The significance of bile pigment deconjugation by beta-glucuronidase in canine hyperbilirubinemia.

In dogs, the differentiation between haemolytic and cholestatic hepatobiliary diseases cannot be achieved by measuring of the unconjugated:conjugated bilirubin ratio, which is in contrast with generally held clinical concepts. The overlap of the bilirubin ratios between the two groups of icterus-generating diseases might in part be explained by deconjugation of conjugated bilirubin. Enzymatic cleavage by hepatic beta-glucuronidase might result in higher unconjugated bilirubin (UCB) fractions in cholestatic disease. The influence of deconjugation of bilirubins by beta-glucuronidase was investigated in 25 healthy dogs and 35 dogs with spontaneous hyperbilirubinemia due to either hepatobiliary or haemolytic disease. UCB and its mono- and diconjugates were measured by alkaline methanolysis and HPLC in plasma and liver tissue. The activity of beta-glucuronidase was also measured in both liver and plasma. In addition, semiquantitative histochemical quantitation of bilirubins in liver tissue was performed. The concentration and the fraction of UCB in plasma of dogs with hepatobiliary disease were not significantly different from those of dogs with autoimmune haemolytic anaemia. There was a correlation between the fraction of UCB in liver and plasma of jaundiced dogs (r = 0.42, P less than 0.01) and between the histochemically estimated and the biochemically measured total bilirubin concentration in liver tissue. There was no correlation between the beta-glucuronidase activity and either unconjugated or monoconjugated bilirubin in plasma or liver of diseased animals. The fraction and the concentration of UCB in the liver of dogs with hepatic and with haemolytic disease were identical. It is concluded that beta-glucuronidase activity is not the significant factor in explaining the similar levels and fractions of UCB in dogs with hyperbilirubinemia due to either hepatobiliary or haemolytic disease.