Bilirubin cycles enterohepatically after ileal resection in the rat

Patients with ileal disease, resection, or bypass are at increased risk of developing pigment gallstones, but the pathophysiological mechanisms are unknown. The aim of this study was to test the hypothesis that ileectomy induces enterohepatic cycling of bilirubin.

Ileectomy or sham operation was performed in adult male Sprague-Dawley rats with the following control procedures: no operation, ileal transection, proximal or distal jejunectomy, ileocolonic transposition, and ileocecectomy. Bilirubin and bile salt secretion rates were measured after bile duct cannulation performed 3-11 days after intestinal surgery. Also measured were bilirubin and bile salt concentrations in the colon as well as indices of hemolysis in blood.

Compared with controls, bilirubin secretion rates were increased significantly 3-5 days after ileectomy, distal jejunectomy, ileocolonic transposition, and ileocecectomy, with no hemolysis occurring. Bile salt secretion rates also increased significantly after ileectomy but decreased markedly with prevention of coprophagy, whereas bilirubin secretion rates remained elevated. By 8-11 days after surgery, intestinal adaptation normalized bile salt reabsorption, and hypersecretion of bilirubin was abolished. Colonic levels of unconjugated bilirubin and bile salts were increased fivefold and eightfold respectively in ileectomized animals, but unconjugated bilirubin levels remained normal in bile.

These results are consistent with the hypothesis that enterohepatic cycling of bilirubin occurs with bile salt malabsorption.