino acid substitution favors
the formation of methemoglobin, and is thus associated with methemoglobinemia.
 5. Hemoglobin S-an abnormal hemoglobin in which valine has replaced glutamic acid due to a
genetic mutation or change in DNA coding. This causes Hb to become less soluble under
decreasing oxygen concentrations and to polymerize into crystals that distort RBC into a sickle-
shape. Associated with sickle-cell anemia.

HEMOGLOBIN carries oxygen to the cells from the lungs and carries CO2 away from the cells to the
lungs. Blood leaving the lungs is 98% saturated with oxygen. On the other hand, in normal venous blood
returning from tissues, the saturation of hemoglobin is 75%.
• HEMOGLOBIN IS ESSENTIAL to the ability of erythrocytes to transport oxygen and
carbon dioxide, and a single erythrocyte contains up to 300 million hemoglobin molecules. Hb
synthesis begins in the erythroblasts and continues through the normal normoblast stage.

• Hemoglobin (Hgb) Test-measures the grams of hemoglobin contained in 1 dl of whole blood and
provides an estimate of the oxygen-carrying capacity of the RBC. Hgb value depends on number
of RBC and amount of Hgb in each RBC. A low Hgb value indicates anemia (low blood
oxygen).

Normal Concentrations of Hemoglobin:

• Women = 12-16gm/dl
• Men = 14-18gm/dl
• Infants = 14-20gm/dl

Carbaminohemoglobin-a hemoglobin that carries CO2 from tissues to the lungs. While 97% of all O2
is transported by Hb, only 30% of CO2 is carried by Hb; the rest attaches to H2O to form carbonic acid
(H2CO3).
• Carbonic anhydrase-a blood enzyme that increases blood CO2 carrying capacity.

• Most CO2 is combined with HCO3- in blood.

ERYTHROPOIETIN-a glycoprotein hormone PRODUCED IN KIDNEYS that STIMULATES RED

BLOOD CELL PRODUCTION by bone marrow. Erythropoietin, thus erythrocytes production is
regulated by a negative-feedback mechanism that is sensitive to the amount of oxygen delivered to the
tissues (particularly the kidneys).

• ANOXIA (low oxygen)-leads to a greater production of erythropoietin, while increased oxygen

supply leads to a decreased production. The site of action of erythropoietin is at the
hemocytoblast (a pluripotent stem cell). Testosterone enhances erythropoietin production,
while estrogenic female sex hormones depress its production.

ERYTHROCYTE-a biconcave disc 7.5 microns in diameter that LACK NUCLEI &
MITOCHONDRIA. Contains hemoglobin, and a lipid membrane containing lipoproteins and specific
blood group substances (A, B, O).
• Erythrocyte’s principal function is to TRANSPORT OXYGEN & CARBON DIOXIDE.

• Men have 5.1-5.8 million cells/cu mm blood. Women have 4.3-5.2 million cells/cu mm blood.
 • Hematocrit-proportion of erythrocytes in a sample of blood (46.2% males; 40.6% for females).

• The amount of bile pigments excreted by the liver is a good indication of the amount of
erythrocyte destruction per day.

• Carbonic anhydrase-found in greatest concentration in erythrocytes, carbonic anhydrase

increases the rate of H2CO3 dissociation.

HEMOSTASIS-complex process by which platelets, plasma, and coagulation factors interact to

CONTROL BLEEDING. Calcium ions are also involved in blood clotting.

• Through a three-part process, the circulatory system guards against excessive blood loss. In this
process, vascular injury activates a complex chain of events vasoconstriction, platelet
aggregation, and coagulation that LEADS TO CLOTTING. Clotting process stops bleeding
without hindering blood flow through the injured vessel.

• Platelets agglutinate and plug small, ruptured vessels during hemostasis.

• 3 Essential Blood Clotting Steps:

1. Production of thrombin from prothrombin during the clotting process requires a
prothrombin activator formed either by an extrinsic pathway or an intrinsic pathway.
A tissue factor (tissue thromboplastin) not normally present in blood participates in the
extrinsic pathway, but only factors present in the blood participate in the intrinsic
pathway.

2. Prothrombin activator-acts enzymatically to catalyze thrombin formation from

prothrombin.

3. Thrombin-acts as an enzyme to convert fibrinogen into fibrin threads that enmesh red
blood cells and plasma to form the clot itself.

• When blood vessels are ruptured and tissues damaged, BOTH extrinsic and intrinsic pathways
are activated. In CIRRHOSIS of the liver, prothrombin and fibrinogen levels are deficient.

Daily Mineral Requirements in Blood:

• Calcium = 800mg
• Phosphorus = 1.5 grams
• Magnesium = 300-350mg
• Sodium = 500mg
• Potassium = 2-4 grams
• Iron = men (10mg) women = (18mg)

BLOOD TYPES:
1. Type AB- (universal recipient) indicates both antigens (alloantigens). Both antibodies
(agglutinins) are absent from AB blood plasma.

2. Type A-contains A antigens (agglutinogens) on erythrocytes. Contains anti-B antibodies

 (agglutinins) in plasma.

3. Type B- contains B antigens (agglutinogens) on erythrocytes. Contains anti-A antibodies

(agglutinins) in plasma.

4. Type O-( universal donor) has neither A or B antigen. Contains antibodies (anti-A and anti-B
agglutinins) in plasma.

Blood incorrectly cross-matched and transfused will cause agglutination (clumping) of the donor’s
erythrocytes.

Blood Coagulation Compounds: Ca2+, Prothrombin, Fibrinogen, Thromboplastin, thrombin, and fibrin.


HEART PHYSIOLOGY

CARDIAC CYCLE-period from the beginning of one heartbeat to the start of the next heartbeat. SA node
discharge begins the cardiac cycle which lasts about 0.8 seconds. The heart repeats TWO alternating
phases that make up the cardiac cycle:

1. Systole-the phase of ventricular CONTRACTION and EMPTYING. Ventricular contraction

increases pressure forcing the mitral (bicuspid) and tricuspid valves to close.
• Opening of aortic and pulmonary valves occurs.
• Ejection of blood into the aorta and pulmonary artery occurs.
• During a normal cardiac cycle, the isometric contraction phase of ventricular systole
occurs following closure of the A-V valves (first heart sound). The blood pressure in the
aorta is at its lowest during this time. During isovolumetric ventricular contraction, ALL
valves are closed.
• Sound heard during systole is due to turbulent blood flow through the artery.
• Systolic BP may be abnormally high during increased arterial compliance.

2. Diastole-the phase of ventricular RELAXATION and FILLING.

• Closing of aortic and pulmonary valves.
• Opening of the tricuspid and mitral valve occurs.
• Flow of blood from the atria into the ventricles occurs.
• Blood volume in the ventricles is GREATEST AT THE END OF DIASTOLE.
• LARGEST VOLUME of blood flows through the left coronary artery during
diastole.

Important:
• Both atria contract simultaneously, followed by simultaneous contraction of both ventricles.

• Contraction of the atria is not essential for movement of blood into ventricles; even if the atria
fail to function, the ventricles still pump a considerable amount of blood.

Cardiac Conduction System-an electrical conduction system that regulates the heartbeat, or contraction
of the myocardium. 4 structural and functional components of the CCS:

1. Sinoatrial node (SA node “heart pacemaker”)-located in the posterior wall of the right atrium
near the opening of the superior vena cava. Rhythmical impulses originate in the SA node and
spread through the atria. Normally, the rate of the heart beat is determined by the SA node.

2. Atrioventricular node (AV node)-located within the lower right interatrial septum. An impulse is
delayed in the AV node for about 0.1 sec to allow the atria to contract before ventricular
contraction.

3. AV bundle (bundle of His)-originates in the AV node, dividing into two bundle branches that
 extend down the two sides of the interventricular septum. Has the slowest rate of conduction.

4. Purkinje fibers-originate from the right & left bundle branches, extending to the papillary muscles
and lateral walls of the ventricles.

Bundle of His (atrioventricular bundle)-a network of fibers that ARISES in the AV node and continues
along the right interventricular septum, dividing in the interventricular septum to form right and left bundle
branches. Fibers from the bundle of His rapidly spread the cardiac impulse throughout both
ventricles via Purkinje fibers.

Purkinje fibers-distal portions of the left and right bundle branches, fan across the subendocardial
surface of the ventricles, from the endocardium through the myocardium. As the cardiac impulse spreads,
Purkinje fibers cause the ventricles to contract. Directly causes the ventricles to contract.

Remember: Cardiac impulses start in the SA node and spread over the atrial muscle fibers producing
atrial contractions. After reaching the AV node, the impulses travel through the bundle of His and Purkinje
fibers, producing coordinated ventricular contractions.

SA node→atrial muscle→AV node→His bundle & bundle branches→Purkinje fibers→ventricular

muscle contraction

FIRST HEART SOUND (“LUB”)-heard when CLOSURE OF ATRIOVENTRICULAR VALVES (A-

V valves) at the beginning of ventricular contraction. The first heart sound is largely due to vibrations of
the taut A-V valves immediately after closure and to the vibration of the heart walls and major vessels
around the heart.
• Louder and longer than the second heart sound.

• Systole starts with the first heart sound, and diastole ends with the first heart sound.

• Tricuspid and bicuspid valves are the Atrioventricular valves (A-V valves).

SECOND HEART SOUND (“DUB”)-associated with closure of the SEMILUNAR VALVES

(pulmonary and aortic valves) as the ventricles begin to relax following their contraction. The second
sound is due to vibrations of the taut, closed semilunar valves and to the vibration of the walls of the
pulmonary artery, aorta, and ventricles.
• Diastole begins with the second heart sound.

• Aortic valve close before the pulmonary valve causing “splitting” of the second heart sound.

ATRIOVENTRICULAR VALVES-tough, fibrous tissue flaps of endocardium secured to papillary

muscles of the ventricular walls by chordae tendineae. Consists of two valves:
1. Tricuspid valve-situated between the right atrium and right ventricle surrounding the AV orifice. It
is composed of 3 flaps (cusps) that prevent backflow of blood from right ventricle into the right
atrium during ventricular contraction.

2. Mitral valve (bicuspid valve)-situated between the left atrium and left ventricle surrounding
the AV orifice. It is the only valve with 2 flaps (cusps) that prevent backflow of blood from the
 left ventricle to the left atrium during ventricular contraction.

Atrioventricular valves are usually open, but are forced shut as the pressure in the ventricles increases,
thus preventing the flow of blood back into the atria while the ventricles are contracting.

SEMILUNAR VALVES-prevent blood from returning to the ventricles after the ventricles have
completed their contractions. Pressure opens them, and reverse pressure closes them. They remain closed
until the ventricles contract.
• Aortic semilunar valve-located at the entrance to the ascending aorta, composed of 3 cusps that
prevent a backflow of blood from the aorta into the left ventricle during ventricular relaxation.

• Pulmonary semilunar valve-located at the entrance to the pulmonary trunk, composed of 3 cusps
that prevent backflow of blood from the pulmonary artery into the right ventricle during ventricular
relaxation.

Important: at no time during the cardiac cycle are all heart valves open at the same time.

Normal Electrocardiogram (ECG or EKG) consists of:

1. P wave-represents atrial depolarization prior to their contraction. It’s the electrical recording
from the body surface of atrial depolarization and precedes atrial contraction.

2. T wave-represents ventricular repolarization.

3. QRS complex-represents ventricular depolarization prior to their contraction.

4. S-T segment-represents the period when the ventricles are depolarized. The only isoelectric
period when the entire ventricle is completely depolarized.

5. P-R interval-an index that represents the length of time between the beginning of atria
contraction and beginning of contraction of the ventricles (approximately 0.16 seconds). PR
interval is an index of the conduction time between atria and ventricles. PR interval varies
with heart rate (when HR increases, PR interval decreases). PR interval is an index of atrial
depolarization and conduction through the AV node. P-R interval is related to propagation of the
cardiac impulse b/t SA & AV nodes.

6. Q-T interval-the entire period of depolarization and repolarization of the ventricles.

An ECG showing extra P waves before each QRS complex indicates partial heart block (or second-
degree block).

An ECG that shows DISSOCIATION of the P wave and QRS complex indicates complete heart
block; there is no correlation between the P wave and QRS-T complex on the ECG. P wave and QRS
complex are dissociated in a complete 3rd degree heart block.

Standard bipolar limb leads of the ECG:

• I = Right arm (-) and left arm (+)
• II = Right arm (-) and left leg (+)
 • III = Left arm (-) and left leg (+)

Standard unipolar limb leads of the ECG:

• AVR = Right arm (+)
• AVL = Left arm (+)
• AVF = Left leg (+)

(-) is the NEGATIVE TERMINAL of the electrocardiograph and (+) is the POSITIVE TERMINAL
of the electrocardiograph.

Since all normal ECG’s are similar, it does not matter greatly which ECG lead is recorded when you
want to diagnose the different cardiac arrhythmias. However, to determine the extent and type of
damage in the ventricles or atria, it matters greatly.

CHEST LEADS are designated as V1, V2, V3, V4, V5, & V6. These are six different places along the
anterior chest wall.

TWO REFRACTORY PERIODS:

1. Absolute Refractory Period-period during which another action potential cannot be elicited no
matter how large the stimulus. The absolute refractory period of a nerve action potential is
determined by the duration of sodium inactivation gate closure.
• The maximal number of impulses that a nerve fiber can carry is determined by the duration
of the absolute refractory period.

2. Relative Refractory Period-begins at the end of the absolute refractory period and continues
until the membrane potential returns to the resting level. An action potential can only be elicited
only if the stimulus is larger than usual. The relative refractory period of a nerve corresponds
to increased potassium permeability.

Ventricular muscle is the cardiac muscle with the longest refractory period (.25-.3 seconds). Atrial
muscle has a shorter refractory period of ~.15 seconds. Thus, the rhythmical rate of contraction of the
atria can be much faster than the ventricles. This long refractory period (absolute refractory
period) of cardiac muscle prevents the heart from undergoing tetanus when stimulated, which would halt
blood flow and cause death. The cells cannot respond to any stimulus.

Skeletal muscle cells have a short refractory period. This allows them to be stimulated to contract a
second time before they have relaxed from an initial contraction.

FRANK-STARLING LAW-states the greater the heart is filled during diastole, the greater the
quantity of blood pumped into the ascending aorta. It demonstrates the matching of cardiac output
(what leaves the heart) with venous return (what returns to the heart). The greater the venous return,
the greater the cardiac output.
• Frank-Starling Law is the mechanism that allows the heart to adjust intrinsically to changing
demands; also states the initial length of cardiac muscle fibers affects strength of contraction.
• It matches cardiac output to venous return.
• The basis of the law is the intrinsic ability of the heart to adapt itself to changing loads of inflowing
 blood.
• It is the mechanism that normally allows the heart to pump automatically whatever amount of blood
flows into the right atrium from the veins.

AN IMPORTANT FEATURE OF FRANK-STARLING LAW is that within reasonable limits, changes

in arterial pressure load, against which the heart is pumping, have almost no effect on the amount of blood
pumped by the heart (cardiac output). The significance of this effect is the following: Regardless of the
arterial pressure, the most important determining factor in the amount of blood pumped by the
heart is still the right atrial pressure generated by the entry of blood into the heart.

BLOOD FLOW is directly proportional to the pressure difference between the two ends of the vessel,
but inversely proportional to the fractional resistance to the blood flow through a vessel. This relationship
is expressed as Flow = Pressure/Resistance.

This relationship states that the greater the pressure, the greater flow rate. It also states flow rate
decreases with increased resistance. Factors influencing resistance are expressed as:

THE LARGER THE VESSEL, THE LESS RESISTANCE (it is the 4th power of the radius). This
means if the radius is doubled, resistance will decrease by a factor of 16. The radius of a vessel can be
altered by the contraction of smooth muscle in a vessel wall. When the smooth muscles constrict, the
diameter is decreased and resistance is greatly increased.

CARDIAC OUTPUT (CO)-the single most important factor used in relation to the circulation. Cardiac
Output is transports substances to and from the tissues. It’s the volume of blood pumped per minute
by each ventricle. CO = STROKE VOLUME x HEART RATE.
• The average resting cardiac output is 5.6 liters/minute for men, and 10-20% less for women. CO
varies depending on the level of body activity, age, body size, heart condition. Changes in CO are
produced by changes in heart rate and stroke volume.

• Stoke volume (SV)-the amount of blood ejected from the ventricle on each heartbeat, expressed
as:

SV =(End-diastolic volume) – (End-systolic volume). Average SV = 70-80ml.

VENOUS RETURN-blood returning to the heart via inferior & superior vena cavae. Under normal
circumstances, the rate of venous return is the MAJOR FACTOR that determines cardiac output. It
affects stroke volume, which along with heart rate, directly determines cardiac output. Factors assisting
in venous return to the heart:
1. contraction of skeletal muscles.
2. pressure changes in the thorax and abdomen during breathing.
3. presence of valves.
Factor influencing CARDIAC OUTPUT (heart rate x stroke volume)
1. Heart Rate-controlled by the autonomic nervous system, body temperature, ions, and epinephrine
and norepinephrine from the adrenal medulla.

2. Stroke Volume: affected by End-systolic volume-effected by ventricular filling, length of

diastole, and venous return. End-systolic volume is also effected by ventricular emptying, strength
of contraction (determined by degree of stretch of cardiac muscle, sympathetic division of ANS,
and epinephrine/norepinephrine from the adrenal medulla).

Vessels of the circulatory system are divided into two circuits that leave and return to the heart:
1. Pulmonary Circuit-(low pressure, low resistance)carries blood from the right side of the heart
to the lungs and back to the left side of the heart. Blood enters the pulmonary circuit from the right
ventricle of the heart through the pulmonary trunk, which divides into the right and left pulmonary
arteries. These pulmonary arteries divide into lobar arteries, that again divide into pulmonary
capillaries located in the walls of tiny alveoli of the lungs. Pulmonary circuit vessels only supply
alveoli. The remainder of lung tissue is supplied by small bronchial vessels of the systemic
circuit.
▪ Pulmonary vessels contain 9% of the entire blood volume of the body.
▪ Heart contains 7% of the entire blood volume of the body.

2. Systemic Circuit-its vessels transport/supplies blood to all tissues and organs of the body
EXCEPT lung alveoli. Blood from the left ventricle enters the systemic circuit through the aorta.
It is from the aorta that all of the arteries of the systemic circuit branch.
• 84% of the entire blood volume of the body is in the systemic circulation. Systemic
circulation supplies blood flow to all body tissues except the lungs. The 84% is broken down
as follows:
▪ 64% in the systemic veins (veins contain greatest volume of blood).
▪ 13% in arteries.
▪ 7 % in arterioles and capillaries.

The volume of blood flow per minute IS THE SAME IN BOTH CIRCUITS. Both systemic and
pulmonary circulations have the SAME FLOW RATE.

ARTERIES-transport oxygenated blood under high pressure away from the heart to the cells,
tissues, and organs. Arteries have strong muscular walls that enable blood to flow rapidly through the
arteries to tissues. Note: pulmonary and umbilical arteries are the only arteries that contain
deoxygenated blood.

ARTERIOLES-small vessels with a diameter less than 0.5mm. Arterioles have a small lumen and
relatively thick tunica media composed entirely of smooth muscle, with very little elastic tissue.
Arterioles are the primary resistance vessels and determine the distribution of cardiac output.
Arterioles are the last small branches of the arterial system that act as control valves through which
blood is released into capillaries. Arterioles have the THICKEST walls of smooth muscle (thick tunica
media).
• Arterioles play a major role in regulating blood flow into the capillaries. Constricting the
arterioles restricts blood flow into capillaries, while dilation allows blood to enter capillaries
 more freely.

• Decreased arterial blood pressure which can occur upon standing (postural hypotension) is
normally overcome through constriction of systemic arterioles.

CHANGES IN BLOOD PRESSURE are due mainly to alternations in RESISTANCE by

ARTERIOLES:
• For this reason, constriction of arterioles is the most likely cause of hypertension. The greater
resistance encountered by blood, the harder the heart must pump, and the more pressure it must
generate to keep the blood circulating.
• Resistance at the arterioles is THE GREATEST OF ANY PART of the systemic circulation.
It accounts for 50% of the resistance of the entire systemic circulation. Arterioles have strong
muscular walls capable of closing the arteriole completely or allowing it to be dilated several
fold, thus vastly altering blood flow to capillaries. Arterioles act as control valves through
which blood is released into the capillaries.

Total Peripheral Resistance (TPR)-the resistance to blood flow by the entire systemic circulation.
TPR is decreased during exercise due to the accumulation of vasodilator metabolites (lactate,
potassium ions, and adenosine) caused by the increase in metabolism of the exercising muscle. Arterial
vasodilation accounts for the overall decrease in TPR.

3 major effects are essential for the circulatory system to supply significant blood flow to muscles
during exercise:
1. mass discharge of the sympathetic nervous system throughout the body with consequent
stimulative effects on the circulation.

2. increase in cardiac output (stroke volume x heart rate).

3. increase in arterial pressure: Mean Arterial Pressure = Cardiac Output x Total Peripheral
Resistance

DURING EXERCISE the dilation of blood vessels in active skeletal muscles greatly increases blood
flow to muscles. At the same time, sympathetic vasoconstrictor activity causes a compensatory
constriction of vessels elsewhere in the body. There is also an increase in sympathetic nerve activity to
the heart, and decrease in parasympathetic nerve activity.
▪ Venous return is enhanced also by increased pumping effects of the contracting skeletal muscles and
by sympathetic vasoconstrictor effects. As a result, both heart rate and stroke volume increase,
causing cardiac output to increase.

▪ During exercise, the increase in cardiac output is greater than the decrease in total peripheral
resistance. Thus, mean arterial pressure rises. MAP = CO x TPR

Total Pulmonary Resistance-the resistance to blood flow by the entire pulmonary circulation.

3 Factors Affect the magnitude of the resistance the blood encounters as it flows through vessels:
blood viscosity, vessel length, & vessel radius (most powerful).
▪ Vessel Radius-resistance is inversely proportional to the fourth power of the vessel
 radius. Vessel radius can vary greatly, especially arterioles.

▪ Blood Viscosity-resistance is directly proportional to the viscosity of the blood (does not
vary greatly) and vessel length (is constant). Blood flow is inversely proportional to the
resistance of blood vessels.

CAPILLARIES-the site of the fluid exchange and nutrients between the blood and interstitial
spaces. Capillaries determine the distribution of extracellular fluid between plasma and interstitial
fluid. Capillary walls are very thin and consist of a single layer of endothelial cells surrounded by a
thin basal lamina of the tunica intima. There is no tunica media or adventia. Capillary diameter is
directly influenced by the byproducts of metabolism. Note: the amount of blood that flows through the
capillaries per minute = the amount of blood that flows through the aorta per minute.

VEINS-function as conduits for transporting deoxygenated blood from tissues back to the heart.
Veins have larger lumens (blood pressure is the lowest in veins) and thinner walls than the arteries they
accompany. Some contain valves (veins of the limbs) that allow blood to flow toward the heart, but not
away from it. They are similar in form to the heart’s semilunar valves. PULMONARY VEINS-the only
veins that transport oxygenated blood, & HAVE THE HIGHEST OXYGEN TENSION. Pulmonary
veins bring oxygenated blood to the left atrium. VEINS HAVE A THIN TUNICA MEDIA!

VENULES-very tiny veins that collect blood from capillaries, and gradually coalesce into progressively
larger veins.

BAINBRIDGE REFLEX-a nervous reflex initiated by an excess amount of blood returning to the right
atrium. This causes stretching of the right atrium, which initiates this reflex. Bainbridge reflex
increases heart rate, which helps to pump the extra blood. Bainbridge reflex also prevents damming
of blood in the veins, atria, and pulmonary circulation.

• Receptor cells in the right atrium are sensitive to pressure and stretch. Atria stretch receptors
that elicit the Bainbridge reflex transmit their afferent signals through the vagus nerves to
the medulla of the brain. Then, efferent signals are transmitted back through both the vagal
(parasympathetic) and sympathetic nerves to increase the heart rate and strength of the contractions.

Heart rate is controlled by ANS innervations; sympathetic (norepinephrine) stimulation increases

heart rate, while parasympathetic (acetylcholine) stimulation decreases heart rate. The main centers
for autonomic cardiac control are located in the medulla oblongata of the brain stem.

The first 4 thoracic spinal nerves (accessory nerves) contribute ADRENERGIC fibers to the heart
and affect the heart’s irritability. Sympathetic effects include:
1. Increase in the rate of discharge of the sinoatrial node (SA node = “heart pacemaker”). The rate
of discharge of the SA node sets the rhythm for the entire heart.

2. Increase in excitability of all portions of the heart.

3. Production of more rapid, forceful contractions.

PARASYMPATHETIC FIBERS innervate the heart by the VAGUS NERVES. The right vagus nerve
is the most important nerve to the heart (it goes to the SA node). The left vagus nerve innervates the
AV node. Parasympathetic effect on the heart include:
1. decrease in the rate of discharge of the SA node.
2. decrease in excitability of the AV node (regulates heart beat)
3. decreases excitability of the heart by increasing membrane permeability to potassium (K+) ions.

CHEMORECPTORS-special nervous chemical receptors located in several areas outside the brain.
Chemoreceptors are important in detecting changes in oxygen in the blood, by responding to changes in
carbon dioxide and hydrogen ion concentrations. These chemoreceptors then transmit nervous signals to
the respiratory center in the brain to help regulate respiratory activity (medulla oblongata).
• Carotid bodies-contain the largest number of chemoreceptors important for detecting changes
in oxygen in the blood (detect low oxygen tension) and help regulate respiratory activity. Carotid
bodies are located bilaterally in the bifurcations of the common carotid arteries in the neck.

• Aortic bodies-also contain a lot of chemoreceptors, located along the arch of the aorta.

BARORECEPTORS-mechanoreceptors in the carotid sinus and aortic arch that SENSE PRESSURE
CHANGES in response to alterations in arterial wall tension. Respond fast to changes in blood pressure.
Sense blood pressure and relay information to the CNS (brain) so proper BP can be maintained.

ORTHOSTATIC HYPOTENSION-excessive BP drop when an upright position is assumed due to a

decrease in systolic BP of 20mm Hg, or drop in diastolic BP of 10mm Hg within 3 minutes of standing
compared to BP from the stitting or supine position.


VITAMINS, MINERALS, & DEFICIENCIES

Fat-Soluble Vitamins: A, D, E, K.

Water-Soluble Vitamins: B-complex, C (Ascorbic acid), vitamin H (Biotin)

Vitamin B-complex-a group of water-soluble vitamins including thiamine (vitamin B1), riboflavin
(vitamin B2), niacin, pantothenic acid (vitamin B3), biotin (vitamin H), pyridoxine (vitamin B6), folic
acid, and cobalamin (vitamin B12). Vitamin B-complex occurs chiefly in yeast, liver, eggs, and some
vegetables. B12 deficiency can result in pernicious anemia due to lack of intrinsic factor.

BIOTIN (Vitamin H)-synthesized by intestinal bacteria, required for the carboxylation of acetyl CoA
into malonyl CoA (an intermediate in fatty acid synthesis), and coenzyme necessary in the initial steps
of fatty acid synthesis.
• Functions: essential for activity of many enzyme systems involved in amino acid and protein
metabolism. Also required for the carboxylation of acetyl CoA into malonyl CoA (an intermediate
in fatty acid synthesis).

• Dietary Sources: liver, kidney, milk, egg yolk, yeast.

• Deficiency: fatigue, depression, nausea, dermatitis, muscular pains, loss of hair.

• AVIDIN-a protein found in uncooked egg whites that binds to and INACTIVATES BIOTIN, and
when present in abundance, can result in biotin deficiency. Avidin is an important dietary
component due to its ability to inactivate BIOTIN.

THIAMINE (Vitamin B1)- water-soluble vitamin involved in carbohydrate & amino acid metabolism.
• Dietary Sources: meat (pork and organ meats), grains, dry beans/peas, fish, poultry.

• Deficiency: Adult Beri-Beri-a severe thiamine deficiency syndrome found in areas where
polished rice is the major component of the diet. Beri-Beri causes dry skin, irritability, disorderly
thinking, and progressive paralysis. Thiamine deficiency can also cause Korsakoff Syndrome &
Wernicke.

RIBOFLAVIN (VITAMIN B2)-a constituent of two flavin nucleotide coenzymes (FAD and FMN) that
function with some enzymes (flavoproteins) that catalyze oxidation-reduction reactions. Riboflavin
derivatives function as coenzymes in redox reactions.
• Dietary Sources: milk, leafy vegetables, fresh meat, egg yolks.

• Deficiency: leads to Angular Cheilosis-cracks at corner of mouth; dermatitis; Glossitis-tongue

appearing smooth and purplish-red; angular stomatitis, red-itching eyes; slow wound-healing.

PANTOTHENIC ACID (calcium pantothenate)-found in Coenzyme A which functions in the entry of

pyruvic acid into the Kreb’s cycle and in degradation of fatty acids. B3 is also a component of fatty acid
synthase. Pantothenic acid is an integral part of coenzyme A.
• Dietary Sources: widely distributed in all foods; eggs, liver, and yeast.
• Deficiency: causes fatigue, sleep disturbances, impaired coordination, diarrhea, GI, and renal
problems.

FOLIC ACID (folate or folacin)-a vitamin that functions in coenzymes specifically involved in the
transfer and utilization of the single carbon moiety. Folic acid plays a key role in one-carbon
metabolism, and is essential for the biosynthesis of the purines and the pyrimidine (thymine). Folic
acid is STORED IN LIVER and may be synthesized by bacterial flora of the GI tract.
• Functions: involved in synthesis of purines and thymine required for DNA formation.

• Dietary Sources: liver, kidney, yeast, mushrooms, and green vegetables.

• Deficiency: Megaloblastic anemia, diarrhea, Glossitis. Folic acid deficiency is the most common
vitamin deficiency in the U.S. especially among pregnant women and alcoholics.

VITAMIN B6 (Pyridoxal, Pyridoxine, Pyridoxamine)-vitamin derivatives of pyridine, differing only in

the nature of the functional group attached to the ring. All three components serve as precursors of the
biologically active coenzyme pyridoxal phosphate (functions as a component of coenzymes for
enzymes that catalyze TRANSAMINATION REACTIONS of amino acids).

• B6 deficiencies are rare, but are observed in women taking oral contraceptives (“pill”) and in
alcoholics.

• Dietary sources: meats (liver), vegetables, whole-grain cereals, and egg yolks.

VITAMIN C (Ascorbic Acid)-an antioxidant & cofactor required for hydroxylation of proline &
lysine.
• Body Functions:
o C.T. synthesis and normal bone matrix formation.
o Essential for hydroxylation of lysine & proline in collagen synthesis, capillary integrity,
and oral mucosa integrity.
o Diets high in vitamin C reduce risks of certain cancers.

• Dietary Sources: citrus fruits, tomatoes, green peppers, broccoli, spinach, strawberries, melon.

• Vitamin C Deficiency: leads to SCURVY (degeneration of skin, teeth, vessels, epithelial

hemorrhages); delayed wound healing, and anemia.

NIACIN (nicotinic acid)-a component of NAD+ and NADP+ formed from the amino acid tryptophan.
High supplemental doses effectively treats hyperlipidemia Niacin derivatives function as coenzymes
in redox reactions.
• Functions: component of NAD+ and NADP+ involved in glycolysis & Kreb’s cycle.
• Dietary Sources: liver, meat, fish, grains, legumes, poultry, and peanut butter.
• Deficiency: leads to PELLAGRA-symptoms are diarrhea, dermatitis, and mental disturbances
(dementia).
 o A diet rich in tryptophan prevents a niacin deficiency.

VITAMIN D (1,25-dihydroxycholecalciferol)-fat-soluble vitamin involved in calcium metabolism.

• Functions: promotes growth and mineralization of bones & teeth; calcium and phosphorus
metabolism (bone formation). Vitamin D and parathyroid hormone both increase serum calcium.

• Dietary Sources: fish-liver oil, eggs, dairy, fortified milk, and margarine.

• Deficiency: causes a net demineralization of bone resulting in Rickets (children) & Osteomalacia
(adults).

• Vitamin D is the most toxic fat-soluble vitamin.

7-dehydro-cholesterol-an intermediate in cholesterol synthesis converted into cholecalciferol (vitamin

D3) in the dermis and epidermis of humans exposed to sunlight. Preformed vitamin D is a dietary
requirement only in individuals with limited exposure to sunlight.
• Vitamin D3 (cholecalciferol) is not biologically active, but is a precursor of the physiologically
active vitamin D, 1,25-dihydroxycholecalciferol produced in the KIDNEY. The most prominent
actions of active vitamin D is to regulate plasma levels of calcium & phosphorus.

• Formed from 7-dehydro-cholesterol, Vitamin D3 (cholecalciferol) is converted into the

metabolite 25-hydroxycholecalciferol in the LIVER, while 25-hydroxycholecalciferol is
converted to 1,25- dihydroxycholecalciferol in the KIDNEY.

VITAMIN E (Tocopherol)-fat-soluble vitamin that serves as an antioxidant to prevent free radicals from
oxidizing compounds like polyunsaturated fatty acids. Vitamin E is the LEAST TOXIC of all fat-
soluble vitamins (Vitamin D is the MOST toxic).
• Dietary sources: vegetable oil and seeds, green leafy vegetables, margarines, shortenings.
• Major body functions: functions as an antioxidant inhibiting the breakdown of unsaturated
fatty acids. Also treats sterility and various abnormalities of the muscles, RBC, liver, and
brain.
• Deficiency: vitamin E deficiency is almost entirely restricted to premature infants.

VITAMIN B12 (Cobalamin or Cyanocobalamin)-synthesized only by microorganisms and not present

in plants. B12 is the only vitamin that contains essential mineral elements, and is the first substance
containing cobalt found to be vital to life. Vitamin B12 may be present in inadequate quantities in a
strictly vegetarian diet.
• Dietary sources: muscle and organ meats, eggs, diary (not present in plant foods).
• Major body functions: involved in formation of methionine, and converting methylmalonyl
CoA to succinyl CoA.
• B12 Deficiency: Pernicious Anemia, neurologic disorders, and Glossitis.
o Vitamin B12 is widely used to treat pernicious anemia.
o Deficiency is caused by the absence of Vitamin B12 intrinsic factor produced in the
STOMACH by gastric parietal cells. Intrinsic factor is necessary for vitamin B12
absorption from the digestive tract.
VITAMIN A (Retinol)-fat-soluble vitamin required to form the visual pigments of rod and cone cells.
• Functions: a constituent of rhodopsin (visual pigment); maintenance and differentiation of
epithelial tissues; and has a role in mucopolysaccharide synthesis, bone growth and remodeling.
• Dietary Sources: widely distributed in green and yellow vegetables and fruits.
• Deficiency: causes Xerophthalmia (keratinization of ocular tissue); night blindness.

Vitamins A, C, and D are required for the normal production of sound dentin and enamel. However,
deficiency of vitamin A will affect enamel more than dentin. A deficiency in vitamin C affects dentin
more, due to collagen.

VITAMIN K (phylloquinone or anti-hemorrhagic factor)-required for blood clotting, vitamin K is a fat-

soluble vitamin synthesized by the normal action of intestinal bacteria. Vitamin K decreases
coagulation (clotting) time, and is present in low concentrations in milk (iron is also found in low
concentration in milk). Iron & vitamin K are in low concentrations in MILK.
• Functions: promotes the synthesis of prothrombin and other clotting factors by the liver.
• Dietary Sources: green and yellow vegetables; small amount in cereals, fruits, and meats.
• Deficiency: retarded blood clotting, excessive bleeding.
• Warfarin-a synthetic analog of vitamin K, that acts as a competitive inhibitor of prothrombin
formation.
• A derivative of vitamin K is the coenzyme for the carboxylation of glutamate side chains.


FAT SOLUBLE VITAMINS & DEFICIENCY

• Vitamin A-helps maintain normal body growth and health of specialized tissues, especially the
retina. Involved in production of rhodopsin (photopigment). Deficiency results in NIGHT
BLINDNESS, skin lesions, xerophthalmia (keratinization and dryness of tissues in the eye).
o Vitamin A function to promote differentiation of epithelial cells.

• Vitamin D-essential in bone formation. Deficiency results in OSTEOMALACIA in adults, RICKETS

in children, and Rachitic rosary. Bone thinning is a symptom.

• Vitamin E-functions as an antioxidant. Deficiency results in NEUROLOGIC DYSFUNCTION.

• Vitamin K-involved in blood clotting. Deficiency results in TENDENCY TO HEMORRHAGE

(bruise and bleed). Vitamin K is necessary for formation of PROTHROMBIN (Factor II).

VITAMINS & DEFICIENCES:

• Vitamin B1 (thiamine)-deficiency leads to wet and dry beriberi. High cardiac output; peripheral
neuropathy. Pins and needles sensation, especially in feet.

• Vitamin B2 (riboflavin)-deficiency leads to angular cheilosis (skin fissures/cracks at the angles of the
mouth) and glossitis (inflammation of the tongue).

• Vitamin B3 (niacin, nicotinic acid)-deficiency leads to PELLEGRA, dementia, dermatitis, diarrhea.

• Vitamin B6 (pyridoxine)- deficiency leads to Chilosis, glossitis; anemia. Skin fissures at the angles of
the mouth; inflammation of the tongue; number of red blood cells is below normal.

• Vitamin B12 (Cobalamin)-deficiency leads to Megaloblastic anemia (i.e. pernicious anemia);

neurologic dysfunction. Anemia where there is a predominant number of megaloblasts and few
normoblasts. Anemia and pins-and-needles sensation.

• Folic acid-deficiency leads to Megaloblastic anemia; neurologic dysfunction is not a feature as in

vitamin B12 deficiency. Anemia where there is predominant number of megaloblasts (abnormally large
nucleated RBC).

• Vitamin C (Ascorbic Acid)-deficiency leads to SCURVY, defective formation of mesenchymal tissue

and osteoid matrix; defective wound healing. Swollen, bleeding gums; muscle, joint, and bone pain;
abnormal bleeding. SCURVY-characteristics are swollen, bleeding gums accompanied by muscle,
joint, and bone pain. Poor wound healing and hemorrhages into the skin are also symptoms.

FLUORIDE-found primarily in drinking water. Fluoride does not make enamel harder, but reduces the
rate of enamel solubility (by inactivating proteolytic enzymes). The concentration of fluoride in body
fluids is regulated by an equilibrium relationship between bone and urinary excretion.
 • Fluoride deficiency leads to dental caries, and fluoride toxicity leads to tooth enamel mottling and
discoloration, increased bone density, & calcification.
• Fluoride facilitates remineralization (MOST IMPORTANT ANTICARIES EFFECT)

FLUORIDE FACTS: enhances enamel mineralization and decreases enemal solubility.

• Excreted by the kidney and deposited in calcified tissues (i.e. skeletal).
• Passes slowly through the placental barrier.
• Tasteless, colorless, and odorless at 1ppm.
• Converts hydroxyapatite to fluoroapatite by substituting OH ion with the fluoride ion.
MINERALS-inorganic substances essential to life. Minerals serve structural and regulatory functions.
Two classes of minerals:
• Major minerals (more than 0.005% of body weight): calcium, chloride, magnesium, phosphorus,
potassium, sodium, & sulfur.
o Sulfur-a constituent of active tissue compounds, cartilage, and tendon.
o Potassium-acid-base balance, body water balance, nerve function, muscle relaxant.
o Sodium-acid-base balance, body water balance, nerve function.
o Magnesium-activates enzymes involved in protein synthesis.

• Trace minerals (less than 0.005% of body weight): chromium, cobalt, copper, fluoride, iodine,
iron, manganese, molybdenum, selenium, and zinc.
o Cobalt-major component of vitamin B12.
o Copper-component of enzymes involved with iron metabolism and nerve function.

General Functions of Minerals:

• Maintenance of acid-base balance.
• Coenzymes or catalysts for biologic reactions.
• Components of essential body compounds.
• Transmission of nerve impulses and regulation of muscle contractions.
• Maintenance of water balance.
• Growth of oral and other body tissues.

ZINC-stabilizes cell membranes, functions in taste acuity, required in collagen formation, and essential
in cell-mediated immunity.

CALCIUM & IRON are minerals most frequently in short supply in the American diet.


PHYSIOLOGIC DISORDERS

ALKAPTONURIA (homogentisuria)-a tyrosine disorder due to the failure to catabolize tyrosine

beyond the intermediate (homogenistic acid) that is excreted in the urine and MAKES URINE APPEAR
BLACK. It results from a deficiency of a dioxygenase (homogentisate). Usually, the condition does not
result in any serious ill effects. Maple Syrupe Disease

ALBINISM-a genetic disorder involving the incomplete failure to convert TYROSINE into melanin
due a deficiency of tyrosinase enzyme. A tyrosine disorder.

PHENYLKETONURIA (PKU)-an abnormal presence (excess) of phenylketone and other metabolites of

phenylalanine in the urine. Phenylketonuria is caused by the absence or a deficiency of phenylalanine
hydroxylase (enzyme that converts phenylalanine into tyrosine). Accumulation of phenylalanine is toxic
to brain tissue, and impairs normal development of the brain causing severe mental retardation. Tyrosine
disorder.

CYSTINURIA-a hereditary condition characterized by excessive urinary excretion of cystine and other
amino acids. Cystinuria is caused by a defect in the renal tubules that impairs reabsorption of these
amino acids.

DIABETES-most common pancreatic endocrine disorder; a metabolic disease involving most

carbohydrates (glucose) and lipids. Diabetes is caused by an absolute deficiency of insulin (Type 1) or
the resistance of insulin’s actions in the peripheral tissues (Type 2). Cardinal symptoms of diabetes:
(polydipsia, polyuria, polyphagia, weight loss, loss of strength).

1. Diabetes (Type 1)-no insulin secretion, develops in childhood affecting 10-20% of individuals.
Type 1 destroys pancreas beta cells, symptoms develop rapidly, and ketosis develops if
untreated. Treatment: insulin injections, dietary management. Not associated with obesity.

2. Diabetes Mellitus (Type 2)-insulin secretion may be normal or exceed normal, develops in
adults, representing 80-90% of diabetes. Results from loss of insulin receptor function in
target tissues causing reduced sensitivity by insulin’s target cells. Associated with obesity,
and symptoms develop slowly. Ketosis development is rare. Treatment: dietary control and
weight reduction, occasionally treat with oral hypoglycemic drugs.

DIABETES INSIPIDUS-results from decreased production of antidiuretic hormone (vasopressin).

Diabetes insipidus is a disorder in which insufficient levels of antidiuretic hormone (ADH) cause
excessive thirst (polydipsia) and excessive production of very dilute urine (polyuria). ADH naturally
prevents the body from producing too much urine.
• ADH is unique in that it is produced in the hypothalamus, then stored and released into the
bloodstream by the posterior pituitary gland. The primary site of action of antidiuretic
hormone is on the distal tubules and collecting ducts in the kidney.
 • HYPOACTIVITY of the posterior pituitary gland or destruction of the supraoptic nuclei of the
hypothalamus results in diabetes insipidus. Due to lack of ADH which is produced in the
supraoptic nuclei (hypothalamus), but secreted by the posterior pituitary gland.

• ADH DEFICIENCY results in failure of tubular reabsorption of water in the kidney and
consequent passage of a large amount of urine and great thirst (extreme polyuria and polydipsia).

• In diabetes insipidus, body fluid volumes remain close to normal as long as the person drinks
enough water to compensate for the increased clearance of water in the urine.

NEPHROGENIC DIABETES INSIPIDUS-a congenital and familial form of diabetes insipidus due to
failure of the renal tubules to reabsorb water. There is excessive production of antidiuretic hormone
(ADH), but the renal tubules fail to respond.

GAUCHER’S DISEASE-a lipid metabolism disorder caused by a deficiency of Glucocerebrosidase.

It’s a hereditary disorder that leads to accumulation of glucocerebrosides (glycosingolipid) in cells of
the mononuclear phagocyte system. It is caused by a deficiency in the enzyme glucocerebrosidase
causing enlargement of the spleen and liver.

LIPOSES-lipid storage diseases caused by abnormalities in enzymes that break down (metabolize) fats.
Liposes result in a toxic accumulation of fat-by-products in tissues.

Niemann-Pick Disease-hereditary disorder in which the deficiency of the enzyme sphingomyelinase

causes accumulation of sphingomyelin. It is most common in Jewish families. There is enlargement of
the spleen and liver, anemia, fever, and neurologic deterioration. Death usually occurs by age 3.

Tay-Sachs Disease-a hereditary disorder in which the deficiency of the enzyme hexosaminidase A results
in the accumulation of gangliosides especially in CNS neurons. It’s the most common form of liposes,
occurring primarily in Eastern Jewish families. Tay-Sachs is characterized by CNS degeneration with
severe mental and motor deterioration. Death occurs by age 4.
• Tay-Sachs is an inborn error of metabolism involving hexosaminidase A which normally degrades
Gangliosides in gray matter, but the enzyme is not present.

HURLER’S SYNDROME-caused by a deficiency of the enzyme e-L-iduronidase resulting in

accumulation of the mucopolysaccharides heparin sulfate and dermatan sulfate in the heart, brain,
liver, and other organs. Hurler’s is characterized by dwarfism and mental retardation. Death occurs by
age 10.

ADDISON’S DISEASE (Adrenocortical Insufficiency)-life-threatening condition caused by partial or

complete failure of adrenocrotical function. It may be the result of autoimmune processes, infection,
neoplasm, or hemorrhage in the gland. Over 90% of the adrenal cortex is destroyed before obvious
symptoms occur.
• Addison’s is characterized by hypotension, bronzing of the entire skin, low levels of serum
sodium, chloride, and bicarbonate with an increase in serum potassium.

• Oral signs include diffuse pigmentation of the gingiva, tongue, hard palate, and buccal
mucosa. Although cutaneous pigmentation most likely disappears after therapy, pigmentation of the
 oral tissues persists. Addison’s disease is treated by administering cortisol (hydrocortisone) or
prednisone.

• Addison’s results when underactive adrenal glands produce low amounts of corticosteroids.

• strikes at any age and affects males and females equally.

• 30% of people with Addison’s disease, the adrenal glands are destroyed by a cancer,
amyloidosis, and infection (tuberculosis), or another identifiable disease. 70% of people with
Addison’s the cause is unknown, but suspected that the adrenal glands are destroyed by an
autoimmune reaction.

Waterhouse-Friderichsen Syndrome-a catastrophic adrenal insufficiency and vascular collapse due to

hemorrhagic necrosis of the adrenal cortex. Most often found with meningococcal meningitis.

JAUNDICE-a yellow discoloration of skin, sclera, and tissues caused by HYPERBILIRUBINEMIA.

The yellow discoloration of the skin and whites of the eyes are caused by abnormally high levels of
bile pigment (BILIRUBIN) in the bloodstream.
• Hemoglobin (the part of the RBC that carries oxygen) is broken down into bilirubin which is
carried to the liver and excreted into the intestine as a bile component. If bilirubin excretion is
prevented, excess conjugated bilirubin passes into the bloodstream, causing jaundice.

• Jaundice is very common and is the leading manifestation of liver disease. It occurs at any age
and either sex. Jaundice is a symptom of liver disease, gallstones, pancreatic cancer, and acute
biliary obstruction.

• Normal plasma concentration of bilirubin averages 0.5mg per 100ml of plasma. In jaundice,
plasma bilirubin concentration can rise to 40mg per 100ml.

• Common Causes of Jaundice: increased destruction of RBC with rapid release of bilirubin into
the blood. Obstruction of bile ducts or damage to liver cells which cause the inability of bilirubin
to be excreted into the GI tract.

SHOCK-a set of hemodynamic changes that diminish blood flow below a level to provide adequate
oxygen for the metabolic needs of organs and tissues. Slow blood flow = decreased cardiac output.
• Shock symptoms include: tiredness, sleepiness, and confusion, cold, sweaty skin that is bluish and
pale. Pulse is weak and rapid, and blood pressure drops. REDUCED CARDIAC OUTPUT IS
THE MAIN FACTOR IN ALL TYPES OF SHOCK.

SHOCK STAGES:
1. Non-progressive (early) stage-compensatory mechanisms (increased heart rate and peripheral
resistance) maintain perfusion to vital organs.

2. Progressive stage-metabolic acidosis occurs (compensatory mechanisms are no longer

adequate).

3. Irreversible stage-organ damage, survival is impossible.

SHOCK TYPES:
1. Anaphylactic shock-occurs with severe allergic reaction. First sign of anaphylaxis is skin rash
followed by respiratory constriction.

2. Cardiogenic shock-circulatory collapse resulting from pump failure of the left ventricle, most
often caused by massive myocardial infarction.

3. Hypovolemic shock-produced by a reduction in blood volume. Caused by severe hemorrhage,

dehydration, vomiting, diarrhea, and fluid loss from burns.

4. Neurogenic shock-caused by severe injury or trauma to the CNS and reactive peripheral
vasodilation.

5. Septic shock-due to severe infection caused by endotoxin from gram (-) bacteria.

HYPERTHYROIDISM-caused by excessive production of thyroid hormone THYROXIN (T4). T4

primarily stimulates cellular metabolism, growth, and differentiation of all tissues. Excess T4 leads to
high basal metabolism, fatigue, weight loss, excitability, elevated temperature, and generalized
osteoporosis. Oral manifestations are not too remarkable, but if the disturbance begins early in life,
premature tooth eruption and loss of the deciduous dentition are common.
• Clinical Features: restlessness, nervousness, irritability, and insomnia, heat intolerance
(sweating), tachycardia (rapid heart rate), fine hair, diarrhea, tremor (shakiness), early tooth
eruption.

• Grave’s Disease (Toxic Diffuse Goiter)-the most common hyperthyroidism that occurs mainly
in women 20-40yrs. Grave’s is an AUTOIMMUNE DISORDER of the butterfly-shaped thyroid
gland that typically arises after infection or physical or emotional stress. Typical signs of
hyperthyroidism are present plus a GOITER and EXOPHTHALMOS (bulging eyes =
Proptosis). If you detect a goiter during an extra-oral examination, refer the patient for a
physician consultation.

• Plummer’s Disease (Toxic MultiNodular Goiter)-results from the presence of many toxic thyroid
nodules (adenomas) within the thyroid gland. It is uncommon in adolescents and young adults and
tends to increase with age. Exophthalmos (bulging eyes) is RARE.

HYPOTHYROIDISM (Underactive Thyroid)-a common endocrine disorder where the thyroid gland
does not produce enough thyroid hormone caused by inadequate iodine in the diet or Hashimoto’s
thyroiditis. Affects mainly women > 60 years old.

• Clinical Symptoms: fatigue, cold intolerant, constipation, dry skin, weight gain, PUFFY FACE,
muscle aches, thinning hair, hypotension, slowed HR (bradycardia), depression, impaired memory,
delayed tooth eruption.

• HASHIMOTO’S DISEASE (Thyroiditis)-autoimmune disease where the immune system attacks

the thyroid gland causing primary hypothyroidism. THE MOST COMMON CAUSE OF
HYPOTHYROIDISM IN THE U.S. Potential causes include genetics, hormones, excessive
iodine, or radiation exposure.
 ▪ Most common symptoms: GOITER (occurs when pituitary gland senses low thyroid
hormone and secretes more TSH to stimulate the thyroid gland), fatigue, WEIGHT GAIN,
pale/puffy face, cold intolerant, joint or muscle pain, constipation, thin or brittle hair,
depression, slow heart rate, low BP, and delayed tooth eruption. May cause an enlarged
tongue.

• MYXEDEMA (Advanced Hypothyroidism)-very severe and potentially fatal hypothyroidism in

adults, much more common in ADULT WOMEN than men. Characterized by puffiness of face
and eyelids, swelling of tongue and larynx. Skin becomes dry, and rough, and hair sparse.
Individual has a low basal-metabolic rate and low body temperature, poor muscle tone, low
strength, tires easily, and are mentally sluggish. Myxedema is treated with thyroid replacement
hormones. If a patient suddenly stops taking Synthroid, in rare instances, MYXEDEMA COMA
may result.

• CRETINISM-congenital untreated hypothyroidism (lack of thyroid hormone) at birth

resulting in severely stunted physical and mental growth, expressionless puffy face, often
uncooperative, delayed tooth eruption, malocclusion, macroglossia, and increased caries and
periodontal diseases. May be due to an iodine dietary deficiency during pregnancy. Uncommon
today in the developed world.

 METABOLISM
ATP is produced by:
1. Substrate-level phosphorylation-high-energy phosphate intermediates are formed and transferred
to ADP to produce 4 ATP. This occurs in glycolysis and citric acid cycle (Kreb’s). Glycolysis is
the first phase and Kreb’s cycle (citric acid cycle) is the second phase of respiratory
metabolism.

2. Electron-transport phosphorylation-electrons move down the ETC and chemiosmosis occurs.

Because energy generated by the transfer of electrons through the ETC to O2 is used in ATP
production = oxidative phosphorylation. It is the 3rd and final phase of respiratory metabolism
of glucose and other substrates. Reduced coenzymes (NADH & FADH2) generated earlier in
glycolysis and the Kreb’s cycle are reoxidized, and electrons they release are transported through
a series of membrane-bound carriers (flavoproteins, iron-sulfur proteins, coenzyme Q, and
cytochromes) to establish a proton gradient across a membrane, a terminal acceptor (oxygen) is
reduced, and ATP is synthesized by chemiosmosis.

Oxidative phosphorylation-occurs in the mitochondrial inner membrane, glycolysis occurs in the

cytoplasm, and the Kreb’s cycle occurs in the mitochondrial matrix. Remember: cells of the blood do not
contain an active mitochondrial electron transport system. During oxidative phosphorylation, the
energetically unfavorable proton gradient is created using energy from ELECTRON TRANSFERS.

3. Photophosphorylation-occurs as a result of photosynthesis (which also involves the ETC).

The final steps in aerobic generation of ATP involves the transfer of electrons from the reduced
coenzymes (NADH and FADH2) to oxygen, and the combination of protons (H+) with oxygen to form
water and regenerate NAD+ and FAD. These activities are accomplished by the electron transport
system (found in the inner membrane of mitochondria).
• Oxidation of 1 NADH by the electron transport chain forms 2.5 ATP.
• Oxidation of 1 FADH2 by the electron transport chain yields 1.5 ATP.

ELECTRON TRANSPORT CHAIN-found in the inner mitochondria membrane, composed of a

specific sequence of electron carriers (flavoproteins, iron-sulfur proteins, coenzyme Q, and
cytochromes). During oxidative phosphorylation, the energetically unfavorable proton gradient is
created using energy from electron transfers.

ETC components are separated into 4 protein-lipid complexes (I, II, III, IV): There are 4 electron-
carrier complexes each representing a fraction of the entire respiratory chain. Each of the 4 complexes
has it own unique composition, and is capable of catalyzing electron transfer through a portion of the
chain.
1. Complex I-contains NADH dehydrogenase complex is the electron donor. Catalyzes electron
transfer to ubiquinone.
 2. Complex II (succinate dehydrogenase complex)-catalyze electron transfer to ubiquinone.

3. Complex III (ubiquinone-cytochrome c oxidoreductase complex)-carries electrons from

ubiquinone to Cytochrome c.

4. Complex IV (Cytochrome oxidase complex)-completes the sequence by transferring electrons

from Cytochrome c to oxygen. Its protein components are cytochromes a and a3.

The major source of ATP in aerobic organisms. AEROBIC BREAKDOWN of a single glucose
molecule produces a net profit of 36-38 ATP.
• Substrate-level phosphorylation produces a 4 ATP (2 during glycolysis & 2 during Kreb’s cycle).
• Oxidative phosphorylation during electron transport produces 32-34 ATP.
• Under strict anaerobic conditions, the catabolism of 1 glucose molecule yields a net of 2 ATP and
2 lactic acid molecules.

Protein Kinases-enzymes that phosphorylate certain amino acid residues in specific proteins to
regulate activities of other enzymes. Protein kinases regulates the activity of key enzymes through
phosphorylation.

Citric Acid Cycle (Kreb’s Cycle)-the cycle starts with the 4-carbon compound oxaloacetate, adds 2
carbons from acteyl CoA, loses 2 carbons as CO2, and regenerates the 4-carbon compound oxaloacetate.
• “tricarboxylic acid TCA cycle” is initiated by the condensation of acetyl coenzyme A &
oxaloacetate.
• Kreb’s cycle is controlled by regulation of several enzyme activities found in the mitochondria.
The most important of these regulated enzymes are citrate synthase, isocitrate dehydrogenase,
and α-ketoglutarate dehydrogenase complex.
• 2 ATP are formed for each glucose molecule metabolized.
• pyruvate which enters the Kreb’s cycle, is generated by the glycolysis of glucose or protein
catabolism.
• Aspartic acid and oxaloacetic acid are interconvertible.
• Oxaloacetic acid and alpha-ketoglutaric acid are found in the Kreb’s Cycle (citric acid cycle).

Embden-Meyerhof Pathway-a specific glycolytic pathway by which glucose is converted to lactic acid
(the end-product of glycolysis under anaerobic conditions). It is the most common pathway used by a
large number of anaerobic and facultatively anaerobic bacteria. Oral bacteria also use this pathway.
• Pyruvate is reduced to lactic acid (is cariogenic) via fermentation. This glycolytic pathway results
in the net production of 2 ATP per molecule of glucose metabolized.
• Embden-Meyerhof Pathway is also a glycolytic pathway used by many AEROBIC bacteria. It
results in the net production of only 1 ATP per glucose molecule metabolized. Aerobic
bacteria lack the key enzyme 6-phosphofructokinase of the Embden-Meyerhof pathway.

• Embden-Meyerhof Pathway: Glucose:Fructose-1,6-diphosphateF2 Pyruvate→lactic acid.

• LACTIC ACID-an acid that is a product of bacterial glycolysis and is CARIOGENIC.

PYRUVATE-the BRANCH POINT MOLECULE OF GLYCOLYSIS. Fates of Pyruvate:

 1. converted into lactate: lactate dehydrogenase (LDH) converts pyruvate to lactate in the cytosol.
It is the major fate for pyruvate in RBC, the lens and cornea of the eye, medulla of kidney, testes,
and leukocytes.

2. converted into acetyl CoA: pyruvate dehydrogenase converts pyruvate to acetyl CoA in
mitochondria. This acetyl CoA can then enter the citric acid cycle or be used as the building block
for fatty acid synthesis.

3. converted into oxaloacetate: pyruvate carboxylase converts pyruvate to oxaloacetate. This

reaction replenishes the citric acid cycle intermediates and provides substrate for
gluconeogenesis. Pyruvate carboxylase is found in the liver and brain, but not in muscle.

4. converted into ethanol: pyruvate is reduced to ethanol, which occurs in yeast and certain
microorganisms, but not in humans.

During intense exercise LACTATE accumulates in muscle. Under strenuous exercise, stored muscle
glycogen is broken down into lactate by fermentation, yielding two ATP per glucose molecule
degraded.
• Lactic Acid Fermentation thus provides extra ATP energy quickly, supplementing the basal ATP
production resulting from the aerobic oxidation of other fuels via the citric acid cycle.

• During recovery, some lactate formed in the muscles is transported to the liver and used to
form glucose, which is released to the blood and returned to the muscles to replenish their
glycogen stores. This pathway (glucose→lactate→glucose) is the CORI CYCLE.

These enzymes participate in GLYCOLYSIS (anaerobic process of carbohydrate metabolism) that

occurs in the CYTOSOL (cytoplasm) of all cells:
1. Hexokinase-converts glucose to glucose-6-phosphate (phosphorylation).

2. Phosphoglucose isomerase-converts to glucose-6-phosphate into fructose-6-phosphate

(isomerization).

3. Phosphofructokinase-converts fructose-6-phosphate to fructose 1,6-biphosphate. The pace of

glucolysis is critically dependent on the level of activity of this enzyme.

4. Aldolase-converts fructose 1,6-biphosphate into dihydroxyacetone phosphate and glyceraldehyde

3-phosphate (an aldolytic reaction). Aldolase causes the transition from 6-carbon metabolites
into 3-carbon metabolites.

5. Triose Phosphate Isomerase-converts dihydroxyacetone phosphate into glyceraldehyde 3-

phosphate.

6. Glyceraldehyde 3-Phosphate Dehydrogenase-converts glyceraldehydes 3-phosphate into 1,3-

bisphosphoglycerate (high-energy phosphate compound is formed).

7. Phosphoglycerate Kinase-converts 1,3-biphosphoglycerate into 3-phosphoglycerate (first ATP

generating step).
 8. Phosphoglyceromutase-converts 3-phosphoglycerate into 2-phosphoglycerate (a mutase is an
enzyme that catalyzes an intramolecular shift of a chemical group).

9. Enolase-converts 2-phosphoglycerate into phosphoenolpyruvate (sodium fluoride inhibits

enolase thus inhibiting glycolysis). Sodium fluoride inhibits glycolysis by inhibiting enolase.

10. Pyruvate Kinase-converts phosphoenolpyruvate into pyruvate (second ATP formed).

PENTOSE PHOSPHATE PATHWAY (pentose shunt, hexose monophosphate pathway, or

phosphogluconate pathway)-is prominent in tissues actively carrying out biosynthesis of fatty acids
and steroids from small precursors like the mammary glands, adipose tissue, adrenal cortex, and liver.
Large amounts of NADPH are required in the reductive synthesis of fatty acids from acetyl CoA
(specifically the reduction of double bonds and carbonyl groups). NO ATP REQUIRED IN THE
PENTOSE PHOSPHATE PATHWAY.
• Tissues less active in synthesizing fatty acids (skeletal muscle), are not involved in the pentose
phosphate pathway.

• Pentose Phosphate Pathway produces carbon dioxide (CO2), NADPH, & five-carbon sugars
used for DNA and RNA. It is controlled by inhibition of glucose 6-phosphate dehydrogenase by
NADPH.

• In irreversible oxidative reactions of the pentose phosphate pathway, one carbon of glucose 6-
phosphate is released as carbon dioxide; NADPH is generated; and ribulose 5-phosphate is
produced.

• In reversible non-oxidative reactions, pentose phosphates produced from ribulose 5-phosphate

are converted to glycolytic intermediates fructose 6-phosphate & glyceraldehydes 3-phosphate.
The major role of Pentose Phosphate Pathway is NADPH production for reductive
biosynthetic reactions (e.g. fatty acid synthesis) and production of essential pentose
(especially D-ribose, used in the biosynthesis of nucleic acids). ATP IS NOT REQUIRED!
 ORAL CAVITY PHYSIOLOGY
SALIVA-is HYPOTONIC since salivary ductal cells are impermeable to water, and reabsorbs more
solute (sodium and chloride) than they secrete (potassium and bicarbonate ions). Thus, saliva has high
potassium and bicarbonate ion concentrations, but low sodium & chloride concentrations. Saliva
Functions:
• Digestion-initial starch digestion by salivary enzyme ----------amylase (ptyalin) secreted by
parotid gland---------.
• Lubrication of food by mucus.
• Protection of the mouth and esophagus by dilution and buffering of ingested foods.
• Saliva provides buffering action, facilitates deglutition, prevents demineralization, enhances
flavor, but DOES NOT initiate protein digestion.

Saliva Composition: 97-99.5% water, contains electrolytes (sodium, potassium, chloride, and
bicarbonate ions). Contains kallikrein, which leads to bradykinin production (a vasodilator).
• The major saliva electrolytes are sodium, calcium, potassium, and bicarbonate.

Control of Salivary Secretion: both parasympathetic and sympathetic stimulations cause secretion, with
parasympathetic have the greatest effect. Vagal stimulation increases saliva production, so vagotomy
(or atropine) inhibits saliva production and produces dry mouth.
• pH of saliva is between 6.0-7.0.

• Two-thirds of the 1.0-1.5 liters of saliva produced per day by the average adult comes from
submandibular glands, ¼ comes from the parotid glands, and the rest is produced by sublingual
and buccal glands. Most saliva comes from the SUBMANDIBULAR GLANDS.

Salivary Glands Produce 2 Types of Secretions:

1. Mucous-contains mucins (proteins attached to polysaccharides). Lubricates mouth and food.

2. Serous-contains salivary amylase (ptyalin) enzyme which splits starch into alpha-dextrin,
maltotriase, and maltose.

Salivary glands are EXOCRINE GLANDS because they have striated ducts lined by stratified
cuboidal epithelial cells or simple low columnar epithelium. Salivary glands produce MUCOUS,
SEROUS or BOTH types of secretions. Salivary flow is controlled by the PNS (parasympathetic
nervous system from CN VII & IX).

• Parotid Glands and Glands of Von Ebner produce ONLY SEROUS secretions.
• Sublingual and buccal glands produce purely MUCOUS secretions.
• Submandibular glands produce mucous and serous secretions (mixed), but MOSTLY serous.

ENAMEL-most calcified dental tissue and highly mineralized structure containing 95% inorganic
matter. The hydroxyapatite crystals (made of calcium and phosphate) are the largest mineral constituents
(90-95%) of this inorganic matter.
 • Ameloblasts-produce the enamel matrix (organic matrix) composed of protein components
amelogenins and enamelins. This organic matrix makes up 1-2% of enamel and water makes up
4%.

• Enamel is semipermeable which allows fluoride ions to be absorbed onto hydroxyapatite crystals
forming fluorapatite. The tooth becomes more resistant to bacteria-producing acids because
fluorapatite has a lower solubility product constant than hydroxyapatite (harder to degrade).

• ENAMEL IS HARDER THAN BONE because enamel hydroxyapatite crystals are larger and
more firmly packed. These tightly packed masses of hydroxyapatite crystals are enamel prisms
(the structural units of enamel). Enamel hydroxyapatite crystals are 4x larger than those in
bone, dentin, and cementum.

ENAMEL HYPOPLASIA-a defect in enamel matrix FORMATION. The enamel of primary and
permanent teeth appear pitted. Radiographically, the enamel is either absent or very thin over tips of
cusps and interproximal areas.
• Vitamins A, C, & D are involved in tooth development and calcification.

• Lack of vitamins A, C, & D during tooth formation can induce enamel hypoplasia.

• Enamel is hard in context, but thin and deficient in amount. The etiology may be hereditary or
environmental (caused by nutritional deficiencies such as vitamin A or D, inadequate calcium
intake, fluorosis, congenital syphilis, high fever, injury or trauma to the mouth.

• HYPOPLASIA results only if the assault occurs during the time the teeth are developing.
Either dentition may be involved. The teeth appear pitted, yellow to dark brown in color, with
open contacts. Radiographically, the enamel appears absent or very thin, especially over the cusp
tips and interproximally.

• Enamel hypocalcification-a defect in the MINERALIZATION of the formed enamel matrix.

CARIES activity is directly proportional to the consistency, frequency, and oral retention of
fermentable carbohydrates ingested. If you eat large amounts of fermentable carbohydrates only at
mealtimes, the extensiveness of caries is greatly reduced as opposed to eating fermentable carbohydrates
in small amounts throughout the day (frequency is most important). Strep mutans and lactobacilli are
the two major cariogenic bacteria.

FIRST EVENT in caries development is the deposit of plaque on the teeth. Plaque arises primarily as
a result of enzymatic reactions using sucrose and saliva. Large numbers of bacteria (mainly Strep mutans
and Lactobacilli) inhabit this plaque and are readily available to cause caries. However, these bacteria
depend greatly on carbohydrates (sucrose) for their food. When carbohydrates are available, their
metabolic systems are strongly activated and they multiply. They form acids (especially lactic acid) and
proteolytic enzymes.

• When the acidity level (pH) of the tooth surface drops below 5.5, teeth demineralization
proceeds faster than remineralization, causing a net loss of mineral structure.
• Extracellular dextrans are the structural component of plaque formed from sucrose by bacterial
enzymes (glycosyl transferases) located on the cell surface of certain lactic acid bacteria (e.g. S.
mutans and Lactobacilli). Dextrans are essential for the cariogenicity of these bacteria.

 MUSCLE PHYSIOLOGY
MOTOR UNIT-a motor neuron and all the muscle fibers it innervates.
• Each muscle is composed of several muscle fibers.
• Each muscle fiber is innervated by a single alpha-motor neuron.
• Each alpha-motor neuron innervates many muscle fibers.
• All of the fibers innervated by a motor neuron contract when that motor neuron fires an action
potential.

For fine control, a single alpha-motor neuron innervates only a few muscle fibers. For larger movements,
a single alpha-motor neuron innervates thousands of muscle fibers.

3 Types of Motor Units:

1. Fast fatigable (large motor neurons).
2. Slow fatigue-resistant (small motor neurons).
3. Fast fatigue-resistant (small motor neurons).

Size Principal- motor units are recruited in order of the size of the motor neuron, from small (fire first;
generate the smallest force) to large (fire last; generate the largest force).

Two Types of Muscle Receptors:

1. MUSCLE SPINDLES (detect stretch)-are found within the belly of muscles, and consist of small,
encapsulated intrafusal fibers that run parallel with the main muscle fibers (extrafusal fibers). The
finer the movement required, the greater number of muscle spindles in a muscle. Spindles detect
both static and dynamic changes in muscle length. The muscle spindle has 3 components:
1. specialized muscle fibers (intrafusal fibers).
2. sensory terminals (annulospiral ending): group Ia and II afferents.
3. motor terminals: gamma motor neurons (fusomotor fibers). Activating the gamma motor
neuron maintains spindle sensitivity.

• Muscle spindle is arranged in PARALLEL with the main muscle fibers (extrafusal fibers).

• Strong stimulation of muscle spindles in the muscles of mastication cause contraction of the
stimulated muscles (e.g. stimulate spindles in the masseter muscle, the master contracts).

Extrafusal fibers-make up the bulk of muscle, are innervated by alpha-motor neurons (efferents), and
provide the force for muscle contraction.

Intrafusal fibers-fibers encapsulated in sheaths to form muscle spindles. Innervated by gamma-motor

neurons (efferent neurons). Nuclear bag and Nuclear chain Fibers are the two main types of intrafusal
fibers are encapsulated in sheaths to form muscle spindles.
• Nuclear bag fibers-detect fast, dynamic changes in muscle length. Innervated by group Ia
afferents (fastest in the body).
 • Nuclear chain fibers-detect static changes in muscle length. Innervated by slower group II
afferents.

A sensory (afferent) neuron transmits afferent (sensory) nerve impulses from the receptor (peripheral
ending of a sensory neuron) to the spinal cord. A motor (efferent) neuron, transmits efferent nerve
impulses from the integrating center in the spinal cord to an effector (muscle cell).

GOLGI TENDON ORGAN (detect tension)-innervated by a single group of Ib sensory fiber. Golgi
tendon organ is arranged in SERIES with extrafusal fibers.
REFLEX-an automatic response to a stimulus. SPINAL CORD acts as a relay and reflex center. Two
important spinal reflexes influence the contraction of skeletal muscles:

1. Stretch Reflex-functions to maintain muscle tone for posture, to increase efficiency for
locomotion, to smooth out movements, and acts as a site of coordination for higher-order inputs.
• Stretch reflex is initiated as skeletal receptors (muscle spindles are sensitive to muscle
length). This reflex stimulates the stretched muscle to contract. Ex: patellar reflex (knee jerk
reflex) where striking the patellar tendon at the knee causes the quadriceps muscles to contract
and swing the leg forward.

• Tone is essential for many normal body functions like holding the spine erect, eyes open, and
jaw closed. The tone of the muscle is usually maintained by the stretch reflex. When the
muscle is stretched, so is the muscle spindle that records the change in length (and how fast)
and sends signals to the spine, which conveys this information. This triggers the stretch
reflex, which attempts to resist the change in muscle length by causing the muscle to contract.
This basic function of the muscle spindle helps maintain muscle tone and protect the body
from injury.

• When the stretch reflex stimulates the stretched muscle to contract, antagonistic muscles that
oppose the contraction are inhibited. This occurrence is “reciprocal inhibition” and the
neuronal mechanism that causes this reciprocal relationship is “reciprocal innervation”.
▪ Reciprocal inhibition is the process by which extensor muscles acting at a joint are
inhibited by stretch of a flexor muscle acting on the same joint.

2. Tendon reflex-initiated at receptors called neurotendinous organs (golgi tendon organs)

sensitive to tension that occurs most frequently as a result of muscular contraction. Tendon reflex
stimulates the contracted muscle to relax, and can also be stimulated by percussing the tendon of a
muscle.
• Golgi Tendon Reflex-is the reverse of the stretch reflex. Golgi tendon organs
participate in reflex loops with the opposite effect of muscle spindles. Functions:
o Regulate the force of contraction.
o Flexion reflexes move limbs AWAY from stimuli (i.e. step on a tack).
o Reflex elements are sites of convergence for voluntary movement.

SKELTAL MUSCLE FIBERS:

1. FAST-TWITCH FIBERS (Type II) are twice as large in diameter arranged with few muscle
 fibers per motor unit. They deliver extreme amounts of power for a few seconds to a minute.
Short, rapid movements Enable fine, careful movements (contraction of extraocular muscle of the
eye).
• high myosin-ATPase activity, high glycogen content, and fast speed/intensity of contraction.
• White in color (no myoglobin).
• low resistance to fatigue and low oxidative capacity (fast twitch use glycolysis to generate
energy).
• Contain higher concentrations of glycolytic enzymes for anaerobic glycolysis
• few mitochondria and fewer capillaries surrounding them
• many and highly extensive sarcoplasmic reticulum and T-tubules.

Think Chicken: white meat (white muscle) is in the breast and used for intermittent wing flapping.

2. SLOW-TWITCH FIBERS (Type I)-deliver prolonged strength of contraction over many

minutes or hours. Slow twitch fibers are mainly organized for endurance (especially for the
generation of aerobic energy). Adapted for long, sustained contractions
• Red (myoglobin) color, small diameter.
• low myosin-ATPase activity, low glycogen content, and low speed/intensity of contraction.
• high resistance to fatigue and high oxidative capacity (oxidative metabolism is used for
energy).
• low enzymes for anaerobic glycolysis, many mitochondria and capillaries, & high
myoglobin content.
• few sarcoplasmic reticulum and T-tubules.

Think Chicken: dark meat (red muscle) is in the thighs used for sustained posture maintenance.

MUSCLE CELLS use creatine phosphate to store energy. Muscle cells use this phosphorylated form
of creatine to store energy. Normal metabolism cannot supply energy as quickly as a muscle cell can use
it, so an extra storage source is needed. The phosphate group can be quickly transferred to ADP to
regenerate the ATP necessary for muscle contraction. Used for immediate source of energy for muscle
contraction (ATP→ADP→Phosphoric Acid).

Phosphate compounds found in living organisms are divided into two groups based on their standard
free energies and hydrolysis:
1. Higher phosphate group-transfer potential than ATP:
• Phosphoenolpyruvate, Acetyl phosphate, 1,3-diphosphoglyceric acid, Carbamoyl
phosphate, & Creatine phosphate.

2. Lower phosphate group-transfer potential than ATP:

• Glucose-1-phosphate, Glucose-6-phosphate, Fructose-1,6-diphosphate, and Creatine.

Hydrolysis of ATP (adenosine triphosphate) provides the immediate source of energy for muscle
contraction. Although a muscle fiber contains only enough ATP to power a few twitches, its ATP “pool”
is replenished as needed. 3 sources of high-energy phosphate keeps the ATP “pool” filled: Creatine
phosphate, glycolysis of glycogen, & cellular respiration in the mitochondria of muscle fibers.
• Adenosine triphosphate (ATP)-the chemical substance that is the immediate energy
 source for muscle contraction.

Contraction of skeletal muscle is controlled by the nervous system. Nerve impulses traveling down the
motor neurons of the sensory-somatic branch of the nervous system cause the skeletal muscle fibers at
which they terminate to contract. The junction between the terminal of a motor neuron and a muscle fiber
is a neuromuscular junction (myoneural junction).
• During an isotonic contraction, the A band does not change its width or length. However, the I
band, sarcomeres, two consecutive z-lines, and elastic elements DO change.

WHEN A NERVE IMPLUSE ARRIVES at the neuromuscular junction, calcium ions enter the nerve
terminal causing release of acetylcholine from synaptic vesicles inside the motor neuron.
Acetylcholine then binds to the muscle fiber plasma membrane causing depolarization which triggers an
action potential (action potential travels along the membrane and t-tubules). This action potential
triggers the release of calcium ions form the sarcoplasmic reticulum leading to interactions between
thick (myosin) and thin (actin) filaments of the sarcomeres of the fibers. These interactions are
responsible for the development of tension and the shortening of the fibers.

• A submaximal direct stimulus to a skeletal muscle tissue will cause some of the fibers to
contract, not the whole muscle. Only contraction of some fibers occurs.
• The ratio between the amount of work done and total energy expended determines the mechanical
efficiency of muscular contraction.

Action potentials in the skeletal muscle cell membrane initiate depolarization of T-tubules. T-tubules
open calcium ion release channels in the sarcoplasmic reticulum. The calcium ions released from the
sarcoplasmic reticulum bind to TROPONIN (Troponin C). Calcium binds to troponin C on the thin
(actin) filaments, causing a conformational change in troponin that permits the interaction between actin
and myosin.

WHEN CALCIUM IONS BIND TO TROPONIN skeletal muscle contraction is initiated. Calcium
ion binding to troponin causes tropomyosin molecules move from its blocking position, permitting
actin and myosin to interact. High energy myosins bind weakly to actin subunits. However, when
inorganic phosphate is released from the myosins, the myosins bind tightly to actin subunits. Energy stored
in the high-energy myosins is discharged, and the myosin heads swivel, pulling on the thin filaments. This
repeating pulling of the thin filaments past the thick filaments toward the centers of the sarcomeres
draws the Z-lines closer, and muscle fiber shortens (contracts). This process is repeated as long as
calcium ions are bound to troponin and ATP is available. Once calcium ions are returned to the
sarcoplasmic reticulum, tropomyosin moves back into its blocking position and prevents further
interaction between high-energy myosins and actin subunits. Contraction stops, and the muscle fibers
relax. Note: cardiac muscle contraction is initiated by slow inward movement of calcium ions.
• Sarcomere-the basic contractile unit of muscle myofibril.

Composition of MYOFILAMENTS: contains thick filaments (composed mainly of myosin protein) and
thin filaments (composed of the proteins: actin, tropomyosin, and troponin (C, T, and I).


RESPIRATION

ALVEOLAR VENTILATION-the volume of atmospheric air that enters the alveoli (either per breath or
per minute) that participates in gas exchange between the alveoli and blood.

• In respiration, the elimination of hydrogen ions from a substrate is always associated with
elimination of electrons.

• Alveolar ventilation is the BEST way to determine effective breathing.

Alveolar Ventilation= Respiratory Rate (RR) x (tidal volume – dead space).

• Alveolar ventilation is a good criterion to determine effectiveness of breathing.
• RR = breaths per minute
• Minute ventilation = tidal volume x breaths/min

EXCHANGE of oxygen and carbon dioxide between the lungs and blood occurs INSIDE ALVEOLI.
• Anatomical dead space-air-filled passageways where no gas exchange occurs (nose, pharynx,
trachea, and bronchi). Anatomical dead space depends on the size of the individual (average value
is 150ml)

When the lungs are in the resting position, the pressure inside them (INTRAPULMONARY
PRESSURE) IS EQUAL TO ATMOSPHERIC PRESSURE. At sea level, the resting intrapulmonary
pressure is 760mm Hg which is the atmospheric pressure that pushes against the inner walls of the lungs
and opposes their collapse.

When the lungs are in the resting position after a normal exhalation, the collapsing force of the lungs is
equal to a pressure of 4mm Hg. This pressure is caused by the elastic C.T. of the lungs and surface tension
of the fluid coating the alveoli, which favors a reduction in lung size.

INTRAPLEURAL PRESSURE (recoil pressure)-the pressure within the pleural cavity that pushes
against the outer walls of the lungs and also favors their collapse. In the resting position, intrapleural
pressure is 4mm Hg less than atmospheric pressure. Hence, the intrapleural pressure is approximately
756mm Hg. During normal respiration, intrapleural pressure is SUBATMOSPHERIC.

Important: forces favoring lung collapse (4mm Hg collapsing force of the lungs, and 756mm Hg
intrapleural pressure) are balanced by a force that opposes their collapse (760mm Hg intrapulmonary
pressure). As a result of this balance, the lungs remain expanded and do not collapse.
• Under normal circumstances, intrapulmonary pressure IS ALWAYS GREATER than
intrapleural pressure (intrapulmonary pressure > intrapleural pressure).

PULMONARY VENTILATON-the total volume of gas per minute inspired or expired. Sensory
information is coordinated in the brain stem. The output of the brain stem controls the respiratory
muscles and the breathing cycle. Pulmonary ventilation is influenced by arterial PO2, arterial PCO2,
and arterial pH.

Receptors for CO2, O2, & H+:

1. central (medullary) chemoreceptors-located in medulla; stimuli that increase breathing rate are ↓
pH &↑ PCO2.
2. peripheral chemoreceptors: located in the carotid and aortic bodies; stimuli that increase breathing
rate are ↓ PO2 (if less than 60mm Hg)↑ PCO2, and ↓ pH.

Factors that simulate Central & Peripheral chemoreceptors, and interact to regulate Breathing:
• Arterial PO2 (partial pressure of oxygen in arterial blood)-very low PO2 in arterial blood
increases pulmonary ventilation.

• Arterial PCO2 (partial pressure of carbon dioxide in arterial blood) the major stimulus for the
respiratory centers. Elevated arterial PCO2 increases ventilation.

• Arterial pH-a low arterial pH (increased H+ concentration) increases ventilation.

Lung Stretch Receptors-located in smooth muscle of the airways, and are stimulated by DISTENSION
OF THE LUNGS. Distention causes lung stretch receptors to initiate the Hering-Breuer Reflex-
prevents over inflation of the lungs. It is mainly a protective mechanism that prevents the lungs
from overfilling during inspiration. During inspiration, lung stretch receptors increase their activity, and
stimuli are sent over the afferent vagus nerve to the respiratory control centers in the brain (medulla).
When the stimuli reach the critical level, inspiration stops. Hering-Breur Reflex is not important in
controlling respiration during normal breathing.

Other Receptors that Control Breathing:

• J receptors-located in alveolar walls; when stimulated J receptors cause rapid, shallow breathing.
• Irritant receptors-located between airway epithelial cells; are stimulated by noxious substances
(e.g. dust, pollen).
• Joint and muscle receptors-activated during exercise to stimulate breathing.

Remember: CARBON DIOXIDE CONCENTRATION in the blood (PCO2) is the MOST

IMPORTANT STIMULUS for the respiratory control center (medulla). ↑ PCO2 increases respiration
by stimulating central chemoreceptors, while a decrease in PCO2 inhibits respiration.

LUNG VOLUMES & CAPACITIES:

1. Vital Capacity (VC)-the greatest amount of air that one can exchange in a forced respiration;
approximately 4500ml. VC = TV+IRV+ERV.

2. Tidal Volume (TV)-the amount of air inspired or expired with each breathe (~500ml). Normal
respiration rate (RR) is about 12 times per minute.

3. Functional Residual Capacity (FRC)-the amount of air remaining in the lungs at the end of
normal expiration. This air is used to provide air to alveoli that will aerate the blood evenly
between breaths. FRC = ERV + RV. If FRC is larger than normal, nitrous sedation will take
longer.
 4. Inspiratory Reserve (IRV)-the extra volume of air that can be inspired over and above the
normal tidal volume (by taking a deep breath) ~3000ml.

5. Expiratory Reserve (ERV)-extra volume of air that could still be expired past the normal
expiration of tidal volume (by forcefully expelling a deep breath); ~ 1100ml.

6. Minute Respiratory Volume (MRV)- volume of air moved into the respiratory passageways in
one minute. MRV = TV x RR.

7. Total Lung Capacity-the maximum volume that the lungs can be expanded with the greatest
possible inspiratory effort. Cannot be measured through spirometry. Must use gas dilution or body
plethysmography.

8. Residual Volume (RV)-volume of air remaining in the lungs (alveoli) at the end of a forced
maximal expiration. ~1200ml. Not measured through spirometry. Must use gas dilution or body
plethysmography.

Factors that determine the speed at which gas DIFFUSES through the Respiratory Membrane:
1. Thickness of Membrane-it is advantageous to have a thin respiratory membrane since oxygen
and CO2 diffuse across it during respiration. The rate of diffusion through the membrane is
inversely proportional to the membrane thickness. As thickness increases diffusion rate
decreases.

2. Surface Area of Membrane-the rate of diffusion is directly proportional to the surface area.
Emphysema decreases surface area, which impedes exchange of gases.

3. Gas Solubility & MW-the number of molecules of a gas that dissolve in a liquid depends on the
solubility of the gas in the liquid and on the pressure of that gas in the atmosphere. By increasing
the pressure of the gas, more molecules of it dissolve in the liquid. Under specific conditions, a
gas that is dissolved in a liquid can then be considered to exert a pressure or partial pressure (e.g.
PO2 and PCO2).

