Cholelithiasis

BASICS

DESCRIPTION

The presence of cholesterol, pigment, or mixed stones (calculi) within the gallbladderPediatric Considerations
Most gallstones in children are pigment stones associated with blood dyscrasias.

EPIDEMIOLOGY

Incidence

2% of the U.S. population develops gallstones annually.

Prevalence

8–10% of the U.S. population with gallstones; 20% >65 years of age
Female > male (2 to 3:1)

ETIOLOGY AND PATHOPHYSIOLOGY

Gallstone formation is a complex process mediated by genetic, metabolic, immune, and environmental factors. Gallbladder sludge (a mixture of cholesterol crystals, calcium bilirubinate granules, and mucin gel matrix) serves as the nidus for gallstone formation. Bile supersaturated with cholesterol (cholesterol stones) precipitates as microcrystals that aggregate and expand. Stone formation is enhanced by biliary stasis or impaired gallbladder motility.
Decrease in bile phospholipid (lecithin) or decreased bile salt secretion
Excess unconjugated bilirubin in patients with hemolytic diseases; passage of excess bile salt into the colon with subsequent absorption of excess unconjugated bilirubin in patients with inflammatory bowel disease (IBD) or after distal ileal resection (black or pigment stones)

RISK FACTORS

Age peaks in patients 60 to 80 years of age; female gender, pregnancy, multiparity, obesity, and metabolic syndrome
Caucasian, Hispanic, or Native American descent
High-fat diet rich in cholesterol
Cholestasis or impaired gallbladder motility in association with prolonged fasting, long-term total parenteral nutrition (TPN), following vagotomy, long-term somatostatin therapy, and rapid weight loss
Hereditary (p.D19H variant for the hepatic canalicular cholesterol transporter ABCG5/ABG8).
Medications (birth control pills, estrogen at high doses, long-term corticosteroids)
Viral hepatitis, biliary tract infection, and stricture (promotes intraductal formation of pigment stones)

GENERAL PREVENTION

Regular exercise and dietary modification may reduce the incidence of gallstone formation.
Lipid-lowering drugs (statins) may prevent cholesterol stone formation by reducing bile cholesterol saturation.
Ursodiol (Actigall) taken during rapid weight loss helps prevent gallstone formation.

COMMONLY ASSOCIATED CONDITIONS

90% of people with gallbladder carcinoma have gallstones and chronic cholecystitis.

DIAGNOSIS

HISTORY

Most patients are asymptomatic (80%): 2% become symptomatic each year. Over their lifetime, <50% of patients with gallstones develop symptoms.
Episodic right upper quadrant or epigastric pain lasting >15 minutes and sometimes radiating to the back (biliary colic—due to transient cystic duct obstruction); pain is usually postprandial, particularly following a fatty meal but sometimes awakens patients from sleep (nocturnal); most patients develop recurrent symptoms after a first episode of biliary colic.
Other symptoms include nausea, vomiting, indigestion or bloating sensation, and fatty food intolerance.
Gallstone-related complications (such as gallstone pancreatitis [GP]) may be first manifestation of gallstone disease.

PHYSICAL EXAM

Physical exam is usually normal in patients with cholelithiasis in the absence of an acute attack.
Epigastric and/or right upper quadrant tenderness (Murphy sign) is a traditional physical finding associated with acute cholecystitis. Murphy sign has limited sensitivity and specificity.
Charcot triad: fever, jaundice, right upper quadrant pain historically associated with cholangitis
Reynolds pentad: fever, jaundice, right upper quadrant pain, hemodynamic instability, mental status changes; also classically associated with ascending cholangitis
Flank and periumbilical ecchymoses (Cullen sign and Grey Turner sign) in patients with acute hemorrhagic pancreatitis
Courvoisier sign: palpable mass in the right upper quadrant in patient with obstructive jaundice most commonly due to malignant tumors within the biliary tree or pancreas

DIFFERENTIAL DIAGNOSIS

Peptic ulcer diseases and gastritis; hepatitis
Pancreatitis; cholangitis; gallbladder cancer; gallbladder polyps
Acalculous cholecystitis; biliary dyskinesia; choledocholithiasis

DIAGNOSTIC TESTS & INTERPRETATION

Ultrasound (US) is the preferred diagnostic modality for cholelithiasis (high sensitivity and specificity).

