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Gallbladder & extrahepatic bile ducts

Gallbladder nonneoplastic

Cholelithiasis


Editorial Board Member: Kimberley J. Evason, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Bilal Khan, D.O.
Upasana Joneja, M.D.

Last author update: 20 August 2025
Last staff update: 20 August 2025

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PubMed Search: Cholelithiasis

Bilal Khan, D.O.
Upasana Joneja, M.D.
Page views in 2025 to date: 6,035
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Videos | Sample pathology report | Differential diagnosis | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2 | Practice question #3 | Practice answer #3
Cite this page: Khan B, Joneja U. Cholelithiasis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/gallbladdercholelithiasis.html. Accessed September 14th, 2025.
Definition / general
  • Cholelithiasis, commonly known as gallstones, is a condition characterized by the formation of crystalline deposits in the gallbladder, resulting from an imbalance in bile composition
  • One of the most common pathologic conditions encountered in the adult gastrointestinal tract (StatPearls: Gallstones [Cholelithiasis] [Accessed 22 May 2025])
Essential features
  • Gallstones primarily consist of crystalline deposits of cholesterol, bilirubin polymers or other bile components
  • Risk factors
    • Modifiable: diet, increased estrogen exposure (i.e., female sex hormone use, obesity, multiparity), rapid weight loss, low physical activity, medications, total parenteral nutrition
    • Nonmodifiable: genetics, ethnicity, increasing age, female sex
  • Most cases are asymptomatic but gallstones can cause significant morbidity including biliary colic, cholecystitis and pancreatitis
  • Ultrasound is the diagnostic test of choice
  • Treatment: lifestyle modification, (laparoscopic) cholecystectomy if symptomatic (Syst Rev 2022;11:267)
Terminology
  • Gallstone
  • Cholelith
  • Calculus
ICD coding
  • ICD-10
    • K80.0 - calculus of gallbladder with acute cholecystitis
    • K80.1 - calculus of gallbladder with other cholecystitis
    • K80.2 - calculus of gallbladder without cholecystitis
    • K80.3 - calculus of bile duct with cholangitis
    • K80.4 - calculus of bile duct with cholecystitis
    • K80.5 - calculus of bile duct without cholangitis or cholecystitis
    • K80.6 - calculus of gallbladder and bile duct with cholecystitis
    • K80.7 - calculus of gallbladder and bile duct without cholecystitis
    • K80.8 - other cholelithiasis
  • ICD-11
    • DC11.0 - calculus of gallbladder or cystic duct with acute cholecystitis
    • DC11.1 - calculus of gallbladder or cystic duct with other cholecystitis
    • DC11.2 - calculus of gallbladder or cystic duct with cholangitis
    • DC11.3 - calculus of gallbladder or cystic duct without cholecystitis or cholangitis
    • DC11.4 - calculus of bile duct with cholangitis
    • DC11.5 - calculus of bile duct with cholecystitis
    • DC11.6 - calculus of bile duct without cholangitis or cholecystitis
    • DC11.7 - intrahepatic cholelithiasis
Epidemiology
Sites
  • Gallbladder
    • Gallstones can be luminal or intramural
    • Gallstones typically impact at the neck of the gallbladder, proximal to the cystic duct but can also obstruct the common bile duct (choledocholithiasis) or small bowel (gallstone ileus) (see Diagrams / tables)
Pathophysiology
  • Gallstones form due to supersaturation and precipitation of bile components (i.e., cholesterol, bilirubin, calcium, fatty acids) (Curr Opin Gastroenterol 2018;34:71)
    • Bile supersaturation: bile becomes supersaturated, leading to the formation of crystals that become trapped in gallbladder mucus, resulting in gallbladder sludge
    • Crystal nucleation and stone formation: crystals coalesce to form stones
    • Stone aggregation: stones agglomerate and can migrate into adjacent structures (i.e., biliary tree, small bowel) causing obstruction, inflammation and pain
  • 4 main types of stones (Scand J Gastroenterol 1990;25:720, Gastroenterol Clin North Am 2010;39:157, PLoS One 2013;8:e74887, Liver Res 2017;1:42)
    • Cholesterol stones: excess triglycerides and supersaturation of cholesterol, which leads to the formation of cholesterol monohydrate crystals
    • Pigment stones: supersaturation of bilirubin polymers (i.e., increased unconjugated bilirubin in bile)
      • Black pigment stones: derive from excess unconjugated bilirubin, most notably in the form of calcium bilirubinate
      • Brown pigment stones: derive from increased conversion of conjugated bilirubin to unconjugated bilirubin (secondary to bacterial or parasitic infection), as well as calcium soaps (i.e., palmitate), cholesterol and mucin
    • Mixed stone: contain ≥ 2 components, usually a combination of cholesterol plus pigment or salts
    • Other stones that are not classified as cholesterol, pigment or mixed exist and are classified according to their mineralized components (calcium, aluminum, silicon, etc.)
Etiology
  • Multifactorial etiology depending on stone type (Biomolecules 2022;12:550, World J Gastrointest Surg 2024;16:1130)
    • Increased age
    • Gallbladder hypomotility (i.e., bile stasis leads to precipitation of bile components; often associated with total parenteral nutrition)
    • Cholesterol stones: most commonly due to hypercholesterolemia, gallbladder stasis or deficiency in bile salts / acids (normally increase solubility) or phospholipids (i.e., lecithin)
      • Genetic predisposition: increased risk with apolipoprotein E genotype (Eur J Clin Invest 2018;48:e12935, Metabolites 2021;11:682)
      • Increased estrogen (i.e., female sex, multiparity, exogenous female sex hormone)
        • Estrogens increase expression of hepatic LDL receptors, causing a cascade of increased cholesterol uptake and HMG CoA reductase stimulation to increase cholesterol synthesis
      • Rapid weight loss can cause increased cholesterol secretion, altered bile composition, increased mucin production, hormone alterations and gallbladder stasis
      • Metabolic disorders: insulin resistance / diabetes (insulin resistance increases circulating cholesterol), dyslipidemia
      • Medications
        • Exogenous female sex hormone (i.e., oral contraceptives)
        • Fibrates (i.e., clofibrate): increased HMG CoA reductase activity decreases cholesterol conversion to bile acids by reducing cholesterol 7 alpha hydroxylase activity, causing excess biliary cholesterol secretion
        • Octreotide: somatostatin decreases postprandial cholecystokinin, leading to bile stasis (Cancer 1997;79:830)
    • Pigment stones
      • Black pigment stones
        • Elevated unconjugated bilirubin, which may be increased in hemolytic disease, cirrhosis, ileal dysfunction / bypass (i.e., Crohn's disease) and cystic fibrosis, leads to higher risk of black pigment stone formation (J Clin Invest 1980;65:1301)
      • Brown pigment stones
        • Bacterial or parasitic infection of the gallbladder or biliary tree
        • Pathogenic beta glucuronidases deconjugate bilirubin, causing unconjugated bilirubin precipitation and subsequent stone formation
        • Commonly associated with Escherichia coli, Ascaris lumbricoides and Clonorchis sinensis infection (J Appl Microbiol 2024;135:lxae096)
Diagrams / tables

