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Anatomy - Final - Exam - Notes

Anatomy and Physiology (Ryerson University)

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Anatomy Final Exam Notes

Blood (Chapter 17)


Functions of Blood
1. Distribution
Delivery of O2 and nutrients
Transport of metabolic waste and hormones
2. Regulation
Maintain body temp
Maintain normal pH (bicarbonate buffer)
Maintain fluid balance
3. Protection
Prevent blood loss
Prevent infection
Some immune functions

Composition of Blood (Formed elements and plasma)


55% Plasma
• 90% water
• Contains various solutes including hormones, nutrients, gases, proteins etc..
◦ Plasma proteins include albumin (important blood buffer), globulins and fibrinogens
• Makes of 55% of whole blood
45% Erythrocytes (hematocrit)
• Amiotic (full of haemoglobin, no room for nucleus)
• Special characteristics that contribute to gas exchange
◦ Biconcave shape provides huge surface area for its small size and all of cell's cytoplasm is
close to the surface
◦ Over 97% haemoglobin
◦ Generates ATP anaerobic and therefore does not consume any O2
• Each haemoglobin contains 2 alpha and 2 beta polypeptide chains and 4 heme groups, each
heme contains a central iron molecule, each RBC contains 250 million haemoglobin
• Haemoglobin is contained in erythrocyte in order to prevent it from increasing viscosity of
blood and osmotic pressure
• Erythropiesis
◦ All cells arise from a hemocytoblast in red marrow and permanently develop into a specific
type of blood cell
◦ Erythropiesis: myeloid stem cell-> proerythroblast-> basophilic erythroblasts (produce huge
amounts of ribosomes-> polychromatic erythroblast-> orthochromatic erythroblast (once all
of its haemoglobin is aquired, organelles are ejected, nucleus degenerates and pinches off)->
reticulocyte (young erythrocyte which enters blood stream and turns into mature erythrocyte
within 2 days)
▪ Reticulocyte count provides a rough index of rate of RBC formation
▪ During first 2 phases cells divide many times, haemoglobin is synthesized and iron
accumlates
▪ Stem cell to reticulocyte is approx 15 days
• Regulation of Erythropoiesis
◦ Hormone controls
▪ Erythropoitin (EPO)- stimulates formation of erythrocytes

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• When kidney cells become hypoxic O2 sensitive enzymes can not carry out function
of degrading HIF (hypoxia inducible factor) HIF accumulates and accelerates
synthesis and release of EPO
• Too many erythrocytes or too much O2 decreases EPO production
◦ Dietary requirements- raw materials required include amino acids, lipids, carbohydrates,
IRON, B vitamins also used for DNA production
• Destruction of Erythrocytes
◦ Lifespan 100-120 days
◦ Erythrocytes become fragmented with age and get trapped in small circulatory channels,
often the spleen
◦ Macrophages engulf old erythrocyte, haemoglobin separates and iron is recycled. Protein is
recycled into amino acids and heme group is degraded to bilirubin which is picked up by the
liver and secreted as bile
• Erythrocyte disorders
• Anemias- blood O2 carrying capacity is too low to support normals metabolism (3 categories:
blood loss, not enough blood cells produced, too many RBCs destroyed)
◦ Sickle cell anemia- sickle cell erythrocyte results from a single amino acid change in the
beta chain of haemoglobin, causes beta chains to link together under low O2 conditions,
forming stiff, spiky rods that rupture easily and can clog blood vessels
• Polycythemias- abnormally high amount of erythrocytes causing blood to become too viscous.
◦ Blood doping is artificially induced polycythemia
1% Buffy Coat (leukocytes and platelets)
• Platelets- megakaryocyte cell fragments
◦ Formation regulated by thromopoietin
• Leukocytes- the only true blood cells
◦ Immune functions
◦ 2 groups
▪ Granulocytes (functionally phagocytes)- includes neutrophils (active phagocytes),
eosinophils (attack parasitic worms and increase during allergic reaction) and basophils
(contain histamine, enhance inflammatory response)
▪ Agranulocytes (lack visible granules)- includes lymphocytes (immune cells) and
monocytes (differentiate into macrophages)
◦ Leuokopoiesis- directed by colony- stimulating factors and interleukins released by
supporting cells of the red bone marrow and mature WBCs
◦ Homeostatic imbalance includes leukaemias and mononucleosis

Hemostasis
3 Stages of Hemostasis
1) Vascular spasm- vasonconstriction, a strongly constricted artery can reduce blood loss for 20-30
minutes
2) Platelet plug formation- aggregation occurs, forming a plug that temporarily seals blood vessel
wall
Von Willenbrand factor stabilizes bound platelets forming a bridge between platelets and collagen
Adenosine diphosphate- aggregation agent that causes more platelets to stick to the the area
Serotonin and thromboxane A2- enhance vascular spasm and platelet aggregation
3) Coagulation- reinforcing platelet plug with fibrin threads that act as molecular glue which is
effective in sealing larger breaks
Process involving procoagulants turns blood to a gel

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Clot Retraction
Platelets contain actin myosin, as they contract they pull on surrounding fibrin strands, squeezing
serum from the mass, compacting the clots and drawing ruptured edges closer
As this is occuring the vessel is healing
Fibronolysis- removes unneeded clots when healing has occurred
Plasmin- produced when plasminogen is activated, destroys the clot (Begins within two days and
continues until is gone)

Factors Limiting Clotting (Prevent clot from becoming too large)


1) Swift removal of clotting factors
2) Inhibition of activating clot factors

Factors Preventing Undesirable Clotting


1) Smooth, intact endothelium prevent platelet pile up
2) Antithrombic substances prevent platelet adhesion
3) Vitamin E is an anticoagulant

Hemostatic Imbalance
1) Thromboembolic Disorders
Thrombus- clot that develops and persists in unbroken vessel
Embolus- clot that breaks away and begins circulation in the blood
Anticoagulant drugs include aspirin, heparin and warfarin, dabigatran is an alternative to warfarin
2) Bleeding disorders
Commonly caused by platelet deficiency and deficits of some clotting factors
Thrombocytopenia- deficiency of platelets
Impaired liver function can cause severe bleeding as liver is unable to synthesize clotting factors
Hemophilias- several hereditary bleeding disorders that have similar signs and symptoms
3) Disseminated Intravascular Coagulation
Widespread clotting in intact vessels, residual blood becomes unable to clot which can lead to blockage
and severe bleeding

Blood Typing
• Blood group is based on agglitinogen (antigen) present on red blood cell membrane
Genotype Phenotype Antigens on Serum Antibodies
Erythrocytes (Isohemaggliutinogens)
(Agglutinogen)
AA or AO A A Anti- B
BB or BO B B Anti- A
AB AB (Universal A and B None
recipient and least
common)
OO O (Universal donor None Anti-A and Anti-B
and most common) (Causes transfusion
reaction)

Bombay Phenotype- Rare blood type where individual with A, B, or AB group will appear as O

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Cross matching tests- Tests whether recipient's serum will agglutinate donor's RBCs or vice versa
Antigen- Anything the body perceives as foreign, generates an immune response
Blood Loss
Losing 15-30% of blood causes pallor and weakness
Losing 30%+ causes severe shock and can be fatal
Whole blood transfusions are used when blood loss is substantial
Packed red cells- used in other cases and are preferred for restoring O2 capacity

Blood Transfusion Reactions


When mismatched blood is transfused, the recipient's agglutinins clump the foreign RBCs, this may
block vessels. Clumps are then lysed and released Hb can cause renal shutdown
Two main problems
1) Transfused blood can not carry O2
2) Clumped RBCs in small vessels hinder blood flow to tissues beyond those points
Also, haemoglobin that escapes can cause renal shutdown leading to death

RH Blood Groups
• 52 Rh agglutinogens called Rh factors (common ones are C,D,E)
• Haemoltyic disease of a newborn
◦ The body of Rh- mothers carrying second Rh+ baby can cause a reaction against the baby
with antibodies, leads to severe clotting and can caused erythroblastosis fetalis
◦ Treatment involves injecting the mother with Rhogam to prevent a reaction

The Heart (Chapter 18)


Pericardium and layers of the heart wall
• Pericardium- double walled-sac
◦ Fibrous pericardium- loosely fitting superficial part of sac, protects heart and anchors it to
surrounding tissue, prevent overfilling
◦ Serous pericardium- deep to fibrous pericardium, thin, slippery
▪ Parietal layer- lines internal surface of fibrous pericardium, attatches to large arteries
exiting the heart
▪ Visceral layer/ epicardium- integral part of heart wall
▪ Between parietal and visceral layers is the pericardial cavity which contains a film of
serous fluid
• Pericarditis- inflammation of pericardium
• Cardiac tempande- large amount of fluid seep into cavity and impair heart function
• Layers of the heart wall
◦ Epicardium- visceral layer of serous pericardium
◦ Myocardium- cardiac muscle that forms bulk of heart
◦ Endocardium- sqamous epithelium lining heart chambers and covering fibrous skeleton of
valves

Heart Chambers
• 2 atria
◦ Right atrium
◦ Left atrium
◦ Blood enters right atrium via 3 veins
▪ Superior vena cava- returns blood from body areas superior to diaphragm
▪ Inferior vena cava- returns blood fro body areas below diaphragm

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▪ Coronary sinus- collects blood draining from myocardium


◦ Four pulmonary veins enter left atrium
• 2 ventricles
◦ Right ventricle forms most of hearts anterior surface, left ventricle dominates posterior
◦ Trabeculaue carneae mark interior of chambers, play a role in valve function
◦ Right ventricle pumps to pulmonary trunk which routes blood to lungs
◦ Left ventricle ejects blood into aorta

Valves
• 2 AV Valves
◦ One at each atria-ventricular junction
◦ Open in relaxation, closed in contraction, prevents backflow
◦ Right AV valve- tricuspid (3 cusps)
◦ Left AV valve- bicuspid (2 cusps)
• 2 SL Valves
◦ Guard bases of large arteries issuing from ventricles
◦ Aortic semilunar valves
◦ Pulmonary semilunar valves
◦ Open in contraction, closed in relaxation, prevents backflow
◦ Each have 3 cusps
• There are no valves guarding entrance to venae cavae and pulmonary veins, some blood does
spurt back, but it is minimal
• Insufficient values force heart to repump the same blood continuously
• Valvular stenosis- valve become stiff, constricting the opening, compels heart to contract more
forcefully

Systemic Circulation and Pulmonary Circulation


• The right side of the heart is the pulmonary circuit pump, it pumps blood through the lungs
where the blood picks up O2 and dumps CO2.
• The left side of the heart is the systemic circuit pump, it pumps blood through the body's
tissues , supplying them with O2 and nutrients and removing CO2 and waste
• Pathway of blood through the heart
◦ O2 poor systemic blood enters the right atrium, passes right ventricle, through pulmonary
trunk to the lung and back to the left atrium via the pulmonary veins.
◦ Oxygen laden blood entering the left atrium from the lungs flows into the left ventricle and
then into the aorta which provides the functional supply of all body organs. Systemic veins
return the O2 depleted blood to the right atrium.

