High Resolution Light Microscopic Morphological and Microvascular Changes in an Acutely Induced Renal Papillary Necrosis

Abstract

Morphological changes were followed in semi-thin glycolmethacrylate sections, after treating male Wistar rats with a single ip dose of 2-bromoethanamine (BEA) hydrobromide (100 mg/kg) to induce renal papillary necrosis. Medullary interstitial cells had irregular nuclei at 4 hr and focal necrosis by 8 hr which spread from the papilla tip to the cortico-medullary junction from 12 hr. Increased mucopolysaccharide staining was observed in the papilla tip at 4 hr, and was lost from those regions where necrosis had developed by 48 hr. Endothelial platelet adhesion, first seen at 8 hr, was very marked at 18 hr, but affected capillaries in necrotic regions only, up to 144 hr. The absence of extravasated Monastral Blue B demonstrated the integrity of the medullary microvascular endothelia. The distal nephron showed degenerative changes at 12 hr and cell exfoliation at 18 hr. Cortical changes were confined to PAS-positive casts in the collecting duct and loop of Henle from 8 hr and dilatation of distal and proximal tubules at 8 and 72 hr, respectively. There was active repair at the junction between viable and necrotic tissue in the papilla from 24 hr with mitoses in the collecting ducts and loops of Henle. Normally the urothelium is less than 3-4 cells thick, but upper urothelial proliferation followed BEA administration. Hyperplasia was especially marked at the mouth of the ureter and in the pelvis opposite the region of necrosis (7-8 cells thick at 18 hr) and had only partially resolved by 144 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced Hexachloro-1:3-butadiene Nephrotoxicity in Rats with a Preexisting Adriamycin-Induced Nephrotic Syndrome

“…Advanced regeneration and repair was evident 21 days after HCBD treatment. In the ADR-pretreated rats the HCBD-induced lesion was more severe and affected the entire cortex (24).…”

“…Advanced regeneration and repair was evident 21 days after HCBD treatment. In the ADR-pretreated rats the HCBD-induced lesion was more severe and affected the entire cortex (24).Statistics. Statistically significant differences between groups were determined by 2-tailed Students' t-test, with p < 0.05 considered to be statistically significant.…”

Renal Papillary Necrosis

“…The typical sequence of events after exposure to low doses of analgesics was degeneration of interstitial cells, evidenced by cytoplasmic edema, dilation of organelles, and increased proteoglycan production, followed by damage to the endothelial cells and loops of Henle. Platelet thrombi occur, and tubular lumens ll with cellular debris (14). Experimentally, the rst of these changes is visible by electron microscopy 1 to 4 hours after dosing with bromoethylamine (BEA), and with light microscopy after 4 hours (14).…”

“…Platelet thrombi occur, and tubular lumens ll with cellular debris (14). Experimentally, the rst of these changes is visible by electron microscopy 1 to 4 hours after dosing with bromoethylamine (BEA), and with light microscopy after 4 hours (14).…”

“…One possible mechanism is a direct toxic effect on cells in the medulla. The initial target in analgesic nephropathy may be the medullary interstitial cell, as previously mentioned (1,14,19). Toxic effects to the interstitial cells could come about from reactive intermediates, acetylation of critical cellular proteins, or inhibition of cellular functions (8,20).…”