A 40-year-old woman comes to the office due to recurrent episodes of postprandial abdominal pain. The pain is in the right upper quadrant and is associated with nausea. The patient has no fever, jaundice, or loss of appetite. Other medical conditions include obstructive sleep apnea and obesity. The patient takes no medications. She has never had any surgeries. She does not use tobacco, alcohol, or illicit drugs. The patient is afebrile. Blood pressure is 140/90 mm Hg. BMI is 38 kg/m². Examination shows tenderness in the right upper quadrant. Abdominal ultrasound demonstrates multiple gallstones. A gross specimen obtained from laparoscopic cholecystectomy is shown in the image below: Which of the following is the most likely mechanism responsible for gallstone formation in this patient?

Question

Quizplus · Accepted Answer

Bile is stored and concentrated within the gallbladder and is involved in digestion and absorption of dietary fats and removal of waste products (eg, bilirubin, cholesterol) for excretion in feces. Gallstones usually occur when one such waste product supersaturates the bile, resulting in precipitation and eventual stone formation. In the United States, most gallstones are due to the supersaturation of cholesterol, which usually precipitates out of bile with calcium salts and mucin, forming white or yellow cholesterol stones, as seen in this patient. Cholesterol stone formation occurs due to the following: Increased cholesterol synthesis: Hypercholesterolemia, caused by diet, genetics, diabetes mellitus, medications (eg, oral contraceptives), or obesity (increased HMG-CoA reductase activity), results in hypersecretion of cholesterol into the bile. Gallbladder hypomotility: Pregnancy, medications (eg, somatostatin), prolonged fasting, parenteral nutrition, and spinal cord injury lead to gallbladder stasis, which promotes excessive water resorption from bile and concentration of cholesterol. Decreased bile acid synthesis (or recirculation): Fibrates (eg, fenofibrate) inhibit bile acid synthesis, increasing cholesterol concentration within the bile. Decreased bile acid resorption at the ileum (eg, due to Crohn disease) also promotes cholesterol concentration. Increased calcium or mucin concentration: Rapid weight loss (eg, gastric bypass) promotes increased calcium and mucin concentrations in the bile, which trap cholesterol crystals and promote stone formation. (Choices A and E) Increased enterohepatic cycling of bilirubin occurs with ileal disease (eg, Crohn disease), as the loss of bile acids promotes reabsorption of unconjugated bilirubin. Increased efflux of bilirubin into bile also occurs with hyperbilirubinemia from chronic hemolysis (eg, sickle cell disease). Because of high bilirubin concentrations, these mechanisms promote the formation of black pigment stones, not cholesterol stones. (Choices B and C) Although both decreased bile acid synthesis (eg, due to fibrate medications) and gallbladder hypomotility (eg, due to pregnancy, prolonged fasting, or spinal cord injury) promote the formation of cholesterol gallstones, this patient does not have risk factors for either etiology. Educational objective: Most gallstones occur due to the supersaturation of cholesterol, which precipitates out of bile with mucin and calcium salts to form white or yellow cholesterol stones. Factors that promote the formation of cholesterol stones include increased cholesterol synthesis, gallbladder hypomotility, increased calcium or mucin concentration, and decreased bile acid synthesis or recirculation.

A 40-Year-Old Woman Comes to the Office Due to Recurrent