4. Pressure Difference between the two Sides of the Membrane-a net diffusion will occur from
a region of high pressure to a region of low pressure. Partial pressure of oxygen in alveoli is
greater than the pressure of oxygen in the blood. Thus, there is a net diffusion of oxygen from the
alveoli into the blood. When the pressure of the gas in blood is greater than the partial
pressure in the alveoli (as is true for CO2), net diffusion from blood into alveoli occurs.

RESPIRATORY CONDITIONS:
1. Apnea-transient cessation or absence of breathing.

2. Hyperapnea-abnormally deep and rapid breathing.

3. Dyspnea-unpleasant sensation of difficulty in breathing.

4. Hypercapnea-excess CO2 in arterial blood (hypoventilation).

 5. Hypocapnea-below normal CO2 in arterial blood (loss of CO2 due to hyperventilation).

6. Respiratory arrest-permanent cessation of breathing (unless corrected).

7. Hyperventilation-increased pulmonary ventilation in excess of metabolic requirements.

Hyperventilation results in the loss of carbon dioxide (CO2) from the blood (hypocapnea), thus
causing a decrease in blood pressure and sometimes fainting.

8. Hypoventilation-underventilation in relation to metabolic requirements. Hypoventilation results

in an increased level of carbon dioxide (CO2) in the blood (hypercapnea). Arterial CO2 tension
is the most important test for hypoventilation.

Two situations that excite respiratory neurons and increase respiration are an increase in [H+] in the
arterial blood (↓pH), and an increase in arterial blood PCO2. These two situations are closely related
since any time the partial pressure of CO2 increases (PCO2), the concentration of H+ ion also
increases (or ↓pH) because CO2 combines with water to form carbonic acid. Carbonic acid then
dissociates into H+ ions and bicarbonate. These hydrogen ions decrease pH (more acidic) of arterial
blood, thus increasing respiration.


REPRODUCTION

OVULATION-occurs as a result of the estrogen-induced LH surge. Ovulation is the discharge of an

ovum (oocyte) from the mature follicles (Graafian follicle) of the ovary. Ovulation occurs as a result of
the cyclic ovarian cycle and pituitary endocrine function. The anterior pituitary secretes gonadotropins
FSH and LH (with LH predominating).
• Late in the proliferative (follicular) phase, estrogen levels peak, FSH secretion decreases, and
LH secretion increases, surging at mid-cycle (around day 14). The LH surge leads to final
maturation of the follicle, rupture of follicle, and ovulation.

• Without LH, even though large quantities of FSH are available, the follicle will not progress to the
ovulation stage.

• The ruptured, mature follicle forms corpus luteum (secretes estrogen and progesterone).

• FSH & LH are glycoproteins that act in female ovaries and male testis.

OVULATION-occurs 14 days before menses, regardless of cycle length. The average menstrual cycle
occurs over 28 days, although the normal cycle may range 22-34 days. Menstrual Cycle:
1. Menstrual phase- cycle starts with menstruation (cycle day 1) which usually lasts 5 days.

2. Proliferative (follicular) phase-lasts from cycle day 6 to day 14. LH and FSH act on the ovarian
follicle (mature ovarian cyst containing the ovum). This leads to estrogen secretion, which
stimulates buildup of the endometrium. Late in this phase, estrogen levels peak, FSH secretion
declines, and LH secretion increases, surging at mid-cycle (around day 14). Then, estrogen
production decreases, the follicle matures, and ovulation occurs.

3. Ovulation day-day 15; occurs as a result of the estrogen-induced LH surge (causes ovulation).

4. Luteal (secretory) phase-lasts 14 days. FSH and LH levels drop. The corpus luteum develops,
and synthesizes estrogen and progesterone. If fertilization does not occur, the corpus luteum
degenerates (becomes nonviable corpus albicans). As a result, estrogen and progesterone levels
decrease until their levels are too low to keep the endometrium in a fully developed secretory
state. Note: the endometrial lining is shed as menstrual fluid during menstruation, or menses.

5. Decreasing estrogen and progesterone levels stimulate the hypothalamus to produce GnRH,
and the cycle begins again.

Significant results of the female sexual cycle: only a single mature ovum is normally released from
the ovaries each month so that only a single fetus can begin to grow at a time. Also, the uterine
endometrium is prepared for implantation of the fertilized ovum at the required time of the month.

ESTROGEN-a class of steroid hormones that contain 18 carbons and an aromatic ring. Estrogen
causes development of female secondary sex characteristics at puberty (breast development), &
maintains pregnancy. On average, females reach puberty 1 or 2 years earlier than males.
• In females, puberty is marked by the first episode of menstrual bleeding = menarche.
• At puberty, an alteration in brain function increases gonadotropin-releasing hormone (Gn-RH)
secretion by the hypothalamus. Gn-RH stimulates FSH and LH secretion by the anterior
pituitary gland, which leads to an increased production of estrogens (androgen hormone) by the
ovaries.
• FEMALE PUBERTY EVENTS (ex: enlargement of vagina, uterus, and uterine tubes, deposition
of fat in the breasts and hips) are the result of increased production of estrogens by the
ovaries.
• Estrogen is effective at very low concentrations and generates a slowly developing long-term
response in target tissues by binding to an intracellular receptor.

PROGESTERONE-its most important function is it promotes secretory changes in the uterine

endometrium during the latter half of the monthly female sexual cycle to prepare the uterus for
implantation of the fertilized ovum.

GONADOTROPINS secretion from the pituitary gland between 10-15 year of age marks the onset of
puberty.

At puberty, an alteration in brain function leads to an increased production of gonadotropin-releasing

hormone (Gn-RH) by the hypothalamus. Gn-RH stimulates FSH and LH secretion (gonadotropins) by
the anterior pituitary gland. These gonadotropins stimulate growth and function of the testis.
Specifically, FSH promotes the maturation of sustentacular cells (Sertoli cells) involved in sperm
development and maturation. LH stimulates interstitial cells (Leydig cells) of the testis to produce
testosterone.

Onset of puberty varies, but usually occurs between 10-15 years of age. Puberty events (e.g.
enlargement of the penis, scrotum, and testes, hair growth, and voice changes) result from increased
testosterone production by the testes. These changes are secondary sex characteristics.

• During childhood, a boy does not secrete gonadotropins, thus has little circulating testosterone.

• Pituitary gonadotropins stimulate testes functioning and testosterone secretion.

• Puberty marks the development of male secondary sexual characteristics.

• During puberty, the penis and testes enlarge, and the male reaches full adult sexual and
reproductive capability.

• A male child is considered to reach his full adult sexual capabilities at the end of puberty. This
means after puberty, the male child is capable of reproduction.

Precocious Puberty-a condition in which the changes associated with puberty begin at an
unexpectedly early age due to an excess of androgenic (in boys) and estrogenic (in girls) substances
produced by the adrenal cortex. These substances resemble the male and female sex hormones.

 SENSORY ORGANS
EAR-consists of three major parts:

1. External Ear-consists of the external part (pinna) and ear canal. It receives sound waves.
• Auricle (pinna)-directs sound waves.
• External auditory canal (meatus)-contains hair and cerumen (brown earwax); serves as a
resonator.

2. Middle Ear (tympanic cavity)-an air-filled cavity in the temporal bone that communicates
anteriorly with the nasopharynx via the Eustachian (Auditory) tube (pharyngotympanic tube).
Middle ear communicates posteriorly with the mastoid air cells and the mastoid antrum through
the aditus ad antrum. Eustachian tube serves to equalize air pressure in the tympanic cavity and
nasopharynx.
• Auditory tube-regulates pressure.

• Ossicles (malleus (hammer), incus (anvil), stapes (stirrup)-three small bones linked
together to transmit sounds.

• Stapedius muscle (smallest skeletal muscle in the body) and tensor tympani muscle.

• Middle ear infections (otitis media) are quite prevalent and may become extensive due
to connection to both the mastoid air cells and the nasopharynx by way of the
Eustachian tube.

3. Inner Ear-formed by a bony labyrinth and a membranous labyrinth. Consists of the acoustic
apparatus, vestibular apparatus, semicircular canals, and a bony and membranous labyrinth:
• Vestibule apparatus (saccule and utricle)-associated with sense of balance.
• Semicircular canals-concerned with equilibrium.
• Cochlea (contains two membranes: vestibular and basilar)-portion of inner ear
responsible for hearing.
• Organ of Corti-a spiral organ that contains hair cell receptors for hearing and is
responsible for sound perception.
A SOUND IS CHARACTERIZED by pitch, loudness, and timbre (quality):
1. Pitch-related to the frequency of the sound wave. The higher the frequency of a sound wave,
the higher the pitch of the sound wave. (frequency is measured in hertz (Hz). PITCH of a sound
is related mainly to the frequency of the sound wave.

2. Loudness-related to the intensity and amplitude of the wave. The greater the amplitude of a
sound wave, the greater the intensity of the sound wave, and the louder the sound. (intensity is
measured in decibels (dB). Intensity of sound depends mainly on sound wave amplitude.

3. Timbre (quality)-of a sound is related to the presence of additional sound wave frequencies
superimposed on the principal frequency.

RETINA-innermost coat of the eyeball. It’s the intraocular structure that contains nerves that sense light
and the blood supply that nourishes them. Rods receive visual stimuli and sends them to the brain.
Photoreceptor neurons (rods and cones) are the visual receptors of the retina. RODS & CONES
CONTAIN PHOTOPIGMENTS. There are 4 different photopigments, each consisting of a protein
(opsin) to which a chromophore molecule (retinal-produced from vitamin A) is attached. Opsins differ
from pigment to pigment and confer specific light-sensitive properties on each photopigment.
• Rhodopsin deficiency is due to a decrease in dietary intake of vitamin A.

RODS-contain a photopigment (rhodopsin). Rod’s response indicates different degrees of brightness,

but the entire rod system cannot discriminate color (black and white only). Rods are numerous in the
periphery of the retina.
▪ During dark adaptation (night vision) rhodopsin is synthesized in the rods.
▪ Rods are more abundant than cones, have higher sensitivity, and lower acuity.

CONES-primarily responsible for color vision. There are 3 types of cones (red, green, blue), and each
cone contains a different photopigment that is selectively sensitive to a particular wavelength of light.
Cones are concentrated in the center of the retina (especially in the fovea).
▪ Cones are the principal photoreceptors during daylight or in brightly lit areas.

IRIS-intraocular structure (circular colored area of the eye) that controls the amount of light that enters
the eye by opening and closing like the aperture of a camera lens. The size of the pupil is controlled by
the papillary sphincter muscle, which opens and closes the iris.

INTRAOCULAR STRUCTURES:
1. Sclera-tough white outer layer that maintains the size & form of the eyeball. Turns yellow during
Jaundice.

2. Cornea-transparent dome on the eye surface that serves as a protective covering and helps focus
light on the retina at the back of the eye.

3. Iris-the circular colored area of the eye (the amount of pigment in the iris determines eye color).
Ciliary body-made of 3 muscles and the iris. It controls lens thickness.

4. Pupil-circular opening (black area) in the middle of the iris through which light enters the eye.

5. Lens-situated directly behind the iris at the papillary opening by changing its shape, the lens
focuses light onto the retina.

6. Choroid-lines the inner aspect of the eyeball beneath the retina; highly vascular.

Eyeball Has Two Fluid-Filled Segments:

1. Anterior Segment- front 1/3 of the eye that includes structures anterior to the vitreous humour
(cornea, iris, ciliary body, and lens). In the anterior segment, there are two fluid-filled spaces
(anterior chamber located between the corea’s posterior surface and iris), and the posterior
chamber (located between the iris and front of the vitreous). Aqueous humor (gelatinous fluid that
resembles plasma) fills theses spaces within the anterior segment to provide nutrients to
surrounding structures.

2. Posterior segment-the back 2/3 of the eye that includes the anterior hyaloid membrane,
vitreous humor, retina, choroid, and optic nerve.
EYE DISORDERS:
1. Hyperopia (farsightedness) is corrected with a CONVEX lens. Objects close to you appear
blurred. Light focuses behind the retina, and is corrected with a convex lens.

2. Myopia (nearsightedness)-distant objects appear blurred. Light focuses in front of the retina and
is corrected with a CONCAVE lens. Contraction of ciliary muscle, constriction of pupils, and
convergence of eyeballs are ways to accommodate for near vision.

3. Astigmatism-occurs when the lens curvature is not uniform; corrected with a cylindrical lens.

4. Presbyopia-the inability of the eye to focus sharply on nearby objects resulting from loss of
elasticity of the lens with advancing age. It is corrected with a convex lens.

5. Miosis-constriction of the pupil caused by a normal response to an increase in light, certain drugs,
or pathological conditions.
6. Mydriasis-the prolonged abnormal dilation of the pupil induced by a drug or by a disease.

 RENAL (KIDNEY)
NEPHRON-kidney’s basic structural and functional unit. Each nephron consists of a tubular apparatus
(glomerulus) and collecting duct. Each glomerulus is inside a glomerular capsule (Bowman’s capsule),
and consists of a cluster of capillaries. Nephron Parts and Function:

• Proximal convoluted tubule-secretion of hydrogen ions; reabsorption of glucose, amino acids,

sodium, chloride, phosphate, calcium, and water. Most water reabsorption occurs here.

• Thin Descending limb of loop of Henle- reabsorption of water.

• Thick Ascending limb of loop of Henle-reabsorption of sodium and chloride (NaCl). This NaCl
reabsorption is the basis for the countercurrent multiplier activity of the kidney. This region is
impermeable to water.

• Distal Convoluted Tubule-secretion of H+ and K+ ions, and reabsorption of Na+ (all controlled
by aldosterone).
o The distal end of each distal convoluted tubule joins the distal ends of neighboring
nephrons, forming a larger collecting duct or tubule. The collecting duct secretes hydrogen
ions and reabsorbs water (controlled by antidiuretic hormone).

• TUBULAR FLUID OSMOLALITY IS HIGHEST IN HENLE’S LOOP. Loops of Henle are

responsible for the establishment of an osmotic gradient within the medulla of the kidney.
Processes that occur in nephrons, ultimately leading to urine formation include glomerular filtration,
tubular reabsorption, and tubular secretion.
• Normal urine consists of sodium, chloride, potassium, calcium, magnesium, sulfates, phosphates,
bicarbonate, uric acid, ammonium ions, creatinine, and urobilinogen. Urine is secreted by the
kidneys, transported by ureters, stored in the bladder, and voided through the urethra.

• Normal urine is clear, straw-colored, slightly acidic, with an odor of urea. The normal specific
gravity of urine is between 1.005-1.030. Urine formation is important in regulating the acid-base
balance and in maintaining the normal osmotic pressures of intracellular fluids.

• DIURESIS-caused by a decrease in the tubular reabsorption of water.

• Causes of dilute urine: absence of ADH and Diabetes insipidus.

• Causes of concentrated urine: decreased plasma volume, cellular dehydration, Diabetes mellitus,
and excess ADH.

Countercurrent Mechanism-a system in the renal medulla that facilitates urine concentration as it passes
through the renal tubules. Countercurrent mechanism is responsible for the secretion of hyperosmotic
urine and requires the penetration of the loop of Henle into the renal medulla for the development of a
medullary osmotic gradient. It is essential for the production of an osmotically concentrated urine,
and depends on the special anatomical arrangement of the loops of Henle and vasa recta (capillaries
supplying the medulla). Countercurrent Mechanism involves 2 basic processes: (explains functioning
of the kidney)

1. Countercurrent multiplication in the loops of Henle depends on repetitive reabsorption of NaCl

by the thick ascending loop of Henle and continued inflow of new NaCl from the proximal tubule
into the loop of Henle. Sodium chloride reabsorbed from the ascending loop of Henle keeps
adding to the newly arrived sodium chloride, thus “multiplying” its concentration in the medullary
interstitium. Countercurrent multiplier activity in the kidney depends on active reabsorption
of sodium ions in the ascending limb of the loop of Henle.

2. Countercurrent exchange in the medullary blood vessels (vasa recta). Vasa recta DO NOT
create the medullary hyperosmolarity, but prevent it from being dissipated.

By the time blood leaves the medulla, it has lost all the extra salts it gained = countercurrent exchange.

KIDNEYS normally excrete 1-2 liters of urine per day. When tubular secretion and reabsorption
processes are complete, the fluid remaining in the tubules is transported to other components of the
urinary system to be excreted as urine. Urine consists of water and other materials that were filtered or
secreted into the tubules, but not reabsorbed.

Although 180 L per day of glomerular filtrate are produced, the kidneys normally excrete only 1-2
liters of urine each day. 99% of the filtrate is returned to the vascular system, while 1% is excreted as
urine. Water and substances the body needs are returned to the blood, whereas waste products and excess
fluid and solutes remain in the tubules are excreted from the body as urine.
• Reabsorption-the return of filtered molecules from the renal tubules to the blood. Most fluid
reabsorption occurs in the proximal convoluted tubules.

• Tubular fluid-the filtrate that leaves the glomerular capsules and flows along the other portions of
the renal tubules.

• Both tubular secretion & reabsorption can occur by active transport or passive mechanisms.

INULIN-a starch filtered but not reabsorbed by the kidney tubules. Inulin is given orally, and freely
filtered from the glomerular capillaries into glomerular capsules with the glomerular filtrate, but it does
not undergo tubular secretion or reabsorption. The glomerular filtration rate is estimated from the
length of time needed for the inulin to appear in urine. If plasma clearance of a substance that is freely
filtrated is less than that of inulin, then there is a net reabsorption of the substance in the tubules.
Glomerular filtration rate can be determined by the clearance of inulin.
• Glomerular filtration rate (GFR) is measured by a substance filtered, but not reabsorbed or
secreted (like inulin).

PLASMA CLEARANCE RATE of a substance is the rate at which the substance is eliminated or
cleared from the plasma by the kidneys during one pass and is EQUAL TO RENAL PLASMA
FLOW. By determining the plasma clearance of certain substances, the glomerular filtration rate (GFR)
and rate of plasma flow through the kidneys can be determined (renal plasma flow). This information
is useful in assessing kidney function. Plasma clearance of inulin indicates glomerular filtration rate.

• Para-aminohippurate (PAH) is filtered and secreted. Glucose and sodium chloride are filtered
and subsequently reabsorbed. INULIN IS ONLY FILTERED, not reabsorbed or secreted by the
kidney tubules.
• Assessment of blood urea nitrogen (BUN) and serum creatine also helps determine kidney
function. These tests evaluate glomerular function by assessing GFR.

• A substance actively secreted by the kidney is helpful in measuring renal blood flow, renal plasma
flow, tubular maximum, and filtration fraction. IT IS NOT HELPFUL IN MEASURING GFR.

GLOMERULAR FILTRATION-the filtration process as blood flows through the kidney. Some of the
plasma (16-20%) is filtered out of the glomerular capillaries into the glomerular capsules of the renal
tubules as the glomerular filtrate. This glomerular filtrate contains most plasma components, but is
protein free (the osmotic pressures of plasma and glomerular filtrate are the same).

• Most glomerular filtrate is reabsorbed in the PROXIMAL CONVOLUTED TUBULE.

Approximately 2/3 of the glomerular filtrate is reabsorbed in the proximal convoluted tubule since
these tubules have freely permeable cell membranes.

• Normally, the kidneys produce 180 liters of glomerular filtrate per day.

• Glomerular capillary hydrostatic pressure is the main force causing glomerular filtration.

• Glomerular filtration is favored by the pressure of blood within the glomerular capillaries and
opposed by the pressure of fluid within the glomerular capsules and by the osmotic forces exerted
by unfiltered plasma proteins within the glomerular capillaries.

Glomerular Filtration Rate (GFR) is increased by:

• Vasodilation of afferent arterioles increases glomerular capillary hydrostatic pressure.
• Vasoconstriction of efferent arterioles increases glomerular capillary hydrostatic pressure.
• Decreased pressure in Bowman’s capsule.
• Decreased plasma colloid osmotic pressure decreases glomerular capillary oncotic pressure.

Increased sympathetic stimulation preferentially constricts afferent arterioles, lowering glomerular

capillary hydrostatic pressure and GFR. Urea, glucose, amino acids, and plasma electrolytes appear in
equal concentrations in both glomerular filtrate and in plasma. Steroid hormones are NOT in equal
concentrations.

DECREASE IN GFR: caused by constriction of the afferent arteriole, ureteral stones, and increased
plasma protein concentration of glomerular capillary blood.

AMMONIA is produced from the metabolism of the following compounds:

1. Amino Acids-are quantitatively THE MOST IMPORTANT SOURCE OF AMMONIA
 because most western diets are high in protein and provide excess amino acids that are
deaminated to produce ammonia. Many tissues (especially LIVER), form ammonia from amino
acids by the aminotransferase and glutamate dehydrogenase reactions.

2. Glutamine: the kidneys (specifically TUBULAR CELLS) form ammonia from glutamine by the
action of renal glutaminase. Most of this ammonia is excreted into the urine as NH4+ (an important
mechanism for maintaining the body’s acid-base balance.

3. Amines: amines obtained from the diet and monoamines that act as hormones or neurotransmitters
to form ammonia by the action of amine oxidase enzyme.

4. Purines & Pyrimidines: in the catabolism of purines and pyrimidines, amino groups attached to
the rings are released as ammonia.

LIVER IS THE PRIMARILY TISSUE RESPONSIBLE FOR UREA FORMATION, and is

qualitatively the MOST IMPORTANT DISPOSAL ROUTE FOR AMMONIA. Urea travels in blood
from the liver to the kidneys where it passes into the glomerular filtrate. The level of non-protein nitrogen
in blood is due mainly to the UREA level.

KIDNEYS REGULATE ACID-BASE balance by secreting hydrogen ions (H+) into renal tubules &
reabsorption of bicarbonate ions (HCO3-).
• HYDROGEN IONS are secreted into the tubules by kidney tubular cells. The secretion
mechanism derives H+ ions from carbonic acid. The enzyme carbonic anhydrase is present
inside tubular cells, and catalyzes the formation of carbonic acid from carbon dioxide and water.
Some of the carbonic acid dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3-).
The H+ ions are secreted into the tubules, the HCO3- ions pass out of the tubular cells and into the
blood where they are filtered into glomerular capsules and reabsorbed by tubular cells.
o CO2 + H2O + carbonic anhydrase→carbonic acid→H+ + HCO3-

• PHOSPHATE COMPOUNDS (HPO42-) and AMMONIA (NH3) act as buffers to tie up H+

ions in the tubular fluid. Phosphate compounds are excreted in combination with a cation (Na+).
Ammonium ions are excreted in combination with anions (Cl-).

• Ammonia is formed in tubular cells by deamination of certain amino acids (especially glutamic
acid). Ammonia helps reduce the H+ concentration in body fluids by a mechanism involving the
reabsorption of sodium into blood.

• Phosphate and ammonium excretion measurements provide good information on the amount of acid
being eliminated by the kidneys.

 LIVER
LIVER-gland made of mainly hepatocytes, that PRODUCE BILE. Located in the upper right quadrant
of the abdomen, below the diaphragm. Involved in detoxification of metabolites, protein synthesis, and
produces biochemical for digestion (via emulsification of lipids).

LIVER FUNCTIONS:
• Gluconeogenesis (synthesis of glucose from non-carbohydrates). Glycogen storage regulation.
• Bile formation
• Protein metabolism (deamination) of amino acids, urea formation, plasma protein synthesis,
synthesis of amino acids, decomposition of red blood cells.
• Steroid conjugation and hormone production, carbohydrate storage, prothrombin synthesis
and fibrinogen production.
• Detoxification, and regulation of blood sugar level (glucose level).

LIVER has important functions in PROTEIN METABOLISM:

1. Deamination of amino acids is required before they can be used for energy or converted into
carbohydrates or fats.
2. Formation of urea by the liver removes ammonia from the body fluids. If the liver fails to do this,
the result is hepatic coma and death.
3. Formation of plasma proteins by the liver accounts for 90% of all plasma proteins.
4. Among the most important functions of the liver is its ability to synthesize certain amino
acids and other important chemical compounds from amino acids.

The nonessential amino acids can all be synthesized in the liver. To do this, a keto-acid with the same
chemical composition (except at the keto oxygen) as the amino acid is first synthesized. Then, the amino
radical is transferred through transamination from an available amino acid to the keto acid to
replace the keto oxygen.

UREA PRODUCTION occurs almost exclusively in the LIVER, and is the fate of most ammonia that
is channeled there. The urea formed in the urea cycle is passed by the bloodstream to the kidneys and
excreted into the urine. The level of non-protein nitrogen in the blood is due primarily to the level of urea.
• ammonia and aspartate are the two nitrogen atoms incorporated into urea that enter the urea cycle.
• Urea is produced by the hydrolysis of arginine.
• The first two reactions leading to the synthesis of urea occur in the mitochondria, while the
remaining urea cycle enzymes are in the cytosol.
• urea formed by the urea cycle is passed via the bloodstream to the kidneys where it is excreted into
urine.

90% of gluconeogenesis occurs in the LIVER, while the KIDNEYS provide 10% of newly
synthesized glucose molecules (kidney is a minor contributor of newly synthesized glucose). During
prolonged starvation, the KIDNEYS become major glucose-producing organs.
GLUCOKINASE-an enzyme FOUND ONLY IN LIVER and functions at a significant rate only after
a meal. Glucokinase uses ATP to catalyze the phospohrylation of glucose to glucose-6-phosphate during
glucogenesis (process of glycogen formation). Other tissues use hexokinase to do the same thing as
glucokinase. Glucokinase gives the liver an advantage over other cells in taking up glucose after a
meal.

HMG CoA reductase-the major regulatory enzyme of cholesterol synthesis. Although cholesterol is
synthesized in most body tissues where it serves as a component of cell membranes, cholesterol is
produced mainly in the liver. Cholesterol is primarily used by mammalian cells as a component of cell
membranes.
• Cholesterol is synthesized from acetyl CoA; key intermediates in cholesterol biosynthesis are
HMG CoA, mevalonic acid, isopentenyl pyrophosphate, and squalene.

• In the liver, bile salts are formed from cholesterol in certain endocrine tissues; cholesterol is
converted to steroid hormones (testosterone, cortisol, progesterone, and estradiol), the most potent
naturally occurring human estrogen.

• Cholesterol absorption depends on the presence of bile salts in the intestinal lumen.
Cholesterol is mostly esterified with fatty acids when circulating in blood plasma. Circulating
cholesterol is taken into cells where it inhibits synthesis of additional cholesterol from acetyl
CoA via HMG CoA reductase. This provides an intrinsic feedback control system to prevent
excessive increase in plasma cholesterol concentration.

• Most endogenous cholesterol in the liver is converted into CHOLIC ACID.

• NADPH is required for de novo synthesis of cholesterol.

• A deficiency of choline in the diet can cause abnormalities in lipid metabolism.

LIVER releases glucose back into circulating blood during exercise. This extra glucose is taken up
by skeletal muscle and BRAIN. Glucose is the major fuel for the brain, oxidizing 140g/day into carbon
dioxide and water, producing ATP. The brain contains no significant stores of glycogen so it completely
depends on blood glucose availability.
• liver has the major responsibility of maintaining blood glucose levels. Glucose is required
especially by tissues like the brain & RBC (red blood cells oxidize glucose to pyruvate and
lactate).

• liver releases glucose into the blood during muscular activity and in the interval between
meals. The released glucose is from the breakdown of stored glycogen, and from formation of new
glucose by gluconeogenesis.
• In skeletal muscle, the glucose is phosphorylated, then degraded by glycolysis to pyruvate,
which is converted to acetyl-CoA and oxidized via the citric acid cycle (Kreb’s). In maximally
active tissues, this source of glucose is not enough and stored muscle glycogen must be broken
down to lactate by fermentation.

• Glucose is the major end product of carbohydrate ingestion. The presence of glucose in urine
proves a person has exceeded his renal threshold for glucose. Fasting leads to decreased liver
glycogen.


GASTROINTESTINAL SYSTEM

GASTRIC SECRETIONS include mucus, hydrochloric acid (HCL), pepsinogen, and intrinsic factor.

Stomach has mucus-secreting cells that line its entire surface. Stomach mucosa has 2 types of tubular
glands:
1. Oxyntic (gastric) glands: secrete HCL, pepsinogen, intrinsic factor, and mucus.
2. Pyloric glands: secrete mainly mucus, and some pepsinogen and gastrin hormone (secreted by
enteroendocrine cells = gastrin cells = G cells)

Stomach glands produce 2-3 liters of secretions (gastric juice) per day. The pH of gastric secretion is 1.0-
3.5. The mucus produced by mucus-secreting cells is very alkaline protecting the stomach wall from
exposure to highly acidic gastric secretion.

Gastric Secretions are Regulated Neural & Hormonal Mechanisms:

1. Neural Mechanism (Regulation)-influenced by parasympathetic fibers of the vagus nerves;
causes increase secretion of pepsinogen (and subsequently pepsin) HCL, and a slight
increase in mucus secretion.

2. Hormonal Mechanism (Regulation)-takes place by mean of the hormone GASTRIN. When food
enters the stomach, it stimulates gastric mucosa (enteroendocrine cells) to secrete gastrin. Gastrin
then stimulates HCL secretion by parietal cells of the gastric glands (oxyntic glands) and
pepsinogen by chief cells. Involves gastrin secretion by G cells of the gastric mucosa.
• GASTRIN secretion causes an increase in HCL production, activation of the pyloric
pump, relaxation of the pylorus, and contraction of the lower esophageal sphincter.
Gastrin stimulates HCL secretion from parietal cells.

Neural and Hormonal control mechanisms are interrelated because vagal activity also causes gastrin
release. Gastrin secretion is inhibited by hydrochloric acid (HCL) feedback regulation.

Salivary secretion is effected entirely by nervous mechanisms. Nerve impulses travel to salivary
glands via the autonomic nervous system. Both parasympathetic (mostly) and sympathetic stimulation
cause salivary secretion.

Gastric Secretion occurs in 3 Phases:

1. Cephalic phase-in response to sight, taste, smell. Parasympathetic impulses from vagus nerve
initiate secretion of gastric juice (HCL and pepsinogen). Cephalic phase is a reflex mediated
by the vagus nerve.

2. Gastric phase-food induced distension of the stomach plus chemical breakdown of protein
stimulates the release of gastrin which then stimulates gastric juice secretion. Gastric phase
accounts for about 70% of the total gastric secretion associated with eating a meal.
 3. Intestinal phase-chyme entering the duodenum causes distension and increases osmotic pressure
which initiates a neural reflex (enterogastric reflex) that inhibits gastric motility and secretion.
This reflex slows the release of chyme from the stomach when the small intestine is already filled.

The presence of fat in the chyme also stimulates the duodenum to secrete gastric inhibitory peptide
(GIP) that inhibits gastric function.

Typical gastric gland in the stomach mucosa is composed of mucous neck cells, chief (zymogenic) cells,
and parietal (oxyntic) cells:
1. Mucous Neck cells-secrete mucus and some pepsinogen.
2. Chief (peptic or zymogenic) cells-secrete pepsinogen.
3. Parietal (oxyntic) cells-secrete hydrochloric acid (HCL) and intrinsic factor in the stomach.

MUCUS-adheres to and lubricates the stomach walls, and protects the gastric mucosa. IgA bathes
mucous surfaces.

PEPSIN-formed inside chief cells in the form of PEPSINOGEN which has no digestive activity.
However, once pepsinogen is secreted and contacts the previously formed pepsin in the presence of
HCL, it is immediately converted to form active pepsin.
• Most important function of HCL in the stomach is ACTIVATION OF PEPSINOGEN TO
FORM PEPSIN. HCL secretion from parietal cells is stimulated by gastrin

Enteroendocrine cells (gastrin or G cells) of the pyloric glands of the stomach secrete GASTRIN.
Gastrin is absorbed in the blood and carried to the oxyntic glands (gastric glands) in the body of the
stomach where it stimulates parietal cells to secrete HCL.

CHYME-the semifluid contents of the stomach consisting of partially digested food and gastric
secretions. It is the resulting mixture passed from the stomach to the duodenum after the food has been
mixed with stomach (gastric) secretions. The volume and composition of chyme that enters the
duodenum (beginning in the small intestine) exerts a major influence on gastric motility and on the
rate of gastric emptying.
• When a portion of the small intestine becomes distended with chyme, the stretch of the intestinal
wall elicits localized rhythmic contractions called SEGMENTATION that occurs at a rate of
11-12 cycles per minute in the duodenum, and at a progressively slower rate down to 6-7 cycles
per minute in the terminal ileum. Segmentation contractions chop chyme many times per minute to
promote progressive mixing of the food with digestive secretions of the small intestine.

• Intensity of segmentation contractions are influenced by mechanical, neural, and hormonal

inputs. Example: distension of the intestine by chyme and parasympathetic vagus nerve neural
activity both increase contractile force, while sympathetic neural activity decreases contractile
force.

• Gastric motility and emptying are influenced by distension of the stomach (via neural reflexes
and gastrin) and by volume and composition of chyme in the duodenum (via enterogastric reflex
and intestinal hormones).
SMALL INTESTINE SECRETIONS: mucus, intestinal juice, pancreatic juice, and bile:
1. Mucus-secreted by goblet cells (present in the small and large intestines) and by Brunner’s gland
(present in the first few centimeters of the duodenum).

2. Intestinal juice-secreted by goblet cells and enterocytes that cover crypts of Lieberkuhn in the
small and large intestines. The pH of the secretions in the small and large intestines is 7.5-8.0.
Brunner’s gland secretion is slightly more alkaline (8.0-8.9).

3. Pancreatic juice- (normal pH is 8.0-8.3) secreted by exocrine portion of the pancreas acinar
cells. It contains a watery fluid high in bicarbonate ion concentration and enzymes (trypsin,
chymotrypsin, and carboxypeptidase) that are involved in protein digestion.

4. Bile-has a pH 7.8 produced by the liver and stored in gallbladder to aid in emulsification,
digestion, and absorption of fats.

 DNA & RNA
RIBOSOMES-small cellular structures floating free in the cytoplasm (polyribosomes) that contain
rRNA and PROTEIN. At a ribosome, amino acids are linked together in the order specified by
mRNA to form a polypeptide or protein (protein synthesis or translation). Ribosomes have enzyme-
like activity, and catalyze the formation of peptide bonds that link amino acids to each other. Ribosomes
are often attached to the cytosol surface of the ER membrane (when attached, they are called rough
endoplasmic reticulum).
• 70s ribosomes- sites of protein synthesis (translation) in bacterial cells and chloroplasts.

• 80s ribosomes-sites of protein synthesis (translation) in the cytoplasm of eukaryotic cells.

3 Types of RNA involved in PROTEIN SYNTHESIS:

1. MESSENGER RNA (mRNA)-molecules carry information (genetic code) from DNA in the
nucleus to ribosomes in the cytoplasm, where polypeptides and proteins are synthesized
(translation). MRNA is the template for protein synthesis. mRNA is the least abundant RNA.

2. TRANSFER RNA (tRNA)-transports activated amino acids to ribosomes to be used in

assembling the protein molecule; amino acids are linked together in the order specified by
mRNA to form polypeptides and proteins. Amino acyl-tRNA synthetase-a group of ligases
(enzymes) that ensures the correct amino acid is incorporated for a particular codon during
protein synthesis. Individual enzymes are highly specific for one amino acid. tRNA functions
to activate and select specific amino acids for protein synthesis.

3. RIBOSOMAL RNA (rRNA)-the major component of ribosomes, which are the physical and
chemical structures on which protein molecules are actually assembled. rRNA is the most
abundant RNA, then tRNA, then mRNA (least abundant). rRNA is found in the nucleolus.

NUCLEIC ACIDS (DNA & RNA)-complex molecules composed of phosphate groups, nitrogenous
bases, and five-carbon sugars. Nucleic acids store and transmit information to synthesize the
polypeptides and proteins in the body’s cells. Nucleic acids are complex molecules composed of:
1. nitrogenous bases (purines and pyrimidines)
2. five-carbon sugars (pentoses)
3. phosphate groups (contain phosphorus and oxygen).

The backbone of nucleic acids is made of alternating phosphate and pentose units, with a purine or
pyrimidine base attached to each. A single base-sugar-phosphate unit = nucleotide. Without the phosphate
group, the molecule is a nucleoside. These individual nucleotides are linked together to form a
polynucleotide chain (the link or bond is between a phosphate group of one nucleotide and the sugar of the
next).

The hydrolysis of nucleic acids produces: pentoses, phosphates, purine and pyrimidine bases, ribose,
adenine, deoxyribose, and phosphoric acid. It does NOT produce acetic acid.
IF THE POLYNUCLEOTIDE CHAIN contains RIBOSE sugar, the chain = Ribonucleic Acid (RNA). If
the polynucleotide chain contains the sugar DEOXYRIBOSE the chain = Deoxyribonucleic Acid (DNA).

DNA BACKBONE is hydrophilic, highly polar, and constant throughout the molecule, and consists of
deoxyriboses linked by “phosphodiester bridges”. The backbone of RNA consists of ribosomes linked by
the same “phosphodiester bridges”.
• successive nucleotides of DNA and RNA are covalently linked through phosphate-group
“bridges or linkages” (5’-hydroxyl group of one nucleotide unit is joined to the 3’-hydroxyl
group of the next nucleotide by a phosphodiester linkage). The links between monomeric
units of nucleic acids are Phosphodiester bonds. Thus, the covalent backbones of nucleic acids
consist of alternating phosphate and pentose residues, and the characteristic bases may be regarded
as side groups joined to the backbone at regular intervals.

• DNA and RNA backbones are hydrophilic and highly polar.

• Hydroxyl groups (OH) of the sugar residues form hydrogen bonds with water.

• The ribose phosphate portion of purine and pyrimidine nucleotides comes from 5-phosphoribosyl-
1-pyrophosphate (PRPP) which is synthesized by ATP and ribose 5-phosphate is primarily
formed by the pentose phosphate pathway.

THE MOST IMPORTANT ASPECT OF DNA DOUBLE HELIX is SPECIFICITY of base pairing.
• The two antiparallel polynucleotide chains of double-helical DNA are not identical in either
base sequence or composition, but are complementary to each other. Wherever adenine appears in
one chain, thymine is found in the other. Wherever guanine is found in one chain, cytosine is in the
other. Watson & Crick deduced this specificity of base pairing because of stearic and
hydrogen-bonding factors.

• Watson-Crick Structure-the two chains or strands of the helix are ANTIPARALLEL, so that one
strand runs 5’ to 3’ (five prime to three prime) and the other runs 3’ to 5’ (three prime to five
prime).

• DNA double helix is held together by two forces: hydrogen bonding between complementary
base pairs and base-stacking interactions. 3 hydrogen bonds form between (G & C), 2
between A=T.

PURINE & PYRIMIDINE BASES that are opposite one another (adenine with thymine and guanine with
cytosine) in each polynucleotide chain are linked together by hydrogen bonds. These two linked chains
form a double spiral coil = double helix. This base pairing (A-T and G-C) is called complementary
base pairing. Complementary base pairing also exists in RNA, but uracil replaces thymine and binds
with adenine.

Bases carry genetic information, whereas, sugar and phosphate groups perform a structural role.
• Adenine (A) and Guanine (G) = PURINE BASES in both DNA and RNA.
• Thymine (T) and Cytosine (C) = PYRIMIDINE BASES in DNA.
• Uracil (U) and Cytosine (C) = PYRIMIDINE BASES in RNA. A pyrimidine found only in RNA.
PURINE BASES consumed in the human diet in the form of DNA or RNA are mostly excreted as
URIC ACID catalyzed by the enzyme Xanithine oxidase-an enzyme that catalyzes formation of uric
acid from purines bases (adenine & guanine).

Ultraviolet light produces pyrimidine dimers in human DNA. DNA damaged by UV light is due to
induction of dimerization by way of covalent bonds between adjacent thymine or cytosine groups.

In all DNA, the number of thymine residues equals the number of adenine residues, and guanine residues
equals the number of cytosine residues. Also, purine residues equals the sum of pyrimidine residues
(A+G = T+C). Melting temperature of the double helix is a function of base composition.

TRANSCRIPTION-process where DNA serves as a template for the assembly of RNA molecules (all 3
types). Transcription involves RNA polymerase. It’s the cellular process of making RNA from DNA.
DNA→RNA.
HYDROLYSIS OF DNA yields: Phosphoric Acid, Deoxyribose (sugar), & Nitrogenous Bases (adenine,
guanine, thymine, and cytosine). A complete DNA molecule consists of two ANTIPARALLEL
polynucleotide chains or strands that run in opposite directions to one another (one strand runs 5’e3’, the
other runs 3’35’).

HYDROLYSIS OF RNA yields: Phosphoric Acid, Ribose (sugar), and Nitrogenous Bases (adenine,
guanine, uracil, and cytosine).

RIBOSE & URACIL are the only differences between RNA and DNA hydrolysis. DNA is double-
stranded; RNA is single-stranded.

• Replication Forks-sites where DNA synthesis (replication) occur.

• Helicases unwind the helix.

• Topoisomerases (DNA Gyrase) prevents extreme helix supercoiling due to unwinding at the
replication forks.

GENETIC CODE-the degenerate nature of the genetic code implies that many amino acids are
designated by more than one codon (triplet). There are multiple codons for each amino acid. The most
striking feature of the genetic code it is degenerate (a given amino acid may be specified by more than one
codon).
• Codon (triplet)-is a sequence of three adjacent nucleotides (e.g. AUG) in a nucleic acid that codes
for a specific amino acid during protein synthesis. Selenocysteine, tryptophan and methionine
are coded by only one codon. The other 18 amino acids are coded by two or more. Codons that
specify the same amino acid are synonyms.
o Initiation (start) codon (AUG)-signals the beginning of polypeptide chain synthesis.

o Termination (stop or nonsense) codons-(UAA, UGA, UAG)-signal the end of

polypeptide chain synthesis.

When an amino acid has multiple codons, the difference between codons is in the 3rd base (at the 3’
end).
ANTICODON-a specific sequence of 3 nucleotides in a transfer RNA, complementary to a codon
for an amino acid in a messenger RNA. Remember: the two RNAs are paired antiparallel; the first
base of the codon (always reading in the 5’;3’ direction) pairing with the third base of the anticodon.

GENETIC RECOMBINATION EXPERIMENTS depend heavily on 2 enzymes: Restriction

endonuclease & DNA ligase. Nuclease cleaves the DNA to be cloned and a plasmid DNA.
• The specificity of the nuclease is such that when mixed, the DNA to be cloned and the plasmid
DNA will anneal and can then be joined together by a DNA ligase (connects the gap between
Okazaki fragments).

• The first organism used for DNA cloning was E. coli and is still the most common host cell.
Bacterial cloning vectors are plasmids, bacteriophages, and cosmids.

• Advances in DNA technology (DNA cloning) are revolutionizing many aspects of medicine,
agriculture, and other industries. Commercial products of recombinant DNA technology are
human insulin (for diabetes), anticoagulants (tissue plasminogen factor), erythropoietin (for
anemia) and human growth hormone (for dwarfism).

Other enzymes used in recombinant DNA technology (gene cloning):

1. DNA polymerase I-fills in the gaps in duplexes by step-wise addition of nucleotides to the 3’ end.

2. Reverse transcriptase-makes a DNA copy of an RNA molecule.

3. Exonucleases-removes nucleotides from 3’ ends of a DNA strand.

REVERSE TRANSCRIPTASE-an RNA-directed DNA polymerase enzyme. Certain RNA viruses

contain within the viral particle a unique RNA-directed DNA polymerase = reverse transcriptase. On
infection, the single-stranded RNA viral genome and the enzyme enter the host, and the reverse
transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA.

• The RNA viruses containing reverse transcriptase are RETROVIRUSES. The human
immunodeficiency virus (HIV) and retrovirus that causes AIDS. AZT drug inactivates HIV
reverse transcriptase (due to its high affinity for AZT).

• Reverse transcriptase is also involved in GENE CLONING (DNA CLONING).

TRANSCRIPTION & TRANSLATION


 COMPOUNDS & SUBSTANCES
HEPARIN-unlike other glycosaminoglycans that are extracellular compounds, heparin is an intracellular
component of MAST CELLS that lines arteries, especially in the liver, lungs, and skin. Heparin is a
powerful anticoagulant used to treat lung, blood vessel, and heart disorders, and during or after open
heart of bypass surgeries.
• Small quantities are produced by basophil cells of the blood.
• Heparin’s concentration in blood is normally slight (small), so that only under limited
physiological conditions does it have significant anticoagulant effects.
• Heparin is contained in secretory vesicles or granules inside mast cells and basophil cells of the
blood (basophils are functionally identical to mast cells). Mast cells are abundant in the tissue
surrounding the capillaries of the lungs and to lesser extent in the capillaries of the liver.
• Heparin enhances the removal of fat particles from the blood after a fatty meal.

• Administration of Heparin: results in an increase in bleeding time due to the lack of thrombin
formation. Heparin is used to treat patients who have suffered from a coronary thrombosis.
Heparin is a blood thinner.

HISTAMINE-a chemical messenger that mediates a wide-range of cellular responses. Histamine is a

powerful vasodilator formed by decarboxylation of histidine (an amino acid). Histamine is found in
all tissues (especially Mast Cells) and in blood basophils, the highest histamine concentration is in the
lungs. Histamine is secreted by mast cells as a result of allergic reactions or trauma.
• When tissue injury occurs, histamine is liberated by damaged tissue into the surrounding fluids.
This increases local blood flow and increases permeability of the capillaries and venules,
allowing large quantities of fluid and protein to leak into the tissues (characteristic “wheal”).

Histamine has powerful pharmacologic actions mediated by two RECEPTORS:

1. H1 receptors-mediate typical allergic and anaphylactic responses to histamine
(bronchoconstriction, vasodilation, increased capillary permeability).
2. H2 receptors-mediate other responses to histamine, like increased secretion of gastric acid and
pepsin.

Histamine causes these responses:

1. ↓ blood pressure, vasodilation (especially arterioles).
2. HCL secretion, bronchoconstriction.
3. ↑ vascular permeability (especially in capillaries and venules).

TYROSINE-the amino acid that synthesizes DOPAMINE, NOREPINEPHRINE, & EPINEPHRINE.

• Phenylalanine-an amino acid that is very easily converted into tyrosine.

TRYPTOPHAN-the amino acid that synthesizes SEROTONIN (5-hydroxytryptamine) & niacin.

Serotonin is released from platelets upon damage to blood vessel walls.
• Serotonin is a potent vasoconstrictor that increases vascular peripheral resistance. In gastric
 mucous membranes, serotonin is secreted by the enteroendocrine cells and causes the smooth
muscle contractions.

• In the brain, serotonin is a neurotransmitter.

• Lysergic acid diethylamide-interferes with the action of Serotonin in the brain.

PROSTAGLANDINS-prostaglandins, and related compounds thromboxanes and leukotrienes

(collectively know as Eicosanoids) are extremely potent compounds that elicit a wide range of
physiologic responses. Prostaglandins differ from true hormones since they are formed in almost all
tissues rather than in specialized glands, and act locally rather than after transport in the blood to distant
sites of action. Prostaglandins modulate the actions of hormones rather than act as hormones themselves.
• Prostaglandins are 20-carbon fatty acids that contain a five-carbon ring. Major classes include
PGA, PGB, PGE, and PGF.

• Prostaglandins are synthesized by a broad variety of tissues and have a very short half-life, and
generally act locally on or near the tissues that produced them. Prostaglandins are made inside
cells from polyunsaturated fatty acids.

• Arachidonic Acid-an unsaturated fatty acid that is the common precursor of prostaglandins.

• Prostaglandins synthesis is inhibited by (aspirin & cortisol). Prostaglandins enhance

inflammatory effects, whereas aspirin and cortisol diminishes inflammation. Cortisol inhibits
phospholipase A activity.

• Aspirin, indomethacin, ibuprofen, and phenylbutazone are NSAIDs and inhibit prostaglandin
biosynthesis by interfering with the enzymatic insertion of oxygen (they inhibit prostaglandin
endoperoxide synthase).

PROSTAGLANDINS and related substances (prostacyclin, thromboxanes, and leukotrienes) are

chemical messengers present in almost every body tissue. Prostaglandins act primarily as local
messengers that exert their effects in the tissues that synthesize them.
• Prostaglandins, Prostacylcin, & Thromboxanes are formed by the cyclooxygenase pathway.

ARACHIDONIC ACID (an unsaturated fatty acid)-the major compound that forms prostaglandins,
prostacyclin, thromboxanes, and leukotrienes. Arachidonic acid is a part of phospholipids in the
plasma membranes of cells. When a cell is stimulated by a neurotransmitter or hormone, a plasma-
membrane enzyme (phospholipase A) is activated and splits arachidonic acid away from the
phospholipids.
• Different metabolic pathways utilize different enzymes that convert arachidonic acid into different
the messengers.

• Prostaglandins, Prostacylcin, & Thromboxanes are formed by the cyclooxygenase pathway by

the cyclooxygenase enzyme.

• LEUKOTRIENES are formed by the enzyme lipoxygenase in the lipoxygenase pathway.


 CHEMISTRY
ISOLECTRIC POINT (isoelectric pH)- pH at which the number of positive charges EQUALS the
number of negative charges. It’s the pH at which a solute has no net electric charge and thus does
not move in an electric field. It is designated pH for that solute.
• For a solution containing a mixture of amino acids, the different amino acids can be separated on
the basis of the direction and relative rate of their migration when placed in an electric field at a
known pH.

• Example: the amino acid glycine has a net negative charge at any pH above its pH and will thus
move toward the positive electrode (anode) when placed in an electric field. At any pH below
its pH, glycine has a net positive charge and will move toward the negative electrode
(cathode). The farther the pH of a glycine solution is from its isoelectric point (pH), the greater the
net electric charge of the population of glycine molecules.

• At physiologic pH, all amino acids have both a negatively charged carboxyl group (-COO-) and
positively charged amino group (-NH3+) and are called dipolar ions (ZWITTERIONS).

Isotonic Solution-a solution when placed on the outside of cell will not cause osmosis. The cell will not
shrink or swell. A 0.9% solution of sodium chloride or a 5% glucose solution are isotonic to each other
to and blood (have the same osmotic pressure as blood).

Hypertonic Solution-a solution when placed on the outside of a cell will cause osmosis out of the cell
and lead to cell shrinkage. Sodium chloride solutions greater than 0.9% concentration are all hypertonic.

Hypotonic Solution-a solution when placed on the outside of a cell will cause osmosis into the cell and
lead to swelling and cell lysis. Any solution of sodium chloride with less than 0.9% concentration is
hypotonic.

ISOTOPES-stable or radioactive forms of an element with identical chemical properties, but

different atomic weight than the naturally abundant form of the element. Isotopes of a give element
have the same number of nuclear protons but different number of neutrons. Naturally occurring elements
are usually mixtures of isotopes so their atomic weights are an average of values for the mixture.
• Isotopes have the same atomic number, but different mass numbers (Mass number = protons +
neutrons) in a nucleus.
• radioactive forms of isotopes are used as TRACERS.

BUFFERS-prevent a change in pH when H+ ions are added or removed from a solution.

• Buffer Systems-consist of a weak acid (proton donor) and a “salt” or conjugate base of that
acid (proton acceptor). Buffer systems minimize pH changes caused by an excess of acids or
bases. These buffer systems reduce the effect of an abrupt change in H+ ion concentration by
converting a strong acid or base (which normally would dissociate completely releasing a
large number of free H+ or OH- ions) into a weak acid or base (which dissociates less readily
releasing a smaller number of free H+ or OH- ions).
Major Buffer Systems:
1. Sodium bicarbonate carbonic acid buffer system-the major buffer in extracellular fluid.

2. Phosphate buffer system-the minor buffer in the extracellular fluid.

3. Protein buffer system-intracellular proteins absorb hydrogen ions generated by the body’s
metabolic processes. Proteins contain many functional groups with different pK’s. An increase in
PK means a stronger ability to bind hydrogen ions. Important: Hemoglobin is a major
intracellular buffer.

4. Blood Buffers: H2CO3, NaHCO3, Na2HPO4, and NaH2PO4. Blood buffers maintain the
proper blood pH, the most important being carbonic acid (H2CO3). Carbonic acid is most
important due to carbon dioxide being eliminated very rapidly through the lungs. Carbonic
acid/bicarbonate buffer system maintains the physiological pH of plasma.

HENDERSON-HASSELBALCH EQUATION-describes the relationship between pH, pK (the

negative log of the dissociation constant), and the concentrations of an acid and its conjugate base. It is a
useful way to restate the expression for the dissociation constant of an acid (Ka). HHE describes the
quantitative relation between the concentration of a weak acid (HA) and its conjugate base (A-).

Dissociation constant of an acid (Ka) is: Ka = [H+] [A-]/[HA]

• The larger Ka, the stronger the acid, because most HA has been converted into H+ and A-.
Conversely, the smaller the Ka, the less acid has dissociated, and thus the weaker the acid.

HHE was derived from the equation for the dissociation constant: pH = pKa + log [A-]/[HA].
• HHE shows that pH = pK when an acid is half neutralized.
• pH of a buffer system depends on the pK of the weak acid & ratio of molar concentrations of salt
and weak acid.
• optimum pH for an enzyme is the pH of the most rapid reaction rate.

BLOOD is normally slightly ALKALINE (pH range 7.35-7.45). Blood’s acid-base balance is
controlled precisely because even a minor deviation from the pH normal range severely affects
many organs.

Body’s 3 Mechanisms to control Blood’s Acid-Base Balance:

1. Excess acid is excreted by the kidneys, largely in the form of ammonia.

2. Body uses pH buffers in the blood to guard against sudden changes in acidity. The major
blood buffers are bicarbonate and hemoglobin.

3. Excretion of carbon dioxide; blood carries carbon dioxide to the lungs where it is exhaled.
Respiratory control centers in the brain regulate the amount of carbon dioxide exhaled by
controlling speed and depth of breathing.

An abnormality in one or more of these pH control mechanisms can cause one of two major disturbances
in acid-base balance: acidosis or alkalosis.
1. ACIDOSIS-a condition in which the blood has too much acid (or too little base), often resulting
 in a decrease in blood pH (increase in H+)
2. ALKALOSIS-a condition in which the blood has too much base (or too little acid), occasionally
resulting in an increase in blood pH (decrease in H+).

Depending on the cause of the condition, acidosis or alkalosis may be respiratory or metabolic:
1. Metabolic acidosis is excessive blood acidity characterized by an inappropriately low level of
bicarbonate in the blood. Major causes include chronic renal failure, diabetic ketoacidosis,
lactic acidosis, poisons and diarrhea.

2. Respiratory acidosis is excessive blood acidity caused by a buildup of carbon dioxide in the
blood as a result of poor lung function or slow breathing (decrease in respiratory rate). Major
causes are hypoventilation, emphysema, chronic bronchitis, severe pneumonia, pulmonary
edema, and asthma.

3. Metabolic alkalosis is a condition in which the blood is alkaline because of an inappropriately

high level of bicarbonate. Major causes are vomiting acidic gastric contents or ingesting
alkaline drugs, use of diuretics (thiazides, furosemide, ethacrynic acid), and overactive adrenal
gland (Cushing’s syndrome or use of corticosteroids).

4. Respiratory alkalosis-a condition in which the blood is alkaline because rapid or deep breathing
results in a low blood carbon dioxide level. Major causes are hyperventilation (from anxiety),
pain, cirrhosis of the liver, low levels of oxygen in the blood (high altitude), and aspirin overdose.
It is much LESS COMMON then respiratory acidosis. Caused by exhaling large amounts of
carbon dioxide.

• Normal blood bicarbonate-carbonic acid ratio is 20:1. 10:1 ratio indicates uncompensated
acidosis.

• When the pH of blood falls below normal (around 7.3), the CNS becomes so depressed, that the
person first experiences disorientation and later may become comatose. Treated by ingesting sodium
bicarbonate.

• Alkylosis (pH of blood above normal)-results in over excitability of the CNS (may lead to tetany).
Treated by ingesting ammonium chloride.

CALORIMETRY-method of measuring heat or energy loss. Putting a person in a tank of water and
noting the water temperature change can measure human body heat. The body heat causes this change.
1. Direct Calorimetry-measurement of the amount of heat made by the body’s processes; a method
of measuring energy released by the cells. Oxidative reactions (e.g. evaporation, radiation,
conduction, and convection) PRODUCE HEAT.

2. Indirect Calorimetry-human calorie use is measured by the amount of oxygen breathed in

(inhaled) and amount of carbon dioxide breathed out (exhaled) during a given time.

ENTHALPY-the heat content of a system.

ENTROPY-a thermodynamic parameter that measures the extent of RANDOMNESS OR

DISORDER in a system. 2nd law of thermodynamics-states in any chemical or physical process, the
entropy of the universe tends to INCREASE.

PRINCIPAL ENERGY LAWS that govern every organization are derived from the two famous laws of
thermodynamics. They apply only to closed systems (entities where no energy can be exchanged).
• Heat being a form of energy, is subject to the principal of energy conservation; this principal is the
First Law of Thermodynamics (the total energy, including heat, in a closed system is conserved).
The first law states the total quantity of energy in the universe remains constant (conservation of
energy principal).

• HEAT, being a form of energy, can be transformed into work and other forms of energy, and vice
versa. However, this transformation of heat energy is subject to a very important restriction called
the Second Law of Thermodynamics and is given in 3 equivalent forms:
1. Heat flows spontaneously from a hot body to a cool one.
2. One cannot convert heat completely into useful work.
3. Every isolated system becomes disordered in time.

SECOND LAW (Carnot’s principal) is controlled by ENTROPY. Second law states that the quality of
this energy is degraded irreversibly (this is the principal of the degradation of energy).
CERTAIN CHEMICAL REACTIONS proceed spontaneously until equilibrium is reached. Reactions
that proceed with the release of energy are exergonic. Because the products of such reactions have less
free energy than the reactants, the free-energy change (.G) is negative. Chemical reactions in which the
products have more free energy than the reactants are endergonic. For these reactions GG is positive.

HEAT-GENERATING MECHANISMS: includes increased metabolism, shivering, and

vasoconstriction of cutaneous blood vessels. Shivering is the most potent mechanism for increasing
heat production.
• Mechanisms for heat loss include vasodilation of cutaneous blood vessels and increased
sympathetic outflow to the sweat glands. Both heat generating and heat loss mechanisms are
activated by the posterior hypothalamus. Human body temperature generally remains relatively
constant; thus, heat gained equals heat lost.

• Mechanisms that increase body temperature: shivering, ATP hydrolysis, exothermic reactions, and
increased thyroxine release.

HEAT IS TRANSFERRED between the body and environment by these heat transfer mechanisms:
1. Radiation-the emission of heat in the form of infrared rays. The body is continually exchanging
heat by radiation with object in the environment. The surface body temperature is usually
higher than the surface temperature of most objects in the environment. Most body heat is
lost via radiation.

2. Conduction & Convection-conduction is the transfer of thermal energy due to direct contact
between two objects aided by convection, which is when air molecules exchange heat with the
body surface and move away to be replaced by other molecules.

3. Evaporation-the conversion of a liquid into vapor. Heat is lost when water evaporates from the
 body surfaces. Water is lost from body surfaces in 2 ways:
1. insensible water loss-occurs by way of exhaled air and through the skin.
2. sweating-active fluid secretion by the sweat glands. Sweat must evaporate to produce its
cooling effects. Sweating is a more effective means of cooling in low humidity
environments than in high humidity environments.

COVALENT BONDS-strong bonds in biological system that are not normally broken under biological
conditions unless by enzymatic catalysis. This is in contrast to weak bonds (hydrogen and ionic bonds)
that which are easily broken under normal biological conditions of temperature and pressure.
• Covalent bonds are forces that hold atoms together formed when the atoms of a molecule share
electrons. Two examples of covalent bonds are (PEPTIDE & DISULFIDE) bonds. Hydrogen,
oxygen, nitrogen, and carbon are capable of forming one, two, three, and four covalent bonds
respectively. Carbon is very versatile and forms covalent single, double, and triple bonds.

• Denaturation does not destroy covalent bonds in proteins.

WEAK BONDS-(Hydrogen, Ionic, and van der Waals interactions)-are easily broken, but are very
important because they help to determine and stabilize the shapes of biological molecules. Ex: weak
bonds are important in stabilizing the secondary structure (w-helix and --sheets) of proteins.
Hydrogen bonds keep complementary strands of DNA together and also participate in enzymatic catalysis.
These interactions are individually weak, but collectively strong. Denaturing agents (organic solvents,
urea, and detergents) act primarily by disrupting the hydrophobic interactions that make up the stable
core of globular proteins.
• Ionic, hydrogen, and hydrophobic bonds are non-covalent bonds found in proteins.

 CARBOHYDRATES
MONOSACCHARIDES (Simple Sugars)-the simplest carbohydrates classified based on the number of
carbon atoms they contain. Monosaccharides: FRUCTOSE, GALACTOSE, GLUCOSE, MANNOSE,
RIBOSE, XYLOSE, GLYCERALDEHYDE, GLUCURONIC ACID.
• trioses (glyceraldeyde and dihyroxyacetone)-monosaccharides with 3 carbons.
• tetroses (erythrose)-monosaccharides with 4 carbons.
• pentoses (ribose)- monosaccharides with 5 carbons.
• hexoses (glucose)-monosaccharides with 5 carbons.

Aldoses-monosaccharides with an aldehyde as their most oxidized functional group (glyceraldehydes).

Ketoses-monosaccharides with one keto group per molecule as their most oxidized functional group
(dihydroxyacetone is the simplest ketose and only one with no optical activity).

Naming the configurations of simple sugars (monosaccharides) and amino acids is based on the absolute
configuration of glyceraldeyde. Symbols (L & D) refer to the absolute configuration of the 4 constituents
around the chiral carbon (asymmetric carbon). In the D form, the hydroxyl group is on the right; in the L
form, it is on the left. Sugars in the D form related to D-glyceraldehyde, are the most common in
nature.

Monosaccharides can be linked by glycosidic bonds to (disaccharides, oligosaccharides, and

polysaccharides). Glycosidic bonds form when the hydroxyl group on the anomeric carbon of a
monosaccharide reacts with an –OH or –NH group of another compound (alcohol, purine, pyrimidine, or
another sugar). Maltose, lactose, and sucrose (disaccharides that consist of 2 monosaccharides joined
by an O-glycosidic bond). If oxygen is involved, this bond is O-glycosidic; if nitrogen is involved, the
bond is N-glycosidic.

DISACCHARIDES (sucrose, lactose, maltose)-are composed of two monosaccharides.

1. Maltose-consists of two glucose moieties. Maltase-intestinal enzyme that converts maltose into
glucose.

2. Lactose-consists of glucose and galactose. Lactase-intestinal enzyme the converts lactose into
glucose and galactose.

3. Sucrose-consists of glucose and fructose. Sucrase (invertase)-the intestinal enzyme converts

sucrose into glucose and fructose via hydrolysis.

The final digestion of disaccharides into absorbable monosaccharides is completed by enzymes in

the small intestine (maltase, lactase, & sucrase). These monosaccharides can then be absorbed by
enterocytes.

POLYSACCHARIDES (GLYCANS)-contain > 12 monosaccharide units linked by glycosidic bonds.

• Homopolysaccharides (starch, glycogen, dextrans, & glucans) contain only a single
 monosaccharide species.

• Heteropolysaccharides (glycosaminoglycans) contain many different monosaccharide species.

Found in bacterial cell walls made of alternating N-acetylglucosamine and N-acetylmuramic acid
units.

• GLYCOGEN, STARCH, & GLYCOSAMINOGLYCANS are polysaccharides.

Starch & Glycogen are the two most important storage polysaccharides:
1. STARCH-found in PLANTS. Contains two glucose polyers, amylose (unbranched) and
amylopectin (highly branched g-1,4 linkages). Both amylose and amylopectin are rapidly
hydrolyzed by alpha-amylase (an enzyme secreted by the salivary glands and pancreas). The
main component of plant cell walls is CELLULOSE (an insoluble fiber).

2. GLYCOGEN-like amylopectin, it’s a branched polymer of glucose, but is more highly

branched (h-1,6 linkages) and very compact. Glycogen is highly abundant in the liver. The
glucose units of glycogen can enter the glycolytic pathway after removal by two enzymes,
glycogen phosphorylase and glucantransferase.
• Alpha-1,6 linkages occur in glycogen at branch points between glucose units.
• Carbohydrate is stored in the body mainly as glycogen.

DEXTRANS-polysaccharides of glucose obtained from YEAST & BACTERIA. Streptococcus mutans

produce dextran from sucrose. Dextran-a “sticky” polymer of glucose molecules linked together in
-1,6 linkages with some --1-3 branches. Dextran is produced outside of bacterial cells by
dextransucrase (glycosyl transferase) enzyme that splits sucrose into glucose and fructose, and links
the glucose molecules into a dextran polymer. Dextran is deposited as a thick glycocalyx around the cell
and is essential for the cariogenicity of Streptococcus mutans.
• Levans (fructans)-also increases the adhesion of bacteria to tooth surfaces and promotes
dental plaque formation. It is formed from the fructose moiety of sucrose by the enzyme levan
sucrase. Levans are the reserve nutrients for bacteria.

GLYCOSAMINOGLYCANS (Heteropolysaccharides)-the most abundant heteropolysaccharides in

the body (GAGs). GAGs are long, unbranched polysaccharides containing a repeating disaccharide unit
that contains one of two modified sugars (N-acetylgalactosamine or N-acetylglucosamine) and a uronic
acid (glucuronate or iduronate). GAGs are important structural components of C.T.
• GAGs are highly negatively charged molecules with extended conformation that imparts high
viscosity to the solution. GAGs are located on the surface of cells or in the extracellular
matrix (ECM). GAGs are highly viscous with low compressibility making them ideal for
lubricating fluid in the joints. GAGs rigidity provides structural integrity to cells and provides
passageways between cells, allowing cell migration.

• Glycosaminoglycans are important structural components of C.T. (adipose tissue, cartilage,

bone, and collagenous, elastic, and reticular fibers). Found in bacterial cell walls made of
alternating N-acetylglucosamine and N-acetylmuramic acid units. The organic matrix of bone is
composed largely of collagen and glycosaminoglycans.
Glycosaminoglycans (6 Types):
1. Chondroitin sulfate-most abundant glycosaminoglycan (GAG) in the body. Primarily found in
cartilage. Also found in tendons, ligaments, bone, and aorta. It consists of alternating units of D-
glucuronic acid and N-acetylgalactosamine. Found mainly in cartilage and in extracellular matrix.

2. Hyaluronic acid-large polymers that is a lubricant, shock absorber, and the CEMENT
SUBSTANCE OF TISSUES. Found in synovial fluid, vitreous humor of eye, and ECM of loose
C.T. Hyaluronic Acid is a unique GAG because it does not contain any sulfate and is not found
covalently attached to proteins.
• Hyaluronic acid consists of alternating units of D-glucuronic acid and N-
acetylglucosamine. It is in bone, cartilage, tendons, synovial fluids, and the vitreous
humor of the eye. It is synthesized in the Golgi Apparatus.
• Hyaluronidase-an enzyme that hydrolyzes hyaluronic acid. Hyaluronate-a highly
polar, salt, polyanion of hyaluronic acid; a glycosaminoglycan considered an
extracellular matrix component. Promotes depolarization of ground substance.

3. Heparin sulfate-contains higher acetylated glucosamine than heparin. Located in basement

membranes, and components of cell surfaces. Occurs in the cell membranes of most cells.
Consists of alternating units of a sulfated N- acetylglucosamine and either L-glucuronic acid or L-
iduronic acid, which may also be sulfated. HEPARIN HAS THE HIGHEST PROPORTION
OF SULFATE.

4. Heparin-serves as an anticoagulant. A component of intracellular granules of mast cells that line

arteries of the lungs, liver, and skin.

5. Dermatan sulfate-found mostly in skin. Also, in blood vessels and heart valves. Consists of
alternating units of a sulfated N-acetylgalactosamine and L-iduronic acid which can be sulfated.

6. Keratan sulfate (keratosulfate)-the most heterogenous GAG. Found in the cornea of the eye,
bone, and cartilage aggregated with chondroitin sulfates. It consists of alternating units of a
sulfated N-acetylglucosamine and D-glucuronic acid. “Keratin” is NOT a GAG!

EXTRACELLULAR SPACE IN ANIMAL TISSUES is filled with a gel-like material, the

extracellular matrix (ground substance) holds tissue cells together and provides a porous pathway for
the diffusion of nutrients and oxygen to individual cells. Ground substance-composed of an interlocking
meshwork of heteropolysaccharides (glycosaminoglycans) and fibrous proteins. Hyalurondiase
depolymerizes ground substance.

PROTEOGLYCANS (mucopolysaccharides)-consist of a core protein with glycosaminoglycans (GAGs)

attached in a brush-like fashion. The linkage of GAGs to the core protein involves a specific trisaccharide
composed of two galactose residues and one xylose residue. The protein cores are rich in serine and
threonine residues, which allow multiple GAG attachments.
• Most glycosaminoglycans in the body are linked to core proteins forming
PROTEOGLYCANS (mucopolysaccharides).

GLYCOPROTEINS-proteins with a carbohydrate attached to them. The carbohydrate portion differs

from that of proteoglycans because it is shorter and branched. Glycoproteins serve as enzymes,
hormones, antibodies, and structural proteins. Glycoproteins are often attached to cell membranes, and
are involved in cell-to-cell interactions. A mucin is a glycoprotein.

GLYCOLIPIDS (sphingolipids)-found in the cell membrane with the carbohydrate portion extending
into the extracellular space. Glycolipis are derived from the lipid ceramide. This class of compounds
includes cerebrosides and gangliosides.

REDUCING SUGARS-contain a free anomeric carbon that can be oxidized. If the oxygen on the
anomeric carbon (the carbonyl group) of a sugar is not attached to any other structure, that sugar is a
reducing sugar. A reducing sugar can react with chemical reagents and reduce the reactive component.
Note: the anomeric carbon itself becomes oxidized. Important: this reaction is the basis of a reducing-
sugar test (free glucose) used by clinical laboratories to screen for diabetes and other inborn errors
involving the inability to metabolize other reducing sugars.

▪ Because the reducing groups of both glucose and fructose are involved in the glycosidic bond,
sucrose is not a reducing sugar (sucrose contains no free anomeric carbon).

▪ Reducing Sugars: LACTOSE, MALTOSE, GLUCOSE, FRUCTOSE, GALACTOSE

▪ Renal Glucosuria-the presence of glucose in urine caused by low insulin level, high blood sugar,
impaired tubular reabsorption, or high glomerular filtration rate. Glucosuria with hyperglycemia
usually occurs in Diabetes Mellitus patients.

 LIPIDS
LIPIDS-organic compounds that do not dissolve in water, but dissolve in alcohol and other organic
solvents. The major lipids are FATS (the most common lipids), phospholipids, and steroids.
• Lipids are NONPOLAR, CARBON-CONTAINING, AMPHIPATHIC, and HYDROPHOBIC. They
are most common in cell membranes.

CHOLINE-amine compound IMPORTANT IN FAT METABOLISM. Choline is synthesized by the

body found in most animal tissues. Choline is essential for metabolism of fats (triglycerides) in the
body.
▪ Choline is a natural amine classified in the vitamin B complex, and is a constituent of
many biologically important molecules (acetylcholine and lecithin). Choline prevents
deposition of fats in the liver and facilitates fat movement into the cells.

▪ Choline is also a source of transferable methyl groups in metabolism.

▪ Choline deficiency leads to hepatic cirrhosis, which leads to impaired kidney function,
hypertension, high blood cholesterol, and heart disease. Choline deficiency in the diet
can cause abnormalities in the metabolism of fats/lipids.

PHOSPHOLIPIDS-complex lipids, similar to fats, but with a phosphorus and nitrogen-containing

compound replacing one of the fatty acid molecules. MAJOR STRUCTURAL COMPONENTS OF
CELL MEMBRANES. 3 Phospholipid Types:
1. Lecithin-a group of phospholipids that upon hydrolysis yield two fatty acid molecules and a
molecule each of glycerol, phosphoric acid, and choline. Lecithins are water-soluble emulsifiers.

2. Cephalins (Kephalins)-a group of phospholipids having hemostatic properties and found

especially in nervous tissue of the brain and spinal cord. Cephalins resemble lecithin, except
they contain either 2-ethanolamine or L-serine in the place of choline.

3. Sphingomyelins-a group of phospholipids found in nerve tissue and yield sphingosine, choline, a
fatty acid, and phosphoric acid upon hydrolysis. They are membrane constituents.

Basic Structure of Phospholipids: Glycerol + 2 Fatty acids + Phosphate group + R group

LIPOPROTEINS-lipids cannot move in body fluids due to their hydrophobic nature so to enable
transport in the body, lipids combine with beta-globulins (proteins) to form LIPOPROTEINS. After lipids
are absorbed through the intestine, they combine in blood plasma with polypeptide chains to give a
distinct family of lipoproteins classified by density. Since lipids are much less dense than proteins, there
is an inverse relationship between the lipid content and density (i.e. high lipid content means low density
particle). The major components of lipoproteins are triacylglycerols (triglycerides), cholesterol,
cholesterol esters, phospholipids, and proteins (the protein component alone is an apolipoprotein). Types
of Lipoproteins:
 1. Chylomicrons-LEAST DENSE BLOOD LIPOPROTEIN; most triglyceride and least protein
content. Transport both dietary and endogenous triacylglycerols around the body.

2. VLDLs (very low-density lipoproteins)-more dense than chylomicrons; high concentration of

triglycerides, and moderate concentrations of phospholipids and cholesterol. Transport
endogenous triacylglycerols to various tissues (primarily muscle and adipose tissue).

3. LDLs (low-density lipoproteins)-denser than VLDL; less triglyceride and more protein content.
Has highest (very rich) content of cholesterol and its esters. LDLs are the major cholesterol
carriers from blood to all tissues. LDL molecules enter cells by receptor-mediated endocytosis.
LDL transports cholesterol, cholesterol esters, and phospholipids from the liver.

4. HDLs (high-density lipoproteins)-MOST DENSE BLOOD LIPOPROTEIN; has the lowest

triglyceride (little cholesterol) and highest protein content (protein rich). Transfers apoproteins to
chylomicrons and VLDLs.

Chylomicrons-the LARGEST, but LEAST DENSE lipoprotein. Chylomicrons contain a high

proportion of triacylglycerols, and are assembled in the intestinal mucosa as a means to transport dietary
cholesterol and triacylglycerols to the body. Chylomicrons function to deliver dietary triacylglycerols
to adipose tissue and muscle, and dietary cholesterol to the liver.
• Chylomicrons are PLASMA LIPOPROTEINS consisting of a large droplet of triacylglycerols
stabilized by a coat of protein and phospholipid. They carry fatty acids obtained in the diet to the
tissues in which they are consumed or stored as fuel.

• The remnants of chylomicrons, depleted of their triacylglycerols (triglycerides) but still containing
cholesterol, move through the bloodstream to the liver, where they are taken up, degraded in
lysosomes, and their constituents recycled.

• Chylomicrons are the LEAST DENSE blood lipoproteins because they have the most
triacyglycerol and the least protein content.

Lipoproteins are transported into the cells via receptor-mediated endocytosis. LIPOPROTEINS are
lipid-binding proteins responsible for transport in the blood of triglycerides, phospholipids,
cholesterol, and cholesterol esters from the liver to tissues or organs.

ACETYL CoA-used by the liver to synthesize KETONE BODIES (acetoacetate, β-hydroxybutyrate,

acetone). During conditions that increase gluconeogenesis (diabetes, starvation):
▪ Adipose tissue breaks down its triacylglycerol stores into fatty acids and glycerol which are
released into the blood. Through r-oxidation process, the liver converts fatty acids into acetyl CoA
which is used by the liver to synthesize ketone bodies (acetoacetate, --hydroxybutyrate, acetone).
The liver cannot oxidize ketone bodies and release them into the blood for transport to peripheral
tissues where they are reconverted to acetyl CoA and oxidized by the Kreb’s Cycle (citric acid
cycle). KETONE BODIES ARE IMPORTANT SOURCES OF ENERGY FOR
PERIPHERAL TISSUES. Ketone bodies are soluble in aqueous solution and thus do not require
carriers in the blood. Unlike fatty acids, ketone bodies can be oxidized by the brain.
▪ Acetone is not utilized by the body as fuel; it is a non-metabolizable side product.
 ▪ Ketone bodies are produced as a result of lipid and amino acid breakdown.
▪ Acetyl CoA is a common intermediate of metabolism of carbohydrates, fatty acids, and amino
acids.
▪ Under circumstances that cause acetyl-CoA accumulation (starvation or untreated diabetes),
thiolase catalyzes the condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the parent
of the ketone bodies. The glycerol is converted into glucose.

The use of fat instead of glucose for energy leads to an excess of ketone bodies. This condition disturbs
normal acid-base balance and homeostatic mechanisms leading to KETOSIS.
▪ KETOSIS-a condition of abnormally elevated concentration of KETONE BODIES in the body
tissues and fluids. Ketosis occurs when fatty acids are incompletely metabolized, a
complication of untreated diabetes mellitus, starvation, and alcoholism. It is characterized by
ketones in the urine (ketonuria), potassium loss in the urine, and a fruity odor of acetone on the
breath. KETONE BODIES: acetone, K-hydroxybutyrate, and acetoacetate.
▪ A diabetic coma is caused by the buildup of ketone bodies; commonly fatal unless appropriate
therapy is given promptly. Glucose is effective in reversing ketosis in a non-diabetic patient.
▪ Excessive use of fat as an energy source (e.g. starvation) or disturbances in carbohydrate
metabolism, can lead to acidosis, ketonuria, and ketosis. During extended fasting, the brain,
liver, cardiac muscle, and skeletal muscle are able to use ketones and/or fatty acids as a fuel
source.
▪ β-hydroxybutyrate is also called D-β-hydroxybutyrate or 3-hydroxybutyrate.

GLUCOSE-MAJOR SOURCE of ACETYL CoA for FATTY ACID SYNTHESIS. Acetyl CoA for
fatty acid synthesis comes mostly from the glycolytic breakdown of glucose.
1. Glucose is first degraded to pyruvate by aerobic glycolysis in the cytoplasm.

2. Pyruvate is then transported into the mitochondria, where pyruvate forms acetyl CoA (by
pyruvate dehydrogenase) and oxaloacetate (by pyruvate carboxylase).

3. Acetyl CoA and oxaloacetate condense to form CITRATE- transported out of the mitochondria
into the cytoplasm (where fatty acid synthesis occurs). Citrate splits to generate cytoplasmic
acetyl CoA for fatty acid synthesis.

CITRATE-positive modulator that allosterically regulates the enzyme catalyzing the rate-
controlling step in the de novo synthesis of fatty acids

Fatty Acid Synthesis

Acetyl CoA→Malonyl CoA→Malonyl-ACP→Acetyl-ACP→Acetoacetyl-ACP→Butyryl-ACP→Fatty

Acid

o Malonyl-CoA-the three-carbon intermediate that participates in the biosynthesis of fatty acids,

but not in their breakdown (catabolism).

o Acetyl CoA carboxylase-enzyme involved in fatty acid synthesis.

FATTY ACID BREAKDOWN (catabolism)-occurs in MITOCHONDRIA. During fatty acid

catabolism, the fatty acid is transported to the liver by employing CARNITINE as a carrier substance.
Once inside the mitochondria, the fatty acid splits away from the carnitine and is oxidized (via beta
oxidation) to acetyl-CoA. The acetyl-CoA molecules enter the citric acid cycle (Kreb’s cycle) to form
carbon dioxide and hydrogen atoms. Hydrogen is then oxidized to form ATP.

FATTY ACID BIOSYNTHESIS-occurs in the CYTOSOL and involves two carbon additions from
acetyl-CoA and an acyl protein (ACP). A key intermediate in the synthesis of fatty acids is malonyl-
CoA which is formed from acetyl-CoA, bicarbonate, and carbon dioxide. This irreversible reaction is
the committed step in fatty acid synthesis.

• Coenzyme A (CoA)-a pantothenic acid containing coenzyme involved in both fatty acid
synthesis and catabolism. It also participates in activation of carboxyl groups.

• Acetyl CoA is a common intermediate of metabolism of fatty acids, amino acids, and
carbohydrates.

FATTY ACID SYNTHESIS:

• Fatty acid synthesis occurs in the cytosol while fatty acid breakdown (catabolism) occurs in the
mitochondria.

• Fatty acid synthesis involves two carbon additions from acetyl-CoA and an acyl protein (ACP).

• The important step in fatty acid synthesis is the first step in which acetyl-CoA, carbon
dioxide, and bicarbonate form malonyl-CoA.

• Fatty acid synthesis is not a simple reversal of F-oxidation used for the catabolism of fatty acids.

• Fatty acid synthesis and breakdown require phosphopantothenic acid.

• CO2 or bicarbonate are required in the biosynthesis of fatty acids because CO2 is incorporated
into acetyl CoA forming malonyl CoA (an intermediate in the synthetic process).

FAT (Triglyceride or Neutral Fat) contains three fatty acid molecules combined with one molecule of
glycerol. A fatty acid is a long-chain compound with an even number of carbon atoms and terminal
COOH group. Fatty acids can be monounsaturated (has one C=C), or polyunsaturated (has multiple
bonds between carbon atoms). In humans, FATTY ACID SYNTHESIS OCCURS PRIMARILY IN THE
LIVER

• Triglycerides provide more than half the energy requirements of some organs (liver, heart, and
resting skeletal muscle). When hormones signal the need for metabolic energy, triglycerides stored in
adipose tissue are brought out of storage and transported to the tissues (skeletal muscle, heart, renal
cortex) where the fatty acids are oxidized for energy production. Triglycerides are not membrane
constituents.

BILE SALTS-steroids with detergent properties used to emulsify lipids in foodstuff passing through
the intestine to enable fat digestion and absorption through the intestinal wall. BILE SALTS are secreted
by the liver, stored in the gallbladder, and passed through the bile duct into the intestine when food
passes through. Bile salts aid in intestinal digestion and absorption of lipids by emulsifying and
solubilizing them in micelles.

• CHOLATE & DEOXYCHOLATE are the most abundant bile salts in humans. They are normally
conjugated with either glycine or taurine to give glycocholate & taurocholate respectively.

BILE SALTS perform two actions in the INTESTINAL TRACT:

1. Most important, bile salts help in the absorption of fatty acids, monoglycerides, cholesterol,
and other lipids from the intestinal tract (form water-soluble complexes (micelles) with fatty
acids and glycerides).

2. Bile salts have detergent action on fat particles in food to decreases surface tension of the
particles, and allows agitation in the intestinal tract to break the fat globules into minute sizes.
After taking part in fat digestion and absorption, most bile salts are reabsorbed into portal
circulation.

EPINEPHRINE & GLUCAGON hormones are secreted in response to low blood glucose levels,
activate adenylate cyclase in the adipocyte plasma membrane, raising the intracellular
concentration of cAMP. cAMP-dependent protein kinase, then phosphorylates and activates hormone-
sensitive triacylglycerol lipase which catalyzes the hydrolysis of the ester linkages of triglycerides
(forming fatty acids and glycerol). The fatty acids released combine with serum albumin and travel to
tissues where they dissociate from albumin and diffuse into the cytosol of the cells in which they will
serve as fuel. Note: Insulin inhibits adenyl cyclase and thereby diminishes lipolysis.

GLYCEROL released by lipase action is phosphorylated by glycerol kinase, and the resulting glycerol-
3-phosphate is oxidized to dihydroxyacetone phosphate. This compound is then converted to
glyceraldeyde-3-phosphate by the enzyme triose phosphate isomerase. Glyceraldehyde-3-
phosphate is then oxidized via glycolysis.

ESSENTIAL FATTY ACIDS cannot be synthesized in sufficient amounts by the body and must therefore
be obtained in the diet (mainly from lipids). All fatty acids are building blocks of phospholipids and
glycolipids, and are thus needed for the synthesis of cell membranes. Fatty acids are also fuel
molecules (cells derive energy from the oxidation of fatty acids). LINOLEIC, LINOLENIC, &
ARACHIDONIC ACIDS ARE ESSENTIAL FATTY ACIDS.
• Linoleic and arachidonic acids serve as precursors to prostaglandins.

Fats are classified by number of double bonds between carbon atoms in the fatty acid molecules.
1. Saturated Fat-contains no bonds between carbon atoms:
• Arachidic acid, Behenic acid, Butyric acid, Capric acid, Caproic acid, Caprylic acid,
Lauric acid, Myristic acid, Palmitic acid, Stearic acid

2. Monounsaturated fat-has one double bond b/t carbon atoms:

• Erucic acid, Oleic acid, Palmitoleic acid

3. Polyunsaturated fat-has multiple double bonds between carbon atoms:

• Arachidonic acid, Linoleic acid, Linolenic acid

 PROTEINS & AMINO ACIDS
PEPTIDE BONDS (Amide Bonds)-covalently joins amino acids in proteins. Peptide bonds covalently
join the -carboxyl group of one amino acid and the o-amino group of another amino acid in the protein
chain. Peptide bonds are extremely stable and cleavage involves the action of proteolytic enzymes.
Peptide bond characteristics:
• No freedom of rotation around the bond; it has a partial double-bond character which means it is
shorter than a single bond and is thus rigid and planar.
• Bonds involving the B-carbon can rotate freely.
• It is generally a trans bond (instead of cis).
• It is uncharged but polar.
• Peptide bonds can also be formed by removing a water molecule between the carboxyl group
of one amino acid, and the amino group of a second amino acid.

