Cholestasis Produced by Combinations of Manganese and Bilirubin
The early observations with manganese and bilirubin suggested that the observed cholestatic mechanism might be due to intracanalicular precipitation of a manganese/ bilirubin aggregate. This hypothesis was supported by the finding of yellow acellular material in the bile ducts, although canalicular plugs were not evident. With electron microscopy, the infusion of bilirubin after injection of manganese resulted in more severe ultrastructural alterations than those observed with manganese given alone. The abnormalities included increased canalicular dilatation, the presence of prominent cytoplasmic vacuoles and swollen areas of pericanalicular cytoplasm. In addition, fibrillar electron-dense material was observed within the canaliculi, vacuoles, pericanalicular ectoplasm, and bile ducts; these findings were not observed in animals treated only with manganese. The ultrastructural alterations were consistent with an obstructive process. If the infusion of bilirubin followed the injection of manganese by 24 hr, the effects on bile flow and hepatic ultrastructure were very mild and not different from those of rats given manganese alone.