Gallbladder & extrahepatic bile ducts
Gallbladder nonneoplastic
Cholelithiasis
Author: Hanni Gulwani, M.B.B.S.
Last author update: 1 September 2012
Last staff update: 1 May 2023
Copyright: 2003-2025, PathologyOutlines.com, Inc.
PubMed Search: Cholelithiasis[TI] gallbladder[TI] full text[sb]
Table of Contents
Definition / general | Clinical features | Cholesterol stones | Pigment stones | Diagnosis | Treatment | Gross description | Gross images | Microscopic (histologic) descriptionCite this page: Gulwani H. Cholelithiasis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladdercholelithiasis.html. Accessed January 7th, 2025.
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)
Clofibrate:
- 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
Symptoms:
- Usually none but may have biliary colic (severe, right upper quadrant pain)
Complications:
- 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
Report:
- 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)
Diagnosis
- 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
Treatment
- 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)