Another covalent bond that occurs in many proteins is the disulfide bond. It is formed from the sulfhydryl
group (-SH) of each of two cysteine residues, to produce a cystine residue. These strong, covalent bonds
help stabilize the structure of proteins and prevent them from becoming denatured in the extracellular
environment. Examples: hormone insulin & immunoglobulins (antibodies).
• Residue-a single amino acid unit within a polypeptide chain.
• Cystine-an amino acid found in many proteins, especially keratin, and is the major source of
metabolic sulfur.

ELASTIN-a C.T. protein rich in small, nonpolar aliphatic residues like glycine (1/3 of all residues),
proline, alanine, valine, leucine, and isoleucine. It contains a small amount of hydroxyproline (non-
standard amino acid; derivative of proline) and no Hydroxylysine.
• In contrast to collagen, which forms tough fibers with high tensile strength, elastin is a connective
tissue protein with rubber-like properties. Elastic fibers can be stretched several times their
normal length—elastin gives these fibers the capacity of returning to their original lengths
after being stretched.

• Tropoelastin-the polypeptide subunit of elastin fibrils.

• Elastin fibers are formed as a 3-D network of cross-linked polypeptides that involve lysine, which
are covalently linked to produce a desmosine cross-link.

COLLAGEN-contains approximately 1000 amino acids (1/3 are Glycine). Collagen is 35% glycine,
21% proline, and 11% alanine. Hydroxyproline and hydroxylysine are also present. The basic structural
unit of collagen is TROPOCOLLAGEN, the longest known protein formed from procollagen secreted
by fibroblasts. Collagen is also present in reticulin, a component of reticular fibers.
• Collagen consists of 3 chains that wind around each other to form a triple helix.

• Tropocollagen is a protein molecule found in collagen and reticular fibers only.

• Collagen is THE MOST ABUNDANT PROTEIN IN THE BODY and is found in collagen
 fibers that are very strong and inelastic. Vitamin C influences collagen formation, which is the
organic matrix found in dentin and cementum. Collagen is the major protein component of
cementum.

• Hydroxyproline and hydroxylysine are nonstandard amino acids present in few other proteins.
For this reason, their concentration in a tissue is a good estimate of the collagen content. They
are not used directly in the protein synthesis reactions, and are formed by the hydroxylation of
proline & lysine which involves.-ketoglutarate, oxygen, and vitamin C (ascorbic acid).
o Hydroxyproline concentration is used to estimate the amount of collagen present in tissue.

• Collagen & reticular fibers make up the stroma of all lymphoid tissues EXCEPT THYMUS.

PROTEINS-large, complex molecules formed from AMINO ACIDS. Generally, amino acids have a
central or alpha carbon attached to a hydrogen atom (H), carboxyl group (COOH), amino group
(NH2), and a fourth group “R” that differs from one amino acid to another. 20 different amino acids
(that possess different R groups) are commonly found in proteins in the body.

PROTEINS are formed from amino acids by reactions that bond the amino group of one amino acid
to the acid carboxyl group of another = peptide/amide bond. Two amino acids joined together by a
peptide bond form a dipeptide. Ten or more amino acids linked in a chain by peptide bonds form a
polypeptide chain. A protein is a polypeptide chain of 1000 or more amino acids linked by peptide
bonds.

PROTEINS differ from each other because each has a distinct number and sequence of amino acid
residues. The amino acids are the alphabet of protein structure. No other property so clearly distinguishes
one protein from another. The best method to determine three-dimensional structure of a protein is by x-
ray diffraction
1. Primary Structure-the sequence of amino acids in a protein linked by covalent peptide bonds
and includes any disulfide bonds.

2. Secondary Structure-the spatial arrangement of sequenced amino acid residues in a

polypeptide chain. The most common secondary structures are the α-helix (coiled conformation
of a peptide chain), β-sheets (an extended, zigzag arrangement of a polypeptide chain), and β-
bends (reverse turns).

3. Tertiary Structure-overall 3-Dimension conformation of the polypeptide (e.g. globular, fibrous,

and pleated sheet).

4. Quaternary Structure-the spatial arrangement of subunits in a protein that consists of more than
one polypeptide chain.

PROTEIN DEFICIENCY signs:

• Lack of vigor and stamina, weakness, mental depression,
• Poor resistance to infection, impaired wound healing, and slow recovery from disease.
• XEROSTOMIA IS NOT A SIGN OF PROTEIN DEFICIENCY.

Many nutrients are synthesized in the body. Nutrients that cannot be synthesized in the body are called
essential nutrients (must be consumed in diet). Essential nutrients include amino acids (in proteins),
certain fatty acids (in fats and oils), minerals, and vitamins. 9 of the 20 amino acids in proteins are
essential nutrients (obtained in the diet).

Of the 20 amino acids commonly found in proteins, 11 are not essential in the adult diet because
they are synthesized in the body. 11 amino acids synthesized in mammals have simple pathways
(nonessential amino acids) which means they are not needed in the diet.

• Essential Amino Acids (9): methionine, threonine, isoleucine, lysine, leucine, valine, tryptophan,
phenylalanine, and histidine. OBTAINED IN THE DIET. (Pvt. Tim Hall)

• Non-Essential Amino Acids (11): glutamate, glutamine, proline, arginine, serine, glycine, cysteine,
aspartate, asparagines, alanine, and tyrosine. SYNTHESIZED IN THE BODY.

Amino acids can be ketogenic, glucogenic, or both based on the nature of their metabolic end products.
• Ketogenic-amino acids whose catabolism yields either acetoacetate or one of its precursors,
acetyl CoA or acetoacetyl CoA. Examples: leucine and lysine.

• Glucogenic-amino acids whose catabolism yields pyruvate or one of the intermediates of the citric
acid cycle ((-ketoglutarate, oxaloacetate, fumarate, and succinyl CoA). Examples include the
remaining amino acids.

• Glucogenic and Ketogenic-amino acids whose catabolism yields ketogenic and glucogenic end-
products. Examples (tyrosine, isoleucine, phenylalanine, & tryptophan).

TYROSINE-produced by hydroxylation of the essential amino acid PHENYLALANINE. Phenylalanine

is an essential amino acid needed for optimal growth in infants and for nitrogen equilibrium in adults.
• Hydrophobic amino acids have side chains that contain:
1. Aliphatic groups (valine, leucine, isoleucine).
2. Aromatic groups (phenylalanine, tyrosine, and tryptophan).

Dopamine, thyroid hormones (triiodothyronine & thyroxine), melanin, norepinephrine, and

epinephrine are all synthesized from the non-essential amino acid TYROSINE.
• Albinism-a genetic disease that results from the incomplete metabolism of tyrosine.

Serotonin (5-hydroxytryptamine), melatonin, niacin, and the nicotinamide moiety of NAD and NADP
are formed from the essential amino acid TRYPTOPHAN.

Negative nitrogen balance (nitrogen output exceeds intake)-may be caused by a dietary lack of
essential amino acids.

MYOGLOBIN (muscle hemoglobin)-resembles blood hemoglobin in function, but has only one heme as
part of the molecule and one-fourth the molecular weigh. Remember: Hemoglobin contains 4 hemes that
potentially associate with 4 oxygen molecules.
• myoglobin increases the rate of oxygen transport within the muscle cell.
• myoglobin is a heme-protein in cardiac and skeletal muscles.
• myoglobin functions as a reservoir for oxygen and an oxygen carrier.
 • myoglobin consists of a single polypeptide chain structurally similar to the individual polypeptide
chains of the hemoglobin molecule.

MYOGLOBIN has a much greater affinity for oxygen than hemoglobin, making it well suited for its
biological function within muscle cells, which is to store oxygen and make it available to
mitochondria. Myoglobin is much better at this than Hb because its very high affinity for oxygen at low
pO2 enables it to bind and effectively store oxygen. Hemoglobin and myoglobin are specialized
proteins, adapted for different kinds of oxygen-binding functions.

ALBUMIN-plasma protein of the HIGHEST CONCENTRATION in PLASMA that transports many

small molecules in the blood (bilirubin, calcium, progesterone, and drugs). Albumin is very important
in maintaining the oncotic pressure of blood (keeping the fluid from leaking out into the tissues). Because,
unlike small molecules like sodium and chloride, albumin’s concentration in blood is much greater than it
is in extracellular fluid. Albumin is synthesized in the LIVER.

Plasma Proteins act as buffers that help stabilize the pH of the internal environment. Intracellular
proteins absorb H+ ions generated by the body’s metabolic processes. ALBUMIN, GLOBULIN, &
FIBRINOGEN are the 3 major plasma proteins.
• Globulins (alpha, beta, and gamma)-alpha and beta function as transport molecules. Gamma
globulins (immunoglobulins) are circulating antibodies that act in the immune response.

• Fibrinogen-a blood-clotting protein.

Other plasma proteins are lipoproteins (chylomicrons, VLDL, LDL, HDL) responsible for transporting
blood triglycerides, phospholipids, cholesterol, and cholesterol esters from the liver to tissues and
organs. Transferrin (iron transport) and prothrombin (a blood-clotting protein).

HISTONES-small basic proteins positively charges at physiological pH due to their high content of
Arginine and Lysine (amino acids). The chromatin of eukaryotic cells consists of DNA complexed with
histones in nucleosomes.
• 5 major classes of histones: (H1, H2A, H2B, H3, and H4). Due to their positive charge, histones
form ionic bonds with the negatively charged DNA. Histones help neutralize the large negative
charge of the DNA phosphate groups.

CHROMATIN-the chromosomal material randomly dispersed throughout the nucleus. It consists of

fibers that contain protein (histones) and DNA in approximately equal masses. These histones
package and order the DNA into structural units (nucleosomes). Nucleosomes-repeating subunits of
chromatin, consisting of a DNA chain coiled around a core of histones.
• Gene regulatory proteins-non-histone proteins also found in chromatin important in controlling
DNA interactions with other molecules.

• Nucleoprotein-the combination of DNA with proteins. Some viruses are nucleoproteins. Certain
viruses isolated in crystalline form are found to be nucleoproteins.

CARBOHYDRATES-are the principal source of CARBON. Ten of the nonessential amino acids
contain carbon skeletons derived from glucose. Note: Tyrosine, the 11th nonessential amino acid, is
synthesized by hydroxylation of the essential amino acid phenylalanine.

NON-ESSENTIAL AMINO ACIDS-are synthesized in mammals, have simple pathways, and are not
needed in the diet. Nonessential amino acids: glutamate, glutamine, proline, arginine, serine, glycine,
cysteine, aspartate, asparagines, alanine, and tyrosine.

• Nonessential amino acids can be synthesized from α-keto acids, an α-amino acid (NH3+
donor), a specific transaminase enzyme, and the coenzyme pyridoxal phosphate (vitamin B6).
These amino acids include alanine, aspartate, and glutamate. The other nonessential amino acids
are synthesized by amidation (glutamine and asparagines).

• Proline-synthesized from glutamate and contributes to the tertiary structure of most proteins.

• Serine-important in the active sites of trypsin and chymotrypsin.

Amino acids are found in PROTEINS. Amino acid’s general structure is: H3N+--C—H.

• With the exception of the R group, this structure is common to all W-amino acids. The central or
T-carbon is in the center. Attached to this a hydrogen atom (H), a carboxyl group (COOH),
an amino group (H3N+), and the R group. In all amino acids except glycine, the N-carbon
atom has 4 different substituents (in glycine, the R group is a hydrogen atom (H).

• Amino acids can lose their nitrogen-containing amino groups and be converted to α-keto acids
(alpha-keto acids) that can ultimately enter the Kreb’s cycle by way of pyruvic acid or the Kreb’s
cycle component oxaloacetic acid, both of which are α-keto acids. An A-keto acid is similar to an
amino acid except it has oxygen rather than an amino group bonded to its --carbon.

• When proteins are broken down and used for energy, most of this energy is derived from the
oxidation of o-keto acids (pyruvate, oxaloacetate, and --ketoglutarate). These substances can then
enter the Kreb’s Cycle.

STEREOISOMERS (Optical Isomers or Enantiomers)-compounds with the same composition and

same order of atomic connections, but different molecular arrangements. In all standard amino acids
except (glycine), the I-carbon is asymmetric, bonded to 4 different substituents groups (carboxyl
group, amino group, R group, and hydrogen atom). This carbon is the “chiral center”. The four
different substituents can occupy two different arrangements in space that are nonsuper-imposable mirror
images of each other. These two forms are called stereoisomers (optical isomers or enantiomers). All
molecules with a chiral center are optically active.

Classifying and naming STEREOISOMERS is based on the absolute configuration of the 4

substituents of the asymmetric carbon atom. The reference compound to which all other optically
active compounds are compared is the smallest sugar to have an asymmetric carbon (glyceraldehyde).
Naming of configurations of simple sugars and amino acids is based on the absolute configuration of
glyceraldehydes, as established by x-ray diffraction analysis.

The stereoisomers of all chiral compounds having a configuration related to L-glyceraldehyde are
designated L (“left”), and the stereoisomers related to D-glyceraldehyde are D (“right”). D-amino
acids are found in some antibiotics and in bacterial cell walls.
• All AMINO ACIDS found in proteins have the L-CONFIGURATION.

METHIONINE and CYSTEINE are two amino acids with SULFUR containing side chains (R-
groups).

AMINO ACIDS can be grouped into classes based on the properties of their R groups, in particular,
their polarity or tendency to interact with water at biological pH (near pH 7.0). This polarity varies
widely, from totally nonpolar or hydrophobic (water-insoluble) to highly polar (hydrophilic or water
soluble). 5 Main Classes:
1. Non-Polar, Aliphatic R groups: alanine, valine, leucine, isoeucine, glycine, methionine, and
proline.

2. Polar, Uncharged R groups: serine, threonine, cysteine, asparagines, and glutamine.

3. Aromatic Amino Acids: have an aromatic ring and can absorb light. Ex: phenylalanine, tyrosine
(polar), tryptophan, and histadine.

4. Negatively Charged (Acidic) R-groups: aspartate and glutamate

5. Positively Charged (Basic) R-groups: lysine, arginine, and histidine.

CYTOCHROMES-iron containing (heme) electron transfer proteins that are components of the electron
transport chain that is found in the inner mitochondrial membrane of cells. The chain is the final
common pathway by which electrons derived from different fuels of the body flow to oxygen. Electron
transport and ATP synthesis by oxidative phosphorylation proceed continuously in all cells of the body
that contain mitochondria. Cytochromes-electron or proton-transfer proteins containing one or several
heme groups.

• Cytochromes receive electrons from the reduced form of coenzyme Q (ubiquinone). Each contains
a heme group made of a porphyrin ring containing an iron atom. This Cytochrome iron atom is the
electron carrier and is reduced when the Cytochrome accepts an electron (Fe3+ Fe2+).

• Cytochromes are distinguished by differences in their light-absorption spectra and are designated
b,c1, c, a3, and a. These differences are a result of the heme prosthetic group. Cytochromes a3
and a are the terminal members of the electron transport chain. They exist as a complex,
which is called Complex IV or Cytochrome oxidase complex.

• Prosthetic groups of cytochromes have 4 five-membered, nitrogen-containing rings in a cyclic

structure = porphyrin. The four nitrogen atoms are coordinated with a central Fe ion that can be
either Fe+2 or Fe+3. These porphyrins are also found in the heme protein hemoglobin. Glycine is a
major precursor to the biosynthesis of these rings.

α-KETOGLUTARATE-gives rise to GLUTAMATE, which forms glutamine, proline, and arginine.

3-PHOSPHOGLYCERATE-gives rise to SERINE, which forms glycine and cysteine.

OXALOACETATE-gives rise to ASPARTATE, which then forms asparagines, methionine, threonine,
and lysine. (Threonine is the precursor of isoleucine).

PYRUVATE-gives rise to alanine, valine, leucine, and isoleucine (Isoleucine is formed by pyruvate or
threonine).

PHOSPHOENOLPYRUVATE & ERYTHROSE-4-PHOSPHATE-produce shikimate, which is

converted to CHORISMATE. CHORISMATE-gives rise to tryptophan, tyrosine, and phenylalanine.
(Tyrosine can also be synthesized from phenylalanine.

RIBOSE-5-PHOSPHATE-gives rise to HISTIDINE.


 ENZYMES
A major role of PROTEINS is to SERVE AS ENZYMES. Properties of Enzymes:
1. Enzymes have enormous catalytic power. Enzymes accelerate reactions by factors of at least a
million.

2. Enzymes are highly specific, in the reaction catalyzed and in their choice of reactants (substrates).

3. Enzyme activity is sometimes regulated. Digestive enzymes are regulated, as they are activated at a
physiologically appropriate time and place. (allosterism, zymogen activation, and competitive
inhibition are enzyme regulation methods).

4. Enzyme-catalyzed reactions area characterized by formation of a complex between substrate and

enzyme (ES complex). The binding occurs in a pocket on the enzyme = active site.

5. Equilibrium of a reaction is unaffected by the enzyme. This means an enzyme accelerates the
forward and reverse reaction precisely by the same factor.

6. Enzymes function to LOWER ACTIVATION ENERGY of the reaction they catalyze to enhance the
reaction rate.

7. Many enzymes REQUIRE COFACTORS that frequently are METAL IONS or vitamin derivatives.

8. Optimum pH for an enzyme is the pH of most rapid reaction rate.

PLASMIN (Fibrinolysin)-proteolytic enzyme that dissolves fibrin. Plasmin is normally present in

blood in an inactive form (plasminogen). Plasminogen activators-substances that convert plasminogen
to plasmin, which decomposes fibrin and dissolves clots.

FIBRINOGEN-soluble protein normally present in plasma that is essential to the blood clotting
process. It is converted into an insoluble, thread-like polymer (fibrin) by the enzyme thrombin.
Thrombin is produced from the inactive plasma protein precursor prothrombin (formed and stored in
the liver). In the presence of thromboplastin and calcium ions, prothrombin is converted to thrombin.
Research has shown thrombin acts upon the arginyl-glycine linkages (specific peptide bonds) in
fibrinogen to produce a fibrin monomer. Fibrinogen is the normal substrate of thrombin.

AMYLASES-enzymes that hydrolyze starch:

1. Alpha-amylase-converts starch to oligosaccharides (salivary amylase (ptyalin) and pancreatic
amylase are this type, as both hydrolyze 1,4 glycosidic bonds in starch yielding alpha-dextrin,
maltotriose, and maltose). Maltase, alpha-dextrinase, and sucrase in the intestinal brush border
then hydrolyze the oligosaccharides to glucose. These enzymes are inactivated by acidic gastric
juices (hydrochloride acid).

2. Beta-amylase-converts starch to maltose and dextrins.

 3. Glucamylase-converts starch to glucose.

Only monosaccharides (glucose, galactose, fructose) are absorbed in the small intestine. Lactase
degrades lactose to glucose and galactose, isomaltase degrades branching oligosaccharides to glucose,
and sucrase degrades sucrose to glucose and fructose.

MICHAELIS CONSTANT (Km)-the concentration of substrate at which 50% of the active sites are
filled. Km is a measure of the strength of the ES complex (enzyme-substrate complex): a high Km
indicates weak binding, a low Km indicates strong binding. Michaelis Constant (Km)-numerically equal
to the substrate concentration that gives half-maximal velocity. Km is expressed in units of molarity.
• Expressed as Km = [S], when Vo = ½ Vmax.

• Km is equal to that substrate concentration at which Vo (initial reaction velocity) is ½ Vmax.

• Km values of enzymes range widely. For most enzymes, Km lies between 10-1 and 10-6m. Km
value for an enzyme depends on the particular substrate and environmental conditions
(temperature and ionic strength).

• Km values for enzyme-substrate reactions: increase in the presence of a competitive

inhibitor and are not affected in the presence of a noncompetitive inhibitor.

• Maximum rate (Vmax) is attained when the enzyme sites are saturated with substrate.

ALLOSTERIC ENZYME-a regulatory enzyme with catalytic activity modulated by the reversible,
non-covalent binding of a specific metabolite (allosteric modifier) at an allosteric site other than the
active site.
• Allosteric enzymes usually show a complex relationship between the velocity and substrate
concentration. They DO NOT follow Michaelis-Menton kinetics.
• Allosteric enzymes frequently catalyze a committed step early in a metabolic pathway.
• Allosteric enzymes often have two or more subunits each with substrate binding sites that exhibit
cooperativity.
• Allosteric activators cause the enzyme to bind substrate more readily, while allosteric inhibitors
cause the enzyme to bind substrate less readily.

INHIBITORS of enzymes DECREASE THE RATE OF ENZYMATIC REACTIONS.

• Reaction velocity increases with enzyme concentration if the substrate concentration is constant.

• At Vmax, all active sites are saturated with substrate.

• Reaction velocity increases with temperature until a maximum is reached (if the temperature gets too
high, the enzyme will denature).

ENZYMES are subject to 3 types of (REVERSIBLE INHIBITION):

1. Competitive inhibition-the competitive inhibitor resembles the substrate and binds to the enzyme
active site. The substrate is then prevented from binding to the same active site. The hallmark of
competitive inhibition is the inhibition can be overcome by increasing the substrate
 concentration.
• A competitive inhibitor of an enzyme increases Km without affecting Vmax.
• Competitive inhibition: (reversed by increasing substrate; Vmax remains constant,
and Km increases).

2. Noncompetitive inhibition-the inhibitor and substrate can bind simultaneously to an enzyme. This
means their binding sites do not overlap. Because the inhibitor and substrate do not compete for the
same site, noncompetitive inhibition cannot be overcome by increasing the substrate concentration.
The noncompetitive inhibitor binds to either a free enzyme or the ES complex. The inhibitor binds to
the enzyme or ES complex at a site different from the active site.
▪ Noncompetitive inhibition: (is not reversed by increasing substrate, Vmax is
decreased, and Km is unchanged).

3. Uncompetitive inhibition-like noncompetitive, the inhibitor and substrate bind at different sites that
do not overlap. However, an uncompetitive inhibitor will only bind to an enzyme with a substrate
already attached (ES complex).

IRREVERSIBLE INHIBITORS-substrates that combine with or destroy a functional group on the

enzyme essential for the enzyme’s activity.

UDP-Glucose-the precursor for glycogen synthesis. Glucose enters the cell and is phosphorylated to
glucose 6-phosphate by hexokinase (in most tissues) or by glucokinase (in liver). To initiate glycogen
synthesis, glucose 6-phosphate is reversibly converted into glucose 1-phosphate by
phosphoglucomutase. This glucose 1-phosphate is then converted to UDP-glucose by the action of UDP-
glucose pyrophosphorylase.

Glycogen synthase-the key regulatory enzyme for glycogen synthesis. It transfers glucose residues
from UDP-glucose to the non-reducing ends of a glycogen molecule. Glycogen synthase is responsible for
making 1,4 linkages in glycogen.
• Glycogen synthase has phosphorylated and dephosphorylated forms. The active enzyme,
glycogen synthase “a” = dephosphorylated form. Glycogen synthase “b” = phosphorylated form and
is the less active enzyme.

• Glycogen phosphorylase-breaks down glycogen and has two forms (a and b). However, the
phosphorylated form is the active enzyme (a) and the dephosphorylation form is the inactive
enzyme (b).

Both enzymes (glycogen synthase & glycogen phosphorylase) are phosphorylated at specific serine
residues.

GLUCONEOGENESIS-biosynthesis of glucose from non-carbohydrate molecules. It occurs

primarily in the liver, and its role is to provide glucose for export to other tissues when other sources of
glucose are exhausted. Typically, it involves the conversion of amino acids into pyruvate or
phosphoenolpyruvate, which is then converted to glucose. Glucose 6-phosphatase is essential for this
transformation, and catalyzes the last step of this process in which glucose 6-phosphate is hydrolyzed into
glucose.
 • In gluconeogenesis, pyruvate is converted into glucose.
• In glycolysis, glucose is converted into pyruvate.

Key reaction of Gluconeogenesis:

• PyruvatePOxaloacetate (catalyzed by pyruvate carboxylase).
• OxaloacetateOPhosphoenolpyruvate (catalyzed by phosphoenolpyruvate carboxy-kinase).
• Fructose 1,6-biphosphateFfructose 6-phosphate (catalyzed by fructose 1,6-biphosphatase).
• Glucose 6-phosphatelglucose (catalyzed by glucose 6-phosphatase).

Glucose 6-phosphatase-an enzyme found most abundantly in the LIVER. It is also in the kidneys, but
is NOT present in muscle or the brain. G6P does NOT contain a high-energy bond.

PHOSPHATASES-any group of enzymes that liberate inorganic phosphate from phosphoric esters.
1. Alkaline Phosphatase-an enzyme that either increases the local concentration of inorganic phosphate
or activates collagen fibers in way to cause deposition of calcium salts. It is involved in bone
mineralization, hydrolysis of phosphoric esters, and function optimally at pH 8.6. Osteoblasts
that are actively depositing bone matrix secrete large quantities of Alkaline phosphatase.
• Most alkaline phosphatase in normal serum is derived from bone, but is present throughout the
body. High levels of alkaline phosphatase are seen in Paget’s disease of bone and
osteosarcomas, while low levels are seen in cases of hypophosphatasia.

2. Acid Phosphatase-a phosphatase with optimum functioning at pH 5.4 present in the prostate gland.
High levels of acid phosphatase are seen in carcinoma of the prostate gland.

Creatine Phosphate (phosphocreatine)-an organic compound found in muscle tissue, and is capable of
storing and providing energy for muscular contraction.

Pyrophosphatase-acid anhydride hydrolase that may also play a role in bone mineralization.

Glutamate-pyruvate transaminase (GPT or alanine aminotransferase ALT)-an enzyme present in

the heart, but highly abundant in the LIVER.

Some enzymes show high activity in only one or a few tissues, and the presence of increased enzyme
levels in plasma reflects the damage to corresponding tissues.
• LIVER: GPT & GOT (glutamate-oxaloacetate transaminase or aspartate aminotransferase-AST).
GPT & GOT enzymes are elevated in nearly all liver diseases.

• HEART: creatine kinase (CK or creatine phosphokinase-CPK), lactate dehydrogenase (LDH),

glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT).

Plasma levels of these enzymes are commonly determined in the diagnosis of myocardial infarction, and
are especially useful when the ECG is difficult to interpret.

Creatine kinase (CK) is the FIRST HEART ENZYME TO APPEAR IN BLOOD AFTER AN MI
(HEART ATTACK), then GOT, then GPT and LDH.

ZYMOGENS-enzymatically inactive precursors of proteolytic enzymes. Digestive enzymes that

hydrolyze proteins are produced and secreted as zymogens in the stomach and pancreas, and are
converted to their active forms by removing a peptide fragment in the lumen of the digestive tract. Many
digestive proteases are produced and secreted as inactive ZYMOGENS:
1. Pepsinogen-synthesized in the stomach; pepsin is the active form.
2. Chymotrypsinogen-synthesized in the pancreas; chymotrypsin is the active form.
3. Trypsinogen-synthesized in the pancreas; trypsin is the active form.
4. Procarboxypeptidase A-synthesized in the pancreas; carboxypeptidase A is the active form.
5. Procarboxypeptidase B-synthesized in the pancreas; carboxypeptidase B is the active form.
6. Proelastase-synthesized in the pancreas; elastase is the active form.

The presence of amino acids (from protein digestion) in the small intestine (duodenum) stimulates
the release of two polypeptide hormones of the digestive tract (cholecystokinin (CCK) and secretin).
These hormones cause release and activation of pancreatic ZYMOGENS (e.g. trypsinogen,
chymotrypsinogen, proelastase, elastase, and procarboxypeptidase A and B) are secreted in inactive
forms (zymogens) activated in the small intestine as follows:

• Trypsinogen is activated to Trypsin by Enteropeptidase (enterokinase)-an enzyme produced by

intestinal cells that CONVERTS TRYPSINOGEN TO TRYPSIN.

Trypsin converts the pancreatic zymogens into their ACTIVE FORMS.

1. Pepsinogen-secreted by chief cells of the stomach is activated to pepsin by HCL.

2. Trypsin-cleaves peptide bonds in which the carboxyl group is contributed by lysine and arginine
(basic amino acids).

3. Chymotrypsin-cleaves peptide bonds in which the carboxyl group is contributed by the aromatic
amino acids or by leucine.

4. Elastase-cleaves at the carboxyl end of amino acid residues with small, unchanged side chains
like alanine, glycine, or serine.

5. Carboxypeptidase A-cleaves aromatic amino acids; B cleaves basic amino acids (lysine &
arginine).

UBIQUINONE (Coenzyme Q)-energy-rich molecules such as glucose or fatty acids are metabolized by
a series of oxidation reactions of the electron transport chain ultimately yielding CO2 and water. The
metabolic intermediates of these reactions donate electrons to specialized coenzymes (NAD+ and FAD)
which pass electrons to the electron transport chain (ETC). In the ETC, flavin mononucleotide
(FMN) & coenzyme Q (ubiquinone) pass the electrons to heme-containing cytochromes which
transfer the electrons to oxygen.
• ETC components are inside the inner membrane of the mitochondria.

• FAD is derived from riboflavin; NAD is derived from niacin.

• Coenzyme Q (ubiquinone) is not derived from a vitamin (the body synthesizes it).

• Each cytochrome consists of a heme group associated with a protein; Cytochrome a + a3 is also
 called cytochrome oxidase.

• Oxygen is the ultimate electron acceptor and is reduced to water.

• COENZYME-a non-protein substance (organic cofactor) that combine with an apoenzyme (the
protein portion of a complex enzyme) to form a haloenzyme (a complete, catalytically active
enzyme system).

GLUTAMATE DEHYROGENASE-an enzyme of the oxidoreductase class that catalyzes the oxidative
deamination of glutamate to form α-ketoglutarate, using either NAD+ or NADP+ as an electron
acceptor. The reversible reaction has a major function in the synthesis and degradation of glutamic acid
and, via transaminases, other amino acids as well.
• Oxidative deamination reactions occur primarily in the liver and kidney and provide α-
ketoacids (for energy) and ammonia (source of nitrogen in urea synthesis).

• AST & ALT are transaminases (animotransferases) not involved in oxidative deamination
reactions.

• Histidine is deaminated by histidase to form ammonium ion (NH4+) and urocanate.

• Serine and Threonine are deaminated by serine dehydratase. Serine is converted to pyruvate, and
threonine to e-ketobutyrate; ammonium ion is released.

• Glutaminase deaminates glutamine to glutamate and ammonium ion

• Asparaginase deaminates asparagines to aspartate and ammonium ion.

TRANSAMINATION REACTIONS: involve the transfer of an amino group from one amino acid to an
-keto acid. Enzymes that catalyze transamination reactions are TRANSAMINASES
(aminotransferases). Glutamate and G-ketoglutarate are often involved in these reactions, serving as
one of the amino acid//-keto acid pairs. Pyridoxal phosphate (PLP)-is derived from vitamin B6, and
serves as the cofactor for transamination reactions.

FIRST STEP in the catabolism of all amino acids involves removal of the α-amino group. Once
removed, this nitrogen can be incorporated into other compounds or excreted.

NITROGEN IS TRANSFERRED from one amino acid to another by transamination reactions,

which always involves two different pairs of amino acids and their corresponding e-keto acids (glutamate
and --ketoglutarate usually serve as one of the pairs); transaminases (aminotransferases) catalyze the
transfer of amino groups, and all transaminases require the coenzyme pyridoxal phosphate.

In contrast to transamination reactions that transfer amino groups, oxidative deamination reactions
result in the liberation of the amino group as free ammonia (NH3). These reactions occur primarily in
the liver and kidney and provide o-ketoacids (for energy) and ammonia (a source of nitrogen in urea
synthesis). Enzymes involved in deamination reactions are glutamate and dehyrogenase (for glutamate),
histidase (for histidine) and serine dehydratase (for serine and theonine).
ALL AMINOTRANSERASES (transaminases) share a common prosthetic group, PYRIDOXAL
PHOSPHATE (PLP). PLP is the coenzyme form of pyridoxine or vitamin B6. PLP functions as an
intermediate carrier of amino groups at the active site of transaminases. PLP undergoes reversible
transformations between its aldehyde form, pyridoxal phosphate (PLP), which accepts an amino group,
and its aminated form (pyridoxamine phosphate-PMP), which donates its amino acid to an α-keto acid.

CARBONIC ANHYDRASE-are ZINC-CONTAINING ENZYMES that catalyze the reaction between

carbon dioxide and water (CO2 & H2O). It is one of the FASTEST enzymes found in high
concentrations in erythrocytes (RBC). Waste CO2 released from respiring tissues into blood plasma
enters the erythrocyte. Within the erythrocytes, carbonic anhydrase facilitates the combination of
carbon dioxide and water to form carbonic acid (H2CO3). Carbonic acid can dissociated into H+ ions
and bicarbonate ions (HCO3-). HCO3- reenters the blood plasma for transport to the lungs. Since HCO3-
is much more soluble in blood plasma than CO2, this roundabout route increases the blood’s capacity to
carry carbon dioxide from the tissues to the lungs. In the lungs, HCO3- reenters the erythrocyte and
combines with H+ ions to form carbonic acid, which is split by carbonic anhydrase into carbon dioxide
and water. This carbon dioxide diffuses into the alveoli and is exhaled.
• Carbonic anhydrase also functions in the KIDNEY with the reabsorption of bicarbonate ion.

• Although not required for CO2 and water to form carbonic acid, carbonic anhydrase greatly
increases the reaction in both respects (formation and dissociation).

• Most of the carbon dioxide (CO2) is transported in the blood as bicarbonate ion (HCO3-). It
is converted to carbonic acid (H2CO3) more rapidly in whole blood than in plasma. The reason
for this is that whole blood contains erythrocytes with carbonic anhydrase, while plasma does not
contain erythrocytes.

PHOSPHOFRUCTOKINASE-its activity level controls the rate of glycolysis. The irreversible

phosphorylation reaction catalyzed by phosphofructokinase is the most important control point of
GLYCOLYSIS. The phosphofructokinase reaction is the rate-limiting step in glycolysis, and requires
an input of energy from ATP:

Fructose-6-Phosphate→→→phosphofructokinase→→→Fructose 1,6-Bisphosphate

THIS ALLOSTERIC ENZYME is stimulated by ADP and AMP, and is inhibited by ATP & citrate.
The enzyme is most active when the energy of a cell is low. This enzyme does not function in association
with a membrane, while (adenylate cyclase, coenzyme Q, reductase, and succinate dehydrogenase all
do).

ALDOLASE-converts fructose 1,6-bisphosphate (6-carbon metabolite) into two 3-carbon metabolites,

dihydroxyacetone phosphate and glyceraldehydes 3-phosphate. This is the aldolytic reaction of
glycolysis. Aldolase is plentiful in skeletal and heart muscle tissues.

Phosphoglucose isomerase-catalyzes the isomerization of glucose 6-phosphate to fructose 6-phosphate.

Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehydes 3-
phosphate.
OSMOTIC PRESSURE of a solution depends on the number of solute particles present and not on
their nature. Sodium chloride, potassium, and chloride will ionize into two ions thus, their osmotic
pressure differs from the osmotic pressure of glucose.
• Osmosis-the net diffusion of WATER through a semipermeable membrane caused by a
concentration difference.
• Osmotic pressure-the pressure that develops in a solution due to net osmosis into that solution; it
is affected by the number of dissolved particles per unit volume of fluid. Note: intracellular (fluid
within cells) and interstitial fluid (fluid that surrounds cells) body fluids have similar total
osmotic pressures.

OSMOLARITY-the osmotic pressure of a solution expressed in osmols per kilogram of the solution.

OSMOLALITY-the osmotic pressure of a solution expressed in osmols per kilogram of water.

Potassium is the MAJOR INTRACELLULAR CATION. Its concentration is higher in intracellular

fluid (ICF) than in extracellular fluid (ECF).

TOTAL BODY WATER-composed of 2/3 intracellular fluid and 1/3 extracellular fluid (of which ¼ is
plasma & ¾ interstitial fluid).
1. Intracellular Fluid-the fluid within cells. Major cations are K+ and Mg2+. Major anions are
protein and organic phosphates. It contains the largest amount of body water (2/3).

2. Extracellular Fluid-the fluid outside cells, made of the interstitial fluid and plasma. Major cation
is Na+. Major anions are Cl- and HCO3-.

• Interstitial fluid (tissue fluid)-the fluid that surrounds and BATHES THE CELLS OF
TISSUES (found in tissue spaces). Its main component is extracellular fluid, which
includes plasma and transcellular fluid. Same composition as plasma, except it has little
protein too.

• The average person has about 10 liters that provides cells with nutrients and a means of
waste removal. Consists of water solvent containing sugars, salts, fatty acids, coenzymes,
hormones, neurotransmitters, and cellular waste products.

 BONE DISORDERS
FRACTURE-the most common bone lesion. Healing of fractures involves 3 phases:
1. Inflammatory phase-characterized by formation of a blood clot.
2. Reparative phase-characterized by formation of a callus of cartilage, replaced by a bony callus
(compact bone).
3. Remodeling phase-the cortex is revitalized.

Reasons Fractures Fail to Heal (non-union):

1. Ischemia-the navicular bone of the wrist, femoral neck, and lower third of the tibia are all poorly
vascularized and thus, subject to coagulation necrosis after a fracture.
2. Excessive mobility-pseudoarthrosis or a pseudojoint may occur.
3. Interposition of soft tissue-between the fractured ends.
4. Infection-most likely with compound fractures.

Fat Embolism-most often a sequela of fractured bones due to the mechanical disruption of bone
marrow fat and by alterations in plasma lipids.

Osteochondroma-a benign tumor made of bone and cartilage, found most frequently near the ends of
long bones. Most common in patients 10-25 years old.

OSTEOCHONDROSES-a group of diseases that affects the growth plate during childhood, resulting
in abnormal bone growth and deformity. Their cause unknown. Different diseases affect different bones,
characterized initially by degeneration and aseptic necrosis followed by regeneration and reossification.
Types of Osteochondroses:
1. Osgood-Schlatter Disease-inflammation of bone and cartilage at the top of the SHINBONE.
Usually develops between ages 10-15 more common in athletic boys. Major symptoms: pain,
swelling, and tenderness at the top of the shin. It usually involves the tibial tubercle of the knee.

2. Legg-Calve-Perthes Disease-destruction of the growth plate in the neck of the thighbone.

Develops between ages 5-10, more common in boys. Caused by poor blood supply to the neck
of the thighbone. Main symptoms are hip pain and problems walking.

3. Scheuermann’s Disease-relatively common condition in which backache and humpback

(kyphosis) are caused by changes in vertebrae. Usually begins in adolescence, affecting mostly
boys. Symptoms are rounded shoulders and persistent mild backache.

4. Kohler’s bone Disease-a rare form of inflammation of bone and cartilage (osteochondritis)
affecting one of the small bones (navicular bone) in the foot. Usually affects children (boys 3-5
years). Symptoms are swollen foot with limping.

OSTEOMALACIA-caused by VITAMIN D DEFICIENCY in adults. Characterized by a gradual

softening and bending of the bones with varying severity of pain. This softening of the bones occurs
because the bones contain osteoid tissue that failed to calcify due to lack of vitamin D.
 • All bones are effected, specifically their epiphyseal growth plates which have closed. It is
identified radiographically by diffuse radiolucency that can mimic osteoporosis. Bone biopsy is
often the only way to differentiate between osteoporosis and osteomalacia.

• Osteomalacia is the ADULT FORM OF RICKETS, appearing more in women. It may be

asymptomatic until fracture occurs.

RICKETS-is OSTEOMALACIA in CHILDREN that causes skeletal deformities. It is usually

accompanied by listlessness, irritability, & generalized muscular weakness. The teeth in a child with
rickets are effected by: delayed eruption, malocclusion, and developmental abnormalities of the
dentin and enamel, and a higher caries rate. In rickets, the bones become bowed because of failure of
osteoid tissue to calcify.

OSTEOMYELITIS-a bone infection usually caused by BACTERIA. Osteomyelitis is an acute

pyogenic infection of bone, usually caused by bacteria (Staphylococcus aureus) introduced by trauma,
surgery, or direct extension from a nearby infection, or via the bloodstream.
• Common infection sites: distal end of the femur, proximal end of tibia, and proximal end of
humerus. It often present symptoms of pain, redness, and swelling in the affected area. Fever and
malaise are usually evident.

OSTEOPOROSIS-a decrease in BONE MASS caused by impaired synthesis or increased

resorption of bony matrix protein. It results in predisposition to pathologic fractures. Common in thin,
elderly, white women, and clinically associated with postmenopausal state (estrogen deficiency),
physical inactivity, hyperthyroidism, and calcium deficiency. Treatment: estrogen therapy, calcium
supplements, vitamin D.

OSTEONECROSIS-bone death affecting the maxilla and mandible. Associated with bisphosphonate
therapy. Symptom: bone exposure through a gingival lesion that does not heal. Most common after
extractions, but can occur spontaneously.

OSTEOPETROSIS (marble bone disease, Albers-Schonberg Disease)-an uncommon hereditary bone

disorder of marked increased density of bones, causing skeleton abnormalities. Caused by failure of
osteoclastic activity. It begins in infancy, and symptoms include: poor growth and poor weight gain
(failure to thrive), easy bruising, abnormal bleeding, and anemia. The liver and spleen can enlarge,
blindness and progressive deafness may occur.

NON-NEOPLASTIC BONE DISEASES:

1. Achondroplasia-one of the most common causes of DWARFISM. An autosomal dominant
disorder characterized by short limbs with normal-sized head and trunk.

2. Osteogenesis imperfecta-a rare, hereditary disorder (“brittle bones”) that demonstrates the
effect of inadequate osteoid production. OI results in skeletal fragility, thin skin, poor teeth, thin
sclera with a blue appearance, a tendency towards macular bleeding, and hypermotility of joints.
The teeth are poor because of malformation of dentin (dentinogenesis imperfecta). Patients have
a history of multiple fractures.
 3. Fibrous dysplasia-normal bone is replaced by fibrous tissue. There are 3 classifications
depending on extensiveness of skeletal movement: Monostotic (one bone); Polyostotic (more
than one bone); Polyostotic with associated endocrine disturbances (Albright’s
Syndrome).Pathologic fractures are often the presenting complaint.

OSTEOARTHRITIS (degenerative arthritis, degenerative joint disease)-MOST COMMON JOINT

DISORDER. Osteoarthritis is a chronic joint disorder where degeneration of joint cartilage and
adjacent bone that can cause joint pain and discomfort. Osteoarthritis is classified as primary
(idiopathic) when the cause is unknown, and secondary when caused by another disease (e.g. Paget’s
disease), or an infection, deformity, injury, or overuse of a joint. It has a higher incidence in women (after
age 50).
• Morphologic changes include Eburnation of bone: polished, ivory-like appearance of bone.

OSTEOPHYTE: bony spur formation is a cardinal feature of osteoarthritis. Osteophytes fracture and
float into synovial fluid along with fragments of separated cartilage (called joint mice).
• Heberden’s nodes-osteophytes (bony spurs) located in distal interphalangeal joints of fingers.

• Bouchard’s nodes-osteophytes (bony spurs) in proximal interphalangeal joints of fingers.

• joints most often affected: intervertebral joints of the spine, phalangeal joints of fingers, knees,
and hips.

RHEUMATOID ARTHRITIS (RA)-a chronic, severely damaging form of arthritis (systemic

inflammatory disorder) that affects certain joints especially in the hands, feet, knees, ankles, elbows, and
wrists. RA begins at any age, but the first symptoms appear before age 50. Women are affected more than
men. Cause is unknown.

• RA involves an inflammatory and fibrosis of the capsule around joints, and affects underlying bone
and cartilage.

• PANNUS-classic microscopic lesion of rheumatoid arthritis.

• Still’s Disease-a type of RA in young people, that can also affect adults.

• Cause of rheumatoid arthritis is unknown, but it may be initiated by a bacterial or viral infection.
Some people have a genetic tendency to develop the disease. Research suggests it may be an
autoimmune disease. 50% of this risk for RA may be genetic. Smoking is the greatest non-genetic
risk for RA.

• There is an association between RA and Epstein-Barr Virus (EBV) and HHV-6.

• RA is marked by proliferative inflammation of the synovial membranes causing deformity,

ankylosis, and invalidism. The earliest changes in rheumatoid arthritis occur in the SYNOVIA.

• RA Characteristics: serum anti-IgG antibodies (rheumatoid factor), subcutaneous rheumatoid

nodules, fatigue, malaise, anorexia, weight loss, fever, and myalgias, symmetric polyarthritis.
Rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, dermatomyositis, and
 scleroderma are all COLLAGEN DISEASES. They all have in common inflammatory damage to
C.T. and blood vessels with disposition of fibrinoid material.

PAGET’S DISEASE (Osteitis Deformans)-characterized by normal serum calcium and phosphorus

with a markedly increased serum alkaline phosphatase. Paget’s Disease is a chronic disorder of the
skeleton in which areas of bone grow abnormally, enlarging, and becoming soft. Paget’s can affect
any bone, but most commonly affects the pelvis, thighbone (femur), skull, shin, spine (vertebrae),
collarbone (clavicle), and upper arm (humerus). Paget’s is characterized by a marked increase in bone
remodeling. The cause is unknown, although it tends to run in families. It occurs chiefly in white,
elderly males. The signs and symptoms are pain in the affected area, hearing and vision problems, an
enlarged head, and intra-orally, the teeth spread. Symptoms develop slowly, and patients are
predisposed to developing osteosarcomas. COTTON-WOOL APPERANCE OF BONE.
• Paget’s Disease of bone is characterized by an extremely high level of alkaline phosphatase,
normal levels of calcium and phosphorus, skull enlargement, and increased incidence of
osteogenic sarcoma.
• Paget’s may be discovered due to change in hat size; affected areas may be warm to the
touch; and it often results in deafness.
VON RECKLINGHAUSEN’S DISEASE (osteitis fibrosa cystica)-bone disease caused by
hyperparathyroidism, characterized by decreased serum phosphorus and increased serum calcium and
alkaline phosphatase. Serum acid phosphatase levels are elevated in patients with prostate cancer.

Metastatic Calcification-the deposition of calcium salts in previously undamaged tissues due to excess
blood calcium and occurs particularly in hyperparathyroidism and hypervitaminosis D.

Dystrophic Calcification-the most frequent type of pathologic calcification where calcium salts are
deposited in dead or degenerating tissues. Secondary to disease of the tissue affected.

ACUTE HYPOCALCEMIA-in the human, it usually causes no other significant effects besides tetany
because tetany kills the patient before other effects develop.

CALCINOSIS-calcifications in or under the skin, often associated with scleroderma & dermatomyositis.

GOUT-a disorder of sudden, recurring attacks of very painful arthritis caused by the deposition of
monosodium urate crystals that accumulate in the joints because of an abnormally high uric acid
level in blood (hyperuricemia). Gout is an inherited disorder of PURINE metabolism. (uric acid is an
end product of purine metabolism, specifically xanithine metabolism).
• Most typically seen in adult men.
• Most often affects the joint at the base of the big toe (condition called podagra).
• Hard lumps of urate crystals (tophi) are deposited under the skin around joints.
• An abnormally high uric acid level in the blood (hyperuricemia).

THE GENETIC DEFECT causes either an increased production of uric acid, or reduction in the ability
of the kidneys to excrete uric acid (almost 25% of all people who have gout develop kidney stones). In
either case, the result is an increase in the level of uric acid in the blood. It also commonly affects the
instep, ankle wrist, and elbow. When the joints are affected, the condition is called gouty arthritis.
PSEUDOGOUT-a disorder of intermittent attacks of painful arthritis caused by deposits of calcium
pyrophosphate crystals. It usually occurs in older people, and affects men and women equally.

 HORMONAL & ENDOCRINE DISORDERS
ACROMEGALY-excessive growth caused by OVERSECRETION OF GROWTH HORMONE by
the anterior pituitary gland in the ADULT. Usually begins between ages 35-55, long after the end plates
of bones have closed. Thus, bones become deformed, but not elongated. Common Findings of
Acromegaly:
• Gradual marked enlargement of the head, face, hands, feet, and chest.
• Excessive perspiration and offensive body odor.
• Prognathism (mandible protrudes).
• Enlarged tongue and deep voice.

Pituitary Gigantism-oversecretion of growth hormone DURING CHILDHOOD before end plates of

long bone close; leads to bone growth and abnormal height.

Dwarfism (pituitary dwarfs)-arrested growth; these people frequently have limbs and features not
properly proportioned or formed. Dwarfism is caused by undersecretion of growth hormone.

HASHIMOTO’S THYROIDITIS (autoimmune thyroiditis)-most common thyroiditis and most

common cause of hypothyroidism. Etiologic bases of Hashimoto’s thyroiditis is AUTOIMMUNE.

• For unknown reasons, the body turns against itself in an autoimmune reaction, creating
antibodies that attack the thyroid gland. There is diffuse lymphocytic infiltration with germinal
center formation. It is most common in elderly women and tends to run in families.

• It is fairly common and affects women more than men. It may occur in people with certain
chromosomal abnormalities, including Turner’s, Down, and Klinefelter’s syndromes. There is
increased incidence in persons with pernicious anemia, diabetes mellitus, or Sjogren’s
syndrome. Symptoms of hypothyroidism are (fatigue, slowed speech, cold intolerance, dry skin,
coarse hair, puffy face).

SUBACUTE GRANULOMATOUS THYROIDITIS (Giant cell) -probably caused by a virus,

beginning much more sudden than Hashimoto’s thyroiditis.
• Silent lymphocytic thyroiditis-occurs most often in women, just after childbirth causing the
thyroid to become enlarged without becoming tender. Most people recover completely from both of
these disorders.

Autoimmune Disease-a disease resulting from an immune reaction produced by an individual’s white
blood cells or antibodies acting on the body’s own tissues. In Hashimoto’s disease, there is the
production of antibodies in response to thyroid antigens and the replacement of normal thyroid
structures with lymphocytes and lymphoid germinal centers.

HYPERTHYROIDISM-caused by excessive production of thyroid hormone (THYROXIN).

Thyroxin’s primary role is to stimulate cellular metabolism, growth, and differentiation of all tissues. In
excess, it leads to high basal metabolism, fatigue, weight loss, excitability, elevated temperature
(heat intolerance, sweating), generalized osteoporosis, fine hair, diarrhea, tremor (shakiness),
tachycardia (rapid heart rate). Oral manifestations are not common, but if the disturbance begins early
in life, premature tooth eruption and loss of deciduous dentition are common. Two types of
Hyperthyroidism:
1. Graves Disease (toxic diffuse goiter)-most common form that occurs mostly in women ages 20-
40. Usually arises after an infection or physical or emotional stress. Typical signs of
hyperthyroidism are present plus goiter and exophthalmos (bulging eyes).

2. Plummer’s Disease (toxic multinodular goiter)-caused by the presence of many toxic thyroid
nodules (adenomas) within the thyroid gland. Plummer’s is uncommon in adolescents and young
adults, and increases with age. Exophthalmos (bulging eyes) is rare.

HYPOTHYROIDISM-a clinical feature is WEIGHT GAIN, cold intolerance, lowered pitch of voice,
mental and physical slowness, constipation, dry skin, coarse hair, and puffiness of face, eyelids, and
hands.

• Myxedema-very severe hypothyroidism in adults, much more common in women than men.
Myxedema is characterized by puffiness of face and eyelids, swelling of tongue and larynx. The skin
becomes dry and rough, and hair becomes sparse. The individual has a low basal-metabolic rate and
low body temperature, poor muscle tone, low strength, and gets tired easily. Mentally they are
sluggish. Myxedema is alleviated by administering thyroid hormones.

• Cretinism-severe hypothyroidism in a child, due to lack of thyroid hormone causing retardation of

growth and abnormal bone development. Severe mental retardation is caused by improper CNS
development. If recognized early, Cretinism can be improved with thyroid hormones.
▪ Dental findings in a child with hypothyroidism are a large tongue, underdeveloped
mandible and overdeveloped maxilla, delayed eruption of teeth, and deciduous teeth
are retained longer.

HYPERPARATHYROIDISM-a common associated complication is KIDNEY STONES (renal calculi).

Kidney stones form due to an increase in urinary excretion of calcium and phosphate. Osteoporosis, giant
cell granulomas, and metastatic calcifications are all manifestations of hyperparathyroidism.

• Other factors that contribute to kidney stone (renal calculi) formation are kidney infection, vitamin
A deficiency, low fluid intake, a diet too high in calcium-rich foods, and certain metabolic
problems.

PRIMARY HYPERPARATHYROIDISM-the major cause is an adenoma (benign tumor of gallbladder

epithelium). Laboratory findings include hypercalcemia, decreased serum phosphorus, and increased
serum alkaline phosphatase and serum PTH. Clinical characteristics are cystic bone lesions (osteitis
fibrosa cystica or von Recklinghausen’s disease of bone), nephrocalcinosis, kidney stones (renal
calculi), and peptic duodenal ulcers.

• EXCESS LOSS OF CALCIUM in urine stimulates the parathyroid glands to undergo

hyperplasia. This occurs because the feedback mechanism that detects low serum calcium elicits
growth of the gland. The resulting metabolic effects are identical to primary hyperparathyroidism
 effects.

• Secondary Hyperparathyroidism-most often caused by hypocalcemia of chronic renal disease.

• Tertiary hyperparathyroidism-persists after definitive therapy for secondary hyperparathyroidism.

HYPOPARATHYROIDISM-decreased function of parathyroid glands with underproduction of PTH.

Can result in low blood calcium levels, and can lead to muscle involuntary twitching and cramping
(tetany).
• Low blood calcium levels interfere with normal muscle contraction and nerve conduction, resulting
in PARESTHESIA.

• Fatigue, headaches, bone pain, and insomnia, abdominal pain are also common symptoms.

• In rare instances, associated with congenital thymic hypoplasia (DiGeorge’s syndrome).

• Hypoparathyroidism can be caused by accidental surgery excision during thyroidectomy,
autoimmune invasion and destruction is the most common non-surgical cause.

Pseudoparathyroidism-involves a defective end-organ responsiveness to PTH.

DIGEORGE’S ANOMALY (DiGeorge’s Syndrome)-a congenital developmental defect possibly

caused by intra-uterine infection THYMUS & PARATHYROID GLANDS FAIL TO DEVELOP.
DiGeorge’s is not usually hereditary, and occurs in boys and girls.

• There is FAILURE of the THIRD & FOURTH pharyngeal pouches to develop the thymus and
parathyroid glands. Abnormalities of the mandible, ear, and aortic arch are present. The absence of
the thymus results in T-cell deficiency causing the infant to be highly susceptible to intracellular
microorganisms (viruses, TB, and fungi). These children develop tetany due to hypocalcemia
(from absence of the parathyroids), and are likely to die from overwhelming viral infection at an
early age. Defects of the lower face, heart, and great vessels may be present.

• These children have normal B-lymphocytes and form antibodies, but have decreased or absent
delayed-type hypersensitivity.

CUSHING’S SYNDROME (Hypercortisolism)-symptoms are based on the effects of excess cortisol

and/or excess aldosterone. Symptoms: abdominal obesity (abnormal fat deposition), striae, MOON
FACE, BUFFALO HUMP, diabetes, muscle wasting, and osteoporosis
• Ectopic Cushing Syndrome-usually caused by secretion of bronchogenic carcinomas and
pancreatic neoplasms.

FAMILIAL HYPERCHOLESTEROLEMIA-a genetic defect characterized by anomalies (defects) of

receptors for low-density lipoprotein (LDL receptors). Can result in ATHEROSCLEROSIS and its
complications.

DIABETES-the most common PANCREATIC endocrine disorder and metabolic disease involving
mostly carbohydrates (glucose) & lipids owing primarily to a relative or complete lack of insulin
secretion by PANCREATIC BETA CELLS. Diabetes is caused by an absolute deficiency of insulin
(Type I) production by the pancreas or resistance of insulin’s action in peripheral tissues (Type II).

• Classic triad of diabetes symptoms are POLYDIPSIA (excessive thirst), POLYPHAGIA (excessive
hunger), & POLYURIA (large urine volumes).

• Diabetics loose twice as many teeth as non-diabetics, which supports the connection of oral
health and systemic health. Source: Duke University: analyzed data of 37,000 individuals between
1971-2012 to examine tooth loss trends.

INSULIN-a pancreatic hormone secreted by pancreatic beta-cells of ISLETS of LANGERHANS.

Insulin is essential for glucose metabolism and blood glucose homeostasis. Insulin is usually administered
by subcutaneous injection to treat Type 1 “insulin-dependent diabetes”. Effects of Insulin: ↓
gluconeogenesis & ↑ triglyceride storage, glycogen synthesis, & protein synthesis.

DIABETES MELLITUS (TYPE 1 = Insulin Dependent): the most common treatment is INSULIN by
subcutaneous injection. Diabetic emergencies are due to HYPOGLYCEMIA or
HYPERGLYCEMIA.
• Triad of symptoms are POLYURIA (frequent urination), POLYDIPSIA (increase thirst), and
POLYPHAGIA (increased hunger).

• Caused by autoimmune destruction of insulin-producing BETA ISLET CELLS in the pancreas.

Lack of insulin increased glucose in urine and blood.

• HYPOGLYCEMIA (INSULIN SHOCK) is the MOST SERIOUS and MOST COMMON

complication of insulin therapy due to ABNORMALLY LOW BLOOD GLUCOSE (<
 70mg/dl).

• SUDDEN ONSET OF SYMPTOMS include shakiness, nervousness, sweating, chills,

clamminess, dizziness, headache, blurred vision, weakness, confusion, slurred speech, irritability,
heart palpitations (increased heart rate = tachycardia), and blurred vision, but NOT shortness
of breath, hunger and nausea.

DIABETES MELLITUS (TYPE 2 = Non-Insulin Dependent): a chronic disorder more common in

adults that either involves the body’s resistance to secreted insulin, or doesn’t produce enough insulin
to maintain normal blood glucose levels.
• Classic Symptoms: polyuria, polydipsia, and polyphagia. Represents 90% of all diabetes cases.
OBESITY IS THE MAIN CAUSE, with a slow onset of development and symptoms. Ketosis is
rare. Type 2 can be managed with DIET + EXERCISE initially, or supplemented with oral
hypoglycemic drugs like METFORMIN or INSULIN.

• Type 2-DM is treated with the FIRST LINE oral hypoglycemic METFORMIN
(GLUCOPHAGE) to increase the body’s sensitivity to insulin. Contraindicated in conditions
that increase lactic acidosis risk (kidney disorders, lung or liver disease).

• Four oral hypoglycemic treat Type 2 DM if the patient has not responded to diet, weight
reduction, and exercise: Sulfonylureas (Glyburide, Micronase stimulates insulin release from
pancreatic beta cells), Metformin (Glucophage), Thiazolidinediones, and Alpha-glucosidase
inhibitors.

 GASTROINTESTINAL DISORDERS
PANCREATITIS-inflammation of the pancreas often caused by digestion of parts of the organ by
pancreatic enzymes that are normally carried to the small intestine within the pancreatic ducts.

ACUTE PANCREATITIS-caused by obstruction of the normal pathway of secretion of pancreatic juice

into the intestine. Zymogens of the proteolytic enzymes are converted into their catalytically active forms
prematurely, inside pancreatic cells. As a result, these powerful enzymes attack the pancreatic tissue,
causing a painful and serious destruction of the organ (can be fatal).
• Important factors in the etiopathogenesis of acute pancreatitis are biliary tract disease and
alcoholism. Manifestations or consequences of acute pancreatitis are enzymatic hemorrhagic fat
necrosis with calcium soap formation, and resultant hypocalcemia.

• The outstanding symptom of acute pancreatitis is severe, knife-like, upper abdominal pain; its
location corresponds to the inflamed area of the pancreas. Diagnosis is based on the type of pain,
and by detecting elevated lipase (mostly) and amylase enzymes in the patient’s serum and
urine.

• LIPASE & AMYLASE are the enzymes elevated in the blood (serum) of a patient suffering
from acute pancreatitis (lipase is more elevated than amylase). Hypocalcemia may be present.

• Cancer of the pancreas is MOST likely to cause common bile duct obstruction and jaundice.

DUODENAL ULCER-the most common type of peptic ulcer. Occurs in the duodenum, the first few
inches of the small intestine just below the stomach. Gastric ulcers-are less common and usually occur
along the upper curve of the stomach. Esophageal ulcers-are caused by repeated regurgitation of stomach
acid (HCL) into the lower part of the esophagus.

PEPTIC ULCER-a well-defined round or oval sore where the stomach lining or duodenum has been
eaten away by the stomach acid (HCL) and digestive juices (pepsin). Peptic ulcers are sometimes
associated with the intake of aspirin, cigarette smoking, hyperparathyroidism, MEN type 1, and Zollinger-
Ellison syndrome.

• PAIN is the most common symptom of a peptic ulcer. If the ulcer erosion is severe, blood vessels in
the stomach wall are damaged, and stomach bleeding occurs (bleeding ulcer). In extreme cases, a
peptic ulcer can lead to a complication perforation (a hole entirely through the GI tract wall), which
causes an acute peritonitis, and accounts for the majority of deaths.

• HEMORRHAGE is the most common complication of peptic ulcers. It occurs most frequently with
duodenal ulcers. Nearly all duodenal ulcers are benign; up to 10% of gastric ulcers are malignant.

• Peptic ulcers most commonly occur in the fist part of the duodenum.

PEUTZ-JEGHERS SYNDROME-a hereditary condition that affects males and females equally in
which many small lumps (juvenile polyps) appear in a variety of sites in the GI tract (usually in the
jejunum of small intestines). The polyps are not true neoplasms, but are hamartomas that do not
increase the risk of cancer in the intestinal tract.
• characterized by melanin pigmentation of the oral mucosa (lips and gingiva).
• People with Peutz-Jeghers are at increased risk for cancer of the pancreas, breast, lung, ovary,
and uterus.

GARDNER’S SYNDROME-a type of hereditary polyposis where various noncancerous tumors occur
elsewhere in the body and in the intestine. Carries a high risk of colon cancer. Supernumerary teeth.

GALLSTONES-collections of crystals composed of cholesterol or bile pigments.

• Cholelithiasis-gallstones in the bladder.
• Choledocholithiasis-gallstones in the bile ducts. Gallstones that block the common bile duct
result in obstructive jaundice (yellow skin caused by bile pigments becoming deposited in the
skin).

Gallstones are more common in women and in Native American Indians. Predisposing factors include
old age, obesity, hemolytic anemia, a Western diet, diabetes, multiple pregnancies, and use of oral
contraceptives. Most gallstones remain asymptomatic.

CHOLELITHIASIS (strawberry gallbladder)-condition where gallstones are in the gallbladder,

characterized by small, yellow, cholesterol-containing flecks highlighted against a red background in the
lining of the gall bladder. Polyps may form inside the gallbladder and require gallbladder removal.

DIVERTICULOSIS OF THE GALLBLADDER-small, finger-like out-pouchings of the gallbladder

lining that may develop with age. This may cause inflammation and require gallbladder removal.

MALABSORPTION SYNDROMES-disorders that develop because nutrients from food are not being
absorbed properly into the bloodstream from the small intestine. People with malabsorption usually lose
weight. Steatorrhea-stool that is light-colored, soft, bulky, and foul-smelling is the main
characteristic finding in most malabsorption syndromes. Steatorrhea is the most common finding in
intestinal malabsorption syndrome.

1. CELIAC DISEASE-a malabsorption syndrome and inherited disorder in which an allergic

intolerance to gluten (a protein) causes changes in the intestine that results in malabsorption.
Celiac disease can begin at any age, but the initial sign is usually the failure to thrive in an infant
growing normally until cereals are started. It can be fatal in adults due to the development of
lymphoma in the intestine.

2. TROPICAL SPRUE-an acquired disorder in which abnormalities of the small intestine lining
leads to malabsorption and deficiencies of many nutrients. Typical symptoms: steatorrhea,
diarrhea, weight loss, and sore tongue from vitamin B deficiency.

3. WHIPPLE’S DISEASE-a rare disorder that affects mainly men ages 30-60 caused by infection
of the small intestine by the organism Tropheryma whippelii. Symptoms: skin darkening,
inflamed and painful joints, and diarrhea.
 4. INTESTINAL LYMPHANGIECTASIA-a disorder in children and young adults in which lymph
vessels supplying the lining of the small intestine becomes enlarged. Main symptom: massive
fluid retention.

MALABSORPTION can cause deficiencies of all nutrients or of proteins, fats, vitamins, or

minerals. The symptoms vary depending on the specific deficiencies. The absorption of fat-soluble
vitamins (A, D, E, K) is affected to the greatest extent. Vitamin B12 malabsorption occurs in
PERNICIOUS ANEMIA due to the absence of intrinsic factor. This is caused by the destruction of
gastric parietal cells. Vitamin B12 malabsorption also occurs with Crohn’s disease.

TURCOTS SYNDROME-characterized by polyps and tumors of the central nervous system (CNS).

CROHN’S DISEASE-a chronic inflammation of the SMALL INTESTINAL WALL. No cure with
unknown cause. Involves non-necrotizing granulomatous inflammation with ulcers, strictures, and
fistulas. Most commonly involves the ILEUM and COLON.

CARCINOID TUMOR-the most common neoplasm of the appendix; in this location it rarely
metastasizes.

ULCERATIVE COLITIS-a chronic disease where the large intestines becomes inflamed and
ulcerated, leading to episodes of bloody diarrhea, abdominal cramps, and fever.

LIPODOSES-lipid storage diseases caused by abnormalities in enzymes that metabolize fat. Lipidoses
result in a toxic accumulation of fat byproducts in tissues. Lipidoses Storage Diseases:

1. Gaucher’s Disease-a hereditary disorder of lipid metabolism that leads to an accumulation of

glucocerebrosides (glycosphingolipid) in cells of the mononuclear phagocyte system. Gaucher’s
is caused by a deficiency in the enzyme glucocerebrosidase. There is enlargement of the spleen
and liver.

2. Niemann-Pick Disease-a hereditary disorder in which the deficiency of the enzyme

sphingomyelinase results in the accumulation of sphingomyelin. It is most common in Jewish
families. There is enlargement of the spleen and liver, anemia, fever, and neurologic deterioration.
Death usually occurs by age three.

3. Tay-Sachs Disease-a hereditary disorder in which the deficiency of the enzyme hexosaminidase
A results in the accumulation of Gm2 ganglioside, especially in neurons. It’s the most common
form of liposes and occurs primarily in families of Eastern Jewish origin. It is characterized by
CNS degeneration with severe mental and motor deterioration. Death occurs by age four.

4. Hurler’s Syndrome-caused by a deficiency of the enzyme α-L-iduronidase, which results in the

accumulation of the mucopolysaccharides heparin sulfate and dermatan sulfate in the heart,
brain, liver, and other organs. It is characterized by dwarfism and mental retardation. Death
usually occurs by age 10.

MALLORY-WEISS SYNDROME-a laceration of the esophagus and upper part of stomach during
forceful vomiting, retching, or hiccups. Characterized by massive bleeding from lacerations of the
lower esophagus with vomiting of blood caused by severe retching and vomiting. It commonly occurs
after excessive alcohol ingestion. Surgery is usually necessary to stop the bleeding. After repair, the
prognosis is excellent.

HIATAL HERNIA-protrusion of a portion of the stomach from its normal position in the abdomen
through the diaphragm. The cause is unknown, and most people have minor symptoms.

ACHALASIA-a nerve related disorder of unknown cause that can interfere with rhythmic waves of
contraction that propel food down the esophagus (PERISTALSIS), and the opening of the lower
esophageal sphincter. Difficulty swallowing solids and liquids is the main symptom.

ACID REFLUX-a backflow of stomach contents upward into the esophagus. HEARTBURN is the main
symptom.


SKIN DISORDERS

IMPETIGO (pyoderma)-a localized, intra-epidermal skin infection caused by Streptococcus Pyogenes

and Staphylococcus Aureus. Impetigo is a highly infectious skin infection most common in pre-school-
aged children (2-5 years) during warm weather. It results from the invasion of the epidermis by
Staphylococcus aureus or Streptococcus pyogenes. Pus-filled sacs (pustules) form beneath the stratum
corneum, causing inflammation and swelling. The pustules rupture and form a crust.
• Acute glomerulonephritis-one of the more common renal diseases in children, is an
occasional complication of impetigo.

ERYTHEMA MULTIFORME-an acute inflammatory skin disease marked by the symmetrical

eruption of macules, papules, or vesicles of various shapes presenting a multiform appearance. The
characteristic lesion is the target (bull’s-eye-shaped or iris) lesions over the dorsal aspect of the hands
and forearms. It may be allergic, seasonal, or from drug sensitivity. Topical or systemic corticosteroids
are helpful in treating the lesions.
• A common disorder with a peak incidence in the second and third decades of life.
• A disorder characterized by patches of red, raised skin that looks like targets distributed
symmetrically over the body.
• It is usually a reaction to a drug (most often to penicillin) or infectious agent and is commonly
associated with herpes simplex infection.
• It usually heals on its own, but Stevens-Johnson Syndrome (a very severe form of erythema
multiform) can be fatal.

Stevens-Johnson Syndrome-a SEVERE BULLOUS FORM of erythema multiforme that affects

children and young adults. Characterized by the acute onset of fever and eruptive, ulcerative lesions of
the skin, oral mucosa, and eyes. Frequently the genitalia, lungs, and joints are affected. It can have a fatal
termination.

ADDISON’S DISEASE (Adrenocortical insufficiency)-a life-threatening condition caused by partial

or complete failure of adrenocortical function. It may be the result of an autoimmune processes,
infection, neoplasm, or hemorrhage in the gland. Over 90% of the adrenal cortex must be destroyed
before obvious symptoms occur. Addison’s can strike at any age, equally affecting male and females.

• Addison’s is characterized by bronzing of the entire skin. Oral signs are diffuse pigmentation of
the gingiva, tongue, hard palate, and buccal mucosa. Although cutaneous pigmentation disappears
after therapy, pigmentation of the oral tissues persists. Melanosis is a common oral manifestation.
Addison’s disease is treated by administering cortisol (hydrocortisone) of prednisone.

• Addison’s results when underactive adrenal glands produce insufficient amounts of

corticosteroids.

• In 30% of people with Addison’s disease, the adrenal glands are destroyed by a cancer,
 amyloidosis, an infection like tuberculosis, or another identifiable disease.

• In the other 70% of people with Addison’s disease, the cause is unknown, but it is suspected the
adrenal glands are destroyed by an autoimmune reaction.

• Addison’s is characterized by hypotension, asthenia, increased pigmentation of the oral mucous

membrane and skin, low levels of serum sodium, chloride, and bicarbonate with an elevation of
serum potassium. Nausea and vomiting may be present. ↓ Na+, Cl-, HCO3-, but ↑K+

BASAL CELL CARCINOMA-the most common malignant tumor of the SKIN (the most common
skin cancer in humans). It occurs most frequently on the face and scalp of middle-aged to elderly
adults. The tumors begin as very small, shiny, firm raised growths on the skin and enlarge very slowly.
Upper face is a highly common site of Basal Cell Carcinoma.
• Basal Cell Carcinoma tumor is invasive, ulcerative, often indurated, and locally destructive but
DOES NOT METASTASIZE. It is almost always cured by surgical excision and the prognosis
is good. The tumor is radiosensitive, if necessary.

• Histologically, basal cell carcinoma is characterized by clusters of darkly staining cells with a
typical palisade arrangement of nuclei of the cells at the periphery of the tumor cell clusters.

• BCC IS THE MOST COMMON MALIGNANT SKIN TUMOR. It originates in the lowest
(innermost) layer of the epidermis (basal cell layer), and usually develops on skin surfaces
exposed to sunlight. Rather than spread (metastasize) to distant parts of the body, instead, it
invades and destroys surrounding tissues. Basal cell carcinoma is the least likely cancer to
metastasize. Basal cell carcinoma DOES NOT METASTASIZE.

URTICARIA (Hives)-represents enema of the superficial portions of the dermis.

• Angioedema (angioneurotic edema)-a condition in which the edema involves the deeper dermis
or subcutaneous adipose tissue. Both urticaria and angioedema are of rapid onset and can
either be just annoying or life threatening. Therapy includes epinephrine, antihistamines, or
steroids. Two Forms:
1. Hereditary Angioedema-due to autosomal dominant deficiency of activated C1
inhibitor; may be more dangerous due to possible visceral involvement.
2. Acquired Angioedema-often associated with lymphoid tumors.

Urticaria (Hives) Characteristics:

• Common affecting at least 25% of the population at some time during their life.
• Appears as pruritic skin wheals, produced by localized dermal edema due to mast cell
degranulation.
• In variant angioedema, there is edema in the subcutaneous tissue and dermis.
• Most cases are IgE dependent; reactions with allergens cause mast cell degranulation to release
histamine, which increases vascular permeability.

 NEUROLOGICAL DISORDERS
MULTIPLE SCLEROSIS-a demyelinating disease of the CNS in which nerves of the eye, brain, and
spinal cord lose patches of myelin. The cause is unknown, but it is believed to be due to an
autoimmune response where the immune system attacks a person’s own tissues (the body produces
antibodies against its own myelin). Symptoms appear in people 20-40 yrs.; women are more likely than
men to have the disease. It begins slowly and is characterized by exacerbations with long, asymptomatic
remissions. Large amounts of protein in cerebrospinal fluid are characteristic of MS.

• MS Sensory Symptoms: Numbness, tingling, and other abnormal sensations, visual

disturbances, dizziness or vertigo.

• MS Motor Function Symptoms: tremor, weakness, clumsiness, difficulty walking or

maintaining balance, double vision, stiffness, unsteadiness, unusual tiredness, constipation.

• Injectable interferon (a relatively new treatment) reduces the frequency of MS

relapses.

MYASTHENIA GRAVIS-immune system produces autoantibodies that attack Acetylcholine

receptors that lie on the muscle side of the neuromuscular junction causing dysfunction of the
myoneural junction. This decreases the responsiveness of the muscle fibers to acetylcholine released
from motor neuron endings. Difficulty speaking and swallowing, and weakness of the arms and legs are
common. About 10% of people develop a life-threatening weakness of the breathing muscles (a condition
called myasthenic crisis).

Myasthenia Gravis Characteristics:

• Occurs more frequently in women and begins between 20-40 years of age.
• An autoimmune disease in which the neuromuscular junction function abnormally, resulting in
episodes of muscle weakness.
• Most common symptoms are weakness of the eyes (drooping eyelids), double vision (caused by
weak eye muscles), and excessive, specific muscle fatigue after exercise.
• Affects muscles of the face, neck, arms, and legs.
• Drugs that increase the level of acetylcholine (e.g. pyridostigmine or neostigmine) may be given to
for treatment.

EATON-LAMBERT SYNDROME-similar to myasthenia gravis in that it is also an autoimmune

disease that causes weakness. However, Eaton-Lambert syndrome is caused by the inadequate
release of acetylcholine rather than by abnormal antibodies that attack acetylcholine receptors.

TETANY-a clinical neurological syndrome of muscles twitches, cramps, and carpopedal spasm.
When severe, laryngospasm and seizures develop. All of these signs and symptoms reflect irritability of
the central and peripheral nervous systems, usually resulting from low serum levels of calcium. Tetany
normally occurs when the blood concentration of calcium reaches 6mg% (normal is 10mg%). It is lethal
at 4mg%. Causes: Hypoparathyroidism, Rickets (Vitamin D deficiency), Hyperventilation, Uremia.
AMYOTROPHIC LATERAL SCLEROSIS (ALS or Lou Gehrig’s Disease)-disorder that involves
neuron death of voluntary muscles. Characterized by stiff muscles, muscle twitching leading to muscle
wasting. Results in difficulty speaking, swallowing, then breathing. Causing unknown and no cure.


CARDIAC & CEREBRAL DISORDERS

ANGINA (angina pectoris)-the classic symptom of CORONARY ARTERY DISEASE. Angina is a

temporary chest pain or sensation of pressure that occurs when the heart muscle is not receiving enough
oxygen. Angina is a crushing substernal pain that radiates to the left arm, neck, jaw, and shoulder blade.
Most people with chronic angina pectoris feel the pain only when they exercise. The load of the heart
becomes too great in relation to the coronary blood flow. The pain of angina pectoris is similar to
myocardial infarction except angina is relieved by rest or nitrates.

CORONARY ARTERY DISEASE-a condition in which fatty deposits (plaques) accumulate in the
cells lining the wall of the coronary artery and obstruct blood flow. As an obstruction of a coronary
artery worsens, ischemia (inadequate blood supply to the heart muscle) can develop causing heart
damage.
• major complications of coronary artery disease are ANGINA and HEART ATTACK.
Diagnosis of coronary artery disease (the leading cause of death in the U.S.) is usually based on
patient history, especially with characteristic risk factors (high blood pressure, elevated
cholesterol, cigarette smoking, overweight, and inactivity).

MYOCARDIAL INFARCTIONS-most commonly caused by coronary atherosclerosis (causes

interruption in the blood supply to the heart). Signs and symptoms: crushing pain in the chest area over the
heart, sweating, and GI upset. Myocardial infarctions are very common in males and postmenopausal
females. The prognosis of patients is fairly good if they reach the hospital. Most deaths occur outside the
hospital.

4 SERUM ENZYMES INCREASED AFTER a person suffers a MYOCARDIAL INFARCTION:

1. Serum Glutamate-Pyruvate Transaminase (SGPT).
2. Serum Glutamate-Oxaloacetic Transaminase (SGOT).
3. Serum Lactic Dehydrogenase (LDH).
4. Creatine Kinase (CK) = the first enzyme released in the blood after a heart-attack.

Arrhythmias (irregular heartbeats)-the most common cause of death in the early hours after the
onset of a myocardial infarction (heart attack). Arrhythmias may seriously interfere with the heart’s
pumping ability or may cause the heart to stop pumping effectively, leading to a loss of consciousness or
death. Arrhythmias account for 50% of deaths shortly after myocardial infarctions. Other
complications of myocardial infarction are cardiogenic shock, heart failure, ventricular rupture, and
embolism.

INECTIVE ENDOCARDITIS-inflammation of the smooth lining of the heart (endocardium), most often
from a bacterial infection. Infective endocarditis is an infection of the endocardium and heart valves.
Two types:
1. Acute infective endocarditis-most often caused by Staphylococcus aureus; often associated with
IV drug users. Causes more severe damage to the heart.
 2. Subacute (bacterial) endocarditis-caused by less virulent organisms like Streptococcus viridans
(alpha-hemolytic streptococcus); tends to occur in patients with congenital heart disease or
valvular heart disease.

Infective Endocarditis Facts:

• The mitral valve is the most commonly involved. Mitral valve & aortic valve are involved in
about 45% of cases; the tricuspid valve is involved in more than half the cases involving IV drug
users.
• A bacterial (less often, fungal) infection of the endocardium and heart valves.
• Can occur suddenly and be life-threatening within days (acute infective endocarditis), or it can
develop gradually over a period of weeks to months (subacute infective endocarditis).
• Characterized by accumulation of bacteria and blood clots on the valves (vegetations), that can
break loose and travel to vital organs where they can block arterial blood flow.
Diseased heart valves are areas where circulating bacteria (streptococci and staphylococci) accumulate
(form vegetations) and cause infection. Vegetations may separate from the heart valves and form emboli.

BACTEREMIAS in any patient with heart valve abnormalities may result in SBE. Other cardiac
abnormalities that may cause SBE include tetralogy of fallot, congenital aortic stenosis, patent ductus
arteriosus, and ventricular septal defects.

CONGESTIVE HEART FAILURE (CHF)-a serious condition in which the quantity of blood pumped
by the heart each minute (cardiac output) is insufficient to meet the body’s normal requirements for oxygen
and nutrients. Usually the left ventricle fails first, soon followed by right-side failure. The earliest and
most common clinical signs of CHF:
• exertional dyspnea
• paroxysmal nocturnal dyspnea (patient wakes up gasping for air)

Other CHF signs: peripheral edema (swollen ankles), Cyanosis, Orthopnea (sitting or standing in order
to breath comfortably), and high venous pressure.

LEFT-SIDED HEART FAILURE (LS-CHF): caused by coronary heart disease, hypertension, aortic
and mitral valvular disease, and myocardial diseases. A life threatening complication of LS-CHF is
pulmonary edema. The MOST reliable postmortem indicator of left ventricular cardiac failure is
chronic passive congestion of the lungs.

The most common cause of right-sided heart failure (RS-CHF) is preceding failure of the left
ventricle (LS-CHF). Pure RS-CHF is uncommon, but the most common cause of pure RS-CHF is Cor
pulmonale (right ventricular strain caused by lung disease or disease of pulmonary blood vessels). It is
usually the direct result of resistance to blood flow through the lungs. RS-CHF causes systemic
venous congestion and peripheral edema (swollen ankles).

ACUTE PERICARDITIS-inflammation of the pericardium (the flexible, stretchable, two-layered sac

that envelops the heart) that begins suddenly and is often painful; the inflammation causes fluid and blood
products like fibrin, RBC, and WBC to pour into the pericardial space.

CARDIAC TAMPONADE-the accumulation of fluid in the pericardium, which puts pressure on the
heart and interferes with its ability to pump blood. This can occur after a large myocardial infarction.
The dead heart musculature of a ventricle can rupture, causing blood loss into the pericardial space.
Because the heart is compressed, blood cannot flow into the right atrium and the patient can die
suddenly of decreased cardiac output. Signs of cardiac tamponade include distended neck veins,
hypotension, decreased heart sounds, tachypnea, and weak or absent peripheral pulses.
• CARDIAC TAMPONADE IS THE MOST SERIOUS COMPLICATION OF
PERICARDITIS, & is most likely to cause a SUDDEN ARREST OF HEART FUNCTION.

• Dissecting Aneurysm-results in aortic rupture most often into the pericardial sac causing fatal
cardiac tamponade.

CONSTRICTIVE PERICARDITIS-post-inflammatory thickening and scarring of the membrane

(pericardium) producing cardianc chamber constriction. Can be caused by tuberculosis (TB).

EDEMA-occurs when the volume of interstitial fluid exceeds the capacity of the lymphatics to return it to
the circulation. The physical cause of edema is positive pressure in the interstitial fluid spaces.
Conditions that cause extracellular fluid edema:
1. increased capillary pressure due to blockage of a vein.
2. decreased plasma colloid osmotic pressure due to decreased plasma protein.
3. increased interstitial fluid colloid osmotic pressure caused by a lymphatic obstruction.
4. increased capillary permeability which may occur in certain allergic responses.
5. when capillary filtration exceeds capillary absorption.
6. Inflammation causes local edema by dilating arterioles.
7. venous constriction and standing, cause increased capillary hydrostatic pressure and cause edema.

Prolonged sweating decreases extracellular volume and increases osmotic pressure due to increased
plasma protein.

Constriction of arterioles causes decreased capillary hydrostatic pressure causing decreased net
pressure across the capillary wall.

RHEUMATIC FEVER-inflammation of joints (arthritis) & heart (carditis) resulting from a

streptococcal infection of the throat. Aschoff Body-the classic lesion of rheumatic fever.
• Rheumatic Fever is a complication of an acute streptococcal infection, almost always a
pharyngitis (sore throat) caused by Streptococcal pyogenes (group A, -hemolytic Streptococcus).
Although rheumatic fever may follow a streptococcal infection, it is not an infection, but an
inflammatory reaction to an infection, affecting many body parts (joint, heart, skin).

• Rheumatic Fever is most common in children (5-15 years old). The onset is usually sudden.
Typically, symptoms begin several weeks after the disappearance of a streptococcal sore throat.
The major symptoms of rheumatic fever are joint pain (arthritis), fever, chest pain, or
palpitations caused by heart inflammation (carditis), jerky, uncontrollable movements (Sydenham’s
chorea), a rash (erythema marginatum), and small bumps (nodules) under the skin. Treatment:
penicillin and rest.

• All layers of the heart and heart valves are involved. MITRAL VALVE is the most frequently
 affected.

• Heart inflammation (carditis) disappears gradually within 5 months, but it may permanently
damage the heart valves, resulting in rheumatic heart disease. The valve between the left atrium
and ventricle (MITRAL VALVE) is most commonly damaged. The mitral valve may become leaky
(mitral valve regurgitation), abnormally narrow (mitral valve stenosis), or both. The pulmonary
valve is RARELY involved.

ASCHOFF BODY-is the typical lesion of rheumatic myocarditis (fever). It is an area of focal
interstitial myocardial inflammation characterized by fragmented collagen and fibrinoid material, by
large, unusual cells (Anitschkow cells), and by occasional multinucleated giant cells (Aschoff
myocytes).