Coronary Circulation
• Myocardium is too thick to diffuse nutrients, heart gets nourishment through coronary
circulation
• Coronary arteries arise from base of aorta and encircle heart in coronary sulcus
◦ Left coronary artery runs toward left side of heart, divides into 2 major branches
▪ Anterior interventricular artery- supplies blood to interventricular septum and anterior
walls of both ventricles
▪ Cirumflux artery- supplies left atrium and posterior walls of left ventricle
◦ Right coronary artery- courses to right side of heart, gives rise to 2 branches
▪ Right marginal artery- serves myocardium of lateral side of heart
▪ Posterior interventricular artery- runs to the heart apex, supplies posterior ventricular

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walls
◦ Blood delivery to the myocardium occurs during relaxation
• Coronary veins- paths roughly follow arteries, veins join to form coronary sinus which empties
blood into right atrium
• Angina pectoris- thoracic pain caused by fleeting deficiency in blood delivery to myocardium,
can lead to MI

Myocardial Contraction
• Myocardial cells at rest usually -85mv
• Automaticity/ autorhythmicity- some cardiac muscle is self excitable
• Events of Contraction
◦ Depolarization
◦ Plateau phase
◦ Re-polarization
• Energy Requirements: Cardiac muscle is abundant in mitochondria and is dependant on aerobic
respiration
• Heart Physiology
◦ Ability of heart to contract is intrinsic, however heart is supplied with autonomic nerve
fibers that can alter the basic rhythm
▪ Intrinsic conduction system – activity of the heart is a result of gap junctions and
conduction system which consists of noncontractile cardiac cells specialized to initiate
and distribute impulses
• Conduction system consists of SA and AV nodes, AV bundle and bundle branches
and subendocardial conducting network
◦ SA node has the fastest response to depolarization and sets the sinus rhythm
• Unstimulated contractile cells maintain a stable resting membrane potential
• Autorythmic cells have an unstable membrane potential that continuously
depolarizes, drifting slowly towards threshold
• These spontaneous changing membrane potentials (pacemaker potentials) initiate
action potentials that spread and trigger contractions
◦ Action potentials of pacemaker cells
▪ Pacemaker potential
▪ Depolarization
▪ Repolarization
◦ Sequence of excitation
◦ SA node generates impulses
◦ Impulse pause at AV node
◦ AV bundle connects atria to ventricles
◦ Bundle branches conduct the impulses through the interventricular septum
◦ The subendocardial conducting network depolarizes the contractile cells of both
ventricles
◦ Excitation- Contraction Coupling
1. Ca2+ induced Ca2+ release upon depolarization
Ca2+ that entered through sarcolemma triggers opening of Ca2+ channels in sarcoplasmic reticulum,
leads to more Ca2+ in cytosol
2. Ca2+ binds to troponin, revealing myosin binding sites of actin
3. Repolarization- cytosolic Ca2+ decreases
Active transport of Ca2+ back to SR
Also exit to extraculluar fluid via Na+-Ca2+ channels

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4. Long refractory periods (prevents tetanic contraction)


No summation of contractions

Electrocardiogram
• 3 waves
◦ P wave- results from movement of depolarization wave from SA node through to atria
(Approx 0.08s in length)
▪ Approx 0.1s after P wave begins, atria contract
◦ QRS complex- results from ventricular depolarization and precedes ventricular contraction
(Approx 0.08s in length)
◦ T wave- results from ventricular re polarization (Approx 0.16s)

Cardiac Cycle

• Heart Sounds
◦ Basic rhythm- lub-dub, pauses, lub-dub
▪ Pause indicates period of relaxation
▪ First sound (lub) occurs as AV valves close
▪ Second sound (dub) occurs as SL valves close
◦ Two other weak sounds are audible
◦ Heart murmurs- obstruction causes blood flow to become turbulent and generates abnormal
heart sounds
▪ Incompetent valve- fails to close properly
▪ Stenotic valve- fails to open properly
• Cardiac Cycle- includes all events associated with blood flow through heart during one
complete heart beat
◦ Ventricular filling- mid to late diastole- blood returning from circulation is flowing
passively through atria and open AV valves into ventricles, following depolarization atria

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contract, compressing blood into chambers, blood is propelled into ventricles, atria relax,
ventricles depolarize
◦ Ventricular systole (atria is diastole)- As atria relax, ventricles begin contracting, walls close
in on blood in their chambers, AV valves close, isovolumetric contraction phase, then SL
valves are forced open and blood rushes from ventricles into aorta and pulmonary trunk
◦ Isovolumetric relaxation- early diastole- ventricles relax, blood remaining in their chambers
(end systolic volume) is no longer compressed , blood in aorta and pulmonary trunk flows
backward, toward heart, closing SL valves and once again ventricles are completely closed
◦ At a normal heart rate of 75bmp, cardiac cycle lasts 0.8s

Cardiac Output
CO = HR x SV
• Cardiac reserve- difference between resting and maximal CO
• SV represent the difference between EDV and ESV
• Regulation of SV
◦ Preload- degree of stretch of heart muscle before contraction (high preload- high SV)
▪ Frank- starling law of heart- greater EDV gives optimal sarcomere length which gives
better stretch and therefor better contractiblity
◦ Contractility- contractile strength achieved at a given muscle length
◦ Afterload- back pressure exerted by arterial blood (pressure ventricles must overcome to
eject blood)
• Regulation of HR
◦ Autonomic regulation- when emotional or physical stressors act, sympathetic nerve fibres
release norepinephrine which binds to receptors, causing threshold to be reached quicker
◦ Chemical regulation- hormones (epinephrine and thyroxine) and ions (potassium and
calcium)
◦ Other factors include age, gender, exercise and temp
Activation of the sympathetic nervous system increases HR and contractility
Activation of the parasympathetic nervous system decreases HR but has little effect on contractility

Homeostatic Imbalance
• Congestive heart failure- pump is inadequate and can not meet circulation needs
• Coronary atherosclerosis- fatty build up that clogs coronary arteries
• Persistent high blood pressure- myocardium must exert more force to open AV valve eventually
causing myocardium to weaken
• Multiple MI- depresses pumping efficiency as scar tissue replaces dead heart cells
• Dilated cardiomyopathy- ventricles stretch and become flabby, myocardium deteriorates

Developmental Aspects
• The heart begins as a mesodermal tube
• By day 20 the endothelial tubes begin to fuse
• By day 22 the heart starts pumping blood
• By day 24 the heart continues to elongate and bend
• By day 28 the bending continues
• The fetal heart has 2 lung bypasses (foramen ovale and ductus arteriosus)
• Congenital heart defects
◦ Ventricular septal defect- superior part of interventricular septum fails to form (1/500 births)
◦ Coarctation of aorta- part of aorta is narrowed, increasing work load of left ventricle
(1/1500 births)

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◦ Tetralogy of falot- multiple defects including (1/2000 births)


▪ pulmonary trunk too narrow and pulmonary valve stenosed
▪ Hypertrophied right ventricle
▪ Ventricular septal defect
▪ Aorta opens from both ventricles

Blood Vessels (Chapter 19)


Blood Vessels
• 3 types
◦ Arteries- carry blood away from heart
▪ Arteriole system
• Elastic arteries- thick walled, near heart, large lumens make them low resistance
pathways, pressure reservoirs due to elastin present in all 3 tunics
• Muscular arteries- deliver blood to specific body organs, thickest tunica media, more
active in vasocontriction
• Arterioles- smallest, mainly smooth muscle with scattered elastic fibres when
arterioles constrict, tissues served are bypassed but when arterioles dilate the blood
flows into local capillaries
◦ Capillaries- provide direct access to nearly every cell in the body, exchange of gas and
materials
▪ 3 types
• Continuous capillaries (least permeable)- abundant in skin and muscles, endothelial
cells joined by tight junctions, leave gaps and which are large enough for limited
passage
• Fenstrated capillaries- endothelial cells are riddled with oval pores (fenestrations),
found where active capillary absorption of filtration occurs
• Sinusoid capillaries (most permeable)- highly modified, leaky capillaries, only in
liver, bone marrow, spleen, adrenal medulla, have large irregularly shaped lumens
with few tight junctions and many intracellular clefts which allows large molecules
and blood cells to pass through. Lining contains stellate macrophages
▪ Blood flow through capillaries
• 4 routes
◦ Lipid soluble- diffuse through lipid bilayer
◦ Water soluble- fluid filled intercellular capillary clefts
◦ Fenstrations
◦ Active transport (larger molecules, proteins, etc....)
▪ Bulk flow- fluid is forced out of capillaries through clefts at arterial end of capillaries
bed, most returns to bloodstream
▪ Hydrostatic pressure- force exerted by a fluid pressing against a wall
▪ Colloid osmotic pressure- force opposing hydrostatic pressure
▪ Net filtration pressure- considers all forces in capillary bed
◦ Veins- carry blood to heart
▪ Venules- capillaries united
▪ Veins- venules united
▪ Venous valves- folds of tunica intima, abundant in limbs where gravity gives resistance
to flow
▪ Venous sinuses- highly specialized, flattened veins with extremely thin walls, receive
support from surrounding tissues
• Vascular anastomoses- special interconnections between blood vessels

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◦ Arterial anastomoses- arteries supplying small area, provide collateral channels


◦ Arteriovenous anastomoses- connect arterioles and venules
◦ Venous anastomoses- connect veins, more common
• Walls of blood vessels
▪ Tunica intima- inner most later, contains endothelium
▪ Tunica media- middle layer, circularly arranged smooth muscle and elastin, vasomotor
nerve fibres cause vasocontriction or vasodilation, regulation of circulatory dynamics
▪ Tunica externa- external layer, woven collagen fibres for protection and anchoring
◦ In larger vessels lunica externa contrains vasa vasorum that nourish tissues of vessel wall
◦ Capillaries are only simple squamous epithelium

Physiology of Circulation
• Sources of resistance
◦ Blood viscosity
◦ Total blood vessel length (longer vessel = greater resistance)
◦ Blood vessel diameter
• Blood pressure

◦ Arterial blood pressure reflects how much elastic arteries can stretch and the volume of
blood forced into them
◦ Pulse pressure- the difference between systolic and diastolic pressure
◦ Mean arterial pressure- pressure that propels blood to the tissues
▪ Considers the fact that heart does not spend same amount of time in systole and diastole
▪ MAP= diastolic pressure + pulse pressure/ 3
◦ Capillary blood pressure is significantly lower because of fragility of capillaries
◦ Venous return (3 mechanisms)
▪ Muscular pump
▪ Respiratory pump
▪ Sympathetic venoconstriction
• Short term regulation of blood pressure
◦ Neural controls
▪ 2 main goals
1. Maintain adequate MAP by altering blood vessel diameter
2. Altering blood distribution to respond to specific demands of various organs
• Vasomotor centre- controls diameter of blood vessels, transmits impulse down
vasomotor fibers
◦ Blood pressure is modified by:
▪ Baroreceptor reflexes
• Baroreceptors- stretch receptors, when stretched they send an inhibitory
impulse that decreases blood pressure
◦ 3 mechanisms
▪ Arteriolar vasodilation- decreased output from vasomotor centre
allows arterioles to dilate, peripheral resistance and MAP fall
▪ Venodilation- decreased output from vasomotor center allows veins to
dilate, decreases venous return and CO
▪ Decreased cardiac output- as CO falls, so does MAP
▪ Chemoreceptors
• Transmit impulse to cardioaccelery center which activates reflexes
(regarding O2)

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◦ Higher brain centre = medulla oblongata


▪ Hormone controls
• Adrenal medulla hormones- epinephrine, norepinephrine- increase CO and
local vasoconstriciton
• Angiotesin 2- stimulates vasoconstriction
• Atrial natriuretic peptide (ANP) (from heart) – reduction of blood volume
and BP
• ADH- helps restore arterial pressure in extreme dehydration
• Long term regulation of blood pressure (renal mechanisms)
◦ Alter blood volume
◦ Decreased blood volume leads to fall in blood pressure
◦ Direct renal mechanisms
▪ Alters blood volume independently of hormones
▪ Blood volume or blood pressure rises, filtration rate speeds up
◦ Indirect renal mechanisms
▪ Renin- angiotensin-aldosterone mechanisms
▪ Blood pressure declines, kidney releases renin which enzymatically converts
angiotensinogen to angiotension 1, angiotensin converting enzyme (ACE)
converts it to angiotension 2 which acts in 4 ways
• Stimulates secreting of aldosterone
• Prods release of ADH
• Triggers thirst
• Promotes vasoconstriction
Lymphatics and Immune System (Chapter 20 and 21)
Lymphatic vessels
• Transport begins at lymphatic capillaries, very permeable due to minivalves
◦ Proteins in interstitial fluid are unable to enter blood but do enter lymphatic capillaries
◦ Lacteals- lymphatic capillaries that absorb fat
• Lymph flows to connecting vessels then to trunks then to ducts
◦ Trunks drain lymph at lumbar, bronchomediastinal, subclavian, jugular and intestinal trunks
◦ Right lymphatic duct drains lymph from right upper limb, head and thorax
◦ Thoracic duct receives lymph from rest of body
◦ Each terminal duct empties lymph into venous circulation at junction of internal jugular
vein and subclavian vein

