VI.

PATHOPHYSIOLOGY
A. THEORETICAL BASED (SOURCE: GASTROINTESTINAL AND LIVER DISEASE BY SLEISENGER AND FORDTRAN)

NON-MODIFIABLE FACTORS MODIFIABLE FACTORS

*Age Increase in age = increase in Increased activity of 3- *Obesity
prevalence of gallstones hydroxyl-3-methylglutaryl
coenzyme A reductase *Rapid
*Gender Women = more estrogen weight
than men Caloric
loss
restriction
*Pregnancy Increased progesterone
*Total
Prolonged fasting parenteral
Increased estrogen nutrition
Sphincter of
Gallbladder volume Oddi fails to
Estrogen(in men) *Drugs
is doubled relax
*Disease
of the Receptors that
Increased hepatic Lipid-lowering
ileum radiate the
LDL receptor
reabsorption of bile
Fibric acid
Decreased derivative
Increased clearance of
bile acid pool
plasma LDL cholesterol
Decreases
activity of
Decreased plasma
cholesterol
LDL; increased
7α-
plasma HDL
ceftriaxone hydroxylase

Decreases bile
40% is secreted and unmetabolized into bile
acid
contrentations
Acetyl CoA BILE
Produces cholesterol as fatty
cholesterol
acid ester
transferase(ACAT)
Secondary acid: Tertiary acid:
Primary acid:
Cholesterol is stored in the liver deoxycholate and ursodeoxycholate
chenodeoxycholate
lithocholate
Low ACAT and cholate
activity

enlarged Cholesterol ester pool Secreted by ATP-binding cassettes

superfamily from hepatocytes into bile

Supply of free cholesterol

ABCG5 with ABCB11 transports
for bile acid formation and ABCB4 transports
ABCG8 trasports bile acids
lipoprotein assembly phospholipids
cholesterol
Secretion of bile salts
Endoplasmic If mutated
reticulum(synthesizes cholesterol Correlates with
with HMG CoA reductase(rate- arachidonic acid
limiting enzyme)
Precursor of
Increases activities of prostaglandin
HMG CoA reductase

Gallbladder

Increase solubility of
Acidifies bile
calcium salts

Precipitation
less favorable
 Stimulates hepatic
cholesterol
secretion into bile

Stimulates mucin
secretion

Increased rate Made up of

of cholesterol hydrophobic regions
synthesis that can bind to
cholesterol,
phospholipid and
Decreased flow of
bilirubin
bile into
gallbladder
Accelerates nucleation with
Bile becomes unconjugated bilirubin
more lithogenic
Cholesterol is
carried in the form Supersaturated
of vesicles bile

Unilamellar Sludge and

coalesce into gallstone
multilamellar formation

Less stable Biliary sludge

stasis

Stone