Diagnosis of Rheumatic Fever is made when two major, or one major, and one minor criteria (Jones
criteria) are met.
• Major criteria: carditis, arthritis, chorea, erythema marginatum, and subcutaneous nodules.
• Minor criteria: fever, arthralgias, history of rheumatic fever, EKG changes, and lab tests.

CEREBRAL INFARCTION (STROKE)-an infarction of the cerebrum due to an arterial occlusion by a

thrombus or an embolus from the heart or carotid artery. Common signs and symptoms are sudden
paralysis of one side of the body, and numbness on the other side of the body.

CONCUSSION-a brief loss of consciousness and sometimes memory after an injury to the brain that
doesn’t cause obvious physical damage. Concussions cause brain malfunction, but do not cause visible
structural damage. Most people recover completely within a few hours or days. Once complication is
post-concussion syndrome.

HEMATOMA-the localized hemorrhage (escape of blood from the vasculature) within a tissue or organ.
Intracranial hematomas are collections of blood within the brain (subdural hematoma) or between the
brain and skull (epidural hematoma).
• Subdural hematomas-originate from bleeding from veins around the brain, and are a consequence
of head injury. Signs and symptoms are confusion, headaches, disorientation, and fluctuating
levels of consciousness or coma. These signs may gradually develop over time, occurring several
hours or even days after initial injury.

• Epidural hematomas-originate from bleeding from an artery. Usually caused by skull fractures.
Symptoms begin immediately (severe headache) and can lead to a deep coma.

TEMPORAL ARTERITIS-a chronic inflammatory disease of large arteries.

POLYARTERITIS NODOSA-a disease in which segments of medium-sized arteries become inflamed

and damaged, reducing the blood supply to the organs they supply.

CONGESTION (hyperemia)-a localized increase in the volume of blood in capillaries and small
vessels.
1. Active congestion (active hyperemia)-results from localized arteriolar dilation (e.g.
inflammation, blushing). Causes congestion in the early stages of inflammation.
 2. Passive congestion (passive hyperemia)-results from obstructive venous return or increased
back pressure from congestive heart failure. Two forms:

• Acute passive congestion-occurs in shock or right-sided heart failure.

• Chronic passive congestion-characterized by edema of alveolar walls and “heart

failure.” cells. Congestion of the lung is most often caused by left-sided heart failure.
Congestion of the liver is most often caused by right-sided heart failure.

If Hypertension is not diagnosed and treated with antihypertensive drugs, the individual can “wear out”
(cardiac failure), “blow out” (cerebrovascular accident), or “run out” (renal failure).

Prolonged Hypertension damages 3 organs:

1. HEART (60% die of complications)
2. BRAIN (15% die of complications)
3. KIDNEYS (25% die of complications)


HYPERTENSION (HTN) CLINICAL FINDINGS

Hypertension-a chronic condition where blood pressure in arteries is elevated. Measured by systolic and
diastolic, depending on the if the heart muscle is contracting (systole) or relaxed between beats
(diastole), which equals the maximum and minimum pressure, respectively. Normal BP at rest is between
100-140 mmHg systolic (top reading) and 60-90 mmHg diastolic (bottom reading). Hypertension is
when BP is above 140/90 mmHg or anyone on anti-hypertensives.

Cardiovascular: Blood pressure persistently above 140/90 (arterioles are constricted, causing abnormal
resistance to blood flow). Angina pain (insufficient blood flow to coronary vasculature).
• Dyspnea on exertion (left-sided heart failure).
• Edema of extremities (right-sided heart failure). Peripheral edema, liver congestion.
• Intermittent claudication (decrease in blood supply from the peripheral vessels to the legs).

Neurologic: severe occipital headaches with nausea and vomiting; drowsiness; giddiness; anxiety; mental
impairment (vessel damage within the brain, characteristic of severe hypertension).

Renal: Polyuria; nocturia, diminished ability to concentrate urine; protein and RBC in urine. (arteriolar
nephrosclerosis (hardening of arterioles within the kidney); 25% die of renal failure.

Ocular: retinal hemorrhage and exudates (damage to arterioles that supply the retina).

SECONDARY HYPERTENSION-is hypertension secondary to known causes; the most common cause
is from KIDNEY DISEASE. Causes of Secondary Hypertension:
• Kidney disease-renal artery stenosis, pyelonephritis, glomerulonephritis, kidney tumors, polycystic
kidney disease.
• Hormonal disorders-primary aldosteronism (Conn’s syndrome), acromegaly, Cushing’s syndrome,
pheochromocytoma.
• Drugs-oral contraceptives, corticosteroids, amphetamines.
• Congenital anomalies-coarctation of the aorta.

ESSENTIAL HYPERTENSION-hypertension of unknown etiology, and accounts for 90-95% of

cases. If left untreated, it can lead to retinal changes, left ventricular hypertrophy, and cardiac failure.
• Genetic factors: family history of hypertension, and is more common and more severe in blacks.
• Environmental factors: stress, obesity, smoking, and physical inactivity.

 RENAL DISORDERS
AMYLOIDOSIS-a disease in which amyloid (unusual protein normally not in the body, but accumulates
in various tissues). It is uncommon and usually affects adults (middle-age and older). Renal disease is the
first manifestation of amyloidosis. Many forms of amyloidosis exist:
1. Primary amyloidosis-cause is unknown; it is associated with abnormalities of plasma
cells (as is multiple myeloma) which may also be associated with amyloidosis. Typical
sites of amyloid buildup are the heart, lungs, skin, tongue, thyroid gland, intestines, liver,
kidney, and blood vessels.
2. Secondary amyloidosis-is secondary to another disease such as TB, rheumatoid arthritis,
or familial Mediterranean fever. Amyloid builds up in the spleen, liver, kidneys, adrenal
glands, and lymph nodes.
3. Hereditary amyloidosis-affects nerves and certain organs.

Amyloid-Associated Conditions include: Alzheimer’s disease, Familial Mediterranean fever,

Diabetes mellitus (type 2), and Senile amyloidosis. Deposits of amyloid are found in all of these
conditions. Ex: diabetes mellitus (type 2) has deposits of amyloid (amylin) in islet cells.

Accumulations of Endogenous Pigments:

1. Melanin-formed from tyrosine, and synthesized in melanocytes in stratum basale. Increased
melanin pigmentation is common in Addison’s Disease, while decreased melanin pigmentation
is seen in Albinism & Vitiligo.

2. Bilirubin-a yellowish breakdown product of normal HEME CATBOLISM caused by the

clearance of aged RBC that contain hemoglobin. Bilirubin accumulates in blood and organs
producing JAUNDICE. Jaundice is mostly caused by hemolytic anemia, biliary obstruction, and
hepatocellular disease. Bilirubin in excreted in BILE and URINE.

3. Hemosiderin-an insoluble, iron-containing protein derived from ferritin. It normally occurs in

small amounts within macrophages of bone marrow, liver, and spleen. It can accumulate in tissues
in excess amounts:
• Hemosiderosis-occurs when hemosiderin builds up in tissue macrophages. Usually doesn’t
cause tissue or organ damage. Often associated with thalassemia major.

• Hemochromatosis (bronzed disease)-an extensive accumulation of hemosiderin

throughout the body. There is tissue and organ damage. Most often is a hereditary disorder
that develops in men over 40 years old.

HEMATURIA-blood in the urine caused by bladder or kidney disease, glomerulonephritis, kidney

stones, kidney cysts, sickle-cell anemia, and hydronephrosis. Disorders characterized by the presence
of blood:
1. Hematemesis-vomiting bright red blood, indicating rapid upper GI bleeding. Commonly
associated with esophageal varices (common in alcoholics) or peptic ulcers. The rate and
 source of bleeding are determined by endoscopic examination. Treatment requires replacement of
blood by transfusion and administration of IV fluids to maintain fluid and electrolyte balance.

2. Hemoptysis-the coughing up of blood from the respiratory tract. Blood-streaked sputum often
occurs in minor upper respiratory infections or in bronchitis. Patients suffering from tuberculosis,
pneumonia, or bronchogenic carcinoma may also experience hemoptysis. The main symptom of
idiopathic pulmonary hemosiderosis (iron in the lungs) is hemoptysis.

NEPHROTIC SYNDROME (NEPHROSIS)-a syndrome (collection of symptoms) caused by many

diseases affecting the kidney, resulting in massive PROTEINURIA, Hypoalbuminemia, generalized
edema, hyperlipidemia, & hypercholesterolemia. These symptoms result from increased permeability of
glomerular capillaries. Diseases that can cause nephrotic syndrome: amyloidosis, cancer, diabetes,
leukemia, and SLE. Proteinuria is a major component of nephrotic syndrome.

PYELONEPHRITIS-renal inflammaton that most commonly occurs from a URINARY TRACT

INFECTION (Cystitis), especially in the presence of transient or persistent backflow of urine from the
bladder into the ureters or renal pelvis. It is a bacterial infection (E. COLI) of the renal pelvis
characterized by fever, flank pain, and tenderness.
1. Acute Pyelonephritis-an active infection of the renal pelvis, where the pelvis becomes inflamed
and filled with pus. Abscesses often develops.

2. Chronic Pyelonephritis-extensive scar tissue is formed in the kidney, and renal failure becomes
possible. It most often results from urinary reflux.

NEPHROLITHIASIS (Nephrocalcinosis)-the presence of calculi (kidney stones) within the renal

pelvis or calyces, produced by environmental, metabolic, and infection causing obstruction, infection,
hematuria, and pain. Are common and affect men more than women. Increased excretion of calcium in
the kidneys results in Nephrolithiasis.
• Many STONES are asymptomatic until they pass into the ureter. When this happens, it causes renal
colic (characterized by severe pain). Complications include obstruction of the ureter, acute or
chronic pyelonephritis, and hydronephrosis.

• HYPERPARATHYROIDISM IS THE MOST LIKELY CAUSE OF NEPHROLITHIASIS.

Excessive amounts of circulating PTH cause hypercalcemia leading to kidney stone formation.

MALIGNANT NEPHROSCLEROSIS (malignant hypertension)-a condition associated with severe

high blood pressure (malignant hypertension) in which the smallest arteries (arterioles) in the kidneys
are damaged, and kidney failure progresses rapidly.
• Malignant Hypertension-a severe hypertension causing degenerative changes in the walls of the
blood vessels throughout the body. Hemorrhages occur in the retina, kidney, and other areas.
Cerebral function is altered.

CHRONIC HYPERTENSION leads to reactive changes (arteriosclerosis) in the smaller arteries and
arterioles throughout the body. The vascular changes are particularly evident in the kidney, where the
changes cause loss of renal parenchyma (benign nephrosclerosis).
NEPHRITIC SYNDROME-a syndrome characterized by inflammatory rupture of the glomerular
capillaries with resultant bleeding into the urinary space. Clinical symptoms include Nephritis,
Hematuria, Hypertension, and Renal failure. Disorders manifested by the nephritic syndrome:
1. Acute glomerulonephritis-prototype of the nephritic syndrome; immune complex disease.

2. Rapidly progressive glomerulonephritis-progresses rapidly to renal failure.

3. Goodpasture’s Syndrome-glomerulonephritis associated with circulating antibodies against

basement membrane antigens.

4. Alport’s Syndrome (Hereditary Nephritis)-kidney function is poor, blood present in urine, and
deafness and eye abnormalities may occur.

• Nephritis-inflammation of the kidneys.

• Glomerulonephritis-inflammation of the glomeruli of the kidney.
• Benign Prostatic Hypertrophy (BPH)-enlargement of the prostate gland. It is not malignant or
inflammatory, but usually progressive and may lead to obstruction of the urethra.

ACUTE PROLIFERATIVE GLOMERULONEPHRITIS (Poststreptococcal Glomerulonephritis)-

inflammation of the glomeruli resulting in the sudden appearance of blood in the urine, with clumps of
RBC (CASTS) and variable amounts of protein in the urine.
• It most often follows or accompanies infection (strep throat) with certain strains of group A β-
hemolytic streptococci (S. pyogenes). It most commonly affects children.

• An IMMUNE COMPLEX DISEASE where glomeruli are damaged by the accumulation of

antigen from dead streptococci clumped together with the antibodies that neutralize them.
These clumps (immune complexes) coat glomeruli membranes and interfere with their filtering
function. Rheumatic fever is also related to streptococcal cross-antigenicity.

• Classic symptoms: fluid retention, periorbital edema; diminished urinary output, dark, tea-
colored urine; and elevation of blood pressure. Hematuria with RBC casts and proteinuria are
also characteristic.


KIDNEY CYSTIC DISEASES

Polycystic Kidney Disease-a hereditary disorder where many cysts form in both kidneys. The kidneys
grow larger, but have less function. Two types:
1. Adult Polycystic Kidney Disease-an autosomal dominant disease; starts in 30-40s, occurs
bilaterally; manifested clinically by hypertension, hematuria, and flank pain. Frequently associated
with berry aneurysm of the circle of Willis. MOST COMMON INHERITED KIDNEY
DISORDER.

2. Infantile Polycystic Kidney Disease-an autosomal recessive disease, evident at birth; results in
death shortly after birth.

Medullary Cystic Disease-a disorder where kidney failure develops along with cysts deep within the
kidneys (in medulla). It is uncommon and affects older children.

Medullary Sponge Kidney-a congenital disorder in which the urine-containing tubules of the kidneys are
dilated, causing the kidney tissue to appear spongy. Infection may exist and kidney stones may form.

UROLITHIASIS-an obstructive condition resulting from the presence or formation of calculi

(calcium stones) in the urinary tract. Most of these calculi are CALCIUM STONES. Accounts for 80-
90% of urinary stones composed of calcium oxalate, calcium phosphate, or both.

AN OBSTRUCTION ANYWHERE along the urinary tract-from the kidneys (where urine is produced),
to the urethra, (through which urine leaves the body)—can increase pressure inside the urinary tract and
slow urine flow. Urinary tract obstruction manifest clinically by:
• Renal colic-excruciating flank pain caused by the passage of a stone into the ureters.

• Hydronephrosis-distention of the kidney with urine caused by backward pressure on the kidney
when urine flow is obstructed.

• Infection-occurs at the obstruction site. Kidney infections are usually caused by bacteria
ASCENDING from the lower urinary tract.

Pyelonephritis & Benign Prostatic Hypertrophy involve URINARY TRACT OBSTRUCTION.

RENIN-a small protein enzyme PRODUCED in the KIDNEYS. Renin is synthesized and stored in an
inactive form (PRORENIN) in the juxtaglomerular cells of the kidneys and released in response to low
arterial blood pressure. Renin raises arterial pressure helping to correct the initial fall in pressure.
DECREASE IN ARTERIAL PRESSURE = INCREASES KIDNEY RENIN SECRETION.

• RENIN acts on the precursor substance Angiotensinogen (manufactured by the liver and is
present in blood). Renin converts angiotensinogen to angiotensin I. Then, angiotensin I is
converted to angiotensin II by a converting enzyme associated with the walls of blood capillaries
in the lungs.
• ANGIOTENSIN II-stimulates the synthesis and secretion of ALDOSTERONE by the zona
glomerulosa of the adrenal cortex. Aldosterone-increases NaCl (sodium chloride) reabsorption
by the kidney’s distal convoluted tubules and collecting ducts to increase blood volume arterial
pressure.

 OCULAR DISORDERS
TRACHOMA-prolonged infection of conjunctiva caused by the bacterium Chlamydia trachomatis.
Trachoma is highly contagious in its early stages and is transmitted by eye-hand contact, certain flies, or
contaminated articles (towels and handkerchiefs). Trachoma is one of the chief causes of blindness in
some parts of the world.
• Common in poverty-stricken parts of dry, hot Mediterranean countries and Far East.

• In the early stages of trachoma, the conjunctiva is inflamed, reddened, irritated, and a
discharge appears.

• In the later stages of trachoma, the conjunctiva and cornea become scarred, causing the
eyelashes to turn inward, and vision to become impaired.

OTHER CONJUNCTIVA DISORDERS:

1. Keratoconjunctivitis Sicca-a long standing dryness of both eyes, leading to dehydration of the
conjunctiva and cornea. Dry eyes may be a symptom of diseases like rheumatoid arthritis, SLE, or
Sjogren’s syndrome.

2. Inclusion conjunctivitis-a conjunctivitis (inflammation of the eye conjunctiva) caused by

Chlamydia trachomatis that often affects newborns, but is also contracted by adults in swimming
pools or during sexual contact. It is characterized by enlarged papilla on inner eyelids and a
purulent discharge.

3. Pinkeye (acute contagious conjunctivitis)-an acute, contagious form of conjunctivitis, caused by

the bacterium Hemophilus aegyptius and characterized by inflammation of the eyelids and
eyeballs with a mucopurulent discharge.

UVEITIS-inflammation of the uveal tract of the eye (iris), ciliary body, and choroids. Causing redness,
pain, and blurred vision. Mainly affects people 20-50 years old. Caused by infection, injury, or
autoimmune.

 AUTOIMMUNE DISORDERS
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)-a chronic inflammatory disease (autoimmune
disease) that commonly involves the skin, serosa, joints, kidneys, heart, blood vessels, blood cells,
and CNS. It typically affects young adult women, with acute attacks and remissions recurring over
several years. Hematologic disorders are common. Renal failure occurs in most patients and is the
usual cause of death. Severe CNS involvement may appear. Acrocyanosis (Raynaud’s phenomenon) is
often associated with SLE. Immunosuppressive therapy and corticosteroid medication allow prolonged
survival. SLE Characteristics:
• Appearance of erythematous malar “BUTTERFLY RASH” on the face (cheeks and bridge of
nose); skin rash, sensitivity to light, mouth sores
• Fluid around the lungs, heart, or other organs.
• Arthritis, kidney, nerve, or brain dysfunction, anemia.
• Many autoimmune diseases are associated with characteristic auto-antibodies. Anti-DNA and
anti-Sm antibodies appear to be specific to SLE.
• Immune-complex-mediated hypersensitivity is a reaction of SLE the produces the MOST
visceral damage.

SJOGREN’S SYNDROME- an autoimmune disease marked chiefly by CHRONIC

INFLAMMATION caused by white blood cell infiltration of the salivary and lacrimal glands. It
usually progresses to fibrosis and atrophy of these glands. IgA is the most abundant antibody in
SALIVA.
• Findings found in Sjogren’s Syndrome:
1. Associated C.T. disorders (e.g. rheumatoid arthritis).
2. Xerostomia (dry mouth).
3. Keratoconjunctivitis Sicca (dry, burning eyes),
4. Peripheral neuropathy and sicca syndrome.

All 3 symptoms of the triad rarely occur in one patient. A definite diagnosis can be made only when at
least two of the symptoms are present. It is less common than rheumatoid arthritis and more prevalent in
women than men. Occasionally, the lymphocytic infiltration is massive and causes enlargement of the
glands (called Mikulicz’s syndrome).

• The decrease in salivation may cause rampant caries reminiscent of radiation caries due to a shift
toward a more acidogenic microflora

TYPE III HYPERSENSITIVTY REACTIONS-caused by IMMUNE COMPLEX DISEASES (serum

sickness, systemic lupus erythematosus, rheumatoid arthritis, and glomerulonephritis). Type 3
hypersensitivity reactions involve soluble antigens, antibodies, and complement, that initiate an
inflammatory response. This inflammatory response is part of the normal immune response, but if there
are large excesses of antigen, the antigen-antibody-complement complexes may circulate and become
deposited in various tissues. Inflammatory reactions from such deposition of immune complexes can
cause physiological damage to kidneys, joints, vascular endothelium, and skin.
 • Arthus reaction, Farmer’s lung, Cheesemaker’s lung, Pigeon fancier’s disease, serum sickness, and
rheumatoid arthritis (RA).

TYPE III Hypersensitivity Reactions:

1. SERUM SICKNESS-an acute, self-limited disease that occurs 6-8 days after injecting a
foreign protein (bovine albumin), characterized by fever, arthralgias, vasculitis, & an acute
glomerulonephritis. Serum sickness is an example of a systemic Arthus reaction.
• Serum sickness is a reaction that is a type of immune complex disorder (Type 3
hypersensitivity) that results when patients are given large doses of foreign serum (most
often horse serum). The antigens in these serums stimulate an immune response. Immune
complexes form between the residual antigens and circulating antibody. These antigen-antibody
complexes are then deposited at certain body sites (joints, kidneys, and vessel walls).

2. ARTHUS REACTION-another type of immune complex disorder that involves severe local
sensitivity at the site of injection of antigen. This reaction requires prior sensitization. When an
antigen-antibody complex initiates such a reaction in alveoli, symptoms include fever, cough, and
difficulty breathing. Symptoms typically develop over 4-6 hour period. The attack subsides within
a few days.

3. SYSTEMIC LUPUS ERYTHEMATOSUS (Lupus)-an autoimmune disease that results in

episodes of inflammation of joints, tendons, and other C.T. and organs.

HISTAMINE DOES NOT PLAY A ROLE IN ABOVE TYPE 3 HYPERSENSITIVITY

REACTIONS.

 IMMUNOLOGY
MAIN FUNCTION of the IMMUNE SYSTEM is to prevent or limit infections by microorganisms
(bacteria, viruses, fungi, and parasites). Protection is provided by cell-mediated and antibody-
mediated (humoral) arms of the immune system:

1. CELLULAR IMMUNITY-a specific acquired immunity involving T cells. It acts to resist

most intracellular pathogens (bacteria and viruses). It involves soluble factors from T-
lymphocytes (lymphokines) and macrophages (monokines).
• Cell mediated immunity (arm) consists primarily of T-lymphocytes (e.g. helper T cells and
cytotoxic T cells).

2. HUMORAL IMMUNITY (antibody-mediated immunity)-immunity produced by the activation

of the B-lymphocyte population which produces immunoglobulins (IgA, IgD, IgM). Circulating
antibodies are produced by plasma cells (are differentiated B cells) within lymphatic tissue. The
key to humoral immunity is the ability of antibodies to react specifically with antigens. This
type of immunity provides PROTECTIONS AGAINST ENCAPSULATED BACTERIA.
• Antibody-mediated immunity (humoral immunity) involves B-lymphocytes & plasma cells.

Complement & Phagocytes are two other MAJOR IMMUNE SYSTEM COMPONENTS.

NATURAL (INNATE) IMMUNITY-immunity that occurs naturally as a result of a person’s genetic

constitution or physiology, and does not arise from a previous infection or vaccination. It is
nonspecific, does not improve after exposure to the organism, and its processes have no memory.
• Natural immunity (innate) is resistance not acquired through contact with an antigen.

ACQUIRED IMMUNITY-occurs AFTER EXPOSURE to an agent, improves upon repeated

exposure, and is specific. It is mediated by antibody and T-lymphocytes (T helper and cytotoxic T cells).
The cells responsible for acquired immunity have long-term memory for a specific antigen. Acquired
immunity is specific, improves after repeated exposure, and has “long-term” memory for an antigen.

ACQUIRED IMMUNITY-occurs naturally and artificially. It can be ACTIVE or PASSIVE.

• Naturally (innate) Active immunity-person is exposed to an antigen and the body produces
antibodies.

• Naturally (innate) Passive immunity-antibodies (IgG) passed from mother to fetus during
pregnancy and IgA passed from mother to newborn during breast-feeding.

• Artificially Active immunity-vaccination with killed, inactivated, or attenuated bacteria or

toxoid.

• Artificially Passive immunity-injection of immune serum or gamma-globulin.

ACTIVE IMMUNITY-the host actively produces an immune response consisting of antibodies and
activated helper and cytotoxic T lymphocytes. The main advantage of active immunity is
RESISTANCE IS LONG TERM (years). The major disadvantage is its SLOW ONSET.

PASSIVE IMMUNITY-antibodies are preformed in another host. It is not as permanent and does not
last as long as active immunity. Main advantage is IMMEDIATE AVAILABILITY OF
ANTIBODIES; the major disadvantage is the SHORT DURATION (months).

HYPERSENSITIVITY-an exaggerated immunological response upon re-exposure to a specific antigen

(positive skin test after having a disease). HYPERSENSITIVITY REACTIONS:

1. TYPE I (anaphylactic type) immediate hypersensitivity: a specific cytotropic antibody (IgE) binds
to receptors on basophils and mast cells and reacts with a specific antigen. IgE antibody mediated-
mast cell activation and degranulation. Ex: “Hay fever”, asthma, anaphylaxis.
• During a Type I hypersensitivity reaction, leukotrienes and prostaglandins D2 are generated
from Arachidonic acid. Also causes atopic allergies.

2. TYPE II (cytotoxic type) cytotoxic antibodies: cytotoxic (IgG, IgM) antibodies form against cell
surface antigens. Complement is usually involved. Ex: Autoimmune hemolytic anemias, antibody-
dependent cellular toxicity (ADCC), Goopasture disease.

3. TYPE III (immune complex type) immune complex disease: Antibodies (IgG, IgM, IgA) formed
against exogenous or endogenous antigens. Complement and leukocytes (neutrophils, macrophages)
are often involved. Ex: Autoimmune disease (SLE, rheumatoid arthritis), most types of
glomerulonephritis.

4. TYPE IV (cell-mediated type)-delayed type hypersensitivity: Mononuclear cells (T lymphocytes,

macrophages are the cellular infiltrates) with interleukin and lymphokine production. Ex:
Granulomatous diseases (tuberculosis, sarcoidosis).

5. TYPE V (auto-immune Disease)-reaction that occurs when IgG antibodies directed toward cell
surface antigens have a stimulating effect on their target. Ex: Graves Disease (antigen-antibody
complex on the follicular cell surface causes excess secretion of thyroid hormone as if were TSH).
ATOPIC ALLERGIES-caused by a localized expression of Type I hypersensitivity reactions. The
interaction of antigens (allergens) with cell-bound IgE on the mucosal membranes of the upper
respiratory tract and conjunctival tissues initiates a localized Type I hypersensitivity reaction.

Atopic Allergies (ATOPY)-a hereditary disorder marked by the tendency to develop immediate allergic
reactions to substances such as pollen, food, dander, and insect venoms. IgE antibodies are associated
with Atopic Allergies which include:
1. Hay Fever-when the allergen interacts with sensitized cells of the upper respiratory tract.
Symptoms include coughing, sneezing, congestion, tearing eyes, and respiratory difficulties. The
primary mediator is histamine, released from sensitized mast and basophil cells.

2. Bronchial asthma-the allergic reaction primarily affects the lower respiratory tract. It is common
in children characterized by shortness of breath and wheezing. Specific IgE antibodies or
nonspecific inhaled irritants provoke mast cell degranulation; histamine, leukotrienes (SRS-As),
 and other mediators are released to cause bronchospasm and bronchial mucus secretion.

ANAPHYLATOXINS-substances that may cause RELEASE OF HISTAMINE and other compounds that
cause hypersensitivity, thus triggering some, or all of the symptoms of anaphylaxis. Complement
components C3a, C4a, C5a are anaphylatoxins that cause degranulation of mast cells with release
of mediators (e.g. histamine), leading to increased vascular permeability and smooth muscle
contraction, especially contraction of the bronchioles leading to bronchospasm.
• C5a is by far, the MOST POTENT ANAPHYLATOXINS. Anaphylaxis caused by these
components is less common than anaphylaxis caused by Type I (IgE-mediated) hypersensitivity.

• Anaphylatoxins produce inflammation, cause enhanced capillary permeability, induce smooth

muscle contraction, and cause hypotension.

COMPLEMENT FIXATION-the binding of active complement to a specific antigen-antibody pair used

in diagnostic tests such as Wassermann test (for syphilis), to detect the presence of a specific antigen or
antibody. Only IgM and IgG fix complement.

ANAPHYLACTIC SHOCK (severe anaphylaxis)-a serious condition that occurs suddenly in an

allergic individual exposed to an antigen. It may occur within seconds or minutes after exposure (i.e.
injection of a drug into a patient allergic to this drug may lead to death). The first symptoms of severe
anaphylaxis are intense anxiety, weakness, sweating, shortness of breath, and generalized urticaria.
Constriction of the bronchioli and drop in blood pressure are usual causes of death.
• Immediate treatment for anaphylactic shock: in a conscious patient (inject epinephrine IM or
subcutaneously. In an unconscious patient (inject epinephrine intravenously). Maintain the airway
(remember ABCs of CPR).

• Anaphylactic shock (anaphylaxis)-a physiological shock resulting from an anaphylactic

hypersensitivity reaction (i.e. penicillin or bee stings). In severe cases, death results in minutes.
This anaphylactic reaction involves the degranulation of mast cells and release of histamine,
heparin, platelet-activating factors, SRS-As, and serotonin into the bloodstream. HISTAMINE IS
RESPONSIBLE FOR THE PRINCIPAL SYMPTOMS OF ANAPHYLAXIS.

SLOW-REACTING SUBSTANCES OF ANAPHYLASIS (SRS-As)-consists of LEUKOTRIENES

(C4, D4, E4). SRS-As are responsible for the development of much of the clinical symptomatology
associated with allergic-type reactions. Leukotrienes are 100-1000x as potent as histamine or
prostaglandins in constricting bronchi.

• ONCE ARACHIDONIC ACID is generated by inflammatory cells and injured tissues, it is

metabolized through two pathways:
1. Cyclooxygenation pathway-produces prostacyclin, prostaglandins & thromboxanes.
2. Lipoxygenation-produces leukotrienes, HETEs, & diHETEs.

In asthma, the allergen reaction occurs in the bronchioles of the lungs. The most important products
released from the mast cell are SRS-As (the primary mediators of asthma), which causes spasm of
bronchiolar smooth muscle.
COMPLEMENT SYSTEM-part of the immune system that functions to DESTROY FOREIGN
SUBSTANCES directly or in conjunction with other immune system components. The complement system
comprises more than 25 proteins that act in a cascade with one protein activating the next protein. Two
distinct pathways activate the complement system (it may be activated at C1 or C3):
1. Alternate pathway-activated by certain microbial products (endotoxins) or antigens. Activation
at C3 is “alternate pathway”.

2. Classical pathway-activated by specific antibodies bound to their antigens (immune complexes).

Activation at C1 is “classical pathway”, and is the result of immune complexes.
• C1 is a constituent of the classical complement pathway, and is composed of three
proteins (C1q, C1r, and C1s). Calcium is required for C1 activation. C1 is made in GI
epithelium.

Complement system is activated at either C1 or C3. Activation at C3 (alternate pathway) is due to

bacterial endotoxins. Both pathways lead to C3b production (the central molecule of the complement
cascade). Either pathway results in CELL LYSIS.
• CYTOLYSIS-the lysis of bacteria or of cells (tumor or RBC) by insertion of the membrane
attack complex-derived from complement activation, and is the end product of activation of the
complement cascade. The membrane attack complex consists of C5b, C6,C7,C8 and C9, and
causes cytolysis.

Biologic consequences of complement activation: chemotaxis of phagocytes, immune adherence and

opsonization, anaphylatoxin activity, and membrane activity.

CHEMOTAXIS-cell movement to the inflammatory site in response to chemical signals during an

infection. Neutrophils are highly attracted to injured tissue through CHEMOTAXIS and are the
FIRST RESPONDERS to inflammation (they are the most abundant WBCs in the body).

COMPLEMENT-complement proteins are synthesized mainly by the LIVER, but some are made in
macrophages. Complement is a group of serum proteins that are the primary mediator of antigen-
antibody reactions. Complement’s 25 different proteins participate in lysis of foreign cells,
inflammation, and phagocytosis. Complement is present in normal human serum, is heat-labile, but is
NOT an immunoglobulin.
• COMPLEMENT consists of at least 25 serologically nonspecific glycoproteins designated C1,
C2, C3 and so on. They are present in normal blood serum and plasma, and are activated
sequentially in a cascade-like mechanism, which allows them to combine with antibodies and
destroy bacteria and other foreign cells.

IMMUNOGLOBULINS (antibodies)-glycoproteins found in blood serum synthesized by plasma cells

in the spleen and lymph nodes in response to the detection of a foreign antigen. Immunoglobulins mediate
anaphylaxis, atopic allergies, serum sickness, and Arthus reactions.

SIgA (“secretory immunoglobulin”)- immunoglobulin (antibody) present in various secretions

(SALIVA, tears, breast milk, and especially colostrums). IgA is one of the most prevalent humoral
antibodies (second only to IgG) produced by the body. SIgA is resistant to hydrolysis by microbial
proteolytic enzymes.
 • IgA is important in the respiratory, GI, and urinary tracts where it plays a major role in protecting
surface tissues against invasion by pathogenic microorganisms. The primary function of SIgA
is prevention of penetration of mucosa by microorganisms.

• IgA provides the primary defense at mucosal surfaces such as bronchioles, nasal mucosa,
vagina, prostate, and intestine. IgA molecules bind with surface antigens of microorganisms,
preventing the adherence and ingress of antigen through the mucosa of the respiratory, GI, and
urinary tracts.

• IgA is the second most abundant; occurs in body secretions and protects surface tissues;
synthesized by PLASMA CELLS in the mucous membranes of the GI, respiratory, and urinary
tracts.

IgG-the MOST ABUNDANT, and only immunoglobulin that CROSSES THE PLACENTA; main
defense against various pathogenic organisms.

IgD-makes up less than 1% of immunoglobulins; present on the membrane of many circulating B-cells. Its
function is unknown or not fully understood.

IgM-LARGEST immunoglobulin, first antibody produced in response to infection; powerful activator

of the complement system. First antibody produced by infants.

IgE-present only in only trace amounts in serum; reagenic activity resides in this immunoglobulin;
protects external mucosal surfaces; tightly bound to its receptors on mast cells and basophils; responsible
for Type I hypersensitivity reactions (allergic and anaphylactic).
• IgE is involved in HIVES and HAY FEVER

HAPTEN-a small foreign molecule that IS NOT IMMUNOGENIC ALONE, but can react with a
specific antibody. Haptens have antigenic determinants, but are too small to elicit the formation of
antibodies by themselves. They can do so when covalently bound to a “carrier” protein. Many drugs
(ex: penicillins) are haptens and the catechol in plant oil that causes poison oak is a hapten. Haptens are
not immunogenic, because they cannot activate helper T cells.

PLASMIDS-extra-chromosomal, double-stranded, circular DNA molecules capable of replicating

independent of the bacterial chromosome. Multiple drug resistance is related most closely to bacterial
plasmids. Most antibiotic resistance in bacteria is caused by genes carried on plasmids.

• Plasmids confer conjugal fertility, carry genetic information, and exist as extra-chromosomal
elements in bacteria.

• PLASMIDS are extra chromosomal genetic structures that can replicate independently within
a bacterial cell. The molecules of DNA are separate from the bacterial chromosomes and
determine traits not essential for the viability of the organism, but that in some way change the
organism’s ability to adapt.

• R (resistance) factor is an example: MOST ANTIBIOTIC RESISTANCE in bacteria is caused

by genes carried on plasmids. Plasmids can be passed from one bacterium to another, and are
 replicated in later generations of any bacterium carrying them.

IMMUNOGENS (antigens)-molecules that induce an immune response. Antigens include ALL

PROTEINS (proteins are the most antigenic), most polysaccharides, nucleoproteins, and
lipoproteins.
• Epitope-the antibody binding site on an antigen for a specific antibody.

IMMUNOFLUORESCENCE (fluorescent antibody)-a technique where fluorescent dyes (fluorescein

and rhodamine) are covalently attached to antibody molecules and are made visible by UV light in the
fluorescence microscope. Such “labeled” antibody can be used to identify antigens on the surface of
bacteria.
• Immunofluorescence is the most frequently employed diagnostic laboratory technique for the
microscopic detection of antigens in tissue secretions or in cell suspensions.

RADIOIMMUNOASSAY (RIA)-a method used for the quantification of antigens or haptens that can be
radioactively labeled.

ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)-a sensitive immunoassay that uses an

enzyme linked to an antibody or antigen as a marker for detecting a specific protein, especially an
antigen (toxin). ELISA can be used for the quantification of either antigens or antibodies in patient
specimens.

PRECIPITATION (Precipitin)-a test where the antigen is a solution. The antibody cross-links antigen
molecules in variable proportions and aggregates (precipitates) form.

AGGLUTINATION-a test where the antigen is a particulate (e.g. bacteria and RBC). Antibody
(agglutinins), because it is divalent or multivalent, cross-links the antigen multivalent particles and forms
a latticework, and clumping (agglutination) is seen. If the antigens are on the RBC surface and adding
antibody leads to clumping of the cells = Hemagglutination. Hemagglutination is the basis for blood
typing and distinguishing the presence of A type antigen or B type antigen on the surface of human
RBC.

BLOOD TYPES:
1. TYPE AB (blood)-indicates BOTH antigens (alloantigens); both antibodies (agglutinins) are absent
from type AB blood plasma. UNIVERSAL RECIPIENT. Contains A and B antigens.

2. TYPE O (blood)-has neither A nor B antigen (agglutinogens) on erythrocytes, but contains antibodies
(agglutinins anti-A and anti-B in its plasma. UNIVERSAL DONOR.

3. TYPE A (blood)- plasma components are devoid of anti-A, but contain A antigens on erythrocytes,
and anti-A antibodies (agglutinins) in plasma.

4. TYPE B (blood)-plasma components are devoid of anti-B agglutinins, but contain B antigens on
erythrocytes, and Anti-A antibodies in plasma.

CYTOKINES-hormone-like soluble proteins secreted by lymphocytes, macrophages, fibroblasts, and

platelets that act as intercellular messengers to regulate many cell functions especially functions
involving immunologic and inflammatory responses. Cytokines: interleukins, interferons,
lymphokines, & monokines.

INTERLEUKINS-act as messengers between leukocytes involved in immunologic or inflammatory

responses:
• Interleukin-1 (IL-1)-produced by activated macrophage-derived factor that stimulates activities
of T-cells, B-cells, and macrophages.

• Interleukin-2 (IL-2)-a lymphocyte-derived factor that stimulates antigen-activated T helper and

T killer cells. Activates killer T-cells.

• Interleukin-3 (IL-3)-a T-cell product that stimulates the growth and differentiation of various
blood cells.

INTERFERONS-a family of inducible glycoproteins produced by eukaryotic cells in response to viral

infections. Interferon proteins are elaborated by infected host cells that protect non-infected cells from
viral infections. Interferons do not block the entry of the virus into a cell, but prevent the replication
of viral pathogens within protected cells.

• Interferons are not antiviral substances, as they have no direct effect on viruses. Their
antiviral action is mediated by cells in which they induce an antiviral state. Interferon is a
nonspecific resistance factor (as are lysozyme, complement, etc.) because interferon proteins do
not exhibit specificity toward a particular pathogen, which means interferon produced in response
to one virus is also effective in preventing replication of other viruses. Interferons act to prevent
the replication of a range of viruses by inducing resistance.

• Interferons are a group of glycoproteins produced by eukaryotic cells in response to viral

infections. They are elaborated by infected host cells and protect non-infected cells from viral
infections. Interferons are nonspecific resistance factors that inhibit the growth of viruses by
blocking translation of viral proteins. Interferons are cytokines with immunomodulating functions.

MONOKINES-cytokines produced by the activation of monocytes.

LYMPHOKINES-cytokines produced by sensitized lymphocytes.

CHEMOKINES-a group of cytokines that attract either macrophages or neutrophils to the infection site.

HISTAMINE-substance formed from histidine by decarboxylation and released from coarse

cytoplasmic granules from tissue MAST CELLS & BASOPHILS. In the early stages of acute
inflammation, histamine mediates the contraction of endothelial cells, increasing vascular
permeability. Histamine is liberated by degranulation triggered by the following stimuli:
• Binding of specific antigen to basophil and mast cell membrane bound IgE.
• Binding of anaphylatoxins (C3a and C5a) to specific cell-surface receptors on basophils and
mast cells.
• Histamine release from mast cells or basophiles requires IgE antibodies to be attached to
mast cells to react with the antigen.
Histamine is responsible for the principal symptoms of ANAPHYLAXIS. Histamine release within
the body causes: increased capillary permeability, increased gastric secretion, bronchiolar
constriction, and fall in blood pressure.
• Histamine plays a major role in immediate hypersensitivity of asthma, urticaria, and anaphylaxis

SEROTONIN (5-hydroxytryptamine)-a compound in blood platelets and serum that causes

vasoconstriction. Acts as a neurotransmitter and is synthesized from the amino acid TRYPTOPHAN by
enteroendocrine cells in the gut and bronchi. Its actions are similar to histamine. Serotonin increases
constricts blood vessels and stimulates platelet aggregation (blood clotting). Most serotonin is found
in cells of the intestinal mucosa. Smaller amounts of serotonin occur in platelets and in the CNS.
• In the CNS, Serotonin acts as a neurotransmitter and an inhibitor of pain pathways in the
spinal cord. Its action in the brain controls a person’s mood, and may cause sleep.

• Serotonin is secreted in tremendous quantities by CARCINOID TUMORS (rare, slow-growing

tumors composed of chromaffin tissue).

• Serotonin is a neurotransmitter in the brain, plays a role in temperature regulation, sensory

perception, and in onset of sleep.

• Lysergic acid diethylamide blocks the action of serotonin in the brain.

BRADYKININ-a vasoactive kinin that mediates vascular permeability, arteriolar dilation, and pain.
Bradykinin is a POTENT VASODILATOR produced by the action of kallikrein (generated by
activated Hageman factor, factor XIIa) on an alpha 2-globulin (kininogen). It may be involved in BP
regulation.

PROSTAGLANDINS and related substances (prostacyclin, thromboxanes, and leukotrienes) are

LOCAL CHEMICAL MESSENGERS present in almost every body tissue, and exert their effects in the
tissues that synthesize them.

ARACHIDONIC ACID (an unsaturated fatty acid)-the major compound from which prostaglandins,
prostacyclin, thromboxanes, and leukotrienes are derived. Arachidonic acid is a part of phospholipids
in the plasma membranes of cells. When a cell is stimulated by a neurotransmitter or hormone, a plasma-
membrane enzyme (phospholipase A) is activated, and splits arachidonic acid from the phospholipids.

Different Metabolic Pathways utilize different enzymes to convert arachidonic acid into the
different messengers:
• To form prostaglandins, prostacyclin, or thromboxanes, CYCLOOXYGENASE PATHWAY
utilizes the enzyme cyclooxygenase.

• To form leukotrienes, the LIPOXYGENASE PATHWAY utilizes the enzyme lipoxygenase.

CYTOCHROMES-respiratory enzymes capable of undergoing alternate reduction and oxidation.

Cytochromes contain a central iron atom cycled between the oxidized ferric state (Fe3+) and the
reduced state (Fe2+). Through a series of oxidation-reduction reactions, the electron is passed to a
terminal electron acceptor. Cytochromes are chemically related to hemoglobin. Types of
Cytochromes:
 • Cytochrome oxidase-the terminal enzyme in the chain of events that constitutes cellular oxygen
consumption. Found in mitochondria.

• Cytochrome P450-important in drug metabolism. Found in liver microsomes (small particles of

fragmented endoplasmic reticulum with attached ribosomes).

• Cytochrome b-a cytochrome of the respiratory chain.

• Cytochrome b5-a Cytochrome in the endoplasmic reticulum.

Fibrinolysin (Plasmin)-a proteolytic enzyme derived from plasminogen essential in blood clot
dissolution (fibrinolysis). It is the most important fibrinolytic protease. Plasmin is NOT a component of
the body’s nonspecific disease mechanism.

Plasminogen-the inactive precursor to plasmin present in tissues, body fluids, circulating blood, and
clots.

Fibrinogen-a plasma protein essential for coagulation of blood, and is converted to fibrin by thrombin
and ionized calcium.

Fibrin-a stringy, insoluble protein responsible for the semisolid character of a blood clot. It serves as a
template for fibroblasts to repair tissue and wall off the area to infection. It is the product of the action of
thrombin on fibrinogen in the clotting process. Fibrin threads then entraps blood cells, platelets, and
plasma to form a blood clot.

Fibrinolysis-restores blood flow in the vessels occluded by a thrombus and facilitates healing after
inflammation and injury.

In the presence of thromboplastin and calcium ions, prothrombin is converted to thrombin, which then
converts fibrinogen to fibrin. Fibrin threads then entraps blood cells, platelets, and plasma to form a
blood clot.

 CELLULAR DISORDERS
HISTIOCYTOSIS X-can affect a single site, (bone or lymph nodes), or can involve multiple organs.
These diseases are characterized by proliferation of histiocytes (macrophages) of loose connective
tissue. Histiocytosis X includes:
1. Eosinophilic granuloma-most benign form of histiocytosis X. More common in males (20 years
age). May be totally asymptomatic, however, there may be local pain or swelling. In the mouth, the
mandible is most likely affected, with teeth on the affected side being loose with signs of
gingivitis.

2. Letterer-Siwe disease-syndrome that affects infants (2 and under) and is fatal. Child develops a
skin rash with persistent fever and malaise. Anemia, hemorrhage, splenomegaly,
lymphadenopathy, and localized tumefactions over bones are usually present. Oral lesions are
uncommon.

3. Hand-Schuller-Christian Disease-occurs early in life, usually before age 5. It is more common in

boys. There is a triad of symptoms (exophthalmos, diabetes insipidus, and bone destruction-
skull & jaws). Oral signs include bad breath, sore mouth, and loose teeth. Treatment: radiation
and chemotherapy. Prognosis is poor.

Histiocytosis Characteristics:
• It’s a group of disorders characterized by the proliferation of histiocytic cells (macrophages)
that closely resemble the Langerhan’s cells of the epidermis.

• Birbeck granules-tennis racket-shaped cytoplasmic structures, are characteristic markers of

histiocytic cells.

• Etiology and pathogenesis are unknown.

• It is also called Langerhans Cell Histiocytosis (LCH) and Differentiated Histiocytosis (DH).

BRUTON’S AGAMMAGLOBULINEMIA (X-linked Agammaglobulinemia)-rare disorder

characterized by the absence of the serum immunoglobulin IgG; associated with an increased
susceptibility to infection caused by pyogenic bacteria.
1. Transient Agammaglobulinemia-common in infancy before six weeks of age. Mature B cells are
temporarily unable to produce antibodies.

2. Congenital (Bruton’s Agammaglobulinemia)-a rare sex-linked disorder that results in decreased

production of antibodies. Treatment involves repeated administration of IgG to maintain adequate
levels of antibody in the circulatory system. Patients with Bruton’s are deficient in antibodies and
susceptible to repeated infections (mostly bacterial and fungal). This results from the failure of
B cells (B-lymphocytes) to differentiate into plasma cells which produce antibodies.

3. Acquired Agammaglobulinemia-usually occurs in association with a malignant disease like

 leukemia, myeloma, or lymphoma.

X-linked Agammaglobulinemia (Bruton’s agammaglobulinemia): Infants born with Bruton’s

agammaglobulinemia develop bacterial infections of the lung, sinuses, and bones, (Hemophilus,
Streptococcus, and Neisseria). Affects only boys, resulting in a decreased amount, or absence of B-
lymphocytes, and very low levels of antibodies. Normal circulating T cells (T-lymphocytes).

 GENETIC DISORDERS & MUTATIONS
MUTATION-a stable, heritable change in the nucleotide sequence of genetic nucleic acid (DNA),
resulting in an alteration in the products coded for by the gene. Mutation result from 3 types of
molecular changes:
1. Base substitutions-one base is inserted in place of another; results in either a missense or
nonsense mutation.

2. Frame-shift mutation-occurs when one or more base pairs are added or deleted.

3. Transposons (insertion sequences) or deletions are integrated into the DNA.

BASE SUBSTITUTIONS result in Missense and Nonsense mutations:

1. Missense mutation-occurs when the base substitution results in a codon that simply causes a
different amino acid to be inserted. Missense mutations result in the substitution of one amino
acid for another.

2. Nonsense mutation-occurs when the base substitution generates a termination codon that
prematurely stops protein synthesis. These mutations almost always destroy protein function.
(UAA, UGA, UAG)

3. Transverse mutation-a point mutation involving base substitution in which the orientation of
purine and pyrimidine is reversed (a purine is replaced by a pyrimidine, or a pyrimidine by a
purine).

4. Transition mutation-a point mutation caused by BASE ANALOGUES involving substitution of

one base pair for another by replacement of one purine by another purine, and of one pyrimidine
by another pyrimidine without changing the purine-pyrimidine orientation.

MUTATIONS are caused by various mutagens (UV light, radiation, chemicals, and certain viruses).
Mutations include base substitution (nucleotide substitutions), frame-shift mutations, insertions
(transposons), and deletions.

MUTATIONS are caused by: chemicals, radiation, UV light, and viruses:

• Chemicals-nitrous oxide and alkylating agents alter the existing base; benzpyrene (in tobacco
smoke) binds to existing DNA bases and causes frame-shift mutations.
• Ionizing Radiation (gamma and x-rays)-produces free radicals that can attack DNA bases.
• Ultraviolet light-has lower energy than x-rays, causes the cross-linking of the adjacent pyrimidine
bases to form dimers (thymine dimers result in inability of the DNA to replicate properly).
• Viruses-bacterial virus Mu (mutator bacteriophage) causes frame-shift mutations or deletions.

Radiosensitive Cells: immature, high metabolism, proliferation, & growth rate, non-specialized.
• Highly radiosensitive cells-lymphocytes, bone marrow blood-forming cells, reproductive cells,
epithelial cells of GI tract.
Radioresistant Cells: mature, low metabolism, proliferation, & growth rate, highly specialized. Ex:
nerve cells, mature bone cells, and muscle cells.

SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID)-the most serious

immunodeficiency disorder. It’s the most dangerous type of congenital (inherited) immunodeficiency that
results from a failure of STEM CELLS to differentiate properly. Individuals with SCID have no B
or T lymphocytes and are incapable of any immunological response. These children die before age 2.

WISKOTT-ALDRICH SYNDROME-affects only boys and causes eczema, low platelet count, and a
combined deficiency of B and T lymphocytes that lead to repeated infections. Children who survive past
age 10 usually develop cancers (lymphoma and leukemia).

ATAXIA-TELANGIECTASIA-an inherited disorder that affects both the immune system and nervous
system. This disorder generally progresses to intense muscle weakness, paralysis, dementia, and death.

HYPER-IgE SYNDROME (Job-Buckley Syndrome)-an immunodeficiency disorder of very high levels

of IgE antibodies and repeated infections with Staphylococcus bacterium. Treatment: continuous
antibiotics.

WILSON’S DISEASE (hepatolenticular degeneration)-inherited disorder of COPPER

METABOLISM causing cirrhosis of the liver, degeneration of basal ganglia in the brain, and
deposition of green pigment in the periphery of the cornea. Wilson’s characteristics are excessive
deposits of copper in liver cells, degenerative changes in the brain, and a greenish-brown ring at the
outer margin of the cornea

TURNER’S SYNDROME-condition affecting girls in which one of the two X-chromosomes is

partially or completely missing. Turner’s syndrome is manifested by webbing of the neck, small stature,
sexual infantilism, ovarian fibrous streaks, and high gonadotropin levels with low estrogen levels, and
increased incidence of cardiovascular defects (most notably coarctation the aorta). Females are usually
STERILE.

KLINEFELTER’S SYNDROME-a condition found in males, usually associated with one or more
extra X chromosomes (XXY or XXXY). These people have small testis, enlarged breasts, a feminine
distribution of pubic hair, and mild mental retardation. Boys tend to be tall with long legs. Klinefelters is
associated with advanced maternal and paternal age.

TRIPLE X SYNDROME- girls with 3 X chromosomes have lower intelligence than their normal
siblings. Girls are sometimes sterile.

DISEASES DIAGNOSED BY KARYOTYPING:

• Klinefelter’s syndrome (XXY)
• Turner’s syndrome (XO)
• Triple X syndrome (XXX)
• Trisomy 18-extra chromosome 18 (Edward’s syndrome)
• Trisomy 21- extra chromosome 21 (Down syndrome)

TRISOMY 21 (DOWN SYNDROME)-caused by an extra chromosome 21 affecting 1/700 births.

Physical and mental development is delayed; many physical abnormalities present (small head, broad, flat
face with slanting eyes and short nose). The tongue is large, and ear small and low set. Heart defects are
common. Affected people live until 30-40 years.

TRISOMY 18 (EDWARD’S SYNDROME)-caused by an extra chromosome 18; affecting 1/3000

births. Facial abnormalities combine to give the face a pinched appearance. Head is small, and ear
malformed and low set. Survival for more than a few months is rare; severe mental retardation.

TRISOMY 13 (PATAU’S SYNDROME)-caused by an extra chromosome 13; affecting 1/5000 births.

Severe brain and eye defects, and mental retardation are common. Fewer than 20% survive past 1year
age.

BEHCET’S SYNDROME-a chronic, relapsing inflammatory disease that can produce recurring, painful
mouth sores, skin blisters, genital sores, and swollen joints. There is also formation of pus-like fluid in
the anterior chamber of the eye (hypopyon). Pyodermas (pus-producing skin diseases) are common and
there is often involvement of the CNS in a variety of forms.

ANKYLOSING SPONDYLITIS-a C.T. disease characterized by inflammation of the spine and large
joints, causing stiffness and pain.

REITER’S SYNDROME-inflammation of the joints and tendon attachments at the joints, often
accompanied by inflammation of the eye’s conjunctiva and the mucous membranes (mouth, urinary tract)
and by a distinctive rash.

POLYMYALGIA RHEUMATICA-a condition causing severe pain and stiffness in the muscles of the
neck, shoulders, and hips.

VON HIPPEL-LINDAU DISEASE-characterized by hemangiomas of the retina and cerebellum. Also

associated with cysts of the liver, kidney, adrenal glands, and pancreas.

MARFAN’S SYNDROME-an uncommon hereditary C.T. disorder resulting in abnormalities of the eyes,
bones, heart, and blood vessels. Patients are tall and thin, with abnormally long legs and arms with
spider-like fingers.

 RESPIRATORY DISORDERS
CYSTIC FIBROSIS-an autosomal recessive hereditary disorder that causes certain EXOCRINE
GLANDS to produce abnormal secretions (increased viscosity of mucus and increased sodium and
chloride concentrations in sweat and tears). This results in symptoms that mainly affect the digestive
tract and lungs. The mucus-producing glands in the airways of the lungs produce abnormal secretions
that clog the airways and allow bacteria to multiply.
• Cystic Fibrosis Complications: chronic pulmonary disease, pancreatic insufficiency, and
meconium ileus (a form of intestinal obstruction in newborns).

• Cystic Fibrosis is the MOST COMMON INHERITED DISEASE LEADING TO DEATH

among white people in the U.S.

• CYSTIC FIBROSIS. Most common symptom is a chronic, productive cough with foul-smelling,
purulent sputum.

PNEUMOCONIOSES-pulmonary diseases caused by inhalation of inorganic dusts. The most

important factor in the production of symptomatic pneumoconiosis is the capacity of inhaled dusts to
stimulate fibrosis of the lungs. Main symptoms: chronic dry cough & shortness of breath. Types of
pneumoconiosis are named based on the substance inhaled:
1. Coal Worker’s Pneumoconiosis (Black Lung Disease)-caused by inhalation of coal dust that
contains carbon and silica. Can cause no disability or can progress to bronchiectasis, pulmonary
hypertension, or death from respiratory failure.

2. Anthracosis-caused by carbon dust inhalation, endemic in urban areas. Typically harmless.

3. Silicosis (stone mason’s disease)-caused by prolonged inhalation of silica (quartz) dust. It’s the
oldest occupational lung disease seen in glass manufacturers and stone-cutters. THE MOST
SERIOUS PNEUMOCONIOSES and is associated with increased susceptibility to TB.

4. Asbestosis-caused by prolonged inhalation of asbestos fibers. It results in marked predisposition

to bronchogenic carcinoma and to malignant mesothelioma of the pleura and peritoneum.

EMPHYSEMA-the major cause is CIGARETTE SMOKING. Emphysema is associated with

pollutants, genetic factors, cigarette smoking, and infection. In emphysema, alveoli become over
distended, and alveoli walls alveoli break down and are often replaced by fibrous tissue. This greatly
reduces the surface area across which gaseous exchange can occur.
• A person with emphysema has progressive, labored breathing characterized by prolonged,
expiratory effort, and increased susceptibility to infection. This person has two problems: the
lungs are “fixed” in inspiration and the respiratory surfaces of the lungs have deteriorated so
much that they are no longer adequate to accomplish normal gas exchange.

• Patients with severe, uncomplicated pulmonary emphysema have normal or increased total lung
capacity.
Emphysema is morphologically classified according to the location of the lesions within the lungs:
• Centrilobular-mainly affects the lung’s upper lobes. Cigarette smoking is the major cause.
• Panacinar-lower lobes of lungs are mostly affected. Familial antiproteinase (serum alpha 1-
antitrypsin) deficiency is associated with this emphysema.
• Localized (paraseptal)-found at the lung apex of an upper lobe.

LUNG ABSCESS-a pus-filled cavity in the lung surrounded by inflamed tissue caused by an infection.
ASPIRATION is the most common cause of lung abscess, often in the setting of altered
consciousness. ALCOHOLISM is the single most common condition predisposing to lung abscess.
Persons suffering from drug overdose, epileptics, and patients with neurologic dysfunction impairing the
gag reflex are also at risk.
• MOST COMMON ORGANISMS encountered in lung abscesses caused by aspiration are
Staphylococcus, Pseudomonas, Klebsiella, and Proteus.

• Almost all patients with a lung abscess have COUGH AND FEVER.

• The production of large amounts of foul-smelling sputum is one of the most characteristic
symptoms of a lung abscess. Also, dyspnea, chest pain, and cyanosis may exist.

Lung Abscess is most commonly caused by aspiration of anaerobic bacteria/material from

decayed/carious teeth, vomitus, or foreign material from the oral cavity. Other lung abscess causes:
• Complication of pneumonia or bronchiectasis.
• Septic arterial embolus from a heart valve.

CHRONIC BRONCHITIS-a productive cough occurring for at least three months of the year for a
least two consecutive years. Chronic Bronchitis has a strong association with cigarette smoking (90%
of all cases are smokers). The bronchial glands are enlarged, causing excess secretion of mucus.
Chronic bronchitis often leads to Cor pulmonale (enlargement of the right ventricle of the heart),
airway narrowing, and obstruction along with the squamous metaplasia of the bronchial tree.
• Patients with chronic bronchitis are predisposed to lung cancer (bronchogenic carcinoma) by
causing squamous metaplasia of bronchial epithelium.

• A chronic lung abscess, TB, lobar pneumonia, bronchogenic carcinomas, and pulmonary
embolism all present a productive cough (a cough containing sputum). Sputum contains mucus,
cellular debris, bacteria, blood, or pus.

• Chronic Bronchitis is the primary disease of CIGARETTE SMOKERS.

PULMONARY EDEMA-most commonly caused by LEFT VENTRICULAR FAILURE (congestive

heart failure). Pulmonary Edema is EXCESSIVE FLUID IN THE LUNGS, which may accumulate in
the interstitium, alveoli, or in both. Physiologically, pulmonary edema is caused by an increase in intra-
capillary hydrostatic pressure or increase in capillary permeability.

• LVF is caused by chronic passive congestion of the lungs. In addition to CHF, pulmonary edema
can be caused by drug overdose (barbiturates and opiates), drowning, mitral stenosis, or viral
infection. Left-sided heart failure or shock may be associated with pulmonary edema.
 • Pulomonary Edema Signs and Symptoms:
o Orthopnea-shortness of breath (dyspnea) when lying flat. Relieved by sitting upright
propped up in bed or sitting in a chair. Caused by increased blood distribution to the
pulmonary circulation. Often a symptom of pulmonary edema or left ventricular heart
failure.

• Major Complications: diffusion hypoxia and respiratory failure.

BRONCHIECTASIS-an irreversible, abnormal dilation of the bronchi or bronchioles caused by

destruction of their supporting structures by a chronic necrotizing infection. Common in children with

ATELECTASIS-a shrunken and airless state of the lung, or portion of the lung, due to failure of
expansion or resorption of air from alveoli. Common in premature infants due to a lack of surfactant
(causes alveoli to collapse).

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)-disorders characterized by

AIRFLOW OBSTRUCTION during respiration. Main symptoms: shortness of breath, cough, sputum
production.
1. Bronchial Asthma-obstructive disorder marked by dyspnea and wheezing expiration caused by
episodic narrowing of the airways.

2. Chronic Bronchitis (Blue Bloater)-productive cough characterized by hypersecretion of mucus.

Inflammation of the lining of bronchial tubes (narrows airways); less air able to flow with
resulting heavy mucus or phlegm, from severe breathing and coughing attacks, “smokers cough”,
more prevalent in females.

3. Emphysema (Pulmonary emphysema “Pink Puffer”)-often co-exists with chronic bronchitis,

labored breathing, and increased susceptibility to infection. Over-inflated alveoli air sacs;
dyspnea with increased respiratory rate, chronic coughing with expectoration, wheezing, barrel
chest, more prevalent in older males.

4. Bronchiectasis-copious purulent sputum, hemoptysis, and recurrent pulmonary infection.

5. Secondary pulmonary hypertension is most often caused by COPD.

PNEUMONIA-an infection of the lungs involving the air sacs (alveoli) and tissues around them.
Often pneumonia is the final illness in people who have other serious, chronic diseases. It is the most
common fatal infection acquired in the hospital, characterized by chills and fever, productive cough,
blood-tinged sputum, and hypoxia with shortness of breath. It is most often caused by Streptococcus
pneumoniae. It is classified anatomically as either bronchopneumonia (affects infants and elderly) or
lobar pneumonia (affects middle-aged people).
• Predisposing Factors to Pneumonia: alcoholism, cigarette smoking, diabetes, heart failure,
COPD.

LOBAR PNEUMONIA-most frequently caused by Streptococcus pneumoniae. There is inflammation

and consolidation of the entire lobe(s) of the lungs. IT IS DIFFUSE and common in middle-aged
people.
MANY ORGANISMS (Staphylococcus aureus, Haemophilus influenza, and Klebsiella pneumoniae),
cause bronchopneumonia. Inflammation of the walls of smaller bronchial tubes (bronchioles) and
adjacent alveoli and alveolar ducts are present. It has a patchy distribution, often in lower lobes.

 BLOOD & HEMODYNAMIC DISORDERS
THROMBOCYTOPENIA-dominated clinically by petechial cutaneous bleeding, intracranial bleeding,
and oozing from mucosal surfaces. Characterized by decreased platelet count which causes prolonged
bleeding time. THE MOST COMMON CAUSE OF BLEEDING DISORDERS.

IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)-a bleeding disorder due to a deficiency in

the number of platelets causing multiple bruises, petechiae, & hemorrhage into the tissues. ITP is a
common complication of Leukemia, Aplastic Anemia, & Aggressive Cancer Chemotherapy.
• Bleeding Time is a test that is abnormally prolonged in ITP.

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)-a severe and frequently fatal form

characterized by thrombocytopenia, hemolytic anemia, renal insufficiency, fever, and neurologic
abnormalities.
• Purpura-blood spots or hemorrhages of the skin and mucous membranes that result in the
appearance of purplish spots or patches.

• Petechiae-small reddish-purple, pinpoint hemorrhages flush with the skin surface.

• Ecchymosis (Bruise)-a discoloration of an area of skin or mucous membranes due to the

extravasation of blood into the subcutaneous tissues due to trauma or hemorrhage.

ARTERIOSCLEROSIS (“hardening of the arteries”)-a general term for several diseases where an
artery wall becomes thicker and less elastic.
• Atherosclerosis-most important and most common Arteriosclerosis disease where fatty
material (atherosclerotic plaques) accumulate under the inner lining of the arterial wall
(degenerative changes in the walls of arteries). These plaques gradually narrow or occlude blood
vessels, causing impaired blood circulation. AORTA and CORONARY ARTERIES are the
MOST OFTEN AFFECTED by Atherosclerosis.

• Atherosclerosis is the most important contributor to arterial thrombosis.

RISK FACTORS for developing Atherosclerosis:

• Increased age, high blood cholesterol levels (hyperlipoproteinemia)
• Hypertension (high blood pressure)
• Diabetes mellitus
• Cigarette smoking
• Obesity, heredity, lack of exercise.
• Atherosclerosis is more common in men in all age groups and in post menopausal women.

Atherosclerosis Signs & Symptoms: changes in skin color, temperature, headache, dizziness, and
memory defects.

Atherosclerosis Consequences: results in Ischemic heart disease (coronary artery disease), heart
attack (myocardial infarct), stoke, or aneurysm formation.

ANEMIAS-conditions where the number of red blood cells (RBC) or the amount of hemoglobin inside
them is below normal. Symptoms: fatigue, weakness, inability to exercise, and lightheadedness.
• Anemia Etiology: excessive bleeding, decreased RBC production, increased RBC destruction
(hemolysis).

1. HEMOLYTIC ANEMIAS-anemias due to shortening of red cell life span (increased RBC
destruction). Examples: erythroblastosis fetalis, sickle-cell anemia, thalassemias, and
hereditary spherocytosis.
o observations that typify hemolytic anemias are elevated unconjugated bilirubin,
kernicterus, and elevated urine urobilinogen.

2. MACROCYTIC ANEMIA-any anemia where the average size of the circulating RBC is larger
than normal. Often caused by a deficiency of folic acid and vitamin B12 (cyanocobalamin).

3. MICROCYTIC ANEMIA-any anemia where the average size of the circulating RBC is smaller
than normal. Most often associated with chronic blood loss or a nutritional anemia, as in iron-
deficiency anemia.

4. MEGALOBLASTIC ANEMIA-any anemia usually caused by a deficiency of vitamin B12 or

lack of dietary folic acid. Characterized by macrocytic erythrocytes. Includes pernicious anemia
and anemias caused by folic acid deficiency (sprue and megaloblastic anemia of pregnancy).

5. PERNICIOUS ANEMIA-a megaloblastic anemia caused by lack of VITAMIN B12. It’s a

chronic, progressive, megaloblastic anemia caused by the lack of secretion of the intrinsic
factor in normal gastric juice. Intrinsic factor is necessary for adequate absorption of vitamin
B12 (vitamin B12 is necessary for maturation of erythrocytes). As a result, fewer erythrocytes
than normal are produced, and those that are produced are macrocytic and appear hyperchromatic.
Oral manifestation is ATROPHIC GLOSSITIS. Pernicious anemia patients are prone to gastric
carcinomas.

6. APLASTIC ANEMIA-caused by inadequate production of erythrocytes due to the inhibition or

destruction of red bone marrow caused by radiation, toxins, and medications. In drug-induced
aplastic anemias, erythrocytes (RBCs) appear normochromic (normal concentration of Hb), and
normocytic (normal in size).

7. THALASSEMIAS (major and minor)-a group of inherited disorders caused by an imbalance in

the production of one hemoglobin chain are produced, resulting in low levels of erythrocytes and
abnormal hemoglobin.
• beta-thalassemia-insufficient beta chain is produced resulting in a microcytic cells with
insufficient beta hemoglobin, filled with excess alpha chain. Hemoglobin B

8. SICKLE CELL ANEMIA-the result of the production of abnormal hemoglobin (hemoglobin S)

due to a genetic defect common in AFRICAN AMERICANS. The globin part of hemoglobin is
abnormal due to the amino acid valine being substituted for glutamic acid in the sixth position of the
 hemoglobin molecule. When the abnormal Hb molecules are exposed to low oxygen concentrations
(hypoxic conditions), they form fibrous precipitates with the erythrocytes, distorting them into the
sickle-shape.
• Because sickle-shaped hemoglobins are fragile, they break up as they travel through blood
vessels, causing severe anemia, blocked blood flow, organ damage, and possibly death.
Non-healing leg ulcers and recurrent bouts of abdominal chest pain are common.

• Sickle-cell anemia is an autosomal recessive disease. Usually, individuals with two genes
for adult (A) hemoglobin and those with hemoglobin S genes can be heterozygous (AS) or
homozygous (SS); the former (AS) have sickle-cell trait, while (SS) have sickle-cell
disease.

• Sickle-cell anemia almost exclusively affects blacks. It’s an inherited condition

characterized by sickle-shaped RBCs and chronic hemolytic anemia. The RBC contains an
abnormal form of hemoglobin that reduces the amount of oxygen in the cells, causing them to
become crescent or sickle-shaped.

• Sickle-shaped cells block and damage capillaries in the spleen, kidneys, brain, bones, and
other organs, reducing their oxygen supply.

ANEMIA is a NEWBORN can result from:

• Excessive blood loss during delivery.
• Excessive destruction of red blood cells.
• Impaired production of red blood cells.

Sometimes large numbers of red blood cells are destroyed as in the hemolytic disease of the newborn
(erythroblastosis fetalis), because the mother produces antibodies against the fetus’ RBC during
pregnancy.
• Erythroblastosis fetalis usually results when the fetus has RH+ blood (from the father), and
the mother has RH-negative blood. The mother responds to the incompatible blood by producing
antibodies against it. These antibodies cross the placenta into the fetus’ circulation, where they
attach to it and destroy the fetus’ RBCs leading to anemia. It can also result from blood type
incompatibilities. Example: the mother may have type O blood, and the fetus has type A or B
blood.

PATIENTS WITH HEMOLYTIC ANEMIAS often have problems due to an increase in bilirubin
levels. Bilirubin is the breakdown product of hemoglobin released from dying erythrocytes. Examples:
• Elevated levels of urobilinogen (a compound formed in the intestine by the reduction of bilirubin).
• Elevated levels of unconjugated bilirubin (water-insoluble bilirubin). Normally, unconjugated
bilirubin combines with serum albumin to become water-soluble (conjugated bilirubin) in the liver
and is then be secreted with other bile components into the small intestine. Kernicterus-toxic
accumulation of unconjugated bilirubin in the brain & spinal cord.

Conditions Associated with Prolonged Bleeding Time (Thrombocytopenia):

• A patient taking Dicumarol-inhibits formation of prothrombin in the liver.
• A patient taking heparin-acts as an antithrombin by preventing platelet aggregation.
 • Idiopathic thrombocytopenic purpura-often associated with leukemia; a decrease in the number
of platelets.
• Von Willebrand’s disease-deficiency of vWF (von Willebrand’s factor); results in impaired
platelet adhesion.
• Long-term treatment with aspirin; aspirin is a cyclooxygenase inhibitor; results in impaired
production of thromboxanes, important platelet aggregants.
• Bernard-Soulier disease-a hereditary platelet adhesion disorder.
• Patients with cirrhosis of the liver-have hypoprothrombinemia (abnormally small amounts of
prothrombin in the circulating blood). Prothrombin is formed and stored in liver parenchymal
cells. In cirrhosis, there is profuse damage to parenchymal cells.

HEMOPHILIA-in Hemophilia A and B (factor VIII and IX) lead to NORMAL BLEEDING TIME,
platelet count, and PT time. In Hemophilia A and B, there is a PROLONGED PTT (partial
thromboplastin time) = a clotting test to detect plasma factor deficiencies.
• Hemophilia A and B are inherited as a sex-linked recessive trait by which males are affected and
females are carriers.
• Most people afflicted with hemophilia have type A and are under age 25.
• The signs, symptoms, and clinical manifestations include excessive bleeding from minor cuts,
epitaxis, hematomas, and hemarthroses.
• Chronic complications are impaired renal function and osteoarthritis.

Classes of Hemophilia:
1. Hemophilia A-the classic hemophilia caused by a deficiency of normal coagulation Factor VIII
(antihemophilic factor) due to a genetic deficiency that is sex-linked recessive.

2. Hemophilia B (Christmas Disease)-due to a deficiency in factor IX (plasma thromboplastin

component).

3. Hemophilia C (Rosenthal’s syndrome)-not-sexed linked, less severe bleeding. Due to a

deficiency of factor XI (plasma thromboplastin antecedent).

4. von Willebrand’s disease-inherited as an autosomal dominant bleeding disorder that occurs with
equal frequency in both sexes due to a deficiency in von Willebrand factor (a large glycoprotein
that binds factor VIII and facilitates platelet adhesion to collagen). Important in formation of a
platelet plug.

HEMOPHILIA is NOT associated with prolonged bleeding time. Bleeding Time (BT) is normal in
HEMOPHILIA patients, but PTT (Partial Thromboplastin Time) is prolonged. Normal BT, but
prolonged PTT.

MYELOPROLIFERATIVE DISORDERS-conditions in which cells that produce blood cells (myeloid

stem cells) develop and reproduce abnormally in the bone marrow. Common characteristics are peak
incidence in middle-aged and elderly persons, increase in blood basophils, serum uric acid, and
prominent splenomegaly.

THROMBOCYTHEMIA-a rare chronic myeloproliferative disorder characterized by an increased

number of platelets, leading to abnormal blood clotting or bleeding. Causes fatigue, vision changes,
headaches. Most common in people over age 50.

POLYCYTHEMIA VERA (primary polycythemia or erythemia)-a rare disorder of blood cell

precursors, resulting in an excess of red blood cells (its the opposite of anemia).
• Polycythemia Vera Characteristics: erythrocytosis, leukocytosis, thrombocytosis, &
splenomegaly, and a decrease in erythropoietin concentration.

• Secondary polycythemia-an excess of RBC caused by conditions other than polycythemia vera.
These include chronic hypoxia associated with pulmonary disease, residence at high altitudes
(Osker’s disease), and heavy smoking or the secretion of erythropoietin associated with adult
polycystic kidney and tumors.

MYELOFIBROSIS-a disorder in which fibrous tissue replaces precursor cells that produce normal
blood cells in the bone marrow, resulting in an increased number of immature red and white blood cells,
and abnormally shaped RBC’s, anemia, and enlarged spleen.

CHRONIC MYELOCYTIC LEUKEMIA (myeloid, myelogenous, granulocytic)-a disease in which a

cell in the bone marrow becomes cancerous and produces a large number of abnormal granulocytes.
PHLEBITIS (thrombophlebitis)-the inflammation and clotting of a vein that usually occurs in people
with varicose veins (enlarged superficial veins in the legs). Symptoms: localized pain, swelling, and
skin redness. Because the blood in the vein is clotted, the vein feels like a hard cord under the skin.
Phlebitis subsides by itself.
• Phlebitis can occur in any vein in the body, but most often affects VEINS OF LOWER
EXTREMITIES.

CARBON MONOXIDE-inhibits the capacity of hemoglobin to function as an oxygen carrier because

hemoglobin has an affinity for carbon monoxide that is 200x greater than its affinity for oxygen. Inhaling
high levels of CO (e.g. fumes from a car engine or home heating system) can cause coma or irreversible
brain damage due to oxygen deprivation.
• Carbon monoxide ATTACHES TO HEMOGLOBIN OF RBC & BLOCKS Hb CAPACITY
TO CARRY/BIND OXYGEN.

• When there are even small amounts of carbon monoxide in the air that is breathed, they
preferentially occupy Hb oxygen-binding sites. This Hb-carbon monoxide bond is so strong that
very little carbon monoxide is removed from the blood. Patients with fatal, acute CO
poisoning exhibit cherry-red discoloration of blood, skin, mucosa, and tissues. Ultimately, death
occurs due to hypoxia (lack of O2).

Other Environmental Chemical Agents & Their Manifestation:

• Carbon tetrachloride-hepatocellular damage
• Mercuric chloride-severe renal tubular necrosis and GI ulceration
• Cyanide poisoning-prevents cellular oxidation, results in odor of bitter almonds.
• Methyl alcohol-blindness
• Lead toxicity-basophilic stippling of RBC’s
EMBOLUS-a mass (detached BLOOD CLOT = thrombus), an air bubble or a foreign body, that
moves within a blood vessel to lodge at a site distant from its place of origin. The danger from an
embolus is it can lodge in vascular beds of vital organs, occluding blood flow and causing infarction.
• The most common source of a Pulmonary embolism is thrombophlebitis (a thrombus formed
within a vein). Femoral vein is the common source of origin of the thrombus which then
occludes a blood vessel in the lung.

TYPES OF EMBOLISM:
1. Thromboembolism-embolism formed from a blood clot (thrombus); most frequent form of
embolism.
2. Fat emboli-usually occurs from severe multiple fractures.
3. Gas emboli-most often occurs after a penetrating chest injury or surgery. Caisson disease
(decompression sickness) which occurs in divers is a type of gas embolism.
4. Amniotic fluid emboli-caused by escape of amniotic fluid into the maternal circulation. Leads to
disseminated intravascular coagulation. May cause maternal death.
5. Cerebral emboli-almost always arises from arterial or atrial thrombi.

ATHEROSCLEROSIS-the most important contributor to arterial thrombosis.

Conditions predisposing to venous thrombosis include heart failure, extensive tissue damage, bed rest,
pregnancy, oral contraceptives, age, obesity, and smoking. Morphologically, an arterial thrombus shows
alternating red and white laminations (lines of Zahn). Venous thrombi are more uniformly red; the lines
are distinct.

THROMBUS-a solid mass of clotted blood that develops in and is attached to a blood vessel wall.
Thrombus formation is enhanced by endothelial injury, an alteration of blood flow, and hypercoagulability
of blood. A whole thrombus may detach to form a large embolus or fragments may break off to generate
small emboli. Thrombosis-the formation of an intravascular blood clot.

TYPES OF THROMBI:
1. Agonal thrombus-forms in the heart during the dying process after prolonged heart failure.

2. Mural thrombus-forms due to damage to the ventricular endocardium (usually left ventricle, after
a myocardial infarction). A major complication of a mural thrombus is a cerebral embolism.
Cerebral embolism is a complication of myocardial infarction, atrial fibrillation, and
atherosclerosis of the aorta.

3. White thrombus-a thrombus composed chiefly of blood platelets.

4. Red thrombus-formed rapidly by the coagulation of stagnating blood, composed of RBC.

5. Fibrin thrombus-formed by repeated deposits of fibrin from circulating blood. It usually does not
completely occlude the vessel.

EDEMA (Localized Edema)-the abnormal ACCUMULATION of fluid in interstitial spaces or body

cavities caused by:
• increased capillary permeability = main factor underlying localized edema in inflammation
 • increased capillary blood pressure.
• Increased interstitial fluid colloid osmotic pressure.
• Decreased plasma colloid osmotic pressure.
• Lymphatic obstruction.

TYPES OF EDEMA:
1. Anasarca-generalized edema.
2. Hydrothorax-excess serous fluid in the pleural cavity.
3. Hydropericardium-excess watery fluid in the pericardial cavity.
4. Ascites (hydroperitoneum)-excess serous fluid in the peritoneal cavity.
5. Trasudate-non-inflammatory edema fluid resulting from altered intravascular hydrostatic or
osmotic pressure. Transudate has a LOWER protein concentration than exudates.
6. Exudate-edema fluid from increased vascular permeability due to inflammation.

RIGHT-SIDED Congestive Heart Failure results in PERIPHERAL EDEMA, while LEFT-SIDED

Congestive Heart Failure results in PULMONARY EDEMA.

SHOCK-a set of hemodynamic changes that diminish blood flow below a level that provides adequate
oxygen for the metabolic needs of organs and tissues.
• Symptoms of Shock: tiredness, sleepiness, confusion; cold, sweaty skin that becomes bluish and
pale; weak, but rapid pulse, and drop in blood pressure.

• REDUCED CARDIAC OUTPUT is the MAIN FACTOR in all types of SHOCK.

TYPES OF SHOCK:
1. Hypovolemic Shock-produced by a reduction in blood volume. Caused by severe hemorrhage,
dehydration, vomiting, diarrhea, and fluid loss from burns.

2. Cardiogenic Shock-circulatory collapse caused by pump failure of the left ventricle, most often
caused by massive myocardial infarction.

3. Septic Shock-shock caused by a severe infection, caused by the endotoxin from gram-negative
bacteria. Most bacterial endotoxins are composed of lipoprotein-polysaccharide complexes.

4. Neurogenic Shock-caused by SEVERE TRAUMA to Central Nervous System (CNS).

5. Anaphylactic Shock-occurs with a severe allergic reaction. First sign is usually a skin rash,
followed by respiratory depression, then GI disturbances, and finally cardiac distress.

STAGES OF SHOCK (3):

1. Non-progressive (early) shock-compensatory mechanisms (increased heart rate & peripheral
resistance) maintain profusion to vital organs.

2. Progressive-stage (advanced shock)-metabolic acidosis occurs (compensatory mechanisms

are no longer adequate). The body produces excess acid in the advanced stages of shock, when
lactic acid is formed through the metabolism of sugar.
3. Irreversible stage-organ damage results; survival is impossible.

 LIVER DISORDERS
HEPATITIS B (Serum Hepatitis)-an infectious double-stranded DNA virus (transmitted by DNA)
producing liver inflammation and necrosis. Severity varies from an asymptomatic carrier state to
fulminant hepatitis; chronic hepatitis is common. Hepatitis B is LESS EASILY transmitted than
Hepatitis A virus. Important: Hepatitis D only occurs in people infected with Hepatitis B.

• Transmitted through contaminated blood or blood products. Transmission commonly occurs

among injection drug users who share needles, and between sexual partners (both heterosexual
and male homosexual). The 3 main modes of transmission are blood, sex, and perinatally from
mother to newborn. Hepatitis B is commonly transmitted by blood and blood-derived products.

• HEP B incubation period is 60-90 days; and can result in carrier state or chronic liver disease.

• Signs & Symptoms are similar to Hepatitis A (fever, malaise, abdominal pain, anorexia, nausea),
but there is a longer incubation period (2-3 months). Hepatitis B symptoms are develop slower
but last longer. Most patients fully recover, but some develop chronic liver disease.

• Anti-HBsAg (antibody to Hepatitis B surface antigen) in a patient’s serum protects the patient
against Hepatitis B. Hepatitis B is associated with the “Dane Particle” (the entire Hepatitis B
virion).

HEPATITIS A (“Infectious Hepatitis”)-an infectious LIVER disease, characterized by hepatocellular

necrosis and jaundice. HEP A is caused by an RNA non-enveloped enterovirus transmitted by the
fecal-oral route. Hepatitis A most often occurs in YOUNG ADULTS.
• Predisposing Factors: overcrowding, poverty, unsanitary conditions, shellfish from contaminated
water, mental institutions, and male homosexuals. Initial symptoms: fever, malaise, abdominal
pain, anorexia, jaundice) of Hepatitis A appear after an incubation period of 3-6 weeks.

• DAMAGE TO LIVER CELLS also results in increased serum levels of transaminase

enzymes, such as transaminases, normally active in liver cells. Detection of increased serum
levels of these enzymes is used to diagnose Hepatitis A. In most cases, HEP A, the infection is
self-limiting and recovery occurs within 4 months.

• presence of surface antigen (A or B) in a patient’s serum indicates the patient is potentially

infectious for Hepatitis (carrier state). Also, these Hepatitis viruses are highly heat-resistant
(more so than AIDS virus). Autoclaving properly kills Hepatitis A.

• Hepatitis A is spread by fecal-oral transmission; parental infection DOES NOT occur; its
incubation period is 21-45 days; it does NOT cause a chronic carrier state; and is also called
“Infectious Hepatitis”.

HEPATITIS C (non-A or non-B Hepatitis)-a serum hepatitis caused by a virus antigenically different
from Hepatitis A and B. Hepatitis C is the most common cause of transfusion-mediated hepatitis. It is
usually much milder than A or B, but is otherwise clinically indistinguishable from them. It is a single-
stranded enveloped RNA virus associated with the highest level of chronic disease state. 50% of people
are not aware they are Hepatitis C positive, thus most people go untreated. Treatment: antivirals.

BILIRUBIN-the yellow breakdown product of normal HEME catabolism when the body clears old red
blood cells that contain hemoglobin. EXCRETED IN BILE & URINE, and causes the yellow color of
bruises and in jaundice. Also causes the BROWN color of feces when it is converted to STERCOBILIN.

JAUNDICE-yellow discoloration of the skin, sclera (whites), and tissues by

HYPERBILIRUBINEMIA. Jaundice is caused by abnormally high levels of the bilirubin bile pigment
in the bloodstream. Hemoglobin (the part of the RBC that carries oxygen) is broken down into bilirubin,
which is then carried to the liver and excreted into the intestine as a bile component. If bilirubin
excretion is hindered, excess conjugated bilirubin passes into the bloodstream, causing jaundice.
Juandice is highly common and leading manifestation of LIVER DISEASE. It occurs at any age and
either sex. Jaundice is a symptom of many disorders/conditions:
• Liver disease (hepatitis, cirrhosis) liver cell damage
• Acute biliary obstruction (bile duct obstruction) (increases the conjugated bilirubin in serum).
• Hemolytic anemia; excessive hemolysis
• Carcinoma of the head of the pancreas.
• Gallstones (cholelithiasis).
• Erythroblastosis fetalis.

LIVER is the most uncommon site of infarcts, but is most capable to regenerate after injury. Infarcts are
common in the brain, heart, kidney, adrenals, and intestines.

BRAIN is the MOST susceptible to infarction due to systemic arterial thromboembolism.

Bilirubin is conjugated or unconjugated:

• Conjugated bilirubin is formed by the conjugation of bilirubin with glucuronic acid. Acute
biliary obstruction produces an increase in conjugated bilirubin in serum.

