Tubulointerstitial Diseases

+ are clinically heterogeneous disorders
+ share similar features of tubular and interstitial injury
+ In severe and prolonged cases, the entire kidney may become involved, with glomerular dysfunction and even renal failure



+ 2 categories
+ + acute tubular necrosis
+ + acute or chronic tubulointerstitial nephritis
+ Pathophysiology
+ + kidneys exposed to unusually high concentrations of toxins
+ + kidneys have the highest blood supply of all tissues (about 3.5 mL/g/min)
+ + unbound solutes leave the circulation via glomerular filtration at ≥ 100 mL/min
+ + toxic agents are delivered at a rate 50 times that of other tissues and in much higher concentrations
+ + When urine is concentrated, the luminal surfaces of tubular cells may be exposed to molecule concentrations 300 to 1000 times greater than that of plasma
+ + The fine brush border of proximal tubular cells exposes an enormous surface area
+ + A countercurrent flow mechanism increases ionic concentration of the interstitial fluid of the medulla (and thereby increases urine concentration) up to 4 times the plasma concentration
+ factors can affect cellular vulnerability after exposure to toxins
+ Tubular transport mechanisms separate drugs from their binding proteins, which normally protect cells from toxicity
+ Transcellular transport exposes the interior of the cell and its organelles to newly encountered chemicals
+ Binding sites of some agents (eg, sulfhydryl groups) may facilitate entry but retard exit (eg, heavy metals)
+ Chemical reactions (eg, alkalinization, acidification) may alter transport in either direction
+ Blockade of transport receptors may alter tissue exposure (eg, diuresis from blockade of adenosine A1 receptor may decrease exposure)
+ Finally, the kidneys have the highest O2 and glucose consumption/g and are therefore vulnerable to toxins affecting cell energy metabolism

source