Initial Tests (lab, imaging)

Leukocytosis and elevated C-reactive protein level are common in acute calculus cholecystitis.
US is the preferred imaging modality. US detects gallstones in 97–98% of patients.
Thickening of the gallbladder wall (≥5 mm), pericholecystic fluid, and direct tenderness when the probe is pushed against the gallbladder (sonographic Murphy sign) are associated with acute cholecystitis.
CT scan has no advantage over US except for detecting distal common bile duct (CBD) stones.
MR cholangiopancreatography (MRCP) is reserved for cases of suspected CBD stones. However, MRCP has no therapeutic value, and preoperative MRCP is not more cost-effective than initial cholecystectomy with cholangiography in the diagnosis of patients with suspected CBD stones and patients with mild to moderate GP.
Endoscopic US is as sensitive as endoscopic retrograde cholangiopancreatography (ERCP) for detection of CBD stones in patients with GP.
Hepatobiliary iminodiacetic acid (HIDA) scan is useful in diagnosing acute cholecystitis secondary to cystic duct obstruction. It is also useful in differentiating acalculous cholecystitis from other causes of abdominal pain. False-positive tests can result from a fasting state, insufficient resistance of the sphincter of Oddi, and gallbladder agenesis.
Cholecystokinin (CCK)-HIDA is specifically used to diagnose gallbladder dysmotility (biliary dyskinesia).
10–30% of gallstones are radiopaque calcium or pigment-containing gallstones (visible on plain x-ray). A “porcelain gallbladder” is a calcified gallbladder (also visible by x-ray) associated with chronic cholecystitis and gallbladder cancer.

Test Interpretation

Pure cholesterol stones are white or slightly yellow. Pigment stones may be black or brown. Black stones contain polymerized calcium bilirubinate, most often secondary to cirrhosis or hemolysis; these almost always form within the gallbladder. Brown stones are associated with biliary tract infection, caused by bile stasis, and as such primarily form in the bile ducts.

TREATMENT

GENERAL MEASURES

Treat symptomatic cholelithiasis. For adult patients with uncomplicated symptomatic cholelithiasis, surgery is no more effective than conservative management in the short term (≤18 months).
Conservative therapy is preferred during pregnancy; surgery in the 2nd trimester if necessary.
Prophylactic cholecystectomy for patients with calcified (porcelain) gallbladder (risk for gallbladder cancer), patients with large stones (≥3 cm), patients with sickle cell disease, pediatric gallstones, patients planning an organ transplant, and patients with recurrent pancreatitis due to microlithiasis

Geriatric Considerations
Gallstones are more common in the elderly. Age alone should not alter the therapeutic plan.

MEDICATION

First Line

Analgesics for pain relief
- NSAIDs are the first-choice treatment for pain control which is equivalent to opioid therapy.
- Opioids are an option for patients who cannot tolerate or fail to respond to NSAIDs.
Antibiotics for patients with acute cholecystitis
Prophylactic antibiotics in low-risk patients do not prevent infections during laparoscopic cholecystectomy (LC).

ISSUES FOR REFERRAL

Patients with retained or recurrent bile duct stones following cholecystectomy should be referred for ERCP.

SURGERY/OTHER PROCEDURES

Surgery should be considered for patients who have symptomatic cholelithiasis or gallstone-related complications (e.g., cholecystitis) or in asymptomatic patients with immune suppression, porcelain gallbladder, giant gallstones (≥3 cm) or family history of gallbladder cancer.
Open and LC have similar mortality and complication rates. LC is the current gold standard.
In well-selected patients, robotic cholecystectomy (RC) is an alternative to LC. RC is associated with higher cost, and has not been shown to be superior to LC in terms of pain and risk of complication.
- Conversion to open procedure is based on clinical judgment.
- In 10–15% of patients with symptomatic cholelithiasis, CBD stones are detected by intraoperative cholangiogram (IOC). CBD stone(s) can be removed by laparoscopic CBD exploration or postoperative ERCP.
- Indocyanine green (ICG) near-infrared florescence cholangiography has been shown to reduce bile duct injuries and conversions to open surgery during laparoscopic or robotic cholecystectomy for patients with acute and chronic cholecystitis.
Early LC (<24 hours after diagnosis of biliary colic) decreases hospital stay and operating time. For patients with acute cholecystitis, early LC (<7 days of clinical presentation) is safe and may shorten the total hospital stay versus delayed LC (>6 weeks after index admission with acute cholecystitis) (1)[A].
Percutaneous cholecystostomy (PC) is used for high-risk patients with cholecystitis or gallbladder empyema. Interval cholecystectomy is recommended.
Symptomatic patients who are not candidates for surgery or those who have small gallstones (5 mm or smaller) in a functioning gallbladder with a patent cystic duct are candidates for oral dissolution therapy (ursodiol [Actigall]). The recurrence rate is >50% once medication is discontinued.
Transpapillary cystic duct stenting via ERCP or EUS-guided transmural (cholecystogastrostomy or cholecystoduodenostomy) gallbladder drainage via deployment of a lumen-apposing metal stent (LAMS) are novel options for managing severe acute cholecystitis, gallbladder hydrops, or empyema in patients unfit for surgery. It can be used as a bridge to LC.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

