Sodium retention and ascites formation in dogs with experimental portal cirrhosis

Abstract

Experimental cirrhosis was produced in dogs by the sporadic feeding of dimethylnitrosamine for the purpose of studying the temporal relationships between urinary sodium retention, plasma volume expansion, and ascites formation. Sodium retention started about 16 days following the onset of cirrhosis and preceded ascites formation by about 10 days. Plasma volume increased by 9% (P less than 0.05) within 3-4 days of sodium retention and expanded further as ascites accumulated. Splanchnic plasma volume was greater by 161 ml in 10 cirrhotic dogs with ascites than in 14 normal dogs. Nonsplanchnic volume was greater by 96 ml (P less than 0.05). Thus, the "effective" as well as the splanchnic component of the vascular space was expanded. Paracentesis did not cause the re-formation of ascites in five dogs as long as dietary salt was denied. Refeeding permitted reaccumulation of ascites and further plasma volume expansion. Renal perfusion remained constant as dogs became progressively cirrhotic. We conclude that ascites formation depends on the prior retention of urinary sodium, and occurs as an "overflow" phenomenon. A contracted effective plasma volume does not appear to be necessary for continuing sodium retention.

Changes in plasma renin activity in cirrhosis: a reappraisal based on studies in 67 patients and "low-renin" cirrhosis.

“…In support of this interpretation the non-splanchnic component of the total blood volume has been found to be increased in dogs with dimethylnitrosamineinduced cirrhosis, whether or not ascites is present. 17 A number of other factors are also known to result in a reduced PRA including hyperkalemia, hypernatremia, an increased renal perfusion pressure and a decreased renal sympathetic nervous activity. 18 The first two of these factors could be excluded in the present cases and no patient had hypertension to account for an increased renal perfusion pressure.…”

Dogs with experimental cirrhosis of the liver but without intrahepatic hypertension do not retain sodium or form ascites.

“…Analytical techniques for the measurement of inulin, electrolytes, and liver function tests were all previously discussed in detail for this laboratory (4).…”

“…Studies conducted in both the rat (1-3) and dog (4) with experimental portal cirrhosis of the liver, have documented that renal tubular retention of sodium occurs very early in the course of the disease and precedes the formation of ascites. In experiments designed to exclude portal venous hypertension or ascites sequestration from being determinants of urinary sodium retention, extensive studies in our laboratory (4)(5)(6)(7)(8) demonstrated that this first phase, or early sodium retention in canine cirrhosis, is unrelated to arterial hypovolemia, altered systemic hemodynamics, or hyperaldosteronism.…”

“…In experiments designed to exclude portal venous hypertension or ascites sequestration from being determinants of urinary sodium retention, extensive studies in our laboratory (4)(5)(6)(7)(8) demonstrated that this first phase, or early sodium retention in canine cirrhosis, is unrelated to arterial hypovolemia, altered systemic hemodynamics, or hyperaldosteronism. As the liver disease progresses, new factors lead to persistent sodium retention.…”

Medical treatment of ascites in cirrhosis

“…Traditionally, the initiating event of renal sodium and water retention in cirrhosis was considered to be ascites formation (underfilling hypothesis) or primary renal dysfunction due to a hepatorenal reflex (overflow hypothesis) (2). The alterations of systemic, splanchnic and renal haemodynamics, as well as increases in circulating levels of substances that cause sodium retention (3)(4)(5)(6), are compatible with a decrease in effective blood volume as suggested by the underfilling hypothesis.…”