By Mounir Ibrahim, MD; Shashank Sarvepalli, MD; Gareth Morris-Stiff, MD, PhD; Maged Rizk, MD; Amit Bhatt, MD; R. Matthew Walsh, MD; Umar Hayat, MD; Ari Garber, MD, EDD; John Vargo, MD; Carol A. Burke, MD
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services Policy
The prevalence of gallstones is approximately 10% to 15% of the adult US population. 1,2 Most cases are asymptomatic, as gallstones are usually discovered incidentally during routine imaging for other abdominal conditions, and only about 20% of patients with asymptomatic gallstones develop clinically significant complications. 2,3
Nevertheless, gallstones carry significant healthcare costs. In 2004, the median inpatient cost for any gallstone-related disease was $11,584, with an overall annual cost of $6.2 billion. 4,5
Laparoscopic cholecystectomy is the standard treatment for symptomatic cholelithiasis. For asymptomatic cholelithasis, the usual approach is expectant management (“watch and wait”), but prophylactic cholecystectomy may be an option in certain patients at high risk.
Gallstones can be classified into 2 main categories based on their predominant chemical composition: cholesterol or pigment.
About 75% of gallstones are composed of cholesterol. 3,4 In the past, this type of stone was thought to be caused by gallbladder inflammation, bile stasis, and absorption of bile salts from damaged mucosa. However, it is now known that cholesterol gallstones are the result of biliary supersaturation caused by cholesterol hypersecretion into the gallbladder, gallbladder hypomotility, accelerated cholesterol nucleation and crystallization, and mucin gel accumulation.
Black pigment gallstones account for 10% to 15% of all gallstones. 6 They are caused by chronic hemolysis in association with supersaturation of bile with calcium hydrogen bilirubinate, along with deposition of calcium carbonate, phosphate, and inorganic salts. 7
Brown pigment stones, accounting for 5% to 10% of all gallstones, 6 are caused by infection in the obstructed bile ducts, where bacteria that produce beta-glucuronidase, phospholipase, and slime contribute to formation of the stone. 8,9
Risk Factors For Gallstones
Multiple risk factors are associated with the development of gallstones ( Table 1 ).
Age. After age 40, the risk increases dramatically, with an incidence 4 times higher for those ages 40 to 69 than in younger people. 10
Female sex. Women of reproductive age are 4 times more likely to develop gallstones than men, but this gap narrows after menopause. 11 The higher risk is attributed to female sex hormones, pregnancy, and oral contraceptive use. Estrogen decreases secretion of bile salts and increases secretion of cholesterol into the gallbladder, which leads to cholesterol supersaturation. Progesterone acts synergistically by causing hypomobility of the gallbladder, which in turn leads to bile stasis. 12,13
Ethnicity. The risk is higher in Mexican Americans and Native Americans than in other ethnic groups. 14
Rapid weight loss, such as after bariatric surgery, occurs from decreased caloric intake and promotes bile stasis, while lipolysis increases cholesterol mobilization and secretion into the gallbladder. This creates an environment conducive to bile supersaturation with cholesterol, leading to gallstone formation.
Chronic hemolytic disorders carry an increased risk of developing calcium bilirubinate stones due to increased excretion of bilirubin during hemolysis.
Obesity and diabetes mellitus are both attributed to insulin resistance. Obesity also increases bile stasis and cholesterol saturation.
Clinical Presentation Of Gallstones (Cholelithiasis)
Most patients with gallstones (cholelithiasis) experience no symptoms. Their gallstones are often discovered incidentally during imaging tests for unrelated or unexplained abdominal symptoms. Most patients with asymptomatic gallstones remain symptom-free, while about 20% develop gallstone-related symptoms. 2,3
Abdominal pain is the most common symptom. The phrasebiliary colic —suggesting pain that is fluctuating in nature—appears ubiquitously in the medical literature, but it does not correctly characterize the pain associated with gallstones.
Most patients with gallstone symptoms describe a constant and often severe pain in the right upper abdomen, epigastrium, or both, often persisting for 30 to 120 minutes. Symptoms are frequently reported in the epigastrium when only visceral pain fibers are stimulated due to gallbladder distention. This is usually called midline pain; however, pain occurs in the back and right shoulder in up to 60% of patients, with involvement of somatic fibers. 15,16 Gallstone pain is not relieved by change of position or passage of stool or gas.
Onset of symptoms more than an hour after eating or in the late evening or at night also very strongly suggests biliary pain. Patients with a history of biliary pain are more likely to experience it again, with a 69% chance of developing recurrent pain within 2 years. 17