Hepatic Uptake, Conjugation, and Secretion of Bilirubin

Hepatocytes take up bilirubin from the sinusoidal plasma and excrete it after conjugation with glucuronic acid across the canalicular membrane into the bile. The entry and exit steps and the transport of bilirubin within the cell are not completely understood. The following is a plausible interpretation of the available data. 

Since binding of bilirubin to albumin is usually reversible, a small amount of free bilirubin is present in plasma in equilibrium with albumin-bound bilirubin. It is probably this free bilirubin that is taken up at a rate determined by its plasma concentration. As this free bilirubin concentration decreases, more bilirubin is released from albumin and becomes available for uptake. Alternatively, the albumin-bilirubin complex may bind to specific hepa-tocyte plasma membrane receptors, and thereby bilirubin is released to enter the cell. Both models are consistent 

The entry step seems to be carrier-mediated, is saturable, is reversible, and is competitively inhibited by sul-fobromophthalein, indocyanine green, cholecystographic agents, and several drugs. Bile salts do not compete with bilirubin for hepatic uptake. 

Formation of bilirubin diglucuronide. Glucuronidation occurs in two steps via formation of monoglucuronide. Mono-and diglucuronides are more water-soluble and less lipophilic than bilirubin. Conversion of bilirubin to water-soluble products is obligatory for excretion of bilirubin from hepatocytes. M, Methyl V, vinyl UPD-GA, UDP-glucuronic acid. 

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