Functional Hepatocellular Heterogeneity

Abstract

Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures. Therefore, different functions are proposed for the two zones. (a) Oxidative energy metabolism, /3-oxidation, amino acid catabolism, ureagenesis from amino acids, gluconeogenesis, bile acid, and bilirubin excretion and oxidation protection are preferentially located in the periportal zone. (b) Glycolysis, liponeogenesis, ureagenesis from ammonia, and biotransformation are predominantly situated in the perivenous zone. Heterogeneity in the synthesis of plasma proteins also appears to exist.The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen and hormone concentrations, and by a different autonomic innervation of the parenchymal zones.The liver consists of parenchymal and nonparenchymal cells (e.g., Kupffer, endothelial, bile ductule, and connective tissue cells). The parenchymal hepatocytes appear to be rather uniform histologically; histochemically they reveal differences. This heterogeneity has been known for many years, first on a descriptive (1, 2), then increasingly on a functional level (3). The metabolic heterogeneity of liver parenchymal cells has been reviewed recently (4, 5). It is the goal of the following account to summarize the present knowledge of parenchymal heterogeneity and, thereby, to contribute to the understanding of basic liver functions in health and disease. LIVER STRUCTUREThe structural unit which connects parenchymal and nonparenchymal liver cells to a functional unit is still controversial. The classical lobule, in its most recent "sickle zone" modification (6), is characterized by a surface-like inflow of blood directly from the portal tract forming sickle zones of hemodynamic equipotential. The acinus (7), in contrast, is defined by a linear inflow of blood forming berry-type structures of hemodynamic equipotential around the vascular axis of an afferent vessel. Following the bloodstream, at least two different zones can be discerned both in the acinus and sickle zone lobules: the periportal (afferent) zone, which is supplied I Heterogeneity of liver parenchyma appears to be similar in all mammals. Therefore, this article was concentrated to a review of studies mainly with rats.This work was supported by grants from the Deutsche Forschungsgemeinschaft, D-5300 Bonn, Germany.Address reprint requests to: Professor Dr. Kurt Jungermann, Institut fiir Biochemie, Fachbereich Medizin, Georg-August-Universitat, Humboldtallee 7, D-3400 Gottingen, Germany.with oxygen-, substrate-, and hormone-rich blood, and the perivenous (efferent) zone, which receives blood poor in oxygen, substrates, and hormones but enriched in COZ and other products. Since the quality of the blood changes during liver passage it may be assumed that cells in the different zones of the liver parenchyma, whichever functional organization it might have, should possess different structures, enzyma...

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