Lymphoid cells
1. Lymphocytes- arise in bone marrow and mature into T lymphocytes (immune responses) and B
lymphocytes (production on plasma cells which release antibodies)
2. Macrophages
3. Dendritic cells- capture antigens and return them to lymph nodes
4. Reticular cells- produce reticular fiber- stroma which is the support network

Lymphoid tissue
• Roles
1. Houses and provides proliferation site for lymphocytes
2. Furnishes an ideal surveillance point for lymphocytes and macrophages
• Largely composed of reticular connective tissue
• Diffuse lymphoid tissue- loose arrangement of lymphoid cells
• Lymphoid follicle (nodules)- solid, spherical bodies consisting of tightly packed cells

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Lymph nodes
• Functions
1. Filtration of lymph
2. Immune system activation (site of immune response)

Lymphoid Organs
1. Primary Lymphoid Organs
• Lymphocyte development
• Fetal liver, bone marrow and thymus
2. Secondary Lymphoid Organs
• Lymphocyte activation
• Lymph nodes, spleen, and mucosa associated lymphoid tissue (Tonsils, appendix, Peyer's
Patches)

Immune System
• Two intrinsic dense systems:
1.Innate Defences
• Surface barriers- skin and mucosa, produce various substances including acid, enzymes, mucin,
defensins (antimicrobial peptides) and other chemicals
• Internal defences- phagocytes (neutrophils and macrophages), natural killer cells (kill cancer
cells and virus infected cells before adaptive defence is activated by detecting general
abnormalities, induce apoptosis) inflammation, antimicrobial proteins
◦ Antimicrobial proteins
▪ Interferons- secreted by infected cells in an effort to save adjacent cells
▪ Compliment proteins- plasma proteins that compliment immune response
◦ Opsonization- process of coating a pathogen in opsonins (complement proteins or
antibodies that provide handles for phagocyte receptors to bind)
◦ Roles of inflammation- prevents spread of damaging agents, disposes of cell debris and
pathogens, alerts adaptive immune system, sets stage for repair
2.Adaptive Defences
• “Third line of defence”
• Attacks particular foreign substances
• 4 properties
◦ Specificity
◦ Diversity
◦ Memory
◦ Tolerance
• Humoral immunity (B cells) and cellular immunity (T cells)
◦ Humoral immunity
▪ A naive B cell is exposed to an antigen, the cell is activated and cell division occurs, one
of these daughter cells becomes a memory cell, the other divides and produced
antibodies that cirulate and destroy the corresponding antigen by clumping (indirect
attack)
◦ Cellular immunity
▪ Naive T cell recognizes abnormalities that have been presented in fragments on infected
cells surface, T cells bind and are activated, T cells divide similarly to the B cell but
destroy the infected cell by poking holes in it and injecting enzymes (direct attack)
• Helper T cells are required for full activation of most B and T cells.

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◦ Cytotoxic T cells directly attack and kill infected cells


◦ Regulatory cells help maintain tolerance
• Primary response- the first exposure to antigen, response is slow and individual becomes very
sick
• Secondary response- cells recognize the antigen, response is faster and individual does not
become sick
• MHC- Major histocompatability complex, membrane bound glycoproteins that mark out cells
as “self”
◦ Present antigens to T cells
◦ Class 1 MHC proteins are found on all cells
◦ Class 2 MHC proteins are found only on specific antigen presenting cells
◦ In an infected cell, MHC changes and nonself antigens are presented
• Active vs Passive
◦ Active humoral immunity is acquired during an infection or vaccination and provides
immunological memory
◦ Passive immunity is conferred when a donor's antibodies are injected into the bloodstream
or when mother's antibodies cross into the bloodstream, immunological memory is not
established
• Natural immunity is acquired through infection or exposure to antigen, induced immunity is
acquired through vaccine or artificial exposure

Antibodies
• Antibody monomer- 4 polypeptide chains, each has a constant region which determines the
antibodies function and class and a variable region which enables the antibody to recognize its
specific antigen
• Five classes
◦ IgM
◦ IgA
◦ IgD
◦ IgG
◦ IgE
• Antibody functions
◦ Complement fixation
◦ Antigen neutralization
◦ Precipitation
◦ Agglutination

Homeostatic imbalance
• Immunodeficiency- includes AIDs caused by HIV and SCID syndromes, overwhelming
infections are fatal
• Autoimmune diseases- occurs when body regards its own tissues as foreign and mounts an
immune attack against them. Ex rheumatoid arthritis and multiple sclerosis
• Hypersensitivities- abnormally intense reaction to an otherwise harmless antigen

The Respiratory System (Chapter 22)


Functions of the Respiratory System
1. Supply O2
2. Remove CO2

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Components
• 2 zones
◦ Respiratory zone- site of gas exchange (bronchioles, alveolar ducts, alveolar)
◦ Conducting zone- all other resp passages, provide passage and cleanse, humidify and warm
air
• Respiratory membrane
◦ Walls of alveoli are single layer of squamous epithelium cells (type 1 alveolar cells)
surrounded by a thin membrane
◦ External surface of alveoli are densely covered with cobweb of capillaries forming
respiratory membrane with other structures
▪ Gas exchange occurs by simple diffusion through respiratory membrane
◦ Type 2 alveolor cells (cubodial epithelium) are scattered amid type 1 cells and secrete
surfactant and antimicrobial proteins
• Lungs
◦ Terminal bronchioles feed into respiratory bronchioles
◦ Left lung divided into superior and inferior lobes, separated by oblique fissure
◦ Right lung divided into superior, middle and inferior lobes by oblique and horizontal
fissures
◦ Lobules- smallest division of lung visible with naked eye
◦ Blood supply and innervation
▪ Pulmonary circulation- pulmonary arteries deliver systemic venous blood, pulmonary
arteries branch and feed into pulmonary capillary network, pulmonary veins convey
blood to heart
• Low pressure, high volume
▪ Bronchial circulation- bronchial arteries provide oxygenated systemic blood to lung
tissue
• High pressure, low volume, circulation to everything but alveolar
▪ Innervation- parasympathetic and sympathetic motor fibres and visceral sensory fivers
all enter lung through pulmonary plexus
• Parasympathetic fibres- cause constriction
• Sympathetic fibres- cause dilation
◦ Pleurae- form thin serosa, produces pleural fluid which fills pleural cavity allowing for
gliding of lungs during breathing

Breathing
• Pressure relationships
◦ Described relative to atmospheric pressure which is pressure exerted by air surrounding the
body
▪ Negative pressure indicated pressure lower than atmospheric pressure by a certain
amount
◦ Intrapulmonary pressure- pressure in alveoli
▪ Rises as falls with phases of breathing but always eqaulizes with atmospheric pressure
eventually
◦ Intraplueral pressure- pressure in pleural cavity
▪ Fluctuates with breathing, always about 4mmHg less than intrapulmonary pressure
• Pulmonary ventilation
◦ Volume changes lead to pressure changes, leading to the flow of gases to equalize pressure
▪ Boyles law
• P1V1 = P2V2

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• Inspiration
◦ Diaphragm contraction causes height of thoracic cavity to increase
◦ Intercostal muscles- contraction lifts rib cage and pulls sternum superiorly, expanding
diameter or thorax
▪ These actions expand the thoracic dimensions by nearly 500ml
▪ As thoracic dimensions increase, lungs stretch, intrapulmonary volume increases,
intrapulmonary pressure drops 1mmHg, air rushes into lungs along pressure gradient
▪ Inspiration ends when intrapulmonary pressure = atmospheric pressure, intrapleural
pressure declines 6mmHg
• Expiration
◦ Passive, dependant on lung elasticity
◦ As inspiratory muscles relax, thoracic and intrapulmonary volumes decrease, compressing
alveolar
◦ Intrapulmonary pressure rises 1mmHg, when intrapulomary pressure in greater than
atmospheric pressure, pressure gradient forces air out of lungs
• Lung properties
1. Compliance- lungs can stretch
2. Elasticity- lungs can recoil after stretch
• Respiratory Volumes
◦ Tidal volume (TV)- amount of air that moves in and out with each breath
◦ Inspiratory reserve volume (IRV)- amount of air that can inspired forcibly beyond TV
◦ Expiratory reserve volume (ERV)- amount of air that can expelled from lungs after a normal
tidal volume expiration
◦ Residual volume (RV)- air remaining in lungs
• Respiratory Capacities
◦ Inspiratory capacity (IC)- total amount of air that can be inspired after normal TV expiration
(sum of TV and IRV)
◦ Functional residual capacity (FRC)- amount of air remaining in lungs after normal TV
expiration (sum of RV and ERV)
◦ Vital capacity (VC)- total amount of exchangeable air (sum of TV, IRV, ERV)
◦ Total lung capacity (TLC)- sum of all lung volumes
• Pulmonary function tests (spirometry)
◦ Forced vital capacity (FVC)- amount of gas expelled when a subject takes a deep breath and
forcefully exhales maximally and rapidly
◦ Forced expiratory volume (FEV)- amount of air expelled during specific time intervals of
FVC test
• Anatomical dead space is the air-filled volume (about 150ml) of the conducting passageways. If
alveoli become nonfunctional their volume is added to dead space
• Alveolar ventilation is the best index of ventilation efficiency because it accounts for
anatomical dead space
◦ AVR= (TV- dead space) x respiratory rate

Gas Exchange and Transport


• Alveolor gas contains more CO2 and water vapour and less O2 than atmospheric air
• External respiration vs Internal respiration
◦ External respiration- the process of gas exchange that occurs in the lungs
▪ O2 enters capillaries, CO2 leaves blood and enters alveoli
▪ Influenced by partial pressure gradients, thickness of respiratory membrane, surface
area, and ventilation perfusion coupling

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◦ Internal respiration- gas exchange that occurs between the systemic capillaries and the
tissues
▪ CO2 enters the blood, O2 leaves the blood and enters the tissues
• Dalton's law of partial pressures- total pressure exerted by a mixture of gases is the sum of the
pressures exerted independently by each gas in the mixture
• Henry's law- when a gas is in contract with a liquid, the gas will dissolve in the liquid in
proportion to its partial pressure
◦ Blood O2 and Henry's Law
▪ For a liquid and gas at equilibrium, the amount of gas dissolved depends on solubility of
gas in fluid and partial pressure of gas (changes will altitude)
• O2 Transport
◦ Cooperative binding- once one O2 binds, the others bind more easily, unloading of one also
facilitates the unloading of others
◦ Rate of Hb binding and release of O2 is regulated by various factors including:
▪ PO2
▪ Temperature (higher temp= lower affinity for O2)
▪ Blood pH (increased Co2= more acidic= lower affinity for O2)
▪ PCO2
◦ Bohr effect: tense configuration (low O2 affinity)
▪ Stabalized by deceased pH, increased PCO2 in blood and increased temperature
◦ Hb has a higher affinity for O2 in lungs, lower affinity in tissues (related to Bohr effect,
allows for drop off of O2 in tissues)
◦ % saturation = (# of O2 molecules bound) / (# of binding sites) x100
◦ 2,3-biophosphoglyceric acid (2,3-BPG)
▪ Biproduct of anaerobic respiration
▪ Bonds with deoxyhaemoglobin and stabilizes it
• Favours O2 unloading (lowers affinity for O2)
• CO2 Transport
◦ 3 forms
▪ Dissolved in plasma (small amount)
▪ Chemically bound to haemoglobin (carbaminohaemoglobin)
▪ Bicarbonate ions in plasma
◦ Haldane effect- reflects greater ability of reduced hemoglobin to form
carbaminohaemoglobin and buffer H+ by combining with it (dissociation of O2 allows more
CO2 to combine with Hb)

