Nutritional cirrhosis in rhesus monkeys: Electron microscopy and histochemistry

Abstract

A choline-deficient low protein diet was fed to twelve Rhesus monkeys for two years. Eight of the animals died, most of them during the latter part of the first year. Mortality among males was higher than in females. Three of the four surviving animals developed fatty metamorphosis followed by cirrhosis. Eight sequential liver biopsies from each of these animals were studied. Control specimens showed paracrystalline mitochondrial inclusions in the hepatocytes and cytoplasmic crystalloids in the endothelial cells of the hepatic sinusoids and portal vessels. The significance of both structures remains unknown. Striking cytoplasmic vacuoles, possibly produced by anoxia during surgical liver biopsy, were observed in some specimens. The hepatocytes of the animals on the experimental diet, in addition to fatty change, showed mitochondria with bizarre shapes, circular cristae or increased electron opacity. Focal cytoplasmic degradation and Golgi dilatation were prominent. Microvilli developed along the intercellular spaces and became more prominent in the space of Disse. Basement membranes which were rarely continuous could be seen between hepatocytes and sinusoidal lining cells. In Disse spaces and intercellular spaces microfibrils and increased collagen fibers developed. In the later biopsies septa were formed which contained a higher proportion of typical collagen to microfibrils than the fibrillar material in the Disse spaces. The hepatocytes in the cirrhotic nodules stained more strongly for glycogen and were more active in nearly all histochemical enzyme reactions than the hepatocytes in non-nodular areas. This suggests that the nodules differed metabolically from the rest of the parenchyma.