Drug Elimination I

The Liver as an Excretory Organ
As the chief organ of drug biotransformation,
the liver is richly supplied with
blood, of which 1100 mL is received
each minute from the intestines
through the portal vein and 350 mL
through the hepatic artery, comprising
nearly 1/3 of cardiac output. The blood
content of hepatic vessels and sinusoids
amounts to 500 mL. Due to the widening
of the portal lumen, intrahepatic
blood flow decelerates . Moreover,
the endothelial lining of hepatic sinusoids
contains pores large
enough to permit rapid exit of plasma
proteins. Thus, blood and hepatic parenchyma
are able to maintain intimate
contact and intensive exchange of substances,
which is further facilitated by
microvilli covering the hepatocyte surfaces
abutting Disse’s spaces.
The hepatocyte secretes biliary
fluid into the bile canaliculi (dark
green), tubular intercellular clefts that
are sealed off from the blood spaces by
tight junctions. Secretory activity in the
hepatocytes results in movement of
fluid towards the canalicular space.
The hepatocyte has an abundance of enzymes
carrying out metabolic functions.
These are localized in part in mitochondria,
in part on the membranes of the
rough (rER) or smooth (sER) endoplasmic
reticulum.