Oxygen- Haemoglobin Dissociation Curve

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Control of Respiration
• Neural mechanisms
◦ Medullary respiratory centres are the ventral and dorsal respiratory groups
▪ Ventral group likely responsible for rhythmicity of breathing
◦ Pontine respiratory centres influence the activity of the medullary respiratory centres
Breathing Rate and Depth
• Rising CO2 levels cause reflexive increase in breathing rate and depth, low CO2 levels depress
respiration
• O2 levels affect breathing only indirectly by influencing peripheral chemoreceptor sensitivity to
change in CO2 levels
• Arterial O2 levels below 60mmHg is a major stimulus for respiration
• Changes in arterial pH act indirectly through peripheral chemoreceptors to alter ventilation
• Response to hypoventilation
◦ Hypoventilation leads to hypercapnia (high CO2) which leads to acidosis
◦ The response is hyperventilation which leads to hyopcapnia leading to alkalosis
◦ Response is then to lower breathing, cycling through until normal levels are achieved
• Response to exercise
◦ Exercise leads to hyperpnea (not hyperventilation) (arterial PO2 , PCO2 and pH remain
fairly constant)
• Response to altitude
◦ PO2 decreases with altitude, causing hyperventilation initially, PCO2 drops and alkalosis
occurs, affinity for O2 increases
◦ Over time -2,3-DPG increases, this decreases the affinity for O2 and there is more
unloading of O2 in the tissues
◦ In a long term scenario kidneys increase their erythropoitin production, RBC count
increases and there is more O2 carried in the blood

The Digestive System (Chapter 23)


Functions of the Digestive System

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1. Motility
2. Secretion
3. Digestion
4. Absorption
5. Storage
6. Elimination

Digestive Processes
1. Ingestion
2. Propulsion
3. Mechanical breakdown
4. Digestion
5. Absorption
6. Delectation

Components
• 2 main groups of organs
◦ Alimentary canal- GI tract
▪ Digests, breaks down and absorbs
▪ Mouth, pharynx, esophagus, stomach, intestines
▪ Layers of alimentary canal
• Mucosa- secretes, absorbs and protects
◦ Simple columnar (stratified squamous in mouth,esophagus and anus)
• Submucosa- contains lymph vessels and never fibres
◦ Areolar connective tissue, abundant elastic fibers
• Muscularis externa- responsible for segmentation and peristalsis
◦ Inner circular layer, outer longitudinal layer
◦ Often form spincters
• Serosa- outer most layer
◦ Areolar connective tissue covered in mesothelium
◦ Accessory digestive organs
▪ Teeth, tongue, gallbladder, digestive glands, salivary glands, liver, pancreas
▪ Produce secretions that help breakdown food
• Functional anatomy
◦ Mouth- digestion starts here, saliva contains amylase and antimicrobial agents, lubricate
mouth and dissolves chemicals, stimulates taste buds
◦ Salivary glands
▪ Extrinsic (major) salivary glands- outside oral cavity
▪ Intrinsic (minor) salivary glands- throughout oral cavity
▪ Saliva- mainly water, contains antibodies, enzymes and defensins
▪ Salivation- controlled by parasympathetic NS by salivary nuclei in brain stem
◦ Esophagus
▪ Skeletal muscle for upper, smooth muscle for lower
▪ Swallowing
• Buccal phase (upper esophageal sphincter contracts, tongue presses against hard
palate
• Pharyngeal esophageal phase (uvula and larynx rise, tongue blocks off mouth,
esophageal spincter relaxes, food enters)
• Constrictor muscles of pharynx contract

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• Paristalsis
• Gastrointensinal sphincter opens (food enters stomach)
◦ Stomach
▪ Regions
• Cardia- surrounds cardial orifice, where food enters, has mucous glands which
secretes protective secretions
• Fundus- dome-shaped area
• Body- mix of food and stomach secretions
• Pyloris- allows food to pass to intestines, funnel-shaped, narrows to pyloric canal,
terminating at pylorus
• Lining of stomach- simple columnar epithelium, mucus cells
◦ Contains gastric pits and glands
▪ Cells and Secretions
• Mucous neck cells- muscous
• Parietal cells- HCL
• Chief cells- pepsinogen
• Enteroendocrine cells (G cells [gastrin] and ECL cells [histamine, seratonin])
▪ Mucosal barrier- createe from thick coating of bi-carbonate rich mucous on stomach
wall, joined by tight junctions that prevent leaking of gastric juices, damaged cells are
shed and quickly replaced
▪ Essential function of the stomach- intrinsic factor (polypeptide needed for vitamin B12
absorption in intestine)
▪ Digestive processes in stomach
• Gastric secretion
◦ Cephalic (reflex) phase- before food enters stomach
◦ Gastric phase- 3-4hrs
▪ Stimuli- distension, peptides and low acidity
▪ ACH release increases gastric juice output
▪ Neural influences- gastrin
◦ Intestinal phase
• Gastric motility
◦ Propulsion
◦ Grinding
◦ Retropulsion
• Stomach filing
◦ Receptive relaxation of smooth muscle and stomach fundus with food moving
through esophagus into stomach
◦ Gastric accomodation- smooth muscle plasticity, stretch without increasing
tension
• Gastric contractile activity
◦ Peristalsis begins at gastroesophageal sphincter, rippling movement, stronger as
they reach plyoris
• Gastric emptying
◦ 4hrs after meal
◦ Liquids pass straight through
◦ Dependant on duodenum contents
◦ Small Intestine
▪ Duodenum
▪ Jejunum

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▪ Ilieum
▪ Intestinal juice- largely water, contains some mucus, enzyme poor
• Stimulation- hypertonic or acid chyme
◦ Pancreas
▪ Posterior to stomach, endocrine function by pancreatic islets (release insulin and
glucagon)
▪ Pancreatic juice- enzymes for food breakdown, includes bicarbonate solution and
digestive enzymes
◦ Liver
▪ Metabolic and hematological regulation, blood detox, carbohydrate metabolism, lipid
metabolism, vitamin storage (A,D,E,K,B12), iron storage (as ferritin), synthesis os
plasma proteins, bile production and secretion
▪ 4 lobes, tissue arranged in lobules, central vein in the middle
▪ Liver blood flow- hepatic portal system
• Digestion products absorbed into intestinal blood capillaries delivered to liver before
general circulation
◦ Extra capillary network- Intestinal capillaries-> hepatic portal vein -> hepatic
capillaries-> hepatic vein
▪ Liver gets venous blood from intestine, arterial blood from hepatic artery
▪ Bile- bilirubin, bile salts, phospholipids, cholesterol, inorganic ions
• Enterohepatic cirulation- recirculated between liver and intestine
• Gallbladder- stores, concentrates bile, sphincter of Oddi in common bile duct
▪ Large intestine- absorption of water, electrolytes, B, K vitamins and folic acid, no
digestion
• Columnar epithelium, goblet cells, no villi, bacterial flora
◦ Defecation
▪ 12-24hrs to reduce meal residue to feces
• Feces 75% water, 24% solids (bacterial, fibre, small amounts of protein,
sloughed epithelial cells, salts, mucous)
▪ Rectal pressure rises as feces accumulates
▪ Longitudinal rectal muscles contract to increase rectal pressure
• Stretch stimulates defecation reflex
◦ Intrinsic defecation reflex
◦ Parasympathetic defecation reflex
Digestion and Absorption
• Digestion of carbs
◦ Salivary amylase- digests starch
◦ Pancreatic amylase- digests other starch in small intestine
◦ Dextrinase and glucoamylase- act on oligosccharides composed of more than 3 simple
sugars
• Digestion of protein
◦ Pepsinogen- activaed to pepsin- breaks down proteins
◦ Trypsin and chymotrypsin- cleave proteins into smaller peptides
◦ Carbooxypeptidase- splits off one amino acid at a time
◦ Aminopeptidase and dipeptidase- breakdown final amino acid products
• Digestion of fat
◦ Lipases- fat digesting enzymes
◦ Bile salts form emulsions with fat, increasing surface area exposed to enzymes
• Digestion of nucleic acids

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◦ Pancreatic nucleases in pancreatic juice hydrolyse nucleic acids to nucleotide monomers


◦ Nucleosidases and phosphatases break them apart to free bases
• Fluid and electrolyte absorption- small intestine absorbs most water, osmotic gradient set up by
Na+/K+ pumps
◦ Salt and water reabsorption stimulated by aldosterone
◦ Large intestine can also secrete water via active transport of NaCl into intestinal lumen

Week 7- Metabolism

Metabolic Reactions
Metabolic Pathways
• Many steps
• Starts with specific molecules
• Finish with products
• Catalysed by enzymes

Metabolism
• Sum of all chemical reactions in the body
Anabolism and Catabolism
• Anabolism- the general term for all reactions that build larger molecules or structures from
smaller ones
◦ Uses energy
• Catabolism- all process that break down complex structures to simpler ones
◦ Release of energy
◦ Cellular respiration- foods are broken down in cells and some of the energy released is
captured to form ATP
▪ ATP then serves to links energy releasing catabolic reactions to cellular work
• Energy from catabolism drives anabolism

Nutrient Use in Cellular Metabolism


Three stages of metabolism of energy containing nutrients
1. Stage 1- Digestion in GI tract, lumen to absorbable forms, transport via blood to tissue cells
2. Stage 2- Anabolism (incorporation into molecules) and catabolism of nutrients to form
intermediates within tissues
3. Stage 3- Oxidative breakdown of stage 2 products occurs in mitochondria of tissue cells. CO2 is
liberated, and H atoms are removed ultimately delivered to molecular oxygen forming water.
Some energy released is used to form ATP

Catabolic Pathways
• Oxidize organic fuels produced by plants
• Yield ATP
◦ ATP provides energy for cellular work
◦ Involves transfer of electrons
• Fermentation
◦ Partial breakdown of sugars
◦ Without O2
• Cellular respiration
◦ Uses O2 and organic molecules to yield ATP

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◦ C6H1206 + 6O2 ------> 6CO2 + 6H20 + Energy (Redox reaction)


▪ Glucose is broken down
▪ Electrons get transferred from glucose to oxygen
▪ ATP is generated in the process
◦ Importance of cellular respiration
▪ Stepwise transfer of electrons
• Controlled release of energy
NAD+
• Nictotinamide adenine dinucleotide
• Electron acceptor
◦ Carries electrons from glucose
◦ Electrons not transferred directly from glucose to O2
• Coenzyme of dehydrogenase enzyme
◦ Remove pair of hydrogen atoms (2 electrons, 2 protons)
◦ Delivers 2 electrons and 1 proton to NAD+, neutralizes it to NADH (other H released)
• Connecting to energy concepts- NADH is the reduced form of NAD+ and stores potential
energy to be released
• Cellular respiration
◦ Reaction coupling
▪ ATP synthesis (energentically unfavorable)
▪ Glucose hydrolysis (energetically favourable)

Oxidation- Reduction Reactions


• Oxidation- molecule loses electrons, may involve the gain of oxygen or loss of hydrogen
◦ Oxidized substance loses electrons as they move towards the substance that strongly attracts
them
• Reduction- molecule gains electrons
• Oxidation reduction (redox) reactions- when one substances loses electrons (is oxidized) the
other gains electrons (is reduced)
◦ Dehydrogenases- enzymes that catalyse redox reactions in which hydrogen atoms are
removed
◦ Oxidases- enzymes that catalyse the transfer of oxygen
◦ Note: Most enzymes require help of specific co-enzymes derived from B vitamin.
▪ Although enzymes catalyse removal of hydrogen atoms, they can not hold onto the
atom, co-enzymes however can hold the hydrogen
▪ Two important enzymes in the oxidative pathays are nicotinamide adenine dinucleotide
(NAD+) and flavin adenine dinucleotide (FAD)

Phosphorylation
• Note: Reactions driven by ATP are coupled, enzymes shift its high energy phosphate groups to
other molecules which then said to be phosphorylated
• Phosphorylation primes a molecule to change in a way that increases its activity, produces
motion or does work
◦ Substrate level phosphorylation- occurs when high energy phosphate group is transferred
directly from a substrate to ADP to form ATP. This reaction occurs in both the cytosol and
mitochondrial matrix
▪ ATP formed directly during glycolysis and citric acid cycle
◦ Oxidative phosphorlyation- occurs in the mitochondria, carried out by electron transport
proteins that act as proton pumps to create a protein gradient across the inner mitochondrial

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membranes. Source of energy is released when food molecules are oxidized.


