Review: the controversy over the pathophysiology of ascites formation in cirrhosis.

Abstract

The pathogenesis of renal sodium retention and ascites formation in cirrhosis is a subject of much controversy. The generally accepted 'peripheral arterial vasodilatation hypothesis' seems to best explain the mechanism of sodium retention and other clinical findings, such as the hyperdynamic circulation of cirrhosis. However, recent data in pre-ascites and in early ascites do not seem to conform to the peripheral arterial vasodilatation hypothesis. Sodium handling abnormalities can be demonstrated in pre-ascitic cirrhosis when patients are challenged with a sodium load, in the absence of systemic vasodilatation or arterial underfilling. Therefore, an alternative hypothesis with a direct hepatorenal interaction, acting via sinusoidal portal hypertension and/or hepatic dysfunction as the affector mechanism, is proposed to be the initiating event in renal sodium retention in cirrhosis. The second and later process is the development of systemic arterial vasodilatation, possibly due to the presence of excess systemic vasodilators and/or decreased responsiveness of the vasculature to endogenous vasoconstrictors. This, in turn, will lead to a relatively underfilled circulation with consequent activation of neurohumoral systems, promoting further renal sodium retention as described by the peripheral arterial vasodilatation hypothesis and ultimately leading to ascites. When compensatory natriuretic mechanisms fail, refractory ascites develops and hepatorenal syndrome sets in. Thus, renal sodium retention in cirrhosis is the result of interplay of many factors, with direct hepatorenal interaction predominating in earlier stages of the cirrhotic process, while systemic vasodilatation becomes a more important pathogenetic factor as the disease progresses.