Gastrointestinal System - Anatomy and

Physiology
 Gastrointestinal (GI) tract [Alimentary canal] a continuous muscular
digestive tube
 Digests:
o breaks food into smaller fragments
 Absorbs:
o digested material is moved through mucosa into the blood
 Eliminates:
o unabsorbed & secreted wastes.

Lesson 1: GI
Concepts

 Alimentary Canal:
o Mouth, pharynx & esophagus
o Stomach
o Small intestine
o Large intestine

 Accessory digestive organs: teeth, tongue, gall bladder, salivary glands,

liver & pancreas
GI
process

 Ingestion: obtaining food

 Propulsion: moves food along the GI tract by peristalsis (wave-like
muscular contraction)
 Mechanical digestion:
o chewing & mixing with saliva
o mixing in stomach
o segmentation (local constriction in intestine to mix food &
digestive juices)
 Chemical digestion: breaks down food to molecular fragments
(monomers) (Hydrolysis).
o Begins in the mouth with saliva & continues into the small
intestine.
 Absorption: movement of nutrients across the mucosal membrane
into blood/lymph
 Defecation: eliminates unused/indigestible & secreted substances
from the body
GI blood
Supply

Celiac Trunk: Superior Mesenteric Inferior Mesenteric

Supplies blood to, Supplies blood to, Supplies blood to,

 Oesophagus  3rd and 4th part  Distal 1/3rd of

 Spleen of Duodenum transverse
 Stomach  Jejenum colon
 Liver  Ileum  descending colon
 Gallbladder  Appendix  sigmoid colo
 Pancreas  Ascending Colon  rectum
 1st and 2nd part  Caecum  upper anal canal
of duodenum  Proximal 2/3rd
of transverse
colon
Peritoneu
m

Peritoneal Cavity: Visceral Peritoneum Parietal Peritoneum

Potential space containing Covers the external Lines the body wall
fluid that separates surfaces of most
the visceral & digestive organs
parietal peritoneum
Histology of the GI (Alimentary
Canal)

Mucosa Submucosa
 The epithelial membrane that liens Moderately dense CT with blood, nerve,
the GI tract from mouth to anus lymph vessels & lymphoid follicles; rich in
o Secretes mucous, elastic fibers
digestive enzymes &
hormones
o Absorbs nutrients
o Protects from disease &
from the GI contents
 3 layers:
o Epithelium
o Lamina propria (loose ct
contain capillaries
o Muscularis mucosa
Muscularis externa Serosa
 smooth muscle Visceral peritoneum
o Responsible for peristalsis &
segmentation
o Circular layer
o Longitudinal layer
o Sphincters: in some areas the
circular layer thickens; act as
valves
Types of epithelium in Ailmentary
Canal
Organ Epithelium
Mouth Nonkeratinized Stratified Squamous
Pharynx Nonkeratinized Stratified Squamous
Esophagus Nonkeratinized Stratified Squamous
Stomach Simple Columnar
Small Intestine Simple Columnar
Large Intestine Simple Columnar
Anus Nonkeratinized Stratified Squamous

Nerve
Regulation

Nerves
• Intrinsic: (Local): Short reflex
• Submucosal nerve plexus:
regulates glands & mucosal muscle
• Myenteric plexus: controls GI wall & GI motility
• Extrinsic: (CNS): Long reflex
• Parasympathetic NS: enhances gut motility &
secretion
• SNS: inhibits gut motility & secretion
Hormonal
Concepts
Lesson 2:
Mouth

Mouth cavity = Buccal cavity

1)Lips: extend from inferior margin of the nose to the superior margin of the
chin. Red area = red margin, is poorly keratinized & lacks sweat or sebaceous
glands.

2) Palate:

 Hard palate: rigid surface against which food is forced in chewing

 Soft palate: muscular structure that rises & blocks off the nasopharynx
during swallowing

3)Tongue: muscular tentacle composed of interlaced muscle fibers that grips &
repositions food, mixes food with saliva & compresses food to form a food
bolus, prior to swallowing.

