Cholestasis is defined as stagnation, or at least a marked reduction, in bile secretion and flow. Cholestasis can be due to a functional impairment of the hepatocytes in the secretion of bile and/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 thus be classified into intrahepatic or extrahepatic cholestasis, depending upon the level of obstruction to bile flow. Intrahepatic cholestasis or functional cholestasis can be due to a disease involving the liver parenchymal cells and/or the intrahepatic bile ducts. Intrahepatic cholestasis can be further subclassified as intralobular (disease of liver parenchymal cells and transporter molecules) and extralobular (disease involving intrahepatic bile ducts) cholestasis. Extrahepatic cholestasis or obstructive cholestasis is due to excretory block outside of the liver, along with the extrahepatic bile ducts .
Clinically, cholestasis leads to retention of the constituents of bile in blood. The 2 major constituents of bile are bilirubin and bile acids. Thus biochemically, cholestasis is marked by the elevation of predominantly serum alkaline phosphatase. Histologically, the retention of bilirubin in the hepatocytes, bile canaliculi, or bile ducts causes bilirubinostasis and is clinically manifested as jaundice. The stagnation of bile acids, on the other hand, causes typical changes in the periportal region of the liver which is termed as 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 certain cases of severe cholestasis (anicteric cholestasis), and the patient may present with only pruritus but no jaundice. Prominent features of cholestasis are pruritus and malabsorption of fat and fat-soluble vitamins.