For patients with symptomatic cholelithiasis, LC is typically an outpatient procedure. For patients with complications (i.e., cholecystitis, cholangitis, pancreatitis), inpatient care is necessary; acute phase: NPO, IV fluids, and antibiotics; adequate pain control with narcotics and/or NSAIDs

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Follow for signs of symptomatic cholelithiasis.
Follow patients on oral dissolution agents with serial liver enzymes, serum cholesterol, and imaging.

DIET

A low-fat diet may help.

PATIENT EDUCATION

Change in lifestyle (e.g., regular exercise) and dietary modification (low-fat diet and reduction of total caloric intake) may reduce gallstone-related hospitalizations.
Patients with asymptomatic gallstones should be educated about the typical symptoms of biliary colic and gallstone-related complications.

PROGNOSIS

<50% of patients with gallstones become symptomatic.
Cholecystectomy-related mortality is <0.5% in elective cases and 3–5% in emergency cases; morbidity is <10% in elective cases and 30–40% in emergency cases. ~10–15% of patients have associated choledocholithiasis. After cholecystectomy, stones may recur within the biliary tree in patients with associated risk factors.

COMPLICATIONS

Acute cholecystitis (90–95% secondary to gallstones)
GP; ERCP ± sphincterotomy offers no clear benefit in patients with mild GP but reduces complications in those with severe GP (2)[A].
CBD stones with obstructive jaundice and acute cholangitis. In patients undergoing ERCP for CBD stones, early LC reduces the risk of recurrent biliary events (2)[B]; biliary-enteric fistula and gallstone ileus
Gallbladder cancer; Mirizzi syndrome (extrinsic bile duct obstruction caused by gallstones lodged in gallbladder or cystic duct)

Authors

Hongyi Cui, MD, PhD

REFERENCES

Patel H, Jepsen J. Gallstone disease: common questions and answers. Am Fam Physician. 2024;109(6):518–524. [PMID:38905549]
Garcia-Pagan JC, Francoz C, Montagnese S, et al. Management of the major complications of cirrhosis: beyond guidelines. J Hepatol. 2021;75(Suppl 1):S135–S146. [PMID:34039484]

CODES

ICD10

K80.20 Calculus of gallbladder w/o cholecystitis w/o obstruction
K80.21 Calculus of gallbladder w/o cholecystitis with obstruction
K80.01 Calculus of gallbladder w acute cholecystitis w obstruction
K80.00 Calculus of gallbladder w acute cholecyst w/o obstruction
K80.19 Calculus of gallbladder w oth cholecystitis with obstruction
K80.18 Calculus of gallbladder w oth cholecystitis w/o obstruction

SNOMED

266474003 calculus in biliary tract (disorder)
25924004 Calculus of gallbladder with cholecystitis (disorder)
29484002 Cholelithiasis AND cholecystitis without obstruction
50450007 Cholelithiasis AND cholecystitis with obstruction
235919008 gallbladder calculus (disorder)
699050007 Calculus of gallbladder with acute and chronic cholecystitis (disorder)
59771005 Calculus of gallbladder with acute cholecystitis (disorder)
77528005 cholelithiasis with obstruction (disorder)

CLINICAL PEARLS

Most gallstones are asymptomatic.
Transabdominal US is the imaging modality of choice for cholelithiasis (sensitivity, 97%; specificity, 95%).
LC is the preferred surgical procedure for symptomatic cholelithiasis and gallstone-related complications.
Acute acalculous cholecystitis is associated with bile stasis and gallbladder ischemia.
Prophylactic cholecystectomy is not routinely indicated in patients with asymptomatic gallstones.

Last Updated: 2026

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