Perivenous hepatocytes

Primary pulmonary diseases (e.g. primary pulmonary hypertension, pulmonary fibrosis, chronic obstructive respiratory diseases) cause chronic hepatic congestion due to chronic pulmonary heart disease, possibly leading to insufficiency. Hypoxaemia as a result of acute or chronic respiratory insufficiency can impair metabolic liver functions considerably. In 40—70% of patients with cirrhosis, hypoxaemia can be found in about 50% of cases with advanced cirrhosis, a reduced diffusion capacity for CO is detectable. Furthermore, pulmonary tissue contains a high level of glutamine synthetase, so that ammonia detoxification is possible (ultimately by perivenous hepatocytes) before the blood reaches the systemic circulation. In existing pulmonary diseases, localized ammonia detoxification is impaired. 

The biomolecular modes of action of ornithine have been the subject of several experimental investigations. Ornithine activates the enzymes carbamylphosphate synthetase and ornithine carbamyl transferase, which are necessary for the liver-specific process of urea synthesis (133,139) this occurs mainly in the periportal hepa-tocytes (= definitive ammonia detoxification). Glutamine synthesis (binding of ammonia to glutamate) takes place predominantly in the perivenous hepatocytes (= transitory ammonia detoxification). Large amounts of glutamate are necessary for this. Aspartate, ornithine... 

PER see Prohdn efficiency ratio Perilipirv 383,401 Periportal hepatocytes, 253 Perivenous hepatocytes, 253 Permeability, defined, 119 Pernicious anemia as cancer risk factor. 519 folic acid and, 516 parietal cells and, 83 vitamin Biz deficieiKy and, 434,518-519, 523... 

The hepatocytes that are the last to be exposed to the blood traveling through the liver are called perivenous. Finally, the perivenous blood leaves the liver via a vessel called the vena cava. Researchers who ask questions about metabolic zona-tion study the properties of the periportal and perivenous hepatocytes by the techniques of biochemistry, molecular biology, and histology. 

Fig. 9.3 Effect of liver failure on inter-organ trafficking of ammonia. Under normal physiological conditions, ammonia produced by the gut is removed by the liver as urea (periportal hepatocytes) or glutamine (perivenous hepatocytes). Increased ammonia synthesis by the kidney is offset by increased urinary ammonia excretion. In liver failure, skeletal muscle becomes the major route for ammonia detoxification as a result of a post-translational increase of glutamine synthetase. Unlike muscle, the brain does not adapt to liver failure by induction or glutamine synthetase...

The regional expression of xenobiotic metabolizing enzymes determines the zone-specific localization of toxicant damage. Many hepatotoxicants elicit perivenous damage because CYPs are preferentially localized in centrilobular hepatocytes. For example, acetaminophen causes hepatotoxicity because the reactive... 

Hepatocytes display metabolic heterogeneity according to their zonal location within the acinus. (42) (s. p. 24) Specific chemical processes thus proceed exclusively or predominantly in the hepatocytes of the periportal or the perivenous zones. The zonally segregated reactions may also be regulated separately. It seems that, under certain conditions, metabolic processes are also shifted from one zone of the acinus to another. 

RG Tirona, E Tan, G Meier, KS Pang. Uptake and glutathione conjugation of ethacrynic acid and efflux of the glutathione adduct by periportal and perivenous rat hepatocytes. J Pharmacol Exp Ther 291 1210—1219, 1999. 

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