Type of epithelium - Keratinized stratified squamous epithelium

4)
Tonsils

5) Salivary Glands: intrinsic & extrinsic

• Intrinsic glands: scattered throughout the buccal cavity mucosa
•Extrinsic glands: supply most of the saliva; outside buccal cavity & supply
secretions via ducts:
• Parotid
• Submandibular
• Sublingual
 Composition of saliva: (0.75 – 1.5 L per day)
o 97-99.5% H2O
o Electrolytes: Na, K, Ca, Mg, Cl, HCO3- and phosphate
o pH 6.75-7.0
o Amylase: (digestive enzyme)
o Proteins: mucin, lysozyme, & IgA
 Protection from microbes by saliva:
o Mucin: Lubricant
o IgA: Immunglobulins in secretions
o Lysozyme: Bacteriostatic (inhibits bacterial growth)
o Defensins: local antibiotic activity & when activated
promote chemotaxis by WBCs
Lesson 3: Teeth and
Pharynx

Teeth
:  Primary: 2I 1C 2M x 2
= 20 2I 1C 2M
 Permanent: 2I 1C 2PM 3M x 2
= 32 2I 1C 2PM 3M
 Structures
o Crown: exposed above gingiva (gum)
o Root: anchored by periodontal ligament to the bone by a fibrous
joint (gomphosis)

Pharynx: oropharynx & laryngopharynx; muscular wall propels food

to the esophagus
Lesson 4:
Esophagus

 Muscular 25cm tube from laryngopharynx to stomach

 Passes through the diaphragm at the esophageal hiatus
 Gastroesophageal (cardiac) sphincter: A physiologic sphincter that
helps keep esophagus closed when empty
 Consist of the same histology as the ailmentary canal consisting of the
mucosa, submucosa, muscularis externa and serosa
Lesson 5:
Stomach

• Cardiac region: narrow, receives food bolus

• Fundus: bulge that extends supero-laterally to the cardia, reaches the
diaphragm
• Body: mid-portion
• Pyloric antrum: funnel shaped portion narrows to eventually form the;
• Pyloric canal -> Pylorus -> Pyloric sphincter
Rugae

 longitudinal
mucosal folds

 volume about 4L
Histolog
y

• Gastric glands secrete gastric juices

• Mucous neck cells: in the duct portion
• Parietal cells: mid portion of glands secrete HCl & intrinsic factor
•Chief cells: base of gland; secretes pepsinogen a precursor molecule to
pepsin (an enzyme that digests protein)

 Mucosal barrier: protects the stomach from its own secretions

o Viscous mucous overlies a thick coating of HCO3 rich mucous
(secreted by mucous neck cell)
o Tight junctions between epithelial cell of glandular cells are
impermeable to HCl
o Epithelium is replaced every 3-6 days
Gastric Mucosal
Barrier
Digestive process of the stomach

 Acts as a holding vessel for ingested food

 Participates in mechanical & chemical digestion
 Propulsion: Delivers its product (chyme) to the small intestine

Chief cells:

 secrete the inactive enzyme pepsinogen

o Begins the chemical hydrolysis of proteins when
pepsinogen is converted to pepsin (active)
 secrete gastric lipase
o continues the chemical hydrolysis of lipids

Parietal cells:

 secrete HCl (hydrochloric acid) to lower pH to 2.0 (optimal for

chemical digestion in the stomach)
o denatures swallowed proteins, kills bacteria and activates pepsin
 secrete intrinsic factor which forms complexes with vitamin B12 and is
essential for its absorption in the intestine
o lack of intrinsic factor results in pernicious anemia which is a
reduction of red blood cell synthesis due to a vitamin B12
deficiency
 The food that enters the stomach dilutes the HCl component of gastric
juice
which causes the pH to increase above 2
 In response, (G cells) of the gastric glands secrete the hormone gastrin
 Gastrin stimulates the parietal cells to secrete additional HCl to return
the pH to 2
 During the intestinal phase (while food is slowly leaving the stomach),
the intestinal hormones secretin and cholecystokinin (CCK) inhibit HCl
secretion from parietal cells and inhibit the muscularis of the stomach
thus limiting the
rate of acidic chyme movement into the small intestine.
Enterogastric reflex

The enterogastric reflex is stimulated in the duodenum by a pH of 3-4 and in the

stomach by a pH of 1.5. Upon initiation of the reflex, the release of gastrin by G-
cells in the antrum of the stomach is shut off. This in turn inhibits gastric motility
and the secretion of gastric acid (HCl)

Stimulatory and Inhibitory factors involved in enterogastric

reflex
Lesson 6: Small
intestine

• 6-7m long: from pyloric sphincter to the ileocecal

valve
• 3 subdivisions:
• Duodenum
• Jejunum
• Ileum
Duodenum

 Curves around the pancreatic head (~25cm long)

 Contains the hepatopancreatic ampulla: formed by the merger of the bile
duct & the pancreatic duct.
 Hepatopancreatic sphincter controls admission of bile & pancreatic
enzymes to the duodenum

 Jejunum: extends from duodenum to ileum (~2.5m long)

