Cholelithiasis

Author: Fred F. Ferri, MD

Definition

Cholelithiasis is the presence of stones in the gallbladder.

Synonym

Gallstones

ICD-10CM CODES
K80.80		Other cholelithiasis without obstruction
K80.81		Other cholelithiasis with obstruction
K91.86		Retained cholelithiasis following cholecystectomy

Epidemiology & Demographics

•Gallstone disease can be found in 12% of the U.S. population. Of these, 2% to 3% (500,000 to 600,000) are treated with cholecystectomies each year.
•Annual medical expenditures for gallbladder surgeries in the U.S. exceed $5 billion.
•Incidence of gallbladder disease increases with age. Highest incidence is in the fifth and sixth decades. Predisposing factors for gallstones are female sex, pregnancy, age >40 yr, family history of gallstones, obesity, ileal disease, oral contraceptives, diabetes mellitus, rapid weight loss, estrogen replacement therapy.
•Patients with gallstones have a 20% chance of developing biliary colic or its complications at the end of a 20-yr period. Significant predictors of gallstone-related events are large stone (>10 mm), presence of multiple stones, and female sex.

Physical Findings & Clinical Presentation (Table 1

•Physical examination is entirely normal unless patient is having biliary colic; 80% of gallstones are asymptomatic.
•Typical symptoms of obstruction of the cystic duct include intermittent, severe, cramping pain affecting the right upper quadrant.
•Pain occurs mostly at night and may radiate to the back or right shoulder. It can last from a few minutes to several hours.
•Symptoms of gallstone disease and its complications are described in Table 2 and Fig. E1.

TABLE 2 Symptoms of Gallstone Disease and Its Complications

Disease	Pathophysiology	Symptoms
Biliary colic	Transient gallstone impaction at the cystic duct or ampulla of Vater	Intermittent right upper quadrant pain associated with nausea or vomiting. Pain in the epigastrium or radiating to the right scapular tip. Episodes last 30 min to several hours with days or months between episodes.
Acute cholecystitis	Inflammation of the gallbladder caused by obstruction of the cystic duct. May occur in the presence or absence of bacterial superinfection	Patients appear ill and cannot take deep breaths. They have constant pain that lasts 30-60 min and worsens with movement. Persistent common bile duct impaction usually promotes vomiting. Physical examination demonstrates right upper quadrant tenderness with voluntary guarding and a positive Murphy sign (arrest of inspiration during deep palpation over the gallbladder).
Emphysematous cholecystitis	Infection with gas-producing bacteria such as Escherichia coli, Clostridium perfringens, and anaerobic streptococci	Symptoms are similar to those with acute cholecystitis. Gas may be seen on abdominal plain films or CT. Male diabetics are most commonly affected.
Chronic cholecystitis	Persistent inflammation and fibrosis of the gallbladder with poor motor and absorptive function	Patients are usually asymptomatic but may report multiple previous attacks of colic. Porcelain gallbladder develops from chronic inflammation and may progress to carcinoma.
Acalculous cholecystitis	Probably related to biliary stasis in the setting of critical illness and altered gastrointestinal motility	Seen in patients with traumatic injuries, burns, and critical illness, as well as in those receiving total parenteral nutrition. The mortality for this disorder is twice as high as that for acute calculous cholecystitis.
Gallbladder perforation	Stones erode through an inflamed and necrotic gallbladder wall. Stones may travel into the peritoneal cavity or cause adhesions between nearby structures. Bile peritonitis may develop	More than half of patients with gallbladder perforation have fever and a palpable right upper quadrant mass. Mortality in these patients is 30%.

CT, Computed tomography.

From Adams JG et al: Emergency medicine, clinical essentials, ed 2, Philadelphia, 2013, Elsevier.

Figure E1 Schematic depiction of the natural history and complications of gallstones.

Percentages indicate approximate frequencies of complications that occur in persons with gallstones, based on natural history data. The most frequent outcome is for the patient with a stone to remain asymptomatic throughout life. (1) Asymptomatic or biliary pain, (2) acute cholecystitis, (3) cholangitis, and (5) pancreatitis are the most common complications. (4) Mirizzi syndrome, (6) cholecystoenteric fistula, (6) Bouveret syndrome, and (7) gallbladder cancer are uncommon. The sum of percentages is >100% because patients with acute cholecystitis generally have had prior episodes of biliary pain.

(From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 11, Philadelphia, 2021, Elsevier.)

