• Clinical science

Cholelithiasis, choledocholithiasis, cholecystitis, and cholangitis


Cholelithiasis refers to the presence of abnormal concretions (gallstones) in the gallbladder and choledocholithiasis refers to gallstones in the common bile duct. About 10–20% of American adults have gallstones. Gallstones most commonly consist of cholesterol but may be pigmented (due to hemolysis or infection) or mixed. Both cholelithiasis and choledocholithiasis can manifest with postprandial RUQ pain, nausea, and vomiting. The diagnosis is confirmed by ultrasound, although choledocholithiasis may also require ERCP. Symptomatic cholelithiasis is managed with laparoscopic cholecystectomy. Choledocholithiasis requires stone removal, usually via ERCP.

Cholecystitis is inflammation of the gallbladder that most commonly occurs after cystic duct obstruction from cholelithiasis (calculous cholecystitis). Acalculous cholecystitis is less common and seen primarily in critically ill patients. In addition to the Murphy sign (inspiratory arrest during RUQ palpation due to pain), typical signs include fever and RUQ guarding. The diagnosis is made clinically and confirmed via ultrasound. Cholescintigraphy (HIDA scan) is a useful adjunctive diagnostic tool if ultrasound is unrevealing. The definitive treatment for complicated cholecystitis is laparoscopic cholecystectomy, either performed within 72 hours of onset or after a course of antibiotics when inflammation subsides (usually after at least 6 weeks). Complications of cholecystitis include gallbladder gangrene and rupture, empyema, gallstone ileus, emphysematous cholecystitis, and abscess formation. Chronic gallbladder inflammation increases the risk of gallbladder carcinoma, which can present with jaundice and an enlarged, painless gallbladder (Courvoisier sign).

Cholangitis (also known as ascending cholangitis or acute cholangitis) is an infection of the biliary tract. It is caused by obstruction of the biliary tree, which may lead to bile stasis and subsequent bacterial infection. Clinically it is characterized by the Charcot triad, which consists of abdominal pain, fever, and jaundice, although jaundice is not always present. Sepsis and septic shock may develop as a complication of acute cholangitis. The diagnosis should be suspected in patients with fever, laboratory tests showing inflammation, and jaundice or abnormal liver enzymes. Treatment includes resuscitation, broad-spectrum antibiotics, and urgent biliary drainage.


Cholelithiasis Choledocholithiasis Acute cholecystitis Acute cholangitis
  • Bile cholesterol oversaturation, bile stasis, impaired bile acid circulation → precipitation of gallstones in the gallbladder
  • Cholelithiasis → migration of gallstones into the common bile duct
  • Choledocholithiasis → obstruction and stasis within the biliary tract → subsequent bacterial infection
Clinical features
Laboratory findings
  • Normal
Diagnostic imaging
  • US: gallstones with posterior acoustic shadow
  • US: dilated common bile duct, intrahepatic biliary dilatation
  • MRCP or ERCP: filling defect in the contrast-enhanced duct
  • US: gallbladder wall thickening and/or edema (double wall sign)
  • HIDA scan if diagnosis uncertain
  • US: biliary dilation and/or evidence of obstruction (e.g., cholelithiasis)
  • MRCP if diagnosis uncertain


Epidemiology [1][2]

  • Sex: > (2–3:1)
  • Prevalence: approx. 10–20% of the adult population in the US
  • Peak incidence: : > 40 years


Cholesterol stones; ∼ 80% of all stones [1][2]

During pregnancy, increased estrogen levels cause increased secretion of lithogenic bile (rich in cholesterol), resulting in the formation of cholesterol gallstones. Increased progesterone levels cause smooth muscle relaxation, decreased and impaired gallbladder contraction, and subsequent bile stasis and formation of gallstones.

Rule of the 6 Fs: Fat, Female, Fertile, Forty, Fair-skinned, Family history.