 Ileum: from jejunum to ileocecal valve (~3.6m long)

 Jejunum & Ileum function in absorption;

o Intraperitoneal
o Suspended from mesentery whose veins & lymph vessels carry
nutrients away from small intestine
Histolo
gy

 Cell types:
o Mostly absorptive cells
o Goblet (mucous) cells increase in number as the small
intestine progresses
o Enteroendocrine cells - specialized to secrete a particular
hormone that
influences gastrointestinal secretion or motility
o Paneth cells -> secrete protective lysozyme (antibacterial)
o Stem cells -> completely replacing all the absorptive and
goblet cells approximately once every four days
o tuft cells - immunity against parasites
o Peyer’s Patches -> lymphoid follicle in submucosa -> present in
ileum
o Brunners glands (duodenum) -> secrete HCO3- rich mucous to
increase the pH of chyme -> present in duodenum
o
o Villus epithelium is replaced every 3-6 days
o Intestinal Juice: isotonic with blood plasma, slightly
alkaline, low enzyme content
Regulatory Function
 Duodenal regulation of gastric emptying: Feedback mechanisms
monitor the contents being delivered from the stomach
o High fat content
o Low pH (high acidity)
o Hypertonicity (high osmolality)

All result in decreased stomach emptying

Digestive Process
 Optimal digestion requires adequate motility & control of
chemical composition
 pH: acidic chyme must be buffered to allow proper enzyme activity
 Osmolality: chyme is hypertonic & would pull H2O out of circulation;
thus chyme is released in small amounts
 Liver & pancreatic function are required for appropriate delivery of bile
salts & enzymes to the small intestine

 Segmentation: moves intestinal contents back & forth to mix

 Duodenal rhythm for segmentation is greater than the rhythm in the ileum.
o Contents move toward the ileum.
 After most digestion has occurred,
 Peristalsis begins sweeping from duodenum distally
o Occurs in series with each peristaltic wave, originating more
distally.
 Ileocecal valve (sphincter) is relaxed by neural (gastroileal reflex)
impulses from the stomach & hormonal (gastrin) secretion by the
stomach
Lesson 7:
Liver

General
Facts
 Liver produces bile (fat emulsifier) that is stored in & concentrated by
the gall bladder.
 Hepatocytes
o Are liver cells
o Adjust circulating levels of nutrients
 Through selective absorption and secretion
 In a liver lobule form a series of irregular plates arranged like wheel
spokes
 Many Kupffer cells (stellate reticuloendothelial cells) are located in
sinusoidal lining - tissue macrophages present in the liver
 As blood flows through sinusoids
o Hepatocytes absorb solutes from plasma
o And secrete materials such as plasma proteins
Physiology of the liver

1) Metabolic Regulation

 The liver regulates:

o Composition of circulating blood
o Nutrient metabolism (carbohydrate, lipid & amino acid)
o Waste product removal
o Vitamin Storage (A, D, E & K)
o Nutrient storage (iron)
o Drug inactivation
 Composition of Circulating Blood
o All blood leaving absorptive surfaces of digestive tract
 Enters hepatic portal system
 Flows into the liver
 Liver cells extract nutrients or toxins from blood
o Before they reach systemic circulation through hepatic
veins
 Liver removes and stores excess nutrients
o Corrects nutrient deficiencies by mobilizing stored
reserves or performing synthetic activities

2) Hematological Regulation

 Largest blood reservoir in the body

 Receives 25% of cardiac output
 Functions of Hematological Regulation
o Phagocytosis and antigen presentation
o Synthesis of plasma proteins
o Removal of circulating hormones
o Removal of antibodies
o Removal or storage of toxins
o Synthesis and secretion of bile
What is bile?

bile increases the absorption of fats, it is an important part of the absorption of

the
fat-soluble substances, such as the vitamins A, D, E, and K. Besides itsdigestive
function, bile serves also as the route of excretion for bilirubin, a byproduct of red
blood cells recycled by the liver.

 The Functions of Bile

o Dietary lipids are not water soluble
o Mechanical processing in stomach creates large drops containing
lipids
o Pancreatic lipase is not lipid soluble
 Interacts only at surface of lipid droplet
 Bile salts break droplets apart (emulsification)
o Increases surface area exposed to enzymatic attack
o Creates tiny emulsion droplets coated with bile salts
Composition of bile:

 Alkaline solution.
 Bile salts, bile pigments, cholesterol, fats & phospholipids
 Bile salts & phospholipids participate in fat absorption
 Bile salts are conserved by enterohepatic circulation
 Reabsorbed in the ileum
 Return to Liver in hepatic portal blood
 Re-secreted by the Liver
 Bile pigments & bilirubin break down to urobilin then
stercobilin
Lesson 8:
Gallbladder

a muscular pouch that stores bile & expels bile when needed via the cystic
duct & the bile duct.

