- Clinical science
Cholelithiasis refers to the presence of abnormal concretions (gallstones) in the gallbladder. 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. Cholelithiasis can manifest with biliary colic (postprandial RUQ pain) but is most commonly an incidental finding in asymptomatic individuals. The diagnosis is confirmed by ultrasound. Symptomatic cholelithiasis is managed with laparoscopic cholecystectomy.
|Cholelithiasis||Choledocholithiasis||Acute cholecystitis||Acute cholangitis|
|Laboratory findings|| |
|Treatment|| || |
- Imbalance in bile salts, lecithin (stabilizer), cholesterol, calcium carbonate, and bilirubin
- Biliary stasis is a key component in gallstone formation.
- Impaired gallbladder emptying (e.g., due to bowel rest, prolonged total parenteral nutrition, pregnancy ) → biliary sludge → bile stasis (cholestasis)
Cholesterol stones (up to 95% of all stones) 
- Obesity, insulin resistance, dyslipidemia
- Especially during reproductive years due to increased levels of estrogen and progesterone
- Increased estrogen levels cause increased secretion of bile rich in cholesterol, (lithogenic bile), which can result in the formation of cholesterol gallstones.
- Increased progesterone levels cause smooth muscle relaxation, decreased gallbladder contraction, and subsequent bile stasis with formation of gallstones.
- Multiparity or pregnancy
- Age (> 40 years of age)
- European, Native American, or Hispanic ancestry
- Family history
- Drugs: fibrates (inhibition of ), estrogen therapy, oral contraceptives
- Malabsorption (e.g., Crohn disease, ileal resection, cystic fibrosis)
- Rapid weight loss
- Pathophysiology: abnormal hepatic cholesterol metabolism → ↑ cholesterol concentration in bile and ↓ bile salts and lecithin → hypersaturated bile → precipitation of cholesterol and calcium carbonate → cholesterol stones or mixed stones
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) 
- Risk factors
- Pathophysiology: ↑ hemolysis → increase in circulating unconjugated bilirubin → increased uptake and conjugation of bilirubin → precipitation of bilirubin polymers and stone formation
Mixed/brown pigment stones (< 10% of all stones) 
- Risk factors: bacterial infections and parasites (e.g., Clonorchis sinensis, Opisthorchis species) in the biliary tract, sclerosing cholangitis 
- Pathophysiology: infection or infestation → release of β-glucuronidase (by injured hepatocytes and bacteria) → hydrolyzes conjugated bilirubin and lecithin in the bile → increased unconjugated bilirubin and fatty acids → precipitation of calcium carbonate, cholesterol, and calcium bilirubinate (dark color) in bile
- Most gallstones are asymptomatic.
- Biliary colic: constant, dull RUQ pain lasting < 6 hours
- Nausea, vomiting, early satiety
- Bloating, dyspepsia
Only a minority of patients with gallstones are symptomatic!
- Asymptomatic cholelithiasis: No diagnostic workup is required.
Suspected symptomatic cholelithiasis
- Imaging is essential to confirm a clinical diagnosis of cholelithiasis and rule out concurrent choledocholithiasis.
- If choledocholithiasis is suspected : See ''Diagnosis of choledocholithiasis.”
- If the clinical diagnosis is unclear: See “ .”
Laboratory studies are typically normal in uncomplicated cholelithiasis but should be ordered to rule out other acute biliary conditions and/or other causes of acute abdominal pain.
- Indication: best initial test in suspected symptomatic cholelithiasis 
- Characteristic findings 
- Supportive findings: well-defined hypointense (on T2) filling defect(s) within the gallbladder lumen 
CT abdomen with IV contrast 
- Supportive findings (of radiopaque stones): well-defined hyperdense structure(s) within the gallbladder lumen
- Indication: usually performed as part of the routine workup of acute abdominal pain
- Findings and disadvantages: similar to those of CT scan
- See also “Differential diagnosis of acute abdomen.”
Differential diagnoses of intraluminal gallbladder wall pathology
- Cholangiocarcinoma (see biliary cancer)
- Definition: benign tumor of the gallbladder wall with low metastatic potential
- Diagnosis: Ultrasound (transabdominal or endoscopic)
The differential diagnoses listed here are not exhaustive.
- All patients
- Asymptomatic cholelithiasis
- Symptomatic uncomplicated cholelithiasis
- Symptomatic complicated cholelithiasis: See “Acute cholecystitis”, “Choledocholithiasis”, and “Acute cholangitis.”
Treatment of biliary colic 
- Bowel rest: NPO
- Analgesics 
- Spasmolytics (e.g., dicyclomine ): consider as adjuvant therapy with analgesics in patients with severe pain 
- In patients with protracted vomiting consider the following:
Important considerations 
- Consider inpatient management in patients with intractable pain or if there is concern for complications.
- Most patients may be discharged from the ER once pain has settled if there is no evidence of complications.
- Advise patients to avoid foods with a high fat content.
- Schedule an elective cholecystectomy.
- Procedure: elective laparoscopic cholecystectomy
- Symptomatic cholelithiasis
Asymptomatic cholelithiasis with any of the following:
- Increased risk of gallbladder cancer (e.g., gallbladder polyps, porcelain gallbladder, gallstones ≥ 3 cm) 
- Increased risk of developing complications (e.g., immunocompromised patients, multiple gallstones) 
- Increased risk of becoming symptomatic (e.g., hemolytic anemia, patients undergoing gastric bypass surgery) 
- Contraindication: suspected gallbladder cancer (see ''Treatment'' in “Biliary cancer”) 
- Preoperative precautions: Assess for (see '' in all symptomatic patientsDiagnosis of choledocholithiasis”). 
