Endotoxemia and cholestasis

Endotoxemia has been incriminated as a major cause of morbidity and mortality in patients with obstructive jaundice. It has been postulated that absence of gastrointestinal bile salt flow in cholestasis enhances portal absorption of bacterial endotoxin from the intestine, thereby predisposing the host to endotoxemia and its complications. This study re-evaluates this pathologic mechanism, using new quantitative chromogenic and conventional qualitative limulus techniques for the detection of bacterial endotoxin. Female Sprague-Dawley rats underwent either ligation of bile duct or sham operation. Serum total bilirubin, serum bile acid and intestinal bile acid concentrations were determined seven, 14 and 21 days after operation. Chromogenic and conventional qualitative limulus lysate endotoxin determinations were simultaneously performed on postoperative days two, seven, 14 and 21. Serum total bilirubin and bile acid concentrations were elevated and intestinal bile acid levels depressed at days seven, 14 and 21 (p < 0.05). Results of quantitative and qualitative limulus studies failed to demonstrate the coexisting development of portal or systemic endotoxemia in rats with the bile duct ligated after diminution of flow of gastrointestinal bile salt. These data refute the hypothesis that flow of gastrointestinal bile salt enhances portal absorption of intestinally derived endotoxin and suggest alternative mechanisms are involved in the pathogenesis of endotoxemia in obstructive jaundice.