Regulation of Bile Release

 Cholecystokinin (CCK) & secretin released by the small intestine in

response to increased fats in chyme
 CCK:
o Stimulates both Gall bladder & pancreatic secretion
o Relaxes hepatopancreatic sphincter

 Secretin: stimulates bile secretion

Liver Secretion and Gall bladder
emptying
Lesson 9:
Pancreas

Gross
Anatomy
 Head encircled by
duodenum
 Tail abuts the spleen
 Mostly retroperitoneal
Histology

Pancreatic Acini
 Large numbers of Acinar
cells in clusters around
ducts; exocrine (Acini)
o Acinar cells:
Secrete
pancreatic
digestive
enzymes

 Endocrine cell clusters form

the pancreatic islets that
produce insulin & glucagon
Pancreatic Juice

 Pancreatic Juice: Alkaline, watery, contains enzymes & electrolytes

 Proteolytic enzymes are released as inactive forms then are activated
in the duodenum
o Trypsinogen -> Trypsin by the brush border enzyme enterokinase
o Trypsin activates precursors to form carboxypeptidase &
chymotrypsin

 Amylase, lipase, & nuclease are released in their active forms

Hormonal Regulation

 CCK: released in response to fats & protein. Stimulates pancreatic

secretion of enzymes
 Secretin: released in response to HCl. Stimulates pancreatic duct cells to
release HCO3-
Lesson 10: Large
Intestine

Gross
Anatomy
 Ileocecal valve to anus (~1.5m)
 Teniae coli: 3 ribbons of longitudinal smooth muscle
 Haustra: pocket-like segments of large intestine
 Epiploic appendages: fat filled pouches of visceral peritoneum

Components

 Cecum: blind pouch (below ileocecal valve)

 Appendix: attached to cecum (lymphoid)
 Colon: ascending, transverse, descending, sigmoid
o Transverse colon & sigmoid colon are intraperitoneal;
anchored by mesentery. The rest of the colon is
retroperitoneal
 Rectum
 Anal canal
Bacterial flora

 Ferment indigestible CHO: produces about 500ml of gas per day

 Synthesize B complex vitamins & most vitamin K

Digestive Process

 Propulsion:
o Haustra contractions: stretch stimulate haustra to contract
moving (& mixing) contents to next haustra
o Mass peristalsis: long, slow contractile waves moving contents
toward rectum (3-4 per day)
o Gastrocolic reflex: food intake causes mass peristalsis
 H2O reabsorption & vitamin absorption
 Defecation
o Empty rectum receives waste, causing stretch
o Stretch initiates reflex contraction of the rectum & relaxation of
both anal sphincters
o Voluntary control of the external anal sphincter can
postpone defecation
o If suppressed the contraction stops & is reinitiated later
o With defecation rectal muscle contractions are aided by
increased abdominal pressure (valsalva maneuver)
Lesson 11: Overall GI Hormonal
regulation
Lesson 12: Chemical Digestion and absorption of
Specific Food Groups

Mechanism

 Catabolic process: break down of food molecules to monomeric form

that can be absorbed
 Enzymes break molecules by hydrolysis (Adding H2O into a molecular
bond)

Carbohydrates

 Carbohydrates (CHO): complex sugars are broken down to simple

sugars (monomers)
o Simple sugars (monosaccharides): glucose, fructose, & galactose
can be absorbed
o Disaccharides (not absorbed); Three brush border enzymes:
 Sucrose -> Sucrase
 Maltose -> Maltase
 Lactose -> Lactase
 Hydrolyzed into monosaccharides
 Polysaccharides: broken down to smaller & smaller oligosaccharides
o Salivary amylase: breaks starch into 2-8 linked monosaccharide
o Salivary amylase is denatured by HCl in the stomach
 Pancreatic amylase: continues breakdown (mostly to maltose)
 Brush border enzymes act on oligosaccharides of more than 3 simple
sugars
 Sucrose, maltose & lactose are broken down by specific brush border
enzymes (sucrase, maltase, & lactase)
 Monosaccharides are absorbed.
Protein
s  Proteins: broken down to amino acid monomers. Begins in the stomach.
o Pepsinogen is activated to pepsin by HCL
o Pepsin: cleaves peptide bonds associated with tyrosine &
phenylalanine forming polypeptides (+ a few amino acids).
 Pepsin is inactivated by increased pH in the duodenum
 Trypsin & chymotrypsin: pancreatic enzymes that further
breakdown polypeptides.
 Carboxypeptidase (pancreatic & brush border enzyme):
o Splits off single amino acid from the end of polypeptide chain
that contains the carboxyl group

