Mechanisms of Sodium Retention, Ascites Formation, and Renal Dysfunction in Cirrhosis

Abstract

The mechanisms responsible for ascites formation in liver disease have aroused interest throughout the history of medicine. The Egyptians and Greeks believed that there was a relationship between liver disease and ascites. In 300 bc, Erasitratus of Cappadoccia described ascites as a consequence of “hardness of the liver” or liver disease. Several centuries later, physicians discovered the relationship between advanced liver disease and the development of ascites. Numerous studies addressing this issue have discovered that alterations in systemic and splanchnic circulation, as well as functional renal abnormalities, are the culprit of this dreaded complication of cirrhosis. Renal abnormalities occur in the setting of a hyperdynamic state characterized by an increased cardiac output, a reduction in total vascular resistance and an activation of neurohormonal vasoactive systems. This circulatory dysfunction, a consequence of intense arterial vasodilation in the splanchnic circulation, is considered a primary feature in the pathogenesis of ascites. The main factor responsible for local vasodilation seems to be the overproduction of extra-hepatic nitric oxide (NO). Splanchnic vasodilation by decreasing effective arterial blood volume causes homeostatic activation of vasoconstrictor and antinatriuretic factors triggered to compensate for a relative arterial underfilling. The net effect is avid retention of sodium and water as well as renal vasoconstriction in advanced stages. The mechanisms of ascites formation and sodium and water retention in patients with cirrhosis are discussed in this chapter.