across the three zones. The distribution of liver damage result-are the first to show ischemic necrosis (centrilobular necrosis) ing from ischemia and exposure to toxic substances can be ex-in situations of reduced perfusion and the first to show fat ac-plained using this zonal interpretation. cumulation. They are the last to respond to toxic substances
Cells in zone 1 are the first to receive oxygen, nutrients, and bile stasis. Normal variations in enzyme activity, the and toxins from the sinusoidal blood and the first to show number and size of cytoplasmic organelles, and the size of cymorphologic changes after bile duct occlusion (bile stasis). toplasmic glycogen deposits are also seen between zones 1 These cells are also the last to die if circulation is impaired and 3. Cells in zone 2 have functional and morphologic char-and the first to regenerate. On the other hand, cells in zone 3 acteristics and responses intermediate to those of zones 1 and 3.
FIGURE 18.5 • Comparison of the classic liver lobule, portal lobule, and liver acinus. The area indicated in blue shows the territory of each of the three units relating to liver organization and function. The classic lobule has the terminal hepatic venule (central vein) at the center of the lobule and the portal canals containing portal triads at the peripheral angles of the lobule. The portal lobule has a portal canal at the center of the lobule and terminal hepatic venules (central veins) at the peripheral angles of the lobule. The liver acinus has distributing vessels at the equator and terminal hepatic venules (central veins) at each pole.
FIGURE 18.6 • The liver acinus. The liver acinus is a functional interpretation of liver organization. It consists of adjacent sectors of neighboring hexagonal fields of classic lobules partially separated by distributing blood vessels. The zones, marked 1, 2, and 3, are supplied with blood that is most oxygenated and richest in nutrients in zone 1 and least so in zone 3. The terminal hepatic venules (central veins) in this interpretation are at the edges of the acinus instead of in the center, as in the classic lobule. The vessels of the portal canals, namely, terminal branches of the portal vein and hepatic artery that, along with the smallest bile ducts, make up the portal triad, are shown at the corners of the hexagon that outlines the cross-sectioned profile of the classic lobule.
 FOLDER 18.2 Clinical Correlation: Congestive Heart Failure and Liver Necrosis
Liver injury may be triggered by hemodynamic changes in the circulatory system. In congestive heart failure, the heart is unable to provide sufficient oxygenated blood to meet the metabolic requirements of many tissues and organs, including the liver, which is readily affected by hypoperfusion and hypoxia (low blood oxygen content). Zone 3 of the liver acinus is the first to be affected by this condition. The hepatocytes in this zone are the last to receive blood as it passes along the sinusoids; as a result, these cells receive a blood supply already depleted in oxygen. Examination of a liver biopsy specimen from an individual with congestive heart failure shows a distinct pattern of liver necrosis. Hepatocytes in zone 3, which is located around the central vein, undergo ischemic necrosis. Typically, no noticeable changes are seen in zones 1 and 2, representing the periphery of a classic lobule. Necrosis of this type is referred to as centrilobular necrosis. Figure F18.2.1 shows the centrilobular portion of a classic lobule. The multiple round vacuoles indicate lipid accumulation, and the atrophic changes are the result of dying hepatocytes undergoing autophagocytosis. Centrilobular necrosis as a result of hypoxia is referred to as cardiac cirrhosis; however, unlike true cirrhosis, nodular regeneration of hepatocytes is minimal.