 Aminopeptidase & dipeptidase (brush border enzymes) release final

amino acid monomers
Lipid
s  Lipids - require emulsification to disperse fats into microdroplets
which enhances enzyme activity
o Bile salts: surround fat droplets & keep them in suspension
in the aqueous digestive juices
o Pancreatic lipase: cleaves off two fatty acid chains from
triglyceride molecules
 Yields a monoglyceride & 2 free fatty acid

Nucleic Acids

small amounts occur in the diet

 Pancreatic nucleases: Hydrolyze nucleic acids to nucleotide monomers

 Nucleosidases & phosphatases (brush border) break down nucleotides

Absorption

 Taking place mainly in the small intestine

 Most nutrients are absorbed from chyme prior to the ileum (ileum
primarily reabsorbs bile salts)
 Most nutrients cross the mucosa by active transport.
o Some products of lipid digestion are absorbed by diffusion.
o CHO, amino acids & nucleic acid remnants are actively
transported into mucosal cells & then enter capillary blood
Absorption -
Fats
 Monoglycerides & free fatty acids are associated with bile salts &
lecithin (a phospholipid) to form micelles
o Micelles diffuse between microvilli
o The lipid substances leave the micelles & diffuse across the
PM of microvilli
o Inside the intestinal epithelial cell, the components are
reassembled into triglycerides
o Triglycerides are then packaged with cholesterol & phospholipids
into
chylomicrons
o Chylomicrons are exocytosed & diffuse to lymphatic
lacteals to eventually be placed into blood by the
lymphatic system
o Chylomicrons in the blood are hydrolyzed by lipoprotein lipase to
free fatty acids & glycerol prior to tissue absorption
Chylomicro
ns
 Fatty Acid
Absorption

Vitamins
 Some Vit. K & B complex vitamins are absorbed in the large intestine
 Dietary vitamins are absorbed in the small intestine
 Fat soluble vitamins (A, D, E, K) dissolve in dietary fats & are
absorbed after being incorporated into micelles

Electrolytes and Water

 most ions are actively absorbed throughout small intestine
 Na+ is coupled to absorption of glucose & amino acids (cotransport)
 Cl- actively transported into cells; exchange for HCO3-
 K diffuses into the cells
 Iron is transported into cells & bound to ferritin
 Ca2+ absorption regulated by blood Ca2+ levels & Vitamin D
o (Vitamin D is a required cofactor for Ca2+ absorption)

 Water moves freely in both directions across the mucosa

 Active transport of solutes creates an osmotic gradient & H2O follows

 H2O movement changes solute concentrations & effects
absorption of substances that move by diffusion
Gastrointestinal system -
Lab/investigations and Pathology
Lesson 1: Labs and Investigations
Helicobacter Pylori Screening

 Endoscopy / biopsy (Stool sample)

 Urea-breath test (14C Urea Capsule)
 Immunoassay of IgG antibody

Fecal Fat test

 To detect and measure excess fat in the stool; to help diagnose

conditions causing malabsorption
 High fecal fat is the best confirmatory test for steatorrhea but it
gives no information as to the cause.
 The fecal lipids normally are derived from:
o Mucosal cells
o Gastrointestinal flora
o Excretions into the intestinal lumen
o Diet

Schillings test

 Schilling’s test is used for patients with vitamin B12 (cobalamin)

deficiency. The purpose of the test is to determine whether the patient
has pernicious anemia.
 The Schilling’s test is performed by orally administering 57Co-
radiolabeled B12 and quantifying its appearance in the serum, feces or
(most commonly) in the urine.

Occult blood

 Normally, blood detection in stool is easily identifiable by

looking for erythrocytes in the stool.
 But the “OCCULT” (hidden) blood has to be tested with different
methods, e.g. peroxidase (since all heme containing substances
possess peroxidase activity)
 Patients should be placed on meat-free or low-meat diets for three days
before evaluation for occult blood in their stools.
 Test is repeated a few times if needed.
Barium Enema and CT
Scan
 A barium enema is an x-ray exam of the large intestine.
 The colon is filled with a contrast material that contains barium so that
the intestine can be seen on an X-ray. This is done by pouring the
contrast material through a tube inserted into the anus. The barium
blocks X-rays. This causes the barium-filled colon to show up clearly on
the X-ray picture.
 Purpose is to diagnose and follow up the prognosis of IBD and
diverticulitis.