• Free bilirubin (unconjugated) bilirubin- unlike that bound to albumin or conjugated with
glucuronic acid, is toxic to the brain in newborns, and in high concentrations causes irreversible
brain damage (kernicterus = toxic accumulation of unconjugated bilirubin in the brain and
spinal cord).

PORTAL HYPERTENSION-a sustained increase in portal venous pressure almost always a result of
obstruction of blood flow in the portal circuit It often ENLARGES THE SPLEEN (splenomegaly) the
single most important sign of portal hypertension.

• MOST COMMON CAUSE of portal hypertension is CIRRHOSIS OF THE LIVER

(alcoholics). Classic complications of portal hypertension: esophageal varices, splenomegaly,
and ascites.

• Portal hypertension is abnormally high blood pressure in the portal vein (the large vein that
brings blood from the intestine to the liver).
 • Portal hypertension results from thrombosis of the portal vein or liver cirrhosis. It causes
dilation of veins in the lower part of the esophagus, forming ESOPHAGEAL VARICES.

PORTAL HYPERTENSION COMPLICATIONS

ESOPHAGEAL VARICES (varicose veins)-the most COMMON COMPLICATION of portal

hypertension and form in the lower end of the esophagus. These engorged vessels are fragile and
likely to bleed. Portal hypertension is the most common cause of esophageal varices.

• One of the most common causes of death in patients with liver cirrhosis associated with portal
hypertension is upper GI hemorrhage from bleeding esophageal hemorrhages. This causes
massive vomiting of blood (hematemesis).

• Esophageal varices are the most common cause of a MASSIVE HEMATEMESIS in

alcoholics.

ASCITES-an accumulation of free serous fluid n the abdominal cavity. It is almost pure plasma,
containing huge quantities of protein. Ascites occur in long-standing (chronic) rather than short-lived
(acute) conditions. It occurs most commonly in CIRRHOSIS (especially in cirrhosis caused by
alcoholism). Small amounts of fluid in the abdomen usually produce no symptoms, but massive amounts
can cause abdominal distention and discomfort, and shortness of breath.
• Causes of Ascites: cirrhosis, heart failure, intra-abdominal cancer, kidney failure, tuberculosis.

• Ascites is often a complication of alcoholic liver disease and develops from cirrhosis,
esophageal varices, and decreased protein production by the liver.

SPLENOMEGALY-indicates portal hypertension, which causes esophageal varices = the most

common source of massive hematemesis in alcoholics.

CIRRHOSIS-the end-stage of chronic liver disease. Cirrhosis is destruction of normal liver tissue
that leaves non-functioning scar tissue surrounding areas of functioning liver tissue. This impedes
blood circulation through the liver, and is the MOST COMMON LIVER DISEASE (75% are from
alcoholism).
• Signs and Symptoms: ascites, splenomegaly, sudden onset of upper GI bleeding with massive
hematemesis (vomiting blood), and jaundice.

• CHF and biliary obstruction can both lead to cirrhosis of the liver.

• CIRRHOSIS is chronic liver disease characterized by generalized disorganization of hepatic

architecture with scaring and nodule formation. Among people age 45-65, cirrhosis is the 3rd
most common cause of death, after heart disease and cancer. In the U.S. ALCOHOL ABUSE IS
MOST COMMON CAUSE OF CIRRHOSIS.

Cirrhosis Etiologic Agents:

• Alcohol abuse, use of certain drugs, and exposure to certain chemicals.
• Infections (Hepatitis B and C), biliary obstruction, & hemochromatosis (iron overload).
• Wilson’s Disease-a hereditary accumulation of copper in the liver, kidney, brain and cornea.
 • inborn errors of metabolism: galactosemia, glycogen storage diseases, or alpha1-antitrypsin
deficiency.

CIRRHOSIS is associated with an increased incidence of HEPATOCELLULAR CARCINOMA


 INFLAMMATION & NECROSIS
ABSCESS-a confined collection of PUS, that consists of DEAD white blood cells and necrotic tissue. A
wall of proliferating fibroblasts that produce collagen surrounds it. An abscess is the body’s attempt to
prevent further spread of infection and is usually CAUSED BY A BACTERIAL INFECTION.

CYST-an abnormal sac within the body containing AIR or FLUID, and line with EPITHEILIUM.

GRANULOMA-a tumor composed of granulation tissue usually associated with ULCERATED

INFECTIONS. The epithelioid cell (a modified macrophage) is the characteristic cell found in
granulomas. Lymphocytes, plasma cells, and fibroblasts surround the nodule of epithelioid cells.

ACUTE INFLAMMATION

NEUTROPHILS (Polymorphonuclear Leukocytes or PMNs)-circulating white blood cells essential

for phagocytosis and proteolysis in which the bacteria, cellular debris, and solid particles are removed
and destroyed. Neutrophils are the most numerous of the white blood cell population (50-75%), and
are the first inflammatory cells to appear in large numbers at the site of injury.
• infiltrate of neutrophils is most characteristic of the early stages of acute inflammation.
• Neutrophils form enzymes responsible for suppuration.

Neutrophils are especially attracted to injured tissue through CHEMOTAXIS (a chemical attraction
of tissue substances for the leukocytes). Numerous substances are chemotactic for neutrophils including:
• C5a and C3a (anaphylatoxins)-these anaphylatoxins induce a physiological response that results
in blood vessel dilation, hypotension, and increased vascular permeability.

• C5a and C3a anaphylatoxins are the breakdown products of complement (a series of plasma
proteins present in the body fluids that are normally in an inactive state). Once an initial
activating step occurs (usually a specific antigen-antibody complex), causing a sequential,
irreversible cascade of plasma protein activation. The end result of complement activation on a
cell membrane is cell lysis.

ACUTE MENINGITIS-an example of ACUTE inflammation with purulent exudates in response to a

bacteria infection.

ACUTE INFLAMMATION-the INITIAL response of tissue to injury, particularly bacterial infections

involving vascular and cellular responses. 3 major phenomena occur:
1. increased vascular permeability with tissue exudates formed
2. leukocytic cellular infiltration (mainly neutrophils by chemotactic agents C5a and C3a)
3. repair (by regeneration or replacement).

• Local signs of acute inflammation: redness (rubor), heat (calor), swelling (tumor), pain (dolor),
and loss of function. Systemic effects include fever, tachycardia, and leukocytosis (especially
neutrophils)
 • PMNs (Polymorphonuclear Neutrophils)-the MOST PROMINENT INFLAMMATORY
CELLS IN ACUTE INFLAMMATION. PMNs (Leukocytes) predominate in the cellular
phase.
• Other acute inflammation cells (specifically the vascular phase) are basophils, tissue mast cells,
and platelets which all release HISTAMINE. Macrophages appear late in the cellular phase, and
represent a transition between acute and chronic inflammation.

ACUTE INFLAMMATION (2 PHASES):

1. Vascular Phase-involves platelets, tissue mast cells, and basophils that release histamine.
• vasoconstriction-a brief period of vasoconstriction.
• vasodilation-produces congestion due to active hyperemia. Manifested clinically by
redness and warmth of the affected area.
• Increased vascular permeability-results in leakage of proteinaceous fluid (exudates),
which causes edema.

2. Cellular Phase-leukocytes (predominantly polymorphonuclear neutrophils) are the first

defense cell to migrate to the injured tissue by chemotaxis. PMN leukocytes engulf matter by
phagocytosis. This engulfed matter then becomes a phagosome and combines with lysosomal
granules to form a phagolysosome, in which digestion of the engulfed particle occurs.

EOSINOPHILS-predominant inflammatory cells in allergic reactions & parasitic infestations.

Eosinophils increase in number in the bloodstream during an allergic reaction or parasitic infection.

NECROSIS-a set of morphologic changes that accompany cell death INSIDE a living body.
1. Coagulation Necrosis-the basic and MOST COMMON NECROSIS, caused by Ischemia (loss
of blood supply); involves the heart and kidney. Nuclear changes characteristic of Coagulation
Necrosis that are morphologic hallmarks of irreversible cell injury and necrosis are:
• Pyknosis-condensation and shrinking of the cell nucleus with chromatin clumping.
Chromatin-the portion of the cell easily stainable by dyes. It consists of nucleic acids and
proteins.
• Karyolysis-destruction or dissolution of the cell nucleus with fading of the chromatin.
• Karyopyknosis-shrinkage of cell nuclei and condensation of the chromatin.
• Karyorrhexis- fragmentation of the cell nucleus and chromatin.

2. Liquefaction Necrosis-caused by suppuration, abscesses, and ischemic injury to CNS; involves

brain or spinal cord (CNS).
3. Caseous Necrosis-caused by granulomatous inflammation (typical of TB); involves
granulomatous inflammatory sites.
4. Gangrenous Necrosis-caused by putrefactive bacteria acting on necrotic bowel or extremity;
involves lower extremities or bowel.
5. Fibrinoid Necrosis-caused by immune-mediated vascular damage; involves arterial walls.
6. Fat Necrosis-caused by injured pancreas, or trauma to adipose tissue; involves adipose tissue,
pancreas.

AUTOLYSIS-the process of cell death OUTSIDE a living body.

EDEMA resulting from inflammation is caused by increased capillary permeability. EXUDATE
(“pus”)-is the edema fluid characterized by high specific gravity (exceeding 1.020). Exudate is
protein-rich, high specific gravity, glucose-poor, and cell-rich.
• Exudate contents: WBC (neutrophils)-these leukocytes consume glucose, and explains why the
exudates are glucose-poor; cellular debris, plasma proteins, and plasma fluids.

TRANSUDATE-results from increased intravascular hydrostatic pressure or from altered osmotic

pressure. Transudate fluid is thin and watery with few blood cells, low protein content, and a low
specific gravity (less than 1.020). Transudate is present in non-inflammatory conditions.

Most common acute inflammatory reactions contain large amounts of Neutrophils and are
Suppurative (meaning to produce purulent matter). Suppuration is mainly the result of tissue necrosis,
autolysis by proteolytic enzymes, collection of neutrophils (WBC), and buildup of tissue fluid.
CHRONIC INFLAMMATION-develops at an injury site that persists longer than several days.
Chronic inflammation is more proliferative than exudative, and necrosis commonly occurs and recurs.
Examples of chronic inflammation are chronic hepatitis, chronic pyelonephritis, and autoimmune
diseases.
• Granulomatous inflammation-a subtype of chronic inflammation characterized morphologically
by granulomas (examples are TB, sarcoidosis, and silicosis).

• GRANULOMATOUS INFLAMMATION-a subtype of CHRONIC inflammation characterized

by granulomas (nodular collections of specialized macrophages = epithelioid cells). A rim of
lymphocytes usually surrounds granulomas (produced by multinucleated giant cells (Langerhans
giant cells and foreign body giant cells). All other cell types characteristic of CHRONIC
inflammation (plasma cells, eosinophils, and fibroblasts) may be associated with granulomas.
Granulomatous inflammation is associated with areas of caseous necrosis produced by infectious
agents like Mycobacterium tuberculosis.

• Granulomatous inflammation is a typical tissue response elicited by fungal infections, TB,

presence of foreign material (suture or talc), Leprosy, and Sarcoidosis.

• Cellular components of CHRONIC inflammation: lymphocytes, plasma cells, and

macrophages.

• Proliferation is the process most likely to dominate in chronic, granulomatous inflammation.

ETIOLOGIC AGENTS of Granulomatous inflammation: Infectious Agents:

• TB and leprosy, which are mycobacterial diseases.
• Fungal infections (blastomycosis, histoplasmosis, and coccidiodomycosis).
• Spirochètes (Treponema pallidum causes syphilis).
• Cat scratch disease (caused by an unnamed gram-negative organism).
• Foreign material (e.g. suture or talc).
• Sarcoidosis (unknown etiology and non-necrotizing). Growth of tiny inflammatory cells in various
parts of the body.
• Crohn’s Disease: (non-caseating)-inflammation (IBD) of the digestive tract lining (often occurs in
the small intestine and colon).
GAS GANGRENE (Myonecrosis)-caused by Clostridium perfringens (gram + anaerobe common in
food poisoning) that grows in extensively traumatized tissue and produces a variety of toxins (alpha
toxin). Alpha toxin (lecithinase) damages cell membranes of erythrocytes resulting in hemolysis.
Degradative enzymes produce gas in tissues. Gas gangrene is associated with gunshot wounds,
automobile and motorcycle accidents, compound fractures, and septic abortions.
• Symptoms: pain, swelling, and tenderness of the area; moderate fever, tachycardia, and
hypotension.
• Prompt treatment: excision of gangrenous tissue and administration of penicillin G. saves 80% of
patients. Gas gangrene is prevented by proper wound care.

GANGRENE-the decay of bodily tissue due to inadequate blood (nutritive) supply. It’s a form of
necrosis combined with putrefaction. Types of Gangrene:
• Cutaneous gangrene-involves the skin, characterized by sloughing.
• Diabetic gangrene-results from arteriosclerosis associated with diabetes.
• Embolic gangrene-results from obstruction of an artery by an embolus.

 NEOPLASMS (TUMORS)
NEOPLASM-can be benign, pre-cancerous, or malignant (cancer).

TERATOMA-a tumor composed of multiple tissues (is a neoplasm derived from all three embryonic
germ cell layers), including tissues not normally found in the organ in which they arise. It’s a tumor with
tissue or organ components resembling normal derivatives of more than one germ layer. Teratoma occurs
most frequently in the ovary, where it is usually benign and forms dermoid cysts. Teratoma also
occurs in testis, where it is usually malignant, and uncommonly in other sites.

CARCINOMA-a MALIGNANT TUMOR of epithelial origin that occurs in the following variations:
1. Squamous cell carcinoma-originates from stratified squamous epithelium, marked by the
production of keratin.
2. Transitional cell carcinoma-arises from transitional cell epithelium of the urinary tract.
3. Adenocarcinoma-a carcinoma of glandular epithelium.

SARCOMA-a MALIGNANT TUMOR arising from mesenchymal tissue. Examples: osteosarcoma

(bone), leiomyosarcoma (smooth muscle), and liposarcoma (adipose tissue).

KAPOSI’S SARCOMA-a malignant tumor of vascular origin that appears as painless, red-to-purple,
raised patches on the skin, frequently associated with AIDS.
• Kaposi’s Sarcoma-is a malignant neoplasm that originates in blood vessels of the skin. It
involves abnormal vascular proliferation (cancer of the lining of blood vessels). It occurs on
multiple sites, especially the lower extremities. Initial lesions are small, red papules that enlarge
and fuse to form purple-to-brown, spongy nodules. It spreads to lymph nodes and internal organs.
KAPOSI’S SARCOMA IS MOST COMMONLY ASSOCIATED WITH “AIDS”. Non-
Hodgkin’s lymphoma is also a malignant neoplasm often observed in AIDS.

• AIDS-is caused by RNA RETROVIRUS, HIV (also called HTVL-III). The HIV infection is
acquired by sexual contact (homosexual and heterosexual) or from contaminated blood products.
HIV can invade many body cells (macrophages, liver kupffer cells, neurons, bone marrow
cells, and spleen cells). HIV’s primary targets and binds T cells called (CD4 cells) and helper
class of T cells. HIV does not infect T suppressor cells.

• Individuals with AIDS EXHIBIT IMMUNOSUPPRESSION. They are predisposed to

opportunistic infections that produces clinical manifestations. Opportunistic infections
associated with AIDS include Pneumocystic carinii pneumonia, Cryptosporidium enterocolitis,
candidiasis, oral hairy leukoplakia, & mycobacterial infections (M. Tuberculosis). Another
malignant neoplasm associated with AIDS is malignant B-cell lymphoma.

EWING’S SARCOMA-the second most common highly malignant primary bone tumor of CHILDREN
after osteosarcoma. Extremely anaplastic small-cell malignant tumor of bone (mostly arms & legs)
with a morphologic resemblance to malignant lymphoma (histiocytic lymphoma). Radiographically, it is
associated with lamellated or “ONION-SKIN” appearance caused by splitting and thickening of the
cortex by tumor cells. Pain and swelling are the most common symptoms.

• Ewing’s sarcoma tumors follow an extremely malignant course with early metastasis. It affects
males more than females, appearing most commonly in people ages 10-20 (95%).

CHILDREN with EWING’S SARCOMA often have fever and leukocytosis. Histologically, it is often
difficult to distinguish Ewing’s tumor from a neuroblastoma or a reticulum cell sarcoma. Approximately
60% of people with Ewing’s sarcoma are cured with surgery, chemotherapy, and radiation therapy.

OTHER PRIMARY CANCEROUS BONE TUMORS:

1. Osteogenic sarcoma-most common primary malignant bone tumor of mesenchymal origin; most
common in children and young adults. Patients with Paget’s disease have an increased risk of
developing osteosarcomas.

2. Chondrosarcomas-tumors composed of cancerous cartilage cells; must be completely removed

surgically (does not respond to chemo or radiation therapy).

3. Malignant lymphoma of bone (reticulum cell sarcoma)-usually affects people in their 40-50s.
Causes pain and swelling with fracture of damaged bone.

4. Fibrosarcomas-are similar to osteogenic sarcomas.

Metastatic bone tumors-cancers that have spread to bone from their original site elsewhere in the body.
Cancers most likely spread to bone include breast, lung, prostate, kidney, and thyroid cancers.

AUPDoma-an endocrine tumor characterized by amine precursor uptake and decarboxylation (APUD)
and the resultant production of hormone-like substances.

BENIGN TUMOR-a LOCALIZED tumor with a fibrous capsule (encapsulated), limited growth
potential, a regular shape, and well differentiated cells. A benign neoplasm DOES NOT invade
surrounding tissue or metastasize to distant sites. It causes harm only by pressure, overproduction
of a hormone, or hemorrhage following ulceration of an overlying mucosal surface. Benign tumors
usually do not recur after surgical excision. Benign neoplasms include: Papilloma, Adenoma, and
Lipoma.

BENIGN TUMORS grow by expansion. MALIGNANT TUMORS spread by local invasion and
metastasis.

METASTASIS-the spread of a malignant tumor to a secondary site distant and separate from its
primary site; metastasis is an absolute indicator of malignancy. Metastasis occurs by the lymphatic,
hematogenous, or transplantation route. BREASTS and PROSTATE cancer can metastasize to the
mandible.
• Lymphatic metastasis-the tumor first spreads to local and regional lymph nodes where the cancer
disseminates via the blood.

• Hematogenous metastasis-secondary tumor nodules develop in the liver, lung, brain, bone
marrow, spleen, and in soft tissue.
 • Transplantation metastasis-common in carcinomas of the ovaries (rarely, dermoid cysts develop
malignancy), stomach, colon, and pancreas.

THE DEGREE OF LOCALIZATION is the MOST RELIABLE INDICATOR of prognosis of

malignant tumors. The degree of localization is the basis of staging, which is critical to determine if a
cure is likely. A variety of staging tests determine the tumor’s location, size, growth into nearby structures,
and if it has metastasized.
• Malignant Neoplasms (tumors) Characteristics: not well-differentiated (anaplastic), rapid
growth, invasion, metastasis, and immovable. Metastasis is the most important characteristic
that distinguishes malignant from benign. Paresthesia is suggestive of metastatic disease.

• Benign Neoplasms (tumors) Characteristics: well-differentiated, slow growth,

encapsulated/well-circumscribed, localized, and movable.

NEOPLASMS of MUSCLES are rare, but when encountered are usually malignant.
RHABDOMYOSARCOMA-a malignant tumor derived from skeletal muscle (striated), common in
children, but uncommon in adults. Common areas affected are the nasopharynx, orbit, bladder,
vagina, and skeletal muscles of the extremities. Prognosis is poor.
• Rhabdomyoma-the benign tumor that arises in any skeletal muscle of the body producing a mass
(swelling) in the affected muscle. A benign tumor in voluntary (skeletal) muscle.

LEIOMYOMA (Fibroid)-a benign tumor derived from SMOOTH MUSCLE that may occur anywhere
in the body, but is most frequently seen in the uterus. It is the most common tumor of women (25% of
women over 30 years, during the reproductive years). Also occur less frequently in the stomach,
esophagus, and small intestine. Prognosis is good. It is a benign neoplasm of the myometrium of the
uterus.

MALIGNANT MELANOMA-a potentially serious skin cancer in which the tanning cells
(melanocytes) in the skin that produce a dark-colored substance “melanin” undergo uncontrolled growth.
Nearly 50% of cases develop from existing pigmented moles. THE MOST SEVERE SKIN
TUMOR/CANCER.
• Unlike other forms of skin cancer, melanoma easily metastasizes to distant parts of the body.
• Melanoma originates in the pigment-producing cells of the skin (melanocytes), and is most
common in fair-skinned persons. Present in stratum basale layer of the epidermis.
• Melanoma is most often associated with excessive exposure to sunlight.

Malignant Melanoma has 2 Growth Phases:

1. Radial (initial phase)-growth occurs in all directions, but is predominantly lateral within the
epidermis; melanomas in the radial growth phase DO NOT METASTASIZE.
• Lentigo maligna melanoma-occurs on sun-exposed skin. Radial growth phase
predominates. Develops from preexisting lentigo maligna (Hutchinson Freckle).

• Superficial spreading melanoma-most common type; radial growth phase predominates;

frequently found on trunk and extremities.

2. Vertical (later phase)-growth extends deeper into reticular dermis or beyond. Metastasis may
 occur.
• Nodular melanoma- vertical growth phase predominates; poorest prognosis.

KERATOACANTHOMAS-round, firm flesh-covered growths with an unusual central crater

containing a pasty material. They are considered to be a benign neoplasm, but since they closely
resemble SCC, doctors often perform a biopsy. They regress spontaneously without therapy. It a skin
growth that CLOSELY RESEMBLES SQUAMOUS CELL CARCINOMA.

DERMATOFIBROMAS-benign neoplasms that appear as small, red-to-brown bumps (nodules) that

result from an accumulation of fibroblasts.

ACROCHORDON (a skin tag)-extremely common lesion most often found on the neck, armpit, or groin.

ACTINIC KERATOSIS-a premalignant epidermal lesion caused by excessive chronic exposure to

sunlight; especially common on light-skinned elderly people. Can become a squamous cell carcinoma
(is precancerous)

SEBORRHEIC KERTOSIS (Seborrheic warts)-an extremely common benign neoplasm of older

people. They are flesh-colored, brown or black growths that appear anywhere on the skin.

ACANTHOSIS NIGRICANS-a cutaneous disorder marked by hyperkeratosis and pigmentation of the

axilla, neck, flexures, and anogenital region. More than 50% of patients with acanthosis nigricans have
cancer (GI carcinomas, especially the stomach).

SQUAMOUS CELL CARCINOMA (SCC)-a common primary MALIGNANT TUMOR OF SKIN that
arises from keratinocytes in the middle layer of the epidermis. Most frequently in sun-exposed areas
(face and back of hands), most common in the elderly, and often originates in a pre-existing actinic
keratosis (warty lesion occurring on sun-exposed parts of elderly people).

• SCC is characterized by neoplastic epidermal cells often with “keratin pearls”.

• SCC is associated with chemical carcinogens (arsenic), and radiation or x-ray exposure.

• SCC is most often locally invasive, but can infiltrate underlying tissue or metastasize in
lymphatic channels. Treatment involves complete excision or radiation therapy.

• SCC resembles cervical cancer in histologic appearance and biologic behavior. The most
common site for primary squamous cell carcinoma in women is the uterine cervix.

• Skin cancer is the most common malignancy in the U.S.

• Most common intra-oral site is the LATERAL BORDER OF THE TONGUE.

• Most common extra-oral site is the LOWER LIP VERMILLION BORDER.

• Malignant epithelial cells have an increased number of laminin receptors. Laminin (a

glycoprotein) is a major component of basement membranes and has numerous biological activities
 including promotion of cell adhesion, migration, growth, and differentiation.

• SCC is the most common malignant LARYNGEAL TUMOR.

• SCC originates in the middle layer of the epidermis and is the MOST COMMON ORAL
CANCER. 50% die within 5 years.

• SCC is a malignant epithelial tumor accounting for over 90% of all malignant neoplasms of
the oral cavity. It begins as a red area with a scaly, crusted surface that does not heal. As it grows,
the tumor may become somewhat raised and firm, sometimes with a wart-like surface. Eventually,
the cancer becomes an open sore and grows into the underlying tissue. SCC is 2x more prevalent in
males ages 40-65.

• SCC is more common on the lips (lower lip) than intra-orally. The most common site of
intraoral squamous cell carcinoma is the lateral border and ventral surface of the tongue; the
floor of the mouth is the second most common site. SCC of the palate is uncommon and the
dorsal surface of the tongue is almost never affected. Cancer of the mouth floor occurs most
commonly in the anterior segment of the midline, near the orifices of the salivary glands.

• RISK FACTORS for oral squamous cell carcinoma are smoking, alcohol consumption, painful
and ill-fitting dentures, chronic inflammation, and use of smokeless tobacco. Tobacco is the
primary risk factor.

Basal Cell Carcinoma and Squamous Cell Carcinoma are similar as both are invasive, exhibit mitotic
figures, and are cured by early surgical excision.
BREAST CANCER-most common malignancy of women in the U.S., second only to LUNG CANCER
as a cause of death from cancer among women.

• CARCINOMAS OF THE BREAST-are almost all adenocarcinomas and occur in a number of

histologic types, mostly as invasive duct carcinomas. It affects 1 out of 11-13 women during their
lifetime, of which 1/3 die of the disease. Breast cancer is uncommon before age 35. The
strongest association with an increased risk for breast cancer is family history, specifically
breast cancer in first-degree relatives (mother, sister, daughter). Tumors occur most often in the
upper outer quadrant in the left breast.

• A PAINLESS MASS IN THE BREAST is the first sign or symptom. However, retraction of the
skin or nipple and peau d’orange (a swollen pitted skin surface) along with enlargement of the
axillary lymph nodes may be present. Widespread metastasis can occur via the axillary lymph
nodes, usually to the lung, bone, and liver.

• FIBROCYSTIC DISEASE OF THE BREAST is the MOST COMMON CAUSE of clinically

palpable breast mass in women ages 25-50. Signs and symptoms are lumpiness throughout both
breasts. Pain is common, especially prior to the menstruation period. It is not malignant, but can
lead to increased chance of developing carcinoma. Obesity increases breast cancer risk.

COLORETAL CANCER (cancer of large intestine and rectum)-is second in incidence only to
carcinoma of the lung in men, and is third after breast and lung cancer in women. Colorectal cancer is
associated with increased serum concentration of carcinoembryonic antigen (CEA).
• Predisposing factors for colorectal cancer: adenomatous polyps, inherited multiple polyposis
syndromes, long-standing ulcerative colitis, genetic factors, and low fiber, high animal fat diet.

• Treatment: surgery is the only curative treatment for colorectal cancer.

A MALIGNANT NEOPLASM of the colonic or rectal mucosa is almost always an adenocarcinoma.

There is a rapidly increasing incidence with age, starting at age 40. Rectal bleeding with either
diarrhea, abdominal pain, and weight loss are common symptoms. SIGMOID COLON IS THE
MOST COMMON SITE. Tumors on the right side of the colon usually cause constipation and are
not as serious as tumors in the left-side.

PROSTATE CANCER-second most common cause of cancer DEATH among American men. Lung
Cancer is the number one killer from cancer in both men and women.
• MOST PROSTATIC TUMORS are adenocarcinomas that arise in peripheral glands, invade
throughout the prostate, and metastasize to bone (typically pelvis, ribs, and vertebrae), and other
tissues (like the lungs). Prostate cancer is most often diagnosed by RECTAL EXAMINATION.
There is an increasing incidence with age (it is uncommon under age 50). Prostate tumors are
hormonally dependent. Lab findings show elevated levels of acid phosphatase and prostate-
specific antigen (PSA) in the serum of patients with prostate cancer.

• NODULAR HYPERPLASIA OF THE PROSTATE-a benign enlargement of the prostate due

to hyperplastic nodules of stroma and glands distorting the prostate. Nodular hyperplasia
 compresses the urethra and causes urinary tract obstruction. Complications are pyelonephritis,
hydronephrosis, & painful or difficult urination (dysuria). It is not considered to be
premalignant.

LUNG CANCER-the LEADING CAUSE OF CANCER DEATH IN THE U.S. Half of the cancers are
inoperable by the time the patient is first seen in the hospital. Often the first signs of lung cancer are
related to metastasis (particularly to the brain). Other common sites of metastases include the endocrine
glands, skin, liver, and bones. The route of metastasis is through the lymphatic channels. Lung cancer
affects males more than females (4 to 1).
• CIGARETTE SMOKING causes 90% of lung cancers. Tobacco smoking is the most important
etiologic agent in the causation of lung cancer. Benzpyrene is a VERY POTENT carcinogen
found in cigarette smoke.
• The most common lung cancer is ADENOCARCINOMA.

MOST LUNG CANCERS arise from the MAIN BRONCHUS and are called bronchogenic
carcinomas. It is a primary malignant neoplasm of the lung, originating from transformed bronchial
epithelium. More than 90% of lung cancers start in the bronchi (large airways that supply the lungs);
such cancer is bronchogenic carcinoma. Alveolar cell carcinomas originate in the air sacs (alveoli) of
the lung.

BRONCHOGENIC CARCINOMA (4 TYPES): the most common primary lung tumor and cancer
causing most deaths. The most common type of lung cancer is NON-SMALL CELL LUNG CANCER
(85%). Subtypes include:
1. Squamous cell carcinoma (25%)-most arise in the central portion of the lung; appear as a hilar
mass and frequently undergo central cavitation. Clearly linked to cigarette smoking.

2. Adenocarcinoma (35%)-the MOST COMMON TYPE OF LUNG CANCER among men and
women. arises in the periphery, usually in the upper lobes of the lungs; develops on site of prior
pulmonary inflammation or injury (old TB, scars, healed infarcts). Less clearly linked to cigarette
smoking.

3. Small Cell (Oat Cell) carcinoma (25%)-most arise in the central portion of the lung; most
aggressive and highly malignant. Most commonly affects men (80%) and 90% of them are
cigarette smokers. The oat cell observed in these carcinomas is a short, blunty spindle-shaped,
anaplastic cell containing a relatively large, hyperchromatic nucleus with little or no cytoplasm.
SMALL CELL (OAT CELL) IS MOST AGGRESSIVE BRONCHOGENIC CARCINOMA.

4. Large Cell Carcinoma (15%)-arises in the lung periphery; very poorly differentiated cells.

PERSISTENT COUGH is the MAIN SYMPTOM OF LUNG CANCER, and is manifested clinically
by hemoptysis and bronchial obstruction, often with atelectasis and pneumonitis. Symptoms that arise
later are loss of appetite, weight loss, and weakness.
• Many cancers that start elsewhere in the body spread to the lungs. Cancers spread to the lungs most
commonly from the breast, colon, prostate, kidney, thyroid, stomach, cervix, rectum, testis, bone,
and skin.
• Carcinoma of the lung is the #1 killer from cancer in the U.S. Tobacco (cigarette smoking) is
 the primary cause.

Other Diseases Caused by Smoking (Cigarettes):

• Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic
bronchitis.
• Carcinoma of the larynx and oral cavity.
• Increased incidence of carcinoma of the esophagus, pancreas, kidney, and bladder.
• Peptic ulcer-disease
• Low birth-weight infants

PHEOCHROMOCYTOMA-a tumor that originates from chromaffin cells of ADRENAL MEDULLA

GLAND, causing overproduction of catecholamines, powerful hormones that induce HIGH BLOOD
PRESSURE (the most prominent symptom. These tumors are uncommon, often benign, and may occur
in men or women at any age, but are most common between ages 30-60.
• In 50% of the people, HBP is persistent, and in the other 50%, it is paroxysmal (episodic). If the
tumor is derived from extra-adrenal chromaffin cells, it is called paraganglia (metastasis is
more common in this tumor).

• Pheochromocytoma can be associated with MEN (multiple endocrine neoplasia),

neurofibromatosis (von Recklinghausen’s disease), or von Hipple-Lindau disease (multiple
hemangiomas).

NEUROBLASTOMA-a highly malignant tumor of EARLY CHILDHOOD that originates in the

Adrenal Medulla. THE MOST COMMON TUMOR OF CHILDHOOD & INFANCY. Complications
are invasion of abdominal organs by direct spread and metastasis to liver, lung, or bone. The first
symptoms in many children are a large abdomen, sensation of fullness, and abdominal pain, followed
by an abdominal mass. About 90% of neuroblastomas produce hormones (e.g. epinephrine) that
increase heart rate and cause anxiety. Adrenal gland is the primary site of origin of a neuroblastoma.
Appears most often in children!

LYMPHOMAS (malignant lymphoma)-a general term for ordinarily malignant neoplasms of lymphoid
and reticuloendothelial tissues. These neoplasms are circumscribed solid tumors composed of cells that
appear primitive or resemble lymphocytes, plasma cells, or histiocytes. Men are more likely than
women to develop lymphoid tumors. Patients with immunodeficiencies have increased risk for
developing malignant lymphoma. Lymphoma is usually discovered when a patient has a painless
enlarged lymph node, most often in the neck, but sometimes in the armpit or groin. Additional
symptoms may include fever, night sweats, and weight loss. Although lymphomas principally involve
lymph nodes, spleen, liver, and bone marrow, they may infiltrate any organ or soft tissues.
• Lymphadenopathy-the most common initial sign or symptom in patients with malignant lymphoma.

NON-HODGKIN’S LYMPHOMA-a group of related malignant neoplasm that originates most

frequently within lymph nodes and spread throughout the body, characterized by the absence of Reed-
Sternberg cells. Non-Hodgkin’s lymphoma is more common than Hodgkin’s disease, and often observed
in AIDS. 2 Subtypes of Non-Hodgkin’s lymphoma are Burkitt’s lymphoma & mycosis fungoides.

BURKITT’S LYMPHOMA (NON-HODGKINS)-a high-grade B-cell lymphoma closely linked to

EBV.
• African form-closely related to EBV infection (95% of cases). Affects children of middle
African regions. Frequently involves the maxilla or mandible.

• American form-EBV infection is not as common (15% of cases). Usually involves abdominal
organs; tumors of the jaws are rare.

• In the African and American forms of Burkitt’s Lymphoma, the lymph nodes are spared.

• Burkitt’s lymphoma is the first human cancer strongly linked to Epstein-Bar Virus (EBV).

MYCOSIS FUNGOIDES-a rare, persistent, slow-growing type of non-Hodgkin’s lymphoma that

originates from a mature T lymphocyte & affects the skin; it may progress to the lymph nodes and
internal organs.

HODGKIN’S DISEASE-MALIGNANT DISORDER characterized by painless, progressive

enlargement of lymphoid tissue, usually first evident in the cervical lymph nodes. Splenomegaly is
common and most importantly has Reed-Sternberg cancer cells; the actual neoplastic cells with a
distinct appearance under the microscope.
• Symptoms: anorexia, weight loss, generalized pruritus, low grade fever, night sweats, anemia, and
leukocytes. It affects twice as many males as females, and develops between ages 15-35.

• 4 Types:
1. Lymphocyte predominance-3% of cases, few Reed-Sternberg cells, but many
lymphocytes; favorable prognosis.
2. Nodular sclerosis-the most common (67%), small number of Reed-Sternberg cells,
lacunar cells (Reed-Sternberg variant) are prominent; good prognosis.
3. Mixed Cellularity-25% of all cases, moderate number of Reed-Sternberg cells; good
prognosis.
4. Lymphocytic depletion-5% of cases, numerous Reed-Sternberg cells; poorest
prognosis.

• Many researchers believe Hodgkin’s disease starts as an inflammatory or infectious process and
then becomes a neoplasm; others believe it to be an immune disorder. The etiology of Hodgkin’s
disease remains an enigma (unknown).

• There is a relationship between lymphocytic lymphoma & lymphocytic leukemia.

Histologic Features of Malignancy: Anaplasia, Hyperchromatism, Pleomorphism, Abnormal mitosis.

• Differentiation-a measure of a tumor’s resemblance to normal tissue.
• Anaplasia-the absence of differentiation.

HOST RESPONSE TO A MALIGNANCY is best reflected by lymphocytic infiltration at the edge

of the tumor. The most characteristic feature of a malignancy compared to an inflammatory lesion is that
malignancy will grow after removing the causative agent. The most important characteristic of
malignant neoplasms that distinguishes them from benign neoplasms is THEIR ABILITY TO
METASTASIZE.
DYSPLASIA-a type of nonmalignant cellular growth (an epithelial change highly indicative of a pre-
cancerous growth), that may precede neoplastic changes in the tissue. Dysplasia is associated with
chronic irritation of a tissue by a chemical agent (e.g. cigarette smoke), or by a chronic inflammatory
irritation such as chronic cervitis. The tissue appears somewhat structureless and disorganized and
may consist of atypical cells without invasion. Epithelium exhibits acanthosis (abnormal thickening of
prickle cell layer = stratum spinosum).

BENIGN TUMORS derived from mesenchymal origin: (Leiomyoma, Rhabdomyoma, Lipoma,

Fibroma, Chondroma, Papilloma, Adenoma, and Myxoma):
1. Leiomyoma-derived from smooth muscle. Includes the most common neoplasm of women, the
uterine leiomyoma or fibroid tumor.
2. Rhabdomyoma-derived from skeletal muscle.
3. Lipoma-derived from adipose tissue. It is the most common soft tissue tumor.
4. Fibroma-derived from fibrous C.T.
5. Chondroma-derived from cartilage.
6. Papilloma-derived from surface epithelium (e.g. squamous epithelium of the skin or tongue).
7. Adenoma-derived from glandular epithelium.
8. Myxoma-derived from C.T.

CHORISTOMA-a small benign mass of normal tissue misplaced within another organ such as liver
tissue in the intestine wall.

HAMARTOMA-a benign tumor-like overgrowth of cell types that are regularly found within the affected
organ such as a hemangioma, an irregular accumulation of blood vessels.

MULTIPLE MYELOMA-a PLASMA CELL CANCER in which a clone of abnormal plasma cells
multiply and form tumors in bone marrow, which produces a large quantity of abnormal antibodies
(immunoglobulins) that accumulate in blood or urine. Involves bone pain, osteolytic lesions, plasma
cell infiltration of marrow, and synthesis of abnormal immunoglobulins.
• Characterized by appearance of scattered malignant tumors in various bones in the body
(osteolytic lesions); associated with the production of abnormal immunoglobulins and the presence
of Bence Jones protein in urine caused by light chain dimers. This condition occurs mostly in
males ages 50-70.

• Primary malignant neoplasm of PLASMA CELLS most often arising in BONE MARROW.

• Cause is unknown; it is twice as common in blacks; has a slight male predominance, and is
uncommon before age 40.
• Multiple myeloma is characterized by secretion of abnormal immunoglobulins (M protein, most
often IgG or IgA of either kappa or lambda light-chain specificity), destructive (osteolytic)
bone lesions, and replacement of normal marrow cells.

• Abnormal antibody pieces (Bence-Jones protein) build up in the urine.

• Hyperglobulinemia causes RBC rouleaux formation (RBC aggregate together like a stack of
 poker chips) on a blood smear.

• BONE PAIN in the back or hip may be the initial patient complaint. The pain arises from
pressure created by malignant plasma cells on the nerves in the periosteum of the bone.

• X-rays show a distinctive “punched-out” appearance. Other clinical features: anemia,

pathogenic bone fractures, increased susceptibility to infection (most common cause of death),
hypercalcemia, renal failure, and amyloidosis.

LEUKEMIAS-cancer that usually affects WHITE BLOOD CELLS. The cause of most leukemias is
unknown. However, these agents are closely associated with leukemia development.
• Ionizing radiation-increased incidence of leukemias among atomic bomb survivors and
radiologists-usually myelogenous.

• Viruses-a virus called HTVL-1 (human T-cell lymphotrophic virus type 1), which is similar to
the AIDS virus, is strongly suspected to be the cause of a rare type of leukemia (Adult T-cell
leukemia). Leukemic patients have a high antibody titer to the EPSTIEN-BARR VIRUS (EBV).

• Genetic Disorders-Philadelphia chromosome (translocation of chromosomal material from

chromosome 22 to chromosome 9) is present in 90% of patients with chronic myelogenous
leukemia; also, higher incidence of acute leukemia in patients with Down syndrome (mongolism)
= Trisomy 21.

• Certain chemicals (benzene)-benzene and the use of some anticancer drugs increase the risk of
developing leukemia.

Leukemia is classified by the dominant cell type and by the duration from onset to death. Leukemia can
modify the inflammatory reaction.

4 TYPES OF LEUKEMIA (WBC CANCER):

1. Chronic Lymphocytic Leukemia (CLL)-characterized by a large number of cancerous mature
lymphocytes and enlarged lymph nodes. Affects men 2-3 times more than women. The average age
of people with CLL is 60 years old. May be predisposition to older white males of jewish decent.
• CLL includes Sezary syndrome and hairy cell leukemia. Its progression is SLOW,
affecting white blood cells (lymphocytes). Represents 31% of CLL cases, mostly affecting
adults over age 60. THE LEAST MALIGNANT LEUKEMIA.

2. Chronic Myelocytic Leukemia (myeloid, myelogenous, granulocytic)- slow progression,

affecting white blood cells (Myelocytes). Represents 22% of CLL cases, affecting any age.

3. Acute Lymphocytic Leukemia (lymphoblastic)-its progression is RAPID, affecting white blood

cells (lymphocytes). Represents 20% of CLL cases, mostly affecting children ages 3-5 years.

4. Acute Myeloid Leukemia (myelocytic, myelogenous, myeloblastic, myelomonocytic)- its

progression is RAPID, affecting white blood cells (myelocytes). Represents 27% of CLL cases,
mostly affecting ADULTS. The most malignant leukemia.
All types of leukemia occur in an ACUTE or CHRONIC form, but 50% are ACUTE. Acute
myelogenous leukemia is the most malignant type and chronic lymphocytic leukemia the least
malignant.

ACUTE LEUKEMIA-progress rapidly, characterized by the predominance of blasts cells

(lymphoblasts, myeloblasts), that are immature precursors of blood cells. Without treatment, acute
leukemia follows a short and painful course, with death usually occurring within 6-12 months. Acute
Leukemia is most common malignancies of the pediatric age group (under 20 years).

Acute Leukemia Characteristics:

• Abrupt onset (few months) with fever, weakness, malaise, severe anemia, and generalized
lymphadenopathy; bone and joint pain are common in children.

• Principal organs involved are bone marrow, spleen (splenomegaly), and liver (hepatomegaly).
Lymph node enlargement is common in acute lymphocytic leukemia.

• Petechiae and ecchymosis in skin and mucous membranes, hemorrhage from various sites;
bacterial infections are common.

• Lab findings: Leukocytosis 30,000-100,000 per cu. mm with immature forms (myeloblasts and
lymphoblasts) predominating; anemia and thrombocytopenia; bleeding and coagulation times may
be prolonged; tourniquet test is usually positive.

• In 75% of acute lymphocytic leukemia cases, lymphocytes are neither B nor T cells, but are
called “null cells”.

• Untreated patients die within six months; with intensive therapy (chemotherapy, radiation, and
marrow transplants) remissions lasting up to 5 years may be obtained; death is usually due to
hemorrhage (brain) or a superimposed bacterial infection.

ACUTE LYMPHOCYTIC LEUKEMIA (ALL)-a.k.a. lymphoblastic leukemia is the MOST

COMMON PEDIATRIC CANCER. ALL is a life-threatening disease in which the cells that normally
develop into lymphocytes (lymphoblasts) become cancerous and rapidly replace normal cells in the bone
marrow. The peak age is 4 years old, and acute leukemia form is the most responsive to therapy.

ACUTE MYELOID LEUKEMIA (AML)-a life-threatening disease where myelocytes (cells that
normally develop into granulocytes) become cancerous and rapidly replace normal cells in the bone
marrow. AML affects all ages, but mostly adults.

Acute and Chronic leukemias of all types cause ORAL LESIONS. The most common involvement of
oral tissues is seen in acute monocytic leukemia (a subtype of acute myeloid leukemia), in which 80%
of patients exhibit gingivitis, gingival hyperplasia, petechiae, and hemorrhage.
• Spontaneous gingival bleeding in acute leukemia is due to THROMBOCYTOPENIA.

CHRONIC LEUKEMIA-characterized by PROLIFERATIONS of lymphoid or hematopoietic cells

that are more mature than those of the acute leukemias. They progress slowly, have a longer, less
devastating clinical course than acute leukemias, and they constitute ~50% of all leukemias. Clinical
Features:
• Insidious onset with weakness and weight loss-disease may be detected during examination for
another condition (e.g. anemia, unexplained hemorrhages, or recurrent intractable infection).

• Organ involvement similar to acute type-massive splenomegaly is characteristic of chronic

myelogenous leukemia; lymph node enlargement is the main pathologic finding in lymphocytic
type.

• Petechiae and ecchymosis, recurrent hemorrhages, bacterial infections-lymphocytic anemia

may be complicated by autoimmune hemolytic anemia.

• Laboratory Findings-leukocytosis above 100,000 per cu. mm. With mature forms (granulocytes
and lymphocytes) predominating; Philadelphia chromosome and low levels of leukocyte alkaline
phosphatase are common in myelogenous (myelocytic) leukemia.

• Median survival time for patients with chronic myelogenous leukemia is 4 years with death
due to hemorrhage or infection; chronic lymphocytic leukemia runs a variable course; older
patients may survive years even without treatment.

CHRONIC MYELOCYTIC LEUKEMIA (CML)-(myeloid, myelogenous, granulocytic)-

characterized by a specific chromosome marker. It’s a disease in which a cell in the bone marrow
becomes cancerous and produces a large number of abnormal granulocytes (type of WBC).

• CML may affect people of any age and either sex, but is uncommon in children under 10 years old.
Its progress is marked by malaise, fatigue, bleeding gums (abnormal bleeding in general),
purpura, weight loss, and massive splenomegaly. CML patients are highly susceptible to
infections.

• Chromosomal analysis of the leukemic WBC almost always shows a rearrangement of

chromosomes. The leukemic cells almost invariably are associated with the Philadelphia
chromosome-a chromosome that has a specific piece of another chromosome attached to it.

 INFECTIONS
EPIDEMIC-an infection that occurs much more frequently than usual.
PANDEMIC-an infection that has worldwide distribution.
ENDEMIC-an infection constantly present at a low level in a specific population.
CONTAGIOUS-a disease that is highly communicable.

• Many infections are unapparent or subclinical and are only detected by demonstrating a rise in
antibody titer or by isolating the organism.

• Some infections result in a latent state, after which reactivation of the growth of the organism
and recurrence of symptoms may occur.

• Other infections lead to a chronic carrier state, where the organisms continue to grow with or
without producing symptoms in the host.

TUBERCULOSIS-a contagious, potentially fatal infection caused by the airborne bacterium

Mycobacterium tuberculosis (most commonly), M. bovis, or M. africanum. Tuberculosis occurs
worldwide, with the greatest frequency in disadvantaged groups. It is more common among the elderly
and in blacks than white. Tuberculosis is caused by an agent that does not produce exotoxins nor
endotoxins. Tuberculin skin test (Mantoux Tuberculin Test) determines a prior TB exposure.
• PRIMARY TUBERCULOSIS-occurs on first exposure to the organism. Characterized by the
Ghon focus-a lesion at the pulmonary site in the lung and regional lymph nodes. The Ghon focus
and involved hilar lymph nodes make up the Ghon Complex (consists of subpleural parenchyma
and hilar lymph nodes).

• SECONDARY TUBERCULOSIS-disease that develops long after the primary infection, most
commonly due the reactivation of the primary infection. Characterized by tubercle formation
(caseous granuloma) and subsequent cavitary lesions. The lungs are the common infection site
of secondary TB. Secondary TB is complicated by lymphatic hematogenous spread, resulting
in miliary TB. This results in the seeding of several organs with multiple, small, millet, seed-like
lesions.

TUBERCUOSIS TREATMENT involves multiple-drug therapy with Isoniazid (INH), Rifampin, and
Pyrazinamide in the same capsule. Streptomycin and ethambutol may also be used.

INFLUENZA (FLU)-a viral infection that causes fever, runny nose, cough, headache, malaise, and
muscle ache. It is the fever and constitutional symptoms that distinguish influenza from the common cold.
Influenza viruses (A,B,C) are the only members of the orthomyxovirus family. Main mode of
influenza prevention is the VACCINE, which consists of killed influenza A and B viruses. The
influenza viruses have spikes (peplomers) on their outer envelopes important in increasing the virus’s
ability to attach to human cells during the establishment of an infection.

• INFLUENZA A-by far the most common and causes the most severe disease. Amantadine
 (Symmetrel) inhibits influenza A virus replication by interfering with viral attachment and
uncoating. It is effective in the prophylaxis and treatment of influenza A.

• INFLUENZA B-involves Reye’s syndrome, a serious and potentially fatal complication

characterized by encephalopathy and liver degeneration which occurs most commonly in children.
Aspirin given to reduce fever in viral infections is implicated in the pathogenesis of Reye’s
syndrome.

BOTULISM-an uncommon, life-threatening poisoning caused by toxins produced by Clostridium

botulinum (a gram-positive, spore-forming, anaerobic rod). Botulism spores are widespread in soil
and contaminate vegetables and meats. When these foods are canned or vacuum-packed without proper
sterilization, spores survive and germinate in the anaerobic environment. Toxin is produced within
the canned food and ingested preformed.

• BOTULINUM TOXINS (neurotoxins) are the most potent toxins know to humans. These
neurotoxins bind to nerve synapses, blocking the release of acetylcholine from CNS nerve
cells causing loss of motor function. The inability to transmit impulses through motor neurons can
cause respiratory failure and death.

• BOTULISM SYMPTOMS appear 8-48 hours after ingestion of the toxin. Antitoxin and
respiratory support are treatments. The antitoxin can reverse damage, and may slow or stop
further physical and mental deterioration, so the body can heal itself over a period of months.

• BOTULISM CLINICAL FINDINGS: nausea, vomiting, dizziness, Diplopia (double vision),

Dysphagia (difficulty swallowing), muscle weakness, and respiratory failure.

BACTERIAL MENINGITIS-inflammation of the meninges of the brain and spinal cord. Neisseria
meningitis, Hemophilus influenzae (is the most common cause of meningitis in children under age two),
and Streptococcus pneumoniae account for more than 80% of all meningitis cases. Meningitis is most
common in children between ages one month and 2 years.
• Signs and Symptoms: headache, stiff neck, vomiting, and a fever that develops over one to several
days.
• Neisseria meningitis, Hemophilus influenza, Streptococcus pneumoniae account for more than
80% of all cases.
• Waterhouse-Friderichsen Syndrome-an overwhelming, rapidly progressing infection caused by
Neisseria meningitis. It produces severe diarrhea, vomiting, seizures, internal bleeding (bilateral
adrenal hemorrhage), low blood pressure, shock, and often death.

ENCEPHALITIS-inflammation of the brain, caused by an arbovirus (viral encephalitis). VIRUSES

cause most cases of encephalitis.
• Encephalomyelitis-inflammation of the brain and spinal cord, caused by a virus.
• Aseptic meningitis-inflammation of the meninges caused by a virus.

GONORRHEA-a sexually transmitted disease caused by the bacterium Neisseria gonorrhea which
infects the lining (mucous membranes) of male and female urethra; vagina, cervix; rectum, throat, and
conjunctiva of the eyes in both sexes. Gonorrhea often occurs together with Chlamydia and Syphilis.
 • Complications: female sterility, and in newborns (gonococcal ophthalmia which involves infection
of the conjunctiva and may lead to scarring and blindness).
• In men, the first gonorrhea symptoms appear 2-7 days after infection, starting with mild discomfort
in the urethra, followed by mild to severe pain during urination and discharge of pus from the
penis.
• Women often have no symptoms; if they do, the symptoms are frequent and painful urination with
discharge of pus from the vagina.
• Treatment: Gonorrhea is treated with a single injection of ceftriaxone or with doxycycline.

CHLAMYDIAL INFECTIONS-common, asymptomatic, sexually transmitted diseases caused by C.

trachomatis (an obligate, intracellular parasite). Young women who contract Chlamydia may also
require salpingitis (inflammation of the fallopian tubes).

SYPHILIS-a sexually transmitted disease caused by infection with Treponema pallidum (a

spirochete) manifests during the primary stage as hard chancre (an elevated, painless, superficially
ulcerated, firm papule). Gummas are lesions of tertiary syphilis. Syphilis can occur in 3 Stages:
1. Primary Syphilis-a non-painful chancre that appears 3-6 weeks later at the site of local contact.
The lips are the most common site of chancres to appear in primary oral syphilis.

2. Secondary Syphilis-highly infectious stage that occurs 6 weeks after non-treatment of primary
syphilis. A maculopapular rash and condyloma lata (flat-topped papules) appear on the skin
and mucosal surfaces. Also mucus patches in the oral cavity.

3. Tertiary Syphilis-occurs in infected persons many years after non-treatment of secondary

syphilis. The gumma (lump or focal nodular mass) is a lesion of the tertiary stage that most
commonly occurs on the palate and tongue. Neurologic symptoms are evident during this stage.
Tertiary syphilis causes irreversible heart failure, dementia, and disability.

With syphilis, congenital infections in neonates and infants can occur. The prognosis for syphilis is good
if treated early. Parenteral Penicillin G is the drug of choice for treating all 3 stages.
• Syphilis is a disease caused by an agent that DOES NOT produce endotoxins or exotoxins.

ACUTE APPENDICITIS-the most common cause of sudden, severe abdominal pain and abdominal
surgery in the U.S. Its an inflammatory condition of the vermiform appendix occurring when there is an
obstruction of the appendiceal lumen, most often by a fecalith, resulting in proliferation and invasion of
the mucosa.
• Symptoms: nausea, vomiting, fever, and excruciating pain in the lower right abdomen. To avoid a
rupture of the appendix, abscess formation, or inflammation of the lining of the abdominal cavity
(peritonitis), surgery is performed ASAP.

LEUKOCYTOSIS-an abnormally large number of leukocytes (WBC) normally caused by a systemic

bacterial infection. Usually, there is a disproportionate increase in the number of neutrophils
(neutrophilic leukocytosis). Not all bacterial infections increase neutrophils (e.g. typhoid fever &
brucellosis result in depression of neutrophils).

Many viral infections cause a lowered number of leukocytes (leukopenia), particularly neutrophils,
and cause lymphocytosis. A general indication if a disease is of bacterial or viral origin is obtained by
performing a leukocyte count (especially neutrophils).
• normal range for leukocytes is 5,000-10,00 per cu mm of blood.
• occasionally, the circulating levels of leukocytes may reach very high levels up to 100,000 per cu
mm of blood = a leukemoid reaction, and is sometimes difficult to differentiate from leukemia.
• Parasitic infections cause an increase in the number of eosinophils in peripheral blood.
• margination of leukocytes is the lining up of the white blood cells along a vessel wall.

ACTINOMYCOSIS (Lumpy Jaw)-a chronic infection by Actinomyces (usually A.israelii)

characterized by slow-growing, deep, lumpy abscesses that extrude a thin, purulent exudates through
multiple sinuses. It develops chiefly in the jaws and neck, less frequently in the lungs and alimentary
tract.
• The disease occurs after tissue damage contaminated with the endogenous organism, and is treated
with long-term Penicillin therapy.
• Actinomyces are gram-positive filamentous bacteria that normally inhabit the oral cavity and
GI tract. Actinomycotic lesions have “sulfur granules” (colonies of infecting organisms) in them.

LUDWIG’S ANGINA-although rare, Ludwig’s Angina is usually an extension of infection from the
mandibular 2nd and 3rd molars into the floor of the mouth, since their roots lie below the attachment of
the mylohyoid muscle. It is often caused by normal oral flora gaining access through an infected
tooth.

Ludwig’s Angina Characteristics:

• First, it’s a brawny induration that does not pit on pressure. No fluctuance is present. Second,
three facial spaces are involved bilaterally (submandibular, submental, and sublingual spaces).
Third, the patient has a typical openmouthed appearance.

• MOST CASES OF LUDWIG’S ANGINA appear as a MIXED INFECTION. Streptococci are

almost always present.

• Can cause severe swelling of the mouth floor, even forcing the tongue upward, blocking the
airway. Fever and malaise are usually present.

LUDWIG’S ANGINA SOURCE OF INFECTION


 ORAL CAVITY (PLAQUE, CARIES & CALCULUS)
DENTAL CARIES-the primary etiologic agent initiating dental caries is Streptococcus Mutans. Other
bacteria etiologically related to dental caries include:
• Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, Streptococcus fecalis;
Actinomyces viscosus, Actinomyces naeslundii, Actinomyces Israeli, Lactobacillus casei.

• Prerequisites for dental caries development: Cariogenic bacteria, Susceptible host, & supply
of substrate for lactic acid production. Lactic acid-the chief product of carbohydrate metabolism
of Streptococcus mutans.

Bacteria that initiate dental caries must have the ability to produce extracellular insoluble glucans.
• Dextrans & mutans-insoluble glucans (both are glucose polymers) produced by Streptococcus
sanguis, mutans, salivarius, and Lactobacillus species.
• Levans (Fructans)-polymers of fructose produced by Streptococcus salivarius, mutans, and
sanguis, and Lactobacillus casei, and acidophilus.
• Dextrans, mutans, and levans are synthesized from dietary sucrose by cariogenic and plaque
bacteria primarily as extracellular polysaccharides.

Actinomyces viscosus and naeslundii cause ROOT-SURFACE CARIES.

STREPTOCOCCUS is implicated in the dental caries process. S. Mutans, S. Sanguis (the most
frequently isolated Streptococcus in the oral cavity), and S. Salivarius. These bacteria produce dextran
sucrase (glucosyltransferase), which catalyzes the formation of extracellular glucans from dietary sucrose.
Glucan production contributes to the formation of dental plaque which holds the lactic acid
produced by these Streptococci against the tooth. This acid eats through the tooth enamel, creating
caries. The major cariogenic property of S. mutans is its ability to produce the enzyme
glucosyltransferase.

• STREPTOCOCCI properties necessary for caries formation: their adherence to the tooth
surface (colonize on tooth surface), they produce lactic acid which dissolves tooth enamel, and
they produce a polymeric substance (from carbohydrate metabolism) which causes lactic acid to
remain in contact with the tooth. **Streptococci are gram-positive cocci (facultative anaerobes)
and are the most numerous group of bacteria in the oral cavity.

Streptococci found in dental plaque:

• S. Sanguis (produces hydrogen peroxide)
• S. Mutans (is aciduric and produces lactic acid)
• S. Salivarius (found consistently in saliva and on oral soft tissue).
• S. Mitis (produces hydrogen peroxide).
• **Lactobacillus casei is also acidogenic (produces lactic acid).

GINGIVAL SULCUS-an area of stagnation and bacterial proliferation. The sulcus is the principal
oral site for the growth of spirochetes, fusobacteria, and other gram-negative anaerobes. Factors
that contribute to sulcus bacterial growth:
1. increase in gingival crevicular fluid (GCF)
2. desquamation of epithelial cells
3. bacterial acid products.

NORMAL, HEALTHY MOUTH consists mainly of obligate and facultative anaerobes, and
acidogenic bacteria. These bacteria are found in the normal, healthy gingival sulcus that become
opportunistic and influence the course of periodontal treatment.

Acute Necrotizing Ulcerative Gingivitis (ANUG, Vincent’s infection, trench mouth)-a condition that
presents pathognomonic clinical signs & symptoms. ANUG’s two most important clinical signs:
1. Interproximal necrosis and pseudomembrane formation on marginal tissues.
2. History of soreness (pain) and bleeding gums caused by eating and brushing.

• Other signs and symptoms are a fetor oris (offensive odor), low-grade fever, lymphadenopathy,
and malaise. Neutrophil is the dominant WBC in the inflammatory infiltrate of ANUG.

• ANUG OCCURS MOST OFTEN in adults between ages 18-30. Predisposing factors to ANUG
are history of gingivitis, tobacco smoking, gross neglect (poor oral hygiene), fatigue, and stress.

• ANUG BACTERIA: intermediate-sized spirochetes, Prevotella intermedia, Fusobacterium,

Selenomonas. Bacteroides species of bacteria is most commonly associated with the
development of ANUG.

DENTAL PLAQUE-the key etiologic agent in the initiation of gingivitis and periodontal disease.
Plaque is an accumulation of a mixed bacterial community in a dextran matrix. Streptococcus Sanguis is
usually one of the first colonizers of plaque. YOUNG PLAQUE is dominated by gram-positive cocci,
and consists of:
• Gram-positive cocci (40-50%)-Streptococcus species.
• Gram-positive rods (10-40%)-Lactobacillus species.
• Gram negative rods (10-15%)-Fusobacterium and Bacteroides.
• Filaments (4% or less)-Actinomyces and Veillonella species.

AS PLAQUE AGES, bacteria composition changes to 50% gram-positive and 30% gram-negative. The
number of cocci decreases, and number of filaments increases. The number of aerobic bacteria
decreases and the number of anaerobic bacteria increases.

BACTERIAL PLAQUE is the key etiologic agent in the initiation of gingivitis and periodontal
disease. Plaque is an accumulation of a mixed bacterial community in a dextran matrix. It forms on a
cleaned tooth surface within minutes. Different bacteria are found in plaque (cocci, rods, and filaments)
and their proportions change with time, diet, and location. Plaque is 80% water and 20% solids (95% of
which are bacteria)

STAGES OF PLAQUE FORMATION:

1. Formation of the Pellicle (acquired pellicle)-the pellicle is a surface coating of salivary origin
(protein in nature) with some carbohydrate complexes. It is structureless and bacteria-free. It
 forms on a clean tooth surface within minutes because of its salivary origin. It will also form on
crowns, dentures, and porcelain teeth.

2. Bacterial Colonization-the bacteria are deposited on the pellicle in an orderly fashion. The first
group to appear on the surface of the acquired pellicle is streptococci (gram-positive cocci) that
colonize in tremendously large numbers. After the coccal forms are established, rod-shaped
microorganisms (Bacteroides and Fusobacterium) attach to and colonize the tooth surfaces. As
the plaque matures, the bacterial morphology shifts to include filamentous types (Actinomyces).

3. Maturation Stage-saliva continues to provide agglutinating substances and other proteins to the
intercellular matrix, and bacterial intercellular adhesion results. The crystalline structure will
increase, and eventually calcifies (calculus).

SUPRAGINGIVAL PLAQUE-saliva and diet ALTER bacterial composition. It is attached or tooth

associated, consisting primarily of Gram-Positive Facultative Anaerobic Cocci.
• Supragingival Plaque Bacteria: Streptococcus Sanguis, Actinomyces Viscosus, and Naeslundii
predominate. As this plaque ages, vibrios, spirochetes, and gram-negative bacteria predominate.

SUBGINGIVAL PLAQUE-saliva and diet DO NOT ALTER bacterial composition. Can be attached
or loosely adherent (epithelium associated). As pockets form, gram-negative anaerobic rods prevail.
• Subgingival Plaque Bacteria: Actinomyces species, Fusobacterium nucleatum, Treponema species
(spirochetes), and Veillonella.

• Subgingival plaque has more anaerobes than supragingival plaque.

• Gingival inflammation increases as bacterial plaque increase, and inflammation decreases as

plaque decreases.

CALCULUS-mineralized plaque formed by bathing the plaque in a highly concentrated solution of

calcium and phosphorus (i.e. saliva). Inorganic material makes up 70-90% of the composition while
organic material and water make up the remaining composition. Subgingival calculus is dark due to
pigments from blood breakdown.
• Inorganic components of calculus (70-90%): consists of calcium and phosphates with small
amounts of magnesium and carbonate (derived almost entirely from saliva). Hydroxyapatite and
fluoride are also present.

• Organic components of calculus (10%): microorganisms (same as plaque), desquamated

epithelial cells, leukocytes, and mucin.

CALCULUS is calcified and mineralized bacterial plaque. It forms on natural teeth, dentures, and other
dental prostheses. The surface is very rough, covered by a layer of bacterial plaque. Calculus’s main role
in periodontal disease is to serve as a collection site for more bacteria. 3 phases of Calculus Formation:
1. Pellicle formation (begins to form within minutes).
2. Plaque formation (microorganisms grow together to form a cohesive plaque layer).
3. Mineralization of plaque (supragingival and subgingival).
4. 12 DAYS is the average time for calculus formation to take place.
CHLORHEXIDINE GLUCONATE (0.12%)-the most effective antimicrobial agent for reducing
plaque and gingivitis long-term, due its ability to leave the greatest residual concentration
(substantivity) in the mouth after use. Rapidly absorbed onto the teeth and enamel pellicle; and it is
slowly released. Approved by the ADA as an antimicrobial and anti-gingivitis agent. Ex: Peridex and
PerioGard.

Other Topical Antimicrobial Agents:

• Stannous fluoride-antimicrobial action is related to the stannous (tin) ion rather than to the fluoride
ion. It is available in gel form (e.g. Stop, Gel-Kam). ADA accepts stannous fluoride for anti-
caries activity, but NOT FOR anti-plaque or anti-gingivitis purposes.

• Phenolic compounds- ADA approved as antimicrobial and anti-gingivitis agents (ex: Listerine
and Crest Pro Health).

• Quaternary ammonium compounds-not as effective as others in reducing plaque or gingivitis,

best at eliminating bad breath (halitosis). Ex: Scope and Cepacol.

 CELLS & ORGANELLES
MICROBODIES-cellular organelle that contains specialized enzymes whose functions involve
hydrogen peroxide (H2O2). Microbodies isolate metabolic reactions of hydrogen peroxide and contain
catalase (an enzyme that breaks down hydrogen peroxide to oxygen and water). Microbodies are
similar in function to lysosomes, but smaller and only involved in metabolic reactions that involve
hydrogen peroxide (H2O2).
• PEROXISOME-a type of microbody found in eukaryotic microorganisms, it’s a site where
some amino acids are oxidized to produce hydrogen peroxide (H2O2).

• Anaerobic bacteria lack either superoxide dismultase or catalase or both. Anaerobic bacteria
that possess catalase can resist the effects of hydrogen peroxide (H2O2). Anaerobic bacteria
lacking catalase are sensitive to H2O2.

• Superoxide dismutase-catalyzes destruction of O2 free radicals, and protects oxygen-metabolizing

cells against harmful effects of superoxide free radicals.

LYSOZYME-a hydrolytic enzyme in human tears, mucus, and saliva. It cleaves the peptidoglycan
backbone by breaking its glycosyl bonds. The peptidoglycan molecule has two parts: (peptide and
glycan portion).
• Lysozyme attacks/degrades PEPTIDOGLYCAN (murein); it attacks the glycan portion,
which forms the backbone of the peptidoglycan.

• Protoplasts-cells whose cells walls and capsules were removed by enzymatic (lysozyme) or
antibiotic (penicillin) treatment.

LYSOSOMES-tiny, spherical, membrane-bound vesicles produced by GOLGI COMPLEX. These

vesicles contain digestive enzymes produced by the endoplasmic reticulum and then transported to the
golgi complex.

PHAGOSOME-a vesicle that forms around a particle (bacterial or other) within the phagocyte that
engulfed it. It then separates from the cell membrane and fuses with and receives the contents of
cytoplasmic granules (lysosomes). This coupling forms a phagolysosome in which digestion of the
engulfed particle occurs.

LIPOPOLYSACCHARIDE-the main component of the outer membrane of gram-negative bacteria.

It makes up the ENDOTOXIN responsible for many features of disease (e.g. fever and shock), caused
by gram (-) microorganisms.

CHITIN-a structural polysaccharide found in the exoskeletons of insects and crustaceans. Bacteria
LACK chitin.

CELLS of liver, bone marrow, blood (erythrocytes & WBC), skin, and salivary glands have the
ability to retain a latent capacity for MITOTIC DIVISION (regeneration). In circulation, RBC live
120 days, while WBC live only 2-5 hours.
• Cells (or organs) that CANNOT UNDERGO MITOSIS (Cannot Regenerate):
o Neurons in the brain or spinal cord
o Nerve cells
o Skeletal, cardiac, and smooth muscle cells
o Heart and Lungs

• Mitochondria-double membranous structure responsible for cellular metabolism (“cell

powerhouse”).

• Ribosomes-site of mRNA attachment and amino acid assembly (protein synthesis).

• Inclusion Bodies-transitory, non-living metabolic byproducts in the cell cytoplasm. Inclusions may
appear as fat droplets, carbohydrate accumulations, or engulfed foreign matter. Sites of viral
multiplication.

• Golgi Apparatus (complex)-composed of membranous sacs involved in production of large

carbohydrate molecules and lysosomes.

• Endoplasmic Reticulum-organelle that functions in transportation within the cell. Not present in
RBCs and spermatozoa. Two ER Types:
o Rough ER (studded with ribosomes that are the site of protein synthesis).
o Smooth ER synthesizes lipids, phospholipids, and steroids. Abundant in testes, ovaries,
and sebaceious glands. Smooth ER is involved in metabolism of carbohydrates, drug
detoxification, and steroid metabolism.

• Nucleus-controls synthetic activities and stores genetic information. Contains DNA.

• Lysosomes-function in cell death by autolyzing necrotic cells.

AUTOLYSIS-degradative reactions in cells caused by intracellular enzymes indigenous to the cell.

Autolysis usually occurs after the death of the cell.

AUTOLYSIN-an antibody that in the presence of complement causes cell lysis. Autolytic enzymes
produced by the organism then degrade the cell’s own cell wall structures. The result is in the presence
of cephalosporins or penicillins, growing bacteria cells are subject to lysis because without
functional cell-wall structures, the bacterial cell is not protected against osmotic shock.

HETEROLYSIS-cellular degradation by enzymes derived from sources extrinsic to the cell (e.g.
bacteria).

NECROSIS-the sum of intracellular degradative reactions occurring after the death of individual
cells within a living organism.

B-CELLS (LYMPHOCYTES)-white blood cells (WBC) that mature in BONE MARROW and
migrate to lymphoid organs. B-lymphocytes are committed to differentiate into antibody-producing
plasma cells involved in HUMORAL (antibody-mediated) immunity. When an immature B cell is
exposed to specific antigen (they recognize antigen by membrane-bound immunoglobulin), the cell is
activated. It then travels to the spleen or lymph nodes, differentiates, and rapidly produces plasma cells
and memory cells. Plasma cells synthesize antibodies.
• B-cells are found in the germinal centers of the spleen and lymph nodes.
• B-cells are progenitors of plasma cells.
• B-cells function to search out, identify, and bind with specific antigens.
• B-cells ARE NOT INVOLVED with cell-mediated immunity.

T-CELLS (LYMPHOCYTES)-white blood cells (WBC) that complete maturation in the THYMUS
and become thymocytes. T-cells are important in:
• Cell-mediated immunity, Type 4 hypersensitivity reactions (contact dermatitis), and in
modulation of antibody-mediated immunity.
• Major T-cell classes: helper T cells, suppressor T cells, and cytoxic (“killer”) T cells.
• A deficiency of T-lymphocytes can predispose a person to CANDIDIASIS.

Natural Killer T-cells secrete immunologically essential chemical compounds and assist B cells to
destroy foreign proteins, malignant cells. Killer T-cells must first be activated with interleukin-2
(IL-2) secreted by active helper T cells. T lymphocytes are MOST directly involved in contact
dermatitis.

T helper cells-help or assist other T cells and B cells to express their immune functions. T helper cells
are not antigen-specific.

LYMPHOCYTES:
1. T helper cells (TH)- help or assist other T cells and B cells to express their immune functions.

2. Cytotoxic T cells (TC)-kill and lyse target cells that express foreign antigens (cells containing
obligate intracellular parasites and tumor cells).

3. T suppressor cells (Ts)-suppress or inhibit the immune function of other lymphocytes.

4. T memory cells-long-lived cells that recognize previously encountered T dependent antigens.

5. B lymphocytes-differentiate into antibody-producing plasma cells and B memory cells in

response to an antigen.

6. Plasma cells-responsible for ANTIBODY FORMATION & SECRETION during infections..

7. B memory cells-long-lived cells that recognize a previously encountered antigen.

8. Natural killer (null cells, NK)-kill and lyse target cells that express foreign antigens.

 PATHOGEN STERILIZATION & DISINFECTION
STERILIZATION-the killing or removal of all microorganisms, including bacterial spores. Sterilization
refers to the absence of all living forms. Bacterial ENDOSPORES (spores) are the MOST resistant
to sterilization.

DRY HEAT STERILIZATION-proper sterilization time and temperature is 320pF (160FC) for 2
hours OR 3403F (170FC) for 1 hour. Dry heat destroys microorganisms primarily by coagulation of
proteins.

Items usually sterilized by DRY HEAT can be AUTOCLAVED. They should be removed immediately
after cycle to diminish the possibility of instrument corrosion, and dulling of sharp points or edges
(carbon steel instruments). Dulling of unprotected cutting edges is a disadvantage of autoclave
sterilization.

• Instruments must be dry before dry heat sterilization and Ethylene oxide sterilization-an
antimicrobial agent that inactivates cellular DNA. Water interferes with the sterilization
process. Dry heat destroys microorganisms by causing coagulation of proteins.

• Dry Heat Advantages: effective and safe for metal instrument sterilization, and does not dull
or corrode instruments.

• Dry Heat Disadvantages: long cycle, poor penetration, and will ruin heat-sensitive materials.

• BEST way to verify heat sterilization is testing with a BIOLOGICAL INDICATOR.

AUTOCLAVING-proper time and temperature for autoclaving is 250pF (15-20 minutes) at a steam
pressure of 15 pound per square inch. Autoclaving can DULL instruments.
• MOIST HEAT DESTORYS BACTERIA by denaturation of the high protein-containing
bacteria. Autoclave provides sterilization when used at is 250aF (15-20 minutes) because it
applies heat under pressure, which greatly speeds up the denaturation process compared to
boiling water. Usually only 10 minutes is required to destroy all bacteria, but the increased time is
allowed for penetration when instruments are wrapped with thick towels.

• AUTOCLAVE EFFECTIVENESS is best determined by CULTURING BACTERIAL

SPORES. Spore testing of autoclave units is recommended weekly.

• Pre-cleaning is the most important step in instrument sterilization. Debris acts as a barrier to
the sterilant and sterilization process. Ultrasonic instrument cleaning-safest and most effective
method of PRE-CLEANING.

SPORE-FORMING PATHOGENS provide the ultimate test for efficacy of sterilization. Because
bacterial spores are resistant to boiling (100BC at sea level), they must be exposed to a higher
temperature; this cannot be achieved unless the pressure is increased. For this purpose, an autoclave
chamber is used in which steam at a pressure of 15 lb./in. reaches a 121/C and is held for 15-20 minutes.
This kills even the highly heat-resistant spores of Clostridium botulinum, the cause of botulism, with a
margin of safety.

SATURATED STEAM (AUTOCLAVE)-is the most practical, most economical, and most currently
effective sporicide. The most efficient method for destroying viral and fungal microorganisms. Steam
Autoclaves operate in these ranges:
• 1211C (250CF) at a pressure of 15 pounds per square inch (psi) for 15-20 minutes. Kills all
spores.
• 1341C (270CF) at a pressure of 30 psi for a minimum of 3 minutes (“flash cycle”).
To positively destroy all living organisms, the minimum required temperature is 121mC (250CF).
Autoclaving time varies directly with the type of load placed into the chamber. The 3-minute “flash
cycle” is best indicated for unwrapped instruments. When instruments are wrapped, a longer sterilizing
cycle is required to permit adequate penetration of steam for proper disinfection.

DISINFECTANTS are antimicrobial agents that kill (germicide) or prevent the growth (microbiostatic)
of pathogenic microorganisms. Disinfectants are not safe for use on living tissue (as opposed to
antiseptics which are safe) and are applied only to inanimate objects.
1. CHLORINE-the active component of hypochlorite (bleach) used as a disinfectant. Chlorine is a
powerful oxidizing agent that inactivates bacteria and most viruses by oxidizing free
sulfhydryl groups.

2. PHENOL-was the original disinfectant used in hospitals, but is RARELY USED today as a
disinfectant because it is too caustic.

3. FORMALDEHYDE (37% solution in water-Formalin) denatures protein and nucleic acids.

DISINFECTION-the killing of many (but not all) microorganisms. Disinfection does not destroy
spores. Disinfectants are chemicals also applied to inanimate surfaces (lap tops, counter tops, headrests,
light handles). Disinfectants are not safe for use on living tissue.
• The immersion of dental instruments in cold disinfectants will not destroy spores or hepatitis
viruses (they are resistant to physical and chemical agents).

Concentration and contact time are critical factors that determine the effectiveness of an antimicrobial
agent against a particular microorganism. Any or all of the three major portions of microbial cells can be
affected: the cell membrane, cytoplasmic contents (enzymes), and nuclear material.

FILTRATION-a sterilization method for LIQUIDS. The most commonly used filter is composed of
nitrocellulose and has a pore size of 0.22 um. This size will retain all bacteria and spores. Filters work
by physically trapping particles larger than the pore size.

ETHYLENE OXIDE STERILIZATION-ethylene oxide gas has been extensively used as a

sterilization agent, especially for prepackaged, heat-sensitive surgical instruments and disposable
plastic-ware in hospitals. This gas is flammable and fairly toxic to humans, so its general use is limited.
Exposure of materials to ethylene gas must be performed in special sealed chambers. Items must be
cleaned and dried thoroughly before the sterilization process
 • Ethylene oxide sterilization is a SLOW PROCESS (10-16 hours) depending on the sterilized
material.

• Ethylene oxide functions as an alkylating agent by irreversibly inactivating cellular nucleic

acids (DNA) and proteins. It kills by alkylating proteins and nucleic acids.

• Used to sterilize surgical instruments that are sensitive to heat.

Ethylene Oxide Advantages: highly penetrative, does not damage heat-sensitive materials (rubber,
cotton, plastic), evaporates without leaving a residue, and works well for materials that cannot be
exposed to moisture.

ANTISEPTICS-chemical agents similar to disinfectants, but may be applied safely to living tissue.
Soap only REMOVES microorganisms.
• ALCOHOL-the most widely used antiseptic used to reduce the number of microorganisms on the
skin surface in the wound area. Alcohol denatures proteins, extracts membrane lipids, and acts
as a dehydrating agent, which all contribute to its effectiveness as an antiseptic. Even some
viruses (lipophilic viruses only) are inactivated by alcohol. Alcohol drawbacks are that it
evaporates quickly and has diminished activity against viruses in dried blood, saliva, and other
secretions on surfaces due to the presence of tissue proteins and glycoproteins that render alcohol
ineffective. Thus, alcohols are not regarded as effective surface cleansing agents (i.e. cleaning
a dental operatory after patient treatment).

Alcohol requires 70-95% concentration to kill bacteria given sufficient time:

• Isopropyl alcohol (90-95%) is the major alcohol for used in hospitals.
• Ethanol (70%) widely used to clean skin prior to immunization or venipuncture.
• Iodine-is the most effective skin antiseptic used in medical practice. It acts as an oxidizing agent
and combines irreversibly with proteins.

QUATERNARY AMMONIUM COMPOUNDS-are CATIONIC DETERGENTS widely used for

skin antisepsis. Benzalkonium chloride-cationic detergents used as disinfectants and antiseptics.
Gram-positive bacteria are the most susceptible to destruction. These compounds are NOT sporicidal,
tuberculocidal, or viricidal, and are inactivated by anionic detergents (soaps and iron in hard water).

• DETERGENTS-”surface active” agents composed of a long-chain, lipid-soluble hydrophobic

portion and a polar hydrophilic group, which can be a cation, anion, or nonionic group. Detergent
surfactants interact with lipids in the cell membrane through their hydrophobic chain, and with
the surrounding water through their polar group, to disrupt cell membrane function.

ANIONIC SURFACE-ACTING SUBSTANCES-include synthetic anionic detergents and soaps. These

substances alter the nature of interfaces to lower surface tension and increase cleaning. Their primary
value is their ability to remove microorganisms mechanically from the skin surface. Note: Nonionic
chemicals do not possess antimicrobial properties.

2% GLUTARALDEHYDE-the only “cold sterilizer” capable of destroying bacterial spores, viruses,

and vegetative bacteria. Its an alkalizing agent highly lethal to all microorganisms if sufficient contact
time (10 hours) is provided and there is absence of extraneous organic material. In hospitals,
glutaraldehydes are used to sterilize respiratory therapy equipment. Note: Alcohols, chlorhexidine,
and quaternary ammonium compounds are antiseptics.
• Glutaraldeyde is a chemical agent with the BROADEST antimicrobial spectrum of activity.

• Glutaraldehyde Advantages: the most potent category of chemical germicide, capable of killing
spores after 10 hours. It is EPA registered as a chemical sterilant, and it can be used on heat
sensitive materials.

• Glutaraldehyde Disadvantages: a long period is required for sterilization, its allergenic and is
not an environmental disinfectant. It is extremely toxic to tissues.

UNIVERSAL PRECAUTIONS-the MOST effective means of preventing disease transmission in the

dental office is based on the concept of universal precautions. Oral cavity is the primary source of
pathogenic microorganisms in the dental operatory. All patients are considered potential carriers of
blood-borne pathogens, so dentists should wear non-porous protective articles like barrier gowns,
gloves, eye protection, and face shields.

 WOUND HEALING, GRAFTS, & TERATOLOGY
HEALING-the restoration of integrity to an injured tissue. After the inflammatory phase, wound healing
is accomplished by 4 mechanisms that typically occur simultaneously in a cascade to repair the
damaged tissue (hemostasis, inflammation, proliferation, and remodeling).

• First, during HEMOSTASIS, platelets adhere to the injury site, are activated, and aggregate. Then,
the coagulation cascade is activated to form a clot of platelets in a mesh of cross-linked FIBRIN
protein to stop bleeding. Healing then moves to the INFLAMMATION phase where bacteria and
cellular debris are phagocytosed and removed from the wound by WBC and cells divide and
migrate during the PROLIFERATION PHASE where angiogenesis, collagen deposition, and
granulation tissue form and would contraction occurs. During REMODELING, collagen is
remodeled and realigned along tension lines and old cells are removed by APOPTOSIS.

SKIN wounds heal by primary (first) intension or secondary (second) intension.

1. Primary Intention Healing-occurs when wound margins are nicely apposed, as in surgical repair
of a surface wound. With well-approximated wounds, there is little granulation tissue, and the
final scar is minimal. The desired results in all surgical incisions is healing by PRIMARY
INTENTION (first intention).

2. Secondary Intention Healing-occurs when the wound is large and exudative, with a large amount
of necrotic tissue and suppuration formed as part of the inflammatory process. The site fills in
with a highly vascular, pinkish tissue (granulation tissue) which contains fibroblasts and
endothelial cells. This produces large, irregular scars. Glucocorticoids have the greatest effect on
granulation tissue.

Whether a wound heals by primary or secondary intention, healing is determined by the nature of the
wound, not by the healing process itself. The tensile strength of a healing wound depends on the
formation of collagen fibers.

REGENERATION of liver, bone, cartilage, and intestinal mucosa occurs as an adaptive mechanism
for restoring a tissue or organ. Example: after removing 70% of the liver, numerous mitosis of hepatocytes
occurs, reaching a peak at 33 hours. By the 12th day, the mass of liver excised is totally restored. This is
why the liver is the MOST UNCOMMON SITE for infarcts.
• Bone, intestinal mucosa, liver, and cartilage are tissues that CAN REGENERATE.

• STRIATED MUSCLE (skeletal, voluntary, cardiac muscle), smooth muscle, and CNS neurons
DO NOT REGENERATE. Highly specialized tissue has a lesser capability for regeneration.
Example: surface epithelium has a marked capacity for regeneration, while CNS neurons cannot
regenerate.

• Heart, Brain, and Lungs are highly vulnerable to hypoxia and anoxia. These tissues die and
cannot regenerate. However, the heart undergoes hypertrophy in response to injury.
RETICULOENDOTHELIAL SYSTEM (RES or Mononucleuar Phagocyte System)-a diffuse
system constituting all phagocytic cells of the body except granulocytes including the cells present in
bone marrow, spleen, and liver where they free the blood or lymph of foreign matter. RES is a functional
(rather than anatomical) system of the body involved primarily in defense against infection and
disposal of the products of the breakdown of cells. RES is concerned chiefly with phagocytosis and
antibody formation. Phagocytic cells of the RES:
• Microglia-macrophages of the CNS.

• Kupffer cells-phagocytic cells that line blood vessels of the liver.

• Alveolar macrophage (dust cells)-macrophages fixed in the alveolar lining of the lungs (also
called reticulum of the lungs).

• Histiocytes-fixed macrophages in C.T.

RES DISORDERS (Lipid Storage Diseases):

1. Gaucher’s disease-caused by a deficiency of glucocerebrosidase.
2. Niemann-Pick disease-caused by a deficiency of sphingomyelinase (die within a few years).
3. Tay-Sachs disease-caused by a deficiency of hexosaminidase A (rapidly fatal).


GRAFTS

XENOGRAFT (heterograft)-a transfer of tissue between DIFFERENT SPECIES. Xenografts are

often used to treat a severely burned patient. In this case, it is quickly rejected, but provides a cover for
the burn for the first few days. In skin graft rejection, the major host response is a T cell-mediated
immune response (a delayed Type IV hypersensitivity reaction).

