The Response of Jaundiced and Non-Jaundiced Weanling Rats to Thirsting

Abstract

ExtractLitter-mate homozygous and heterozygous weanling rats of the Gunn strain were thirsted and fasted for 24 hours. The response of the animals to thirsting was compared by analysis of solute content of serum and composition of fluid in the renal medullae. The results are given in tables I and II. When the mean values for weight loss and serum solute concentrations were compared, it was found that the jaundiced rats were able to conserve body water as well as the non-jaundiced rats and to generate equally high concentrations of total solute in the tissue water of the renal medulla. Only two of the twelve jaundiced animals showed evidence of failure to develop the expected hypertonicity of the medullary tissue water. This failure was qualitatively similar to that found in adult jaundiced rats. Despite the presence of higher concentrations of bilirubin in serum, the medullary bilirubin content of the jaundiced weanling rat was only 5 % of the concentration found in adult animals. The sodium and urea concentrations in the renal medullary fluid were correlated (p <0.001) in the homozygous jaundiced rats (table IV and fig. 1). A similar correlation was not found in the non-jaundiced heterozygous animals. This finding suggests that the normal rat kidney has at least two mechanisms for renal transport of urea, one of which is sodium dependent and the other sodium independent and that the latter mechanism is inoperative in the jaundiced weanling rat. SpeculationIn vitro studies of bilirubin have previously suggested that toxicity is exerted by its surface activity on mitochondrial membranes. The examination of renal function in the intact jaundiced animal has revealed the possibility that tubular transport systems for urea and sodium are impaired in the presence of high concentrations of bilirubin in the renal medulla. These transport systems involve the maintenance of concentration gradients of sodium and urea across tubular epithelium. Bilirubin, through its surface activity, could impair the selective permeability of the membranes involved in urea and sodium transport within the renal medulla.

The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

“…After 24 h of fluid deprivation, the jj animals only attained a Um.. of approximately 1,500 mosmol/kg H20, while their normal Jj littermates without the defect achieved a U... of approximately 2,500 mosmol/kg H20 (see Table I). These results conflict with previously published observations of Odell (7), who reported finding no significant difference in the urea and nonurea solute concentrations of the inner medulla in weanling jj and Jj rats and concluded that jaundiced weanling jj rats up to 21 days of age have normal medullary function. However, Odell (7) did not determine urine osmolality in the two groups of animals, which would have been a more sensitive method of estimating urine concentrating ability, and this may explain, at least in part, his failure to detect a defect in U.as in the jaundiced weanling jj rats.…”

“…These results conflict with previously published observations of Odell (7), who reported finding no significant difference in the urea and nonurea solute concentrations of the inner medulla in weanling jj and Jj rats and concluded that jaundiced weanling jj rats up to 21 days of age have normal medullary function. However, Odell (7) did not determine urine osmolality in the two groups of animals, which would have been a more sensitive method of estimating urine concentrating ability, and this may explain, at least in part, his failure to detect a defect in U.as in the jaundiced weanling jj rats. Possibly of equal importance in explaining the discrepancy in results between the two studies is the fact that the solute analyses were performed on the entire inner medulla, not just the papillary tip (7).…”

“…Second, the defect in urine concentration is only partially reversible and sometimes irreversible in adult jj Gunn rats, probably because of secondary parenchymal destruction of the renal medulla. Third, the urine concentrating defect is already present in weanling jj Gunn rats by 21 days of age, contrary to a previously published report (7). Fourth, a combination of phototherapy using blue fluorescent lights and oral cholestyramine feeding is the most effective means presently known to lower serum and tissue concentrations of unconjugated bilirubin in the jaundiced jj Gunn rat.…”

“…However, Odell (7) did not determine urine osmolality in the two groups of animals, which would have been a more sensitive method of estimating urine concentrating ability, and this may explain, at least in part, his failure to detect a defect in U.as in the jaundiced weanling jj rats. Possibly of equal importance in explaining the discrepancy in results between the two studies is the fact that the solute analyses were performed on the entire inner medulla, not just the papillary tip (7). As a result the average values for urea and nonurea solute concentrations that obtained undoubtedly underestimated the maximum solute concentration that existed at the papillary tip.…”

“…A causal relationship between the hyperbilirubinemia and the renal defect has been postulated and several observations indirectly support such a relationship. In those animals with impaired urine concentrating ability, tissue concentrations of bilirubin are markedly elevated throughout the kidney, especially in the papilla (4)(5)(6)(7). In the adult jj animals, massive crystalline deposits of bilirubin are found in the renal papilla and are often associated with papillary necrosis (8).…”