Celiac Disease testing

 Done through blood test.

 Antibodies are checked in the presence of gluten in the diet and in its
absence -
> Tissue Transglutaminase Antibodies (tTG-IgA)
 The results are compared to diagnose/reject the condition.
Liver Function Tests

Mechanisms of Liver Dysfunction

 Direct cellular injury

 Blockage in bile flow
 Impaired blood flow

Types of Liver Tests

1. True tests of liver function - Serum Bilirubin, Serum

proteins
2. Biochemical markers of liver injury
3. Biochemical markers of specific liver diseases

True tests of liver function

Bilirubin Formation

a) Serum Bilirubin

 Tetrapyrole structure
 Predominant pigment in bile
 Bilrubin Formation (See image)
 Bilirubin is released by breakdown of Hb and is bound to albumin as
water insoluble indirect bilirubin or unconjugated bilirubin (as its
water insoluble it is not excreted by the kidney)
 Unconjugated bilirubin is converted into water soluble conjugated or
direct bilirubin by conjugating with diglucuronide (which is excreted by
the kidney as
its water soluble)
 Toxic in neonates - kernicterus
 Derived from:
o Senescent RBC (70-80%)
o Hemoproteins (20-30%)
o Ineffective erythropoiesis
Measurement of Serum Bilirubin

 Direct (also called conjugated) bilirubin: less than 0.3 mg/dL

 Total bilirubin: 0.1 to 1.2 mg/dL
 Jaundice if > 3 mg/dl
 Detected by diazo reaction - cleaved to colored azo-dipyrole
o Conjugated reacts rapidly (direct)
o Unconjugated reacts slowly (indirect)

Differential Diagnosis

 Unconjugated hyperbilirubinemia
o Increased bilirubin production (hematological)
o Decreased uptake (drug)
o Decreased conjugation (congenital)
o Inherited - Gilberts Syndrome (common, harmless liver condition
in
which the liver doesn't properly process bilirubin), Dubin
Johnson Syndrome, Rotor's Syndrome, Crigler Najjar
Syndrome
 Conjugated hyperbilirubinemia
o Congenital
o Drug (acetaminophen, allopurinol, anabolic steroids,
chlorpromazine, estrogens, halothane, isoniazid, methyldopa,
phenytoin, protease inhibitors, quinidine, rifampicin, statins, and
sulfa drugs)
o Liver disease
o Biliary obstruction

b) Serum Proteins

Albumin

 50% of all synthesized hepatic protein

 Important transport protein

Serum Albumin Levels

 Long half-life of 20 days

 Large hepatic synthetic reserve
 Decreased with persistent, large injury
 Decreased in chronic liver disease
 Poor prognostic sign
Non-hepatic Causes of Hypoalbuminemia

 Severe malnutrition
 Renal or GI loss
o Glomerulopathy, HIV enteropathy
 High catabolism
o Infections, burns

Globulin

 Transport protein
 Measures total amount of immunoglobulins (antibodies) in the
serum
 decrease in albumin leads to compensatory increase in globulin

Biochemical Markers of Liver Injury

Liver Enzymes

 Low levels always present in serum

 Leak out from cell after injury
 Very sensitive
 Magnitude of abnormality does not correlate well with degree of
injury

1) Aspartate Aminotransferase (AST)

 Present in skeletal muscle, kidney, brain

2) Alanine Aminotransferase (ALT)

 Present principally in liver

AST and ALT

 Elevated in most liver diseases

 Highest levels are in acute liver diseases
 Only slight elevations in chronic liver
diseases
 Usually increase in parallel
AST/ALT in Alcoholic Hepatitis

 Transaminases rarely exceed 300

 AST:ALT >2

Factors Affecting AST/ALT

 Depressed by pyridoxine (vit. B6)

deficiency
 Decreased by uremia and renal dialysis

3) Lactate Dehydrogenase (LDH)

 Component of classic LFT’s

 Highly non-specific

Tests of Impaired Hepatic Excretion Increased In

 Cholestasis
 Intra-hepatic biliary tract obstruction
 Extra-hepatic biliary obstruction

3) Alkaline Phosphatase

 Hydrolyzes phosphate esters at alkaline pH

 Also present in bone, kidney, placenta, intestine
 Mainly liver and bone in adults
 Increased in children from bone growth
 Placental form during pregnancy

