C H A P TE R 61

Liver

STRUCTURE AND FUNCTION

Robert J. Washabau

Cells of the Liver Hepatocytes

Hepatocytes account for 60% to 80% of the liver cell mass (see Table 61-1) and contribute to a wide range of metabolic activity, including carbohydrate, protein, lipid, nucleic acid, porphyrin, metal, vitamin, glutathione, hormone, and xenobiotic metabolism; coagulation factor synthesis; biliary secretion; and immune surveillance.1,5 Hepatocytes have an eosinophilic cytoplasm reflecting numerous mitochondria, and basophilic stippling caused by large amounts of rough endoplasmic reticulum and free ribosomes. Hepatocyte nuclei are round with dispersed chromatin and prominent nucleoli. Anisokaryosis is common and often reflects various degrees of polyploidy, a normal feature of more than 50% of hepatocytes. The average life span of the hepatocyte is 5 to 6 months reflecting their ability to regenerate. Hepatocytes are organized into plates separated by vascular channels (sinusoids), an arrangement supported by a reticulin (collagen type III) network. The sinusoids have a discontinuous, fenestrated endothelial cell lining. The endothelial cells have no basement membrane and are separated from the hepatocytes by the space of Disse, which drains lymph into the portal lymphatics. Hepatocytes are supported by a number of other cell types, which account for 40% of the liver cell mass.

Liver Structure
The hepatic lobule is the anatomic unit of the liver. In the anatomic model, liver lobules are organized into irregular polygons demarcated by connective tissue and composed of plates of hepatocytes radiating outward from the central vein to the portal triads (Figure 61-1). The hepatic acinus is the functional unit of the liver. In the functional model hepatocytes are instead oriented around the afferent vascular system (portal veins and hepatic arteries) just as they anastomose into sinusoids (Figure 61-1), and the central vein is at the periphery of the acinus instead of centrally located as in the anatomic model. The acinus is divided into three contiguous zones (1, 2, and 3) that correspond to distance from the arterial blood supply. Those hepatocytes in closest proximity to the arterioles (zone 1) receive the greatest oxygen content, but are also first in line to be affected by toxins transported from the gut to the portal vein. Zone 3 hepatocytes reside at the periphery of the acinus near the central vein, and zone 2 hepatocytes are interspersed between zone 1 and zone 3 hepatocytes. The anatomic model is perhaps easier to understand, but the functional model serves as a better foundation for understanding liver pathology.1 In either model portal venous and arterial blood flow centripetally, that is, toward the central vein, whereas bile flows centrifugally, that is, away from the central vein. Hepatocytes extract nutrients and oxygen from portal and arterial perfusion, respectively, and produce bile acids and other bile constituents that are transported from hepatocytes into bile canaliculi, ductules, and ducts.

Cholangiocytes
Representing 3% to 10% of liver cell mass, cholangiocytes are also known as biliary epithelial cells.6 They secrete water, bicarbonate, and cations into the bile in the physiologic state, but they may also participate in the immune response as antigen-presenting cells in disease states. The biliary tract is a convergent system of canals that begins in the canaliculi, followed by the bile ducts, and ending with the common bile duct. Bile secretion depends on the function of membrane transport systems in hepatocytes and cholangiocytes and on the structural and functional integrity of the biliary tract. The hepatocytes, constituting the most abundant liver cell population, generate the so-called primary bile in their canaliculi. Biliary canaliculi are blind tubular structures, with a very high surface-to-volume ratio that by means of osmotic gradients favors the formation of bile flow. Cholangiocytes, which constitute 3% to 10% of the liver cells, modify the canalicular bile by secretory and reabsorptive processes as bile passes through the bile ducts, and they are responsible for approximately 30% of bile volume. In contrast to hepatocytes, where secretion is constant and poorly controlled, cholangiocyte secretion is broadly regulated.5,6

Biliary Tract Structure

The basic elements of the biliary tract are the hepatic canaliculi, bile ductules, intralobular ducts, interlobular ducts, hepatic ducts, cystic duct, gallbladder, common bile duct, and the pancreaticobiliary sphincter (of Oddi).2 There are many variations on this central theme, the most important of which are (a) the pancreaticobiliary sphincter is a common physiologic and anatomical channel at the duodenal papilla in the cat3 and (b) there are many anatomic variations in the feline gallbladder, from single gallbladder to bilateral gallbladders, body duplication, fundic duplication, complete duplication, septate, and Y-shaped gallbladder.4

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