Black pigment stones, ∼ 10% of all stones [3][1][4]

Mixed (brown pigment stones); ∼ 10% of all stones [3][1][4][5]

  • Risk factors: bacterial infection in the biliary tract (e.g., Clonorchis sinensis, Opisthorcus species)
  • Pathophysiology: bacterial β-glucuronidase hydrolyzes conjugated bilirubin and lecithin in the bile → increased unconjugated bilirubin and fatty acids → precipitation of calcium carbonate, cholesterol, and calcium bilirubinate in bile

Clinical features [6][7]

  • Most gallstones are asymptomatic.
  • Biliary colic: constant, dull RUQ pain lasting < 6 hours
    • Especially postprandial
    • May radiate to the epigastrium, right shoulder, and back (referred pain)
  • Nausea, vomiting, early satiety
  • Bloating, dyspepsia

Only a minority of patients with gallstones are symptomatic!

Diagnostics [6]

  • Approach: conduct RUQ ultrasound → perform further imaging (EUS or MRCP) if concurrent common bile duct stones are suspected or if US is equivocal
  • Laboratory findings: usually normal in uncomplicated cholelithiasis
  • Imaging:
    • RUQ ultrasound: best initial test (85–90% sensitivity, 99% specificity) [8]
      • Shows gallstones with posterior acoustic shadow, possible sludge
    • Endoscopic ultrasound (EUS) is more sensitive than transabdominal ultrasound.
    • MRCP only if concurrent common bile duct stones are suspected

X-ray is rarely diagnostic because only 10–15% of stones (i.e., pigment stones) are radiopaque. Cholesterol stones are radiolucent!

Laboratory test results (e.g., WBC count, bilirubin, amylase) are usually normal in uncomplicated cholelithiasis!

Treatment [9][10][11][12][13]

Cholecystectomy is usually not indicated in asymptomatic cholelithiasis!

Complications [15][16]


Epidemiology [17][5]

Etiology [7][1]

Clinical features [17][7]

Diagnostics [17]

  • Approach: conduct laboratory tests and transabdominal ultrasound to determine the risk of choledocholithiasis → further confirmatory imaging (MRCP, ERCP, EUS) if clinical suspicion remains high
  • Laboratory findings
  • Imaging
    • Transabdominal ultrasound
      • Dilated common bile duct with possible intrahepatic biliary dilatation [18]
      • Depending on the location, the occluding stone may be visualized.
    • Further confirmatory imaging depends on the estimated risk of choledocholithiasis.[19]
      • High risk → ERCP (see “Treatment” below)
      • Intermediate risk→ MRCP or EUS
      • Low risk → treatment of cholelithiasis (no further imaging)

Treatment [17][19][14]

Complications [20]

  • Gallstone ileus: mechanical ileus due to obstructive gallstones
    • Pathophysiology: perforation and fistula formation between the inflamed gallbladder and bowel → gallstones pass down into bowel lumen
    • Location: most commonly in the terminal ileum and ileocecal valve (intestinal section with the narrowest lumen)
    • Symptoms: abdominal pain and distention, nausea, vomiting
    • Typical signs: pneumobilia
  • Gallstone pancreatitis
  • Acute cholangitis
  • Acute cholecystitis
  • Biliary stricture
  • Hepatic abscess (rare)


Acute calculous cholecystitis (90–95%)

Epidemiology [21]

Etiology [21]

Clinical features [21][22][23][12][7]

  • RUQ pain
    • More severe and prolonged (> 6 hours) than in cholelithiasis
    • Postprandial
    • Radiation to the right scapula
  • Positive Murphy sign: sudden pausing during inspiration upon deep palpation of the right upper quadrant due to pain
  • Guarding
  • Fever, malaise, anorexia
  • Nausea and vomiting

Acute cholecystitis should always be suspected in a patient with a history of gallstones who presents with RUQ pain, fever, and leukocytosis.

