Renal Pathophysiology

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RENAL PATHOPHYSIOLOGY: THE ESSENTIALS

B

Loss of polarity

Apical surface

Loss of brush border

Basolateral surface

Ischemia and reperfusion

Luminal obstruction

A

C

Apoptotic epithelial cell

Viable epithelial cell

Integrin

Tubular lumen

Na+-K+-ATPase

Necrosis and cell death

Epithelial cell with brush border

Tight junction

Backleak

ATN, there is a preferential injury to the thick ascending limb and the terminal segment of the proximal tubule that ends in the outer medulla. Pathogenesis Vascular Abnormalities With acute ischemic injury, there is a loss of renal autoregulation and a par adoxical increase in vasoconstriction resulting from increased cytosolic and mitochondrial calcium concentrations. Outer medullary congestion is an other prominent finding of acute renal ischemia that may contribute to wors ening tissue hypoxia. Endothelial damage from increased oxidant injury has also been proposed to play a role, and oxidant injury may lead to a decrease in endothelial cell nitric oxide synthase (eNOS) and vasodilatory prostaglandins. Tubular Abnormalities How tubular abnormalities in ischemic ATN mediate the fall in GFR is not com pletely understood but involves numerous mechanisms (Figs. 11.5 and 11.6). „ FIGURE 11.5. Sequence of changes in renal tubules (seen in cross section) after isch emia/reperfusion injury. Following ischemia and reperfusion (A) , morphologic changes occur in the proximal tubules, including loss of polarity, loss of the brush border, loss of tight junctions, and redistribution of integrins and Na + -K + -ATPase to the apical surface (B) . Calcium and reactive oxygen species may also have a role in these morphologic changes. Subsequent cell death results from necrosis and apoptosis. Both viable and nonviable cells are shed into the tubular lumen, resulting in the formation of casts and luminal obstruction, with backleak contributing to the reduction in the glomerular fil tration rate (C) . (Modified with permission of American Society for Clinical Investiga tion from Schrier RW, Wang W, Poole B, et al. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest . 2004;114[1]:5-14, permission conveyed through Copyright Clearance Center, Inc. Original illustration in Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med . 1996;334[22]:1448-1460.)

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