A 31-year-old woman comes to the emergency department due to worsening right upper quadrant pain, fever, nausea, and vomiting for a day. The pain increases with deep inspiration. Other medical conditions include uterine fibroids and sickle cell anemia. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 38.6 C (101.5 F), blood pressure is 120/70 mm Hg, and pulse is 102/min. BMI is 24 kg/m2. On examination, the patient appears uncomfortable because of the pain; there is no jaundice. Tenderness and guarding are present over the right upper quadrant. Bowel sounds are decreased. Hemoglobin is 10.1 g/dL and white blood cell count is 18,000/mm3 with 7% band forms. Abdominal ultrasound shows evidence of cholelithiasis and gallbladder wall thickening. Gross inspection of the specimen obtained during laparoscopic cholecystectomy is shown in the image below:
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Which of the following is most likely responsible for this patient's symptoms?
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This patient with fever, right upper quadrant pain, and leukocytosis has acute cholecystitis. Cholecystitis is inflammation of the gallbladder that usually occurs when gallstones obstruct the cystic duct. Gallstones form due to supersaturation of bile constituents (eg, cholesterol, bilirubin), which then crystalize out of solution with other bile components (eg, mucin, calcium, proteins) to produce stones.
Black gallstones, as seen in this patient, form due to the supersaturation of bilirubin, which precipitates with calcium to form multiple small calcium bilirubinate stones. Bilirubin supersaturation occurs through the following mechanisms:
Increased bilirubin production: Chronic hemolysis, as seen in sickle cell anemia, hereditary spherocytosis, and thalassemia, increases circulating levels of free bilirubin, which is taken up by the liver and excreted into bile.
Altered enterohepatic circulation of bilirubin: Ileal disease (eg, Crohn disease) or resection allows bile acids, which are normally reabsorbed in the ileum, to spill into the colon. There, bile acids solubilize unconjugated bilirubin, allowing its reabsorption and concentration within the bile (Choice A).
This patient with sickle cell anemia most likely has chronic hemolysis, which has increased bilirubin efflux into the bile, promoting formation of black stones.
(Choices B and C) Biliary stasis promotes gallstone formation by providing a favorable environment for crystal nucleation and aggregation. Stasis can occur due to gallbladder denervation (eg, transection of the nerves that control gallbladder contraction) or decreased stimulation by enterocytes during prolonged fasting (cholecystokinin is released in response to food). However, stasis usually promotes the formation of yellow cholesterol stones, and this patient did not have prolonged fasting or surgery prior to developing her symptoms.
(Choice D) Cirrhosis can also occasionally promote the formation of black stones due to impaired bile acid synthesis and hyperbilirubinemia (due to cholestasis). However, this patient does not have a history of cirrhosis or stigmata of chronic liver disease (eg, jaundice).
(Choice E) Increased cholesterol synthesis results in the formation of yellow cholesterol gallstones. This typically occurs in the setting of obesity, diabetes mellitus, or certain medications (eg, estrogen-containing oral contraceptives).
Educational objective:
Black gallstones form due to supersaturation of the bile with bilirubin, which precipitates with calcium to form calcium bilirubinate stones. This typically occurs in the setting of chronic hemolysis (eg, sickle cell disease) or altered enterohepatic circulation of bilirubin (eg, Crohn disease, ileal resection).