Diagnostics [21][22][23]

  • Approach: laboratory tests and RUQ ultrasound to identify gallbladder wall inflammation → perform HIDA scan if US not diagnostic but clinical suspicion remains high
  • Laboratory findings
  • Imaging
    • Transabdominal ultrasound
      • Gallbladder wall thickening > 4 mm; (postprandial > 5 mm)
      • Gallbladder wall edema (double wall sign)
      • Possible free fluid surrounding the gallbladder
      • Sonographic Murphy sign
      • Presence of concrement or gallstones
    • HIDA scan (cholescintigraphy) if US is not diagnostic
      • Radioactive tracer 99mTc-hepatic iminodiacetic acid is injected intravenously → selective uptake by hepatocytes → subsequent excretion into bile → can be visualized via a gamma camera
      • Abnormal if gallbladder not visualized within 30–60 minutes: suggests cystic duct obstruction due to edema or obstructing stone
    • MRCP and abdominal CT are not routinely recommended but may be used to evaluate for complications (e.g., choledocholithiasis, perforation).

Treatment [24][14][25]

Subtypes and variants

Acalculous cholecystitis (5–10%) [27]

  • Definition: : an acute necroinflammatory disorder of the gallbladder, usually seen in critically ill patients; , that is not associated with gallstones
  • Etiology: conditions that result in biliary stasis (e.g., multiorgan failure, severe trauma, surgery, sepsis, total parenteral nutrition, prolonged fasting) and a "stressed gallbladder" with reduced perfusion
  • Clinical features: fever, RUQ tenderness
  • Diagnostics
  • Treatment

Emphysematous cholecystitis (rare) [21][22][23]

  • Definition: a rare form of acute cholecystitis that occurs most often in elderly diabetic men
  • Etiology: infection of the gallbladder with gas-forming bacteria (e.g., Clostridium welchii)
  • Clinical features: fever, RUQ pain, absent peritoneal signs with possible crepitus in the abdominal wall (rare); associated with early gangrene and gallbladder perforation
  • Diagnostics: Ultrasound or CT demonstrates air in the gallbladder wall or lumen.
  • Treatment: emergency cholecystectomy

Complications of acute cholecystitis [24]

Complications of chronic cholecystitis

Chronic gallbladder inflammation increases the risk of gallbladder carcinoma!

Complications of laparoscopic cholecystectomy [16]

  • Iatrogenic injury to bile ducts or the hepatic artery (e.g., due to incorrect clipping)
  • Gallbladder fistulae
  • Hemorrhage
  • Subhepatic abscess
  • Postcholecystectomy syndrome: persistent abdominal pain or new symptoms following gallbladder removal
    • Frequency: 10–15% of patients
    • Etiology; : both biliary (e.g., biliary injury, retained cystic duct, sphincter of Oddi dysfunction) and extrabiliary (e.g., irritable bowel syndrome, pancreatitis) causes have been identified.
    • Clinical features: abdominal pain and upper GI tract (e.g., dyspepsia) or lower GI tract (e.g., diarrhea) symptoms
    • Diagnosis: ultrasound or CT scan followed by ERCP (preferred test if intervention is planned) or MRCP
    • Treatment: treat the underlying cause (e.g., sphincterotomy if there is evidence of sphincter dysfunction)


Epidemiology [28]

  • Sex: =
  • Incidence: up to 9% of patients with cholelithiasis
  • Peak incidence: 50–60 years

Etiology [28][29]

  • Risk factors
  • Pathophysiology: biliary tract obstructionbile stasis → bacterial infection infection ascends the biliary tract and can even track into the hepatic ducts

Clinical features [28][29]

Diagnostics [28]

  • Approach: conduct laboratory tests → imaging modality depends on clinical features present
  • Laboratory findings
  • Imaging
    • ERCP (both diagnostic and therapeutic)
    • Ultrasound: biliary dilation, evidence of obstruction (e.g., cholelithiasis)
    • CT scan; MRCP may also be diagnostic

Treatment [29][26][28]


Differential diagnoses


The differential diagnoses listed here are not exhaustive.