Heterogeniteit Van De Leverparenchymcellen

Abstract

SummaryLiver parenchymal cells reveal an important heterogeneity in their functions, which can mainly be linked to their different localization in the simple liver acinus of Rappaport. Hepatocytes of zone 1 are situated close to the vascular axis consisting of a terminal hepatic arteriole and terminal portal venule. As such, these hepatocytes receive blood rich in oxygen, nutrients and bile salts coming from the gastrointestinal tract, and hormonal factors. Metabolically, this region is characterized by the oxydative breakdown of carbohydrates, amino acids and fatty acids. Gluconeogenesis, which is an endergonic process that must be driven by the oxydative catabolism, is also a function of zone 1 hepatocytes. This region of the acinus should always release glucose and this function is induced by high ratio of (glucagon + catecholamines)/insulin in this zone. Acinar zone 1 hepatocytes are the first to receive blood and substrates and contribute predominantly to transport of bile salts and bilirubin and to the secretion of the bile salt-dependent fraction of canalicular bile production.This corresponds to a greater diameter of bile canaliculi and a predominant localization of« Golgirich area » in this region. In patients with longstanding biliary obstruction, « cholate stasis » can be observed histologically, which may represent an accumulation of bile salts in periportal hepatocytes.Perivenous hepatocytes of zone 3 are the most distant from the supplying blood vessels and receive blood that has already exchanged oxygen, nutrients and hormones with cells in zones 1 and 2. Metabolically, this region is characterized by processes that can occur in anaerobic conditions such as glycoly sis and liponeogenesis. This perivenous zone should always take up glucose and this function is induced by a high ratio insulin/(glucagon + catechola mines) in this region.Hepatocytes of zone 3 also contribute predomi nantly to cytochrome P-450 dependent drug metabolism, which corresponds to the predominant lo calization of the smooth endoplasmic reticulum in zone 3. The peculiar susceptibility of perivenous he patocytes during drug-induced liver disease can also be explained by the predominant formation of toxic metabolites in zone 3 by the cytochrome P-450 system.The cells of zone 3 do not contribute significantly to bile salt and bilirubin transport in physiologic conditions but may be « recruted » as the concen tration of incoming bile salts or bilirubin is increa sed. These cells may also contribute to the generation of canalicular bile, more specifically to the formation of the so-called bile salt-non dependent fraction.