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Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. In developed countries, about 10% of adults and 20% of people > 65 yr have gallstones. Gallstones tend to be asymptomatic. The most common symptom is biliary colic; gallstones do not cause dyspepsia or fatty food intolerance. More serious complications include cholecystitis; biliary tract obstruction (from stones in the bile ducts or choledocholithiasis), sometimes with infection (cholangitis); and gallstone pancreatitis. Diagnosis is usually by ultrasonography. If cholelithiasis causes symptoms or complications, cholecystectomy is necessary.

Risk factors for gallstones include female sex, obesity, increased age, American Indian ethnicity, a Western diet, and a family history. Most disorders of the biliary tract result from gallstones.

Pathophysiology

Biliary sludge is often a precursor of gallstones. It consists of Ca bilirubinate (a polymer of bilirubin), cholesterol microcrystals, and mucin. Sludge develops during gallbladder stasis, as occurs during pregnancy or while receiving TPN. Most sludge is asymptomatic and disappears when the primary condition resolves. Alternatively, sludge can evolve into gallstones or migrate into the biliary tract, obstructing the ducts and leading to biliary colic, cholangitis, or pancreatitis.

There are several types of gallstones.

Cholesterol stones account for > 85% of gallstones in the Western world. For cholesterol gallstones to form, the following is required:

• Bile must be supersaturated with cholesterol. Normally, water-insoluble cholesterol is made water-soluble by combining with bile salts and lecithin to form mixed micelles. Supersaturation of bile with cholesterol most commonly results from excessive cholesterol secretion (as occurs in obesity or diabetes) but may result from a decrease in bile salt secretion (eg, in cystic fibrosis because of bile salt malabsorption) or in lecithin secretion (eg, in a rare genetic disorder that causes a form of progressive intrahepatic familial cholestasis).
• The excess cholesterol must precipitate from solution as solid microcrystals. Such precipitation in the gallbladder is accelerated by mucin, a glycoprotein, or other proteins in bile.
• The microcrystals must aggregate and grow. This is facilitated by the binding effect of mucin forming a scaffold and retention in the gallbladder (impaired contractility from the excess cholesterol in bile).

Black pigment stones are small, hard gallstones composed of Ca bilirubinate and inorganic Ca salts (eg, Ca carbonate, Ca phosphate). Factors that accelerate their development include alcoholic liver disease, chronic hemolysis, and older age.

Brown pigment stones are soft and greasy, consisting of bilirubinate and fatty acids (Ca palmitate or stearate). They form during infection, inflammation, and parasitic infestation (eg, liver flukes in Asia).

Gallstones grow at about 1 to 2 mm/yr, taking 5 to 20 yr before becoming large enough to cause problems. Most gallstones form within the gallbladder, but brown pigment stones form in the ducts. Gallstones may migrate to the bile duct after cholecystectomy or, particularly in the case of brown pigment stones, develop behind strictures as a result of stasis and infection.

Symptoms and Signs

About 80% of people with gallstones are asymptomatic. The remainder have symptoms ranging from biliary-type pain (biliary colic) to cholecystitis to life-threatening cholangitis. Biliary colic is the most common symptom.

Stones occasionally may traverse the cystic duct without causing symptoms. Most gallstone migration, however, leads to cystic duct obstruction, which, even if transient, causes biliary colic. Biliary colic characteristically begins in the right upper quadrant but may occur elsewhere in the abdomen. It is often poorly localized, particularly in diabetics and the elderly. The pain may radiate into the back or down the arm. Episodes begin suddenly, become intense within 15 min to 1 h, remain at a steady intensity (not colicky) for up to 12 h (usually < 6 h), and then gradually disappear over 30 to 90 min, leaving a dull ache. The pain is usually severe enough to send patients to the emergency department for relief. Nausea and some vomiting are common, but fever and chills do not occur unless cholecystitis has developed. Mild right upper quadrant or epigastric tenderness may be present; peritoneal findings are absent. Between episodes, patients feel well.

Although biliary-type pain can follow a heavy meal, fatty food is not a specific precipitating factor. Nonspecific GI symptoms, such as gas, bloating, and nausea, have been inaccurately ascribed to gallbladder disease. These symptoms are common, having about equal prevalence in cholelithiasis, peptic ulcer disease, and functional GI disorders.

