PATHOGENESIS OF WATER AND SODIUM RETENTION IN CIRRHOSIS

The pathogenesis of renal sodium and water retention in cirrhosis invo lves extrarenal mechanisms because when kidneys from cirrhotic patient s are transplanted into persons with normal livers, renal sodium and w ater retention no longer occurs. Cirrhosis is accompanied by portal hy pertension, which leads to a hyperdynamic circulatory state. The Perip heral Arterial Vasodilation Hypothesis incriminates a relative underfi lling of the arterial vascular compartment, which leads to the same ne urohumoral responses that occurs in low cardiac output. Activation of the remain-angiotensin-aldosterone axis and the sympathetic system as well as non-osmotic release of vasopressin are well documented in cirr hosis. This sequence of events results in renal water and sodium reten tion, failure to escape from the sodium-retaining effect of aldosteron e, and renal resistance to atrial natriuretic peptide. Dilutional hypo natremia is the strongest predictor of the occurrence of hepatorenal s yndrome. The pathogenesis of the peripheral arterial vasodilation is n ot completely elucidated, but there is evidence for a major role of ni tric oxide (NO). Increased vascular NO production has been demonstrate d in cirrhosis. In the rat model of cirrhosis, normalization of vascul ar NO production with a NOS inhibitor corrects the hyperdynamic circul ation, improves sodium and water excretion, and decreases neurohumoral activation. This insight into the mechanism(s) of the peripheral arte rial vasodilation in cirrhosis should provide new tools in the treatme nt of edema and ascites, a major cause of morbidity and mortality in c irrhosis.