Cholestatic Jaundice

Excerpt

Cholestatic jaundice occurs due to cholestasis, a condition where bile flow significantly reduces or completely stops, leading to bile components (eg, bilirubin) accumulating in the bloodstream. Cholestasis can result from functional impairment of the hepatocytes in the secretion of bile or due to an obstruction at any level of the excretory pathway of bile, from the level of the hepatic parenchymal cells at the basolateral (sinusoidal) membrane of the hepatocyte to the ampulla of Vater in the duodenum.

Cholestatic jaundice can be classified into intrahepatic or extrahepatic cholestasis, depending upon the level of obstruction to bile flow. Intrahepatic or functional cholestasis can be due to a condition involving the liver parenchymal cells or the intrahepatic bile ducts. Extrahepatic or obstructive cholestasis is due to an excretory block outside the liver and the extrahepatic bile ducts. Furthermore, intrahepatic cholestasis can be further subclassified as intralobular, affecting liver parenchymal cells and transporter molecules, or extralobular, affecting intrahepatic bile ducts.

Clinically, cholestasis leads to the retention of bile constituents in the blood. The 2 primary constituents of bile are bilirubin and bile acids. Histologically, the retention of bilirubin in the hepatocytes, bile canaliculi, or bile ducts causes bilirubinostasis, which clinically manifests as jaundice. Biochemically, cholestasis is marked by the elevation of predominantly serum alkaline phosphatase. On the other hand, the stagnation of bile acids causes typical changes in the periportal region of the liver, termed cholate stasis, and presents clinically as pruritus. As the excretion of bilirubin follows hepatocellular pathways different from those of bile acids, serum bilirubin level may be normal in some instances of severe cholestasis (eg, anicteric cholestasis), and the patient may present with pruritus without jaundice. Prominent features of cholestasis are pruritus and malabsorption of fat and fat-soluble vitamins.