AUTOGRAFT-surgical transplantation of any tissue from one part of the body to another located in
the SAME INDIVIDUAL. Also called autogenic graft, autologous graft, autoplastic graft, or
autotransplant.
• Graft of maxillofacial bone has the best chance of success with an autograft.

ALLOGRAFT-composed of tissues taken from an individual of the same species not genetically
related to the recipient (one human to another). Also called homograft, allogenic graft, homologous
graft, or homoplastic graft.

ISOGRAFT-composed of tissues taken from an individual of the SAME SPECIES genetically

identical to the recipient (identical twins). Also called syngraft, syngeneic graft, or isogeneic graft.

THE MOST FEARED CONSEQUENCE OF GRAFT THERAPY in a patient with an

immunodeficiency is a graft versus host reaction. When a graft is rejected the first time and tried again
by the same donor, it will be rejected more rapidly than the first time. Graft versus host reactions can
occur when viable lymphoid cells are present in the graft.

1. HYPERTROPHY-an increase in the size of an organ or tissue due to an increase in the size of
cells.

2. ATROPHY-a decrease in the size of an organ or tissue due to a decrease in mass of

preexisting cells. It most often results from disuse, aging, or disease process.

3. HYPERPLASIA-an increase in the size of an organ or tissue due to an increase in the number
of cells.

4. APLASIA-a failure of cell production. During fetal development, aplasia results in agenesis
(the absence of an organ).

5. HYPOPLASIA-a decrease in cell production, less extreme than aplasia.

6. METAPLASIA-the process where one cell type changes another cell type in response to
STRESS, and generally assists the host to adapt to stress. The most common type of epithelial
metaplasia involves replacement of columnar cells by stratified squamous epithelium.

TERATOLOGY (teratogens)-study of developmental anomalies. Teratogens are chemical, physical,

and biologic agents that cause developmental anomalies. Teratogens can produce death, growth
retardation, malformation, or functional impairment. Susceptibility to teratogens is variable and the
mechanism of teratogenesis is specific for each developmental stage.

• Teratogenic Drugs-can inhibit, interfere, or block metabolic steps critical for normal
mophogenesis. Many drugs or viruses affect specific tissues or organs. Teratogenesis is dose
dependent.

TERATOGENIC AGENTS:
1. Physical agents-radiation, hypoxia, excessive carbon dioxide, and mechanical trauma.
2. Maternal infection- (TORCH complex) Toxoplasmosis, Other agents, Rubella,
Cytomegalovirus, and Herpes simplex.
3. Hormones-sex and corticosteroids.
4. Vitamin deficiencies-riboflavin, niacin, folic acid, and vitamin E.
5. Chemotherapy drugs-treat malignancies.
6. Antibiotics-mitomycin, dactinomycin, and puromycin (used as chemotherapy agents).

COMMENSALISM-an interactive association between two populations of DIFFERENT SPECIES

living together in which one population benefits from the association, while the other is not affected.
Ex: removal of oxygen from a habitat due to the metabolic activities of a population of facultative
anaerobes, creates an environment favorable for growth of obligate anaerobic populations.

SYMBIOSIS-an obligatory, interactive association between members of two populations, producing a

stable condition in which the two organisms live together in close physical proximity. It may, but does not
necessarily benefit each member.

MUTUALISM-a form of symbiosis where both members live together with mutual benefit. Both benefit.

LATENCY-a state of dormancy; existing as a potential (as in tuberculosis or herpes). They may be
latent for extended periods of time and become active under certain conditions.

 BACTERIA
CELLS HAVE EVOLVED into two different types (eukaryotic and prokaryotic).

1. Eukaryotic cells-has a true nucleus with multiple chromosomes surrounded by a nuclear

membrane, and uses a mitotic apparatus to ensure equal allocation of the chromosomes to
progeny cells (human cells, plants, animals, protozoa, and fungi).
• Eukaryotic cells contain organelles (i.e. mitochondria, lysosomes) and larger 80S
ribosomes. Eukaryotes do not contain peptidoglycan.
• Eukaryotes replicate by mitosis.
• Eukaryotic cell membrane contains sterols.

2. Prokaryotic cells-nuclear material is not contained within a nucleus, and consists of a single,
circular molecule of loosely organized DNA lacking a nuclear membrane and mitotic
apparatus (bacteria, mycoplasmas, rickettsia, and chlamydia).
• Contain no organelles & smaller 70S ribosomes. Most prokaryotes (except Mycoplasmas)
have a rigid external cell wall that contains peptidoglycan.
• Prokaryotes replicate by binary fission.
• Prokaryotes do not have sterols in their cell membrane (except Mycoplasmas).

VIRUSES ARE NOT CELLS, they are obligate intracellular parasites that contain either RNA or
DNA. They do not contain organelles, and have a protein capsid and lipoprotein envelope.

GRAM-POSITIVE BACTERIA-have a cell wall that contains teichoic acids & thick peptidoglycan
(murein) layer.
• Murein (Peptidoglycan)-the backbone biochemical of the gram + bacterial cell wall composed
of repeating alternating units of N-acetylglucosamine and N-acetylmuramic acid and has cross-
linked, short peptide chains, some of which have unusual amino acids.

• Gram-Positive cell walls are composed of a thick murein layer (makes up 90% of the cell wall)
and Teichoic acids (are acidic anionic polysaccharides).

GRAM-NEGATIVE CELL WALL is more complex than gram-positive cell wall. It has a thin murein
layer that makes up about 10% of the wall. The cell wall also consists of:
• Lipoproteins are an integral part of the cell wall.
• Lipopolysaccharide layers (endotoxin is equated with this component).
• Phospholipids & Proteins
• Proteins, lipopolysaccharide layers, and phospholipids make up the CELL ENVELOPE of the
gram-negative bacterial cell.

ENDOTOXINS-highly potent LIPOPOLYSACCHARIDES released ONLY from cell walls of gram-

negative bacteria. Minute amounts of endotoxin in the oral mucosa cause inflammation and resorption of
adjacent bone. Endotoxins are constituents of gram-negative microorganisms and is an important
agent in the pathogenesis of inflammatory periodontal disease. Endotoxin has a chemotactic effect on
neutrophillic granulocytes, inducing phagocytosis by these cells. The basic chemical structure of
endotoxins is somatic O polysaccharide, core polysaccharide, & lipid A.
• Endotoxins exert its pathologic effects in part by ACTIVATING THE COMPLEMENT
CASCADE.

• ENDOTOXINS are the lipopolysaccharide component of GRAM-NEGATIVE BACTERIA

cell walls. Because the lipopolysaccharide (LPS) is part of the bacterial cell structure, it is
called endotoxin. While all gram-negative bacteria have LPS in the cell walls, LPS in not toxic
unless released from the cell. The death of gram (-) bacterial cells causes their walls to
disintegrate, releasing LPS toxin. LPS endotoxins exert their pathogenic effects by activating
the complement cascade.

• Endotoxins are lipopolysaccharides that make up cells walls of gram-negative bacteria. They
are not released, are not vaccines (toxoids), and are less toxic than exotoxins, with low
specificity for target cells.

FREE ENDOTOXIN is present in dental plaque and inflamed gingiva. The likelihood that bacterial
endotoxins plays a major role in gingival inflammation is evidenced by a reduction in inflammation by the
removal of plaque, and by a reduction of the inflammatory state with antibiotic treatment.

• Plaque bacteria also produce enzymes (hyaluronidase, collagenase, lysozyme, chondroitin, sulfatase,
elastase, and proteases) that may initiate periodontal disease.

• Antibodies or immunoglobulins are produced by plasma cells in response to oral bacteria or their
byproducts. The most numerous is IgG which neutralizes bacterial toxins by enhancing
phagocytosis.

• Subgingival plaque-the most likely source of bacteria found in diseased periodontal tissue.

EXOTOXINS-proteins in cells walls of gram-positive and gram-negative bacteria. Exotoxins are

released, used as vaccines, are very potent (high degree of toxicity), with a high specificity for target
cells.
ENTEROTOXINS-toxins specific to cells of the mucous membrane of the intestines. Enterotoxin
produced by Staphylococcus aureus causes FOOD POISONING.

CAPSULE-consists of polysaccharides that surrounds the cell wall important in protecting bacterial
cells against phagocytosis by eukaryotic cells. The presence of a capsule is a major factor in
determining the pathogenicity of a bacterium (the ability of a bacterium to cause disease in the
organism it infects).
• Capsules play important roles in these diseases: Haemophilus meningitis, Cryptococcoses,
Pneumococcal pneumonia, and Meningococcemia. *Neisseria gonorrhoeae LACKS a capsule.
• Removing the capsule from an encapsulated bacterium results in increased susceptibility to
phagocytosis.

CAPSULES are ANTIPHAGOCYTIC POLYSACCHARIDES surrounding the cells of strains of (e.g.

Streptococcus pneumoniae-bacteria well known for its LARGE polysaccharide capsule) that permit
bacteria to invade the normal defense mechanisms of the host, allowing them to reproduce and cause the
symptoms of pneumonia. The virulence of other bacteria (Haemophilus influenzae, Klebsiella
pneumoniae, Neisseria meningitides, and Crytococcus neoformans) is also enhanced by capsule
production.

CELL MEMBRANE (cytoplasmic membrane)-a selectively permeable membrane involved in energy

transformations (site of oxidative phosphorylation). The cell membrane is bordered externally by the
cell wall in most bacteria.

Hydrogen Peroxide and free superoxide radicals are two toxic molecules that arise as a byproduct of
aerobic metabolism. Cells possess an elaborate defense system to destroy these toxic molecules
using enzymes like catalase and superoxide dismutase.

CATALASE-catalyzes the decomposition of hydrogen peroxide to water and oxygen. Superoxide

dismutase catalyzes the decomposition of free superoxide radicals into water and hydrogen peroxide,
which is subsequently degraded by catalase.

OBLIGATE ANAEROBES-cannot grow in the presence of oxygen because they lack superoxide
dismutase, catalase, or both. They cannot carry out respiratory metabolism. In the mouth, obligate
anaerobes are part of the normal microflora and opportunistic.
• superoxide dismutase and catalase are enzymes present in both obligate aerobes &
facultative anaerobes. These enzymes are NOT present in OBLIGATE ANAEROBES.
• Anaerobic bacteria obtain their energy requirements from FERMENTATION REACTIONS.

OBLIGATE AEROBES-require oxygen to grow because their ATP-generating system is dependent on

oxygen as the hydrogen acceptor.

FACULTATIVE ANAEROBES-utilize oxygen to generate energy by respiration if it is present, but can

also use the fermentation pathway to synthesize ATP in the absence of sufficient oxygen.

Two Pathways Metabolize Glucose:

1. Anaerobic cycle-occurs in the CYTOPLASM and is only moderately efficient.
2. Aerobic cycle-occurs in the MITOCHONDRIA and results in the greatest release of energy.

RESPIRATION-method of obtaining metabolic energy involving oxidative phosphorylation. It involves

formation of ATP during electron transfer. It can be aerobic (molecular oxygen is the terminal H+
acceptor), or anaerobic (nitrate or sulfate is the terminal hydrogen acceptor).

• Aerobic Respiration-involves a cell membrane respiratory (electron transport) chain composed

of cytochromes, flavoproteins, lipid cofactors, and coupling factors. The electron transport chain is
present in the inner mitochondrial membrane and is the final common pathway by which electrons
derived from different fuels of the body flow to oxygen.

FERMENTATION-a method used by some bacteria to obtain metabolic energy. Fermentation is

characterized by substrate phosphorylation. It involves formation of ATP not coupled to electron
transfer. It requires an intermediate product of glucose metabolism (pyruvate) as the final hydrogen
acceptor.

Oral Cavity (saliva, tongue, plaque)-contains Streptococcus, veillonella, bacteriodes, fusobacterium,

peptostreptococcus, and actinomyces. SALIVA-members of the “VIRIDANS” group of Streptococci
(salivarius, mitis, and sanguis) are predominant in saliva. Gram-positive filaments (Actinomyces) and
gram-negative organisms (Veillonella) are also present.

1. GI tract-Lactobacillus, streptococcus, clostridium, veillonella, bacteroides, fusobacterium,

escherichia, proteus, klebsiella, and enterobacter.

2. Upper respiratory tract (nasal cavity and nasopharynx)-streptococcus, staphylococcus, moraxella,

 neisseria, haemophilis,bacteroides, and fusobacterium.

3. Lower respiratory tract-no normal microbiota.

4. Upper urinary tract (kidneys and bladder)-no normal microbiota.

5. Genitourinary tract (urethra and vaginal tracts)-streptococcus, lactobacillus, bacteroides, and

clostridium.

ANUG (Acute Necrotizing Ulcerative Gingivitis = Vincent’s Angina)-a painfull and ulcerating
infection of the ginigva caused by an anaerobic infection of the gingival margins. Occurs most common
in smokers and people with compromised immunity (immunosuppression). When untreated, destruction
of the gingiva and underlying bone occurs, with interproximal areas affected first. Spirochetes invade
the epithelium and C.T. Prevotella intermedia, Fusobacterium species and Selenomonas species are
also seen in the necrotic zones superficial to the zone of spirochete infiltration. FETID BREATH,
PAINFUL and SPONTANEOUS GINGIVA BLEEDING.
• Prevotella Intermedia & Spirochetes (intermediate-sized spirochetes) are the main bacteria
responsible for ANUG.

PREDOMINANT SUBGINGIVAL BACTERIA associated with gingival health:

• Streptococcus mitis and sanguis
• Actinomyces viscosus and naeslundii
• Rothia dentocariosus
• Staphylococcus epidermis
• Small spirochetes

IgG- immunoglobulin found in the HIGHEST CONCENTRATION in serum samples from patients
with PERIODONTAL DISEASE. High levels of Porphyromonas gingivalis-specific IgG antibodies
are seen in MOST serum samples in patients with adult periodontitis.

RAPIDLY PROGRESSING PERIODONTITIS-most commonly seen in YOUNG ADULTS (20-25

yrs), characterized by marked inflammation, rapid bone loss, and periods of spontaneous remission.
Most of these patients have depressed neutrophil chemotaxis.

JUVENILE PERIODONTITIS-the MOST UNCOMMON SEVERE FORM of periodontal disease

that starts around puberty 12-14 years old. Caused by AA (Actinobacillus Actinomycetemcomitans),
capnocytophaga ochraceus, Prevotella intermedius, and Eikenella corrodens. 2 Types of Juvenile
Periodontitis:

1. Generalized Juvenile Periodontitis-Prevotella intermedius and Eikenella corrodens

predominate. Occurs between ages 12-25 characterized by rapid, severe, periodontal destruction
around most teeth. It appears to be associated with systemic disease (diabetes mellitus type 1,
Down syndrome, neutropenias, Papillon-Lefevre syndrome, and leukemias).

2. Localized Juvenile Periodontitis-gram-negative anaerobes Actinobacillus Actinomycetemcomitans

(AA) and Capnocytophaga ochraceus predominate. Prevotella intermedius and Eikenella corrodens
may be present to a lesser extent.
• LJP occurs in healthy adolescents ages (12-19) characterized by severe periodontal destruction
around either maxillary/mandibular first molars or maxillary/mandibular anterior teeth.

• An outstanding negative feature is the relative absence of local factors (plaque) to explain
the severe periodontal destruction which is present. Possible etiologic factors include a genetic
predisposition or a dysfunction of neutrophils (a chemotactic defect).

• AA and Capnocytophaga ochraceus are also associated with periodontitis in juvenile diabetes.

MYCOBACTERIUM-are gram-positive, non-motile, rod-shaped bacteria:

1. M. tuberculosis-the causative agent of tuberculosis. Tubercle (Ghon focus)-a small, rounded
nodule produced by infection with M. tuberculosis. It is the primary lung lesion of pulmonary
TB. Physiological characteristics of M.tuberculosis: the tubercle bacillus is an aerobe; its growth
is slow; and it does not produce exotoxins or endotoxins.
• M. bovis is MOST closely related to Mycobacterium tuberculosis since it causes bovine
tuberculosis, and can infect people who drink unpasteurized milk.
• Hypersensitivity to M. Tuberculosis is manifested by NECROSIS.
2. M. leprae-the causative agent of leprosy (Hansen’s bacillus).

Mycobacterial and actinomycetes cell walls contain a waxy substance composed of MYCOLIC
ACIDS. Mycolic acids are waxy acids responsible for mycobacteria being acid fast, resistant to
phagocytosis, and allow these bacteria to persist inside of macrophages and neutrophils as intracellular
parasites.

ACID FAST STAIN-most commonly to examine sputum for MYCOBACTERIUM

TUBERCULOSIS.
• Acid-Fast Stain-a method used to diagnose active tuberculosis. It is a method of staining used in
bacteriology in which a smear on a slide is flooded with carbol-fuchsin stain, decolorized with
acid alcohol, and counterstained with methylene blue. Acid-fast organisms resist
decolorization and appear RED against a blue background under a microscope. This property
of being acid-fast is attributable to the presence of lipids and waxes (mycolic acids) in the cell
wall of certain bacteria.

• PPD Skin Test-the classic skin test for tuberculosis. PPD may indicate an infection, but not if the
infection is active. A purified protein derivative (PPD) extracted from mycobacterium tuberculosis
is injected subcutaneosly, and the area near the injection is observed for a delayed
 hypersensitivity reaction (necrosis). A positive test indicates a hypersensitivity to
tuberculoproteins.

SEPSIS (Septicemia)-most bacteria that enter the bloodstream are rapidly removed by white blood cells.
Sometimes, there are too many bacteria to be removed easily, and a sepsis infection develops causing
severe symptoms. Sepsis can lead to a life-threatening condition = SEPTIC SHOCK caused by
Staphylococcus aureus, Escherichia coli, and Klebsiella.
• Sepsis symptoms: fever, weakness, nausea, vomiting, diarrhea, and chills.

BACTEREMIA-presence of viable bacteria in circulating blood. Bacteremia can occur even in

healthy individuals. Ex: after some dental procedures (oral prophylaxis and extractions), bleeding of the
gums results in a transient systemic bacteremia. Clinical signs and symptoms are usually not present.
Bacteremia is why antibiotic pre-medication before certain dental procedures for certain medical
conditions is required. *Anbiotic pre-medication is no longer required for joint replacement unless a
prior bacteriemia before dental treatment (but always consult with the patient’s cardiologist or
orthopaedic surgeon to protect the patient and yourself).

VIREMIA-a viral infection of the bloodstream, that is a major feature of disseminated infections. The
infecting virus is very susceptible to circulating antibodies.

1. Streptokinase (fibrinolysin)-toxin or enzyme produced by Group A Streptococci (S. pyogenes) that

activates plasminogen to form plasmin which dissolves fibrin in clots, thrombi, and emboli.
2. Streptodornase (DNase)-depolymerizes DNA in exudates or necrotic tissue.
3. Hyaluronidase (spreading factor)-degrades hyaluronic acid (ground substance of subcutaneous
tissue).
4. Erythrogenic Toxin-causes the rash of scarlet fever.
5. Streptolysin O-a hemolysin inactivated by oxidation (it is oxygen-labile) and is also antigenic.
6. Streptolysin S-a hemolysin not inactivated by oxygen (it is oxygen-stabile). It is not antigenic.
7. Pyrogenic Exotoxin A-a toxin similar to staphylococcal toxic shock syndrome toxin.
8. Exotoxin B-a protease that rapidly destroys tissue.

STREPTOCOCCI-the primary ACIDOGENIC microorganism in the ORAL CAVITY. Streptococci

outnumber Lactobacilli in the oral cavity. Facultative streptococci is the single MOST NUMEROUS
group of microorganisms in the oral cavity.
• Aciduric-the bacteria is capable of or can tolerate living under acidic conditions.
• Acidogenic- bacteria produces acid (Streptococci and Lactobacilli) produce lactic acid as the
primary fermentation product. Lactic acid is the main caused of enamel decalcification.

Neutralphiles-most bacteria are neutralphiles because they thrive under neutral pH conditions (e.g.
Proteus, Clostridium, Lactobacilli, and Pseudomonas).

Acidophiles-bacteria restricted to growth at low pH values (e.g. Thiobacillus-can grow only at highly
acidic pH near 2.0).

Alkalophiles-bacteria that prefer growth under very alkaline (basic) conditions (high pH values). Ex:
Nitrosomonas thrive best at pH values around 8.5. Vibrio chlorera also grows well in alkaline pH.
LACTOBACILLUS-gram-positive rods that forms chains and occurs in the HUMAN DIGESTIVE
TRACT to aid in MILK digestion. They are the initial colonizers of the intestinal tract. Although
Lactobacillus species are normally present in low numbers in the oral cavity, they are frequently found
in association with DENTAL CARIES (especially Lactobacilus casei).
• Lactobacilli causes progression of existing lesions in coronal caries.

LACTOBACILLUS ACIDOPHILUS is added to commercial milk products to aid individuals unable to

adequately digest milk products (lactose intolerance). The enzymes produced by these bacteria convert
milk sugars to products that do not cause GI problems.

LACTIC ACID BACTERIA (Lactobacillus and Streptococcus species) use the lactic acid fermentation
pathway which reduces pyruvate to lactic acid. These two bacteria are ACIDURIC (can tolerate an
acidic environment) and are the primary bacteria responsible for caries.

• STREPTOCOCCUS MUTANS-the MAIN culprit in DENTAL CARIES (especially smooth

surface caries). The capsule of S. Mutans is an important virulence factor that enhances oral
accumulation.
o A major cariogenic property of S. mutans is its ability to produce Glucosyltransferase
enzyme. Streptococci’s synthesis of insoluble dextran and glucosyltransferase are two
critical factors for initiating caries.

• Actinomyces (viscosus and naeslundii)-the main causative agents of ROOT SURFACE CARIES
(root caries spreads laterally).

ENTEROBACTERIA-one of two major families of gram-negative, facultatively anaerobic motile

rods via peritrichous flagella. Enterobacteria genera: Escherichia, Klebsiella, Proteus, and
Salmonella. These bacteria are highly invasive with the ability to become resistant to antibiotics.

GROUPS OF BACTERIA:

1. Spirochetes: Treponema, Borrelia

2. Helical/vibroid gram-negative bacteria: Spirillum, Campylobacter, Heliobacter
3. Gram-negative aerobic rods and cocci: Pseudomonas, Bordetella, Neisseria, Brucella, Legionella
4. Gram-negative facultatively anaerobic rods: Enterobacteria (Escherichia, Salmonella, Shigella,
Serratia, Proteus, Klebsiella), Vibrio, and Haemophilus
5. Gram-negative anaerobic rods: Bacteroides, Fusobacterium, Prevotella.
6. Rickettsiae and Chlamydia: Rickettsia, Coxiella, Chlamydia
7. Mycoplasmas: Mycoplasma, Ureaplasma
8. Mycobacteria: Mycobacterium
9. Actinomycetes: Streptomyces, Nocardia, Rhodococcus
10. Gram-positive cocci: Staphylococcus, Streptococcus, Enterococcus, Peptosstreptococcus
11. Regular non-spore forming gram-positive rods: Lactobacillus
12. Irregular non-spore forming gram-positive rods: Corynebacterium, Actinomyces
13. Endospore forming rods and cocci: Bacillus, Clostridium

STAPHYLOCOCCUS AUREUS-a coagulase gram-positive coccus that typically grows in grape-like

clusters and is one of the most common bacterial pathogens. The most common cause of suppurative
infections involving the skin, joints, and bones, and is the LEADING CAUSE OF INFECTIVE
ENDOCARDITIS.
• Staphylococcus aureus possesses a surface protein (protein A), that binds the Fc receptor of IgG,
thus blocking complement activation by the classical pathway.

• Staphylococcus aureus cannot invade through intact skin or mucous membranes, and infection
usually begins with traumatic inoculation of the organism. Once inside the body, it secretes
enzymes and toxins that harm most tissues.

• S. aureus infection usually produces suppuration and abscess formation. It causes various
infections (e.g. boils, carbuncles, and styes); scalded skin syndrome and toxic shock syndrome;
osteomyelitis; infections of burns or surgical wounds; respiratory tract infections; septicemia;
bacterial endocarditis; and staphylococcal food poisoning.

• Staphylococcus aureus produces heat-stable toxins and an enterotoxin that causes acute-onset
food poisoning. STAPHYLOKINASE-an enzyme produced by S. aureus

STAPHYLOCOCCUS INFECTIONS are suppurative infections usually caused by S. aureus

(abscesses, endocarditis, impetigo, osteomyelitis, pneumonia, and septicemia). S. aureus causes acute-
onset FOOD POISONING due to its enterotoxins-toxins specific for cells of the intestine.
• Protein A-a component of Staphylococcus responsible for its virulence.
• The cell wall of Staphylococcus bacteria has a protective peptidoglycan coat surrounding it.
• People are the main source associated with staphylococcal food poisoning.
• Staphylococcus grows best and multiplies rapidly between 68b-99-F.
• Staphylococcus is the genera of bacteria MOST COMMONLY FOUND ON SKIN.

COAGULASE-NEGATIVE STAPHYLOCOCCI (less virulent than S. aureus):

1. Staphylococci epidermis-the most frequent cause of infections associated with medical devices.
2. Staphylococci saprophyticus-the frequent culprit of acute urinary tract infections in young
women.

STREPTOCOCCI-aerobic to facultatively anaerobic GRAM-POSITIVE COCCI that grow in pairs

or chains in liquid culture. They are the MOST NUMEROUS group of microorganisms in the ORAL
CAVITY, where they can grow and cause DENTAL CARIES (mainly S. mutans).
• More serious infections caused by Streptococci include: pneumonia (S. pneumoniae), rheumatic
fever (S. pyogenes), and heart valve infections (S. viridans).
• Streptokinase-a bacterial exotoxin produced by hemolytic streptococci that converts
plasminogen to plasmin.

STREPTOCOCCUS PYOGENES-are Group A beta-hemolytic Streptococcus and is one of the most

frequent bacterial pathogens of humans (causes Rheumatic Fever). It is a gram-positive coccus that
occurs in pairs or chains. It is frequently part of the endogenous microflora that colonize the skin and
oropharynx.
• S. Pyogenes is the cause of several acute pyogenic (pus-forming) infections in man (e.g. scarlet
fever, erysipelas, and sore throat “strep throat”).
 • S. Pyogenes elaborates several exotoxins (e.g. erythrogenic toxins and streptolysins S and O).
• Acute suppurative is the inflammatory response associated with an infection caused by pyogenic
pathogens.

Streptococcus Pyogenes fall into 2 Categories:

1. Suppurative Diseases:
• Strep throat-commonly affects children and adolescents.
• Scarlet fever-caused by erythrogenic toxin.
• Erysipelas-acute contagious disease marked by a circumscribed red eruption on the skin,
chills, and fever.
• Impetigo-a localized, intra-epidermal infection of the skin seen in preschool-aged
children.
• Cellulitis-results from traumatic inoculation.

2. Non-Suppurative Diseases:
• Rhemuatic fever-usually begins with a sore throat and after several days there is rapid
rise in temperature, prostration, and inflammation of the joints; the heart is often affected.

• Acute Poststreptococcal Glomerulonephritis-occurs primarily in children; symptoms

include increased fluid retention, dark tea-colored urine, and elevation of BP.

Group B Streptococcus (S. agalectiae)-the leading cause of neonatal pneumonia, meningitis, and sepsis.

TRANSFER of GENETIC INFORMATION between bacteria cells occurs by 3 ways:

1. CONJUGATION-mating of two bacterial cells during which DNA is transferred from the donor
to the recipient cell. In conjugation the physical contact is established through the presence of pili
(sex pilus or conjugation tube). The most important function of bacterial pili in causing human
infectious disease is it allows bacteria to adhere to human cells.
• Bacteria mating process is controlled by an F plasmid (F Factor). The donor male bacterium
is F+ (meaning it carries the F Factor); the recipient female bacterium is F- (meaning it does
not carry F Factor). In conjugation, the greatest amount of genetic information is
transferred from one cell to another (compared to transduction and transformation).
• Conjugation is the genetic ability of a bacterium to grow in the presence of several antibiotics
is passed in vivo from one bacterium to another.

2. TRANSDUCTION-the transfer of bacterial cell DNA from donor cell to recipient cell by a bacterial
virus (bacteriophage). Does not require cell-to-cell contact and is LEAST susceptible to DNase.

3. TRANSFORMATION-process of gene transfer of naked DNA molecules from one bacterial cell
to another. In nature, this requires cell-to-cell contact done mostly in the laboratory. When
purified, DNA is injected into the nucleus of a eukaryotic cell (e.g. human cell), this process is
transfection. Transformed cells are cells that have incorporated DNA by transformation.
• Rough pneumococci grown in the presence of DNA from smooth pneumococci that develop
capsules is an example of transformation.
• Transformation is best described as acquisition of an inheritable trait by bacteria mediated by
 DNA.

Once DNA is transferred by one of these three processes, it can integrate into the host cell chromosome
by recombination (either homologous or non-homologous recombination).

Beta-hemolytic forms are classified into groups (A, B, C, etc.) based on cell wall carbohydrates:
Group A strains are pathogenic to humans and are subdivided into specific antigenic types based on the
cell wall M protein (is closely associated with the virulence of the bacteria). The prototype is S.
pyogenes (causes rheumatic fever, scarlet fever, and sore throat).

Some Streptococcal species produce toxins (hemolysins) that cause lysis of erythrocytes (RBCs). When
these bacteria grow on blood agar plates, zones of clearing are seen around the bacterial colonies.
• Alpha-Hemolytic Streptococci-produce a zone of incomplete hemolysis and green discoloration
adjacent to the colony.

• Beta-hemolytic streptococci produce a clear zone of hemolysis around the colony.

• Gamma-Streptococci PRODUCE NO HEMOLYSIS.

TOXINS produced by Group A beta-hemolytic streptococci include: erythrogenic toxin,

deoxyribonuclease, hemolysins (streptolysins O & S), hyaluronidase, streptokinase, and streptodornase.

TRANSCRIPTION-the SYNTHESIS of mRNA from DNA by DNA-dependent RNA polymerase.

Transcription is the synthesis of RNA from a DNA template. In bacteria, transcription is mediated by
RNA polymerase.

REVERSE TRANSCRIPTION-the formation of DNA from an RNA template. Retroviruses (e.g. HIV,
tumor viruses), are enveloped and contain a linear, single-stranded, positive-sense RNA genome that
utilizes reverse transcriptase process. They use their RNA genome as a template for an RNA-directed
DNA polymerase. These viruses have a virion-associated reverse transcriptase, which makes DNA
copies from RNA. This DNA is then integrated into the host genome. This RNA-directed synthesis of
DNA is the reversal of normal informational flow within the cell.

TRANSLATION-the synthesis of PROTEIN from an RNA template. Translation occurs on ribosomes.

NUCLEOID-area of cytoplasm in prokaryotic cells where DNA is located. Nucleoid is a

membraneless structure or region in prokaryotic cells that contain DNA but does NOT ITSELF
REPLICATE. The nucleoid contains no nuclear membrane, no nucleolus, no mitotic apparatus, and no
histones; so there is little resemblance to the eukaryotic nucleus.

GRANULES (inclusion bodies)-the cytoplasm contains several different granules that are storage areas
for nutrients. Volutin (metachromatic granules) is a reserve of high energy stored in the form of
polymerized metaphosphate used in ATP synthesis. These metachromatic granules are commonly
associated with Pseudomonas aeruginosa and Corynebacterium diphtheriae. Other inclusion bodies
include sulfur granules and PHB (poly-hydroxybutyric acid).

TRANSPOSONS-pieces of DNA that move readily from one site to another, either within or between
DNAs of bacteria, plasmids, or bacteriophages.

PSEUDOMONAS AERUGINOSA-people with cystic fibrosis, burn victims, individuals with cancer,
and patients requiring extensive stays in intensive care units are particularly at risk of infection with
Pseudomonas Aeruginosa.

PSEUDOMONAS-a family of gram-negative, straight or curved motile rods by means of polar

flagella. Most strains are obligate anaerobes. Some produce characteristic fluorescent pigments (P.
aeruginosa). Pseudomonas has the ability to adapt and thrive in many ecological niches, from water, soil,
plants, animals, and humans.
• Once infections are established, Pseudomonas aeruginosa produces toxic proteins that cause
extensive tissue damage and interfere with the human immune defense mechanisms.

Gentamicin-a broad spectrum aminoglycoside antibiotic effective in treating bacteremias caused by

P. aeruginosa.

OPSONIZATION-during phagocytosis, bacteria are ingested by the invagination of the neutrophil

(PMN’s) cell membrane around the bacteria to form a vacuole (phagosome). This engulfment is
enhanced by the binding of IgG antibodies to the surface of the bacteria in the opsonization process.
• C3b component of complement also enhances opsonization (the outer membranes of PMN’s and
macrophages have receptors for the Fc portion of IgG and for C3b).

BACTERIA are easily recognized and phagocytized by leukocytes (PMNs) and macrophages after an
antibody (IgG) or complement component (C3b) “opsonins” react with bacteria to form a coat around
it. This coating process (opsonization) enables the phagocyte to vigorously engulf the particulate
material. Bacteria that do not have capsules surrounding them are phagocytized much easier than
encapsulated bacteria.

NEUTROPILS & MACROPHAGES are the most important PHAGOCYTIC CELLS:

PHAGOCYTOSIS-the ingestion of particulate material (e.g. tissue debris, bacteria) by phagocytic cells
(neutrophils and macrophages). 3 Steps of Phagocytosis:

1. Migration-PMNs (neutrophils) migrate to the site of the particulate matter due to chemotactic
factors (complement component C5a and kallikrein). Two proteins, selectin and integrin mediate
adhesion of PMNs to the endothelium at the infection site. Increased permeability of capillaries
allows PMNs to migrate through the capillary wall to reach the bacteria = diapedesis migration.

2. Ingestion-bacteria are ingested by the invagination of the PMN cell membrane around the bacteria to
form a vacuole (phagosome). This engulfment is enhanced by the binding of opsonins (IgG or C3b) to
the surface of the bacteria = opsonization

3. Killing (Destruction)-phagosomes fuse with cytoplasmic lysosomes, forming phagolysosomes.

Enzymes digest the particulate matter.

PHAGOCYTES:
1. Fixed phagocytes-do not circulate and include fixed macrophages and cells of the
 reticuloendothelial system (RES).
2. Free phagocytes-circulate in the bloodstream and include leukocytes (neutrophils) and free
macrophages.

4 GROWTH PHASES OF THE TYPICAL GROWTH CURVE OF A BACTERIAL CULTURE:

1. Lag Phase-a period following inoculation of a medium during which the number of
microorganisms does not increase.

2. Log Phase (Exponential Growth Phase)-growth is maximal and constant, and there is a
logarithmic increase in population size (cells increase in mass or number). Cidal activity of
antibiotics work best during Log Phase. Log Phase is the best phase to stain bacterial
cultures for study purposes.

3. Stationary Phase-the death rate equals the rate of reproduction, resulting in a zero growth rate.

4. Death Phase-represents the inability of microorganisms to reproduce.

VIBRIO CHOLERAE-a comma-shaped, gram-negative bacillus that produces an extremely potent

enterotoxin that causes CHOLERA (acute diarrheal disease). The clinical manifestation of cholera is
due to a loss of fluid resulting in Hypovolemic shock and metabolic acidosis.

ESCHERICHIA COLI-short, gram-negative, facultatively anaerobic motile rods with peritrichous

flagella. E. coli are normally present in human intestines. Enterotoxin-producing strains of E.coli are
capable of causing mild and severe forms of enterocolitis. E. coli is the most common cause of urinary
tract infections (cystitis).

Bacterial toxins are the most potent poisons and their potency is paralleled by their efficiency as antigens.

SPORES-are primitive, thick-walled usually unicellular cells by which bacteria, fungi, and green
plants reproduce. Spores are able to grow into new organisms without uniting with another reproductive
cell via a process of ASEXUAL REPRODUCTION.
• Active spores have thin cell walls; dormant spores have thick, strong cell walls.

• Spores are specialized resistant cells produced by many microorganisms to enhance the
organism’s survival potential.

BACTERIAL SPORES-serve primarily as a resting or dormant stage in the bacterial life cycle. If
conditions are unfavorable for bacterial growth to continue, ENDOSPORES are formed via a
sporulation process.
• BACTERIAL ENDOSPORE-a heat-resistant spore formed within the cell. The endospore is a
complex, multilayered structure containing peptidoglycan within its complex spore coat and
calcium dipicolinate within its core. This bacterial endospore is very difficult to destroy (more
than HIV, HEP B virus, and TB virus). To destroy the endospore, you must AUTOCLAVE at
(121AC for 20 minutes). Most important ENDOSPORE PRODUCERS are two genera,
BACILLUS and CLOSTRIDIUM.

• Anthrax-caused by Bacillus anthracis.

• Botulism (Clostridium botulism), gas gangrene (C. perfringens) and tetanus (C. tetani).
UROKINASE-enzymes that cleave plasminogen to produce plasmin, causing the liquefaction of fibrin.
Used in medicine to REMOVE BLOOD CLOTS.

Escherichia coli, Vibrio cholera, and Staphylococcus aureus all produce a toxin detectable using ELISA
assay. BACTEROIDS do not produce a detectable toxin.

 ANTIBIOTICS
CANDIDIASIS-an ORAL CAVITY or VAGINAL FUNGAL INFECTION by a Candida species,
usually C. albicans causing an inflammatory, pruritic infection of thick, white discharge. Common in
patients who have a deficiency in T-lymphocytes, patients receiving chemotherapy, and in
immunosuppressed individuals (AIDS patients).
• CANDIDIASIS is a yeast-like FUNGI with chlamydospores that is a normal inhabitant of the
oral cavity and vaginal tract. However, it is normally held in check by the indigenous bacteria of
these areas. Angular cheilitis (bilateral ulcers at the corner of the mouth) has been linked to C.
albicans (characterized by yeast cells and chlamydospores in the oral mucosa).

• Candida is a genera of fungi MOST frequently recovered from healthy mucous membranes.

• ANTIBIOTIC USE is the most common precipitating factor for candidiasis, owing to the
suppression of the competing bacterial flora.

• Disseminated candidiasis (widely distributed in the body) is treated with Amphotericin B.

• NYSTATIN & AMPHOTERICIN B are antifungal and fungistatic; they bind to sterols in the
fungal cell membrane, increasing membrane permeability and permitting leakage of
intracellular contents (these antifungals impair erogsterol synthesis) NYSTATIN is the
antifungal DRUG OF CHOICE for treating CANDIDIASIS.

• Chronic hyperplastic-a type of oral candidiasis that produces a firmly adherent white plaque on
the oral mucosa. Treated with Nystatin.

• Candidiasis in the adult oral cavity may signify a change in the balance of oral microbiota. This
change is often seen in persons taking ANTIBACTERIAL DRUGS.

PENICILLINASE-an enzyme produced by certain strains of STAPHYLOCOCCUS that inactivates

penicillin. Penicillinase DEGRADES THE BETA-LACTAM RING STRUCTURE OF PENICILLIN.

• STRUCTURAL MODIFICATION OF PENICILLIN G, such as in methicillin, renders the

molecule resistant to penicillinases, but narrows the spectrum of action, limiting the primary use of
such antibiotics to the treatment of infections caused by Staphylococcus species. Other
penicillinase-resistant penicillins are cloxacillin, dicloxacillin, nafcillin, and oxacillin.

PENICILLIN only works on growing cells that contain peptidoglycan in their cell wall. Thus,
penicillin shows its greatest bactericidal activity against growing gram-positive bacteria (they have a
thick peptidoglycan or murein layer in their cell wall). Penicillin inhibits the terminal step in
peptidoglycan synthesis. Penicillin affects the bacteria cell wall.
• Penicillin is usually non-toxic to human cells because human cells LACK PEPTIDOGLYCANS.
• Penicillin PREVENTS SYNTHESIS OF PEPTIDOGLYCANS (inhibits cell wall synthesis).
• Staphylococcus is the genera that most frequently develops resistance to penicillin by
 producing an enzyme that attacks penicillin.
• An injection of penicillin into a penicillin-sensitive person may cause death due to constriction of
bronchioli and drop in blood pressure.

ERYTHROMYCIN-the MOST appropriate alternative for treating patients allergic to penicillin who
has an infection caused by bacteria sensitive to penicillin. If a bacteria were susceptible to both penicillin
and erythromycin, then it is inappropriate to treat patients with both antibiotics at the same time because
penicillin is only effective against growing cells.
• Erythromycin is the antibiotic of choice for prophylactic therapy covering dental procedures in
a patient with a heart valve abnormality who is allergic to penicillin. It inhibits protein synthesis.

CEPHALOSPORINS (cefoxitin, cephalothin, & cefamandole)-BROAD-SPECTRUM

ANTIBIOTICS. Cephalosporins are a heterogenous group of natural and semisynthetic antibiotics that
act against a wide range of gram-positive and gram-negative bacteria by inhibiting formation of cross-
links in peptidoglycan (affects cell wall).
• CEPHALOSPORINS are the antibiotic of choice (cephalothin) for treating
STAPHYLOCOCCAL INFECTIONS (ENDOCARDITIS). This avoids complications in cases
where the infecting staphylococcus species produces, l-lactamase (penicillinase). In these
cases, staphylococcus would be penicillin resistant.

• MANY CEPHALOSPORINS (e.g. cefoxitin and cephalothin) are resistant to penicillinase.

Many physicians now use broad-spectrum cephalosporins where the use of narrow-range and more
specifically directed penicillins would be adequate. The danger is broad-spectrum antibiotics
frequently interfere with indigenous bacteria (naturally occurring in the body). Tetracycline and
chloramphenicol are also broad-spectrum antibiotics.

CEPHALOSPORINS & PENICILLIN mode of action is they both AFFECT CELL WALLS.

BASIC MODES OF ACTION OF ANTIBIOTICS

NYSTATIN & AMPHOTERICIN B are ANTIFUNGAL AGENTS referred to as “Polyene

antibiotics” that IMPAIR ERGOSTEROL SYNTHESIS. Ergosterol is the major sterol of fungal
membranes.
• Antifungal drugs affect cell membrane permeability, causing leakage of cellular constituents,
which leads to death of the affected cells.

CLINDAMYCIN-binds to 50S ribosomal subunit, blocking protein synthesis. Clindamycin is a

semisynthetic derivative of lincomycin. Its use is restricted by its side effects (severe diarrhea &
pseudomembranous colitis). Antibiotic alternative for the penicillin-allergic patient.
• CLINDAMYCIN is an antibiotic recommended by the FDA RESERVED FOR SERIOUS
ANAEROBIC INFECTIONS.

• CLINDAMYCIN IS BACTERIOSTATIC and is active against most gram-positive and many

anaerobic organisms, including Bacteroides fragilis. Clindamycin is most effective in treating
infections due to Bacteroides and Fusobacterium species.

• CLINDAMYCIN IS USED IN DENTISTRY to treat certain anaerobic infections due to

Bacteroides species such as periodontal infections, bacteremia, and infective endocarditis.

• Development of pseudomembranous colitis is a major adverse effect (sign of toxicity) of

prolonged clindamycin therapy.

AMOXICILLIN-an antibiotic indicated for patients requiring the administration of prophylactic

antibiotics PRIOR to DENTAL TREATMENT. Adults (2.0g orally 1 hour before appointment);
Children (50mg/kg orally 1 hour prior to appointment).

Patients ALLERGIC TO AMOXICILLIN should take Clindamycin, Cephalexin, or Azithromycin:

• CLINDAMYCIN: 1 hour prior to appointment; Adults (600mg orally); Children (20mg/kg orally).

• CEPHALEXIN: 1 hour prior to appointment by Adults (2.0g orally) & Children (50mg/kg orally).

• AZITHROMYCIN: 1 hour prior to appointment by Adults (500mg orally) & Children (15 mg/kg
orally).
RICKETTSIAL DISEASES-small, gram-negative, aerobic, coccobacillary bacteria (obligate
intracellular parasites). They contain both RNA and DNA, while viruses contain either RNA or DNA.
Human rickettsial infection results from insect bites. The human target cell for all rickettsiae is the
endothelial cell of capillaries and other small blood vessels. Rickettsiae destroys endothelial cells.
Human rickettsial infections present systemic symptoms of headache, myalgias, and fever, followed by a
rash. They are divided into two groups as seen below:

TETRACYCLINE (inhibits protein synthesis) & CHLORAMPHENICOL are BROAD-SPECTRUM

ANTIBIOTICS prescribed to treat RICKETTSIAL DISEASES.

Rickettsialpox-a mite-born infectious illness caused by bacteria (Rickettsia) usually found in mice. Has
oral manifestations, but first symptom is a bump formed at the bite site that leaves a black, crusty scab.
Flu-like symptoms. RASH CAN SPREAD OVER ENTIRE BODY. Treatment: Doxycycline.

 VIRUSES
The CYTOPATIC EFFECT is seen when a virus infects a specific cell culture is characteristic to
EACH VIRUS and is USED TO DETECT & IDENTIFY VIRUSES.

HALLMARK OF VIRAL INFECTION of the cell is the CYTOPATHIC EFFECT (CPE). This
change starts with alterations of cell morphology accompanied by marked derangement of cell function
and culminates in the lysis and death of cells. Not all viruses cause CPE; some can replicate while
causing little morphologic or functional change in the cell.
• CYTOPATHIC REACTIONS include necrosis, hypertrophy, giant cell formation, hypoplasia, and
metaplasia. These cytological changes provide useful presumptive evidence for the diagnosis of the
viruses that induce the cytopathic effects.

• Viruses cause diseases by lysing many cells of the host, transforming cells to malignant cells,
making vital target cells nonfunctional, and disrupting the normal defense mechanisms of the host.

VIRUSES are not sensitive to antibiotics, but are sensitive to INTERFERON which inhibits virus
replication. EPLICATION OF A VIRUS within a host cell depends on the ability of the viral genome
to enter the host cell, to remain functional, and direct the host cell to produce viral macromolecules.
Within the host cell, the viral genome achieves control of the cell’s metabolic activities. The virus then
uses the metabolic capacity of the host cell to produce new viruses. Often, virus replication causes
changes in the host cell, usually causing cell death. For viruses, burst size is the average number of
progeny viruses released per infected cell.

• ALL VIRUSES HAVE a central genetic nucleic acid core (either RNA or DNA) surrounded by
a protein coat. The genome of the virus may consist of double-stranded DNA, single-stranded
DNA, single-stranded RNA, or double-stranded RNA.

• A viral nucleic acid (genome) is composed of either DNA or RNA (but not both) encased in a
protein coat = CAPSID. They are either naked or enveloped, depending if the capsid is
surrounded by a lipid bilayer = ENVELOPE.

• Viruses replicate only in living cells and thus, are OBLIGATE INTRACELLULAR
PARASITES. Viruses depend on host cells for energy production. Viruses CANNOT be
observed with a light microscope, and can pass through filters that retain bacteria.

WAYS TO IDENTIFY VIRUSES:

• Whether or not specific antisera neutralize the virus (cell culture techniques); the most
generally accepted laboratory method for the diagnosis of most common viral infections.
• Morphology of the viral protein coat.
• Nature of the viral nucleic acid (RNA or DNA).
• The ability of ether or chloroform to inactivate the virus.

DNA VIRUSES (except poxviruses), REPLICATE IN THE NUCLEUS and use the host cell DNA-
dependent RNA polymerase to synthesize their mRNA. The genome of all DNA viruses consists of
double-stranded DNA (except for paroviruses), which have a single-stranded DNA genome.

MOST RNA VIRUSES undergo the entire replicative cycle in the cytoplasm (except retroviruses and
influenza viruses) which replicate in the nucleus of the host cell.

POSITIVE &. NEGATIVE POLARITY OF RNA VIRUSES:

• Positive Polarity-an RNA virus with the same base sequence as the mRNA. Examples of
positive polarity RNA viruses are orthomyxoviruses and paramyxoviruses.

• Negative Polarity-an RNA with a base sequence complimentary to the mRNA. Ex: if the mRNA
sequence is G-U-C-A, an RNA with negative polarity would be C-A-G-U and an RNA with positive
polarity would be G-U-C-A.

• Positive or negative polarity, ONLY REFERS TO RNA VIRUSES (not DNA viruses).

The first step in viral gene expression is mRNA synthesis. Positive polarity RNA viruses can use their
RNA genome directly as mRNA, while negative polarity RNA viruses must transcribe their own
mRNA by using the negative strand as a template. Because the cell does not have an RNA polymerase
capable of using RNA as a template, the virus carries its own RNA-dependent RNA polymerase.

The ability of pathogenic microorganisms, including viruses to attach to and invade particular cells and
tissues establishes specific tissue affinities for pathogenic microorganisms.

MOST VIRAL ANTIGENS of diagnostic value or importance are PROTEINS.

RETROVIRUSES-are ONCOGENIC RNA viruses that have their genome surrounded by an inner
protein envelope and outer envelope that contains lipid and glycoprotein SPIKES that attach the
retrovirus to host cells. “Retro” refers to the possession of the enzyme reverse transcriptase (an
RNA-directed DNA polymerase) that transcribes RNA into DNA during the process of viral nucleic
acid synthesis. 3 Retroviruses:
1. Oncovirus (e.g. HTVL)-produces leukemias, lymphomas, breast carcinomas, and sarcomas.
2. Lentivirus (HIV-1 and HIV-2)-causes AIDS
3. Spumavirus-there are no known human pathogens.

RETROVIRUS-is an enveloped, single-stranded, linear positive-polarity RNA virus that causes AIDS.
• HIV TRANSMISSION occur primarily by sexual contact and by transfer of infected blood. HIV
infects and kills helper (CD4) T cells, resulting in depression of both humoral and cell-mediated
immunity. HIV travels throughout the body (especially in macrophages), and induces a distinct
CPE (cytopathic effect) called giant-cell (syncytial) formation.

• Reverse Transcriptase-a viral enzyme unique to RNA tumor viruses (HIV).

RETROVIRUSES-possesses an RNA genome that does not function as a positive or negative sense
molecules, but acts as a template for the production of viral DNA. Retroviruses include Human
immunodeficiency virus (HIV). This is achieved by an RNA-dependent DNA polymerase (reverse
transcriptase) packaged with the RNA genome. The resulting viral DNA integrates into the host cell
genome to provide the template for viral RNA synthesis by host-derived mechanisms.

• RNA VIRUSES: Transcription-occurs in the cytoplasm except RETROVIRUSES &

INFLUENZA viruses which replicate in the host cell nucleus. Transcription involves an RNA-
dependent RNA polymerase except for retroviruses which possess the reverse transcriptase
enzyme (an RNA-dependent DNA polymerase).

DNA VIRUSES: Transcription occurs in the nucleus EXCEPT for POXVIRUSES. Transcription
involves a host-cell DNA dependent RNA polymerase.

BACTERIOPHAGES (phage)-viruses that INFECT BACTERIA; it is a very delicate bacterial virus

that attacks and destroys bacterial cells. Bacteriophages contain a nucleic acid core (DNA or RNA), and
a protein coat.
• Bacteriophages are viruses that infect bacteria and replicate ONLY within specific host
bacterial cells. Viruses are capable of reproduction ONLY INSIDE living cells.

• Lysogeny-the non-disruptive infection of a bacterial cell by a bacteriophage.

HOST CELL-a cell within which a virus replicates. Once inside the host cell, the viral genome takes
control of the cell’s metabolic activities. The virus then uses the host cell’s metabolic capacity to
reproduce new viruses. Often, the replication of these new viruses causes host cell death.

TEMPERATE PHAGE-a bacteriophage with the ability to form a stable, non-disruptive relationship
within a bacterium. It’s a bacteriophage capable of replication by an alternate method in which the phage
genome is incorporated into the bacteria chromosome. It persists through many cell divisions of the
bacterium without destroying the host, in contrast to a virulent phage that lyses and kills its host.
• Lysogenic Bacterium-bacterium that contains a temperate bacteriophage (Corynebacterium
diphtheriae).

• Lysogenic Conversion-the alteration of a bacterium to a virulent strain by the transfer of a DNA

temperate bacteriophage. The classic example of this conversion is in the alteration of
Corynebacterium diphtheriae to a virulent strain. The presence of this temperate phage renders the
bacterium pathogenic (without the phage it would not be harmful).

ONE-STEP GROWTH CURVE-growth curve that describes the lytic reproduction cycle that releases a
large number of phage simultaneously. LYSIS OF THE BACTERIAL CELL releases a large number of
phage simultaneously and, consequently, the lytic reproduction cycle exhibits a one-step growth curve.
• The GROWTH CURVE begins with an ECLIPSE PERIOD during which there are no complete
infective phage particles. Eclipse period is the time between entry of the viral DNA and
formation of the first complete virus within the host cell.

• ECLIPSE PERIOD is part of a longer period (LATENT PERIOD). Like the eclipse period, the
LATENT PEIOD begins when the phage injects DNA into a host cell, but which does not end
until the first assembled virus from the infected cell appears extra-cellularly.

In contrast to bacteria, fungi, and parasites, VIRUSES ARE NOT CELLS (they cannot reproduce
independently, do not have a nucleus or organelles). Viruses are smaller than cells, and cannot be seen
with a light microscope. Almost all viruses are HAPLOID (contain a single copy of their genome,
except RETROVIRUS FAMILY which is DIPLOID).

VIRION (viral particles)-an infectious viral particle that contain either DNA or RNA encased in a
protein coat (CAPSID). Virions are either naked or enveloped, depending on if the capsid is
surrounded by a lipoprotein envelope. Virion capsid is composed of polypeptide units
(CAPSOMERES).
• Some viruses (orthomyxoviruses and paramyxoviruses) have envelopes covered with spikes that
contain either hemagglutinin, neuraminidase, or a fusion protein that causes cell fusion, and
sometimes hemolysis.

VIROIDS-consist solely of a single molecule of circular RNA without a protein coat or envelope.
Viroids cause several plant diseases, but are not implicated in any human disease.

PRIONS-infectious protein particles COMPOSED SOLELY OF PROTEIN. Prions cause “SLOW”

diseases (Creutzfeldt-Jakob disease in humans and scrapie in sheep).

INFECTIOUS MONONUCLEOSIS (KISSING DISEASE)-an acute HSV-4 infection caused by

Epstein-Barr Virus (EBV) that most commonly occurs in young adults (15-25 years of age).
Characterized by sore throat, low-grade fever, enlarged lymph nodes, general fatigue, and weakness.
Hepatomegaly, splenomegaly, and abnormal bruising may exist. Hematologically, there is absolute
lymphocytosis with atypical lymphocytes and a positive heterophile test. Microscopically, Reed-
Sternberg cells may be seen. Spontaneous recovery usually occurs in 2-3 weeks. No antiviral therapy
is necessary for uncomplicated infectious mononucleosis and there is no EBV vaccine.
• It’s a disease of children and young adults caused by Epstein-Barr Virus (EBV).

• Epstein-Barr virus is strongly associated with Burkitt’s lymphoma, nasopharyngeal carcinoma,

and hairy leukoplakia.

• Associated with the production of atypical lymphocytes and IgM heterophile antibodies identified by
the heterophile test.

• Patients with an acute infectious disease (e.g. infectious mononucleosis) have a rising antibody
titer (concentration).


RNA NON-ENVELOPED VIRUSES

RNA NON-ENVELOPED VIRUSES: Picornaviruses (Picornaviridae) are RNA non-enveloped

viruses:
• Enteroviruses-poliovirus, coxsackie viruses, and echoviruses.
• Rhinoviruses-causes the common cold.
• Reoviruses-ROTAVIRUS-most important cause of viral gastroenteritis in young children (<2).
• Hepatitis A-causes infectious hepatitis.

PICORNAVIRUSES-very small, non-enveloped viruses composed of a positive stranded, single-

stranded RNA genome. This family includes enteroviruses (poliovirus, coxsackieviruses,
echoviruses), hepatitis A, rhinoviruses, and reoviruses.

Coxsackieviruses-belong to Picornavirus Family, and are divided into group (A and B) based on the
lesions observed in mice. Coxsackieviruses cause mild infections in humans, and replicate similar to
poliovirus.
• Group A specific Coxsackie Viruses: (herpangina & hand-foot-and-mouth disease). The
location of oral lesions (intraoral loacation) distinguishes these two diseases; the oral lesions of
herpangina appear on the throat, palate, or tongue. Herpangina-a summer illness that produces
vesicular lesions of the uvula, anterior pillars, and posterior pharynx. Oral lesions of hand-foot-
and-mouth disease appear on the buccal mucosa and gingiva

• Group B specific Coxsackie Viral Conditions: (pleurodynia, myocarditis, pericarditis, and

juvenile diabetes).

Rhinovirus-a virus with over 100 different serotypes. It’s the MAIN CAUSE of the COMMON
COLD, this is the main reason developing a vaccine has not been found. Does not cause persistent
infection

Echoviruses-cause aseptic (viral) meningitis, upper respiratory infections, and severe diarrhea in
newborns.

Poliovirus-belongs to the picornavirus family (small, non-enveloped viruses composed of an icosahedral

nucleocapsid and a positive-stranded, single-stranded RNA genome). Causes poliomyelitis.
• Polio virus belongs to the enterovirus group (includes coxsackieviruses, echoviruses, and
hepatitis A virus).

• 3 serologic (antigenic) types of poliovirus are based on different antigenic determinants on the outer
capsid proteins.

• Polio virus is transmitted by the fecal-oral route. There is a vaccine available, but antiviral
therapy is INEFFECTIVE in treating poliomyelitis. Poliovirus DOES NOT establish a latent
infection.
POLIOMYELITIS is caused by the poliovirus (an enterovirus transmitted by consumption of water
with fecal contaminants). It replicates in the oropharynx and intestinal tract before spreading through the
bloodstream to the CNS. It then replicates again in MOTOR NEURONS in the anterior horn of the
spinal cord. Death of these cells results in paralysis of the muscles innervated by those neurons.
• Initial Poliomyelitis symptoms: headache, vomiting, constipation, and sore throat. Paralysis may
follow and is asymmetric and flaccid.
• Poliomyelitis can be prevented by the KILLED VACCINE (SALK VACCINE) or inactivated polio
vaccine (IPV) and a live, attenuated vaccine (SABIN VACCINE) or polio vaccine (OPV).

Hepatitis A virus-causes infectious hepatitis. Its portal of entry is the GASTROINTESTINAL

TRACT.

Hepatitis A virus, Poliovirus, and Rotavirus use the GASTROINTESTINAL TRACT as their portal
of entry.

REOVIRUSES have a unique double-shelled capsid that contains a segmented double-stranded RNA
genome. REOVIRUSES are naked (non-enveloped) RNA viruses with a double-shelled (outer shell
and core) icosahedral capsid containing 10 or 11 segments of double-stranded RNA. Reoviruses replicate
in the cytoplasm. There are 3 groups:
1. Reoviruses-produce minor respiratory tract infections and GI disease.

2. Rotaviruses (gastroenteritis virus type B)-cause infantile diarrhea, and are the most common
cause of gastroenteritis in children (2 and under).

3. Colorado tick fever virus (arbovirus)-causes Colorado tick fever.

VIRAL GASTROENTERITIS-a self-limiting disease, often called the 24-hour or intestinal flu caused
by REOVIRUS. An influenza virus does not cause it, but it is associated with RNA viruses and is
often diagnosed by ELISA on fecal samples. Characteristic symptoms: sudden gastrointestinal pain,
vomiting, and diarrhea. Recovery occurs within 12-24 hours. Dehydration is a major concern,
especially in infants, where viral gastroenteritis is sometimes fatal.


RNA ENVELOPED VIRUSES

RNA ENVELOPED VIRUSES:

• Paramyxoviruses- Measles, mumps, rubella, Hepatitis C viruses, & respiratory viruses (viruses,
respiratory syncytial virus (RSV)).

• Orthomyxoviruses- influenza A, B, C, and parainfluenza.

• Rabies virus and HIV (human immunodeficiency virus).

MUMPS (EPIDEMIC PAROTITIS)-the most common VIRAL DISEASE of the SALIVARY

GLANDS caused by the RNA-Paramyxovirus. Transmitted via salivary or respiratory secretions. 90%
of cases occur before age 14yrs. A major sign is sudden BILATERAL PAROTID GLAND
SWELLING (90% of cases) without purulent discharge from the duct. Patient presents with flu-like
symptoms (mild fever, malaise). Most cases are self-limiting.

RUBELLA VIRUS-a member of the togavirus family and is an enveloped RNA virus composed of an
icosahedral nucleocapsid and a positive-stranded, single-stranded RNA genome. It causes
RUBELLA (German measles) and congenital rubella syndrome. Prevention involves immunization
with the live, attenuated vaccine. Rubella Virus (German measles) is transmitted via
RESPIRATORY DROPLETS.

INITIAL REPLICATION of rubella virus occurs in the nasopharynx and local lymph nodes, where it
spreads via blood to the internal organs and skin. It causes German measles, and is a teratogen (causes
malformation of an embryo or fetus):
• Rubella (German Measles)-a milder, shorter disease than measles. An incubation period (2-3
weeks) is followed by a prodromal period of fever and malaise, which is subsequently followed by
a maculopapular rash (flat, pink spots that first appear on the face and then extremities),
which lasts 2-3 days. Posterior auricular lymphadenopathy is characteristic.

• Congenital Rubella syndrome-when a non-immune woman is infected during the first trimester
(especially the first month), significant congenital malformations can occur to the fetus. The
malformations are widespread and involve primarily the heart (e.g. patent ductus ateriosus), eyes
(e.g. cataracts), and brain (deafness and mental retardation). Rubella is most likely to cross the
placenta and produce congenital defects in the fetus.

RUBEOLA VIRUS-an RNA paramyxovirus that causes MEASLES (RUBEOLA); a skin rash with
Koplik’s spots. Transmitted by respiratory droplets.

GERMAN MEASLES (RUBELLA)-an RNA virus caused by the RUBELLA VIRUS via air droplets
from couging. Facial rash starts two weeks after exposure and spreads to the body. Symptoms: swollen
lymph nodes, fever, sore throat and fatigue. Vaccine is often given with the measles and mumps as
“MMR” vaccine. The prodromal sign of measles that manifests 2-3 days before the actual rash are
KOPLIK SPOTS (clustered, white buccal mucosal lesions).

CORONAVIRUSES-causes the COMMON COLD in adults.

ORTHOMYXOVIRUSES (Influenza Viruses A, B, C)-causes INFLUENZA. Complications are

Reye’s syndrome (B virus) in children.

RESPIRATORY SYNCTIAL VIRUS (RSV)-the only member of the paramyxovirus family (also
includes measles virus, mumps virus, and parainfluenza viruses) that lacks the envelope glycoproteins
hemagglutinin and neuraminidase. Its surface spikes are fusion proteins. The envelope of
paramyxoviruses is covered with spikes that usually contain either hemagglutinin, neuraminidase, or
a fusion protein that causes cell fusion and sometimes hemolysis.
• RSV’s FUSION PROTEINS (surface spikes) causes cells to fuse, forming multinucleated giant cells
(syncytial), which gives rise to the name of the virus. Rebaviron (Virazole) treats severely ill
hospitalized infants. There is no vaccine.

• RSV surface spikes are fusion proteins, not hemagglutinins or neuraminidases.

• RSV is the most important cause of severe pneumonia and bronchiolitis in infants.

• RSV transmission occurs via RESPIRATORY DROPLETS and by DIRECT CONTACT of

contaminated hands with the nose or mouth.

PARAINFLUENZA VIRUSES-cause croup (acute laryngotracheobronchitis) and pneumonia in

children and a disease resembling the common cold in adults. Surface spikes on parainfluenza viruses
consist of hemagglutinin (H), neuraminidase (N), and fusion (F) proteins. Parainfluenza viruses are
transmitted by RESPIRATORY DROPLETS and DIRECT CONTACT. There is no antiviral
therapy nor a vaccine available.

INFLUENZA VIRUSES-shows changes in the antigenicity of its hemagglutinin and neuraminidase

proteins (especially influenza A). Influenza viruses are THE ONLY MEMBERS OF
ORTHOMYXOVIRUS FAMILY. Influenza virus is composed of a unique segmented, single-stranded
negative-stranded RNA genome, a helical nucleocapsid, and outer lipoprotein envelope. The
envelope is covered with two different spikes (which are glycoproteinaceous projections or peplomers),
that contain either hemagglutinin or neuraminidase. Influenza viruses are classified as A, B, C depending
on a nucleocapsid antigen.

• INFLUENZA VIRUSES-are orthomyxoviruses. Paramyxoviruses and orthomyxoviruses are

enveloped, single-stranded negative-stranded RNA viruses. Paramyxoviruses differ from
orthomyxoviruses in that their genomes are not segmented, they have a larger diameter, and their
surface spikes are different. Cytopathic effect for paramyxoviruses is syncytia formation (induces
cells to form multinucleated giant cells).

• INFLUENZA A-has the ability to cause epidemics that depends on antigenic changes in the
hemagglutinin and neuraminidase. There are two types of changes:
1. Antigenic SHIFTS-major changes based on reassortment of genome pieces.
 2. Antigenic DRIFTS-minor changes based on mutations.

• One serious complication associated with outbreaks of influenza is the development of REYE’S
SYNDROME. Reye’s syndrome is an acute pathological condition affecting the CNS. It is
associated with outbreaks of influenza B virus for unknown reasons. Reye’s syndrome is
principally associated with children who have taken aspirin to treat the viral infection (there is
no known direct cause-and-effect between aspirin use and Reye’s syndrome).

RNA virus genome may be SINGLE OR DOUBLE STRANDED, segmented, or non-segmented.



DNA ENVELOPED VIRUSES

• Herpes viruses (Herpes simplex, Varicella-zoster, Epstein –Barr, and Cytomegalovirus).

• Poxviruses (smallpox and Vaccinia virus).
• Hepatitis B virus

HERPES VIRUS-a medium-sized ENVELOPED DNA VIRUS with an icosahedral nucleocapsid

containing linear, double-stranded DNA. Herpes Virus Family contains 5 important human pathogens
that are all structurally similar (large 120-200nm in diameter), second only to poxviruses. Herpes Viruses
replicate in the host cell’s nucleus and are the only viruses to obtain their envelopes by budding
from the nuclear membrane.
1. HSV-1-causes acute herpetic gingivostomatitis, cold sores, and encephalitis.

2. HSV-2-is the primary infection is Herpes genitalis.

3. Varicella-zoster virus-primary infection is CHICKENPOX and SHINGLES.

4. Cytomegalovirus (CMA)-primary infection is Congenital abnormalities (the major VIRAL

cause of birth defects in infants in developed countries.

5. Epstein-Barr virus (EBV)- associated with Burkitt’s lymphoma and nasopharyngeal carcinoma.

Herpes Virus pathogens cause latent and acute (primary) infections. Herpes simplex (HSV) 1 & 2, and
varicella-zoster virus (shingles) cause a VESICULAR RASH. Herpes simplex virus often produces
eosinophilic nuclear inclusion bodies classified as Cowdry type A in infected cells.

Certain Herpes Viruses have ONCOGENIC POTENTIAL (causing cancer) in humans. Epstien-Barr
virus (EBV) is associated with Burkitt’s lymphoma and nasopharyngeal carcinoma.

HERPES SIMPLEX VIRUS type 1 & type 2 are distinguished by antigenicity and lesion location. The
virus replicates in the skin or mucous membrane at the initial site of infection, then migrates up the
neuron and becomes latent in the sensory ganglion cells.

1. Herpes Simplex Virus (Type 1) HSV-1: lesions ABOVE THE WAIST. HSV-1 is transmitted
primarily in saliva (direct contact), and infections mainly occur on the face. HSV-1 becomes
latent after a primary oral infection in trigeminal sensory ganglia.
• HSV-1 causes acute herpetic gingivostomatitis, recurrent herpes labialis (cold sores),
keratoconjunctivitis, and encephalitis.

2. Herpes Simplex Virus (Type 2) HSV-2: lesions BELOW THE WAIST. Transmitted by sexual
contact, and infections occur in the genital area. HSV-2 usually becomes latent in the lumbar and
sacral sensory ganglia.
HERPES SIMPLEX TYPE 1: the inactive HSV-1 virus resides in SENSORY NERVE GANGLIA
(TRIGEMINAL GANGLION), but often reappears later as the “COLD SOAR” usually at the
mucocutaneous junction of the lips. This disease is called “recurrent herpes labialis”. Emotional stress,
trauma, and excessive exposure to sunlight are factors causing the appearance of the recurrent herpetic
lesions on the lips. Acyclovir 5% ointment (Zovirax) has been successful in reducing the duration and
severity of these sores.
• HSV-1 may involve a primary infection (e.g. gingivostomatitis) or recurrent infection (e.g. cold
sores). HSV-1 may be diagnosed by a Tzanck smear for rapid identification when skin lesions
are involved.

• HSV-1 can cause recurrent infections such as keratoconjunctivitis and encephalitis. The primary
infection ranges from subclinical (asymptomatic) to severe systemic infections. Many children have
asymptomatic primary infections.

• HSV-1 CANNOT be treated prophylactically by vaccine.

Primary infection with HERPES SIMPLEX VIRUS is characterized by: average course of 2-3 weeks,
a few mild lesions on the lips or in the mouth that resolve over a week to 10 days. Fever, chills, and
malaise (flu-like symptoms).

• THE PRIMARY INFECTION (primary herpetic gingivostomatitis) usually occurs in a child

under ten years of age who has had no contact with the Type I herpes simplex virus and who
thus has no neutralizing antibodies. It may also affect young adults (15-25). Nearly all primary
infections are subclinical (they may only have flu-like symptoms) and one or two mild sores in the
mouth which go unnoticed by the parents.

• IN OTHER CHILDREN, the primary infection may manifest by acute symptoms (acute
herpetic gingivostomatitis). These include, fever, irritability, cervical lymphadenopathy, fiery red
gingival tissues, and small, yellowish vesicles which rupture and result in painful ulcers on the free
and attached mucosa. The most serious potential problem in a child with this infection is
DEHYDRATION due the child not wanting to eat or drink because of the pain.

• TREATMENT IS SUPPORTIVE and aimed toward the relief of the acute symptoms so that fluid
and nutritional intake can be maintained. Primary herpetic gingivostomatitis usually runs a course of
14-20 days and the ulcers heal without scarring.

OF ALL HERPES VIRUSES, HERPES SIMPLES I & II cause manifestations of recurrent

infection in otherwise healthy people.

EPSTEIN-BARR VIRUS (EBV)-a member of the herpes virus group that causes infectious
mononucleosis and is associated with the subsequent development of two forms of cancer (Burkitt’s
lymphoma and nasopharyngeal carcinoma). EBV is also associated with hairy leukoplakia-a whitish,
nonmalignant tongue lesion seen in AIDS patients.
• EBV virus specifically infects B-lymphocytes and some epithelial cells. It is associated with the
production of atypical lymphocytes and IgM heterophile antibodies identified by the heterophile test
(mononucleosis spot test). This antibody eventually appears in the serum of more than 80% of the
 patients with infectious mononucleosis, hence it is highly diagnostic of the disease.

• Infection with Epstein-Barr virus can cause infectious mononucleosis, which may be characterized
by the appearance of HETEROPHILE ANTIBODIES (antibodies that cross-react with unrelated
antigens like those found on sheep and horse erythrocytes).

Cells with OWL’S EYE INCLUSIONS are often found in urine of individuals with cytomegalovirus
infections.

VARICELLA-ZOSTER VIRUS (VZV)- member of HERPES VIRUS GROUP. Varicella

(chickenpox) is the primary disease it causes, while zoster (shingles) is the recurrent form found in
adults.

1. VARICELLA (CHICKENPOX)-a very contagious disease of childhood spread by respiratory

droplets or direct contact with the lesions. Over 90% of all cases of chickenpox occur in
children under age 9. After an incubation period (2-3 weeks), brief prodromal symptoms of fever
and malaise occur, followed by a maculopapular rash that appears in crops on the trunk and
spreads to the head and extremities. The rash then changes to vesicles, pustules, and finally
crusts that fall off in about one week.
• White specks on the oral mucosa adjacent to the first molar, a bluish-red ring surrounds
these spots; a cold with red and runny eyes; blotchy reddish rash behind the ears and on the
face.

2. SHINGLES (Herpes Zoster)-the adult counterpart of chickenpox. It’s the result of

reactivation of a latent varicella-zoster virus, which has remained latent in the nerve root cells
of the posterior root ganglia of cranial nerve roots (most frequently the TRIGEMINAL
NERVE). It is characterized by the occurrence of painful vesicles on the skin along the course
of the affected cranial or sensory nerve. The pain can last for weeks and can be debilitating.
• Herpes Zoster-is characterized by individual, blister-like lesions affecting specific
dermatomes causing intense, burning pain.
POXVIRUSES-the LARGEST & MOST COMPLEX DNA ENVELOPED VIRUSES. The poxvirus
family includes three viruses: smallpox virus (variola virus), vaccinia virus, and molluscum contagious
virus (MCV). Poxviruses are the largest and most complex viruses.

POXVIRUSES are brick-shaped particles containing an enveloped linear double-stranded DNA

genome. Poxviruses multiply in the cytoplasm of host cells (as opposed to the nucleus) and are usually
associated with skin rashes. Smallpox-an acute, highly infectious, often fatal disease characterized by
high fever, prostration, and a vesicular, pustular rash. Smallpox has been eradicated by global use of the
vaccine, which contains live, attenuated vaccinia virus.


DNA NON-ENVELOPED VIRUSES

DNA NON-ENVELOPED VIRUSES:

• Adenovirus-causes upper and lower respiratory infections.
• Papillomaviruses-cause papillomas (WARTS) on skin and mucous membranes.
• Parvoviruses-cause erythema infectiosum (slapped-cheeks syndrome, fifth disease), aplastic crisis,
and fetal infections.

ADENOVIRUSES-naked (non-enveloped) medium-sized DNA viruses composed of an icosahedral

nucleocapsid and a double-stranded linear DNA genome. They have SPIKES (glycoproteinaceous
projections that are hemagglutinin proteins) protruding from their surfaces involved in the absorption or
attachment of the virus to the host cell. Adenoviruses frequently cause subclinical infections, and are
transmitted by aerosol droplet, the fecal-oral route, and direct inoculation. They are classified into
seven groups (A through G).
Adenoviruses is associated with these diseases:
• acute respiratory infections, acute contagious conjunctivitis (pink eye), and pharyngoconjunctival
fever characterized by fever, pharyngitis, and conjunctivitis.

PHARYNGITIS-inflammation of the pharynx. Main symptom is a SORE THROAT, caused by a

VARIETY OF VIRUSES (adenoviruses and coxsackie viruses).

 VACCINES
FREUND’S ADJUVANT-a mixture composed of mineral oil, lanolin, and killed mycobacteria. Freund’s
Adjuvant is a common experimental adjuvant that consists of killed M. tuberculosis suspended in lanolin
and mineral oil. This adjuvant elicits stronger T- and B-cell mediated responses when antigens alone do
not evoke sufficient immunogenic responses. Adjuvant Functions:
1. ENHANCES ANTIBODY RESPONSE.
2. enhance uptake of the antigen by antigen-presenting cells (APC –macrophages).
3. are added to vaccines to slow down absorption and increase vaccine effectiveness.

When protein antigens are mixed with aluminum compounds, a precipitate is formed that is more
useful for establishing immunity that are the proteins alone. Alum-precipitated antigens are released more
slowly in the body, enhancing the stimulation of the immune response. The use of adjuvants eliminates
the need for repeated booster doses of the antigen, and permits the use of smaller doses of antigen
in the vaccine.

TOXOIDS (immune globulins)-used to protect vaccines because they RETAIN THEIR

ANTIGENICITY but have lost their toxicity. TOXOIDS are inactivated protein exotoxins that induce
the formation of specific antitoxin antibodies that serve as the basis for the specific protection from the
toxin. These vaccines are useful against diphtheria, tetanus, and other diseases. Toxoids are most often
prepared by treating toxins with FORMALDEHYDE. However, not all toxins can be converted to
toxoids by treatment with formaldehyde.

ANTITOXIN-an antibody formed in response to a specific toxin. A serum containing antitoxins can be
used for either treating or preventing certain bacterial diseases.
• Antitoxin can neutralize unbound toxin to prevent the disease from progressing. Tetanus
antitoxin is used to treat and prevent TETANUS. Botulinum antitoxin is used to treat
BOTULISM. Diphtheria antitoxin is used to treat diphtheria.

Acquired immunity occurs NATURALLY & ARTIFICIALLY, and can be active or passive.
1. Naturally Acquired Active Immunity-person is exposed to an antigen and the body produces
antibodies.

2. Naturally Acquired Passive Immunity-antibodies (IgG) passed from mother to fetus during
pregnancy and IgA passed from mother to newborn during breast-feeding.

3. Artificially Acquired Active Immunity-vaccination with killed, inactivated, or attenuated

bacteria or toxoid. Administration of toxoid.

4. Artificially Acquired Passive Immunity-injection of immune serum or gamma-globulin.

Rabies vaccine & clostridium tetani vaccine result in ARTIFICALLY ACQUIRED ACTIVE
IMMUNITY. The purpose of the rabies vaccine and tetanus vaccine is to elicit an immune response
before the onset of disease symptomatology. Effectiveness of this type of vaccine depends on the
relatively slow development of the infecting pathogen prior to the onset of disease symptoms and the
ability of the vaccine to initiate antibody production before the active toxins are produced and released to
the site where they can cause serious disease symptoms.
• Rabies is a viral disease with one the LONGEST INCUBATION PERIODS.

ACTIVE IMMUNITY-induced by vaccines prepared from bacteria or their products.

PASSIVE IMMUNITY-provided by the administration of preformed antibody in immune globulins

(toxoids) preparations.

PASSIVE-ACTIVE IMMUNITY-involves giving both immune globulins (toxoids) to provide immediate

protection and a vaccine to provide long-term protection.

BACTERIAL VACCINES:
• Capsular polysaccharides vaccines
• Inactivated protein exotoxins (toxoids) vaccines
• Killed bacteria and Live attenuated bacteria vaccines

CAPSULAR POLYSACCHARIDE VACCINES:

• Streptococcus pneumonia vaccine (for pneumonia); Neisseria meningitides vaccine (meningitis);
and Haemophilus influenzae vaccine (for meningitis).

TOXOID VACCINES:
• Corynebacterium diphtheriae vaccine (for diphtheria); Clostridium tetani vaccine (for tetany).

KILLED BACTERIAL VACCINES:

• Bordetella pertussis vaccine (treats whooping cough)
• Salmonella typhi vaccine (for typhoid fever). Asymptomatic carriers are a major hazard of
Typhoid fever.
• Vibrio cholerae vaccine (for cholera).

LIVE ATTENUATED BACTERIAL VACCINES:

• Mycobacterium bovis vaccine (TB); Francisella tularensis vaccine (for tularemia); and Coxiella
burnetti vaccine (for Q fever).

Vaccines that contain LIVE VIRUS whose pathogenicity has been attenuated, are used against
MEASLES, MUMPS, & RUBELLA (NOT RABIES). MMR is a bacterial vaccine routinely given in
the U.S.Attenuated virus-a virus whose pathogenicity has been reduced so it will initiate the immune
response without producing the specific disease.

 FUNGI
FUNGI-are EUKARYOTIC and have a complex cell wall. All fungi are GRAM-POSITIVE, and grow
in Sabouraud’s medium and contain both DNA and RNA. There are 2 types of Fungi:
1. Yeasts-grow as single cells that reproduce by ASEXUALLY BUDDING.
2. Molds-grow as long filaments (hyphae) and form a mat or mass = mycelium.

DIMORPHISM (fungi can be dimorphic = have two morphologic forms) a characteristic of some fungi
that form different structures at different temperatures. They exist as molds in the saprophytic, free-living
state at ambient temperatures and as yeasts in host tissues at body temperature. These fungi include
major pathogens Blastomyces, Histoplasma, Coccidioides, and Candida.

MOST FUNGI reproduce ASEXUALLY by forming conidia (asexual spores) form the sides or ends of
specialized structures (conidiophores). Different conidia help in the identification of fungi. Examples of
asexual spores (conidia) include arthrospores, chlamydospores, blastospores, and sporangiospores.

SOME FUNGI reproduce SEXUALLY by mating and forming SEXUAL SPORES. Examples include
zygospores, ascospores, and basidiospores.

MOST FUNGI are OBLIGATE AEROBES; some are facultative anaerobes; but NONE are
obligate anaerobes.

AFLATOXINS-coumarin derivatives produced by ASPERGILLUS FLAVUS that cause liver

damage and tumors in animals, and suspected of causing hepatic carcinoma in humans. Aflatoxins bind
to DNA and prevents transcription of genetic information. Aflatoxins are ingested with spoiled grains and
peanuts are metabolized by the liver into the epoxide (a potent carcinogen).

ASPERGILLUS SPECIES-exist only as MOLDS; they are not dimorphic. Aspergillosis is most
commonly caused by A. fumigatus, A.niger, or A. flavus. This disease has 3 forms:
1. mycetoma-grows in lung cavities.
2. invasive aspergillosis-begins in the lungs, and spreads to other organs.
3. allergic bronchopulmonary aspergillosis-allergy to spores that produces asthma attacks.

CELL WALLS of MOST FUNGI contain CHITIN, GLUCANS, & PROTEINS. Sterols (ergosterol)
are in the fungi cell membrane.

All fungi are SEPTATED (hyphae form transverse walls) EXCEPT fungi in Class Zygomycetes.


MYCOSIS (FUNGAL INFECTIONS)

MYCOSIS-a human fungal infection often exacerbated by various environmental and physiological
conditions. Inhalation of spores or localized colonization on the skin may cause persistent infections, thus
mycoses often start in the LUNGS or on SKIN. Antibiotics are a risk factor for fungal infections and
people with weak immune systems (HIV/AIDS, steroid treatment, chemotherapy, diabetes). Elderly
and youth are especially susceptible due to weak immunity.

• Mycoses are classified based on the TISSUE THEY INITIALLY COLONIZE (superficial,
cutaneous, subcutaneous, systemic mycoses due to primary or opportunistic pathogens).

• Mycosis Treatment: Anti-fungal drugs (Fluconazole or Amphotericin B).

NOSOCOMIAL INFECTIONS-infections acquired during hospitalization, unrelated to the patient’s
primary condition. Nosocomial infections are often caused by:
• Candida albicans, Aspergillus, E. coli, Hepatitis viruses, Herpes Zoster virus, Pseudomonas
aeruginosa, Streptococci, and Staphylococci.

COCCIDIOIDOMYCOSIS (“valley fever” or “San Joaquin fever”)-and infection or lesion in the

LUNG caused by inhalation of dust aerosols containing the highly infectious Coccidioides immitis
arthrospores. A self-limiting infection endemic to hot, dry regions of the southwest U.S. and Central
and S. America. CANNOT be treated with penicillin, as Amphotericin B (an antifungal) is the drug of
choice in treating Coccidioidomycosis. Fluconazole and itraconazole are also used to treat various
fungal infections.

BLASTOMYCOSIS (Gilchrist’s Disease or North American blastomycosis)-caused by Blastomyces

dermatitidis (a dimorphic fungus that exists as a mold in soil and as a yeast in tissue). This fungus is
endemic in North and Central America, growing in moist soil rich in organic material. It forms
hyphae with small, pear-shaped conidia. Inhalation of conidia causes human infection.

HISTOPLASMOSIS-caused by inhaling airborne fungal spores from bird and bad droppings (poop).
Histoplasma capsulatum (an intracellular parasite; dimorphic fungus that exists as mold in soil and as a
yeast in tissue). In the U.S. it is endemic in central and eastern states (especially in Ohio and
Mississippi River valleys). Infection is usually asymptomatic, but may produce a benign, mild
pulmonary illness (primary form of disease). A common cause of pulmonary nodules. The fungal
infection may spread throughout the body, and this disseminated form, though uncommon, is serious.
• In infected tissues, yeast cells of Histoplasma capsulatum are found within macrophages.

• Signs and symptoms occur 3-17 days after exposure and include: fever, chills, headache, dry cough,
and chest discomfort. Chronic infection can cause weight loss and coughing blood.

• Histoplasmosis resembles TB, both clinically and pathologically.

• Histoplasma capsulatum-a fungus that causes systemic disease (most common in lungs), and
 produces tuberculate chlamydospores.

• Histoplasmosis and blastomycosis are rarely acquired from another individual.

• Histoplasmosis are MYCOTIC ORGANISMS found microscopically within reticuloendothelial

cells.

MUCORMYCOSIS (Phycomycosis or Zygomycosis)-a disease MOST often characterized by

HYPHAE growing in and around vessels. It’s a fungal infection that may develop in people with poorly
controlled DIABETES.
• MUCORMYCOSIS is a relatively rare fungal infection caused by saprophytic mold (e.g. Mucor,
Rhizopus, and Absidia). Mucormycosis are DIMORPHIC, and morphologically characterized
by the LACK OF SEPTA IN THEIR HYPHA.

