PRINCIPLES OF TOXICOLOGY - Biology East Borneo

5.1 THE PHYSIOLOGIC AND MORPHOLOGIC BASES OF LIVER INJURY 113A second reason for the susceptibility of the liver to chemical attack is that it is the primary organfor the biotransformation of chemicals within the body. As discussed in Chapter 3, the desired netoutcome 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. Itlowers the biological activity and blood concentrations of a chemical that might otherwise accumulateto toxic levels within the body. For example, it has been estimated that the time required to excreteone-half of a single dose of benzene would be about 100 years if the liver did not metabolize it. Theprimary disadvantage of the liver’s role as the main organ metabolizing chemicals, however, is thattoxic reactive chemicals or short-lived intermediates can be formed during the biotransformationprocess. Of course, the liver, as the site of formation of these bioactivated forms of the chemical, usuallyreceives the brunt of their effects.Morphologic ConsiderationsThe 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 formernormally 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 (Figure5.2). In cross section, these three vessels are called the portal triad. Blood is collected in the terminalhepatic venules, which drain into the hepatic vein. The functional microanatomy can be viewed indifferent ways. In one view, the basic unit of the liver is termed the lobule. Blood enters the lobuleSinusoidBilecanaliculiBileductuleHepaticarteryCentralveinOpening ofsinusoidHepaticlaminaFenestrationin laminaPortalveinFigure 5.2 Hepatic architecture, showing arrangement of blood vessels and cords of liver cells. Reproduced withpermission from Textbook of Human Anatomy, Second Edition, C.V. Mosby Co., St. Louis, MO, 1976.