[Pathogenesis of black gallstones associated with hemolytic disease]

In order to investigate the pathogenesis of black gallstones associated with hemolytic disorders, experimental and clinical studies were performed. Firstly, a one-shot injection of bilirubin and hemolyzed blood, and a continuous injection of bilirubin were performed in mongrel dogs with the aim to analyze the changes of hepatic and gallbladder bile composition. Secondly, gallbladder bile obtained intraoperatively from the patients with black gallstones associated with hemolytic disease, patients with black stones not associated with hemolytic disease and patients with gallbladder polyp were analyzed in order to compare the characteristics of hemolytic patients' bile with those of the model animals. High concentration of total bilirubin and increased proportion of bilirubin monoconjugate (BMC) fraction was observed in the bile of patients with black stone associated with hemolytic disease compared with the bile of the patients of other two groups. Bile pH, total calcium concentration and ionized calcium concentration were similar in all the groups. Total bile lipid concentration of hemolytic patients was decreased but the ratio of total bile acid to total lipid was increased. Both bolus injection of bilirubin and hemolyzed blood produced an increase of total bilirubin concentration and BMC in hepatic bile. Continuous bilirubin injection for 7 days induced an increase of total bilirubin and BMC in both hepatic and gallbladder bile. These results suggest that the conjugating capacity of the hepatocyte is surpassed by the excessive amount of bilirubin produced after hemolysis, producing therefore, an increased BMC and unconjugated bilirubin content in bile. This increased content can precipitate in bile as black gallstones.