A 64-year-old man comes to the office due to acute-onset right upper quadrant abdominal pain, nausea, and vomiting. The patient had an extensive small bowel resection due to bowel ischemia a year ago and has been receiving total parenteral nutrition since then. His other medical problems include atrial fibrillation and hypertension. Examination shows right upper quadrant tenderness on deep palpation. Initial laboratory studies show moderate leukocytosis with normal hepatic transaminase, amylase, and lipase levels. Abdominal ultrasonography reveals gallstones and edema of the gallbladder wall. Review of prior records indicates that he had no gallstones noted on abdominal imaging performed prior to the bowel resection. Which of the following is most likely responsible for the development of gallstones in this patient?
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Cholesterol is secreted in bile, where it is solubilized by bile salts and phosphatidylcholine. If there is more cholesterol than can be dissolved by the bile salts, the cholesterol will precipitate into insoluble crystals, leading to the formation of gallstones. Risk factors for gallstone formation include obesity or rapid weight loss, female sex, glucose intolerance, and hypomotility of the gallbladder (eg, pregnancy, prolonged fasting).
A prolonged course of total parenteral nutrition (TPN) is often complicated by gallstones. In normal individuals, enteral passage of fat and amino acids into the duodenum triggers release of cholecystokinin (CCK), leading to contraction of the gallbladder. The absence of normal enteral stimulation in patients receiving TPN leads to decreased CCK release and subsequent biliary stasis. In addition, patients with extensive resection of the ileum can have disruption to the normal enterohepatic circulation of bile acids, leading to inadequate solubilization of biliary cholesterol and formation of cholesterol crystals.
(Choice B) Advanced liver disease can impair cholesterol conversion to bile acids due to the diminished synthetic ability of injured hepatocytes, leading to supersaturation of the bile with cholesterol. This contributes to the increased risk of gallstones seen in cirrhotic individuals but would be unlikely in this patient with no evidence of hepatocellular dysfunction.
(Choice C) TPN preparations contain glucose, amino acids, and fats based on the individual patient's needs, with additional electrolytes, vitamins, minerals, and trace elements in carefully calculated amounts. Serum triglyceride levels may rise on TPN, but TPN does not contain significant amounts of cholesterol, and serum cholesterol levels do not usually change significantly.
(Choice D) Deficient supplementation of essential fatty acids in TPN is associated with a number of clinical complications, including dermatitis, alopecia, neuropathy, visual disturbances, and ataxia. Gallstones are not related.
(Choice E) Digested peptides and free amino acids in the gastric lumen are a major stimulus for gastrin release, so parenteral nutrition typically results in decreased (not increased) gastrin levels. Moreover, gastrin is not a significant factor in the formation of gallstones.
Educational objective:
The absence of normal enteral stimulation in patients receiving total parenteral nutrition leads to decreased cholecystokinin release, biliary stasis, and increased risk of gallstones. Resection of the ileum can also increase the risk of gallstones due to disruption of normal enterohepatic circulation of bile acids.