Images hosted on other servers:
Common gallstone obstruction sites

Common gallstone obstruction sites

Type I Mirizzi syndrome

Type I Mirizzi syndrome

Clinical features
  • Usually asymptomatic (Dig Dis Sci 2007;52:1313)
  • Symptoms may include
    • Biliary colic: right upper quadrant pain, often postprandial secondary to fatty foods
    • Symptoms associated with gallstone related disease (i.e., cholecystitis, cholangitis), including Charcot triad (fever, jaundice and pain) and Reynold pentad (hypotension plus altered mental status / confusion)
  • Complications may include
    • Acute or chronic cholecystitis
    • Cholangitis
    • Stone impaction
      • Mirizzi syndrome: classified into 5 types based on the nature of bile duct obstruction (World J Gastroenterol 2012;18:4639)
        • Type 1: stone in gallbladder neck or cystic duct causing external compression / obstruction of the common hepatic duct
        • Type 2: gallstone erosion creates cholecystobiliary fistula involving < 33% of the common hepatic duct circumference
        • Type 3: cholecystobiliary fistula involving < 66% of the common hepatic duct circumference
        • Type 4: cholecystobiliary fistula involving > 66% of the common hepatic duct circumference
        • Type 5: Mirizzi syndrome with a cholecystoenteric fistula (with or without gallstone ileus)
    • Choledocholithiasis: stone in common bile duct
    • Gallstone ileus: stone in small intestine
    • Pancreatitis: due to stone impaction near the ampulla of Vater
Diagnosis
  • Ultrasound: first line; ~95% sensitivity / specificity for gallstones ≥ 2 mm (Radiographics 2000;20:751)
  • Plain Xrays: detect 10 - 25% of gallstones that are radiopaque due to calcium (Radiographics 2000;20:751)
    • Cholesterol and brown pigment stones are typically radiolucent
    • Black pigment stones are typically radiopaque
  • Endoscopic retrograde cholangiopancreatography (ERCP) / magnetic resonance cholangiopancreatography (MRCP): highly sensitive and specific for choledocholithiasis (Radiographics 2000;20:751)
  • Computed tomography (CT) scans and magnetic resonance imaging (MRI): not routinely used; can identify gallstones but are less sensitive for acute cholecystitis (Radiographics 2000;20:751)
Laboratory
Radiology description
  • Ultrasound: hyperechoic with posterior acoustic shadowing and gallbladder sludge
    • Sonographic Murphy sign: abrupt cessation of inspiration when the ultrasound probe is pressed over the gallbladder is highly specific for acute cholecystitis
  • CT and MRI / MRCP: useful for visualizing choledocholithiasis and assessing complicated disease such as cholecystitis
  • Diagnostic imaging showing dilation of the common bile duct may suggest choledocholithiasis
  • Reference: StatPearls: Gallbladder Imaging [Accessed 22 July 2025]
Radiology images

