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Cholelithiasis: Overview and Risk Factors

Cholelithiasis, or gallstones, is a common syndrome in which hard stones composed of cholesterol or bile pigments form in the gallbladder. If stones are present in the common bile duct, the condition is called choledocholithiasis. The syndrome occurs in up to 20% of women and 8% of men worldwide.

Most stones are composed of cholesterol. In bile, cholesterol is in equilibrium with bile salts and with phosphatidylcholine. When the concentration of cholesterol rises to the point of supersaturation, crystallization occurs. A sludge containing cholesterol, mucin, calcium salts, and bilirubin forms, and, ultimately, stones develop.

Most cases are asymptomatic. Some result in biliary colic, in which stones intermittently obstruct the neck of the gallbladder and cause episodic right–upper–quadrant pain. Chronic obstruction may result in cholecystitis (infection and inflammation of the gallbladder) or cholangitis (infection and inflammation of the common bile duct). Both syndromes are serious, and, if untreated, may result in sepsis, shock, and death.

Presenting symptoms include episodic right–upper–quadrant or epigastric pain, which generally occurs after eating a large meal and may radiate to the back, right scapula, or right shoulder. Nausea, vomiting, dyspepsia, burping, and food intolerance (especially to fatty, greasy, or fried foods; meats; and cheeses) are common. More severe symptoms, including fever and jaundice, may signify cholecystitis or cholangitis.

Risk Factors

Increasing age. Gallstones are most common in individuals over age 40.

Female gender. Females are more likely to develop gallstones in all age groups, probably due to the effects of estrogens. This increased risk is particularly striking in young women, who are affected 3 to 4 times more often than men of the same age.

Elevated estrogen and progesterone. During pregnancy, oral contraceptive use, or hormone replacement therapy, estrogen and progesterone induce changes in the biliary system that predispose to gallstones.

Obesity. Obesity is a significant risk factor for the development of cholesterol gallstones due to enhanced cholesterol synthesis and secretion.

Rapid weight loss. Bariatric surgery and very–low–calorie diets increase risk of gallstone formation, possibly due to increased concentrations of bile constituents.

Family history. Gallstones are more than twice as common in first–degree relatives of patients with gallstones.

High–fat diet. See Nutritional Considerations.

Cirrhosis. Cirrhosis results in as much as a 10–fold increased risk of gallstones, perhaps due to impaired gallbladder contraction or the high estrogen levels that occur in cirrhotic patients.

Gallbladder stasis. When bile remains in the gallbladder for an extended period, supersaturation can occur, resulting in gallstones. Gallbladder stasis is associated with diabetes mellitus, total parenteral nutrition (probably due to lack of enteral stimulation), postvagotomy, and spinal cord injury.

Ileal disease or resection (as in Crohn’s disease). Altered enterohepatic cycling of bile salts increases risk of gallstone formation.

Hemolytic states. The rapid destruction of red blood cells in sickle cell disease and other hemolytic conditions causes the release of bilirubin, which in turn increases the risk of gallstones.

Medications. Drugs implicated in the development of cholelithiasis include clofibrate, octreotide, and ceftriaxone.

Physical inactivity. The Health Professional’s Follow–up Study suggests that one third of symptomatic cholelithiasis cases could be prevented by 30 minutes of daily aerobic exercise.


Cholelithiasis: Diagnosis and Treatment >>