• Patients with diabetic ketoacidosis, burns, or leukemias are susceptible. It results in black,
dead tissue in the nasal cavity and blocks blood supply to the brain, leading to neurologic
symptoms (headaches and blindness).

OTHER OPPORTUNISTIC AIRBORNE FUNGI that normally fail to induce disease in most normal
persons, but may cause disease in people with SEVERELY SUPRRESSED IMMUNE SYSTEMS are:
1. Cryptococcus-Cryptococcus neoformans causes Cryptococcosis. C. neoformans is an oval,
budding yeast that is not dimorphic. Cryptococcosis is more common than other fungal infections.
This infection is severe only in people with underlying immune system disorders (AIDS).
Cryptococcosis may spread to the meninges, where the resulting disease is cryptococcal
meningitis.

2. Aspergillus-species like Aspergillus fumigatus causes an aspergilloma (“fungus ball”) in the

lungs and Aspergillosis. Aspergillus species exist only as molds and are not dimorphic. They
cause pulmonary infections in people who have AIDS or have undergone organ transplantation.

3. Candida albicans is the most important species of Candida, causes thrush, vaginitis, and other
diseases. C. albicans is an oval yeast with a single bud. Overgrowth of C. albicans in those with
impaired host defenses produces the candidiasis.
• Candida is the genera of fungi most frequently recovered from healthy mucous membranes.
Candida is an ENDOGENOUS opportunistic fungi.

FUNGAL SPORES:
• Unlike bacterial spores, most fungal spores are completely killed when heated at 80°C for 30
minutes. Morphological characteristics (shape, color, and arrangement) of conidia are a useful aid
to identify fungi.

• Conidium- asexual, non-motile FUNGAL SPORES that cause allergies in some people.

CONIDIA (ASEXUAL SPORES):

1. Arthrospores-formed by fragmentation of the ends of hyphae; are the mode of transmission of
Coccidiodes immitis.
2. Chlamydospores-are thick-walled and quite resistant; characteristic of Candida albicans.
 3. Blastospores-formed by budding, as in yeasts; multiple buds are pseudohyphae (also
characteristic of C. albicans).
4. Sporangiospores-formed within a sac on a stalk by molds like Rhizopus and Mucor.

SEXUAL SPORES:
1. Zygospores-single, large spores with thick walls.
2. Ascospores-formed in sacs called ascus.
3. Basidiospores-formed externally on the tip of a pedestal called basidium.

Response to infection by many FUNGI is the formation of granulomas (seen in coccidioidomycosis,

histoplasmosis, blastomycosis).

DERMATOPHYTOSIS-common in people who live in communities with poor sanitation. Griseofulvin

is the most effective antibiotic. Fungi genera that cause dermatophytosis: Trichophyton,
Epidermophyton, & Microsporum.

EPIDEMIOLOGY OF DERMATOMYCOSES

 PARASITES
NEMATODES-roundworms with a cylindrical body and a complete digestive tract. Two types of
nematodes exist based on their primary location in the body.
1. Intestinal nematodes-Enterobius (pinworm), Trichuris (whipworm), Ascaris (giant
roundworm), and Necator and Ancylostoma (the two hookworms).

2. Tissue nematodes-Wuchereria, Onchocerca, and Lao are “FILARIAL WORMS”.

INFESTATION-the presence of parasites on the body (e.g. ticks, mites, and lice) or in the organs (e.g.
nematodes or worms). Infections caused by certain NEMATODES cause MARKED
EOSINOPHILIA (abnormally large numbers of eosinophils in the blood). Eosinophils do not ingest
the parasites, but bind to the surface of the parasites via IgE and secrete cytotoxic enzymes
contained within their eosinophilic granules.

TOXOPLASMOSIS-an infection caused by the protozoan Toxoplasma gondii. Sexual reproduction by

this parasite occurs only in the cells lining the intestine of cats. Eggs (oocytes) are shed in cat’s stool.
People also become infected by EATING RAW MEAT containing the dormant form (cysts) of the
parasite. It may resemble a mild cold or infectious mononucleosis in adults. It is treated with
SULFADIAZINE.
• Humans acquire TOXOPLASMA GONDII by ingesting cysts in POORLY COOKED MEAT
or from CATS.

CRYPTOSPORIDIOSIS-caused by the intestinal protozoan Cryptosporidium parvum. The main

symptom of cryptosporidiosis is WATERY DIARRHEA sometimes accompanied by abnormal cramps,
nausea, and vomiting. It is MOST SEVERE in immunocompromised patients (AIDS) where infection can
be fatal.

PNEUMOCYSTIS CARINII-a protozoan that causes pneumocystis pneumonia in immunocompromised

individuals (AIDS). This lung disease is often fatal. Candidiasis, hairy leukoplakia, and
Cryptosporidium enterocolitis are all opportunistic infections associated with immunocompromised
individuals (AIDS patients).

PROTOZOA-a diverse group of EUKARYOTIC, UNICELLULAR, non-photosynthetic

microorganisms generally LACKING A RIGID CELL WALL.

MALARIA-an INFECTION of RED BLOOD CELLS caused by the parasite PLASMODIUM.

Malaria is spread by the bite of an infected female Anopheles mosquito, a transfusion with
contaminated blood, or injection with a needle previously used by an infected person.
• Malaria is caused by 4 plasmodia: Plasmodium vivax, P. ovale, P. falciparum, and P. malariae. P.
vivax and P. falciparum are more common causes of malaria than P. ovale and P. malariae.

• First symptoms of malaria are mild fever, headache, muscle aches, and chills (flu-like symptoms).
ENLARGED SPLEEN characteristic of malaria is due to congestion of sinusoids with RBC’s.
 • Symptoms can begin in a month after an infected mosquito bite. Early symptoms are nonspecific,
and often mistaken for those of influenza.

• In all types of malaria, total WBC count is usually normal, however, hyperplasia of lymphocytes
and macrophages exists.

• Rapid diagnosis and early treatment are important, especially with falciparum malaria, which is
fatal in up to 20% of infected people.

• Antimalarial drugs (chloroquine, mefloquine, and primaquine) are available, but not 100%
effective for prevention.

ENTAMOEBA HISTOLYTICA-a single-celled parasite that CAUSES AMEBIASIS in humans.

• AMEBIASIS-an infection of the large intestine caused by the non-flagellated protozoan
Entamoeba histolytica. Entamoeba histolytica exists in two forms during its life cycle: the active
parasite (trophozoite) and a dormant parasite (cyst). Acute intestinal amebiasis presents a
DYSENTERY (i.e. bloody, mucus-containing diarrhea). E. histolytica can also produce liver
abscesses.

GIARDIASIS-an infection of the small intestine caused by a flagellated protozoan Giardia lamblia. It
also exists in two forms (trophozoite and cyst). Giardiasis is one the most common parasitic
infections of the SMALL INTESTINE. It is more common in male homosexuals and in people who
traveled to developing countries.

TRICHOMONIASIS-a sexually transmitted disease of the VAGINA (in women) or URETRHA (in
men) caused by a flagellated protozoan Trichomonas vaginalis. T. vaginalis only exists as a trophozoite.
TRICHOMONIASIS IS ONE OF THE MOST COMMON INFECTIONS WOLDWIDE. Symptoms
are more common in women.
• Entamoeba and Trichomonas species are found in the oral cavity, and nonpathogenic when
located here.

Balantidium Coli-a parasitic species of ciliate protozoan that causes the disease BALANTIDIASIS. It is
the only member of the ciliate phylum to be pathogenic to humans.


TOOTH ANATOMY

OCCLUSAL SURFACE-chewing surface of POSTERIOR teeth that consists of cusps, ridges, and
grooves. The occlusal surface is bounded mesiodistally by the marginal ridges and buccolingually by
the cusp ridges.
• Anterior teeth DO NOT HAVE an occlusal surface.

OCCLUSAL TABLE-that area of a tooth bordered facially and lingually by the crests of the cuspal
ridges of facial and lingual cusps, and mesially and distally by the crests of the marginal ridges.

INCISAL EDGE-the cutting edge or biting surface of ANTERIOR teeth.

ANATOMIC CROWN-the part of the tooth covered by enamel.

CLINICAL CROWN-the part of the tooth visible in the oral cavity. It may be larger or smaller than
the anatomic crown. The anatomic crown is shorter than the clinical crown of a tooth during gingival
recession.

INTERPROXIMAL SPACE-triangular space between adjacent teeth cervical to the contact area. The
sides of the triangle are the proximal surfaces of the adjacent teeth, the apex of the triangle is the
area of contact of two teeth, and the base of the triangle is the alveolar bone.
• Interproximal space is normally occupied by the interdental papilla.

EMBRASURES-triangularly shaped spaces between the proximal surfaces of adjacent teeth.

Embrasures diverge buccally, cervically, lingually, and occlusally from the area of contact.
• Pronounced developmental grooves are usually associated with embrasures between permanent
maxillary canines and first premolars; and between permanent mandibular canines and first
premolars.

• LARGEST incisal/occlusal embrasure is between the maxillary lateral incisor & canine.

• Each contact area has 4 Embrasures: BUCCAL, LINGUAL (larger than buccal),
OCCLUSAL/INCISAL, & CERVICAL.

• Embrasure Functions: spillways to direct food away from the gingiva, make teeth more self-
cleansing, protect gingival tissue from undue frictional trauma, while providing the proper degree
of tissue stimulation.

EMBRASURES DO NOT CONTRIBUTE TO ARCH STABILITY.

▪ Embrasures also make the natural hygienic factors in the mouth more effective by exposing
tooth surfaces to oral fluids and the mechanical cleansing action of the tongue, lips, and
cheeks.
PROXIMAL CONTACTS-areas where mesial & distal surfaces of adjacent teeth in the same arch
make contact.
• Support neighboring teeth to stabilize the dental arches.
• Prevent food particles from entering interproximal spaces.
• Protect interdental papillae of the gingiva by shunting food toward the buccal and lingual areas.
• Form embrasures.
• Loss of proximal contact may result in periodontal disease, malocclusion, food impaction, or
drifting of teeth.

Maxillary and Mandibular central incisors are the only four teeth whose MESIAL SURFACES contact
each other. In all other teeth, the mesial surface of one tooth contacts the distal surface of its
neighbor, except the distal surfaces of permanent third molars and primary second molars.

SULCUS-a long depression or v-shaped valley on the occlusal surface of a posterior tooth located
between ridges and cusps. The inclines of a sulcus meet in a developmental groove or extend outward to
the cusp tips.

FOSSA-an irregular depression or concavity.

1. Lingual Fossae-depression found on the lingual surface of incisors.

2. Central Fossae-depressions found on the occlusal surface of molars. Central fossae are formed
by the converging of ridges terminating at a central point in the bottom of the depression.

3. Triangular Fossae-depressions found on occlusal surfaces of molars and premolars slightly

mesial or distal to the marginal ridges. Triangular fossae are sometimes found on the lingual
surfaces of maxillary incisors.

DEVELOPMENTAL GROOVE-a sharply defined, shallow, linear depression formed during tooth
development that usually separates the primary parts of the crown. Developmental grooves separate
lobes or cusps of teeth, and mark the boundaries between adjacent cusps and other major divisional parts
of a tooth (marginal ridges, etc.). Buccal and lingual grooves are developmental grooves found on the
buccal and lingual surfaces of posterior teeth, and are important escape ways for cusps during lateral and
protrusive jaw motions and for food particles during mastication.
• PITS-small pinpoint depressions located at the junction of developmental grooves or at terminals
of these grooves.
• FISSURE-a narrow channel or crevice, sometimes deep, formed at the depth of a developmental
groove. Dental caries (decay) often begins in deep fissures or pits.
• SUPPLEMENTAL GROOVES-small, less distinct, irregularly placed grooves that are
supplemental to developmental grooves and do not demarcate major divisional parts of a tooth.

LOBES-primary centers of calcification that are always separated by developmental grooves that are
very prominent in the posterior teeth and form specific patterns. In anterior teeth, lobes are much less
noticeable and are always separated by developmental depressions.
• MINIMUM number of lobes from which any tooth may develop is FOUR.
• Lobes are much less noticeable on anterior teeth and are separated by developmental depressions.
• Lobes on posterior teeth are represented by cusps and are always separated by developmental
 grooves, which are very prominent on the posterior teeth and form specific patterns.
• Lobes are primary centers for calcification, and is one of the primary sections of formation in
the development of the tooth crown. A lobe is represented by a cusp on posterior teeth and by
mamelons and cingula on anterior teeth.
• All anterior teeth: (3 labial and 1 lingual (cingulum) lobes).
• Premolars: (3 buccal and 1 lingual lobe). Exception is the mandibular second premolar which
has 3 buccal and 2 lingual lobes.
• First Molars (maxillary and mandibular): (5 lobes, one lobe for each 5 cusp).
• Second Molars (maxillary and mandibular): (4 lobes, one for each 4 cusp).
• Third Molars: at least 4 lobes, one for each cusp—variations are seen. Maxillary third molars
often have only 3 cusps.

TUBERCLE-a small elevation of enamel found on the tooth crown (an extra formation of enamel like the
Cusp of Carabelli) located on the lingual surface of the M-L cusp of the maxillary first permanent
molar.
CUSP-an elevation or mound of enamel (larger than a tubercle) found on the occlusal surface of
molar and premolar teeth, and on the incisal edge of canines.

CINGULUM-a bulbous elevation of enamel (larger than a tubercle) that constitutes the lingual lobe
of an anterior tooth. It is found on the cervical third of the lingual surface.

RIDGE-any linear elevation on the surface of a tooth. Ridges are named according to their location,
shape, and size. Two ridges present on ALL TEETH are the mesial and distal marginal ridges.
• Ridges form mesial and distal margins of the occlusal surfaces of premolars and molars, and the
mesial and distal margins of the lingual surfaces of incisors and canines.

OBLIQUE RIDGE-a ridge found ONLY ON MAXILLARY MOLARS that crosses the occlusal
surface obliquely, and is formed by the union of the distal cusp ridge of the M-L cusp, and the triangular
ridge of the D-B cusp.

LABIAL RIDGE-a ridge running cervico-incisally in approximately the center of the labial surface of
the canines.

MARGINAL RIDGES-on incisor and canine teeth (anterior teeth), marginal ridges are located on the
mesial and distal borders of the lingual surface. On posterior teeth, marginal ridges are located on the
mesial and distal border of the occlusal surface.

TRANSVERSE RIDGE-a ridge formed by the union of a lingual triangular ridge of a buccal cusp and a
buccal triangular ridge of a lingual cusp. It runs from the buccal surface to the lingual surface across the
occlusal surface of most posterior teeth.
• TRANSVERSE RIDGE is the union of the buccal and lingual triangular ridge. This ridge crosses
the occlusal surface of most posterior teeth in a buccolingual direction. They occur between
the ML and MB or between the DL and DB cusps on molar, or between buccal and lingual
cusps on premolars.

• Transverse ridge is produced by any union of two triangular ridges.

 • Transverse ridges are very common on mandibular molars and maxillary premolars.

TRIANGULAR RIDGE-a ridge that projects from the cusp tip to the central groove. It is found
only on posterior teeth. (The M-L cusp on maxillary molars has two triangular ridges).
• Triangular ridges descend from the cusp tips of molars and premolars toward the central part of the
occlusal surface. They are called triangular ridges because the slopes of each side of the ridge
is inclined to resemble two sides of a triangle. They are named after the cusps to which they
belong (e.g. the triangular ridge of the buccal cusp of the maxillary second premolar).

BUCCAL (CUSP) RIDGE-a ridge running cervico-occlusally in approximately the center of the
buccal surface of premolars (more pronounced on the first premolars than on second premolars).

CERVICAL RIDGE-a ridge running mesiodistally on the cervical third of the buccal surface of the
crown. Cervical ridge is found on all PRIMARY TEETH, but only on permanent molars.

LINE ANGLE-an angle formed by the junction of 2 surfaces, named according to the surfaces which
form them. (The M-B and D-B line angles protect the interdental papilla by their deflective nature).
• All posterior teeth have 8 line angles: MB, DB, ML, DL, MO, DO, BO, LO.
• All anterior teeth have 6 line angles: M-LA, D-LA, ML, DL, LA-I, L-I. (because the mesial and
distal incisal angles of anterior teeth are rounded, mesioincisal and distoincisal line angles are
considered non-existent, and are spoken of as mesial and distal incisal angles only.

POINT ANGLE-an angle formed and named by the junction of 3 surfaces (e.g. the junction of the
mesial, buccal, and occlusal surfaces of a molar is called the mesiobuccal-occlusal point angle). All
teeth have 4 point angles.


ERUPTION SEQUENCE

3 Cardinal Rules of Tooth Eruption:

1. girls teeth erupt before boys.
2. mandibular teeth before maxillary.
3. slender teeth before stocky.

MIXED DENTITION-a dentition phase during which some of the teeth present in the oral cavity
are permanent, and some are deciduous (primary). The earliest indication of a mixed dentition
consists of the primary dentition and permanent mandibular first molars. There are 3 periods of
dentition in man:
1. Primary dentition (6 months to 6 years)
2. Mixed dentition (6 to 12 years)
3. Permanent dentition (12+ years)

After the permanent teeth have reached full occlusion, small tooth movements occur to compensate
for wear at the contact areas (by mesial drift) and occlusal surfaces (by deposition of cementum at the
root apex).

Usual Exfoliation (Fall-out) Age of Deciduous Teeth:

• Primary central incisors are exfoliated between 6-8 years old.
• Primary lateral incisors are exfoliated between 7-9 years old.
• Primary first and second molars are exfoliated between 10-12 years old.
• Primary canines are exfoliated between 9-12 years old.

RULE OF 4: implies the eruption of 4 teeth every 4 months starting with four teeth at age 7 months:
 APPROXIMATELY ¾ of root formation is complete at the time of eruption. The root
apex is fully developed 2-3 years after eruption.

A typical 6 year-old has all 20 primary teeth and 4 permanent first molars.

A 7-year old child has 18 PRIMARY & 6 PERMANENT TEETH. ALL primary teeth except
mandibular central incisors (20 – 2 = 18). The 6 permanent teeth are:
• Mandibular right and left 1st molars.
• Maxillary right and left 1st molars.
• Mandibular right and left central incisors (2).

Deciduous dental formula: I 2/2 C 1/1 M 2/2 = 10 x 2 =20 (5 per quadrant = 10 per arch)
• THERE ARE NO PREMOLARS (bicuspids) in the deciduous dentition

Permanent dental formula: I 2/2 C 1/1 B 2/2 M 3/3 = 16 x 2 =32 (8 per quadrant = 16 per arch)

NONSUCCEDANEOUS TEETH- do not succeed deciduous teeth.

• Permanent maxillary and mandibular FIRST, SECOND, & THIRD MOLARS.

SUCCEDANEOUS TEETH-in each quadrant, 5 permanent teeth: incisors, canine, and premolars,
succeed or replace the five primary teeth. These are the succedaneous teeth. Molars are not succedaneous
teeth.

ANODONTIA-a developmental abnormality characterized by the TOTAL ABSENCE OF TEETH.

1. Complete true anodontia-a rare condition in which all of the teeth are missing. It may involve
both primary and permanent dentitions; usually associated with hereditary ectodermal
dysplasia.

2. Partial anodontia (congenitally missing teeth)-rather common and usually affects maxillary
third molars, maxillary lateral incisors, and mandibular second premolars. As a rule, if only one
or a few teeth are missing, the absent tooth will be the most distal tooth of any given type (if
molar, then it would be the third molar).

OLIGODONTIA-the congenital absence of MANY TEETH (but not all teet).

HYPODONTIA-the absence of only a FEW TEETH.

TERATOGENS-agents (chemicals) capable of causing developmental abnormalities in utero. The type

of fetal development problem is related to the type of teratogen and time at which the teratogen
interacts with the fetus. Since most organogenesis occurs during the first three months of gestation,
the FIRST TRIMESTER IS THE TIME OF GREATEST SENSITIVITY TO TERATOGENIC
ACTIVITY.
• Drugs can have teratogenic effects that can produce an abnormal fetus.

 DECIDUOUS (PRIMARY) TEETH
DECIDUOUS (primary) teeth begin to FORM in utero at approximately SIX WEEKS, and begin to
calcify at 4 months in utero.
• Ordinarily, a 6-year old child would have ALL (20) PRIMARY TEETH & 4 PERMANENT
FIRST MOLARS (“6-year molars”) clinically visible in the mouth.
• Mandibular centrals erupt between ages 6-7.
• Maxillary centrals erupt between ages 7-8.

PERMANENT TEETH begin to develop at approximately 4 MONTHS of age in utero. Maxillary and
mandibular first molars begin to calcify at birth (first molars are the first to begin calcification).
Mandibular third molars are the last teeth to begin calcifying (at about 8-10 years of age).

PRIMARY vs. PERMANENT TEETH:

1. Primary teeth are LIGHTER in color than permanent teeth.
2. Pulp cavities are proportionally larger in primary teeth.
3. Crowns of primary teeth are more bulbous and constricted than the permanent counterpart.
4. Crown surfaces of all primary teeth are much smoother than permanent teeth (there is less
evidence of pits and grooves).
5. Crowns of primary anterior teeth are wider mesiodistally and shorter inciso-cervically than
their permanent counterparts.
6. Crowns of primary molars are shorter and more narrow mesiodistally at the cervical third than
the permanent.
7. Roots of the primary anterior teeth taper more rapidly than permanent anteriors.
8. Roots of the primary molars are longer and more slender than permanent molars.
9. Enamel ends more abruptly at the cervical line on primary teeth, rather than becoming thinner
as on permanent teeth.
10. Buccal and lingual surfaces of primary molars are flatter above the crest of contour than on
permanent molars.

PRIMARY SPACES are normally present from the time the teeth erupt. Developmental spaces
between the incisors are often present from the beginning, but become larger as the child grows and the
alveolar processes expand. Generalized spacing of the primary teeth is required for proper alignment of
the permanent incisors. This spacing is most frequently caused by the growth of the dental arches.

PRIMATE SPACES in the primary dentition are found in the MAXILLARY ARCH between the
lateral incisors and canines, and in the MANDIBULAR ARCH between canines and first molars.
• Spacing is normal throughout the anterior part of the primary dentition, but is most noticeable in
these two locations.

PRIMARY vs. PERMANANT MAXILLARY CANINE:

1. Primary canine cusp is MUCH LONGER & SHARPER.
2. Primary canine MESIAL CUSP RIDGE is longer than the DISTAL CUSP RIDGE (this is the
 opposite in all other canines).
3. Primary maxillary canines have a M-I cusp ridge LONGER than the D-I cusp ridge.
4. Primary maxillary canine is especially WIDE and SHORT.

CANINES when viewed from the facial resemble a PENTAGON (five-sided).

• All canines have 4 LOBES (3 facial, 1 lingual). The facial lobes are mesiofacial, midfacial, and
distofacial. The cusp tip is on the midfacial lobe.
• canine pulp cavities when viewed from a M-D section, appear pointed at the incisal tip.

THE SUM OF THE M-D WIDTHS of the primary molars in any one quadrant is 2-5mm GREATER
than the permanent premolar teeth that succeed them.

PRIMARY vs. PERMANENT MOLARS:

• Primary molars crowns are shorter and more bulbous with pronounced buccal and lingual
cervical ridges, and a constricted cervical area.
• Primary molars have an occlusal table that is narrower faciolingually.
• Primary molars have shallow anatomy (i.e. short cusps, ridges are not pronounced, and fossae are
not as deep).
• Primary molars have a prominent mesial cervical ridge (distinguishes right from left).
• Primary molars have longer and more slender roots than permanent molar roots. The roots are
extremely narrow mesiodistally and very broad buccolingually.
• Primary molars have very divergent and less curved roots, with little or no root trunk.

Enamel on the occlusal surfaces of primary molars is of UNIFORM THICKNESS and is close to 1mm
thick compared to enamel on permanent molars, which is 2.5mm thick.

PRIMARY MANDIBULAR FIRST MOLAR has a prominent transverse ridge that unites the MB
and ML cusps. This transverse ridge separates the mesial portion from the remainder of the occlusal
surface.
• It does not resemble any other primary or permanent tooth.
• MB cusp is ALWAYS the largest and longest cusp (covers two-thirds of the buccal surface).
• ML cusp is larger, longer, and sharper than the DL cusp.
• Crown is wider M-D than high cervico-occlusally.
• Mesial marginal ridge is very well developed and resembles a cusp.
• It has a prominent mesiobuccal cervical ridge.
• Class II cavity preparations are difficult due to morphology.
• NO CENTRAL FOSSA and 4 PULP HORNS.

PRIMARY MANDIBULAR FIRST MOLAR does not resemble any other primary or permanent
tooth. The general shape of the occlusal surface is oval (wider M-D than B-L). From the occlusal view,
the mesiobuccal angle is acute and prominent because of the mesial cervical ridge on the buccal surface.
The DB angle is obtuse. The occlusal table shape is RHOMBOID. The occlusal table is the chewing
surface inside the cusp ridges and marginal tables.

PRIMARY MAXILLARY FIRST MOLAR-the MOST ATYPICAL of all molars (primary and
permanent), and is an intermediate in form and development between a premolar and molar:
 • SMALLEST MOLAR in all dimensions except F-L diameter. The crown is bicuspid (two cusped).
• Two main cusps: wide M-B and narrow M-L. Indistinct cusps are D-B and D-L.
• MB cusp is always the longest. ML cusp is the second longest, but sharpest.
• Cervical line is higher mesially than distally.
• cervical ridge stands out very distinctly on the mesiobuccal portion of this tooth.
• Occlusal pit-groove pattern is most frequently H-SHAPED.
• number of roots (3) and form of the roots closely resembles the permanent maxillary first molar.

PRIMARY MAXILLARY SECOND MOLAR strikingly resembles the PERMANENT MAXILLARY

FIRST MOLAR (but they are smaller). Primary second molars are larger than primary first molars, and
resemble the form of the permanent first molars.
• Crown is greater F-L > M-D and may have a FIFTH CUSP (Cusp of Carabelli).
• Has a prominent M-B cervical ridge and oblique ridge.
• MB cusp is EQUAL in size or slightly larger than the M-L cusp.
• MB pulp horn is the largest and longest.

• PRIMARY FIRST MOLAR is the primary tooth with the most noticeable morphologic deviations
from permanent teeth.

• PRIMARY SECOND MOLAR has the greatest F-L diameter of all primary teeth.

PERMANENT MANDIUBLAR FIRST MOLAR morphology closely resembles the PRIMARY

MANDIBULAR SECOND MOLAR. However, some differences include:
1. Relative size of the distal cusp. The primary second molar’s M-B, D-B, and distal cusp are almost
equal in size. The distal cusp of the permanent molar, however, is smaller than the other two
cusps.

2. From the buccal aspect, the primary mandibular second molar has a narrow M-D calibration at the
cervical portion of the crown compared with the calibration mesiodistally on the crown at contact
level. The mandibular first permanent molar, accordingly, is wider at the cervical portion.

3. Groove patterns are different on the occlusal surface.

4. Primary tooth has more divergent roots to allow for eruption of the second premolar.

5. Primary tooth has a more prominent facial crest of contour.

PRIMARY vs. PERMANENT MAXILLARY CENTRAL INCISOR:

1. Compared to the permanent central incisor, the incisal edge of the primary central is straighter
and no mamelons are present. This is also true for the primary lateral incisors.

2. The crown of the primary central incisor is larger M-D and has shorter length inciso-
cervically than its permanent counterpart.
• Primary maxillary central incisor has a M-D crown width > incisocervical height.

WHEN EXTRACTING PRIMARY INCISORS in which the roots have been partially resorbed due to
pressure from the developing permanent teeth, the facial part of the remaining root is the longest and most
securely attached to the gingiva.
• Labial and lingual cervical ridges are prominent on all primary central and lateral incisors.

MAMELONS-3 rounded or conical prominences found on the incisal ridge of NEWLY ERUPTING
INCISORS. Mamelons are usually worn off after the tooth comes into functional position. The presence
of mamelons in a teenager or adult is indicative of malocclusion most likely due to an anterior open
bite relationship where the maxillary and mandibular incisors do not touch. Maxillary and mandibular
incisors characteristically have THREE MAMELONS that are centered beneath the three facial lobes.

PRIMARY MANDIBULAR CENTRAL INCISOR-the first deciduous (primary) tooth to erupt,

followed shortly by the maxillary first molar (non-succadenous).
• MANDIBULAR FIRST MOLAR is the first PERMANENT tooth to erupt.

• MANDIBULAR CENTRAL INCISOR is the first SUCCEDANEOUS (primary) tooth to erupt.



SUCCEDANEOUS (PERMENANT) ANTERIOR TEETH

ANTERIOR TEETH with a CINGULUM located in the CENTER OF THE LINGUAL SURFACE:
1. Maxillary lateral incisor and canine
2. Mandibular central incisor

ANTERIOR TEETH with a cingulum located OFF CENTER TO THE DISTAL on the lingual surface:
1. Mandibular lateral incisor and canine
2. Maxillary central incisor

Total number of CINGULA in the dentition is TWELVE (6 maxillary and 6 mandibular anterior teeth).

All mandibular anterior teeth have an inconspicuous cingula, an incisal edge placed slightly lingual, and a
continuous convexity inciso-apically on the facial.

INCISORS all have a cingulum, mesial marginal ridge, and lingual fossa.

IJ means the mesial contact is in the incisal third (I) and distal contact is at the junction (J) of the
incisal and middle thirds. These are all from the facial (occluso-gingivally) aspect. From the incisal
view, all anterior teeth have their contacts in the middle third (M or D) and are centered
faciolingually.

 INCISORS

MAXILLARY CENTRAL INCISOR

Maxillary Central Incisor CROWN: the longest and widest anterior tooth. The distal outline is more
convex than the mesial outline. It is the most prominent tooth in the mouth. Crown outline is wider M-D
than F-L.
• 3 MAMELONS and 4 DEVELOPMENTAL LOBES.
• M and D contact areas are centered faciolingually.
• Contact relationship of maxillary central incisors and maxillary lateral incisors involves all
contacts being centered faciolingually.
• From the mesial aspect, the incisal edge of the crown is on line with the center of the root.
• Anatomic features include a cingula, mamelons, marginal ridges, and cervical ridges.

Maxillary Central Incisor ROOT: 1 root with a single root canal. It is conical with a blunt apex. This
root is the only maxillary tooth root that is as thick at the cervix mesiodistally as faciolingually (the others
are thicker FL than MD).
• A single-rooted tooth with a triangular pulp canal in cross-section with the base of the triangle
located facially and the apex lingually, and a longer mesial than distal side.
• only anterior tooth that DOES NOT have longitudinal grooves on the mesial and distal root
surfaces
• LEAST LIKELY to have a divided pulp canal (has ONE CANAL).
• considering root morphology, it most readily lends itself to rotation during extraction.
• Pulpal outline resembles a GOLF TEE.

Maxillary Central Incisor SURFACES: mesial curvature of the cervical line is larger than any tooth.
The distoincisal corner is more rounded (convex) than the mesioincisal corner. The mesial and distal
contacts are centered faciolingually (as are all permanent incisors). The cingulum is well-developed and
is located off-center toward the distal.
• On permanent teeth, the greatest incisal curvature of a cervical line is on the mesial surface of the
maxillary central incisor.

• Facial surface curves gradually from the facial CEJ more and more lingually until the incisal edge
which is directly over the main axis of the root.

• From the incisal view, visible features of an incisor are the labial and lingual heights of contour,
and mesial and distal contact areas. CERVICAL LINE IS NOT VISIBLE from the incisal view.

• Has the greatest CEJ arc of curvature of any tooth so the CEJ arcs dramatically upwards toward the
incisal edge from the mesial aspect.

Maxillary Central Incisor OCCLUSION: occludes in centric with the mandibular central and lateral
incisors (same in protrusive and there is not contact in retrusive).

Distinguishing Features: maxillary central incisors have the narrowest incisal embrasures. Compared
to other incisors, they have the greatest axial inclination relative to the occlusal plane. Has 3
mamelons and 4 developmental grooves.
• NARROWEST incisal or occlusal embrasure is between the CENTRAL INCISORS.
• LARGEST incisal embrasure is between the maxillary lateral incisor and canine.
• Compared to the large incisal embrasure between the maxillary central and lateral incisors, the
incisal embrasure between the maxillary central incisors is SMALLER.

MAXILLARY CENTRAL INCISOR may have a TRIANGULAR PULP CHAMBER rather than oval.
The base of the triangle will be the facial, and the apex will be the lingual. If it is not triangular, then it
will be oval.


MAXILLARY LATERAL INCISOR

1. Usually equal to or larger than maxillary central incisor in ROOT LENGTH (cervicoapically).

2. Maxillary central, maxillary lateral, and mandibular lateral incisors all have distal contacts more
APICAL than mesial contact areas.

3. Contact relationship between a maxillary central incisor and maxillary lateral incisor is best
described as the contact is centered faciolingually, and the lingual embrasure is wider than the facial
embrasure.

4. Its mesial contact is near the junction of incisal and middle thirds of the crown, and its distal contact
is in the middle third of the crown.

5. DISTOINCISAL ANGLE of the maxillary lateral incisor has the GREATEST CONVEXITY.

6. An anatomic feature most likely to complicate root planning of a maxillary lateral incisor is a
DISTOLINGUAL GROOVE.

7. Most often MISSING CONGENITALLY.

8. Has the greatest variation in CROWN SIZE & FORM.

9. PEG-SHAPED CROWN is an occasional anomalous occurrence.

10. Tooth most likely to exhibit a LINGUAL GROOVE THAT EXTENDS from the enamel onto the
cementum area of the root.

11. In the proximal contact relationship between a maxillary central incisor and maxillary lateral incisor
the lingual embrasure is larger than the facial embrasure.

12. Most often in an abnormal relation and contact with adjacent teeth in the same arch.

13. Carious developmental pit is most likely found in the lingual surface of a maxillary lateral incisor.

14. MOST frequently CONCAVE ON THE LINGUAL SURFACE.

15. PRONOUNCED LINGUAL FOSSA that aids in distinguishing it from a mandibular lateral incisor.


MANDIBULAR CENTRAL INCISOR

1. SMALLEST permanent tooth in the mouth.

2. Most difficult tooth to distinguish between its mesial and distal aspects.

3. No transverse ridge.

4. Mesial contact is in the incisal (occlusal) one-third.

5. From the facial, the M and D contacts are incisal to the junction of incisal and middle thirds.

6. Straight incisal edge, intersects a plane bisecting the tooth into mesial and distal halves at a right
angle to that plane, and crosses the tooth parallel and slightly lingual to a plane bisecting the tooth into
facial and lingual halves.

7. Mandibular central and mandibular lateral incisors most often have concave areas on both M and D
root surfaces.

8. A cross section at mid-root shows the pulp cavity is FLATTENED M-D.

9. FIRST SUCCEDANEOUS TOOTH TO ERUPT.

10. The only anterior tooth where the distoincisal angle and mesioincisal angle are bilaterally
symmetrical. All other anterior teeth have a more rounded D-I angle.


MANDIBULAR LATERAL INCISOR

1. Cervical line on the distal is more apical than on the mesial.

2. DIFFERENCE IN ROTATION OF THE CROWN ON THE ROOT is the most reliable criterion
to distinguish permanent mandibular central incisors from permanent mandibular lateral incisors.

3. Distal half of the crown curves toward the lingual side.

4. From an incisal view, the incisal edge takes an oblique course appearing twisted around the long axis
of the root.

5. CROWN is WIDER mesiodistally than the mandibular central incisor crown.

6. M and D contacts are in the incisal third (D contact is slightly more cervical than the M contact).

7. MANDIBULAR LATERAL INCISOR has a LARGER ROOT in all dimensions than a

mandibular central incisor.

8. NEAR THE ROOF of the pulp chamber, the elliptical form of the pulp cavity is WIDEST in the
MESIODISTAL direction. However, near mid-root, the elliptical form is widest in the
FACIOLINGUAL direction. A small percentage have two canals.

9. Crown of the mandibular lateral incisor TIPS SLIGHLTY DISTAL relative to the root-thus, the
cingulum is slightly off-center to the distal, like the maxillary central incisor, and mandibular
canine. It is unlike the mandibular central incisor whose cingulum is in the center of the lingual
surface.

10. The incisal edge of the mandibular lateral is slightly curved or rotated on the distal. Thus, it is
possible to see a small portion of this distal-incisal edge when viewing this tooth from the mesial
aspect.

11. Distoincisal angle of most anterior teeth is MORE ROUNDED than the mesioincisal angle.

12. M-I angles are MORE SQUARE (acute) than D-I angles (are more obtuse or convex).

13. MANDIBULAR LATERAL INCISOR is clearly distinguished from the MANDIBULAR

CENTRAL INCISOR by its INCISAL EDGE. From an incisal view, the INCISAL EDGE of the
lateral incisor does not form a right angle with a line bisecting the crown labiolingually (as does
the central). Rather, the lateral incisor takes an oblique course, appearing twisted around the long axis
of the root.

Anterior teeth are highly important aesthetically and play an important role in the formulation of speech
sounds (“v”, “f”, and “th”).
Alveolar process is THINNEST in the area FACIAL to mandibular and maxillary central incisors.
Thus, local infiltration may be effective for anesthetizing these teeth).

DIFFERENCE IN ROTATION OF THE CROWN ON THE ROOT provides the MOST RELIABLE
criterion for differentiating permanent mandibular central incisors from permanent mandibular lateral
incisors. The mandibular lateral incisor crown tips slightly to the distal relative to the root (facial view).

MANDIBULAR LATERAL vs. MANDIBULAR CENTRAL INCISORS:

1. Lateral is larger overall (especially mesiodistally).

2. Lateral is not as bilaterally symmetrical as the central incisor.

3. Lateral’s cingulum is slightly distal to the center.

4. On the lateral incisor, the mesial marginal ridge is longer than the distal marginal ridge. On
centrals, mesial and distal marginal ridges are the same length.

5. Lateral incisors have the distal proximal contacts more apical than the mesial contacts. Centrals
are at the same level.

6. Lateral incisors have more rounded distoincisal angles than mesioincisal angles. On centrals, the
angles are nearly the same.

7. Mandibular central and lateral incisors have a lingual cervical line positioned more apically than
the facial cervical line.

CROWN OUTLINES:
1. TRIANGULAR OUTLINE: Mesial and Distal surfaces of ALL ANTERIOR TEETH.

2. TRAPEZOID OUTLINE: M and D (proximal) surfaces of ALL MAXILLARY POSTERIOR

(Molars and Premolar) CROWNS. The longest uneven side is at the cervical line. Lingual and
Facial surfaces of ALL TEETH.

3. RHOMBOIDAL OUTLINE: M and D surfaces of ALL MANDIBULAR POSTERIORS

TEEH.

4. BUCCAL OR LINGUAL OUTLINES: crowns of ALL MANDIBULAR & MAXILLARY

CENTRAL & LATERAL INCISORS from a buccal (labial) or lingual view are TRAPEZOIDAL.
TRAPEZOIDAL OUTLINE has its LONGEST UNEVEN SIDE toward the occlusal or incisal
surface.

3 Characteristics Common to ALL MANDIBULAR ANTERIOR TEETH:

1. Indistinct cingula with smooth lingual anatomy without grooves and pits.
2. Incisal edges are lingual to the root axis line.
3. Continuous convexity incisoapically on the facial surface.


CANINES (CUSPIDS or EYE TEETH)

MANDIBULAR vs. MAXILLARY CANINE:

• Mesial border is MUCH straighter (viewed facially).on a mandibular canine.

• Mandibular canine cusp tip is displaced lingually, while the maxillary canine cusp tip is on or
labial to the root axis line (viewed proximally and incisally).

• Mandibular canine has a cingulum less pronounced and often slightly to the distal, whereas the
maxillary canine cingulum is more pronounced and centered mesiodistally (viewed lingually).

• Mandibular canine has a comparatively narrower mesiodistal dimension (viewed facially).

• Contact areas are located more incisally (IM), for the maxillary canine (JM).

• Mandibular canine has a continuous convex facial surface viewed from the mesial or distal.

• Lingual ridges with mesial and distal fossae are less prominent on mandibular canines (viewed
incisally).

PERMANENT MAXILLARY CANINE is most likely to OCCLUDE with the mandibular canine &
first premolar. THERE IS NO CONTACT ON THE CUSP TIP. The cusp falls in direct alignment
with the facial embrasure between these mandibular teeth. This anterior tooth is unique in that it has
antagonists, in the intercuspal position, in both anterior (canine) and posterior (first premolar) segments
of the opposite arch.

PERMANENT MAXILLARY CANINES are the LAST TEETH TO ERUPT.

• Maxillary canines erupt between ages 11-12 (after premolars).
• Mandibular canines erupt between ages 9-10 (before premolars).

Distal CUSP RIDGE is longest, & MIDDLE FACIAL RIDGE is most prominent on PERMANENT
CANINES.

MAXILLARY & MANDIBULAR CANINES are the only teeth that have LABIAL RIDGES.

FACIAL SURFACE OF CANINES has a pronounced labial ridge that runs cervico-incisally near the
center of the crown in the middle and incisal thirds. Shallow developmental depressions lie mesial and
distal to the labial ridge. On the mandibular canines, the labial ridge and developmental depressions are
not as pronounced.
• Maxillary and Mandibular canines are the only cusped teeth with a FUNCTIONAL LINGUAL
SURFACE rather than a functional occlusal surface.

• Looking at the maxillary canine from an incisal view, the distal portion of the facial surface is
 CONVEX in the middle third and slightly concave in the cervical third. The mesial portion is
convex in the middle third and nearly flat in the cervical third.

• Often from the incisal view, the cervical line is not visible due to the convexity of the crown.

A maxillary right canine is distinguished from a maxillary left canine because THE CANINE’S DISTAL
HALF is more CONVEX than its mesial half.
• Curvature of the cervical line is greater on the mesial side than the distal side.
• Mesial surface is straighter than the distal surface.
• Distal cusp ridge is longer than the mesial cusp ridge.
• Distal contact is more cervical than the mesial contact.


MAXILLARY CANINE (#6 & #11)

1. CROWN FORM from the facial (labial) or lingual view is 5-SIDED (PENTAGONAL).

2. Middle facial lobe on the maxillary canine crown has a CUSP TIP.

3. ROOT IS THE LONGEST & STRONGEST OF THE ANTERIOR TEETH.

4. Maxillary canine is the least likely to have two roots.

5. Mesial contact area is at the junction of the incisal and middle thirds while its distal contact area is
in the MIDDLE THIRD of the crown.

6. Contact areas of anterior teeth are incisal to the middle third of the crown except the distal contact of
the maxillary canine which is in the middle third.

7. From the proximal view, it is positioned in the arch with its axis most nearly VERTICAL.

8. From the mesial, a line bisecting the apex and maxillary canine root passes lingual to the cusp tip.

9. Much more prominent cingulum than the mandibular canine.

10. Middle facial lobe on the maxillary canine crown includes the cusp tip.

11. Facial surface is convex, and the lingual surface has a mesial and distal fossa.

12. From the mesial aspect, the maxillary canine pulp cavity looks like a fish.

13. A faciolingual, longitudinal section of a maxillary canine has its widest dimension of the pulp cavity
faciolingually in the cervical third of the crown.

14. Pulp cavity in a M-D section of a maxillary canine is pointed at its incisal limit.

15. On the crown, the height of contour is normally at the cervical third of both the labial and lingual
surfaces.

16. Maxillary canine is WIDER M-D than the mandibular canine.

17. From the incisal aspect, the crown of a maxillary canine normally exhibits a distal portion that
displays some concavity in its facial outline.

18. Compared to a mandibular canine, a maxillary canine has a shorter crown, more pronounced
cingulum, and has a cusp tip more nearly centered over the root when viewed from the facial aspect.
19. When comparing mesial and distal surfaces of a maxillary canine to determine a right vs. left
maxillary canine, the mesioincisal angle is less rounded than the distoincisal angle, the curvature of
the cervical line is greater on the mesial than distal, and the mesial surface is straighter than the distal
surface.

20. From the incisal aspect when viewing a canine crown the cingulum, lingual fossa, and mesiofacial
developmental depression are seen. CERVICAL LINE CANNOT BE SEEN INCISALLY.

21. From the incisal view, the tip of the cusp in reference to the center of the crown is normally facial and
mesial.

22. Normal lingual anatomy on a maxillary canine contains a cingulum, lingual ridge, mesial and distal
fossae, and mesial and distal marginal ridges. It does not have a lingual cusp or developmental
grooves.

23. Mesial marginal ridge is the crown structure located immediately mesial of the mesiolingual fossa.

24. Permanent maxillary canine is wider through the crowns and the roots on the facial than on the lingual.
Also, its roots are under bone and dictate alveolar wall morphology.

25. Crown is thicker labiolingually and has a longer root than a maxillary central incisor.

26. Pronounced developmental grooves are usually associated with embrasures between permanent
maxillary canines and first premolars, and mandibular canines and first premolars.

27. LARGEST incisal/occlusal embrasure is between the maxillary lateral incisor and canine.

28. In MICP, the maxillary canine can contact both anterior and posterior antagonists.

29. Has at least one contact located within the middle of the crowns incisogingivally.


MANDIBULAR CANINE (#22 & #27)

1. Root in cross section is IRREGULARLY OVAL.

2. In cervical cross-section the root is flattened in a mesiodistal direction.

3. Mandibular canine (facial and lingual) most frequently exhibits a bifurcated root a the facial and
lingual positions.

4. From the facial view, the mesial outline from the contact area to the root apex is relatively straight.

5. Most typically has greater crown bulk distal to the faciolingual bisecting plane of a tooth.

6. Mesial contact is at the INCISAL THIRD.

7. MOST LIKELY TO RESIST INVASION BY CARIES.

8. Has at least one contact located within the middle of the crowns incisogingivally.

9. Crown has a less-pronounced cingula than the maxillary canine crown.

10. Lingual surface of the mandibular canine crown is smooth, relatively flat in the fossa area, poorly-
developed in the marginal ridge and cingulum areas.

11. Mandibular canine is distinguished from maxillary canine because the mandibular canine has a
straighter mesial border viewed facially, its contacts are more incisally, and the cusp tip is displaced
lingually to a midline faciolingually.

12. From the mesial or distal view, the overall facial outline from cusp tip to root apex is made up of one
continuous arc and is different from the outline of a maxillary canine.

13. F-L measurement of a mandibular canine is greater than its greatest M-D measurement.

14. Mesial and distal contact areas (cervico-incisally) are not at equal levels in the canine.

15. Distal contact is in the middle third.


 SUCCEDANEOUS (PERMENANT) POSTERIOR
TEETH
Generally, the contact areas between posterior teeth are located facially and occlusally from the
center of the proximal surfaces.

3 mandibular teeth are aligned so when viewed from the occlusal, a straight line can be drawn that bisects
all contact areas: mandibular first premolar, and mandibular first and second molars. Thus, the
posterior teeth in the mandibular posterior segment of the dentition are aligned in a straight line.

PREMOLARS

MANDIBULAR vs. MAXILLARY PREMOLARS:

1. Mandibular premolar crowns TILT LINGUALLY from a proximal view.

2. Outline of mandibular premolars is RHOMBOIDAL from a proximal view, while the outline of a
maxillary premolar is TRAPEZOIDAL.

3. On mandibular premolars, the lingual cusps are MUCH SMALLER (only 2/3 the height) than the
buccal cusps. On maxillary premolars, the lingual cusps are smaller (but only slightly smaller).

4. From an occlusal view, mandibular premolars are more SQUARE while maxillary premolars are
more RECTANGULAR (in that they are wider buccolingually).

5. Maxillary and mandibular premolars have their long axis most perpendicular to the
horizontal plane when the teeth are in maximum intercuspation (they are the most closely
vertically aligned of all the teeth).

6. Mandibular and maxillary premolars have their long axes more nearly perpendicular to the
horizontal plane when the teeth are in maximum intercuspation.


MAXILLARY FIRST PREMOLAR (#5, #12)

1. Often both the root outline and pulp chamber are KIDNEY SHAPED. Thus, a mid-root section
looks like a figure eight with two root canals.

2. Only premolar with 2 roots & 2 root canals (one buccal, one lingual).

3. LINGUAL ROOT CANAL IS LARGEST.

4. Premolars are most difficult to do root canal treatment on because they are easy to perforate
(especially maxillary first premolars).

5. Key to determining maxillary right vs. left premolar: there is a more pronounced developmental
groove on the mesial.

6. Has a crown concavity that is confluent with a longitudinal groove on the root. This is a
common feature of the MESIAL SURFACE of the maxillary first premolar.

7. Mesial surfaces of maxillary first premolars and distal surfaces of first molars have deep
concavities in cervical areas on their axial surfaces.

8. Maxillary first premolar is the permanent posterior tooth most likely to have a pronounced
concavity on the mesial surface of its crown.

9. Most common anatomic feature that complicates periodontal maintenance in a maxillary first
premolar is its deep concavity on the mesial surface of the tooth.

10. Mesial surface of a maxillary first premolar is most difficult to obtain a close adaptation of
the matrix band at the cervical for an amalgam restoration.

11. A maxillary first premolar is identified by a MARKED MESIAL CONCAVITY in the cervical
areas, a deep sulcus, and long central groove.

12. In cervical cross section, maxillary first premolar sometimes exhibits a root outline and pulp
chamber floor outline that are both KIDNEY-SHAPED.

13. SHARP DEMARCATIONS is between pulp chambers and pulp canals.

14. Has the GREATEST problem when root canal therapy or extractions are considered.

15. F-L crown dimension is greater than its M-D crown dimension.

16. In most cases, the maxillary first premolar differs from the maxillary second premolar in that the
maxillary first premolar has two roots (one facial, one lingual).
17. Mesial inclination of lingual cusps is present on both maxillary first and second premolars.

18. Lingual cusp tip is offset to the mesial on both maxillary first and second premolars.

19. From the proximal view, the maxillary first premolar appears aligned in its arch with the axial
inclination of its roots most nearly vertical.

20. On crowns of maxillary first premolars, the height of contour is normally located in the cervical
third of FACIAL SURFACES.

21. Has the LARGEST CERVICO-OCCLUSAL CROWN HEIGHT of maxillary teeth and STEEPEST
CUSP INCLINES.

22. From the facial view has a mesial cusp ridge longer than its distal cusp ridge.

23. Maxillary first premolar is distinguished from a maxillary second premolar by its longer central
developmental groove and the presence of a mesial marginal developmental groove.

24. Central groove runs in a M-D direction and its mesial contact is toward the M-B line angle.

25. Mesial surface has the deepest concavity found on the mesial surface of any permanent posterior
tooth.

26. MAXILLARY FIRST PREMOLAR is the only premolar with a M-B cusp ridge LONGER
than its D-B cusp ridge. Also, this tooth has a pronounced cervical concavity on the mesial
surface of its crown, as does the distal surface of the maxillary first molar.

27. MAXILLARY FIRST PREMOLAR is usually the LARGEST PREMOLAR. The maxillary
first and second premolars are more alike than the mandibular premolars, and unlike the
mandibular premolars, maxillary first premolars are LARGER than second premolars.
Mandibular first premolar is usually the smallest of all premolars.


MAXILLARY SECOND PREMOLAR (#4, #13)

1. Crown is wider F-L than M-D, and has 2 cusps approximately equal in height.

2. Maxillary second premolar is distinguished from a maxillary first premolar because the maxillary
second premolar usually has A SINGLE ROOT.

3. Maxillary second premolar has 1 root, and its facial and lingual cusps are nearly the same size.

4. A short central groove M-D is a distinguishing characteristic of the maxillary second premolar.

5. Compared to a maxillary first premolar, the central developmental groove of a maxillary second
premolar is shorter with multiple supplementary grooves.

6. Mesial and distal contacts are at the same level, cervicoincisally or cervico-occlusally on the
permanent maxillary second premolars and mandibular central incisors.

7. F and L cusps are nearly the same height.

8. A maxillary second premolar crown outline from the mesial is a trapezoid with the long parallel side
at the cervix. Also, the max second premolar crown outline from the occlusal view is more rounded
than angular.

9. Buccal and lingual cusps are almost EQUAL IN HEIGHT.

10. ONE ROOT (first premolar has two roots).

11. Much more symmetrical and less angular (more ovoid) than the first premolar.

12. THE DB cusp ridge is LONGER than MB cusp ridge (opposite of the first premolar).

13. No mesial developmental depression (first premolar does).

14. Less prominent buccal ridge (first premolar has a prominent buccal ridge).

15. Shorter central groove with more supplemental grooves (first premolar has a long central groove with
minimal supplemental grooves).


MANDIBULAR FIRST PREMOLAR (#21 & #28)

1st PREMOLAR CROWN: (THE SMALLEST PREMOLAR)

• From the buccal, it is longer and has a more prominent buccal ridge than the second premolar. It is
bell-shaped and the cervical is very constricted.

• Has the greatest lingual inclination of the crown from its root in the mandibular arch.

• Has a mesial marginal ridge distinctly SHORTER IN LENGTH and LESS PROMINENT in
HEIGHT that the distal marginal ridge.

1st PREMOLAR ROOT:

• 1 root that is shorter and has a pointed apex (second premolar is longer with a blunt apex). It is
broader facially than lingually, has no distal curvature, and may have slight concavities on the
mesial and distal.

• Roots are broader facially than lingually, usually free of marked distal curvature, and are often seen
with slight concave areas on mesial and distal surfaces.

• Mandibular premolars differ from maxillary premolars in the mandibular premolars have more
rounded roots, crowns tilted lingually, and less developed lingual cusps.

1st PREMOLAR CUSPS:

• Has a large pointed buccal cusp that occupies almost two-thirds of the occlusal surface and has a
prominent triangular ridge. It has a small (it is about two-thirds the height of the buccal cusp),
nonfunctioning lingual cusp (does not occlude with anything).Cavity preparations demand extra
attention because of high buccal and low lingual pulp horns (sometimes there is only ONE
PULP HORN).

• Has a facial cusp with a triangular ridge so uniquely prominent as to frequently separate its mesial
pit from its distal pit.

• SOMETIMES ONLY ONE PULP HORN.

• Most likely to have a second pulp canal in a LINGUAL DIRECTION.

• SMALL, NON-FUNCTIONING LINGUAL CUSP. Thus, mandibular first premolar masticatory

function is MOST similar to the mandibular canine.

• Lingual cusp is similar in development to the cingulum of a canine, and are approximately 2/3 the
height of the facial cusps.

1st PREMOLAR OCCLUSAL PATTERN:

• Small, nonfunctioning occlusal surface that converges toward the lingual. The prominent
triangular ridge of the buccal cusp and the small buccal ridge of the lingual cusp unite to form a
TRANSVERSE RIDGE. Usually there is no central groove (may have mesial and distal pits).
Thus, the placement of separate MO and DO restorations may be required.

• Mesial and distal marginal ridges have little or no contact in the ideal intercuspal relationship. The
contacts are ideally on the mesial or distal triangular fossae, which are found slightly mesial or
distal to the marginal ridges.

• Has a MESIOLINGUAL DEVELOPMENTAL GROOVE that originates in an occlusal pit and

extends onto a proximal surface.

• More occlusal surface is seen from the mesial than the distal.

• The distal marginal ridge forms a prominent elevation on the distal portion of the crown and
measures nearly twice the length of the mesial marginal ridge.

• Mesial marginal ridge is more cervical than its distal marginal ridge.


MANDIBULAR SECOND PREMOLAR (#20, #29)

CROWN: usually develops from 5 lobes (Y-type) and has 3 cusps (1 buccal, 2 lingual). From the
buccal, it is shorter and wider than the first premolar. From the occlusal, it has a SQUARE OUTLINE
and resembles other premolars from the buccal aspect only.
• lingual surfaces of mandibular first and second premolars differ in that the lingual surface of the
mandibular second premolar is much wider M-D and the M-L cusp is higher.

ROOT: 1 root whose apex approximates the mental foramen. The root is thicker and longer than the
mandibular first premolar root.
• Mental foramen is closest to the root apex of the MANDIBULAR SECOND PREMOLAR.
When performing endodontics on this tooth, care must be taken to avoid an overfill that may
impinge on the mental foramen. When viewing an x-ray of this area, the mental foramen is
sometimes misdiagnosed as a premolar abscess. Thus, before performing root canal therapy, make
sure all diagnostic tests confirm the finding. Mental foramen is situated near the apex or apices of
the permanent mandibular first and second premolars.
• Root is circular in cross section.

CUSP: buccal cusp is shorter, not as sharp, and the cusp slopes are less steep than mandibular first
premolar. ML cusp is always larger than DL cusp which may be absent. Lingual cusps are functional.
From a distal view, it is usually possible to see the outline of all 3 cusps.
• tip of the lingual cusp of a mandibular second premolar is closer to the lingual border of the crown.
• TWO LINGUAL CUSPS.
• From a distal view, it is usually possible to see the outline of the 3 cusps.
• In the 3-cusp mandibular second premolar, the cusps from largest to smallest are (facial, ML, and
DL).
• D-L cusps may be completely absent from mandibular second premolar and maxillary third molar.
• Mandibular second premolars and maxillary second molars most frequently have 3 CUSPS.

PITS & GROOVES: central developmental groove is sometimes “U”-shaped or crescent shaped. It
ends in the mesial and distal fossae, where it often joins a MB and DB supplemental groove.
• SINGLE CENTRAL PIT.
• mandibular first and second premolars have a central pit of fossa.
• MOST likely possesses a crescent-shaped central developmental groove.

OCCLUSAL PATTERN: larger occlusal surface than first premolar. Wider on lingual than buccal.
Most frequently has a single central pit. There is no M-L groove or transverse ridge (both are common on
first premolar).
• From the occlusal, coronal outline of a mandibular 2nd premolar is PENTAGONAL or SQUARE.
• 3 DISTINCT OCCLUSAL PATTERNS (occlusal surfaces = Y-type, H-type, and U-type).
• From the occlusal view, the greatest faciolingual diameter of a permanent mandibular second molar
is located in the MESIAL THIRD of the crown.
 • Distal marginal ridges of the mandibular first and second premolars, and mesial marginal ridge of
the mandibular first premolars have little or no contact in ideal centric and eccentric
maxillomandibular contact relationships.
• Oclussocervically, the height of the mesial marginal ridge of a permanent mandibular first molar is
the same as the height of the distal marginal ridge of a mandibular second premolar.

MANDIBULAR SECOND PREMOLARS can have 3 types of occlusal surfaces:

1. Y-type (5 lobes, 3 cusps) is the most common surface.
2. H-type (4 lobes, 2 cusps)
3. U-type (4 lobes, 2 cusps)-central developmental groove will appear crescent-shaped.


MAXILLARY MOLARS

A FISSURED GROOVE is most frequently found on the LINGUAL SURFACE of maxillary molars.
It is called the DISTOLINGUAL DEVELOPMENTAL GROOVE. Due to its presence, occlusal cavity
preparations usually need to be extended onto the lingual surface. The groove originates at an occlusal pit
and terminates in a pit on the lingual surface.

On a maxillary molar the largest, longest, and strongest of the three roots is the PALATAL ROOT. The DB
root is the smallest.
• PALATAL ROOT of a maxillary first molar is the third longest root of any maxillary tooth,
after the maxillary canine and second premolar roots. It is wider mesiodistally than
faciolingually, and has a longitudinal depression on the lingual side of it. It is concave on its buccal
surface. When viewed from the facial, the palatal root apex is in line with the buccal groove.
• Maxillary second molars roots are much LESS SPREAD APART than roots of a first molar. The
maxillary second molar palatal root is straighter than the palatal root of the first molar

PERMANENT MAXILLARY MOLARS may have a TRIANGULAR PULP CHAMBER.

• The base is formed by buccal canals and apex by palatal canals.
• The line connecting the mesial and palatal canal is the LONGEST.
• PULP CHAMBER FLOOR in a maxillary molar is usually triangular due to the triangular position
of the canal orifices.

Mesial root of a mandibular molar in cross-section at mid-root has two pulp canals in the MESIAL
ROOT. The distal root usually has one canal.
• If a cross-section is made just apical to the bifurcation of the roots of a mandibular molar, the
larger, kidney-shaped canal is found in the distal root and the smaller more circular canals are
found in the mesial root.
• MB canal curves more than ML canal.
• Mesial root is typically very thin mesiodistally, much wider faciolingually, and concave on both
mesial and distal surfaces.
• Distal pulp horn is the smallest.
• The pulp horn on the mesial (facially and lingually) is higher than that on the distal (needs to be
kept in mind during operative procedures).

DISTOLINGUAL CUSP on permanent molars is the cusp that gets PROGRESSIVELY SMALLER as
you go posterior in the arch. This is the MOST OBVIOUS CHARACTERISTIC that distinguishes
permanent first, second, and third molars from each other.
• For maxillary molars, the primary cusp triangle is formed by the ML, MB, & DB cusps. DL cusp is
not a part of this primary cusp triangle.

MAXILLARY MOLARS: Maxillary molars can be differentiated from mandibular molars by the
occlusal outlines, root arrangement, and number of roots.
• Permanent maxillary first and second molars, and some maxillary third molars normally have root
trifurcations.
• The primary cusp triangle on the occlusal surface of a permanent maxillary molar is formed by the
mesiolingual cusp, mesiofacial cusp, and distofacial cusp.
• mesiofacial, mesiolingual, and distofacial cusps of the maxillary molars is part of the maxillary
molar primary cusp triangle. The DL cusp is not part of the cusp triangle.
• cross-sectional outline at the cervical level is roughly triangular in a permanent maxillary second
molar.
• For maxillary molar roots, the LINGUAL root is the LONGEST and D-B root is the
SHORTEST.
• Embrasures are usually larger on the lingual than the facial with the contact area within the facial
moiety EXCEPT between maxillary first and second premolars.


MAXILLARY FIRST MOLAR (#3 & 14)

1. RHOMBOID (parallelogram-shape) occlusal outline.

2. 3 ROOTS (1 lingual, 2 facial roots). From largest to smallest (Palatal (lingual) >, M-B, D-B).

3. Most likely to have a distal coronal concavity that may pose special problems when placing a matrix
band.

4. In removing calculus from the root trunk area, the distal root surfaces of maxillary first molars present
the most difficulty.

5. If a root apex were forced into the maxillary SINUS during oral surgery, it would be the root of the
permanent maxillary first molar. Maxillary first molar root tip is most likely to be forced into the
maxillary sinus during surgical removal.

6. The three root furcations of the maxillary first molar from closest to farthest from the cervical line are
(mesial, facial, then distal).

7. PALATAL root is the largest, and has a CONCAVE LINGUAL SURFACE.

8. May have a fourth canal most often located in the MESIOBUCCAL ROOT.

9. Has an OBLIQUE RIDGE that joins the M-L and D-B cusps. The oblique ridge is reduced in height in
the center of the occlusal surface and is nearly level with the marginal ridges.

10. Central groove of the maxillary molar crosses the oblique ridge to connect with the central and distal
pits.

11. Transverse groove of the oblique ridge of a permanent maxillary molar connect the central and distal
pits.

12. On the occlusal surface, the total number of pits is normally the same as found on the occlusal surfaces
of the Y-type mandibular second premolar.

13. Occlusal outline of a permanent maxillary first molar contains two obtuse and two acute angles. The
obtuse angles are M-L and D-B. The acute angles are M-B and D-L.

14. Central pit of the maxillary first molar is formed at the bases of the triangular ridges of the
mesiobuccal, mesiolingual, and distobuccal cusps.

15. Caries is more likely to develop in deeply fissured grooves, on this basis the lingual surfaces of
permanent maxillary first molars, and facial surfaces of permanent mandibular first molars are the
most likely surfaces for caries.
16. Lingual surfaces of maxillary first molars are the most likely surfaces of permanent teeth for pit and
fissure caries to MOST likely occur.

17. Because of the presence of a fissured groove, cavity preparations most frequently need to be extended
from the occlusal surfaces to the lingual of maxillary molars.

18. M-L cusp of a maxillary first molar is the largest and longest cusp of all posterior teeth.

19. Maxillary molars, mandibular molars, and mandibular central incisors all have contact areas at
approximately the same levels cervicoincisally or cervico-occlusally on the mesial and distal.

20. The mesial contact area of a permanent maxillary first molar from the mesial view is facial to the
center of the crown faciolingually.

21. Height of contour occlusocervically is located in the middle third of the lingual surface of a permanent
maxillary first molar.

22. In comparing the rhomboidal and heart-shaped crown outlines of maxillary molars, the crown portion
that differs most in contour and size is the DL crown portion.

23. Most significant differences in the occlusal surface anatomy of maxillary first, second, and third molar
is that the distolingual cusps become progressively smaller.

24. In a M-D cross section, the direction of the enamel rods in the cervical third of the crown of a
permanent maxillary first molar INCLINE APICALLY.

25. From an occlusal view, the M-D width of the lingual portion of the crown is generally greater than the
M-D width of the facial portion of the crown in a permanent maxillary first molar.

26. In the triangle formed by the projection of the orifices of the canals of a maxillary first molar, the line
connecting mesial with lingual is longest.

27. Cusp of Carabelli occurs with sufficient frequency on primary maxillary second molars and
permanent maxillary first molars. Cusp of Carabelli-a small cusp or variable trait found on the M-
L surface of the first molar crown.

28. Lingual embrasures associated with the permanent maxillary first molars are small because maxillary
first molars have broader lingual surfaces than facial surfaces.


MAXILLARY SECOND MOLARS (#2 & #15)

Maxillary 2nd Molar CROWN:

• 2nd molar is smaller than the first molar, especially in its width on the lingual side, which has a
smaller or nonexistent DL cusp and is also smaller M-D. From the occlusal view, the M-B line
angle is the most acute. Buccal is broader than lingual due to absence of the fifth cusp
(Carabelli). It is more angular than first molar.

• Compared to the maxillary 1st molar crown, maxillary 2nd molar crown has a shorter DL groove.

• Viewed occlusally, the M-F line angle area is most ACUTE.

• Buccal groove is shorter an does not have a pit (compared to first molar).

Maxillary 2nd Molar ROOTS:

• 3 roots as long as first molar, but less spread apart M-D and F-L. The roots bend more to the
distal and have a longer root trunk.

• 3 ROOTS (1 lingual, 2 facial roots). From largest to smallest (Palatal (lingual) >, M-B, D-B).

• Cross-sectional outline at the cervical level is triangular in a permanent maxillary 2nd molar.

Maxillary 2nd Molar CUSPS:

• NO cusp of Carabelli. ML cusp is largest, and DL cusp is the smallest (same as maxillary first
molar). On all maxillary molars, the primary cusp triangle is formed by the ML, MB, and DB
cusps. The DL cusp is not part of this triangle.

• Cusp size from largest to smallest is (ML > MB> DB > DL).

• Has a small DL cusp that can be absent, to create a three-cusp tooth.

• DL cusp may also be absent on maxillary third molars and mandibular second premolars.

Maxillary 2nd Molar OCCLUSAL PATTERN: smaller oblique ridge and a more varied pit and
groove pattern than first molar. The transverse groove of the oblique ridge connects the central and
distal pits (same for all maxillary molars).

MAXILLARY 3rd MOLARS (WISDOM TEETH):

1. Most frequently has ONLY 3 CUSPS.
2. Maxillary third molars are the permanent teeth with the MOST VARIABLE OCCLUSAL
ANATOMY.
3. Third molars and maxillary lateral incisors demonstrate the greatest VARIATION in tooth mass.
4. Maxillary third molar has the greatest statistical VARIATION in ROOT ALIGNMENT.
 5. Maxillary third molar is the permanent tooth most likely to show an anomaly in radicular
morphology.

In mandibular molar, maxillary central incisor and lateral incisor, the crown’s M-D measurement is
GREATER than the F-L measurement.


MANDIBULAR MOLARS

Mandibular molars have a decided inclination in a LINGUAL direction. Mandibular molar crowns
TIP DISTALLY relative to the long axis of the root.
• As a result of this decided lingual inclination, the height of contour of the crown is lowered
apically to the middle third. Also, the placement of instruments subgingivally is more difficult on
the lingual side.
• The number of developmental grooves of a mandibular first molar distinguishes it from a
mandibular second molar. However, both have TWO ROOTS, same number of lingual cusps with
similar position, and a lingual groove.

• From a PROXIMAL VIEW the crown outline of a mandibular posterior tooth is RHOMBOIDAL
and has a design flaw that encourages cusp fracture.

• Posterior mandibular teeth have protective crests of contour on facial and lingual surfaces in the
middle or occlusal third of the lingual, and in the cervical third of the facial.

• Mandibular molars have long axes positioned with their root apices facial and their crown lingual.

• A projection of the facial surfaces of mandibular molars would be MEDIALLY located compared
to the anterior border of the ascending ramus.


MANDIBULAR FIRST MOLAR (#19, #30)

1. Occlusal outline is PENTAGON or TRAPEZOID shaped.

2. 5 CUSPS (mesiobuccal is the largest cusp) and 5 pulp horns at eruption.

3. Cusp size from occlusal view: (M-L > D-L > M-B > D-B > D).

4. 2 developmental grooves on the facial surface.

5. 2 pulp canals are usually found in the MESIAL ROOT of a mandibular first molar so special
consideration should be taken in preparing this tooth for endodontic therapy.

6. Permanent mandibular first molar has 2 ROOTS & 3 CANALS.

7. MESIAL ROOT of mandibular first molar has the LARGEST AREA in a mid-root cross-section.

8. Root surfaces of a mandibular first molar all normally exhibit a longitudinal groove except the
DISTAL SURFACE & DISTAL ROOT.

9. MESIAL ROOT is very thin M-D, much wider F-L, and concave on both M and D surfaces.

10. DISTAL PULP HORN is the SMALLEST.

11. M-B and M-L pulp horns are most likely exposed in a cavity preparation of a newly erupted
permanent mandibular first molar.

12. DISTOBUCCAL GROOVE-the developmental groove between the D-B cusp and fifth cusp of a
permanent mandibular first molar.

13. DISTAL CUSP is the SMALLEST and ML cusp is the LARGEST.

14. Mesial fossa is most distinctly separated from the remainder of the occlusal table by a transverse
ridge.

15. M-D measurement of the crown is slightly greater than the F-L measurement.

16. Has the LARGEST M-D measurement of its crown.

17. Height of contour of the facial surface is in the CERVICAL THIRD.

18. Lingual aspect of a mandibular first molar present with the lingual surface of each cusp possessing a
slightly convex shape in the occlusal third.


MANDIBULAR SECOND MOLARS (#18, #31)

1. 4 CUSPS of approximately EQUAL SIZE.

2. From an occlusal view, the greatest F-L diameter of a permanent mandibular second molar is located
in the MESIAL THIRD of the crown.

3. Has facial and lingual grooves that form right angles with the central groove.

4. Roots are closer together than mandibular first molar roots and are more distally inclined.

5. Occlusal groove pattern is CRUCIFIX (+).

6. A newly erupted permanent mandibular second molar has 4 pulp horns.

7. In its proper position relative to the plane of occlusion, the crown of the mandibular second molar
inclines mesially and lingually.

8. Root apices are located inferiorly to the mylohyoid muscle insertion.


 PERIODONTIUM ANATOMY

PERIODONTAL LIGAMENT (PDL) & GINGIVA

PERIODONTIUM (“attachment apparatus”)-tissues that invest and support the teeth. Periodontium
consists of the gingiva, PDL, cementum, alveolar and supporting bone.

3 Features of the Human Dentition that directly affect PDL heath and its hard tissue anchorage in terms
of resisting occlusal forces:
1. Anterior teeth have slight or no contact in the intercuspal position.
2. occlusal table is less than 60% of the overall faciolingual width of the tooth and is generally at
right angles to the long axis of the tooth.
3. mandibular molar crowns are inclined 15-201 toward the lingual, while the root apices are
positioned more facially.

PDL PRINCIPAL FIBERS (collagen fibers)-a connective tissue that consists of bundles of collagen
fibers grouped according to the direction they extend from the cementum of the root to the alveolar bone.
PDL principal fibers connect the root cementum to alveolar bone and are distinguished by their location
and direction. Principal fibers are sometimes classified as belonging to the general group of
alveolodental fibers.

1. Alveolar Crest Fibers-extend from the cervical cementum of the tooth to the alveolar crest that
function to counterbalance the occlusal forces on the more apical fibers and resist lateral movements.

2. Apical Fibers-radiate apically from cementum of tooth to bone. Apical fibers offer the initial
resistance to tooth movement in an occlusal direction. Found in the apical third of the root.

3. Interradicular Fibers (found only in multi-rooted teeth)-extend from the cementum in the furcation
area to the bone within the furcation.

4. Oblique Fibers-obliquely situated with insertions in the cementum and extending more apically in the
alveolus (approximately 1/3 of all principal fibers are oblique fibers). Oblique fibers are more
resistant to forces along the long axis of a tooth (masticatory forces). Found in the middle-third
of the root. Oblique fibers belong to the general group of alveolodental fibers.

5. Horizontal Fibers-run perpendicular from the alveolar bone to the cementum and resists lateral
forces.

SHARPEY’S FIBERS- terminal portions of principal collagen fibers that are embedded into the
cementum and alveolar bone. Sharpey’s fibers anchor the PDL fibers into cementum and bone. The
diameter of Sharpey’s fibers is MUCH GREATER on the bone side than on the cementum side.

PERIODONTAL LIGAMENT is a complex, soft, C.T. containing numerous cells, blood vessels,
lymphatics, nerves, and extracellular substance consisting of fibers (gingival and principal) and ground
substance. The majority of the PDL C.T. fibers are COLLAGEN, and the ground substance is
composed of a variety of proteins and polysaccharides.
• PDL contains: collagenous fibers, cells (fibroblasts, osteoblasts, cementoblasts, and
macrophages), nerves, lymphatics, and blood vessels. PDL DOES NOT HAVE CARTILAGE.

• Specialized PDL cells function to resorb and replace cementum (cementoclasts or cementoblasts);
periodontal ligament (fibroclasts or fibroblasts); and alveolar bone (osteoclasts or osteoblasts).

• PDL becomes very THIN and loses the regular arrangement of its fibers when a tooth loses
its function.

• PDL IS DERIVED FROM THE DENTAL SAC.

PERIODONTAL LIGAMENT occupies the space between the cementum and the periodontal
surface of the alveolar bone. PDL is a soft, fibrous C.T. that is cellular and vascular. PDL functions
include sensory, nutritional, supportive via the fibers, and formative via its cellular elements. PDL does
not maintain the epithelial attachment.
1. Formative (main PDL function)-formation of C.T. components by activities of connective tissue
cells (cementoblasts, fibroblasts, and osteoblasts).
2. Physical-attachment of tooth to bone via PDL principal fibers and the absorption of occlusal
forces.
3. Resorptive-by activities of connective tissue cells (fibroclasts, osteoclasts, and cementoclasts).
4. Nutritive-through blood vessels to the cementum, bone, and gingiva.
5. Sensory-carried by the TRIGEMINAL NERVE, proprioceptive and tactile sensitivity is
imparted through the PDL (sensation of contact between teeth).

PDL becomes THINNER with age due to the deposition of cementum and bone (this happens
primarily in the region of the mandibular canine). Cementum & alveolar bone are the tissues
immediately adjacent to the PDL.

PERIODONTAL LIGAMENT-connective tissue between tooth cementum and alveolar bone. PDL
consists predominantly of regularly arranged bundles of collagen fibers that are white, collagenous,
wavy bundles extending from bone to cementum.
• Periodontal ligament space-the space the periodontal ligament occupies and becomes widened
with occlusal trauma.

• PDL average thickness in the adult is 0.2mm which decreases with age. PDL thickness depends
on age, stage of eruption, and tooth function (PDL is thicker in functioning teeth than in non-
functioning teeth, and thicker in areas of tension than in areas of compression).

• PDL is a highly vascular and cellular connective tissue that surrounds tooth roots and bridges the
cementum with the alveolar bone.

• PDL is shaped like an hour-glass with the narrowest portion at the middle of the root.

• PDL acts as a cushion by ameliorating the impact of forces generated during mastication on the
 alveolar bone.

• Cementicles-calcified bodies lying free within the PDL or fused with cementum of the tooth.

• PDL Functions: PHYSICAL, FORMATIVE/REMODELING, NUTRITIONAL, AND

SESORY.

COMPONENTS OF GINGIVA:
1. FREE GINGIVA (unattached or marginal gingiva)-is the collar of tissue not attached to the
tooth or alveolar bone. Parts of the free gingiva include:
• gingival margin-the occlusal (incisal) border at which the gingiva meets the tooth.

• free gingival groove-separates free gingiva from attached gingiva. Only present in one-
third of adults.

• gingival sulcus-space formed by the tooth and sulcular epithelium laterally, and by the
coronal end of the junctional epithelium (sulcus base) apically.

• interdental gingiva (interdental or interproximal papilla)-component of the free gingiva

that fills the embrasure space between the area of tooth contact (interproximal space). It
occupies the interdental space coronal to the alveolar crest. interdental papilla consists
of two interdental papillae (one buccal and one lingual) connected by the concave-shaped
interdental col. The col conforms to the shape of the contact area and is not present at all
when teeth are not in contact. In the normal, healthy mouth, the interdental papilla is the
shortest cervicoincisally (cervico-occlusally) between the mandibular second premolar
and first molar.

• gingival papillae-fill the interproximal space between teeth.

• incisive papilla-an elevation of gingival tissue found directly lingual to the embrasure
between maxillary central incisors.

FREE GINGIVA extends from the free gingival groove to the gingival margin. Gingival fibers are
found within the free gingiva. Free gingiva extends from the free gingiva groove to the gingival crest.
Healthy free gingiva aids in the self-cleansing process by its close adherence to the tooth surface below
the height of contour of the cervical enamel.

GINGIVAL FIBERS-connective tissue fibers found in the FREE GINGIVA that are continuous with
the C.T. fibers of the PDL, and are often considered part of the periodontal ligament. Gingival fibers are
collagen fibers that provide support for the marginal gingiva and interdental papilla. Gingival fibers
support the gingiva and attach it to the tooth and alveolar bone. 5 Groups of Gingival Fibers:

1. Alveologingival Fibers-insert in crest of alveolar process and spread out through the lamina
propria into the free gingiva.

2. Circumferential Fibers (circular fibers)-encircle the tooth around the most cervical part of the
root and insert into the cementum and lamina propria of the free gingiva and alveolar crest. They
 resists rotational forces applied to a tooth.

3. Dentogingival Fibers-extend from cementum apical to the epithelial attachment and course
laterally and coronally into the lamina propria of the gingiva.

4. Dentoperiosteal Fibers-extend from the cervical cementum over the alveolar crest to the
periosteum of the cortical plates of bone.

5. Transseptal Fibers-extend from tooth-to-tooth, coronal to the alveolar crest and are embedded in
the cementum of adjacent teeth. Not found on the facial aspect, and have no attachment to
alveolar crestal bone. Transseptal fibers maintain integrity of the dental arches, and are
sometimes classified within the principal fiber group of the PDL.

• Gingival apparatus-describes all gingival fibers and the epithelial attachment.

• Gingival ligament-includes the dentogingival, alveologingival, and circumferential fibers.

• Interdental ligament-includes the transseptal fibers.

ATTACHED GINGIVA-the part of the gingiva attached to the underlying periosteum of the alveolar
bone and to the cementum by C.T. fibers and the epithelial attachment. Attached gingiva is present
between the free gingiva and the more movable alveolar mucosa. Attached gingiva boundary is formed
by the mucogingival junction to the free gingival groove.

• Mucogingival junction-separates attached gingiva from the alveolar mucosa, and is NOT part of
the free gingiva.
EPITHELIAL ATTACHMENT-inner layer of cells of the junctional epithelium that attaches the
gingiva to the tooth. Epithelial attachment adheres to the base of the gingival sulcus and is continuous
with the free gingiva. It can be attached to either enamel or cementum.

In the absence of periodontal disease, configurations of the crest of the interdental alveolar septa are
determined by RELATIVE POSITIONS OF THE ADJACENT CEMENTOENAMEL
JUNCTIONS.
WIDTH OF INTERDENTAL ALVEOLAR BONE is determined by the tooth form present.
Relatively flat proximal tooth surfaces call for narrow septa, while in the presence of extremely convex
tooth surfaces, wide interdental septa with flat crests are found.

ALVEOLAR PROCESS-the part of the maxilla and mandible that HOUSES THE TEETH, and
consists of two main parts:
1. Alveolar Bone Proper (cribiform plate or lamina dura)-the thin part of the alveolar process that
immediately surrounds the tooth root and to which the PDL fibers are attached. It has minute
openings that provide passage for vascular and nerve components. It is composed of two layers of
bone (compact lamellar bone and a layer of bundle bone). Bundle bone is the layer that the PDL
fibers insert into.
• Alveolar bone proper is the only essential part of the bone socket, as the supporting
 alveolar bone is not always present.

• Alveolar bone proper is the thin layer of lamellar bone that surrounds the root of the
tooth and is where the periodontal ligament fibers attach.

2. Supporting Alveolar Bone-bone that surrounds the alveolar bone proper and supports the socket.
It consists of:
• Cortical plate (compact lamellar bone)-forms the outer and inner plates of the alveolar
processes. It is thicker in the mandible than in the maxilla.

• Spongy bone (cancellated bone)-fills in area between cortical plates of bone. Spongy
bone is NOT present in the anterior region of the mouth-instead, the cortical plate is
fused to the cribiform plate. This is also true over the radicular buccal bone of the
maxillary posteriors.

ALL ORAL MUCOSA whether keratinized or non-keratinized is STRATIFIED SQUAMOUS

EPITHELIUM.
• Non-Keratinized Oral Mucosa: buccal mucosa, inferior surface of tongue, soft palate, and floor
of mouth.
• Keratinized Oral Mucosa: hard palate, free and attached gingiva.

3 Major Functional Types of Oral Mucosa:

1. Masticatory Mucosa-composed of free and attached gingiva and hard palate mucosa. Masticatory
mucosa epithelium is KERATINZED, and the lamina propria is dense, thick, firm C.T. containing
collagenous fibers.

2. Lining or Reflective Mucosa-covers the inside of lips, cheek, vestibule, lateral surfaces of the
alveolar processes (except mucosa of the palate), floor of the mouth, soft palate, and inferior
surface of the tongue. Lining mucosa is a thin, movable tissue with a thin, NON-KERATINIZED
EPITHELIUM and thin lamina propria.
• Mucogingival junction-junction of the lining mucosa and masticatory mucosa.

3. Specialized Mucosa-non-keratinized epithelium that covers the dorsum of the tongue and taste
buds.

 TOOTH HISTOLOGY & DEVELOPMENT
TOOTH LIFE CYCLE STAGES:
1. Initiation (Bud Stage)-initial interaction between oral epithelium and mesenchyme
(ectomesenchyme), formation of dental lamina.

2. Proliferation (Cap Stage)-tooth shape becomes evident, and the enamel organ is formed.

3. Differentiation (Bell Stage)-involves final shaping of tooth, cells differentiate into specific
tissue-forming cells (ameloblasts, odontoblasts, cementoblasts, and fibroblasts) in the enamel
organ.

4. Apposition-cells that were differentiated into specific tissue-forming cells begin to deposit the
specific dental tissues (enamel, dentin, cementum, and pulp).

5. Calcification-mineralization.

6. Eruption-the emergence of tooth through the gingiva.

7. Attrition-loss of tooth structure.

TOOTH GERM is composed of 3 structures:

1. ENAMEL ORGAN-formed from oral epithelium, derived from ectoderm, and has 4 distinct
cell layers. The enamel organ gives rise to enamel and Hertwig’s epithelial root sheath:
• Outer enamel epithelium (OEE)-the outer cellular layer of the enamel organ (very thin)
that outlines the shape of the future developing enamel organs.

• Inner enamel epithelium (IEE)-innermost cellular layer of the enamel organ (very thin).
Cells in this layer become ameloblasts and produce enamel. IEE is essential for the
initiation of dentin formation once enamel is formed.

• Stratum intermedium-this area lies immediately lateral to the IEE (thicker than OEE
and IEE). Stratum intermedium is essential to enamel formation by preparing nutrients
for ameloblasts of the IEE.

• Stellate reticulum-this area is the central core and fills the bulk of the enamel organ. It
contains lots of intercellular fluid (a mucous type fluid rich in albumin) which is lost just
before enamel deposition.

• AFTER ENAMEL FORMATION is complete, all 4 enamel organ cell layers unite and
form the REDUCED ENAMEL EPITHELIUM. REE is important in forming the
dentogingival junction (an area where enamel and epithelium unite as the tooth erupts into
the mouth). This forms the initial junctional epithelium (epithelial attachment), which
later migrates down the tooth to assume its normal position.
 2. DENTAL SAC-also formed from mesenchyme (ectomesenchyme), which is derived from
neural crest cells. Dental sac surrounds the developing tooth germ and gives rise to cementum,
PDL, and alveolar bone proper.

3. DENTAL PAPILLA- also formed from mesenchyme (ectomesenchyme), which is derived from
neural crest cells. Dental papilla gives rise to dentin and dental pulp. The outer layer of cells of
the dental papilla differentiates into odontoblasts (dentin-forming cells).