Little correlation exists between the severity and frequency of biliary colic and pathologic changes in the gallbladder. Biliary colic can occur in the absence of cholecystitis. Should colic last > 12 h, particularly if accompanied by vomiting or fever, acute cholecystitis or pancreatitis is likely.

Diagnosis

• Ultrasonography

Gallstones are suspected in patients with biliary colic. Abdominal ultrasonography is the method of choice for detecting gallbladder stones; sensitivity and specificity are 95%. Ultrasonography also accurately detects sludge. CT, MRI, and oral cholecystography (rarely available now, although quite accurate) are alternatives (see Testing for Hepatic and Biliary Disorders: Oral cholecystography). Endoscopic ultrasonography accurately detects small gallstones (< 3 mm) and may be needed if other tests are equivocal. Laboratory tests usually are not helpful; typically, results are normal unless complications develop. Asymptomatic gallstones and biliary sludge are often detected incidentally when imaging, usually ultrasonography, is done for other reasons. About 10 to 15% of gallstones are calcified and visible on plain x-rays.

Prognosis

Those with asymptomatic gallstones become symptomatic at a rate of about 2%/yr. The symptom that develops most commonly is biliary colic rather than a major biliary complication. Once biliary symptoms begin, they are likely to recur; pain returns in 20 to 40% of patients/yr, while about 1 to 2% of patients/yr develop complications such as cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis.

Treatment

• Laparoscopic cholecystectomy for symptomatic stones
• Expectant for asymptomatic stones; sometimes stone dissolution

Most asymptomatic patients decide that the discomfort, expense, and risk of elective surgery are not worth removing an organ that may never cause clinical illness. However, if symptoms occur, gallbladder removal (cholecystectomy) is indicated because pain is likely to recur and serious complications can develop.

Surgery: Surgery can be done with an open or laparoscopic technique.

Open cholecystectomy, which involves a large abdominal incision and direct exploration, is safe and effective. Its overall mortality rate is about 0.1% when done electively during a period free of complications.

Laparoscopic cholecystectomy is the treatment of choice. Using video endoscopy and instrumentation through small abdominal incisions, the procedure is less invasive than open cholecystectomy. The result is a much shorter convalescence, decreased postoperative discomfort, improved cosmetic results, yet no increase in morbidity or mortality. Laparoscopic cholecystectomy is converted to an open procedure in 2 to 5% of patients, usually because biliary anatomy cannot be identified or a complication cannot be managed. Older age typically increases the risks of any type of surgery.

Cholecystectomy effectively prevents future biliary colic but is less effective for preventing atypical symptoms such as dyspepsia. Cholecystectomy does not result in nutritional problems or a need for dietary limitations. Some patients develop diarrhea, often because bile salt malabsorption in the ileum is unmasked. Prophylactic cholecystectomy in asymptomatic patients with cholelithiasis is not warranted except in those with quite large gallstones (> 3 cm) or those with a calcified gallbladder (porcelain gallbladder) because of an increased risk of gallbladder carcinoma.

Stone dissolution: For patients who decline surgery or who are at high surgical risk (eg, because of concomitant medical disorders or advanced age), gallbladder stones can sometimes be dissolved by ingesting bile acids orally for many months. The best candidates for this treatment are those with small, radiolucent stones (more likely to be composed of cholesterol) in a functioning nonobstructed gallbladder—normal filling on cholescintigraphy or oral cholecystography or absence of stones in the neck.

Ursodeoxycholic acid 8 to 10 mg/kg/day po dissolves 80% of tiny stones < 0.5 cm in diameter within 6 mo. For larger stones (the majority), the success rate is much lower, even with higher doses of ursodeoxycholic acid. Further, after successful dissolution, stones recur in 50% within 5 yr. Most patients are thus not candidates and prefer laparoscopic cholecystectomy. Stone fragmentation (extracorporeal shock wave lithotripsy) to assist stone dissolution and clearance is now unavailable. Ursodeoxycholic acid, however, has value in preventing stone formation in morbidly obese patients who are losing weight rapidly after bariatric surgery or while on a very low calorie diet.

Last full review/revision December 2007 by Eldon A. Shaffer, MD

Content last modified December 2007