Pathogenesis of sodium and water retention in liver disease

The "Peripheral Arterial Vasodilation" hypothesis most completely explains the clinical spectrum of cirrhosis ranging from compensated to decompensated to the hepatorenal syndrome (Figure 15-1). As the systemic peripheral vasodilation increases, the neurohumoral responses to arterial underfilling are stimulated with resultant renal vasoconstriction, sodium and water retention. Hypoalbuminemia and portal hypertension, as well as local effects of vasodilation at the capillary level, also contribute to ascites formation and peripheral edema. The suppressed plasma renin activity and aldosterone concentrations and exaggerated natriuresis, which are observed in some patients with early cirrhosis during HWI and the supine position, probably indicate greater central translocation of splanchnic fluid in these volume expanded cirrhotic patients when compared with normal subjects. This interpretation is supported by the greater increases in ANF during HWI in these patients when compared with controls. The neurohumoral responses to arterial vasodilation in cirrhosis combine to decrease distal sodium and water delivery, an event which impairs escape from the sodium retaining effects of aldosterone and causes resistance to the distal tubular effect of ANF (Figure 15-3). As discussed, the peripheral arterial vasodilation of cirrhosis is no doubt multifactorial in nature and the resultant arterial underfilling may be worsened by events that could impair the cardiac response to afterload reduction, including bile salt accumulation, alcoholic cardiomyopathy, and tense ascites decreasing cardiac preload. This pathogenetic schema of cirrhosis is compatible with the unifying body fluid volume hypothesis (Figure 15-3), which we have recently proposed.