Gallbladder & extrahepatic bile ducts

Gallbladder nonneoplastic


Last author update: 1 September 2012
Last staff update: 1 May 2023

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PubMed Search: Cholelithiasis[TI] gallbladder[TI] full text[sb]

Hanni Gulwani, M.B.B.S.
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Cite this page: Gulwani H. Cholelithiasis. website. Accessed April 15th, 2024.
Definition / general
  • Also called gallstones
  • Accounts for 1% of national heath care budget
  • Affects 10% of adults in developed countries (80% are silent) vs. < 1% of children
  • 80% of gallstones in West are cholesterol stones with 50% or more crystalline cholesterol monohydrate
  • 20% of gallstones in West are pigment stones composed of bilirubin calcium salts
  • Gallstones impact at neck just proximal to cystic duct
  • Typically within lumen but may be intramural

Risk factors:
  • Pima, Hopi or Navajo (75% of stones are pure cholesterol vs. 25% in industrialized vs. minimal in developing countries), also Scandinavians, Chileans, Mexican Americans, increasing age (> 50% risk by age 80)
  • Fat, fertile [multiple pregnancies], forty, female, obesity (Korean J Gastroenterol 2012;59:27), rapid weight loss, gallbladder stasis, genetic disorders that impair bile salt synthesis / secretion or increase cholesterol levels (serum or biliary), low HDL levels
  • May be influenced by Apolipoprotein E genotype (Ann Epidemiol 2006;16:763)
  • Biliary sludge typically occurs before gallstones
  • Estrogens from birth control pills or pregnancy increase expression of hepatic LDL receptors, which increase cholesterol uptake, which stimulate HMG CoA reductase, which synthesizes cholesterol
  • Pigment stone risk factors are increased unconjugated bilirubin (from hemolytic syndromes, ileal dysfunction / bypass, bacterial contamination of biliary tree)

  • Anticholesterol drug that increases HMG CoA reductase activity and decreases conversion of cholesterol to bile acids by reducing cholesterol 7 alpha hydroxylase activity, causes excess biliary secretion of cholesterol

  • Usually none but may have biliary colic (severe, right upper quadrant pain)

  • 1 - 2% have acute or chronic cholecystitis, choledocholithiasis, cholangitis, empyema, gallstone ileus, acute pancreatitis

Mirizzi syndrome:
  • Rare
  • Stone impacting in cystic duct or gallbladder neck causes extrinsic compression or obstruction of common bile duct, causing jaundice

  • Presence of biliary sludge, number, size and type of gallstones
Clinical features
  • Gallstones are composed of insoluble bile components: cholesterol, calcium bilirubinate, calcium salts (organic and inorganic), bile salts, mucin glycoproteins
  • In U.S., 75 - 85% are cholesterol stones, 15 - 25% are pigment stones
  • Larger stones are associated with carcinoma (Trop Gastroenterol 2012;33:39); also cholesterol, not pigment stones (Aust N Z J Surg 2000;70:667)
  • Calcium stones are gray white and amorphous; very uncommon
  • Calcium carbonate may fill lumen as thick, inspissated, cream gray to yellow green putty-like material
  • Choledocholithiasis: stones in common bile duct
    • 40% of common bile duct stones are brown stones, usually associated with recurrent pyogenic cholangitis and older age (J Int Med Res 2009;37:1220)
    • Primary: originate in common bile duct
    • Secondary: originate in gallbladder
    • ERCP (95% sensitive and specific), ultrasound is only 50% sensitive
Cholesterol stones
  • 75 - 85% of all gallstones
  • Only 10% are pure (at least 90% cholesterol), the remainder are mixtures with at least 60% cholesterol by weight
  • Cholesterol monohydrate precipitates when no longer soluble in bile
  • Initially bile supersaturation with cholesterol occurs
  • Then nucleation (initial crystallization), then stone growth facilitated by bile stasis and mucin hypersecretion
  • Pure and mixed occur predominantly in women
  • Also associated with increasing age, obesity, rapid weight loss, diabetes, ileal disease, multiple pregnancies, total parenteral nutrition, various drugs, specific ethnic groups
  • Adenomatous hyperplasia and Rokitansky-Aschoff sinuses:associated with mixed and cholesterol stones; not associated with pigment stones (Trop Gastroenterol 2002;23:25)
Pigment stones
  • 15 - 25% of all gallstones
  • Associated with increasing age
  • Less than 25 - 35% cholesterol
  • Composed of calcium bilirubinate, calcium salts, mucin glycoprotein
  • Brown (not black) stones associated with infected bile (usually E. coli) due to acute cholecystitis or choledocholithiasis with cholangitis
  • Black stones associated with older age, chronic hemolysis, cirrhosis, sclerosing cholangitis (increased unconjugated bilirubin in bile)
  • Ultrasound (95% sensitive and specific for gallstones 2 mm or larger or gallbladder sludge), Xrays detect 10 - 25% of gallstones that are radiopaque due to calcium
  • Laparoscopic cholecystectomy if symptomatic or in children, Native Americans, patients with sickle cell disease or porcelain gallbladder, stones 3 cm or larger
Gross description
  • 85% are 2 cm or less
  • Cholesterol stones: < 1 cm to 4 cm; single or multiple; white yellow, round / oval with crystalline cut surface
  • Pigmen stones: multiple shiny black stones, 0.2 to 5 cm, rarely brown in U.S. (more commonly brown in Japan)
Gross images

Contributed by Jian-Hua Qiao, M.D.

2 pigment gallstones

Microscopic (histologic) description
  • Minimal / mild lymphocytic mucosal inflammation, Rokitansky-Aschoff sinuses, fibrosis, thickening of muscularis propria, cholesterolosis, focal epithelial metaplasia (pyloric / gastric mucin cell metaplasia or intestinal metaplasia) (Am J Surg Pathol 2003;27:1313)
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