Hepatic Parenchymal and Nonparenchymal Cells in Hemorrhage and Ischemia

Abstract

Although it is widely accepted that ischemia can make a major contribution to organ dysfunction in trauma, shock, and sepsis, the exact mechanisms remain unclear. Since ischemia is, by definition, an imbalance between blood (or oxygen) supply and demand one might predict that susceptibility to ischemia damage might be well modeled by anoxia to parenchymal cells. However, in intact organs, the presence of multiple cell types complicates the response to an ischemic insult. This response is even more complicated when ischemia is followed by reperfusion which exacerbates the injury in intact organs. For instance, vascular endothelial cells have been shown to contain large quantities of xanthine dehydrogenase that can be converted to xanthine oxidase and anoxic stress resulting in the production of oxygen-derived free radicals during reoxygenation [1]. Indeed, in organs such as the heart, such “oxyradicals” of endothelial origin are likely to be major contributors to reperfusion injury [2]. In the liver the situation is further complicated by the presence of a substantial number of macrophages, the hepatic Kupffer cells, and during in vivo reperfusion infiltration by neutrophils which can then constitute a significant population of nonparenchymal cells. Thus, the purpose of this paper is to review the relative susceptibility to ischemic or anoxic injury of hepatocytes and the intact liver.

This work was supported by USPHS grant DK38201 and the Robert Garrett Fund.