central vein artery. This zone corresponds to the periphery of the classic lobules.

• Zone 3 is farthest from the short axis and closest to the terminal hepatic vein (central vein). This zone corresponds to the most central part of the classic lobule that surrounds the terminal hepatic vein.

• Zone 2 lies between zones 1 and 3 but has no sharp boundaries.

The zonation is important in the description and interpretation of patterns of degeneration, regeneration, and specific toxic effects in the liver parenchyma relative to the degree or quality of vascular perfusion of the hepatic cells. As a result of the sinusoidal blood flow, the oxygen gradient, the metabolic activity of the hepatocytes, and the distribution of hepatic enzymes varies across the three zones. The distribution of liver damage due to ischemia and exposure to toxic substances can be explained using this zonal interpretation.

Cells in zone 1 are the first to receive oxygen, nutrients, and toxins from the sinusoidal blood and are the first to show morphologic changes following bile duct occlusion (bile stasis). These cells are also the last to die if circulation is impaired and the first to regenerate. On the other hand, cells in zone 3 are the first to show ischemic necrosis (cen-trilobular necrosis) in situations of reduced perfusion and the first to show fat accumulation. They are the last to respond to toxic substances and bile stasis. Normal variations in enzyme activity, the number and size of cytoplasmic organelles, and the size of cytoplasmic glycogen deposits are also seen between zones 1 and 3. Cells in zone 2 have functional and morphologic characteristics and responses intermediate to those of zones 1 and 3.

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