Читать книгу Autoimmune Liver Disease - Группа авторов - Страница 23

The multiple functions of the liver are facilitated by a functional specialization of the liver parenchyma, known as metabolic zonation, where hepatocytes show different functional and structural characteristics according to their location in the liver acinus. Within each acinus, the functional unit in terms of blood flow, blood rich in nutrients and hormones enters at the portal triad through the portal vein, mixes with oxygen‐rich blood from the hepatic artery, flows through the sinusoids and eventually exits the lobule through the central vein. As the blood flows through the sinusoids there is free exchange of nutrients and metabolites between blood and hepatocytes. Functional variation is observed in hepatocytes based on their location along the portal–central axis. Hepatocytes exhibit a distinct gene expression based on their location within the acinus, which manifests as diverse availability of substrates and concentration of enzymes in different parts of the acinus. Based on this organization and heterogeneity of hepatocytes, the acinus comprises three geographical areas or zones: periportal or zone 1, midzonal or zone 2, and perivenous or zone 3. Hepatocytes in zone 3 contain the drug‐metabolizing P450 enzymes, have a reduced oxygen supply, receive a higher concentration of any toxic product of drug metabolism, and have a reduced glutathione concentration compared with zone 1. This makes them particularly susceptible to drug‐induced liver injury. Also, hepatocytes in zone 1 receive blood with a high bile salt concentration and are therefore particularly important in bile salt‐dependent bile formation, whereas hepatocytes in zone 3 are important in non‐bile salt‐dependent bile formation. Functions such as gluconeogenesis, glycolysis, and ketogenesis appear to be dependent on the direction of blood flow along the sinusoid. For others, such as cytochrome P450 activity, the gene transcription rate differs between perivenular and periportal hepatocytes. This functional zonation is often lost in liver diseases.