Images hosted on other servers:
Cholelithiasis ultrasound

Cholelithiasis ultrasound

Cholelithiasis and choledocholithiasis MRI

Cholelithiasis and
choledocholithiasis
MRI

Prognostic factors
Case reports
Treatment
  • Treatment ranges from lifestyle modification to surgery, depending on clinical features and associated complications (Dtsch Arztebl Int 2020;117:148)
    • Lifestyle modifications: low fat diet, regular exercise and abstaining from prolonged fasting may help minimize symptoms
    • Pharmacologic: ursodeoxycholic acid (ursodiol) can be administered for gallstone dissolution, though the dissolution rate is < 50%
    • Laparoscopic cholecystectomy: standard of care for symptomatic gallstones
    • Open cholecystectomy: reserved for cases where a minimally invasive approach is not feasible or safe
    • ERCP: preoperative, postoperative or intraoperative ERCP is employed in combination with laparoscopic or open common bile duct exploration for choledocholithiasis
    • Cholecystostomy tube: can be placed for unstable patients or poor surgical candidates with cholecystitis
Gross description
  • Gallbladders affected by cholelithiasis may appear thick walled or fibrotic and can contain 1 or multiple stones of varying size
    • Gallstones may be freely luminal, impacted in the cystic duct or biliary tree or embedded within the mucosa or wall
    • Number and aggregate size of the stones can vary, with the largest stones sometimes measuring several centimeters
  • Gallstone types include
    • Cholesterol stones: round or polygonal, pale yellow to brown, with a firm, crystalline radial cut surface; when multiple, they may display faceted surfaces from close apposition
    • Black pigment stones: typically multiple, small, hard, shiny stones with a black external surface and a laminated internal structure
    • Brown pigment stones: usually soft, brown and may be single or multiple
    • Mixed stones: show heterogeneous characteristics depending on composition
    • Calcium stones (rare): gray-white and amorphous
  • Biliary sludge may also be present, sometimes appearing as thick, inspissated, cream-gray to yellow-green putty-like material; in rare instances, radiopaque calcium carbonate may fill the lumen
Gross images

Contributed by Laura Bancer, PA (ASCP) and Bilal Khan, D.O.
Cholesterol stone

Cholesterol stone

Pigment gallstone

Pigment gallstone

Mixed gallstone

Mixed gallstone

Microscopic (histologic) description
  • Stones are typically not submitted for histology
  • Characteristic histologic findings of the hepatobiliary system may exist in pathology associated with cholelithiasis
    • Common findings include chronic inflammation, Rokitansky-Aschoff sinuses, cholesterolosis, epithelial metaplasia
  • Microscopic findings of the gallbladder may assist in stone identification: adenomatous hyperplasia and Rokitansky-Aschoff sinuses are associated with cholesterol and mixed stones but not pigment stones (Trop Gastroenterol 2002;23:25)
Videos

Gallstones (cholelithiasis)

Sample pathology report
  • Gallbladder, laparoscopic cholecystectomy:
    • Chronic calculous cholecystitis

