The association between chronic hemolysis and pigment gallstones is well known but not adequately understood. To define the source and quantity of insoluble pigment resulting from hemolysis, hepatic bile in miniature swine was studied during the intravenous infusion of distilled water. Concentrations of both total bilirubin and insoluble unconjugated bilirubin rose rapidly during the first 2 hr to levels more than seven times above control values. In the third hour, unconjugated pigment continued to increase while total bilirubin plateaued, suggesting that glucuronidation or transport maxima had been reached. Elevations in unconjugated bilirubin could not be accounted for by the intrabiliary hydrolysis of conjugated bilirubin. It is concluded that hemolysis results in the secretion of large quantities of insoluble bilirubin directly into bile. This process may represent an important step in the development of pigment polymers or precipitates.
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