Hypoxic damage to tubules due to blockage of perfusion in acute hematogenous E. coli pyelonephritis of rats.

To determine the role of hypoxia in the evolution of tubular damage in acute pyelonephritis (PN), the blockage of blood flow and injury to peritubular capillaries and tubules were studied morphologically in hematogenous acute E. coli PN of rats. Renal microvessels were stained by in situ intraarterial administration of Alcian blue. The non-occurrence of staining indicated blockage of perfusion. Injury to cortical capillaries and tubules was examined by electron microscope. In areas of inflammation, binding of Alcian blue did not occur in capillaries plugged by polymorphonuclear leukocytes (PMNL-s) and in the majority of glomerules. Ultrastructurally, severe injury to capillaries was found around endothelium-adhered, degranulated PMNL-s containing bacteria: the vessel wall was fragmented, the capillary basement membrane perivascular connective tissue matrix and collagen fibrils had disappeared, and fibrin had deposited intra- and extravascularly. Tubular changes varied from swelling to ischemic necrosis. The observations suggest that tubular damage was related to hypoxia due to preglomerular and capillary perfusion defects, and that PMNL-s injure capillaries via lysosomal enzymes discharged into the capillary fluid during the phagocytosis of bacteria. Since leukocyte plugs in capillaries, PMNL-dependent lytic injury to capillaries and mild ischemic tubular changes, but not ischemic necrosis, have been found in human acute PN previously, the preglomerular vasospasm may cause the tubular necrosis in experimental acute PN.