TABLE 1 Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment of Gallstone Disease

	Biliary pain	Acute Cholecystitis	Choledocholithiasis	Cholangitis
Pathophysiology	Intermittent obstruction of the cystic duct No acute inflammation of the gallbladder	Impacted stone in the cystic duct Acute inflammation of the gallbladder Secondary bacterial infection in ≈50%	Stone passed from the gallbladder via the cystic duct or formed in the BD Intermitted obstruction of the BD	A stone in the BD causing bile stasis Bacterial superinfection of stagnant bile Early bacteremia
Symptoms	Severe, poorly localized, epigastric or right upper quadrant visceral pain growing in intensity over 15 min and remaining constant for 1-6 h, often with nausea Frequency of attacks varies from days to months Gas, bloating, flatulence, and dyspepsia are not related to stones	75% of cases are preceded by attacks of biliary pain Visceral epigastric pain gives way to moderately severe localized pain in the right upper quadrant, back, right shoulder, or, rarely, chest Nausea with some vomiting is frequent Pain lasting >6 h favors cholecystitis over biliary pain alone	Often asymptomatic Symptoms (when present) are indistinguishable from biliary pain Predisposes to cholangitis and acute pancreatitis	Charcot triad (pain, jaundice, and fever) is present in 70% of patients Pain may be mild and transient and is often accompanied by chills Mental confusion, lethargy, and delirium suggest sepsis
Physical findings	Mild-to-moderate epigastric/right upper quadrant tenderness during an attack, with mild residual tenderness lasting days Often, findings are normal	Fever, but usually to <102°F unless complicated by gangrene or perforation Right subcostal tenderness with inspiratory arrest (Murphy sign) Palpable gallbladder in 33% of patients, especially those having their first attack Mild jaundice in 20%; higher frequency in older adults	Often findings are completely normal if the obstruction is intermittent Jaundice with pain suggests stones; painless jaundice and a palpable gallbladder favor malignancy	Fever in 95%, right upper quadrant tenderness in 90% Jaundice in 80% Peritoneal signs in 15% Hypotension and mental confusion (forming Reynolds pentad in combination with Charcot triad) coexist in 15% and suggest gram-negative sepsis
Laboratory findings	Usually normal Elevated serum bilirubin, alkaline phosphatase, or amylase levels suggest coexisting BD stones	Leukocytosis with band forms is common Serum bilirubin level may be 2-4 mg/dl, and aminotransferase and alkaline phosphatase levels may be elevated even in the absence of a BD stone or hepatic infection Mild serum amylase and lipase elevations are seen even in the absence of pancreatitis If serum bilirubin is >4 mg/dl or amylase or lipase is markedly elevated, a BD stone should be suspected	Elevated serum bilirubin and alkaline phosphatase levels are seen with BD obstruction Serum bilirubin level >10 mg/dl suggests malignant obstruction or coexisting hemolysis A transient "spike" in serum aminotransferase or amylase (or lipase) levels suggests the passage of a stone	Leukocytosis in 80%, but the remainder may have a normal WBC count with or without band forms Serum bilirubin level is >2 mg/dl in 80% Serum alkaline phosphatase level is usually elevated Blood cultures are usually positive, especially during chills or a fever spike; 2 organisms are grown in cultures from half of patients
Diagnostic studies	US Oral cholecystography Meltzer-Lyon test	US Hepatobiliary scintigraphy Abdominal CT	ERCP EUS MRC Percutaneous THC	ERCP Percutaneous THC
Natural history	After the initial attack, 30% of patients have no further symptoms Symptoms develop in the remainder at a rate of 6% per yr, and severe complications at a rate of 1%-2% per yr	50% of cases resolve spontaneously in 7-10 days without surgery Left untreated, 10% of cases are complicated by a localized perforation and 1% by a free perforation and peritonitis	The natural history is not well defined, but complications are more common and more severe than for asymptomatic stones in the gallbladder	A high mortality rate if unrecognized, with death from septicemia Emergency decompression of the BD (usually by ERCP) improves survival dramatically
Treatment	Elective laparoscopic cholecystectomy, possibly with IOC ERCP for stone removal or BD exploration if IOC shows stones	Laparoscopic cholecystectomy, possibly with IOC if feasible; otherwise open cholecystectomyBD exploration or ERCP for stone removal if IOC shows stones	Stone removal at the time of ERCP, followed in most cases by early laparoscopic cholecystectomy	Emergency ERCP with stone removal or at least biliary decompression Antibiotics to cover gram-negative and possibly anaerobic organisms and Enterococcus spp. Subsequent cholecystectomy

BD, Bile duct; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; IOC, intraoperative cholangiography; MRC, magnetic resonance cholangiography; THC, transhepatic cholangiography; US, ultrasound; WBC, white blood cells.

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 11, Philadelphia, 2021, Elsevier.

Etiology

•75% of gallstones contain cholesterol and are usually associated with obesity, female sex, and diabetes mellitus; mixed stones are most common (80%); pure cholesterol stones account for only 10% of stones and are the result of biliary supersaturation due to cholesterol secretion into the gallbladder and accelerated cholesterol nucleation and crystallization.
•25% of gallstones are pigment stones (bilirubin, calcium, and variable organic material) associated with hemolysis and cirrhosis. These tend to be black-pigmented stones that are refractory to medical therapy.
•50% of mixed-type stones are radiopaque.