Elevated Alkaline Phosphatase

 Can occur in any liver disease

 Highest with cholestasis or biliary tract obstruction
 Elevated in infiltrative diseases
 Due to increase synthesis and secretion

3) g-Glutamyl Transpeptidase (GGTP)

 Transfers g-glutamyl groups

 Widely distributed
 Sensitive correlate to alkaline phosphatase
 Non-specific (alcoholism, MI, DM, pancreatic disease, renal
failure)
Biochemical Markers of Specific Liver Diseases

1) Viral Hepatitis Serology

 HAV – anti-HAV IgM and IgG

 HBV – HBsAg, anti-HBsAg, and anti-HBcAg
 HCV – anti-HCV, HCV RNA

2) Serum Ferritin

 Widely distributed storage protein

 Levels reflect body iron stores
 Elevated in primary hemochromatosis
 Elevated in acute inflammation and cirrhosis

3) a1-Antitrypsin

 Inhibits serum trypsin

 Major component of a1-globulin
 Deficiency cause of neonatal hepatitis

4)Ceruloplasmin level - Checks blood copper levels, When suspecting Wilsons

disease with specific symptoms such as anemia, jaundice, dystonia

5)Antimitochondrial antibody titer -check autoantibodies related to Primary

Biliary Cholangitis (PBC), if abnormalities seen in liver panel with associated
symptoms such as itching, jaundice, enlarged liver
Lesson 2:
Pathology

Disorders of the
mouth
 Stomatitis is an inflamed and sore mouth
Stomatitis
 It can disrupt a person's ability to eat, talk, and sleep.
 Stomatitis can occur anywhere in the mouth, including the inside of the
cheeks, gums, tongue, lips, and palate.
 Two types:
o Canker sores (or Mouth ulcers)
o Cold sores (or Herpes Labialis) – caused by Herpes Simplex Virus
(HSV)

Canker Cold
Sore Sore
Tonsilliti
s  Tonsillitis is an infection or inflammation of the tonsils.

Mostly viral but could be bacterial as well (caused by

Streptococcus).

Gingivitis (Gum
inflammation)
 Gums get inflamed due to plaques build up.

 Gum bleeding is common, especially during

brushing.
Periodontitis (Gum
disease)
 Bad gingivitis (gum inflammation) can sometimes cause
periodontitis.
 Begins with a bacterial growth in the mouth.
 In severe cases, can cause tooth loss due to gum destruction.

Sjogren’s
syndrome
 Auto-immune disease
 Mostly after 40 years of age and affects more
women
 Characterized by dry eyes and dry mouth.
Disorders of the
esophagus
Esophagitis
1. The swelling of the esophagus is called esophagitis.
2. It can be caused due to infection or irritation of the esophagus.
3. This may result from vomiting, GERD (gastroesophageal reflux disease),
medications, or other factors.
4. Patients experience difficulty swallowing, mouth sores, heartburn, and
other symptoms.
Esophageal
varices
 Esophageal varices develop in liver cirrhosis.
 Esophageal varices is the development of engorged veins that develop
in the esophagus, due to pressure.
 Increased pressure develops when venous return to the liver is
obstructed.
 The most serious danger in esophageal varices is hemorrhage.
 Bleeding esophageal varices require emergency treatment.
Disorders of the
stomach

Hiatal
hernia
 A hernia is the protrusion of part of an organ through a muscular wall or
body opening.
 A hiatal hernia is the protrusion of part of the stomach through the
diaphragm at the point where the esophagus joins the stomach.
 Symptoms include Indigestion and heartburn after eating and possibly
shortness of breath
Gastriti
s  Inflammation, irritation, or erosion of the lining of the stomach is
called gastritis.
 It can be caused by irritation due to excessive alcohol use, chronic
vomiting, stress, the use of certain medications such as aspirin or
other anti- inflammatory drugs, or by a bacterium called Helicobacter
pylori (H. pylori).
 The most common symptoms of gastritis include nausea or recurrent
upset stomach, abdominal bloating and pain, vomiting, a burning
feeling in the stomach, and black or bloody stools.
Peptic ulcers
 Ulcers are lesions of anybody surface where necrotic tissue forms as a
result of inflammation and is sloughed off, leaving a hole.
 Ulcers of the stomach and small intestine are termed peptic ulcers.
 Ulcers of the stomach are called gastric ulcers and those of the small
intestine are called duodenal ulcers.