▪ Electron transport and chemiosmosis
▪ Provides 90% of ATP of cellular respiration

Metabolism of Major Nutrients

1)Carbohydrates
• Glucose breakdown
1. Gylcolysis
Converts glucose to pyruvate
2. Krebs cycle (TCA Cycle or citric acid cycle)
Oxidized pyruvate to CO2
3. Electron transport chain and oxidative phosphorylation
Coverts chemical energy to make ATP

Glycolysis- Splitting of glucose


▪ Uses 2 molecules of ATP per molecule of glucose
▪ Forms 4 molecules of ATP per molecule of glucose, yeilds 2 NADH and 2 H+ per
molecule of glucose and 2 pyruvate molecules
1. Phase 1- sugar activation- phosphorylation activates glucose, glucose is converted to
fructose-1, biphosphate
2. Phase 2- sugar cleavage- fructose-1, biphosphate is cleaved into two 3-carbon fragments
(dihydroxyacetone phosphate and gylceraldehyde 3-phosphate)
3. Phase 3- sugar oxidation- the 3-carbon fragments are oxidized and 4 ATP molecules are
formed
• Phase 1 and 2- Investment
• Phase 3- Payoff
• If O2 is present, pyruvic acids continues to the Krebs cycle, if O2 is not present
fermentation occurs and pyruvic acid is converted to lactic acid
• Enzymes involved include hexokinase, phosphoglucoisomerase, phosphofructoskinase,
aldolase, isomerase.

Krebs Cycle- fuelled by pyruvic acid and fatty acids


◦ Pyruvic acid enters mitochondria by active transport with help of transport protein
◦ Once there, transitional phase occurs (pyruvic acid is converted to acetyl CoA) this a
three step process
1. Decarboxylation- one of the pyruvic acid's carbons in removed and released CO2
gas. CO2 diffuses out of cells into blood, released by lungs
2. Oxidation- remaining 2C fragment (acetic acid) is oxidized by removing hydrogen
atoms which are picked up by NAD+
3. Formation pf acetyl CoA- Acetic acid is combined with coenzyme A to produce the
reactive final product acetyl coenzyme CoA
• Acetyl CoA is now ready to enter Krebs cycle
• Yield per cycle per molecule of acetyl CoA- 1 ATP molecule, 3 NADH, 1 FADH2
◦ Per glucose molecule the yield would be doubled

Electron Transport Chain and Oxidative Phosphorylation- carries out final catabolic reactions that
occur on mitochondrial cristae
• Oxidative phosphorylation

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• Oxidation of high energy electron carriers


◦ Yields energy
• Phosphorylation of ADP to ATP
• Electron Transport Chain
◦ Oxidation of NADH and FADH2
▪ Energy used to pump protons out of mitochondrial matrix
▪ Proton gradient is source of energy
• Drives phosphorylation of ADP
• Chemiosmosis
• Group of electron carriers
◦ 1 membrane of chain reduces the next

Cellular Respiration: Protons and ATP tally


• Cost of ATP
◦ Requires 3 protons to make 1 ATP
◦ 1 proton needed to get phosphate into matrix
◦ Overall cost: 4 protons per molecule of ATP
• 10 protons pumped for each NADH oxidized
• 6 protons pumped for each FASH2 oxidized

Oxidation of 1 glucose molecule yields


• 2 ATP and 2 NADH through gylcolysis
• 2 NADH through pyruvate dehydrogenase
• 6 NADH, 2 FADH2, 2 ATP through TCA cycle

Notes on ATP tally

Gylcogenesis, Glycogenolysis and Gluconeogensesis


• Glycogenesis- when high ATP levels begin to “turn off” glycolysis, glucose molecules are
combined in long chains to form glycogen
• Glycogenolysis- when blood glucose levels drop, gylcogen lysis occurs
• Gluconeogenesis- process of forming new glucose from noncarbohydrate molecules, when too
little glucose is available to “stoke metabolic furnance” glycerol and amino acids are converted
to glucose (occurs in liver)

2)Lipids
• Triglycerides are energy source lipids
• Lipogenesis- triglyceride synthesis
• End products of lipid digestion and cholesterol are transported in blood in the form of
chylomicrons
• Glyercol is converted to gylceraldehyde 3-phosphate and enters the Krebs cycle or is converted
to glucose
• Fatty acids are oxidized by beta oxidation into acetic acid fragments. These are bound to
coenzyme A and enter the Krebs cycle as acetyl CoA. Dietary fats not needed for energy or
structural materials are stored in adipose tissue.
• There is a continual turnover of fats in fat deposits.
• Lipolysis- breakdwon of fats to fatty acids

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• When excessive amounts of fats are used the liver converts acetyl CoA to ketone bodies and
releases them into the blood. Excessive levels of ketone bodies (ketosis) can lead to metabolic
acidosis
• All cells use phospholipids and cholesterol to build their plasma membranes. The liver forms
many functional molecules from lipids
• Triglyceride structure- glycerol and 3 fatty acids

• Proteins
• To be oxidized for energy, amino acids are converted to keto acids that can enter the Krebs
cycle. This involves transamination, oxidative deamination and keto acid modification
• Amine groups removed during deamination (as ammonia) are combined with CO2 by the liver
to from urea which is excreted in urine
• Deaminated amino acids may also be converted to fatty acids and glucose
• Amino acids are the body's most important building blocks. Nonessential amino acids are made
in the liver by transamination
• In adults, most protein synthesis serves to replace tissue proteins and maintain nitrogen balance
• Protein synthesis requires the presence of all 10 essential amino acids. If any are lacking, amino
acids are used as energy fuels.

Metabolic States of the Body


• Body in constant dynamic catabolic anabolic state
• Body draws on nutrient pools to meet varying needs
◦ Amino acid pool- body's total supply of free amino acids from diet or tissue breakdown
◦ Carbohydrate and fat pools are usually considered together
◦ 2 major differences between carb/ fat pool and amino acid pool
▪ Fats and carbohydrates are oxidized directly to produced cellular energy, amino acids
can be used to supply energy only after being converted to a carbohydrate intermediate
(keto acid)
▪ Excess carbohydrate and fat can be stored as such, excess amino acids are not stored as
protein, instead they are oxidized for energy of converted to fat or glycogen for storage
• Absorptive State- (fed state) is the time during and shortly after eating when nutrients are
flushing into blood from GI tract. During this state anabolism exceeds catabolism and nutrients
are stored, glucose is the major energy fuel
◦ Events are controlled by insulin which enhances the entry of glucose into cells and
accelerates its use for ATP synthesis or storage as glycogen or fat
• Postabsorptive State- (fasting state)- period when the GI tract is empty and body reserves are
broken down to supply energy. Net synthesis of fat, gylcogen and proteins ends and catabolism
of these substances begins to occur
◦ Events are controlled by glucagon and sympathetic nervous system which mobilize
glycogen and fat reserves and trigger gluconeogenesis

Sources of Blood Glucose


• Glycogenolysis in the liver
• Glycogenolysis in skeletal muscle
• Lipolysis in adipose tissue and liver
• Catabolism of cellular protein

Glucose Sparing- increased use of noncarbohydrate fuel molecules to conserve glucose

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Week 8- The Urinary System

Kidney Functions
• Regulating the total volume of water in the body and the total concentration of solutes in that
water (osmoality)
• Regulating the concentrations of various ions in the extracellular fluid
• Ensuring long-term acid base balance
• Excreting metabolic wastes and foreign substances
• Producing erythropoietin and renin
• Converting vit D to active form
• Carrying out gluconeogensis during prolonged fasting
Urinary system also includes
• Ureters- tubes that transport urine from kidneys to urinary bladder
• Urinary bladder-temporary storage reservoir
• Urethra- tube that carries urine from bladder to body exterior

Kidney Anatomy
• Three layers of supportive tissue
◦ Renal fascia- outer layer of dense fibrous connective tissue that anchors kidney and adrenal
gland to surrounding structures
◦ Perirenal fat capsule- a fatty mass that surrounds the kidney and cushions it against blows
◦ Fibrous capsule- a transparent capsule that prevents infections from surrounding regions

Renal ptosis- when one or both kidneys drop to a lower position because of change to fat capsule, may
lead to urinary backup which can lead to water in the kidney (hydronephrosis) which can lead to tissue
damage

Internal Kidney Anatomy


• Renal cortex- most superficial
• Renal medulla- deep to cortex, exhibit cone shaped tissue mass called medullary/ renal
pyramids (bundles of urine collecting tubules and capillaries)
◦ Renal columns separate the pyramids
◦ Pyramid and its surrounding tissue constitutes one of eight kidney lobes
• Renal pelvis- funnel shapes tibe continous with ureter leaving hilum
◦ Branching extensions form 2-3 major calyces, each subdivide to form minor calyces that
inclose papillae
▪ Calyces collect urine which drains contiously from papillae and empty it into renal
pelvis, the flows to ureter then to bladder

Blood and Nerve Supply


• Large blood supply, 1/4 of cardiac output
• Renal arteries exit from abdominal aorta , right renal artery longer than left
◦ As each renal artery reaches a kidney it divides into five segmental arteries which further
branch into several interlobar arteries
◦ At cortex-medulla junction they branch into arcuate arteries which radiate cortical radiate
arteries that supply cortical tissue
• Afferent arterioles branching from corticol radiate arteries begin a complex arrangement of
microscopic blood vessels, key element of kidney function

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• Veins trace pathway of arterial supply in reverse


• Renal plexus (autonomic nerve fibres and ganglia) provide nerve supply
• Celiac plexus (sympathetic nerve fibres) regulate blood flow by adjusting arteriole diameter and
influence formation of urine by the nephron

Nephrons
• Structural and functional units of the kidneys
• Carry out processes that form urine
• Collecting ducts collect fluid from several nephrons and convey it to renal pelvis
• Renal corpuscle- consists of a tuft of capillaries called glomerulus and a glomerular capsule
◦ Glmoerulus- fenstrated, large amounts of solute rich but protein free fluid passes from blood
into glomerular capsule
◦ Glomerular capsule
▪ Parietal layer- structural functions only
▪ Visceral layer- podocytes terminate into foot processes which interdigitate as they cling
to the basement membrane. Filtration slits at food processes that allows filtrate to enter
capsular space

Renal tubule and collecting duct


• Renal tubule
◦ Proximal convoluted tubule (PCT)- dense microvili for increased surface area and re
absorption
◦ Nephron loop- descending and ascending limbs
◦ Distal convoluted tubule (DCT) lack microvilli
• Collecting duct
◦ Principal cells- sparse short microvilli and are responsible for maintaining water and Na+
balance
◦ Intercalated cells- abundant microvilli
▪ Type A
▪ Type B
▪ Both play role in maintaining acid base balance of blood

Classes of Nephrons
• Cortical nephrons- most abundant, located almost entirely in cortex
• Juxtamedullary nephrons- originate near cortex medulla junction, play important role in kidneys
ability to produce concentrated urine, long nephron loops that deeply invade the medulla

Nephron Capillary Beds


• Glomerulus- specilazed for filtration, fed and drained by arterioles which maintains high
pressure needed for filtration
◦ Efferent and afferent arterioles
• Pertibular capillaries- cling closely to adjacent renal tubules and empty into nearby venules,
only experience low pressure and readily absorb solutes and water from the tubule cells as these
substance are reclaimed from the filtrate
• Vasa recta- extend deep into medulla paralleling the longest nephron loops. Play a role in
concentrated urine formation
• Juxtaglomerular complex (JGC)- 3 populations of cells that help regulate the rate of filtration
formation and systemic blood pressure
◦ Macula densa- chemoreceptors that monitor NaCl content of filtrate

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◦ Granular cells- act as mechanoreceptirs that sense blood pressure in afferent arteriole
◦ Extraglomerular mesangial cells- pass regulatory signals between macula densa and
granular cells

