Cholelithiasis

Fred F. Ferri, M.D.

Basic Information

Definition

Cholelithiasis is the presence of stones in the gallbladder

Synonyms

Gallstones

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

Epidemiology & Demographics

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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.
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Annual medical expenditures for gallbladder surgeries in the U.S. exceed $5 billion.
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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.
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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

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

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Symptoms of gallstone disease and its complications are described in Table 1.

TABLE1 Symptoms of Gallstone Disease and Its ComplicationsFrom Adams JG et al.: Emergency medicine, clinical essentials, ed 2, Philadelphia, 2013, Elsevier.

Disease	Pathophysiology	Symptoms
Biliary colic	Transient gallstone impaction at the cystic duct or ampulla of Vater	Intermittent RUQ 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 RUQ 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 RUQ mass. Mortality in these patients is 30%.
CT, Computed tomography; RUQ, right upper quadrant.

Etiology

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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.
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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.
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50% of mixed-type stones are radiopaque.

Diagnosis

Differential Diagnosis

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Peptic ulcer disease
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Gastroesophageal reflux disease
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Irritable bowel disease
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Pancreatitis
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Neoplasms
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Nonnuclear dyspepsia
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Inferior wall myocardial infarction
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Hepatic abscess

Laboratory Tests

Generally normal unless patient has biliary obstruction (elevated alkaline phosphatase, bilirubin).

Imaging Studies

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Ultrasound of the gallbladder (Fig. E1) will detect small stones and biliary sludge (sensitivity, 95%; specificity, 90%); the presence of dilated gallbladder with thickened wall is suggestive of acute cholecystitis.

FIG.E1

Calculi in the common bile duct, casting an acoustic shadow.

From Grainger RG et al. [eds]: Grainger and Allison’s diagnostic radiology, ed 4, Philadelphia, 2001, Churchill Livingstone.
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Nuclear imaging (HIDA scan) can confirm acute cholecystitis (>90% accuracy) if gallbladder does not visualize within 4 hr of injection and the radioisotope is excreted in the common bile duct.
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Common bile duct stones can be detected noninvasively by magnetic resonance cholangiopancreatography or invasively by endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography.

Treatment

Nonpharmacologic Therapy

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

Acute General Rx

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The management of gallstones is affected by the clinical presentation.

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Asymptomatic patients do not require therapeutic intervention. Proposed criteria for prophylactic cholecystectomy are described in Table 2.

TABLE2 Proposed Criteria for Prophylactic CholecystectomyFrom Cameron JL, Cameron AM: Current surgical therapy, ed 10, Philadelphia, 2011, Saunders.

Life expectancy >20 years

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 years

Patients in areas with high prevalence of gallbladder cancer

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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.
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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.
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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.
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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.

Disposition

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Complicated gallstone events develop in 8% of patients with incidentally discovered gallstones after 17 years (Shabanzadeh DM, et al.: Gastroenterology 150:156, 2016).
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After ESWL, stones recur in approximately 20% of patients after 4 yr.
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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.
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A potential serious complication of gallstones is acute cholangitis. ERCP and endoscopic sphincterectomy followed by interval laparoscopic cholecystectomy are effective in acute cholangitis.

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Uncommon complications of gallstone disease are summarized in Table 3.

TABLE3 Uncommon Complications of Gallstone DiseaseFrom Feldman M, et al.: Sleisenger and Fortran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.

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)	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
	More common in older adult diabetic men; can occur without stones
			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	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 RLQ if the stone is calcified Contrast upper GI series may demonstrate the fistula
		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
			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 RUQ pain	ERCP demonstrates dilated intrahepatic ducts and extrinsic compression of the common hepatic duct and possible fistula
Mirizzi syndrome		Jaundice and RUQ pain	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
Porcelain gallbladder			Prophylactic cholecystectomy is indicated to prevent carcinoma
BD, bile duct; RLQ, right lower quadrant; RUQ, right upper quadrant.

Ferri – Cholelithiasis