TOOTH HISTOGENESIS EVENTS-the formation and development of tooth tissues:

1. Elongation of inner enamel epithelial cells of the enamel organ influences mesenchymal cells on
the periphery of the dental papilla to differentiate into odontoblasts.
2. Differentiation of odontoblasts.
3. Deposition of the first layer of DENTIN.
4. Deposition of the first layer of ENAMEL.
5. Deposition of root dentin & cementum.

TOOTH DEVELOPMENT depends on a series of sequential cellular interactions between

epithelial and mesenchymal components of the tooth germ. Once the ectomesenchyme influences
the oral epithelium to grow down into the ectomesenchyme and become a tooth germ, the above
events occur.

Korff’s Fibers-the rope-like grouping of fibers in the pulp periphery that are involved in the formation
of the dentin matrix.

DENTINOENAMEL JUNCTION (DEJ)-interface between dentin and enamel. DEJ is the remnant of
the onset of enamel formation. DEJ is the first formed by the tooth germ and remains in evidence in
the formed tooth. DEJ is the area where calcification of a tooth begins, and DEJ morphology is
determined at the BELL STAGE

ODONTOBLASTS-begin dentin formation (dentinogenesis) immediately before enamel formation by

ameloblasts. Dentinogenesis begins with odontoblasts laying down a collagen matrix, moving from
the DEJ inward towards the pulp. The most recent layer of dentin formed is always adjacent to the
pulp surface.

 ENAMEL
ENAMEL-HARDEST substance in the body. Enamel is a HIGHLY MINERALIZED STRUCTURE
containing 95-96% inorganic matter formed from AMELOBLASTS.
• Hydroxyapatite-is made of calcium and phosphate, and is the largest mineral constituent (90-
95%) of enamel’s inorganic matter. Fluoride and zinc are minor inorganic constituents.

• Due to its high inorganic content, enamel appears optically clear on a histologic section of human
tooth.

• Enamel also consists of an organic matrix (1-2%) and water (4%). This organic matrix and water
content decreases as enamel matures. At the same time, the inorganic content increases. In its
mature state, enamel is 96% inorganic mineral.

• Enamel is the hardest substance in the body. It has no nerve supply and is a good thermal
insulator. Dentin actually acts as a cushion for enamel to help withstand the forces of
mastication.

• Enamel is made of enamel rods (prisms), rod sheaths (organic matrix), and a cementing
interred substance (interprismatic substance).

ENAMEL RODS (enamel prisms)-the fundamental morphologic unit of enamel. Each enamel rod is
formed in increments by a single-enamel forming cell (ameloblast). Each enamel rod traverses
uninterrupted through the entire thickness of the enamel. There are 5-12 million enamel rods per crown.
Enamel rods increase in diameter (from 4 up to 8 microns) as they flare outward from the DEJ.
• Enamel rods are aligned PERPENDICULAR TO THE DENTINOENAMEL JUNCTION
(DEJ), except in cervical regions of permanent teeth (oriented somewhat apically).

• Hunter-Schreger Bands-alternating light and dark lines seen in enamel that begin at the DEJ and
end before they reach the enamel surface. Hunter-Schreger bands represent areas of enamel rods
cut in cross-section dispersed between areas of rods cut longitudinally.

• Enamel Tufts-fan-shaped, hypocalcified structures of enamel rods that project from the DEJ into
the enamel proper (function is unknown).

• Enamel Spindles-elongated odontoblastic processes (hair-like) that traverse the DEJ from the
underlying odontoblast. May serve as pain receptors.

• Enamel Lamellae-defects in enamel resembling cracks or fractures that traverse the entire
length of the crown from the enamel surface to the DEJ. Enamel lamellae contain mostly
organic material and may provide an area for decay (bacteria) to enter.

ENAMEL IS THE HARDEST STRUCTURE of the body and the richest in calcium. Enamel contains
90-95% calcium and phosphate salts which make up hydroxyapatite; 1-2% organic matrix, and 4% water.
 • Enamel’s organic matrix consists mainly of protein (rich in proline).

• Enamel is composed or rods or columns in the shape of prisms (enamel prisms) bound together by
an interprismatic substance. Cross striations are indicative of an incremental growth pattern.

• Each rod extends through the entire thickness of the enamel layer.

• Oldest enamel in a fully erupted tooth is located at the DEJ underlying a cusp or cingulum.

• Enamel has no power of regeneration or metabolism, it has no way to combat bacterial invasion,
and no nerve supply, but is a good thermal insulator.

• DENTO-ENAMEL JUNCTION (DEJ)-interface between dentin and enamel; DEJ is the remnant
of the onset of enamel formation.

• Enamel forms more evenly before birth than after birth. Thus, deciduous teeth are almost always
uniform in appearance, while permanent teeth vary in color and degree of calcifications.

• Ameloblasts-enter their first formative state AFTER the first layer of dentin is formed.
Ameloblasts secrete enamel matrix as they retreat away from the DEJ, which then
mineralizes.

• Enamel is produced in a RHYTHMICAL FASHION and derived from ECTODERM.

ENAMEL HYPOCALCIFICATION-a hereditary dental defect in which enamel of teeth is soft and
undercalcified in context, yet normal in quantity caused by defective maturation of ameloblasts.
Teeth are chalky in consistency, the surfaces wear down rapidly, and a yellow to brown stain appears as
the underlying dentin is exposed. This condition affects both primary and permanent teeth.

ENAMEL HYPOPLASIA-caused by a disturbance in the ameloblasts during the enamel matrix

formation. The enamel is hard in context, but thin and deficient in amount. This condition affects both
deciduous and permanent teeth. For example, a metabolic disturbance during the prenatal period will
cause hypoplasia of the primary teeth (specifically, the incisal thirds of anterior teeth and occlusal
surfaces of posterior teeth).

• Turner Tooth-enamel hypoplasia of a permanent tooth due to exposure to infection or trauma from
the primary tooth.

DENTAL FLUOROSIS-an “irreversible” diffuse symmetric hypomineralization disorder of

ameloblasts due to excessive fluoride intake during ENAMEL’s calcification/mineralization period.
Typically causes mottled discoloration and pitting of the enamel of permanent and deciduous teeth.
NOT CAUSED BY REPEATED TOPICAL FLUORIDE APPLICATION.

 DENTIN
DENTIN-specialized avascular C.T. that makes up the bulk of the tooth, extending almost the entire tooth
length. Dentin is hard, elastic, 20% organic (primarily collagen), 75% inorganic (hydroxyapatite =
calcium and phosphate), and 5% retained water and untraceable minerals.
• Dentin is more mineralized than cementum or bone, but less mineralized than enamel. Dentin
is much softer than enamel, but harder than bone or cementum. Dentin is more flexible (lower
modulus of elasticity) than enamel, and its compressive strength is much higher than its tensile
strength.

• Morphologically and chemically, dentin has many characteristics in common with bone.

• Odontoblast-the main cell type in dentin derived from ectomesenchyme.

• Unlike enamel, which is acellular, dentin has a cellular component that is retained after its
formation by odontoblasts.

• Dentin and pulp tissue are formed from the DENTAL PAPILLA. Pulp tissue is a loose, highly
vascular, and non-calcified C.T., while dentin is an avascular and calcified tissue.

DENTIN TYPES (4):

1. Mantle Dentin-the dentin right next to the DEJ (most peripheral layer of dentin). Mantle dentin is the
first layer of dentin formed. The remaining dentin is circumpulpal dentin.

2. Peritubular Dentin-lines each dentinal tubule, and is more mineralized than intertubular dentin
(has a greater content of inorganic salts).

3. Intertubular Dentin-surrounds the peritubular dentin, and is less mineralized (has a lower content of
inorganic salts).

4. Interglobular Dentin-imperfectly calcified matrix of dentin situated between the calcified globules. It
is located near the dentin periphery.

Each dentinal tubule contains the cytoplasmic cell process Tomes’ Fiber of an odontoblast.

DEAD TRACTS-groups of dead, coagulated cytoplasmic processes of dentinal tubules caused by the
aging process of the dentinal tissue, caries, erosion, cavity preparation, or odontoblastic crowding.

1. Primary Dentin-forms the initial shape of the tooth, and is deposited before completion of the
apical foramen. The junction between primary and secondary dentin is characterized by a sharp
change in the direction of dentinal tubules.

2. Secondary Dentin-dentin formed after completion of the apical foramen. It is formed at a slower
rate than primary dentin as functional stresses are placed on a tooth. Secondary dentin is a regular and
 uniform layer of dentin around the pulp cavity.
• Secondary dentin is the tissue formed in response to stimuli produced by carious
penetration of a tooth.

3. Reparative Dentin-formed very rapidly in response to irritants (attrition, abrasion, erosion,

moderately advancing caries, and trauma).

4. Sclerotic Dentin-results from aging and slowly advancing dental caries. The dentin tubules become
calcified and obliterated which blocks access of irritants to the pulp by way of the tubules.

 CEMENTUM
CEMENTUM-hard dental tissue covering ANATOMICAL ROOTS of teeth. Cementum is formed by
PDL cementoblasts, and has these characteristics:
• Cementum is slightly softer and lighter in color (yellow) than dentin.
• Cementum is formed by cementoblasts from the PDL, as opposed to dentin which is formed by pulp
odontoblasts.
• Cementum most closely resembles BONE, except there are no haversian systems or blood
vessels (cementum is avascular, while bone is vascular). Cementum has NO NERVE
INNERVATION.
• 50% inorganic (hydroxyapatite), 40% organic (mainly collagen and protein), and 10% water.
• Cementum is important in ORTHODONTICS because it is more resistant to resorption than
alveolar bone, permitting orthodontic movement of teeth without root resorption.

TWO TYPES OF CEMENTUM (functionally they are the same):

1. Acellular Cementum-contains no cells, and predominates on the coronal two-thirds of the
root. It is thinnest at the CEJ. Formed before the tooth reaches the occlusal plane. The cervical
1/3 is mainly Sharpey’s fibers.

2. Cellular Cementum-contains cementoblasts, inactive cementocytes, fibroblasts from the PDL,

and cementoclasts. Found on the apical third of the root, and is thicker to compensate for
attritional wear of the occlusal/incisal surface and passive eruption of the tooth. Formed after
the tooth erupts. Makes up the apical root ½ which is less calcified, so be carefull with SRP.

MAIN FUNCTION of CEMENTUM is to attach principal fibers of the periodontal ligament to the
tooth. Additional Cementum Functions:
1. compensates for the loss of tooth surface due to occlusal wear by apical deposition of
cementum throughout life.

2. protects the root surface from resorption during vertical eruption and tooth movement.

3. reparative function that allows reattachment of C.T. after periodontal treatment.

CEMENTUM contains 2 types of Collagen Fibers:

1. Sharpey’s Fibers-the terminal portions the PDL principal fibers that are embedded in the
cementum (run perpendicular to cementum) on one end and alveolar bone on the other end.
2. Collagen Fibers-found within the cementum itself running parallel to the cementum surface.

HISTOLOGICALLY, cementum differs from enamel because it has collagen fibers and cellular
components in the mature tissue.

CEMENTIOD-the peripheral layer of developing, uncalcified cementum.

HYPERCEMENTOSIS-excessive formation of cementum around the tooth root after it has erupted
caused by trauma, metabolic dysfunction, or periapical inflammation.

ANKYLOSIS-the fusion of alveolar bone to a tooth due to infection or trauma to the periodontal
ligament. The ankylosed tooth has lost its periodontal ligament space and is truly fused to the alveolar
process or bone.

GOMPHOSIS-a type of fibrous joint in which the conical process is inserted into a socket-like
portion, such as the styloid process in the temporal bone or the teeth in the dental alveoli.

 DENTAL PULP
DENTAL PULP-a highly vascularized and nerve innervated tissue that consists of vital loose C.T.
(collagen + reticulin fibers) and odontoblasts. Formed from the dental papilla of the tooth germ (the
innermost tissue during odontogenesis when dentin forms around the dental papilla). The primary
function of pulp is to form dentin (by odontoblasts).
• Pulp Contents: large nerve trunks and blood vessels, fibroblasts (main pulp cell), odontoblasts,
histiocytes, macrophages, lymphocytes, mast cells, plasma cells, PMNs, eosinophils, and ground
substance, and sometimes pulp stones.

• Nerve Plexus of Raschkow (NPR)-located near the pulp core and monitors painful sensations.
NPR contains A fibers (conduct rapid and sharp pain sensations) and C fibers (conduct dull,
aching pain).

• FREE NERVE ENDING-THE ONLY NERVE ENDING FOUND IN PULP. It’s a specific
receptor of pain. Regardless of the source of stimulation (heat, cold, pressure), THE ONLY
PULPAL RESPONSE IS PAIN.

Anatomically, dental pulp is divided into two portions (coronal and radicular) pulp.
1. Coronal Pulp-located in the pulp chamber and pulp horns (crown portion of tooth).

2. Radicular Pulp-located in the pulp canals (root portion of tooth). Radicular pulp is continuous
with tissues of the periapical area via the apical foramen. Accessory canals extend from the pulp
canals through the root dentin to the PDL.

CENTRAL ZONE (Pulp Proper)-contains large nerves and blood vessels, and is lined peripherally by a
specialized odontogenic area that has three layers (from innermost to outermost):
1. Cell-rich zone-innermost layer that contains fibroblasts.
2. Cell-free zone (zone of Weil)-rich in capillaries and nerve networks.
3. Odontoblastic layer-contains odontoblasts and lies next to the predentin and mature dentin.

With increasing age and exposure of the tooth to physiological functioning, secondary dentin
deposition decreases the diameter of the coronal and radicular pulp cavities.

When a tooth is newly erupted, the dental pulp is large; it becomes progressively smaller as the tooth
is completed. The entire pulp and apical foramen are relatively large in primary teeth and in young
permanent teeth. For this reason, teeth of children and young people are more sensitive to thermal
changes and dental operative procedures than teeth of older people.

Main function of dental pulp is FORMATIVE (to form dentin by odontoblasts). Other pulp
functions:
• Nutritive-pulp keeps organic components of the surrounding mineralized tissue supplied with
moisture and nutrients.
• Sensory-extremes in temperature, pressure, or trauma to dentin or pulp are perceived as PAIN.
 • Protective-the formation of reparative or secondary dentin by odontoblasts.

CELLS FOUND IN DENTAL PULP:

• Fibroblasts (the main cell), odontoblasts, histiocytes (macrophages), and lymphocytes.
• In diseased pulp, plasma cells, PMN’s, monocytes, and eosinophils are present.

PULP is composed of:

• Loose connective tissue (collagen and reticulin fibers).
• Cells (fibroblasts, odontoblasts, histiocytes, and lymphocytes).
• Blood vessels (arteries and veins), nerves, lymphatics, and ground substance.

Main function of dental pulp is FORMATIVE (to form dentin by odontoblasts). Other pulp
functions:
• Nutritive-pulp keeps organic components of the surrounding mineralized tissue supplied with
moisture and nutrients.
• Sensory-extremes in temperature, pressure, or trauma to dentin or pulp are perceived as PAIN.
• Protective-the formation of reparative or secondary dentin by odontoblasts.

PULP CAPPING is more successful in young teeth because:

• Large apical foramen.
• Young pulp contains more cells (odontoblastic) and has more tissue fluid.
• Young pulp has less fibrous elements
• Young pulp is highly vascular, and lacks collateral circulation.

AS PULP AGES:
• Reticulin fibers decreases (the pulp becomes less cellular and more fibrous).
• Size of pulp decreases because of the continued deposition of dentin.
• The number of collagen fibers and calcifications within the pulp (denticles or pulp stones)
increases.

PULP contains both myelinated & unmyelinated nerve fibers that are afferent and sympathetic. The
myelinated fibers are sensory, and unmyelinated fibers are motor (they play a role in regulating the
lumen size of the blood vessels).
• Proprioceptors-respond to stimuli regarding movement ARE NOT FOUND IN PULP.

FREE NERVE ENDING IS THE ONLY NERVE ENDING FOUND IN PULP and is a specific pain
receptor. Regardless of the source of stimulation (heat, cold, pressure), the only response is PAIN.

• Dental pulp functions include the formation of dentin, transmission of pain stimuli, and production
of a defensive reaction when a tooth is exposed to irritation.

• Changes in pulp chamber shape is related to age, attrition, caries, and restorative dental treatment.

• Pulp chamber of a mature tooth contains blood vessels, nerves, and odontoblasts.

• Dental pulp consists of C.T., nerve tissue, and blood vessels.


 PARAFUNCTION & EROSION
ABRASION-wearing away of tooth structure by mechanical means. Two types of abrasion:
1. Toothbrush abrasion-most often results in V-shaped wedges at the cervical margin in the
canine and premolar areas. It is caused by the use of a hard toothbrush and/or a horizontal
brushing stroke and/or a gritty dentifrice.

2. Occlusal abrasion-results in flattened cusps on all posterior teeth and worn incisal edges. It is
caused by chewing or biting hard food or objects, or chewing tobacco.

ATTRITION-wearing away of enamel and dentin from normal function or, more commonly from
excessive grinding or gritting together of teeth by the patient (bruxism). The most noticeable effects
of attrition are polished facets (flat incisal edges, discolored teeth surfaces, and exposed dentin).
Facets usually develop on the linguoincisal of the maxillary central incisors and canines, and the
facioincisal of the mandibular canines.

ABFRACTION-non-carious lesions caused by FLEXURAL forces (occlusal cyclic loading). Enamel at

the CEJ is destroyed when enamel rods separate, causing V-shaped depressions on the tension side and C-
shaped depressions on the side under compression.

EROSION-loss of tooth structure from non-mechanical means due to drinking acidic liquids or
eating acidic foods. Erosion is common in bulimic individuals as a result of regurgitated stomach acids.
It affects smooth and occlusal tooth surfaces.

CARIES-usually found on proximal surfaces, pits and grooves, and cervical thirds. CARIES IS
USUALLY NOT FOUND ON CUSP TIPS (caries is least likely to occur in or on cusp tips). Caries
activity is directly proportional to:
1. Consistency of fermentable carbohydrates ingested.
2. Frequency of ingesting fermentable carbohydrates.
3. Oral retention of fermentable carbohydrates ingested.

 MUSCLES OF MASTICATION & MANDIBULAR
MOVEMENT
MASTICATION-the breaking down or chewing of food so is easily attacked by digestive enzymes.
Functions of mastication are:
1. Incision of food-by the incisors (centrals and laterals).
2. Prehension of food-by the canines.
3. Trituration of food-by the premolars and molars.

MUSCLES OF MASTICATION-the muscles responsible for the movement of the mandible in the
chewing of food. The 4 pairs of mastication muscles: Masseter, Temporalis, Medial pterygoid, Lateral
pterygoid. Muscles of mastication have the major control over all movements of the mandible
(elevation, depression, retraction, protraction, and lateral excursions).

MANDIBULAR RETRUSION-mandibular movement caused by bilateral contraction of the

Temporalis muscle’s POSTERIOR (horizontal) fibers, which are assisted by the suprahyoid muscles
(specifically anterior and posterior bellies of the digastric muscles).

CLOSING THE MOUTH (Mandible Elevators) is caused by bilateral contraction of 3 pairs of

muscles:
1. Anterior (vertical) fibers of the right and left Temporalis muscles.
2. Right and left Masseter muscles.
3. Right and left Medial Pterygoid muscles.

LATERAL EXCURSIONS (moving the jaw sideways)-movement caused by the contraction of one
lateral pterygoid muscle on the opposite side (i.e. the mandible moves left by contracting the right lateral
pterygoid muscle).

LATERAL PTERYGOID MUSCLES -DEPRESS & PROTRUDES THE MANDIBLE.

1. Depression of Mandible (opening the jaw) occurs when the lateral pterygoids pull the
articular discs and condyles ANTERIORLY & DOWN onto the articular eminences. In
opening the jaw or depressing the mandible, the lateral pterygoids are assisted by the anterior
bellies of the digastric muscles (suprahyoid muscles) and the omohyoid muscles (infrahyoid
muscles). These muscles help fix or hold the hyoid bone.

2. Protrusion of Mandible (protruding the jaw) results only from the simultaneous contraction
of BOTH LATERAL PTERYGOIDS. This produces forward movement of the condyle from the
mandibular fossa (articular fossa). They do not need assistance for this movement.
• Protrusive movements are forward symmetrical movements of the mandible guided by the
contact of anterior teeth.

If a patient with a paralyzed right lateral pterygoid muscle is instructed to open his mouth wide, the
mandible will DEVIATE TO THE RIGHT UPON OPENING. The mandible ALWAYS deviates to the
side of the injury.
• if the hypoglossal nerve is damaged from injury or a tumor, the tongue will also deviate
noticeably toward the affected side.

RIGHT LATERAL PTERYGOID MUSCLE is the prime mover in effecting a LEFT WORKING-SIDE
MOVEMENT. Lateral excursions (moving the jaw sideways) results from the contraction of one
lateral pterygoid muscle on the opposite side.
• For a RIGHT WORKING-SIDE MOVEMENT, the prime mover is the LEFT LATERAL
PTERYGOID.
• Protrusive movement is produced when BOTH LATERAL PTERYGOIDS CONTRACT.

MUSCLES THAT ELEVATE THE MANDIBLE (CLOSE THE MOUTH): Closing the mouth
(elevating the mandible) occurs from the bilateral contraction of three pairs (right and left) of muscles:

1. MASSETER-paired muscle that originates from the ZYGOMATIC ARCH (cheekbone) that inserts
and COVERS THE LATERAL SURFACE OF THE RAMUS (ANGLE OF MANDIBLE).
ELEVATES MANDIBLE to occlude teeth. Forms a sling around the angle of the mandible. The
stretch reflex maintains masseter muscle tone. MASSETER IS THE MOST POWERFUL
 MASTICATORY MUSCLE.

2. MEDIAL PTERYGOID-origin is the medial surface of the lateral pterygoid plate (sphenoid
bone) and maxillary tuberosity. Inserts on medial surface of angle of mandible. ELEVATES
(CLOSES) & slightly PROTRUDES MANDIBLE, & MOVES IT LATERALLY. Forms a sling
around the angle of the mandible.
• During an inferior alveolar block injection, the needle passes through the mucous membrane
and buccinator muscle, and lies LATERAL to the medial pterygoid. If the anesthetic needle
passes through the MEDIAL PTERYGOID MUSCLE OR BUCCINATOR during an
inferior alveolar nerve block, trismus can result.

3. TEMPORALIS-fan-shaped, originates from the temporal fossa floor (temple) and deep surface of
the temporal fascia. It passes medially (downward and deep) to the zygomatic arch as a thick tendon
before inserting on CORONOID PROCESS of mandible and anterior border of ramus-posterior to
3rd molars).
• Anterior & superior fibers ELEVATE THE MANDIBLE. Temporalis posterior fibers
RETRACT the MANDIBLE. Maintains resting position during when the mouth is closed.
ELEVATES & RETRACTS the mandible.

• Inserts into the coronoid process of mandible and anterior border of the ramus.

Muscles that open (DEPRESS) Mandible: Omohyoid, Lateral pterygoid, & Digastric (anterior belly).
Muscles that close (ELEVATE) Mandible: Masseter, Medial pterygoid, & Temporalis (anterior fibers)
Muscles that RETRACT Mandible: TEMPORALIS (posterior fibers)
Muscles that cause LATERAL EXCURSION of MANDIBLE: Lateral pterygoids (right or left)

BUCCINATOR MUSCLE (muscle of facial expression)-innervated by buccal branch of facial nerve

(CN VII). Originates from ALVEOLAR PROCESS of maxilla and mandible and
PTERYGOMANDIBULAR RAPHE. COMPRESSES THE CHEEKS and LIPS AGAINST THE
TEETH and hypertrophies with bruxism.

AS A GROUP, suprahyoid muscles RAISE THE HYOID BONE DURING SWALLOWING, assist
lateral pterygoid muscles in depressing the mandible (opening the mouth), and assist the posterior fibers
of the temporalis muscles during retraction of the mandible.

EXTRINSIC MUSCLES OF TONGUE:

1. Genioglossus-originates from genial tubercle of mandible and inserts on dorsum of tongue.
Protrudes the tongue and retracts the tip of the tongue.

2. Hyoglossus-originates from the greater and lesser horn of the hyoid bone. Inserts on the lateral
aspect of tongue. Depresses the tongue.

3. Styloglossus-originates from styloid process, inserts on the lateral aspect of tongue. Retracts and
elevates the tongue.

4. Palatoglossus (glossopalatine)-originates from the palatine aponeuroses and inserts on the side
of the tongue. Elevates the posterior tongue and closes the oropharyngeal isthmus. It aids in
initiating swallowing.

EXTRINSIC TONGUE MUSCLES

INTRINSIC MUSCLES OF TONGUE (Fibers) are named based on three spatial planes in which they
run, and ALTER TONGUE SHAPE:
1. Longitudinal muscle-shortens the tongue (curls the tip).
2. Transverse muscle-narrows tongue.
3. Vertical muscle-flattens and broadens tongue.

SUPRAHYOID MUSCLES:
1. Geniohyoid muscle-draws hyoid and tongue forward.
2. Mylohyoid muscle-raises hyoid and floor of mouth.
3. Digastric muscle (anterior belly)-opens jaw, draws hyoid forward.
4. Digastric muscle (posterior belly)-draws hyoid back, raises hyoid.
5. Stylohyoid muscle-draws hyoid up and back.

*Geniohyoid and Mylohyoid form the floor of the mouth.

INFRAHYOID MUSCLES (innervated by ansa cervicalis):

1. Thyrohyoid-pulls the hyoid inferiorly and raises the larynx.
2. Omohyoid-pulls the hyoid inferiorly.
3. Sternohyoid-pulls the hyoid inferiorly.
 4. Sternothyroid-pulls the larynx inferiorly.

Infrahyoid muscles function to LOWER THE HYOID BONE & LARYNX while steadying the hyoid
bone. This allows the suprahyoid muscles to assist the lateral pterygoid muscles in depressing the
mandible (opening the mouth).


TEMPEROMANDIBULAR JOINT (TMJ)-dual articulation between the condyle of the mandible and
squamous portion (glenoid fossa) of the temporal bone (skull).
• TMJ is a GINGLYMOARTHRODIAL JOINT (rotational and translational); it is a hinging
AND sliding joint. It involves the condylar process of the mandible and glenoid (articular) fossa
of the temporal bone.

• During SLIDING (GLIDING), the disk and condyle move forward (protrude by lateral pterygoid)
and backward (retrude by temporalis).

• During HINGE (ROTATIONAL) MOVEMENT, the mandible is elevated (masseter,

temporalis, medial pterygoid) and depressed (lateral pterygoid). Rotational movement occurs
 mainly between the disc and mandibular condyles in the lower synovial cavity.

• During mandibular lateral excursions (deviation) to one side, the TMJ glides on one side and
rotates on the opposite side.

• Each TMJ is covered by a fibrous capsule, and the non-articular TMJ surfaces are covered with
periosteum.

3 STRUCTURES FORM EACH TMJ’s ARTICULATING PARTS:

1. MANDIBULAR CONDYLE (condyloid process)-elliptically shaped with their long axis oriented
mediolaterally. They are not symmetrical nor identical. The articulating surface or functioning part of
the condyle is on the superior and anterior surfaces of the head of the condyle. This surface is covered
with a vascular layer of fibrous C.T.
• Condyle ROTATES in the fossa, and slides forward along the articular fossa to the articular
eminence (TRANSLATES); the TMJ disc normally moves with the condyle which is wrapped
by the JOINT CAPSULE.

2. ARTICULAR DISC (meniscus)-a dense fibrous (collagenous C.T.) biconcave saddle-shaped

(oval) structure that separates the mandibular condyle and glenoid fossa of the temporal bone.
Articular disc divides the joint into upper and lower cavities. It is a biconcave oval structure
composed of dense, fibrous C.T. located between the mandibular condyle and temporal bone
(specifically, the articular fossa and articular eminence (tubercle) of the mandibular fossa).
• Articular disc lies between the articular (glenoid) fossa of the temporal bone and
mandibular condyle. This articular fossa is the anterior ¾ of the larger mandibular fossa
of the squamous part of the temporal bone.

• Articular disc (meniscus) varies in thickness. The thinner, central intermediate zone
separates thicker portions called the anterior band and posterior band. Posteriorly, the
disc is contiguous with the posterior attachment tissues called the bilaminar zone (a
vascular, innervated tissue). Articular disc consists of dense collagenous C.T. that is
avascular and devoid of nerve tissues in the CENTRAL AREA, but has vessels and
nerves in the PERIPHERHAL area.

• Articular surfaces of the temporal bone is composed of the concave articular glenoid fossa
and convex articular eminence.

• ARTICULAR DISC (Meniscus)-a FIBROCARTILAGE, saddle-shaped (bioconcave)

tissue associated with the TMJ made of dense, irregular C.T. that SEPARATES THE
CONDYLE & TEMPORAL BONE (it divides the TMJ into superior and inferior joint
spaces and prevents bone-to-bone contact), and provides a smooth articulating surface.
Thickest at the posterior, thinner in the center. It moves with the condyle under normal
function. THE DISC IS SURROUNDED and PROTECTED by the FIBROUS C.T.
JOINT CAPSULE. The disc is considered DISPLACED when it lies ANTERIOR to its
usual position.
 • CLICKING and POPPING when opening is caused by DISK DISPLACEMENT WITH
REDUCTION.

• Painful, limited opening (≤ 30mm) WITHOUT SOUND is due to DISK

DISPLACEMENT WITHOUT REDUCTION. Normal, full opening is 40-50mm as
measured from the maxillary and mandibular incisal edges.

• The best diagnostic imaging tests to examine DISK POSITION and FUNCTION is
MAGNETIC RESONANCE IMAGING (MRI) or CONE BEAM (CT).

3. ARTICULAR FOSSA (Glenoid fossa)-the anterior anterior ¾ of the larger mandibular fossa. The
mandibular fossa is a depression in the temporal bone just anterior to the auditory canal. This part of
the mandibular fossa is considered to be a nonfunctioning portion of the joint.
• Articular eminence (articular tubercle)-a ridge that extends mediolaterally just in front of
the mandibular fossa. It is considered to be the functional portion of the joint. It is lined
with a thick layer of fibrous C.T.

Temporal Bone’s Articular Surface-composed of the concave articular fossa (glenoid fossa) and
convex articular eminence (tubercle) that limits forward movement of the condyle.
• SUBLUXATION (slipping of the condyle from its socket) occurs when the condyle head moves
too far ANTERIORLY on articular eminence. Caused by injury to the articular capsule
surrounding the TMJ.

• GOMPHOSIS-a type of fibrous joint in which the conical process is inserted into a socket-like
portion, such as the styloid process in the temporal bone or the teeth in the dental alveoli.

ARTICULAR CAPSULE-thick, fibrous tissue that surrounds the TMJ and is attached above to the
articular eminence (tubercle) and to the margins of the mandibular fossa and below to the neck of the
mandible. Synovial Membrane-lines the articular joint capsule in the superior and inferior spaces of the
joint and PRODUCES SYNOVIAL FLUID for lubrication. It does not cover the articular surfaces or
articular disc.

FIBROUS CAPSULE (capsular ligament) encloses these 3 structures. FIBROUS CAPSULE encloses
the TMJ like a tube. It is a sheet of tissue that surrounds the joint, and is attached above to the articular
tubercle and margins of the mandibular fossa, and below to the neck of the mandible. It is fairly thin
except laterally where it forms the temporomandibular ligament (lateral temporomandibular
ligament). The fibrous capsule has two layers:
1. internal synovial layer (synovial membrane)-a thin layer that secretes synovial fluid that
lubricates the joint.

2. outer fibrous layer-a thicker layer of fibrous tissue reinforced by accessory ligaments
(stylomandibular and sphenomandibular).

3 TMJ LIGAMENTS: attach and determine the farthest boundaries of mandibular movement:
1. Temporomandibular ligament (lateral ligament)-runs from the articular eminence (tubercle) to
the neck of the mandibular condyle. It provides lateral reinforcement for the capsule &
 PREVENTS POSTERIOR & INFERIOR DISPLACEMENT OF THE CONDYLE (prevents
the mandible from excessive retraction or from moving backward). Resists posterior
movement of the mandibular condyle, and is found on the lateral surfaceds of the TMJ.

2. Stylomandibular ligament-separates the infratemporal region anteriorly from the parotid region
behind. Runs from the styloid process of sphenoid bone to the angle of the mandible.
Separates the parotid and submandibular salivary glands, and is taut when the mandible protrudes.

3. Sphenomandibular ligament-attaches to the spine of sphenoid bone & lingula of the mandible.
Becomes taut when the mandible protrudes. A remnant of Meckel’s cartilage and a landmark when
administering an IA nerve block.

TMJ SENSORY innervation is from V3 (MANDIBULAR BRANCH OF TRIGEMINAL) and bloods

supply is from the EXTERNAL CAROTID ARTERY (superficial temporal branch). TMJ
development occurs at 12 weeks in utero when the joint spaces and articular disc develop.
CREPITUS-a grinding, crackling sound at the TMJ during movement due to the wearing away of the
joint’s articular surface.

TMJ-a ginglymoarthrodial joint that differs from most articulations in that the articulating surfaces are
covered with avascular fibrous tissue (fibrocartilage) rather than hyaline cartilage. It has two synovial
cavities (upper and lower compartment). TMJ is protected by (muscles of mastication, synovial fluid,
ligament suspension, and fibrocartilage).

TMJ is a combined HINGE & GLIDING (sliding) joint. TMJ is a ginglymoarthrodial joint
permitting both hinge-like rotation and sliding (gliding) movements. Ginglymus means rotation, and
arthrodial means freely movable. TMJ is a synovial and diarthrodial joint.

TMJ (2 Compartments):
1. Lower (condyle-disc) compartment-only HINGE-TYPE or ROTATIONAL movements occur.
This rotational or hinge-axis opening of the mandible is possible only when the mandible is
retruded in centric relation with a conscious effort by the patient or by the dentist’s control.
During mouth opening, the articular disc moves ANTERIORLY in relation to the articular
eminence.

2. Upper (mandibular fossa-disc) compartment-only SLIDING or TRANSLATORY movements

occurs. When the lateral pterygoid muscles contract simultaneously, the discs and condyles slide
forward down over the articular eminence (protrusion), or can move backwards together
(retrusion) during opening and closing of the mouth, respectively.

 MANDIBULAR MOVEMENTS & POSITIONS
When a mandibular movement to the LEFT is performed, the NON-WORKING CONDYLE (RIGHT)
moves anteriorly, downward, and medially, and also rotates at the same time.
• THE LEFT CONDYLE (WORKING) may move slightly, sliding laterally, turning to the left, and
rotating forwards.

• IN MOVEMENTS TO THE RIGHT, the roles of the condyles are reversed.

During a working side movement of the mandible, the oblique ridge of a maxillary first molar passes
through the DISTOBUCCAL SULCUS of a permanent mandibular first molar.
• In the intercuspal position, the M-B triangular ridge of the maxillary first molar opposes the
mesiobuccal groove of the mandibular first molar.

• In a working side movement (right or left), the M-B cusp of the maxillary first molar passes through
the LINGUAL GROOVE of the mandibular first molar.

• In a working side movement (right or left), the M-B cusp of the maxillary second molar passes
through the FACIAL GROOVE of the mandibular second molar.

WORKING SIDE-the side to which the mandible moves towards. The condyle of the working side is the
working condyle which exhibits a small sliding lateral movement during mandibular lateral excursions
= Bennett movement.

BENNETT MOVEMENT-movement in the early stages of lateral movements when the condyle rotates
with a slight lateral shift in the direction of the movement. Bennett movement refers to the working
side condyle only. Its rotation of the working side condyle in its articular fossa that results in slight
lateral movement of the condyle.
• Bennett movement is also called lateral shift of the mandible or immediate side shift. Bennett
movement influences the mesiodistal position of the cusps of posterior teeth.

• Bennett movement is mandibular LATERAL TRANSLATION that occurs during the earliest
stage of lateral movement.

• During right mandibular movement, on the right side (working side), the condyle moves from
centric to right working. This is Bennett movement.

NON-WORKING SIDE (Balancing Side)-the side opposite the working side.

When the mandible is in its physiologic rest or postural position, contact of teeth is NOT PRESENT.
This position results when the mandible and all of its supporting muscles (eight muscles of mastication
plus the supra- and infrahyoids) are in their resting position.

• FREEWAY SPACE (“interocclusal distance”)-the absence of contact that averages 2-6mm.

During typical empty mouth swallowing, the mandible is braced in the INTERCUSPAL JAW
POSITION (centric occlusion) to allow for proper stabilization.
• EMPTY MOUTH SWALLOWING occurs frequently during the day and is an important
function that rids the mouth of saliva and helps moisten the oral structures. The hourly rate of
non-masticatory swallowing is apparently related to the amount of saliva flow and, in most
instances, may be an involuntary reflex activity.

• Masseter muscles contract and the tip of the tongue touches the roof of the mouth during normal
swallowing.

• Tooth contacts are of longer duration in swallowing than in chewing, but there is wide variation
in frequency and duration form one person to another.

SUPPORTING CUSPS (Stamp or Centric cusps)-maxillary lingual cusps & mandibular buccal cusps
are the supporting cusps when the posterior teeth are in normal, ideal occlusion. Supporting cusps contact
the opposing teeth in their corresponding F-L center on a marginal ridge or fossa. Functioning cusps
(BUCCAL CUSPS OF MANDIBULAR TEETH).
• Centric stops-areas of contact that a supporting cusp makes with opposing teeth (i.e. the M-L cusp
of the maxillary first molar (a supporting cusp makes contact with the central fossa (central stop) of
the mandibular first molar).

• Supporting cusps are more robust and better suited for crushing food than non-supporting cusps.

5 Characteristics of Supporting Cusps:

1. Contact the opposing tooth in the intercuspal position.
2. Support the vertical dimension of the face.
3. Are closer to the F-L center of the tooth than non-supporting cusps.
4. Their outer incline has a potential for contact.
5. Have BROADER, MORE ROUNDED CUSP RIDGES than non-supporting cusps.

NON-SUPPORTING CUSPS (Guiding or Shearing cusps)-maxillary buccal cusps & mandibular

lingual cusps. Non-supporting cusps overlap the opposing tooth without contacting the tooth. These cusps
have sharper ridges that serve to SHEAR FOOD as they pass close to the supporting cusp ridges during
chewing strokes. Non-functonal cusps. PALATAL CUSPS OF MAXILLARY TEETH.

During POSTERIOR CROSS-BITE, supporting and non-supporting cusps are opposite. The
maxillary buccal and mandibular lingual cusps are supporting cusps, and the maxillary lingual and
mandibular buccal cusps are non-supporting (guiding).


POSTERIOR OCCLUSION CONTACTS IN IDEAL

INTERCUSPATION (VERY IMPORTANT SECTION)

OCCLUSION PICKET FENCE

Maxillary First Premolar:

• BUCCAL cusp opposes the facial embrasure between the mandibular first and second premolars.

• LINGUAL cups occlude in the distal triangular fossa of the mandibular first premolar.

• During lateral excursive movements, the maxillary first premolar buccal cusp ridge on the
working side opposes the distal cusp ridge of the first premolar and the mesial cusp ridge on the
second premolar.

Mandibular First Premolar:

• BUCCAL cusp occludes in the mesial triangular fossa of the maxillary first premolar and distal
marginal ridge of the canine.

• LINGUAL cusp of permanent mandibular first premolars do not occlude with anything. Lingual
 cusp is a very small cusp not really acting as a guiding cusp will oppose the lingual embrasure
between the maxillary canine and maxillary first premolar.

Maxillary Second Premolar:

• BUCCAL cusp occludes in the facial embrasure between the mandibular second premolar and
mandibular first molar.

• LINGUAL cusp occludes in the distal triangular fossa of the mandibular second premolar.

Mandibular Second Premolar:

• BUCCAL cusps occlude in the mesial marginal ridge area of the maxillary second premolar.

• LINGUAL cusp opposes the lingual embrasure between the maxillary first and second premolars.

Maxillary First Molar: (5 cusps)

• MB cusp: occludes in the mesiobuccal groove of the mandibular first molar. MB cusp is the key
reference point in the definition of Class I occlusion.
• DB cusp: occludes in the DB groove of the mandibular first molar. This distobuccal groove also
serves as an escapeway for the ML cusp of the maxillary first molar during non-working
excursive movements.
• ML cusp: occludes with the central fossa of the mandibular first molar.
• DL cusp: occludes with the distal marginal ridge of the mandibular first molar and mesial
marginal ridge of second molar.
• Cusp of Carabelli: found on the MESIOLINGUAL aspect of the first molar crown.
• Oblique ridge: opposes the developmental groove between DB and D cusps of the mandibular
first molar.

Mandibular First Molar: (5 Cusps)

• MB cusp: occludes with the mesial marginal ridge (MMR) of the maxillary first molar and distal
marginal ridge (DMR) of the maxillary second premolar.
• DB cusp: occludes in the central fossa of the maxillary first molar.
• D cusp: occludes with the distal triangular fossa of the maxillary first molar.
• ML cusp: opposes the lingual embrasure between the maxillary first molar and second premolar.
• DL cusp: opposes the lingual groove of the maxillary first molar.

Maxillary Second Molar: (4 Cusps)

• MB cusp: occludes with the buccal (facial) groove of the mandibular second molar.
• ML cusp: occludes in the central fossa of the mandibular second molar.
• DL cusp: occludes on the distal marginal ridge (DMR) of mandibular second molar and mesial
marginal ridge (MMR) of mandibular third molar.

Mandibular Second Molar: (4 Cusps)

• MB cusp: occludes in the mesial marginal ridge (MMR) of the maxillary second molar and
distal marginal ridge (DMR) of the maxillary first molar.
• DB cusp: occludes with the central fossa of the maxillary second molar.
• ML cusp: occludes with the lingual embrasure between the maxillary first and second molars.
 • DL cusp: opposes the lingual groove of the maxillary second molar.

Maxillary Third Molar: (3 Cusps)

• ML cusp: occludes in the central fossa of the third mandibular molar.
• DL cusp: is usually missing.

Mandibular Third Molar:

• MB cusp: occludes on the distal marginal ridge of the maxillary second molar and on the mesial
marginal ridge of the maxillary third molar.
• DB cusp: occludes in the central fossa of the maxillary third molar.
• ML cusp: occludes in the lingual embrasure between the maxillary second and third molars.

In ideal intercuspation, ML cusps of permanent mandibular molars occlude with the LINGUAL
EMBRASURE between their class counterpart and the tooth MESIAL to it.

In ideal intercuspation, buccal cusp tips of permanent maxillary premolars oppose the facial
embrasure between their class counterpart and the tooth DISTAL to it.

All maxillary buccal cusps and mandibular lingual cusps are GUIDING CUSPS. The inner occlusal
inclines leading to these cusps are called guiding inclines because in contact movements they guide the
supporting cusps away from the midline. Thus, there are bucco-occlusal inclines (lingual inclines of the
buccal cusps) of the maxillary posterior teeth and linguo-occlusal inclines (buccal inclines of the lingual
cusps) of the mandibular posterior teeth.

During mandibular movements (working or non-working), outer aspects of the lingual cusps of
mandibular molars will not contact their maxillary antagonists. All other areas of buccal and lingual
cusps may contact during mandibular movements (assuming a normal occlusal relationship).


ANTERIOR OCCLUSION CONTACTS IN IDEAL

INTERCUSPATION

Maxillary Central Incisor-overlaps vertically and horizontally with the mandibular central and lateral
incisors, and its lingual surface is in opposition to them.

Mandibular Central Incisor-the labioincisal angle opposes the mesial marginal ridge of the maxillary
central incisor and maxillary central’s lingual fossa.

Maxillary Lateral Incisor-overlaps the mandibular lateral and canine, and the lingual surface is in
opposition to them.

Mandibular Lateral Incisor-the labioincisal angle opposes the distal marginal ridge of the maxillary
central, and the mesial marginal ridge of the maxillary lateral, and the lingual fossa.

Maxillary Canine-cusp tip is in the facial embrasure between the mandibular canine and first premolar.
Its cusp tip does not contact any other tooth.

Mandibular Canine-cusp tip is in the lingual embrasure between the maxillary canine and maxillary
lateral incisor. Its cusp tip does not contact any other tooth.


ANGLE’S CLASSIFICATION OF HUMAN OCCLUSION

(MALOCCLUSION)

1. CLASS I (neutrocclusion)-the most common (70% of population). MB cusp of the maxillary first
molar occludes with the MB groove of the mandibular first permanent molar.
• Maxillary central incisors overlap the mandibular centrals.

• Maxillary canine lies in the labial embrasure between the mandibular canine and
mandibular first premolar (the maxillary canine occludes with the distal half of the
mandibular canine and mesial half of the mandibular first premolar).

2. CLASS II-less common (25% of population). M-B cusp of the maxillary first molar is anterior to the
M-B groove of the mandibular first molar (MB cusp is between the mandibular first molar and second
premolar (the buccal groove of the mandibular first molar is distal to the M-B cusp of the maxillary
first molar). In class II, the mandible is small or micrognathicm and the mandible and chin may appear
small and withdrawn.
• Class II (Division 1): the permenant 1st molars are in class II and permenant maxillary
central incisors are in their normal slightly protruded position (retruded mandible with one
or more maxillary anterior teeth protruded facially).

• Class II (Division 2): permenant 1st molars are in class II and permanent maxillary central
incisors are retruded and tilted lingually (retruded mandible with one or more maxillary
anterior teeth lingually inclined).

• Mandibular central incisors occlude more posterior to the maxillary incisors so that they
may not touch.

• Maxillary canine is mesial to the mandibular canine (the distal surface of the mandibular
canine is distal to the mesial surface of the maxillary canine). Maxillary canine is anterior
to the labial embrasure of the mandibular canine and first premolar (often called
distoocclusion).

3. CLASS III-least common (less than 5% of population). M-B cusp of the maxillary first molar is
between the mandibular first and second molar (the buccal groove of the mandibular first molar is
mesial to the M-B cusp of the maxillary first molar). The M-B cusp of the maxillary first molar is
posterior to the M-B groove of the mandibular first molar. Mandible is large or prognathic, and the
chin may protrude like a bulldog’s does.
• Mandibular incisors overlap anterior to the maxillary incisors.

• Maxillary canine is distal to the mandibular canine (the distal surface of the mandibular
canine is mesial to the mesial surface of the maxillary canine). Maxillary canine is
 posterior to the labial embrasure of the mandibular canine and first premolar (often called
mesioocclusion).

• In an acquired Class III crossbite, as the mandible retrudes, the maxillary lateral
incisor contacts the canine and lateral incisors.

MB CUSP of the PERMANENT MAXILLARY FIRST MOLAR is the REFERENCE POINT in

identifying Angle’s Class I, II, and III occlusion.

OPEN BITE RELATIONSHIPS involve failure of the teeth in both arches to meet properly. Open
bites may be observed in the anterior or posterior region and may be attributable to supraeruption of the
adjacent teeth or infraeruption of the teeth in the area of question. In addition to thumb sucking, open bites
may be caused by deviant growth patterns or a forward tongue position.

• ANTERIOR OPEN BITES (Apertognathia) are much more common in African Americans than
Caucasians, whereas DEEP BITES are much more common in Caucasians.

• A child with an anterior open bite of moderate severity most likely has a THUMB SUCKING
HABIT (or any sucking habit).

MANDIBULAR ARCH is SLIGHTLY SHORTER in length than the MAXILLARY ARCH.

• Sum of M-D diameter of maxillary teeth is ~128mm.
• Sum of M-D diameter of mandibular teeth is ~126mm.

OCCLUSAL PLANE-an imaginary surface related anatomically to the cranium and theoretically touches
the incisal edges of the incisors and tips of the occluding surfaces of the posterior teeth. It is not really a
plane, but represents the mean curvature of the surface.
• Anterior point of the occlusal plane is determined by the position of the anterior teeth.
• Posterior determinants are anatomical landmarks (2/3 the heights of the retromolar pads). Thus, it is
debatable as to the extent of control the dentist may exercise over the orientation of the occlusal
plane.

CURVE OF SPEE-the CONCAVE ANTERIOR-POSTERIOR CURVATURE of the MANDIBULAR

OCCLUSAL PLANE starting at the canine cusp tip, continuing through all posterior buccal cusp tips and
anterior ramus, and ending at the anterior portion of the mandibular condyle.
• Reducing the Curve of Spee can reduce the vertical overlap of teeth.
• Curves upward from anterior to posterior.
• On the Curve of Spee, molar crowns tilt MESIALLY and roots tilt DISTALLY.
CURVE OF WILSON-the MEDIOLATERAL concave curve across one side of the mandibular arch to
the other side. Contacts the buccal and lingual cusps on each side of the arch. Results from an inward
inclination of the mandibular posterior teeth, making the lingual cusps lower than the buccal cusps on the
mandibular arch; the buccal cusps are higher than the lingual cusps on the maxillary arch due to the
outward inclination of the maxillary posterior teeth. FOR MANDIBUALAR TEETH, THE CURVE OF
WILSON IS ALSO CONCAVE AND CONVEX FOR MAXILLARY TEETH.
• Purpose of the Curve of Wilson is to complement paths of the condyles during mandibular
movements.

• With the Curve of Wilson, mandibular crowns tilt lingually and roots tilt buccaly. The crowns of
maxillary teeth incline buccally and roots tilt lingually.

• Curve of Wilson grows deeper posteriorly so the molar have greater inclination than premolars.

• Curve of Wilson causes the buccal cusps of mandibular molars lingual cusps of maxillary molars
APPEAR LONGER than they actually are.

CURVE OF MONSON (Compensating Occlusal Curve)- refers to the plane formed by the combination
of the Curve of Spee and Curve of Wilson. The anteroposterior and lateral 3-D curvature in the
alignment of the occluding surfaces and incisal edges of artificial teeth which is used to develop a
balanced occlusion. The form of the compensating curve is entirely under the dentist’s control (i.e. if
during a try-in evaluation a dentist notes that a protrusive excursion movement results in the separation of
posterior teeth, the problem can be corrected by simply increasing the compensating curve). CONCAVE
FOR MANDIBULAR, CONVEX FOR MAXILLARY.

• Compensating curve allows the dentist to alter the effective cusp angulation without changing
the form of the manufactured denture teeth. The function of this curve is to help provide a
balanced occlusion. A prominent compensating curve is required when there is a steep condylar
path associated with a low degree of incisal guidance.

CURVE OF MONSON


CENTRIC OCCLUSION (MICP), CENTRIC RELATION, & REST

CENTRIC OCCLUSION (MICP)-a “tooth-guided” position defined as the maximum intercuspation

of the teeth. During typical “empty mouth swallowing” the mandible is braced in the inter-cuspal
position.
• when the teeth are in centric occlusion (intercuspal position), the position of the mandible in
relation to the maxilla is determined by the intercuspation of the teeth.

• during centric occlusion, the jaws are most fully closed, so the vertical dimension is the least.

• During centric occlusion, the supporting (contacting cusps) are the lingual or palatal cusps of the
maxillary teeth and the buccal cusps of the mandibular teeth. The lingual cusps of the mandibular
teeth are not in contact during CO.

• Empty mouth swallowing occurs frequently during the day and is an important to rid the mouth of
saliva, and moisten the oral structures. The hourly rate of non-masticatory swallowing is related to
the amount of salivary flow and is usually an involuntary reflex activity.

• Masseter muscles contract and the tongue tip touches the roof of the mouth during normal
swallowing.

• Tooth contacts are longer during swallowing than chewing, but this varies among people.

CENTRIC RELATION (“Retruded Contact Position”)-a “ligament-guided” position that is the

supero-anterior position of the condyle along the articular eminence of the condyle with the
articular disc interposed between the condyle and eminence. This position is an optimum relative
position between all anatomic components, and is a REPEATABLE reference position to mount casts on
the articulator.

CR is the most unstrained, retruded anatomic and functional position of the mandibular
condyle heads in the mandibular glenoid fossae of the TMJs. CR is a “bone-to-bone”
relationship (bones of the upper and lower jaws) independent of tooth contact. The presence or
absence of teeth and type of occlusion are not factors. CR IS INDEPENDENT OF TOOTH
CONTACT and occurs when the condyles articulate with the THINNEST AVASCULAR
PORTION OF THEIR RESPECTIVE DISCS WITH THE COMPLEX IN THE ANTERIOR-
SUPERIOR POSITION AGAINST THE SLOPES OF THE ARTICULAR EMINENCES.

CENTRIC RELATION (CR)-a mandibular position slightly posterior to maximum

intercuspation. It a path of opening and closing without translation of the mandibular condyles in
which the condyles are in their uppermost, midmost positions in the mandibular fossae and related
anteriorly to the distal slope of the articular eminence. Because the mandible rotates around a
transverse axis through the condyle in centric relation movement, guidance of jaw by the dentist in
opening and closing movements that do not have translation is called hinge axis movement. In this
 position (CR), the condyles are in the terminal hinge position. It is a ligament-guided position.

Malposed or super-erupted teeth can cause a discrepancy between CR & CO, so opposing teeth
should not contact when making a CR record to mount diagnostic casts because the contact causes
the mandible to deflect or move away from CR.

Mandible cannot be forced into CR from the rest position because the patient’s reflex
neuromuscular defense would resist the applied force. Rather, the mandible should be relaxed and
gently guided into CR.

To place a patient in CR, have the patient swallow, turning the tongue upward towards the palate,
relax the jaw muscles, or protruding and retruding the mandible can be effective ways to help
record CR.

In fixed and removable prosthodontics, CR should be established PRIOR to designing the

frameworks.

When a CR record is taken in the natural dentition, imprints of the teeth should be confined to
CUPS TIPS and the registration material should not be perforated.

CR is a “ligament-guided” position. CR is the closing end-point of the retruded border

movement (terminal-hinge movement).

Transverse Horizontal Axis (Terminal Hinge Position)-the one relation of the condyles to the
fossae in which a pure hinging movement is possible.

In complete denture prosthodontics, the position of the planned MIC of the teeth in centric
occlusion is established to coincide with the patient’s CR (CO = CR).

PHYSIOLOGIC REST POSITION (Postural Position)-determined by the musculature. The usual

reflex cited as the basis for the postural position of the mandible is the tonic stretch reflex of the
mandible levators (i.e. myotatic reflex). It is a muscle-guided position.

CANINES should ideally provide the predominant guidance through the full range of movement in
lateral mandibular excursions = CANINE PROTECTED (GUIDED) OCCLUSION-an occlusal
relationship where the vertical overlap of the maxillary and mandibular canines produces a disclusion
(separation) of all of the posterior teeth when the mandible moves to either side. All other teeth,
once they move from centric relation, do not contact. If there is contact of other teeth, its is called
“working side” or “non-working side” interference depending on which side the mandible moves
towards.

ANTERIOR GUIDANCE (anterior coupling)-a tightly overlapping relationship of opposing maxillary

and mandibular incisors and canines that produces disclusion of the posterior teeth when the mandible
protrudes and moves to either side. Anterior guidance is the result of horizontal and vertical overlap.

GROUP FUNCTION (unilateral balanced occlusion)-an occlusal relationship in which all posterior
teeth on a side contact evenly as the jaw is moved toward that side.
A TOOTH NORMALLY has contact with two teeth in the opposing arch EXCEPT the
MANDIBULAR CENTRAL INCISORS & MAXILLARY THIRD MOLARS. In the mandible, a tooth
is situated more mesially and lingually than its counterpart in the maxilla. Accordingly, each mandibular
tooth in the intercuspal position contacts two maxillary teeth-its class counterpart and the tooth
immediately mesial to it (i.e. the mandibular first molar makes contact with the maxillary first molar and
second premolar).

• MANDIBULAR CENTRAL INCISORS only occlude with ONE OTHER TOOTH. They only
oppose the maxillary central incisor. Mandibular central incisors will also contact the maxillary
incisors in centric, protrusive, and lateral protrusive movements.


ARTICULATION, OCCLUSAL BALANCE, VDO

ARTICULATION-relationship of teeth during movements into and away from the eccentric position,
while the teeth contact.

BASIC PRINCIPALS FOR OCCLUSAL ADJUSTMENT:

1. Maximum distribution of occlusal stresses in centric relation (CR).
2. Occlusal forces should be borne as much as possible by the long axis of teeth.
3. When there is surface-to-surface contact of flat cusps, change it to point-to-surface contact.
4. Once centric occlusion (CO) is established, never take the teeth out of centric occlusion.

OVERJET-the HORIZONTAL overlap or protrusion of the maxillary ANTERIORS commonly present

in Class II, division I malocclusion. Overjet is typically 2-4 mm measured with a probe. Think of a “jet
airplane” flying horizontally.

OVERBITE-the VERTICAL overlap of maxillary anteriors over mandibular anteriors common in Class
II, division II malocclusion.

ARCON ARTICULATOR (Articulated Condyle)-an articulator with its condylar elements on the
LOWER member of the articulator and condylar path elements on the UPPER member. The angle
between the condylar inclination and occlusal plane is FIXED on this articulator. ANGLE BETWEEN
CONDYLAR INCLINATION & OCCLUSAL PLANE REMAINS CONSTANT (MORE
ACCURATE).
• Commonly used for diagnostic mounting of study casts to allow examination of occlusal contacts
in the retruded contact position and analysis of tooth contacts during excursive movements of the
mounted models.

• Occlusal records in right and left lateral excursions are necessary for setting both the medial and
superior condylar guides.

• Fabrication of cast and porcelain restorations to ensure correct tooth contacts in occlusion and
mandibular movements.

NON-ARCON ARTICULATOR (Non-Articulated Condyle)-has condylar elements on the upper

member and condylar path elements on the lower member. Angle between condylar inclination and
occlusal plane is NOT CONSTANT (NOT FIXED) WHEN OPEN vs. CLOSED (LESS
ACCURATE). Most popular design to fabricate dentures.

• Non-adjustable-has a SMALL AXIS OF ROTATION.

• Semi-adjustable-gives a closer approximation of the axis of rotation & teeth and does not allow
intermediate tracking of condylar elements.
 • Fully adjustable: reproduces ALL border movements including progressive side shift and
immediate side shift (BENNET’S MOVEMENT).

WORKING SIDE: teeth on the side the mandible is moving toward. When the mandible moves to the
right and maxillary and mandibular teeth on the RIGHT side is the working side. For acceptable working
contact, a denture must have the canine and at least 4 other cusps contacting the opposing teeth.

BALANCING SIDE: the side OPPOSITE to the side the mandible is moving toward. When the
mandible moves to the right, the maxillary and mandibular teeth on the LEFT is the balancing side (with
natural teeth, the balancing side = non-working side). For acceptable balancing side contact, at least 3
cusps must touch, but NOT THE CANINE.

PROTRUSIVE-forward movement of the mandible during which there must be at least 3 points of
contact (the anterior incisor, and one tooth on EACH side of the arch as far posterior as possible).
• Protrusive record, records the relation of the maxilla & mandible, and is used to set the horizontal
condylar guidance on the articulator. Made with mandibular anterior teeth 6mm forward of CR, or
with mandibular & maxillary anterior teeth edge-to-edge).

• Christensen’s Phenomenon-the space that opens b/t posterior teeth during anterior movement of the
mandible. Amount of posterior separation is affected by both the incisal guidance and the horizontal
condylar guidance.

• Protrusive Movement-accomplished when the mandible is moved straight forward until the
maxillary and mandibular incisors contact “edge-to-edge”. This movement is bilaterally symmetrical
in that both sides of the mandible move in the same direction. The mandible can protrude ~10mm.

BILATERAL BALANCED OCCLUSION-the stable simultaneous contact of opposing upper &

lower teeth in CR position with a smooth bilateral gliding contact to any eccentric position within the
normal range of mandibular function, developed to lessen or limits tipping or rotation of denture bases in
relation to the supporting structures. MAXIMUM NUMBER OF TEETH CONTACT IN ALL
EXCURSIONS (CENTRIC & ECCENTRIC POSITIONS) for DENTURE STABILITY. USED
WHEN SETTING DENTURE TEETH.

Posterior Teeth Contacts in a Balanced Occlusion:

Cusp-to-fossa contact in centric occlusion (MICP) in an ideal Class I occlusion.
►

During lateral excursions, opposing cusps contact on the WORKING SIDE.

►

During lateral excursions, on the balancing side, maxillary lingual cusps (lingual inclines) contact
►

mandibular facial cusps (lingual inclines).

Balanced occlusion occurs when a complete denture has balance on the working side, non-working side,
and in protrusion. This assumes the denture has been constructed in proper CR and VDO. BILATERAL
BALANCED IS THE OCCLUSION FOR COMPLETE DENTURES.

5 Factors To Establish Balanced Articulation (some of these, if not all, are controlled by the dentist):
1. Inclination of the condylar guidance which is completely dictated by the PATIENT.
2. Inclination of the incisal guidance (horizontal and vertical overlap).
 3. Inclination of the occlusal plane (plane of orientation).
4. Convexities of the compensating curve.
5. Angle and height of cusps.

GROUP FUNCTION (“Unilateral Balanced Occlusion”)-ALL TEETH ON THE WORKING SIDE

CONTACT DURING WORKING MOVEMENT. ONLY working side contacts from anterior and
posterior teeth and no non-working side contacts. USED FOR SINGLE CROWNS/TEETH.

ALL posterior teeth on a side contact evenly as the jaw moves toward that side (working
side). All teeth on the non-working side DO NOT contact. Only teeth on the working side
contact during a lateral excursion.

Non-working (balancing) interferences: occur on inner inclines of FACIAL cusps of

mandibular molars.

Working side (non-balancing) interferences: occur inner aspects of LINGUAL cusps of

maxillary molars.

Protrusive Interferences-occur between DISTAL inclines of FACIAL cusps of maxillary

posterior teeth and MESIAL inclines of FACIAL cusps of mandibular posterior teeth.
Purpose of making a record of protrusive relation is to register the condylar path and adjust
the condylar guides of the articulator so they equal the patient’s condylar paths.

VERTICAL DIMENSION OF OCCLUSION (VDO): in a complete denture patient, when the teeth,
occlusal rims, and central bearing point are in contact, and the mandible is in CR, the LENGTH of the
face is the occlusal vertical dimension.
• VDO is the vertical length of the face as measured between tow arbitrary selected points (one
above and one below the mouth) when the teeth or any substitute material (occlusal rims) are in
contact in CR. Phonetics and esthetics help verify a patient’s vertical dimension of occlusion.

Evalute Correct VDO with 4 Methods:

1. Evaluating overall appearance of facial support.

2. Visual observation of space between occlusal rims at rest.

3. Measurement b/t dots on the face (placed on the tip of nose and chin with a Thompson stick)
when the jaws are at rest and when the rims are in contact.

4. Observation when “s” sound is enunciated accurately and repeatedly to ensure adequate speaking
space between the occlusal rims/occlusal plane.

Excessive VDO may result in trauma to underlying supporting tissues. A CLOSED vertical
dimension is the most likely cause of CHEILOSIS in patients who wear a complete denture with a non-
contributory medical history.
• Establish the VDO BEFORE making a CR record.
• Teeth contact during swallowing, but NOT during speech. If teeth touch during speaking, VDO is
too great.
When the mandible is in it’s physiologic rest (postural position), TEETH DO NOT CONTACT.
Physiologic rest position occurs when the mandible and all of its supporting muscles (8 muscles of
mastication + suprahyoids & infrahyoids) are in their resting posture (there is muscular equilibrium). This
lack of tooth contact is the “freeway space” or “interocclusal distance” and averages 2-6mm. This
position is a “muscle-guided” position and is the beginning and end point of most mandibular movements.

Interocclusal Distance (“Freeway Space”)-the vertical distance or space created when the mandible is
in its physiologic rest position between incisal and occluding surfaces of maxillary and mandibular teeth
or occlusion rims. NEVER INCREASE the freeway space more than 1.5mm.

Rest position of the mandible (postural position) is determined mostly by musculature. The usual
reflex cited as the basis for the mandible’s postural position is the tonic stretch reflex of the
elevator muscles. The rest position is a “muscle-guided” position.

EXCESSIVE VERTICAL DIMENSION (VDO): may result from trauma to underlying supporting
tissues (denture patient), straining of the elevator/closing muscles, and adversely affects interocclusal
clearance (decreased freeway space) causing loss of interocclusal distance in the rest position. Excessive
vertical dimension is the usual causes of CLICKING OF DENTURE TEETH (to treat remount and
fabricate a new complete denture).

• THE MOST CAUSE OF CHEEK-BITING WITH DENTURE PATIENTS IS LACK OF

VERTICAL OVERLAP OF POSTERIOR TEETH. Corrected by reducing the buccal surface of
the offending mandibular tooth to create additional horizontal overlap to provide an escape for the
buccal mucosa. Also caused by overclosure and teeth situated too far buccally.

• Clicking of dentures can also be caused by lack of retention of the maxillary & mandibular
dentures. To treat, if due to underextension, border mold and reline. If due to overextension,
reduce as indicated with PIP and disclosing wax.

• Porcelain teeth can also cause denture clicking. To treat, use acrylic resin teeth. Increased
VDO is the usual cause of contacting/clicking of posterior teeth when a patient speaks.

Decreased vertical dimension (VDO): an occluding vertical dimension causing EXCESSIVE INTER-
OCCLUSAL DISTANCE (increased freeway space) when the mandible is in the physiological rest
position.
• Example: people with no teeth or who have worn dentures for a long time present with the lower
portion of the face scrunched up, or do not show their lips anymore (poor facial profile). To
correct, make new dentures and increase VDO. This decreases inter-occlusal distance (freeway
space).
▪ DECREASED VDO often results in CHEEK BITING.

Factors to consider when verifying VDO:

Pre-extraction records
Amount of interocclusal distance (freeway space) to which the patient was previously accustomed.
Esthetics (facial harmony and facial expression are considered).
Phonetics (speech sounds).
 Length of the lip in relation to the teeth.
Condition and amount of shrinkage of the ridges.

Vertical Dimension of Rest (VDR)-the vertical length of the face measured between two arbitrary points
(1 point above & 1 below the mouth) when the mandible is in the rest position. In a physiologically
healthy individual, there is always a vertical space between the teeth (freeway space) when the mandible
is in the rest position. This position is important in complete denture fabrication because it provides a
guide to the VDO.
VDR = Vertical Dimension of Occlusion (VDO) + Interocclusal Distance.

Balanced Centric Occlusion in partial dentures is necessary for appliance stability. The framework’s
design and relationship of the teeth to the ridges also influence RPD stability.

Bilateral Eccentric Occlusion is NOT an objective in RPD construction, UNLESS the partial
prosthesis is opposed by a complete denture. The vertical relation for RPDs is usually determined by
the remaining natural teeth (unlike complete dentures).

CONDYLAR GUIDANCE-a factor TOTALLY dictated by the patient. It is the mechanical device on
an articulator intended to produce similar guidances in articulator movement that are produced by the
condyle paths during mandibular movements.
• Condylar guidance is completely dictated by the patient and cannot be varied or “adjusted”
by the dentist.

• The inclination of condylar guidance depends on: shape & size of the bony contour of the TMJ
(fossae and disc), action of the muscles attached to the mandible, limiting effects of the ligaments,
and the method used for registration.

• The incline (angulation) of the condylar element on the articulator is anatomically related to the
slope of the condylar articular eminences (condylar inclination).

• When adjusting the condylar guidance for protrusive relationship, the incisal guide pin on the
articulator should be raised out of contact with the incisal guide table. The protrusive record is
probably the LEAST reproducible maxillomandibular record.

• When restoring the entire mouth with crowns, the protrusive condylar path inclination influences
the mesial inclines of the mandibular cusps.

• RETRUSIVE MOVEMENT requires the condyles to move BACKWARD & UPWARD.

• LATERAL MOVEMENTS, the working condyle moves down, forward, and laterally, and non-
working condyles move down, forward, and medially.

• The inclination of the condylar path during protrusive movement forms an average angle of ~30°
with the horizontal reference plane. If the protrusive inclination is steep, the cusp height may be
obviously longer. If the inclination is shallow, the cusp will be shorter. This factor is the MOST
important aspect of condylar guidance that affects the selection of posterior teeth with
 appropriate cusp height.

• In complete dentures, the condyle path during free mandibular movements is governed mainly by
the SHAPE of the fossa and meniscus (articular disc) and the muscular influence.

DETERMINANTS OF OCCLUSION:
• Right & left TMJs.
• Occlusal surfaces of teeth and the neuromuscular system. The concepts of occlusal arrangement
aim to place artificial teeth in harmony with the TMJ and neuromuscular system. If done properly,
it results in minimum stress on the teeth and requires minimal effort by the neuromuscular system
when performing mandibular movements. Optimal occlusion requires minimum adaptation by the
patient.

4 Dentition Features that Effect PDL Health & Hard Tissue Anchorage to Resist Occlusal Force:
1. Anterior teeth have slight or no contact in MICP (intercuspal position).
2. Occlusal table is < 60% of the overall F-L width of the tooth.
3. Occlusal table is at right angles to the tooth’s long axis.
4. Mandibular molar crowns are inclined 15-20° toward the lingual.

4 Theoretical Determinants Required to Restore a Complete & Functional Occlusal Surface:

1. Amount of vertical overlap of anterior teeth. The anterior determinant of occlusion is the
horizontal and vertical overlap relationship of the anterior teeth.
2. Contour of the articular eminence.
3. Amount and direction of lateral shift in the working side condyle.
4. Tooth position in the arch.

However, the jaw relationship most commonly used in the ACTUAL design of restorations is the
ACQUIRED centric occlusion. The height of the pulp horn of a particular tooth is NOT a required
determinant to restore a complete and functional occlusal surface.

CUSP INCLINATION-angle made by the slopes of a cusp with a perpendicular line bisecting the cusp,
measured mesiodistally or buccolingually. Cusp inclination is under the dentist’s control (choosing 30°
teeth, monoplane teeth, etc.).

▪ In a protrusive condylar movement (protrusion), interferences can occur between DISTAL

inclines of maxillary posterior cusps and MESIAL inclines of mandibular posterior cusps.

▪ In a protrusive movement, the mandibular condyles move DOWNWARD & FORWARD.

▪ During protrusive movement, there are occlusal contacts occurring on the maxillary distal inclines
and mandibular mesial inclines. Anteriorly, the facial surface of the mandibular incisors will
contact the guiding inclines (lingual) of the maxillary incisors and canines.

▪ In any restorative case involving ALL teeth in the mouth, the protrusive condylar path inclination
will have its primary influence on the same inclines (distal of maxillary & mesial of mandibular).

▪ The pathway followed by the anterior teeth during protrusion may not be smooth or straight because
 of contact between the anterior teeth and sometimes the posterior teeth.

Centric Interference (Forward Slide)-corrected by grinding MESIAL INCLINES of maxillary

teeth and DISTAL INCLINES of mandibular teeth.

This group function of teeth on the working side evenly distributes the occlusal load. While,
the lack of contact on the non-working side prevents those teeth from receiving destructive,
obliquely directed forces found in non-working interferences, and saves the centric holding cusps
(i.e. mandibular buccal cusps and maxillary cusps) from excessive wear. The advantage is the
maintenance of the occlusion.

MUTUALLY PROTECTED OCCLUSION (“Canine Guided” or Organic Occlusion)-anterior teeth

protect the posterior teeth in all mandibular excursions. Canines DISCLUDE the posterior teeth during
working and non-working movements.
• Canine Guidance is an occlusal relationship exists where the vertical overlap of maxillary &
mandibular canines causes disclusion (separation) of ALL posterior teeth when the mandible
moves to either side. All other teeth do not contact once they move from CR. If there is contact of
other teeth, “working side” or “non-working side” interferences occur depending on which side the
mandible moves towards.

• When placing a crown on a maxillary canine, if you change a canine protected occlusion to group
function, you increase the chance for “non-working side” interferences.

ANTERIOR GUIDANCE (Anterior Coupling)-result of horizontal & vertical overlap of anterior

teeth. A tightly overlapping relationship of opposing maxillary and mandibular incisors and canines that
DISCLUDE the posterior teeth when the mandible protrudes and moves in lateral excursion. Anterior
guidance also affects the surface morphology of posterior teeth. The greater overlap, the longer the
cusp height.

INCISAL GUIDANCE-a measure of the amount of movement and the angle at which the lower incisors
and mandible must move from the overlapping position of centric occlusion to an edge-to-edge
relationship with the maxillary incisors. Incisal guidance is the second end-controlling factor in
articulator movement and is to some degree, under the dentist’s control. Influencing factors are
esthetics, phonetics, ridge relations, arch space, and inter-ridge space.
• Esthetics & phonetics are the main factors the LIMIT a dentist’s control of incisal guidance.
• Incisal guidance on the articulator is the mechanical equivalent of horizontal and vertical overlap.

SUPPORTING CUSPS (“Stamp Cusps” or “Centric Cusps”)-these cusps contact the opposing teeth in
their corresponding F-L center on a marginal ridge or fossa. These cusps are more robust and better
suited to CRUSH food. When posterior teeth are in a normal ideal relationship, maxillary lingual cusps
+ mandibular buccal cusps are considered the SUPPORTING CUSPS.

Centric Stops-areas of contact that a supporting cusp makes with opposing teeth (i.e. the ML cups
of the maxillary 1st molar (a supporting cusp) makes contact with the central fossae (centric stop)
of the mandibular 1st molar.
 5 Characteristics of Supporting Cusps:
1. contact the opposing tooth in the intercuspal position.
2. support the vertical dimension of the face.
3. are closer to the F-L center of the tooth than non-supporting cusps.
4. their outer incline has a potential for contact.
5. have broader, more rounded cusp ridges than non-supporting cusps.

NON-SUPPORTING CUSPS (“Guiding” or “Shearing” Cusps): maxillary buccal (facial) cusps +

mandibular lingual cusps. These cusps overlap the opposing tooth without contacting the tooth and have
narrower and sharper cusp ridges that serve to SHEAR food as they pass close to the supporting cusp
ridges during chewing strokes.

• The inner occlusal inclines leading to the guiding cusps are “guiding inclines” because in contact
movements, they guide supporting cusps away from the midline. Thus, there are the bucco-occlusal
inclines (lingual inclines of buccal cusps) of the maxillary posterior teeth, and the linguo-occlusal
inclines (buccal inclines of lingual cusps) of the mandibular posterior teeth.

In a posterior cross-bite situation, supporting and guiding cusps are opposite. The maxillary buccal
and mandibular lingual cusps are now the supporting cusps and the maxillary lingual and mandibular
buccal are the guiding cusps.

SELECTIVE GRINDING-the reduction of occlusal inferences usually done BEFORE constructing a

fixed bridge or denture for a patient to PREVENT duplicating the deflective occlusal contacts in the
final restoration. The purpose of selective grinding is to remove all interferences without destroying
cusp height. Thus, when interferences exist in centric, but not in lateral excursions, the fossa or marginal
ridge opposing the premature cusp is deepened. It is important that whenever a prematurity is found, the
occlusion be checked in all centric positions before any adjustment is made. If cusps interfere with each
other in excursions, then only the non-holding cusps are ground to prevent a decrease in VDO.
• A common case where it is preferable to selectively grind AFTER a fixed bridge or RPD is in place
is when a FPD or RPD is to be constructed for a space over which the opposing tooth has extruded
slightly. The bridge or partial is frequently constructed to the ideal plane of occlusion and the
opposing tooth is adjusted after insertion.

• The most common complaint after cementation of a fixed bridge is sensitivity to hot & cold and
indicates a deflective occlusal contact. The involved teeth may be sensitive to touch and when
brushing. In these cases, an immediate correction of occlusion must be made.

• Important: if you plan on changing a patient’s vertical dimension using crowns, it is critical to
mount the casts on the true hinge axis (face bow).

With Selective Grinding in Complete Denture Fabrication in Centric Relation (CR):

► Secondary centric holding cusps are the mandibular buccal cusps. Grind these cusps only if there is a
balancing side interference.

► Primary centric holding cusps are the maxillary lingual cusps. Never grind these cusps.
 ► Ideally, selective grinding should result in harmonious cusp-fossa contacts of all upper and lower
fossa (and marginal ridges of premolars). Do NOT grind the upper lingual or lower buccal cusps.
A forward slide from CR can be corrected by grinding the mesial inclines of maxillary teeth and
distal inclines of mandibular teeth.

► Selective grinding of inner inclines of secondary centric holding cusps is done if a balancing (non-
working) side interference exists.

► Only grind cusp tips on maxillary buccal & mandibular lingual (BULL) cusps if they are
premature in centric, lateral, or protrusive movements. Check before grinding.

► Selective Grinding in Working Side (non-balancing side) Relation: the rule for selective grinding
interferences during working side movements follows the rule of BULL (buccal cusp inner inclines
of upper teeth & lingual cusp inner inclines of lower teeth).

► Selective Grinding in Non-Working Side (balancing side) Relation: grind the inner inclines of
mandibular buccal cusps, and NEVER GRIND MAXILLARY LINGUAL CUSPS (primary
centric holding cusps).

OCCLUSAL ADJUSTMENT PRINCIPALS:

1. The maximum distribution of occlusal stresses in centric relation (CR).
2. Forces of occlusion should be borne as much as possible by the long axis of teeth.
3. When surface-to-surface contact of flat cusps occurs, it should be changed to a “point-to-surface”
contact (the cusp tip of the tooth occludes with the flat surface of it’s opposing tooth’s cusp).
4. When centric occlusion is established, NEVER take the teeth out of centric occlusion.
5. Never adjust cusp tips. Only marginal ridges and fossa.

NBDE PART I 1,001+ “HIGH-SPEED DRILL” PREVIEW
1. The medial wall of the axilla is covered by the SERRATUS ANTERIOR MUSCLES (this forms
most of the medial wall). The ribs and intercostal muscles form this wall.
2. The gateway to the mouth is between the SUPERIOR AND MIDDLE CONSTRICTOR
MUSCLES through which passes the stylopharyngeus muscle, glossopharyngeal nerve, and
stylohyoid ligament.

3. Major portions of the hard and soft palate are derived from the PALATINE SHELVES.

4. Difference between cellular and acellular cementum is CEMENTOBLASTS. Acellular

cementum lacks cellular components and covers 1/3-1/2 of the root. Cellular cementum is
more permeable, and covers 1/3-1/2 of the root apex where it binds to dentin.

5. The left coronary artery emerges from the beginning of the aorta NEAR THE TOP OF THE
HEART to deliver oxygen-rich blood to the heart.

6. Cholesterol is carried from the blood to the liver to be degraded and exerted by LDL.

7. ANTERIOR wall of axilla is formed by PECTORALIS MAJOR & MINOR.

8. Basilar artery (supplies brain with oxygen-rich blood) is formed by the two VERTEBRAL
ARTERIES at the junction of the medulla oblongata and pons. The basilar artery supplies blood
to the posterior part of circle of Willis.

9. Side of the palm is innervated by the ULNAR NERVE which enters the palm of the hand and
passes superficially to the flexor retinaculum and courses through the WRIST.

10. SERRATUS ANTERIOR (“big swing muscle”) is INNERVATED by the LONG THORACIC
NERVE (a branch of the brachial plexus).
11. INTERCOSTAL ARTERIES supply blood between the ribs (intercostal space), and are
located between the INTERNAL & INNERMOST INTERCOSTAL MUSCLES.
12. ENAMEL COMPONENTS include HYDROXYAPATITE (calcium phosphate), AMELOGINS,
AMELOBLASTINS, TUFTELINS, & ENAMELIN PROTEINS, OSTEONECTIN, &
HYALURONATE. ENAMEL DOES NOT CONTAIN COLLAGEN.

13. Basal Metabolic Rate (BMR): measures the amount of ENERGY expended while at rest in a
neutrally temperate environment, in the post-absorptive state (inactive digestive system due to 12
hours of fasting).

14. NUCLEUS AMBIGUUS is the nucleus that innervates the muscle derived from the
BRACHIAL ARCHES. It gives rise to efferent motor of the VAGUS NERVE terminating in the
laryngeal and pharyngeal muscles.
15. Injury to the SPINAL ACCESSORY NERVE causes an INABILITY TO RAISE THE
SHOULDER & ADDUCT THE SCAPULA (this nerve provides MOTOR to the
sternocleidomastoid and trapezius muscles).

16. VEINS that drain into the cavernous sinus (large collection of thin-walled veins) are the
OPHTHALMIC VEINS and SUPERFICIAL MIDDLE CEREBRAL & CORTICAL VEINS.
17. The INTERNAL CAROTID ARTERY & CRANIAL NERVES III, IV, V1, V2, & VI all pass
through the cavernous sinus (blood filled space). GALL BLADDER epithelium consists of
SIMPLE COLUMAR EPITHELIUM lining characterize by recesses.
18. Braches of the SUBCLAVIAN ARTERY (upper thorax and collar bone) on both sides are the
INTERNAL THORACIC, VERTEBRAL, & THYROCERVICAL TRUNK,
COSTOCERVICAL TRUNK, & DORAL SCAPULAR ARTERY.

19. TENDON of the TENSOR VELI PALATINI muscle glides around the PTERYGOID
HAMULUS (hook-like process of the medial pterygoid plate).
20. These are constant throughout the CNS: ENDOTHELIUM, SMOOTH MUSCLE, &
VASOVSORUM.

21. Skeletal muscle can HYPERTROPHY and have SHORTER ACTION POTENTIAL.

22. Parasympathetic innervation to the submandibular glands is provided by the CHORDA

TYMPANI (branch of facial nerve that synapses in the submandibular ganglion after which it
follows the lingual nerve, leaving the lingual nerve as it approaches the gland.

23. Most keratinized and numerous taste buds are the FILLIFORM PAPILLAE.
24. Abucent nerve: ABDUCTS THE LATERAL RECTUS MUSCLE OF EYE.

25. First branch of the subclavian artery is the VERTEBRAL ARTERY.

26. The HAZARD COMMUNICATION STANDARD requires DENTISTS to ENSURE

CHEMICAL SAFETY IN THE WORKPLACE by providing training, protective attire, labeling
chemical containers, and maintaining MSDS.

27. PERSONAL PROTECTIVE EQUIPMENT includes GLOVES, GOWNS, EYE

PROTECTION, & MASKS.
28. The process by which ALL life forms in an environment are COMPLETELY DESTROYED is
STERLIZATION.

29. STERILIZATION methods include STEAM UNDER PRESSURE AUTOCLAVE,

CHEMICAL VAPOR, DRY HEAT, and ETHYLENE OXIDE.

30. RED BLOOD CELLS are the cellular component of blood that caries OXYGEN and they do
NOT contain a nucleus.
31. SICKLE-CELL ANEMIA is a genetic condition that primarily affects AFRICAN
 AMERICANS due to a HEMOGLOBIN “S” DEFECT.
32. A common oral manifestation in patients with ACUTE MONOCYTIC LEUKEMIA (AML) is
GINGIVAL ENLARGEMENT.
33. GHOMPHOSIS is a joint that binds teeth to bony sockets (dental alveoli) in the maxilla and
mandible.
34. PDL proprioception is via the MESENCEPHLIC NUCLEUS.

35. Non-articulating surface of the TMJ is composed of PERIOSTIUM.

36. Smooth surface caries is caused by STREPTOCOCCUS MUTANS.

37. Junctional epithelium contains HEMIDESMOMES & BASAL LAMINA.

38. INCISIVE FORAMEN is an opening in the hard palate bone where blood vessels and nerve pass
through (ex: NASOPALATINE NERVES & SPEHNOPALATINE ARTERIES).
39. MAXILLARY 1st PREMOLAR & MAND 1st MOLAR MESIAL ROOTS are HOUR-GLASS
SHAPED.

40. Maximum opening of the mandible is 50mm.

41. There is no border movement in the REST POSITION.

42. The dental pulp contains FENESTRATED BLOOD VESSELS.

43. The EXTERNAL ACOUSTIC MEATUS lays POSTERIOR TO THE TMJ.

44. Maximum blood supply is found in the TMJ’s BILAMINAR ZONE.

45. The two-dimensional ANTERIOR-POSTERIOR CURVATURE of the MANDIBULAR

OCCLUSAL PLANE starting at the canine cusp tip, continuing through all posterior buccal cusp
tips and anterior ramus, and ending at the mandibular condyle is the CURVE OF SPEE.
46. The MEDIOLATERAL U-SHAPED CURVE of the occlusal plane of maxillary and mandibular
posterior teeth is the CURVE OF WILSON.

47. The HORIZONTAL overlap or protrusion of the maxillary anteriors, common in Class II,
division I malocclusion is OVERJET.
48. The VERTICAL overlap of maxillary anteriors over mandibular anteriors common in Class II,
division II malocclusion is OVERBITE.
49. Lateral misalignment of the arches resulting in the BUCCAL positioning of the mandibular molars
relative to the maxillary molars is POSTERIOR CROSSBITE.

50. Clinical features like GOITER, EXOPTHALMOS, WEIGHT LOSS, and GRAVE’S
DISEASE Exopthalmos) are associated with HYPERTHYROIDISM.
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