Quantitative studies of liver atrophy after portacaval shunt in the rat

Background. It is well known that portacaval shunting ultimately leads to a decrease in liver volume and hepatic function, but the mechanism is uncertain. The aim of the present study was to evaluate the effect of portacaval shunting (PCS) upon the morphological changes that occur in the liver in rats after port caval. anastomosis. Materials and methods. Sixty-six male rats underwent either PCS (n = 35) or sham operations (n = 31). Hormone levels were determined in blood samples taken just before removal and weighing of the livers. Hematoxylin and eosin-stained sections were used for quantitative morphometric analysis. Apoptosis, mitosis, and cellular organelles also were assessed quantitatively. Results. There was a significant reduction in the liver mass together with testosterone levels in PCS rats in comparison with sham rats. The distance between presinusoidal and postsinusoidal vessels was reduced from 500 mu m in the sham rats to 299 mu m in the PCS rats (P = 0.000001). Within the same group, there was a significant reduction in the area of hepatocyte nuclei in zone 3 in comparison with zone 1. Electron microscopy revealed a highly significant (P = 0.0007) reduction in the membrane-bound cytoplasmic organelles of zone 3 hepatocytes in PCS rats in comparison with the sham rats. Apoptosis was increased in zone 3 in PCS rats (P = 0.00001), whereas in zone 1 of the same group, there was an associated increased in mitosis (P = 0.000001). Overall, the degree of apoptosis was in excess of mitosis, resulting in a general loss of liver mass. Conclusion. Morphometric analysis at cellular and subcellular levels confirms the morphological findings of liver atrophy in PCS rats. The mechanism of atrophy is a complex one. Portacaval shunting leads to hepatic atrophy that, in turn, results in microcirculatory and hormonal changes that further contribute to liver cell loss in this animal model. (C) 2006 Elsevier Inc. All rights reserved.