Selective Biliary Obstruction: A Model for the Study of Lipid Metabolism in Cholestasis

Abstract

The metabolic changes associated with cholestasis are diverse and may be related either directly or indirectly to failure of bile secretion. Thus, abnormalities in lipid and lipoprotein metabolism could result from the effects of: (1) failure of lipids to be secreted into bile; (2) qualitative or quantitative changes in the lipoproteins of plasma or intestinal lymph; or (3) altered liver cell function not directly attributable to the first two factors. In this paper, a method is presented which allows these factors to be analyzed separately by permitting obstructed and unobstructed liver tissue from the same animal to be compared in regard to structure and function. In this model, selective biliary obstruction, light microscopic changes consistent with cholestasis are found in the obstructed median lobe but not in the unobstructed right lobe. By electron microscopy, osmiophilic material is present in the canaliculi on the obstructed side, while on the unobstructed side the prominent Golgi apparatus, moderately dilated canaliculi, and intact microvilli suggest increased bile secretory activity. Tissue concentrations of total and free cholesterol and of phospholipids are similar in unobstructed and obstructed hepatic lobes. In serum, levels of cholesterol, phospholipid, and alkaline phosphatase are significantly elevated; an abnormal lipoprotein, characteristic of biliary obstruction, also appears. It is anticipated that selective biliary obstruction will be useful in the experimental approach to further elucidate the abnormalities in lipid and lipoprotein metabolism in cholestasis, and the process of bile secretion in general.