Ischemic Acute Tubular Necrosis Light Microscopy

The pathologic changes in ischemic ATN are often subtle but are easily discernible with well-fixed tissue. Both proximal and distal tubules are affected. The proximal tubules are dilated and the lining cells flattened.

Brush border staining is reduced or absent (Fig. 15.1). This combination of changes causes proximal tubules to resemble distal tubules ("distaliza-tion") and is also known as simplification of tubules so that one nephron segment cannot easily be differentiated from another. Distal tubules, including the thick ascending limb of Henle, are dilated and lined by flattened cells. Tamm-Horsfall protein containing casts, sometimes incorporating granular material, are frequently present but are not specific for ATN. In addition, pigmented (tan-brown) granular casts are characteristic; many studies have concluded that heme pigment is responsible for this appearance. Oxalate crystals are commonly present and are located in the thick ascending limb, distal tubule, and collecting duct. It should be noted that the crystals are usually not numerous; marked accumulation of oxalate crystals is most commonly observed in ethylene glycol poisoning. Overt or extensive necrosis of tubular cells is neither common nor regularly observed. Instead, loss of individual cells, manifested by incomplete epithelial lining of tubules, is present. This change requires well-fixed tissue and a practiced eye to demonstrate. It is often referred to as the "nonreplacement" phenomenon. There are often desquamated cells or cellular debris in the lumina (Fig. 15.2).

Ischemic tubular necrosis is frequently associated with disruption of tubular walls (including cell loss and basement membrane disruption) with spillage of contents into the adjacent interstitium. It also may be associated with localized inflammation, sometimes in the form of granulomata. However, inflammation is not constantly present. The interstitium is diffusely edematous and infiltrated by a small number of lymphocytes and monocytes. The outer medullary vasa recta often contain large numbers of nucleated circulating cells including lymphocytes and monocytes, both

Figure 15.1. Tubular cells are flattened and many proximal cells lack brush border staining; lumina are relatively dilated [periodic acid-schiff (PAS) stain].
Figure 15.2. One tubule contains cells and debris in lumen and is incompletely lined by epithelium (PAS stain).

mature and immature forms, and granulocyte precursors. These cells are in greater concentrations in the vasa recta than in other renal vascular beds. The glomerular capillary tufts are usually unaltered. However, there are several reasonably common abnormalities: there may be some degree of capillary collapse and dilatation of Bowman's space. Additionally, tubular metaplasia ("tubularization") of parietal epithelial cells may be evident in recovery. Solez and colleagues (5) assessed these morphologic changes as to their frequency in active renal failure, recovery phase, and normal controls. In their landmark study, they noted that the following were more common in biopsies from patients with renal failure: vasa recta leukocyte accumulation, tubular cell necrosis, regeneration (mitotic figures), dilatation of Bowman's spaces, loss of brush border staining, tubular casts, and interstitial edema and inflammation. However, only cellular necrosis and loss of brush border staining distinguished biopsies from patients with acute renal failure from those of patients in recovery from renal failure.

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