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Kidney and Urinary Tract Function

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forms, however, they are difficult to distinguish from other causes of renal insufficiency.

SUMMARY CONCEPTS (continued)

Tubular and Interstitial Disorders Several disorders cause histologic and functional altera- tions that affect renal tubular structures, including the proximal and distal tubules. Most of these disorders also affect the interstitial tissue that surrounds the tubules. Although these disorders, sometimes referred to as tubu- lointerstitial disorders , may occur in the progression of diseases that primarily affect the glomerulus or as sec- ondary manifestations of other diseases such as diabetes mellitus, they can also occur as a primary event. These diseases have diverse causes and different pathogenic mechanisms. They include acute tubular necrosis (dis- cussed in Chapter 26), tubulointerstitial nephritis, acute and chronic pyelonephritis, reflux nephropathy, and nephropathy induced by drugs and toxins. Tubulointerstitial Nephritis Tubulointerstial nephritis represents acute or chronic inflammation of the renal tubules and surrounding interstitium. In chronic tubulointerstitial nephritis there is infiltration with mononuclear leukocytes, interstitial fibrosis, and widespread tubular atrophy. The tubulointerstitial disorders are distinguished clinically from glomerular diseases by the absence, in the early stages, of such hallmarks of nephritis and nephrosis as hematuria and proteinuria, and by the presence of disorders in tubular function. These dis- orders, which are often subtle, include the inability to concentrate urine, as evidenced by polyuria and noctu- ria; interference with acidification of urine, resulting in metabolic acidosis; and diminished tubular reabsorp- tion of sodium and other substances. 5 In their advanced ■■ Glomerular disorders alter the permeability of the glomerular capillary membrane to plasma proteins and blood cells to produce either a nephritic or nephrotic syndrome. The nephritic syndromes, which evoke an inflammatory response in the glomeruli and a decrease in glomerular permeability, are characterized by hematuria with red cell casts in the urine, diminished GFR, azotemia, oliguria, and hypertension.The nephrotic syndromes, which increase glomerular capillary membrane permeability, are characterized by massive proteinuria, hypoalbuminemia, generalized edema, lipiduria, and hyperlipidemia. ■■ Chronic glomerulonephritis represents the chronic phase of a number of specific types of glomerulonephritis.

Pyelonephritis Pyelonephritis is a renal disease affecting the tubules, interstitium, and pelvis of the kidney. Acute pyelone- phritis is caused by bacterial infection; whereas chronic pyelonephritis is a more complex disorder involving not only bacterial infection but other factors such as reflux. Most infections of the kidney are ascending infections that occur secondary to infections of the lower urinary tract (discussed in Chapter 27). Acute Pyelonephritis Acute pyelonephritis is an acute suppurative inflamma- tion of the kidney caused by bacterial infection. 4,5,21,22 Escherichia coli is the causative agent in about 80% of cases. Less common causative organisms include Enterobacteriaceae , Pseudomonas species, group B Streptococcus, Staphylococcus, and enterococci. 21 There are two forms of acute pyelonephritis: uncomplicated and complicated. Uncomplicated acute pyelonephri- tis most commonly occurs in healthy young women without structural or urinary tract obstructions or other contributing factors. Complicated acute pyelone- phritis occurs in children or adults with structural or functional urinary tract abnormalities or predisposing medical conditions. Factors that contribute to the devel- opment of complicated acute pyelonephritis are outflow obstruction, catheterization and urinary instrumenta- tion, vesicoureteral reflux, pregnancy, and neurogenic bladder. There are two routes by which bacteria can gain access to the kidney: ascending infection from the lower uri- nary tract and through the bloodstream (hematogenous spread). Ascending infection from the lower urinary tract is the most important and common route by which bac- teria reach the kidney. The hematogenous route results from seeding of the kidneys by bacteria from distant loci in the course of septicemia or infective endocarditis. 5 It is more likely to occur in debilitated, chronically ill per- sons and those receiving immunosuppressive therapy, and with nonenteric bacteria such as staphylococci and certain fungi. Although outflow obstruction is an important predis- posing factor in the pathogenesis of ascending infection, it is incompetence of the vesicoureteral orifice that allows bacteria to ascend the ureter into the renal pelvis. 4,5 The ureter normally inserts into the bladder at a steep angle and in its most distal portion courses parallel to the blad- der wall, forming a mucosal flap 4 (Fig. 25-11A). The flap acts as a one-way valve: it is normally relaxed, allow- ing urine to flow into the bladder, but is compressed against the bladder wall during micturition, preventing urine from being forced into the ureter. In persons with vesicoureteral reflux, the ureter enters the bladder at an approximate right angle such that urine is forced into the ureter during micturition (Fig. 25-11B). It is seen most commonly in children with urinary tract infections