A Comparison of Acute Reversible Pre- and Postsinusoidal Portal Hypertension on Salt and Water Retention in the Dog

Abstract

To define the relationship between portal hypertension and renal excretion of salt and water, two acute animal models of portal hypertension were investigated. In both models, it was necessary for systemic and renal hemodynamics to remain unchanged during the creation of portal hypertension so as to eliminate the effects of change in these parameters on renal excretion.In eight dogs, portal hypertension was induced by controlled tightening of a ligature around the superior hepatic vein and changes in hemodynamics were prevented by controlled i.v. titration with canine plasma. Rises in portal pressure 9.3 k 2.6 to 15.6 f 2.3 cm HZO were associated with significant decreases in urine volume 1.57 k 0.53 to 0.66 k 0.21 ml per min (p < 0.05) and urinary sodium excretion 1340 & 82 to 145 k 76 mEq per min (p < 0.05)]. In contrast, similar experiments in five dogs in which the portal vein was partially ligated with increases in portal pressure from 8.3 f 0.6 to 18.6 & 0.5 cm HzO resulted in no change in urinary volume or sodium excretion.Acute reversible portal hypertension induced by hepatic vein constriction is associated with acute reversible retention of water and salt in the absence of changes in renal blood flow and creatinine clearance which only occur when the liver is involved and not with portal vein constriction.Many patients with advanced cirrhosis develop renal sodium retention and ascites. In the past, this sodium retention has been thought to be the result of fluid loss into the ascitic "third space" secondary to increased hydrostatic pressure in the hepatic sinusoids and splanchnic capillaries with a decrease in effective circulatory volume and appropriate alteration in renin and aldosterone secretion. Although plasma volume measurements in cirrhotics are actually normal or slightly elevated, it has been postulated that the ('central'' or nonsplanchnic component is decreased and the splanchnic component increased. Lieberman, in 1969, presented data from studies in human cirrhosis which suggested that renal sodium retention actually preceded the development of ascites, and was in fact, a contributing factor in the development of ascites (1). He postulated the existence of some hepatic factors which altered renal sodium handling independent of volume changes and the reninaldosterone regulatory mechanisms.

Impairment of natriuresis and diuresis induced by intrarenal adrenoceptor mechanisms in an experimental model of cirrhosis in rats

“…Such alterations are probably due to tubular function deficits, while cirrhotic patients with ascites also present with glomerular filtration rate changes that interfere with sodium excretion [24]. As a whole, experimental evidence suggests that intrahepatic hypertension with impairment of venous hepatic flow is the primary causal agent responsible for the initiation of sodium retention in cirrhosis in humans and animals [25, 26, 27].…”

Afferent mechanisms of sodium retention in cirrhosis and hepatorenal syndrome

“…The available evidence indicates that: (1) the liver, and likely the hepatic circulation, has an afferent sensor that modulates the efferent pathway of volume regulation (that is, a 'volume' sensor); (2) cirrhosis or restriction of hepatic vein flow raises intra-hepatic vascular resistance, increases sinusoidal pressure, decreases portal vein blood flow, and increases hepatic artery flow (Figure 4a). [104][105][106][107][132][133][134][135][136] Either because of changes in the intra-hepatic physical forces or changes in the composition of the 'mixed' intra-hepatic blood (for example, oxygen tension, hormones, concentration of substances absorbed in the gut, and so on), abnormal sodium retention is initiated and edema develops (Figure 4a); (3) cirrhosis alone is not sufficient to induce edema. Institution of a side-to-side porto-caval shunt prevents (if performed before induction of cirrhosis) or corrects (if performed after cirrhosis) renal sodium retention.…”

“…Institution of a side-to-side porto-caval shunt prevents (if performed before induction of cirrhosis) or corrects (if performed after cirrhosis) renal sodium retention. 81,105,107,109,110 This could be due to decreases in sinusoidal pressure 164 or maintenance of mixing of portal venous and hepatic arterial bloods irrigating the liver (Figure 4b); (4) in contrast, institution of end-to-side porto-caval shunt only partially decreases the elevated sinusoidal pressure 84,[164][165][166] and prevents mixing of the venous and arterial hepatic blood supplies as the portal vein blood is diverted to the inferior vena cava. Under these conditions and despite normalization of portal vein pressure, sodium retention continues unabated (Figure 4c).…”

“…It has long been known that patients with Budd-Chiari syndrome (that is, hepatic vein thrombosis) develop increased intra-hepatic vascular pressure and edema and that normalization of the pressure by a side-to-side porto-caval shunt corrects the ECFV expansion. 104 Similarly, in experimental animals, increasing the intra-hepatic vascular pressure by occlusion or stenosis of the hepatic veins 15,[105][106][107] induces renal salt and water retention. Moreover, subsequent decompression of the intra-hepatic hypertension by a sideto-side porto-caval shunt, resolves this salt and water retention.…”

“…15,105 In marked contrast, end-to-side porto-caval shunts are ineffective in reversing renal salt retention despite reversal of the portal hypertension. 15,105 Indeed, hepaticinitiated salt and water retention requires abnormal intrahepatic circulation rather than portal hypertension; while tightening of the hepatic veins decreases renal salt and water excretion, 15,[105][106][107] portal hypertension because of partial ligation of the portal vein has no effect. [106][107][108] Cirrhosis alone is not sufficient to induce renal salt retention…”