GERD (Gastroesophageal reflux disease)

 Backflow of stomach acid into the esophagus is called GERD
 Esophagus is not equipped to handle stomach acid, therefore acid
causes scaring of the esophageal walls.
 Most common symptom is heartburn, an uncomfortable burning
sensation.
 More severe symptoms: difficulty swallowing, chest pain
 Reflux into the throat can cause sore throat
 Complications include esophageal erosions, esophageal ulcer and
narrowing of the esophagus (esophageal stricture)
Gastroenteriti
s  Gastroenteritis is an inflammation of the stomach and intestines.
 Symptoms include nausea, vomiting, and diarrhea.
 The onset may be abrupt and violent with rapid loss of fluid and
electrolytes.
 Possible causes are bacterial or viral infection, chemical toxins,
lactose intolerance, or other food allergy.
 Contaminated food is one of the common reasons.
Disorders of
Intestines

Zollinger Ellison
Syndrome
ZE syndrome is a condition in which a gastrin-secreting tumor or hyperplasia
of the islet cells in the pancreas causes overproduction of gastric acid,
resulting in recurrent peptic ulcers.

Celiac
Disease
 Celiac Disease is a disease in which the small intestine is
hypersensitive to gluten, leading to difficulty in digesting food.
 It causes overtime damage to the gut wall.
Crohn's
Disease
 Crohn's disease is a life long inflammatory bowel disease (IBD)
 Parts of the digestive system get swollen and have deep sores called
ulcers.
 Crohn's disease usually is found in the last part of the small intestine
and the first part of the large intestine. But it can develop anywhere in
the digestive tract, from the mouth to the anus.
Disorders of the
colon
Ulcerative colitis
 Ulcerative colitis is a disease that causes inflammation and sores (ulcers)
in the lining of the large intestine (colon).
 It usually affects the lower section (sigmoid colon) and the rectum. But
it can affect the entire colon.
 In general, the more of the colon that's affected, the worse the
symptoms will be.
Irritable bowel
syndrome
 IBS is a widespread condition involving recurrent abdominal pain and
diarrhea or constipation, often associated with stress, depression,
anxiety, or previous intestinal infection.
 Causes are unknown.
 IBS symptoms include diarrhea, constipation, and abdominal cramps.

Diverticuliti
s  Diverticulosis happens when pouches (diverticula) form in the wall of the
colon.
 If these pouches get inflamed or infected, it is called diverticulitis.
 Diverticulitis can be very painful.
Pseudomembranous
colitis
 Pseudomembranous colitis, is inflammation of the colon associated
with an overgrowth of the bacterium Clostridium difficile (C. diff).
 It is also called antibiotic-associated colitis or C. difficile colitis.
 This overgrowth of C. difficile is most often related to recent antibiotic
use.

Choler
a  Cholera is an infectious disease that causes severe watery diarrhea.
 The diarrhea can lead to severe dehydration and even death if
untreated.
 It is caused by eating food or drinking water contaminated with a
bacterium called Vibrio cholerae.
Hemorrhoid
s  Enlarged (varicose) veins in the lining of the rectum near the anus.
 Hemorrhoids may be internal or external.
 Causes of hemorrhoids include heredity, poor dietary habits, inadequate
fiber, overuse of laxatives, and lack of exercise.

Disorders o the accessory

organs
Appendicitis
 Appendicitis is an acute inflammation of the appendix.
 The pain of appendicitis often begins in the middle of the abdomen and
shifts to the lower right quadrant.
 Nausea, vomiting, and fever are often symptoms.
Jaundic
e  Jaundice is a yellow or orange discoloration of the skin, tissues, and the
whites of the eyes.
 Jaundice is caused by a build-up of bilirubin, a pigment that is
normally secreted in the bile and removed from the body in the
feces.
 Types:
o Obstructive Jaundice
o Hemolytic Jaundice

Hepatiti
s  Hepatitis is inflammation of the liver caused by a number of factors.
 Several viruses have been identified as causing hepatitis.
 Important causes are hepatitis A, hepatitis B, hepatitis C, and
hepatitis D.
 Hepatitis also causes jaundice.
Liver
Cirrhosis
 Cirrhosis is a slowly progressing disease in which healthy liver tissue is
replaced with scar tissue, eventually preventing the liver from functioning
properly.
 The scar tissue blocks the flow of blood through the liver and slows
the processing of nutrients, hormones, drugs, and naturally
produced toxins.
 It also slows the production of proteins and other substances made by the
liver.
Gallstones
(Cholelithiasis)
 Gallstones are little pebble-like substances that form in the gallbladder, a
small organ located under the liver that helps with digestion.
 These stones develop because cholesterol and pigments in bile
sometimes form hard particles.