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The liver plays an essential role in the maintenance of metabolic homeostasis. Hepatic functions include the synthesis, storage, and breakdown of glycogen. In addition, the liver is important in the metabolism of lipids; the synthesis of albumin, clotting factors, and other important proteins; the synthesis of the bile acids necessary for absorption of lipids and fat-soluble vitamins; and the metabolism of cholesterol.20,54 Hepatocytes facilitate the excretion of metals, most importantly iron, copper, zinc, manganese, mercury, and aluminum; and the detoxification of products of metabolism, such as bilirubin and ammonia.29,62 Generalized disruption of these important functions results in manifestations of liver failure: hyperbilirubinemia, coagulopathy, hypoalbuminemia, hyperammonemia, and hypoglycemia.41,74 The hepatic functions can also be selectively altered by exposure to hepatotoxins.54 Disturbances of more specific functions result in accumulation of fat, metals, and bilirubin, and the development of fat-soluble vitamin deficiencies.20,54

The liver is also the primary site of biotransformation and detoxification of xenobiotics.46,133 Its interposition between the gut and systemic circulation makes it the first-pass recipient of xenobiotics absorbed from the gastrointestinal tract into the portal vein. The liver also receives blood from the systemic circulation and participates in the detoxification and elimination of xenobiotics that reach the bloodstream through other routes, such as inhalation or cutaneous absorption.20,118

Many xenobiotics are lipophilic inert substances that require chemical activation followed by conjugation to make them sufficiently soluble to be eliminated. The liver contains the highest concentration of enzymes involved in phase I oxidation-reduction reactions, the first stage of detoxification for many lipophilic xenobiotics.46,133 Conjugation of the reactive products of phase I biotransformation with molecules such as glucuronide facilitates excretion.133 (Chap. 12) Although many xenobiotics that are detoxified in the liver are subsequently excreted in the urine, the biliary tract provides a second essential route for the elimination of detoxified xenobiotics and products of metabolism.20,29

Two pathologic concepts are used to describe the appearance and function of the liver; a structural one represented by the hepatic lobule, and a functional one represented by the acinus. The basic structural unit of the liver characterized by light microscopy is the hepatic lobule, a hexagon with the central hepatic vein at the center and the portal triads at the angles. The portal triad consists of the portal vein, the common bile duct, and the hepatic artery. Cords of hepatocytes are oriented radially around the central hepatic vein, forming sinusoids. The acinus, or "metabolic lobule" is a functional unit of the liver. Located between two central hepatic veins, it is bisected by terminal branches of the hepatic artery and portal vein that extend from the bases of the acini toward hepatic venules at the apices. The acinus is subdivided into three metabolically distinct zones. Zone 1 lies near the portal triad, zone 3 near the central hepatic vein, and zone 2 is intermediate.20,...

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