- Timing: : as early as possible in uncomplicated symptomatic cholelithiasis 
- Complications: See “Cholecystectomy” section for details.
Cholecystectomy is usually not indicated in asymptomatic cholelithiasis!
Nonsurgical alternatives 
- Patients at high risk of complications due to surgery or anesthesia (e.g., recent myocardial infarction)
- Patients unwilling to undergo surgery
- Expectant management 
Oral bile acid dissolution therapy
- May be useful in dissolving pure cholesterol stones (i.e., radiolucent stones) that are < 0.5 cm 
- Ursodeoxycholic acid
- Duration of therapy: 6–24 months 
- Advantage: symptomatic improvement even if stones are not completely dissolved 
- Ineffective in mixed stones
- High recurrence rates 
- Long duration of therapy
- Requires repeat imaging to track treatment response
Extracorporeal shock wave lithotripsy (ESWL)
- Useful in mixed stones
- Short duration of therapy
- May need to be combined with endoscopic sphincterotomy for stone clearance
- Does not prevent recurrence 
- Injury to adjacent solid organs (rare)
- Supportive care: See “Initial supportive therapy of acute biliary disease.”
- Identify and treat concurrent choledocholithiasis: See “Diagnosis of choledocholithiasis.”
- Nonurgent surgery consult or outpatient referral to evaluate for elective cholecystectomy
- Surgical removal of the gallbladder
- Symptomatic cholelithiasis
- Asymptomatic cholelithiasis with any of the following:
- Increased risk of gallbladder cancer 
- Increased risk of developing complications 
- Increased risk of becoming symptomatic 
- Acute calculous cholecystitis
- Absolute: none; risks are primarily related to anesthesia
Surgical risk scores
Timing of cholecystectomy depends on the indication and individual surgical risks.
- Symptomatic uncomplicated cholelithiasis: electively, but as early as possible 
- Uncomplicated choledocholithiasis: within 72 hours of ERCP-guided stone clearance 
- Complicated cholelithiasis or choledocholithiasis: depends on the severity of complication and the patient's anesthesia risks
- Mild biliary pancreatitis: during the same hospital admission 
- Acute cholecystitis (see ''Treatment'' in “Acute cholecystitis” for details) 
- Acute cholangitis: ∼ 6 weeks after successful ERCP-guided stone clearance 
- Current standard of care for most indications of cholecystectomy 
- Open cholecystectomy
Intraoperative and early postoperative complications
- Transmural bowel injury
- Surgical site infection
Postcholecystectomy bile leak 
- Clinical features
- Incisional hernia (at trocar site)
- Biliary stricture
- Biliary-enteric fistula
- Definition: chronic diarrhea after removal of the gallbladder 
- Pathophysiology: Removal of the gallbladder → no reservoir of bile → entry of excess bile acids into the colon → osmotic diarrhea 
- May also be functional or due to other undiagnosed causes of diarrhea
- Diagnostics: SeHCAT test 
- Treatment: Preferred first-line agent is cholestyramine. 
- Postcholecystectomy syndrome: persistent RUQ pain or new symptoms following gallbladder removal 
- Acute biliary pancreatitis
- Biliary-enteric fistula: Cholecystoenteric/choledochoenteric fistula (rare) , which can cause gallstone ileus (rare) 
Complications due to gallstone impaction at the gallbladder neck or infundibulum
Mirizzi syndrome 
- Definition: extrinsic compression of the common bile duct (or any extrahepatic bile duct) by gallstone(s) impacted in the cystic duct or the infundibulum of the gallbladder 
- Clinical features: similar to choledocholithiasis
- Imaging findings (preferably ERCP/MRCP)
- ERCP-guided CBD stent placement may be considered preoperatively to allow for biliary drainage. 
- Open cholecystectomy may be preferred if diagnosed preoperatively. 
- Complications 
- Cholecystocholedochal fistula: an abnormal communication between the gallbladder and the common bile duct
- Cholecystoenteric/choledochoenteric fistula (biliary-enteric fistula): an abnormal communication between the gallbladder or the CBD with the adjacent bowel
- Gallstone ileus: due to biliary-enteric fistula
Gallbladder mucocele (gallbladder hydrops) 
- Definition: marked distension of the gallbladder with sterile mucinous content due to chronic biliary outflow obstruction
- Etiology 
- Impacted gallstone at the gallbladder neck (most common)
- Resolved acute cholecystitis 
- Tumors at the gallbladder neck or CBD (e.g., GB polyps, cholangiocarcinoma, carcinoma of pancreatic head)
- Acute inflammatory conditions (e.g., Kawasaki disease)
- Extrinsic compression of the biliary outflow tract (e.g., lymphadenopathy, adhesions, strictures)
- Pathophysiology: chronic biliary outflow obstruction → resorption of bile and secretion of mucin by biliary mucosa → collection of mucinous secretion within the gallbladder with no outflow → gross distension of the gallbladder
- Clinical features: asymptomatic mass in the RUQ; no signs of infection
- Imaging (preferably ultrasound or CT): grossly distended fluid-filled gall bladder without signs of inflammation 
- In children with no evidence of cholecystitis: trial of conservative management 
- In adults: laparoscopic cholecystectomy 
We list the most important complications. The selection is not exhaustive.