PRINCIPLES OF TOXICOLOGY

A second reason for the susceptibility of the liver to chemical attack is that it is the primary organ
for the biotransformation of chemicals within the body. As discussed in Chapter 3, the desired net
outcome of the biotransformation process is generally to alter the chemical in such a way that it is (1)
no longer biologically active within the body and (2) more polar and water-soluble and, consequently,
more easily excreted from the body. Thus, in most instances, the liver acts as a detoxification organ. It
lowers the biological activity and blood concentrations of a chemical that might otherwise accumulate
to toxic levels within the body. For example, it has been estimated that the time required to excrete
one-half of a single dose of benzene would be about 100 years if the liver did not metabolize it. The
primary disadvantage of the liver’s role as the main organ metabolizing chemicals, however, is that
toxic reactive chemicals or short-lived intermediates can be formed during the biotransformation
process. Of course, the liver, as the site of formation of these bioactivated forms of the chemical, usually
receives the brunt of their effects.
Morphologic Considerations
The liver can be described as a large mass of cells packed around vascular trees of arteries and veins
(see Figure 5.2). Blood supply to the liver comes from the hepatic artery and the portal vein, the former
normally supplying about 20 percent of blood reaching the liver and the latter about 80 percent.
Terminal branches of the hepatic artery and portal vein are found together with the bile duct (Figure
5.2). In cross section, these three vessels are called the portal triad. Blood is collected in the terminal
hepatic venules, which drain into the hepatic vein. The functional microanatomy can be viewed in
different ways. In one view, the basic unit of the liver is termed the lobule. Blood enters the lobule
Bile
ductule
Hepatic
artery
Portal
vein
5.1 THE PHYSIOLOGIC AND MORPHOLOGIC BASES OF LIVER INJURY 113
Sinusoid
Central
vein
Opening of
sinusoid
Bile
canaliculi
Hepatic
lamina
Fenestration
in lamina
Figure 5.2 Hepatic architecture, showing arrangement of blood vessels and cords of liver cells. Reproduced with
permission from Textbook of Human Anatomy, Second Edition, C.V. Mosby Co., St. Louis, MO, 1976.