Electron microscopic studies on hepatic alkaline phosphatase in experimentally induced biliary obstruction of the rat.

The alterations of the alkaline phosphatase (ALP) activity in the rat liver following bile duct ligation were investigated by electron microscopical techniques. Serum ALP activity reached the maximum at 24 hours after ligation and two isozymes of ALP, high molecular and low molecular one, appeared in the serum. Bile canaliculi became dilated at 48 hours after ligation and the microvilli were destructed and diminished in number. ALP activity was observed almost only on the bile canalicular membrane of the liver cells in the control. On the other hand, in the bile duct-ligated rat, the ALP activity on the canalicular membrane was markedly increased initially, then it appeared on the lateral membrane, and finally on the sinusoidal membrane also. It was not stainable on the canalicular membranes which lacked microvilli. The proposed pathway through which hepatic ALP enters the blood stream in bile duct-ligated rats is as follows: ALP, being synthesized in the microsomes of hepatocytes, is initially transferred to the bile canalicular membrane and diffused to lateral membrane through tight junction, reaches to sinusoidal membrane then released into the blood stream.