Gallbladder & extrahepatic bile ducts

Gallbladder nonneoplastic

Cholelithiasis

Topic Completed: 1 September 2012

Minor changes: 12 February 2021

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Cite this page: Gulwani H. Cholelithiasis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladdercholelithiasis.html. Accessed October 24th, 2021.

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

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

Images hosted on other servers:

Two pigment gallstones

Microscopic (histologic) description

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