Mechanisms of Urine Formation


• 3 processes
◦ Glomerular filtration- produces protein free filtrate
▪ Passive process using hydrostatic pressure
▪ Filtration membrane, 3 layers
• Fenstrated endothelium of glomerular capillaries
• Basement membrane
• Foot processes of podocytes of glomerular capsule
▪ Pressure that impact filtration
• Outward pressures- promote filtrate formation
◦ Hydrostatic pressure in glomerular capillaries
◦ Colloid osmotic pressure in capsular space
• Inward pressures- inhibit filtrate formation
◦ Hydrostatic pressure in capsular space
◦ Colloid osmotic pressure in golmerular capillaries
• Glomerular filtration rate- volume of filtrate fromed each minute, proportional to 3
factors
◦ Net filtration pressure- controlled by changing diameter of arterioles
◦ Total surface area available for filtration- area available for filtration can be
contracted
◦ Filtration membrane permeability- fenestrations make it very permeable
• Regulation of glomerular filtration
◦ Intrinstic controls- renal autoregulation
▪ Myogenic mechanism
▪ Tubuloglomerular feedback mechanism
◦ Extrinsic controls- neural and hormonal mechanisms
▪ Sympathetic nervous system controls
▪ Renin- angiotensin aldosterone mechanism
◦ Other factors affecting GFR- adenosine and prostaglandin, locally acting
angiotensin 2
◦ Tubular res absorption- selectively moving substances from filtrate back into blood

◦ Tubular secretion- selectively moving substance from blood to filtrate

Evaluation of Kidney Function


• Renal clearnance- volume of plasma from which the kidneys clear a particular substance in a
given time , done to determine GFR
◦ Renal clearance = concentration of the substance in urine x flow rate of urine formation /
concentration of the substance in plasma (C= UV/ P)
• Urine- note the physical characteristics such as colour, transparency and odor
• Chemical composition of urine- 95% water, 5% solutes, urea is second largest component,
derived from breakdown of amino acids, other solutes include Na+, K+, PO43-, SO4

Urine Transport and Storage

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• Ureters- slender tubues that convey urine from kindeys to bladder


◦ Each begins at L2 as a continuum of the renal pelvis
◦ 3 layers
▪ Mucosa- contains transitional epithelium
▪ Muscularis- two smooth muscle sheets
▪ Adventitia- covering ureters external surface, fibrous connective tissue
• Urinary bladder
◦ Interior of bladder had opening for ureters and urethra
◦ Smooth triangular region of bladder has trigone
◦ 3 layers of bladder wall
▪ Muscoa containing transitional epithelium
▪ Muscular layer
▪ Fibrous layer
• Urethra
◦ Thin walled, muscular tube that drains urine from bladder and conveys it out of the body
◦ At the bladder- urethral junction, smooth muscle thickens to form the internal urethral
sphincter
◦ External urethra spincter surround urethra as it passes through the urogenital diaphragm and
it voluntarily controlled
◦ Females urethra is 3-4cm
◦ Males urethra is 20cm long and has 3 regions
▪ Prostatic urethra- runs with prostate
▪ Intermediate part of urethra- runs through the urogenital diaphragm, extends 2cm from
prostate to beginning of penis
▪ Spongy urethra -passes through penis and opens at its tip via external urethral orifice

Micturition
• Urination/ voiding
• For this to occur, 3 things occur simultaneously
◦ Detrusor must contract
◦ Internal urethral sphincter must open
◦ External urethral sphincter must open
• Accumulating urine stretches bladder wall which initiates the micturition reflex

Developmental Aspects of the Urinary System


• Three sets of kidneys develop from intermediate mesoderm
◦ Pronephric, mesonephric and metanephric)
• Metanephros excrete urine by 3rd month of development

Week 9- Fluid, Electrolyte and Acid-base Balance

Body Water Content


• Function of age, mass, sex, body fat

Fluid Compartments
• Intracellular fluid compartment
◦ Consists of trillions of tiny compartments (cells)
• Extracellular fluid compartments

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◦ Remaining 1/3 of fluid


◦ 2 subcompartments
▪ Plasma
▪ Interstitial fluid

Composition of body fluids


• Electrolytes and nonelectrolytes
◦ Nonelectrolytes- have bonds that prevent them from dissociating in solution ex glucose,
lipids, creatinine, urea
◦ Electrolytes- chemical compounds that dissociate into ions in water, can conduct and
electrical current ex salts, acids, bases and some proteins

Fluid movement among compartments


• Osmotic and hydrostatic pressures regulate the continuous exchange and mixing of body fluids
• Substances must pass plasma and If to reach ICF
◦ Exchanges between plasma and IF occur across capillary walls
◦ Exchanges between IF and ICF occur across plasma membranes

Water balance and ECF osmolality


• Metabolic water- body water produced by cellular metabolism (aka water of oxidation)
• Insensible water loss- water that vaporizes out of lungs or diffused directly through skin
• Rise in osmolality triggers:
◦ Thirst
◦ Release of ADH
• Decline inhibits both these

Regulation of water intake


• Thirst mechanism
◦ Osmoreceptors- increased osmolaity activates receptors
◦ Dry mouth
◦ Decrease in blood volume/ pressure

Influence of ADH
• ADH levels low- most water reaching ducts is not reabsorbed resulting in dilute urine and
reduced volume of body fluids
• ADH levels high- aquaporins inserted in principal cell apical membrane and nearly all filtered
water is reabsorbed, small volume of concentrated urine is excreted

Disorders of water balance


• Dehydration
• Hypotonic hydration
• Edema

Electrolyte Balance
• Role of Sodium- exert bulk of ECF osmotic pressure and control water volume and distribution
in body
• Regulation of sodium balance
◦ linked to ECF volume and blood pressure regulation, involves neural and hormonal controls
◦ Aldosterone promotes sodium reabsorption to maintain blood volume and pressure

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◦ Declining blood pressure and falling filtrate NaCl concentration stimulate granular cells to
release renin which enhances systemic blood pressure, Na+ reabsorbtion and water
excretion
◦ Atrial natruretic peptide causes systemic vasodilation and inhibits renin, aldosterone and
ADH release
◦ Estrogens and glucocorticoids increase retention of sodium, progesterone promotes sodium
and water excretion
◦ Cardiovascular system senses changing blood pressure and prompts changes in sympathetic
vasomotor activity

Regulation of Potassium Balance


• Renal tubular secretion of K+ in response to:
◦ Changes in K+ of ECF
▪ Increase secretion if ECF is high
◦ Changes in pH of peritubular fluid
▪ Decrease secretion if peritubular pH drops (more H+ is secreted in exchange for Na+)
◦ Aldoesterone levels
▪ Hormone stimulates secretion

Regulation of Calcium Balance


• Factors
◦ Calcium reserves in bone
◦ Digestive absorption
◦ Loss at kidnets
• Hormones
◦ Raise Ca2+ -parathyroid hormone (PTH, calcitriol)
◦ Decrease Ca2+ -calcitonin

Regulation of Phosphate
• Needed for bone minerization
• Reabsorbed in PCT (stimulated by calcitriol, inhibited by PTH)
• Fecal loss (but intestinal absorption supported by calcitriol and PTH)

Chloride Regulation
• Most abundant anion in ECF
• Absorbed across digestive tract with Na+
• Follows Na in PCT
• Less Cl- absorbed during acidosis (HCO3- favoured)
• Minimal loss in sweat and urine

Acid- Base Balance


• Balance between prodution and loss of H+
• Kidneys- secrete hydrogen ions into urine, generate buffers that enter bloodstream
• Lungs- eliminate CO2
• Narrow limit for ECF pH (7.35-7.45)
• Important for stability of plasma membranes, protein structure, enzyme function

Buffers
• Stabalize pH by providing or removing H+

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• Usually in combination of weak acid with its conjugate base (anion)


• 3 main body buffer systems
◦ Carbonic acid biocarbonate- important in ECF
◦ Phosphate- important for ICF and urine
◦ Protein- due to amphoteric nature of protein, carboxylic acid and amino group

Homeostatic Imbalances

Week 10- The Reproductive System

Anatomy of Male Reproductive System


• Testes
◦ Surrounded by two tunics
▪ Tunica vaginalis- outer layer, 2 layers derived from outpocketing of peritoneum
▪ Tunica albunginea- deep later, fibrous capsule
◦ Divided into 3 lobules that each contain coiled seminiferous tubules that produce sperm
▪ Myloid cells surround each seminiferous tubule and contract to help squeeze sperm and
testicular fluids through tubules
▪ Tubules converge to form a straight tubule that conveys sperm into rete testis and then to
efferent ductules and then its enters the epididymis
◦ Intersitial endocrine cells (Leydig cells) lie in soft connective tissue and produce andorgens
which is secreted into surrounding interstitial fluid
• Scrotum
◦ Located outside of the body since viable sperm can not be produced in abundance at core
body temperature, scrotum is approx 3 degrees lower than body temp
◦ Dartos muscle- layer of smooth muscle in superficial fascia that wrinkles the skin
◦ Cremaster muscles- bands of skeletal muscle that arise from internal oblique muscles that
elevate the testes

• Accessory sex glands empty secretions into ducts during ejaculatorion are the seminal glands,
the prostate and the bulbo-urethral glands
• Penis
◦ Dorsal and ventral surface are named in reference to erect penis
◦ Contains spongy urethra and 3 long cylindrical bodies of erectile tissue each covered by
dense fibrous connective tissue
▪ Erectile tissue- network of connective tissue and smooth muscle with vascular spaces
◦ Corpus spongiosum- surrounds urethra
◦ Corpora cavernosa- paired erectile bodies that make up most of penis
• Duct system
◦ Sperm delivered from testes through epidiymis, ductus deference, ejaculatory duct and
urethra
◦ Epididymis
▪ Sperm maturation and storage
▪ Tightly colied, 6m long
▪ Becomes vas deferns

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▪ Lined with ciliated columnar epithelium which secretes fluid to support sperm
▪ Smooth muscle wall moves sperm along
◦ Vas deferens
▪ Continues from epididymis
▪ Passes through inguinal canal in abdomen
▪ Reaches posterior side of bladder
▪ Lined with partially ciliated columnar epithelium
▪ Ampulla- expanded portion
▪ Joins with duct of seminal vesicle and together for ejaculatory duct which passes
through the prostate gland to join the urethra
◦ Seminal vesicles
▪ Posterior side of bladder
▪ Coiled membranous pouches
▪ Lining secretes fluid into ejaculatory duct
• Alkaline (pH modifies pH of sperm)
• Fructose (provides energy for sperm)
• Prostoglandins (promotes muscular contractions of female genital tract)
◦ Urethra
▪ Conveys both urine and semen
▪ 3 regions
• Prostatic urethra- portion surrounded by prostate
• Intermediate part of urethra- membranous urethra, in urogenital diaphragm
• Spongy urethra- runs through penis and opens to outside of external urethral orifice
• Accessory Organs
◦ Prostate
▪ Encircles urethra, inferior to bladder
▪ Has capsule with fibrous connective tissue that divides gland into lobes each with 40-50
tubules
▪ Secretes fluid into urethra
• Thin, milky, alkaline
• Adjusts sperm pH
• Enhances sperm motility
◦ Bulbo-Urethral Glands
▪ Inferior to prostate
▪ Enclosed by fibers if urethral sphincter
▪ Tubules secrete fluid into urethra
• Mucus like, lubricates the penis
• Semen
◦ Sperm is 2% of semen
◦ Remaining
▪ Fluids from seminal vesicles (60%)
▪ Fluids from prostate gland (35%)
▪ Fluids from bulbourethral glands (3%)
◦ Typical ejaculation is 2-5mL, approx 20-100 million spermatozoa per mL
◦ pH 7.2-8.0
◦ Contains prostaglandins, relaxin, ATP, ingredient to suppress female immune response,
antibiotic chemicals, clotting factors
• Physiology of Male Resproductive System
◦ Erection

