Renal Pathophysiology

CHAPTER 11 Acute Kidney Injury

319

Acute Tubular Necrosis There are two major types of ATN: postischemic and toxic (Table 11.1). Regardless of the mechanism, ATN is associated with two major histo logic changes and normal glomeruli : „ Tubular necrosis with denuding of the epithelial cells; the tubular injury tends to be most prominent in the proximal tubules and in the thick as cending limb of the loop of Henle. „ Occlusion of the tubular lumens by cellular debris and casts and, with he molysis or rhabdomyolysis, by precipitation of heme pigments It is now appreciated that complex mechanisms involving the vasculature and renal tubular epithelium converge in ischemic ATN to cause the dramatic reduction in GFR that is the hallmark of this injury (10% of normal GFR). Figures 11.4 and 11.5 summarize the major events contributing to the renal injury. Furthermore, the anatomy of the nephron renders certain tubular seg ments susceptible to ischemic injury. Although the kidneys receive 20% of car diac output, the renal medulla normally exists on the brink of hypoxia, due in part to high metabolic activity required for transport processes and low blood flow to this segment. The hairpin configuration of the vasa recta capillaries (essential for normal operation of the countercurrent mechanism) results in the exchange of oxygen between the oxygen-rich blood leaving the cortex and entering the descending capillary limb and the oxygen-poor blood draining the inner medulla in the ascending capillary limb (Fig. 11.4). The net effect is that the PO 2 bathing the cells of the thick ascending limb of the loop of Henle is normally as low as 10 to 20 mm Hg. It might therefore be expected that the tu bular cells in the medulla would be most susceptible to ischemic injury. Both animal and human studies have suggested that, in many cases of postischemic

CHAPTER 11 Acute Kidney Injury

O 2 diffusion

Cortex

100

50

Outer medulla

50 20

25 10

15

12

Inner medulla

PO 2 consumption (mm Hg)

10

8

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„ FIGURE 11.4. Development of hypoxia (with the tissue PO 2 falling below 10 mm Hg) in the renal medulla due to the exchange of oxygen between the de scending and ascending limbs of the vasa recta capillaries ( straight arrows ) and oxygen consumption by the medullary cells ( curved arrows ). (Modified from Brezis M, Rosen S, Silva P, et al. Renal ischemia: a new perspective. Kidney Int . 1984;26[4]: 375-383. Copyright © 1984 International Society of Nephrology. With permission.)