Nonpharmacologic Therapy

Lifestyle changes (avoidance of diets high in polyunsaturated fats, weight loss in obese patients; however, avoid rapid weight loss)

Acute General Rx

•The management of gallstones is affected by the clinical presentation.
•Asymptomatic patients do not require therapeutic intervention. Proposed criteria for prophylactic cholecystectomy are described in Table E3.
•Surgical intervention is generally the ideal approach for symptomatic patients. Laparoscopic cholecystectomy is preferred over open cholecystectomy because of the shorter recovery period and lower mortality rate. Between 5% and 26% of patients undergoing elective laparoscopic cholecystectomy will require conversion to an open procedure. Most common reason is the inability to clearly identify the biliary anatomy.
•Laparoscopic cholecystectomy after endoscopic sphincterectomy is recommended for patients with common bile duct stones and residual gallbladder stones. Where possible, single-stage laparoscopic treatments with removal of duct stones and cholecystectomy during the same procedure are preferable. Percutaneous cholecystectomy is an alternative for patients who are critically ill with gallbladder empyema and sepsis.
•Patients who are not appropriate candidates for surgery because of coexisting illness or patients who refuse surgery can be treated with oral bile salts: Ursodiol or chenodiol. Candidates for oral bile salts are patients with cholesterol stones (radiolucent, noncalcified stones), with a diameter of ≤15 mm and having three or fewer stones. Candidates for medical therapy must have a functioning gallbladder and must have absence of calcifications on CT scans.
•Extracorporeal shock wave lithotripsy (ESWL) is another form of medical therapy. It can be used in patients with stone diameter of ≤3 cm and having three or fewer stones.

TABLE E3 Proposed Criteria for Prophylactic Cholecystectomy

Life expectancy >20 yr
Calculi >2 cm in diameter
Calculi >3 mm and patent cystic duct
Radiopaque calculi
Gallbladder polyps >15 mm
Nonfunctioning or calcified gallbladder ("porcelain" gallbladder)
Women <60 yr
Patients in areas with high prevalence of gallbladder cancer

From Cameron JL, Cameron AM: Current surgical therapy, ed 14, Philadelphia, 2023, Saunders.

Disposition

•Complicated gallstone events develop in 8% of patients with incidentally discovered gallstones after 17 yr.
•After ESWL, stones recur in approximately 20% of patients after 4 yr.
•Patients with at least one gallstone <5 mm in diameter have a greater than fourfold increased risk of presenting with acute biliary pancreatitis. A policy of watchful waiting in such cases is generally warranted.
•A potential serious complication of gallstones is acute cholangitis. ERCP and endoscopic sphincterectomy followed by interval laparoscopic cholecystectomy are effective in acute cholangitis.
•Uncommon complications of gallstone disease are summarized in Table 4.

TABLE 4 Uncommon Complications of Gallstone Disease

Complication	Pathogenesis	Clinical Features	Diagnosis/Treatment
Emphysematous cholecystitis	Secondary infection of the gallbladder wall with gas-forming organisms (Clostridium welchii, Escherichia coli, and anaerobic streptococci) More common in older adult diabetic men; can occur without stones	Symptoms and signs similar to those of severe acute cholecystitis	Plain abdominal films may show gas in the gallbladder fossa US and CT are sensitive for confirming gas Treatment is with IV antibiotics, including anaerobic coverage, and early cholecystectomy High morbidity and mortality rates
Cholecystoenteric fistula	Erosion of a (usually large) stone through the gallbladder wall into the adjacent bowel, most often the duodenum, followed in frequency by the hepatic flexure, stomach, and jejunum	Symptoms and signs similar to those of acute cholecystitis, although sometimes a fistula may be clinically silent Stones >25 mm, especially in older adult women, may produce a bowel obstruction, or "gallstone ileus"; the terminal ileum is the most common site of obstruction Gastric outlet obstruction (Bouveret syndrome) may occur rarely	Plain abdominal films may show gas in the biliary tree and/or a small bowel obstruction in gallstone ileus, as well as a stone in the right lower quadrant if the stone is calcified Contrast upper GI series may demonstrate the fistula A fistula from a solitary stone that passes may close spontaneously Cholecystectomy and bowel closure are curative Gallstone ileus requires emergency laparotomy; the diagnosis is often delayed, with a resulting mortality rate of ≈20%
Mirizzi syndrome	An impacted stone in the gallbladder neck or cystic duct, with extrinsic compression of the common hepatic duct from accompanying inflammation or fistula	Jaundice and right upper quadrant pain	ERCP demonstrates dilated intrahepatic ducts and extrinsic compression of the common hepatic duct and possible fistula Preoperative diagnosis is important to guide surgery and minimize the risk of BD injury
Porcelain gallbladder	Intramural calcification of the gallbladder wall, usually in association with stones	No symptoms attributable to the calcified wall per se, but carcinoma of the gallbladder is a late complication in ≈20%	Plain abdominal films or CT show intramural calcification of the gallbladder wall Prophylactic cholecystectomy is indicated to prevent carcinoma

BD, Bile duct; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; GI, gastrointestinal; IV, intravenous; US, ultrasound.

From Feldman M et al: Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 11, Philadelphia, 2021, Elsevier.

Related Content

Gallstones (Patient Information)
Cholecystitis (Related Key Topic)
Choledocholithiasis (Related Key Topic)

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