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▪ Sexual excitment tirggers a parasympathetic reflex that promotes release of nitric oxide
locally which relaxes smooth muscle in penile blood vessel walls, dilating arterioles and
allowing erectile bodies to fill with blood
▪ Expansion of corpora cavernosa compresses drainage veins in order to retard blood
outflow
▪ Corpus spongiosum expands slightly, main function is to keep urethra open during
▪ CNS responds to sexual stimuli by activating parasympathetic neurons that innervate
internal pudendal arteries ejaculation
◦ Ejaculation
▪ Under sympathetic control
▪ When impulses provoking erection reach critical level a spinal reflex is initiated and
discharge of nerve impulses occurs over sympathetic nerves
▪ Bladder sphincter constricts preventing expulsion of urine or reflux of semen into
bladder
▪ Reproductive duct and accessory glands contract, emptying contents into urethra
▪ Semen in urethra triggers a spinal reflex through somatic motor neurons, semen is
propeeled from urethra
▪ Activity of sympathetic never fibres constricts the internal pudendal arteries, reducing
blood flow to penis and forces blood out
• Spermatogenesis
◦ Sequence of events in seminiferous tubules of testes that produces male gametes
◦ Healthly adult produces 400 million sperm per day
◦ Diploid chromosomal number- normal chromosome number in most body cells, symbolized
as 2n, in human 46
◦ Haploid chromosomal number- number of chromosome in gametes, symbolized as n, in
humans 23
◦ Mitosis- type of division that occurs with most body cells, distributes replicated
chromosomes equally between daughter cells so that each daughter cells receives a full set
of chromosomes identical to the mother cell
◦ Meiosis- type of nuclear division that occurs in gonads, consists of 2 consecutive nuclear
division that follow one round of DNA replication, product is 4 daughter cells instead of 2,
each with half as many chromosomes as diploid body cells (reduces 2n to n) introduces
genetic variation because each of the haploid daughter cells only has some of the genes of
each parent
▪ 2 nuclear divisions, each consisting of 4 phases
• Meiosis 1- reduction division of meiosis
◦ Reduces chromosome number from 2n to n
◦ Similar to mitsosis expect in prophase 1 the replicated chromosomes seek out
their homologous partners and pair up with them (synapsis) forms tertad.
Crossovers (chiasmata) then occurs where one end of one maternal and one
paternal chromatid wrap around each other within the tetrad.
◦ During metaphase tetrads line up randomly and during anaphase the sister
chromotids and homologous chromosomes are distributed to opposite end of the
cell
◦ Results in two copies of one member of each homologous pair and none of the
other in each daughter cell and a haploid chromosomal number but twice the
amount of DNA
• Meiosis 2- equal division of meiosis
◦ Mirror mitosis in every way except that chromosomes are not replicated before it

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begins, instead sister chromatids are parcelled out among four cells
◦ Reduces chromosomal number by half
◦ Introduced genetic variability
◦ Events in Seminiferous Tubules
▪ Spermatogenic cells- give rise to sperm in a series of division and cellular
transformations
▪ Mitosis of Spermatogonia- forming spermatocytes
• Spermatogonia- outer most tubule cells, divide continuously by mitosis, until
puberty all daughter cells become spermatogonia. After puberty each mitotic
division of a spermatogonium results in type A and type B daughter cells
◦ Type A remain basal lamina
◦ Type B get pushed to lumen and become a primary spermatocyte destined to
produce 4 sperm
▪ Meiosis- Spermatocyte to Spermatids
• Each spermatocyte undergoes meiosis 1, forming two smaller haploid cells
(secondary spermatocytes)
• These continue rapidly to meiosis 2, producing spermatids
• Midway through spermatogenesis the developing sperm turn off all the their and
compact their DNA
▪ Spermatogenesis- Spermatids to sperm
• Sperm must undergo speriogenesis during which is elongates, sheds its excess
cytoplasmic baggage and forms a tail, result is a spermatozoon
• Head of sperm contains DNA, acrosome adheres to the top of the nucleus, midpiece
contains mitochondria spiraled around tail . Long tail is a flagellum
• Sustenocytes- sertoli cells, divide seminiferous tubule into two compartments.
◦ Basal compartment- contains spermatogonia and earliest primary spermatocytes
◦ Adluminal compartment- includes meiitically active cells and tubule lumen
◦ Tight junctions between sustenocytes form the blood testis barrier
• Hormone Regulation
◦ Gonadotropin releasing hormone (GnRH)
▪ From hypothalamus
▪ Stimulates FSH and LH release
◦ Follicle stimulating hormone (FSH)
▪ From anterior pituitary
▪ Stimulates spermatogenesis
◦ Luteinizing hormone (LH)
▪ From anterior pituitary
▪ Stimulates androgen production
◦ Inhibin
▪ From sertoli cells
▪ Blocks FSH secretion

The Female Reproductive System


• Ovaries
◦ Ovarian ligament anchors the ovary medially to the uterus, the suspensory ligament anchors
it laterally to the pelvic wall the mesovarium suspends it in between, suspensory and
mesovarium are part of broad ligament that support uterine tubes, uterus and vagina
◦ Each ovary is surrounded by a fibrous tunica albunginea

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◦ Ovary has an outer cortex which houses forming gametes and inner medulla containing
largest blood vessels and nerves
◦ Ovarian follicles- each consists of an immature egg (oocyte) surrounding cells are follicle
cells if there is a single layer present, granulosa cells when more than one layer is present
◦ Primordial follicles- single layer of follicle
◦ Vesicular follice- fully mature, central fluid filled cavity
• Female Duct System
◦ Fallopian tubes- receive the ovulated oocyte, site of fertilization
▪ At time of ovulation the uterine tube bends to drape over the ovary while the fimbriae
stiffen and sweep the ovarian surface cilia on fimbriae create currents that carry an
oocyte into the uterine tube
▪ Peristalsis and cilia carry oocyte microvilli produce secretions that keep oocyte moist
and nourished
◦ The Uterus
▪ Receives, retains and nourishes a fertilized ovum
▪ Major portion- body, rounded region- fundus, narrowed region- isthmus
▪ Uterine wall
• Perimetrium- incomplete outermost serous layer
• Myometrium- middle layer, contracts during childbirth
• Endometrium- muscosal lining of uterine cavity, embryo implants here, two layers
◦ Stratum functionalis- functional layer undegoes cyclic changes
◦ Stratum basalis- basal layer, deeper, thinner, forms a new functionalis when
menstruation ends
◦ The Vagina
▪ 3 coats
• Outer fibroelastic adventita
• Smooth muscle muscularis
• Inner mucosa
• Vagina has an acidic pH which helps destroy bacteria but is also hostile to sperm
◦ External Genitalia
▪ Mons pubis
▪ Labia majora and labia minora
▪ Clitoris
▪ Greater vestibular glands- release mucous into vestibule and help keep it moist and
lubricated
◦ Mammary glands
• Oogenesis
◦ In fetal period oogonia (diploid stem cells of ovaries) multiply rapidly by mitosis,
primordial follicle appear as oogonia transform into primary oocytes and become
surrounded by follicle cells
◦ Primary oocytes begin first meiotic division but do not complete prophase 1
◦ At birth female has lifetime supply of eggs, by puberty 300, 000 remain
◦ Before puberty all recruited primordial follicle undergo atresia, at puberty FSH rescues a
small number of growing follicles each month
◦ In each cycle one rescued follicle is the dominant follicle and continues meiosis 1,
producing 2 haploid cells, the smaller one is the first polar body and the larger one is the
secondary oocyte
◦ First polar body may continue meiosis 2, secondary oocyte arrest in metaphase 2 and is
ovulated and deteriorates if not fertilized, if fertilization does occur the oocyte completes

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meiosis 2 and yielding an ovum and a second polar body


• Ovarian Cycle
◦ 2 phases
▪ Follicular phase- period when dominant follicle is selected and begins to secrete large
amounts of estrogen (1-14th day of ovarian cycle, may fluctuate) ovulation then occurs
▪ Luteal phase- period of corpus luteum activity (days 14-28, remains constant)
◦ Ovulation
▪ Ovary wall rupture and expels the secondary oocyte into peritoneal cavity
▪ Mittelschmerz- twinge of pain associated with this
• Uterine (Menstrual Cycle)
◦ Coordinated with phases of ovarian cycle, dictated by gonadotropins released by anterior
pituitary
◦ Day 1-5- menstrual phase- uterus sheds deepest part of endometrium
◦ Day 6-14- endometrium rebuilds itself, under the influence of rising blood levels of
estrogens, cervical muscus in thinned to form channels for sperm passage
◦ Day 14- ovulation occurs
◦ Day 15- 28- secretory (postovulatory) phase- endometrium prepares for an embryo to
implant, progesterone causes funcitonal layer to covert to a secretory layer, cervical plug
forms
• Female sexual response
◦ Sexual excitement causes clitoris, vaginal muscosa, bulbs of vestibule, and breasts to
engorge with blood
◦ Vestibular glands lubricate vagina
◦ No refractory period

Development of the Reproductive System


• Determination of genetic sex- sex chromosomes in each gamete determines sex
◦ X chromosome- body cells of females have XX
◦ Y chromosomes- body cells of males have XY, if not Y present development will occur as
female, males sperm determines the sex of the child
◦ Gonads of both male and female begin developing in week 5 of gestation as masses of
mesoderm (gonadal ridges)
▪ Soon primordial germ cells migrate to them, the seed the developing gonads with stem
cells destined to become spermtogonia or oogonia, ridges then form testes of ovaries
• Testes formation begins week 7
• Ovary formation begins week 8
▪ During week 8 external genitalia begin to form
▪ About 2 months after birth testes begin their descent toward scrotum, stimulated by
testosterone
• Gubernaculum- extend from testis to floor of scrotum and guides testes down
▪ Ovaries descend during fetal development

Week 11- Pregnancy and Development

Time line
• Gestation period- development occurs
• Fertilzation- 8 weeks- conceptus is called an embryo
• 9 weeks- brith- conceptus is called a fetus
• First trimester- months 1-3 (fertilization, implantation, placenetation, embroyogensis)

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◦ Embryonic and early fetal development


◦ Rudimentary organ systems appear
• Second trimester- months 4-6
◦ Organs and organ systems complete most of development
• Third trimester- months 7-9

Events leading to fertilization


• Sperm transport and capacitation- only a few thousand are conducted by reverse peristalsis
into uterine tube
◦ Sperm newly deposited into vagina are incapable of penetrating an oocyte. They must first
be capaciatated over 2-10 hours, motility must be enhanced and membranes must become
fragile
◦ Sperm bear olfactory receptors that respond to chemical stimuli and allow sperm to navigate
to egg
• Acrosomal reaction and sperm penetration- once in immediate vicinity of oocyte sperm
weaves its way through cells of corona radiata
◦ Sperm then binds to ZP3 glycoprotein of zona pellucida which funcitons as a sperm receptor
◦ Binding opens Ca2+ channels which leads to a rise is Ca2+ that triggers the acrosomal
reaction which involves the release of acrosomal enzymes that digest holes through zona
pellucida. Once the path is cleared the sperms head is forced to rock move toward oocyte
membrane.
◦ Sperms postacrosomal collar binds to oocytes plasma membrane receptors, 2 consequences
▪ Causes oocyte to form microvilli that surround sperm head and membranes fuse
▪ Cytoplasmic contents of sperm enter oocyte
• Block to polyspermy
◦ Polyspermy- entry of several sperm into an egg, does not occur in humans
◦ Monospermy- one sperm per oocyte
◦ Once sperm head has entered oocyte waves of Ca2+ are released which activates oocyte to
prepare for second round of cell division. Aslo cortical reaction occurs in which granules
spill their enzymes into extracelluar space beneath zone pellucida, enzymes are zonal
inhibiting proteins and destroy sperm receptor so no more cna entering
◦ As spilled material binds to water it swells and hardens and detaches all sperm still bound to
receptors completing slow block to polyspermy
◦ If polyspermy does occur embryos die
• Completion of Meiosis 2 and Fertilization
◦ As sperms cytoplasmic contents enter oocyte the sperm loses its plasma membrane,
centrosome elaborates its microtubules
◦ On the way, nucleus swells to forms male pronucleus while secondary oocyte completes
meiosis 2 forming the ovum nucleus and second polar body
◦ Ovum nucleus swells and becomes female pronucleus
◦ Mitoic spindle develops between them and pronuclei membranes rupture releasing their
chromosomes together
◦ Maternal and paternal chromosomes combine and produce the diploid zygote and
chromosomes replicate