  • Gallbladder, laparoscopic cholecystectomy:
    • Chronic cholecystitis with cholelithiasis
Differential diagnosis
  • Acute or chronic cholecystitis:
    • Can be associated with stones (> 90% of cases) or without stones (acalculous cholecystitis)
    • Characterized by gallbladder wall thickening and inflammation
    • Chronic cases may show fibrosis and Rokitansky-Aschoff sinuses
  • Choledocholithiasis:
    • Stones in the common bile duct; most commonly secondary type (due to migrated gallstones)
    • Less often, primary bile duct stones can also occur (J Clin Med Res 2022;14:441)
    • May lead to biliary obstruction, jaundice and pancreatitis
  • Pancreatitis:
    • Gallstones are a leading cause of acute pancreatitis, most commonly caused by gallstone obstruction of the distal bile duct, pancreatic duct or ampulla of Vater
    • Characterized by acute inflammation with hemorrhage and necrosis
  • Ascending cholangitis:
    • Due to obstruction of extrahepatic bile ducts, often due to gallstones
    • Characterized by neutrophils within epithelium and lumen of interlobular bile ducts
  • Hydrops / mucocele:
    • Most often due to impacted stones in the cystic duct
    • Characterized by gallbladder distention due to prolonged obstruction, leading to accumulation of mucus or fluid
    • Typically no inflammation
  • Gallbladder malignancy (rare):
    • Cholelithiasis is a major risk factor
    • Up to 50% are detected incidentally in routine cholecystectomy
    • Overall, 5 year survival rate of < 10%
Practice question #1


A 37 year old woman presents with intermittent right upper quadrant pain that worsens after fatty meals. Imaging reveals multiple radiolucent gallstones. Gross examination reveals the findings shown in the image. Biochemical analysis of bile shows supersaturation with a lipid based compound. What is the most likely primary composition of these gallstones?

  1. Calcium bilirubinate
  2. Calcium carbonate
  3. Cholesterol monohydrate
  4. Mixed cholesterol and pigment components
Practice answer #1
C. Cholesterol monohydrate. Most gallstones in Western populations are cholesterol based, primarily composed of cholesterol monohydrate. These stones appear yellow, crystalline and often faceted, as seen in the provided image. They are associated with risk factors such as female sex, obesity, rapid weight loss, pregnancy and metabolic syndrome. Answer B is incorrect because calcium carbonate stones are rare. Answer A is incorrect because calcium bilirubinate is a key component of black pigment stones seen in hemolytic disease. Answer D is incorrect because mixed stones contain a combination of cholesterol and pigment but are less common than pure cholesterol stones.

Comment Here

Reference: Cholelithiasis
Practice question #2


A 52 year old woman presents with postprandial right upper quadrant pain and nausea. Physical examination reveals a positive Murphy sign. Laboratory tests show mildly elevated alkaline phosphatase and normal bilirubin levels. Gross findings following laparoscopic cholecystectomy are shown in the image. Which imaging modality provides the highest sensitivity for detecting the suspected diagnosis?

  1. CT scan
  2. Magnetic resonance cholangiopancreatography (MRCP)
  3. Ultrasound
  4. Xray
Practice answer #2
C. Ultrasound. Ultrasound is the most sensitive and specific imaging modality for detecting gallstones, with 95% sensitivity and specificity. It is the first line diagnostic test, particularly for detecting noncalcified gallstones and gallbladder wall thickening indicative of cholecystitis. Answer A is incorrect because CT scan is less sensitive for small or noncalcified gallstones. Answer D is incorrect because Xray detects only ~10 - 25% of gallstones, as most are radiolucent. Answer B is incorrect because MRCP is excellent for detecting bile duct stones but it is not the first line modality for gallbladder stones.

Comment Here

Reference: Cholelithiasis
Practice question #3


A 67 year old man with hereditary spherocytosis undergoes a cholecystectomy for chronic cholelithiasis. Gross examination reveals the findings shown in the image. Chemical analysis confirms the presence of calcium bilirubinate and minimal cholesterol content. Based on the composition and clinical history, which of the following is the most likely mechanism underlying the formation of these stones?

  1. Bacterial deconjugation of bilirubin in an infected biliary tract
  2. Impaired hepatic bile acid secretion leading to cholesterol nucleation
  3. Increased unconjugated bilirubin precipitation due to chronic hemolysis
  4. Supersaturation of bile with cholesterol due to hepatic overproduction
Practice answer #3
C. Increased unconjugated bilirubin precipitation due to chronic hemolysis. Black pigment stones, as seen in the image, are composed primarily of calcium bilirubinate and are strongly associated with chronic hemolysis (i.e., hereditary spherocytosis, sickle cell disease, thalassemia). Chronic hemolysis leads to excessive production of unconjugated bilirubin, which precipitates in the bile and forms insoluble calcium bilirubinate. Answer D is incorrect because cholesterol stones result from supersaturation of bile with cholesterol, leading to crystallization. These are typically yellow and associated with metabolic conditions. Answer B is incorrect because impaired hepatic bile acid secretion leads to cholesterol stone formation, not pigment stones. Answer A is incorrect because brown pigment stones (not black) are linked to biliary infections, where bacterial beta glucuronidases deconjugate bilirubin, promoting stone formation.

Comment Here

Reference: Cholelithiasis
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