Some Experimental Observations Relating to the Pathogenesis of Renal Papillary Necrosis

SUMMARY Renal papillary necrosis was induced in female Wistar rats by a single dose of vinylamine. Damage to the renal papilla invariably ensued and was evident on light microscopy eight hours later. The changes comprised intracellular and extracellular œdema, endothelial damage, and necrosis of interstitial and epithelial cells ; these changes commenced at the tip of the papilla and spread towards but not beyond its base. The state of the medullary circulation was assessed by using colloidal carbon, which was injected intravenously and allowed to clear from the systemic circulation before tissues were taken for examination. As the lesion progressed, carbon accumulated in vessels, first at the tip and later at the base of the pyramid, and protein in the loops of Henle at the same levels. Extensive carbon labelling of damaged vessels in the early lesion indicated that the circulation continued for a time through this zone. After the histological appearances of necrosis were fully developed, there was no carbon labelling and no circulation could be demonstrated in the damaged tissue. There was no evidence of significant vascular lesions outside the papilla. Intravascular fibrin could not be demonstrated histochemically. It seems probable that vinylamine damages the cells of the medulla, and that there is severe fluid and protein loss into the interstitial tissue. Such fluid loss, in its turn, is followed by impaction of red cells and further slowing of the already sluggish circulation in the venous limbs of the medullary capillary loops. In rats allowed to survive for weeks or months, the necrotic papilla sloughed and the adjacent tissue became covered with epithelium. In the cortex, areas of tubular atrophy, tubular dilatation, and scarring alternated with normal tissue. Such areas of cortical damage were often small and focal. These findings suggest that tubular obstruction is not inevitable after loss of the papilla and that other factors may influence the associated renal cortical scarring. The same general pathological processes determine the occurrence of renal papillary necrosis in various clinical and experimental situations. The observations recorded here suggest that two of these processes are direct local tissue injury and venous circulatory stasis.