ABSTRACT
Bile acids and bilirubin are elevated in serum, giving rise to the cardinal clinical manifestations of cholestasis, itching, and jaundice, respectively. Serum cholesterol levels are also elevated, as are the levels of enzymes normally present in bile, including alkaline phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, and leucine aminopeptidase. Approximately 75% of patients with prolonged cholestasis, of extra- or intrahepatic origin, have alkaline phosphatase values elevated fourfold or more. As understanding of the functions of the hepatocyte developed, the focus on the mechanisms of cholestasis shifted from mechanical obstruction to pathologic changes in the hepatocyte itself. The cholestasis induced by α-napthylisothiocyanate is attributed to the increased permeability of the tight junctions between hepatocytes and bile duct epithelial cells, and the subsequent diffusion of osmotically active solutes from the bile into the plasma. Cytochalasin has a number of effects, including detachment of microfilaments from the plasma membrane and prevention of the polymerization of actin.