Events of Embryonic Development


• Cleavage and Blastocyst Formation
◦ Cleavage- the period of fairly rapid mitotic divisions of the zygote without intervening

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growth
◦ Goal- to produce smalls cells with a high surface to volume ratio which enhances their
uptake of nutrients and O2 and disposal of wastes
◦ Provides large number of cells to serve as building blocks
◦ 36 hours after fertilization- first cleavage division of zygote produced 2 identical cells
(blastomeres) which divide to form morula
◦ Transport of embryo to uterus continues
◦ By day 4-5 consists of 100 cells
◦ Blastocyst hatches from inner structure and tropoblast cells begin to display L- selectin
adhesion molecules
◦ They take part in placenta formation and secrete several factors with immunosuppresive
effects
◦ Inner cell mass becomes embryonic disc which forms embryo proper and 3 extraembryonic
membranes
• Implantation
◦ Window of implantation is opened by surging levels of ovarian hormones in blood
◦ If mucosa is properly prepared, integrin and selectin proteins on trophoblast cells bind
respectively to extracelluar matrix and endometrial cells and blastocyst impants high in the
uterus
◦ Endometrium thickens at point of contact and takes on characteristics of an acute
inflammatory responses
◦ Takes about 5 days
◦ Viability of corpus luteum is maintained by LH-like hormone (human chorionic
gonadotropin. HCG)
▪ This is detectable in a pregnancy test
• Placentation
◦ Formation of a placenta
• Early embryonic development
◦ Woman is clinically pregnant
◦ Even while implantation is occurring the blastocyte is being converted to a gastrula in which
the 3 primary germ layers form and extraembryonic membranes develop
▪ Formation of membranes and layers
• Before becoming three-layered, inner cells divided in 2 (epiblast and hypoblast) and
subdivided inner cell mass is embryonic disc
• Extraembryonic membranes that form during the first 2-3 weeks are amnion, yolk
sac, allantois and chorion
• Amnion provides buoyant protective environments and prevents organs from fusing
together during development
• Yolk sac forms digestive tube and is source of earliest blood cells and blood vessels
• Allantois forms at end of yolk sac and functions for waste removal
• Chorion helps form the placenta
▪ Morphogenesis- shaping of embryo
▪ Gastrilation- during week 3 2 layers transform into ectoderm, mesoderm and endoderm
▪ Organogensis- formation of body organs and organ systems (differentiation, starts with
nervous system)
◦ Development of fetal circulation
▪ First blood cells arise is yolk sac
▪ By end of week 3 embryo has a system of paired blood vessels and two vessels forming
the heart have fused and bent into an S shape

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▪ Week week 3.5 miniature heart is pumping blood


▪ Umbilical arteries and veins and 3 vascular shunts, all are occluded at birth
▪ Blood flows to and from fetal hear, large umbilical vein carries oxygenated blood
returning from placenta to embryonic body, most enters ductus venosus, is eventually
emptied into inferior vena cava where placenta blood mixes with deoxygenated blood
returning from lower parts of fetuses body, mixed blood is then conveyed to right atrium
of heart
▪ Blood entering an leaving heart encounters foramen ovale and ductus arteriosus which
bypasses lungs

Events of Fetal Development


• Rapid growth
• See pg 1084 for changes

Effects of Pregnancy on Mother


• Reproductive organs become engorged
• Vagina develops Chadwicks sign (purple colour)
• Breasts enlarge with blood
• Uterus presses higher into abdominal cavity, exerting pressure on abdominal cavity, presses
against diaphragm, ribs flare and thorax widens
• Lordosis often develops
• Weight gain of 28lbs usually occurs
◦ Metabolic changes
◦ Physiological changes- GI system, urinary system, respiratory system, cardio system,

Paturation
• Rise in estrogen in last stages of pregnancy, 3 important implications
◦ Stimulates myometrial cells of uterus to form abundant oxytocin receptors
◦ Promotes formation of gap junctions between the uterine smooth muscle cells
◦ Antagonizes progesterone’s quieting influence on uterine muscle
• Braxton Hicks contractions- false contractions caused by relaxation of uterus muscles
• Fetal cells begin to produce oxytocin which causes placenta to release prostalglandins which
stimulate synthesis of more gap junctions in uterine smooth muscle, both are strong muscle
strimulants and contractions become more frequent and vigorous
• Increasing cervical distension activate hypothalamus which signals for oxytocin release by
posterior pituitary
• Several postive feedback mechanisms involving prostaglandins and oxytocin are propelled into
action
• Fetal fibronectin changes to lubricant just before true labor beings
• Antiprostalgandins (ibuprofen) can inhibit early stages of labor
• Stages of labor
◦ Dilation
▪ Time from labors onset until cervix is fully dialted (10cm)
▪ Weak but regular contractions begin
▪ At first 15-30 min apart and in superior uterine muscles, last for 10-30 seconds
▪ Lower uterus gets involved and contractions are faster and more vigorous
▪ Eventually amnion ruptures
▪ Last 6-12 hours of more
▪ Engagements occurs when infants head enters the true pelvis

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▪ Descent continues and babies head rotates so that its greatest dimension is in the
anteroposterior line
◦ Expulsion
▪ From dilation to delivery
▪ Strong contractions every 2-3 minutes, lasting 1 minute
▪ May last up to 2 hrs, usually 50 min, 20 minutes in subsequent births
▪ Crowning when largest dimension of babies head distends vulva
▪ Episiotomy may be done to reduce tissue tearing
◦ Placental Stage
▪ Delivery of placenta and its attached fetal membranes
▪ Usually within 30 minutes after birth

Adjustment of Infant to Extrauterine Life


• 1 and 5 minutes after birth infants physical status is assessed based on five signs
◦ Heart rate
◦ Respiration
◦ Color
◦ Muscle tone
◦ Reflexes
• Apgar score- 8-10 indicates healthy
• First breaths
◦ Central adidosis leads to first inspiration which requires tremendous effort
◦ 45 resp/ min during first 2 weeks
◦ Premature infants usually put on resp assistance because of lack of surfactant
◦ Transitional period- 6-8 hours after birth
◦ Occlusion of fetal blood vessels and shunts

Week 12- Heredity

Genetics
• Nuclei of all human cells except gametes contain the diploid number of chromosomes (46)
consisting of 23 pairs of homologous chromosomes
• Two are the 46 are sex chromosomes which determine the genetic sex
• The other 44 are 22 pairs of autosomes that guide the expression of other traits
• Diploid genome makeup represents two sets of genetic instructions, one from egg, other from
sperm

Gene Pairs (Alleles)


• Matched genes at the same location on homologous chromosomes are called alleles
• When two alleles controlling a trait are the same the person is homozygous for that trait
• When the alleles are different the person is heterozygous
• Dominant alleles suppress the expression of its partners
• The allele that is suppressed in the recessive
• Dominant alleles are expressed when present in a single or double does but recessive genes are
only expressed if present in a double dose

Genotype and Phenotype


• Genotype- persons genetic makeup
• Phenotype- the ay that genotype is expressed

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Sexual Sources of Genetic Variation


• Chromosome segregation and independent assortment
◦ During spermatogenesis and oogenesis chance determines how the tetrads align on the
meiosis 1 metaphase spindle and maternal and paternal chromosomes are randomly
distributed to daughter nuclei
◦ This leads to variation in gametes
◦ Additionally in metaphase of meiosis 1 the two alleles determining each trait are segregated
(distributed to different gametes.) Also alleles on different pairs of homologous
chromosomes are distributed independently of each other.
◦ Net result is that each gamete has a single allele for each traits which represents only one of
the four possible parental alleles
◦ Independent assortment results = 2^n, where n is the number of homologous pairs
• Crossover of homologues and Gene Recombination
◦ Crossing over and exchange of chromosomal parts during meiosis 1- genes are arranged
linearly along a chromosomes length and genes on the same chromosomes are said to be
linked because they are transmitted as a unit to daughter cells during mitosis.
◦ Genes can break and precisely exchange gene segments with their homologous counterparts
during meiosis, giving rise to recombinant chromosomes that have mixed contributions
from each parent
• Random fertilization
◦ A single egg will be fertilized with a single sperm completely randomly

Types of Inheritance
• Dominant- recessive inheritance
◦ Reflect the interaction of dominant and recessive alleles
◦ Punnett square is used to determine the possible gene combinations for a single trait that
would result from the mating parents of known genotypes
▪ Only predicts the probability of particular genotypes
▪ Larger number of offspring means a greater chance that ratios will conform to the
prediction
▪ Production of each child is an independent event and does not effect the outcome of the
next child
◦ Dominant traits- human traits dictated by dominant allels includes widows peak, dimples,
freckles
▪ Huntington's disease
◦ Recessive traits- recessive traits include normal vision
▪ Albinism, cystic fibrosis, Tay- Sachs disease
▪ Recessive genetic disorders are more frequent because those who carry a single
recessive allele for a recessive genetic disorder do not express the disease but can pass
the disease on
▪ Few individuals will dominant traits live long enough to pass the trait on
◦ Incomplete dominance- the heteroxygote has a phenotype intermediate between those of
homozygous recessive individuals
▪ Sickling gene- individuals who have double does of the sickling allele have sickle cell
anaemia, those who are heterozygous for the sickling gene have sickle- cell trait
• Multiple Allele Inheritance
◦ Some genes exhibit more than two allele forms
◦ Co-dominant genes are both expressed when present

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• Sex- Linked Inheritance


◦ Inherited traits determined by genes of the sex chromosome
◦ X bears over 2500 genes, Y carries 78 genes
◦ Gene found only on X chromosome- X linked
▪ Passed from mother to child, not from father as children do not receive an X
chromosome from their father
• Polygenetic Inheritance
◦ Many phenotypes depend on several gene pairs at different locations acting in tandem
◦ Continuous or quantitative phenotypic characteristics result

Environmental Factors in Gene Expression


• Environmental factors often override or influence gene expression
• Genotype is unchanging but phenotype can be molded
• Maternal factors including drugs or pathogens can alter gene expression during embryonic
development
• Phenocopies- environmentally produced phenotypes that mimic conditions caused by genetic
mutations
• Equally significant factors that impact expression after birth are nutrition, hormonal defects and
others

Nontraditional Inheritance
• Beyond DNA- Regulation of Gene Expression
◦ Three basis levels of gene control- protein coding genes (1st level), small RNAs (2nd level),
epigenetic marks (3rd level)
◦ Smalls RNAs
▪ Product of abundant RNA only genes found on non-protein coding DNA, form parallel
regulatory system that generates single-stranded microRNAs and short interfering RNAs
▪ These small RNA can act directly on DNA or RNA and can tame transposons
▪ Small RNA control timing of programmed cell death during development and can also
prevent translation of another gene
◦ Epigenetic marks
▪ Continually changing information is stored in proteins and chemical groups that bind
DNA
▪ Chemical tags within cells determine whether DNA is available for transcription or
silenced.
▪ Also accounts for inactivation of one of females X chromosomes in the early embryo
▪ Underlies genomic imprinting which tags genes as paternal or maternal and confers
important functional differences in the embryo
• Extranuclear Inheritance
◦ Not all genes are in the nuclues, 37 genes are in mitochondria and are transmitted almost
exclusively by mother

Genetic Screening, Counselling and Therapy


• Providing information and options for prospective parents
◦ Newborns are routinely screened for a number of disorders
◦ Depending on condition, some screening can occur before conception by carrier recognition
or during fetal testing
▪ Carrier recognition
• Pedigree- traces a genetic trait through several generations and helps predict the

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future
• Blood tests- can detect presence of other unexpressed recessive genes
• Fetal testing
◦ Used when there is a known risk of genetic disorder
◦ Most common type is aminocentesis
▪ Fluid is drawn from amniotic sac and checked for enzymes and other chemicals that
serve as markers for certain disease
◦ Chorionic villus sampling- suctions off bits of the chorionic villi from placenta for
examination
• Human gene therapy
◦ Human Genome Project has allowed research on diagnosis of genetic disease and on its
treatment to improve
◦ Single gene disorder correction is fairly successful
◦ Most common approach is transferring a corrected gene via a virus to affected cells to
restore normal function

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