DISEASE OF RENAL TUBULES AND EVTERSTITIUM

Disease of the renal tubules and interstitium accounts for a large number of cases of renal failure. The main causes of disease are infections, ischemia, and toxic and metabolic disorders.

Acute pyelonephritisis caused by bacterial infection with organisms entering the kidney by two

routes. Ascending infection from the lower urinary tract is most common. Predisposing factors that lead to ascending urinary tract infection are pregnancy, diabetes mellitus, stasis of urine, structural defects of the urinary tract, and reflux of urine from bladder into ureters (vesicoureteric reflux). Bloodstream spread in bacteremic or septicemic states (unusual). Although less common, this seems to be the most likely cause in elderly patients who develop pyrexia of unknown origin, often with rigors, and acute renal failure.

Macroscopically, the kidneys show variable numbers of small, yellowish white cortical abscesses, which are usually spherical, under 2 mm in diameter, and are sometimes surrounded by a zone of hyperemia; the cortical abscesses are often most prominent on the subcapsular surface, after the capsule has been stripped away. In the medulla the abscesses tend to be in the form of yellowish white linear streaks that converge on the papilla. The pelvicalyceal mucosa is hyperemic or covered with a fibrinopurulent exudate. Microscopically, the kidney shows focal infiltration with neutrophils.

Complications: papillary necrosis, pyonephrosis, perinephric abscess.

Chronic pyelonephritisis characterized by chronic interstitial inflammation associated with large scars of the kidney.

Chronic pyelonephritis is a common cause of end-stage chronic renal failure, accounting for about 15%

of all cases. The disease is characterized by interstitial chronic inflammation and scarring, which destroys nephrons. The areas of scarring are associated with distortion of the pelvicalyceal system of the kidney. Renal-induced hypertension may develop and hypertensive-induced vascular damage can increase renal damage.

There are two forms of chronic pyelonephritis: reflux-associated and obstructive. In the most common form, reflux-associated chronic pyelonephritis, reflux of urine from the bladder up the ureters predisposes to recurrent bouts of inflammation, leading to scarring. This occurs in childhood, and disease becomes manifest in early adult life, with progressive impairment of.

In obstructive chronic pyelonephritis, recurrent episodes of infection occur in a kidney in which there is obstruction to the pelvicalyceal drainage. The obstruction, which can be at any level in the lower urinary tract, may be due either to anatomical abnormality or to renal tract stone.

Kidneys have irregular areas of scarring, seen as depressed areas, 1—2 cm in size. The scars are sited over a clubshaped distorted renal calyx and are associated with fibrous scarring of the renal papilla. The most common site for these areas of scarring is the renal calyces at the poles of the kidney.

Histologically the kidney has irregular areas of interstitial fibrosis with chronic inflammatory cell

infiltration. Tubules are atrophic or may be dilated and contain proteinaceous material. Glomeruli show periglomerular fibrosis and many demonstrate complete hyalinization.

Acute tubular necrosisis a common and important cause of reversible acute renal failure. In acute tubular necrosis, metabolic or toxic disturbances cause necrosis of renal tubular epithelial cells. Although the tubular epithelial cells die and are shed, regeneration is possible if the damaging stimulus is corrected, since residual viable tubular epithelial cells can proliferate to re-populate the tubules. It is this regenerative capacity of the tubular epithelial cells that permits adequate tubular functioning after renal transplantation following a prolonged period of hypoxia of the graft.

There are three phases to acute tubular necrosis:

1. Oliguric phase. A damaging stimulus causes necrosis of renal tubular epithelium. There is blockage of renal tubules by necrotic cells, and a secondary reduction in glomerular blood flow (caused by arteriolar constriction) reduces glomerular filtration. Macroscopically, kidneys are diffusely swollen and edematous. Patients develop acute renal failure and oliguria. Supportive measures are required to prevent hyperkalemia and fluid overload.

2. Polyuric phase. Over 1—3 weeks, regeneration of renal tubular epithelium takes place, with removal

of dead material by phagocytic cells, as well as in the form of casts in urine. As tubules open up and glomerular blood flow increases, patients develop polyuria. This is because the regenerated tubular cells are undifferentiated and have not developed the specializations necessary for resorption of electrolytes and water. Replacement of fluid and electrolytes is needed to compensate for excessive loss from urine.

3. Recovery phase. Tubular cells re-establish differentiation and there is restoration of renal function.

Macroscopically, in acute tubular necrosis, kidneys are severely swollen. Microscopically, the lining epithelial cells of the tubules are dead and the tubular lumen are filled with necrotic cell debris.