Cholelithiasis

Cholelithiasis (Gallstones)

• Cholelithiasis-Stone in gallbladder.

Two main types of gallstones.

1) Cholesterol stones

2) Pigment stones

Risk Factors for Gallstones

1) Cholesterol Stones:

• Demography: Northern Europe, US

• Advancing age

• Female sex hormones

-Female gender

-Oral contraceptives

-Pregnancy

• Obesity

• Rapid weight reduction

• Gallbladder stasis

• Inborn disorders of bile acid metabolism

• Hyperlipidemia syndromes

2) Pigment Stones:

• Demography: Asian more than Western, rural more than urban.

• Chronic hemolytic syndromes

• Biliary infection

• Gl disorders: ileal disease (Crohn disease), ileal resection or bypass, cystic fibrosis with pancreatic insufficiency

• However, 80% of individuals have no identifying risk factors other than age and gender.

• Heredity: Family history increases risk.

• Age and gender differences- Major role of hypersecretion of biliary of cholesterol.

• Estrogen exposure- OCP use and during pregnancy increases expression of hepatic lipoprotein receptors and stimulates hepatic HMG-CoA reductase activity, enhancing both cholesterol uptake and biosynthesis Excess biliary secretion of cholesterol.

• Obesity-increase biliary cholesterol secretion.

• Rapid weight reduction- Cholesterol level ↑& amount of bile salts ↓. Long periods of starvation ↓ gallbladder contractions- not enough to empty out bile gallstones

form

• Gallbladder stasis-favorable for both cholesterol and pigment gallstone formation.

• Hereditary factors

Pathogenesis of Cholesterol Stones

• Cholesterol is rendered soluble in bile by aggregation with water-soluble bile salts and water-insoluble lecithins, both of which act as detergents. When cholesterol concentrations exceed solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals.

Four conditions contribute to formation of cholesterol gallstones

(1) supersaturation of bile with cholesterol

(2) hypomotility of gallbladder

(3) accelerated cholesterol crystal nucleation

(4) hypersecretion of mucus in gallbladdertraps nucleated crystals accretion of

more cholesterol and appearance of macroscopic stones.

Pathogenesis of Pigment Stones

• Disorders that are associated with elevated levels of unconjugated bilirubin in bile, such as chronic hemolytic anemias, severe ileal dysfunction or bypass, and bacterial contamination of biliary tree, increase risk of developing pigment stones.

• Unconjugated bilirubin is normally a minor component of bile, but increases when infection of biliary tract leads to release of microbial β-glucuronidases, which hydrolyze bilirubin glucuronides.

• Thus, infection of biliary tract with Escherichia coli, Ascaris lumbricoides, or liver fuke C. sinensis, increases risk of pigment stone formation.

• In hemolytic anemias secretion of conjugated bilirubin into bile increases.

• About 1% of bilirubin glucuronides are deconjugated in biliary tree, and in setting of chronically increased secretion of conjugated bilirubin, there is sufficiently large amount of deconjugated bilirubin left to allow pigment stones to form.

MORPHOLOGY

Cholesterol stones-

• Arise exclusively in gallbladder.

• 100% pure (rare) to around50% cholesterol.

• Pure cholesterol stones- pale yellow,round to ovoid, have a finelygranular, hard external surfacewhich on transection reveals aglistening radiating crystallinepalisade.

• With increasing proportions ofcalcium carbonate, phosphates, andbilirubin, stones take on a gray-white to black color, may belamellated.

• Usually multiple stones present.

• Rarely, a very large stone fillfundus.

.

• Surfaces of multiple stones may berounded or faceted, because oftight apposition.

• Stones composed largely ofcholesterol- radiolucent; sufficientcalcium carbonate found in 10-20%of cholesterol stones-radiopaque.

Pigment gallstones• Brown to black.• Black pigment stones are found in

sterile gallbladder bile and brownstones in infected large bileducts.

• Black stones contain oxidizedpolymers of calcium salts ofunconjugated bilirubin, small amountsof calcium carbonate, calciumphosphate, and mucin glycoprotein,and some cholesterol monohydratecrystals.

• Brown stones contain similarcompounds along with somecholesterol and calcium salts ofpalmitate and stearate.

• Black stones-rarely greater than 1.5cm in diameter, present in greatnumber; are quite friable.

• Their contours are usuallyspiculated and molded.

• Brown stones- laminated and softand may have a soaplike orgreasy consistency.

• 50-75% of black stones areradiopaque due to calcium saltswhile brown stones, containingcalcium soaps, are radiolucent.

Clinical features

• 70-80% asymptomatic throughout life.

• Remainder symptomatic.

• Pain- constant or "colicky" (spasmodic) from an obstructed gallbladder or when small gallstones move down-stream and lodge in biliary tree.

• Inflammation of gallbladder with stones also generates pain.

• Pain is localized to right upper quadrant or epigastrium that may radiate to right shoulder or back.

COMPLICATIONS

• Infammation of gallbladder (cholecystitis)

More severe complications-

• empyema

• perforation

• fistulas

• infammation of biliary tree (cholangitis)

• obstructive cholestasis and pancreatitis.

• Occasionally a large stone may erode directly into an adjacent loop of small bowel, generating intestinal obstruction (“gallstone ileus”).

• Increased risk of gallbladder carcinoma.