Kidneys, Ureters, and Urinary Bladder
The Kidney and Systemic Diseases
Many primary systemic diseases affect the kidney, including diabetes mellitus (DM), essential hypertension, various renovascular diseases, and several toxic and metabolic disorders. Progressive renal disease (diabetic nephrosclerosis, Kimmelstiel-Wilson disease) is a common complication of DM (see chapter 12) and is responsible for renal failure in 30% to 40% of patients with insulin-dependent DM and 20% of those with non–insulin-dependent DM. Benign and malignant nephrosclerosis are the renal manifestations of essential hypertension and must be distinguished from renovascular hypertension, the consequence of renal artery stenosis. Hypertensive vascular diseases affect approximately 20% of the population and, with the complications of myocardial infarction, renal failure, and stroke, constitute a major health hazard. (The cause and pathogenesis of hypertension are discussed in chapter 2.) Systemic vasculitis syndromes frequently affect renal vessels or glomeruli or both (Table 6-1). Toxic nephropathy encompasses a large variety of diseases of different origins causing pathologic changes including cortical necrosis, tubular necrosis, focal hemorrhage, interstitial nephritis, and papillary necrosis. Causative toxins may be exogenous (e.g., drugs, plant toxins, allergens) or endogenic (e.g., toxemia of pregnancy), and the pathogenesis may include immune mechanisms (e.g., Shwartzman-Sanarelli syndrome). Metabolic disturbances such as amyloidosis and hypokalemic and calcium nephropathy also are associated with renal pathology.
TABLE 6-1
SUMMARY OF SYSTEMIC VASCULITIS SYNDROMES (PRIMARY AND SECONDARY)
| Affected Vessel | Entity | Clinical Features |
| Small | Wegener disease Microscopic polyangiitis Henoch-Schönlein purpura Leukocytoclastic vasculitis Postinfectious vasculitis (eg, viral) |
Microhematuria, purpura, hemoptyses, perimyocarditis, episcleritis, vertigo, polyneuritis, melena |
| Medium | Pan(poly)arteritis nodosa Churg-Strauss disease Lupus erythematosus Rheumatoid arthritis Progressive systemic sclerosis |
Infarction in various organs including kidneys, hemorrhage from ruptured microaneurysms, hypertension, renal failure |
| Large | Giant cell arteritis Takayasu arteritis |
Arterial stenoses, phlebothromboses, aortic arch syndrome, subclavian steal syndrome |
Diseases of the Urinary System
Acute renal failure is a sudden reduction in renal function with accompanying oliguria or anuria and potentially fatal outcome. There are 3 types of ARF: prerenal, renal (parenchymal), and postrenal. In prerenal failure, which is reversible, renal function is reduced by factors extrinsic to the kidney, such as hypotension, salt depletion, dehydration, or an obstruction in the urinary tract. Renal (parenchymal) failure follows malfunction of the nephrons in a wide variety of diseases, including acute glomerulonephritis, acute pyelonephritis, toxic nephropathy, and severe circulatory impairments, with the latter resulting in acute tubulointerstitial nephropathy or “shock kidney.” The pathophysiologic derangements in ARF are complex but include reduced and maldistributed cortical blood flow with resulting local ischemia while total blood flow is partially preserved. Postrenal causes of ARF are various forms of urinary tract obstruction.
The kidneys of patients with acute renal failure (ARF) are large and pale, with a pale cortex and a dark, hyperemic medulla. Histologically, the hallmark of the condition is multifocal dilation with epithelial flattening of the distal convoluted tubules and, to some extent, the proximal convoluted tubules. The glomeruli are normal. Tubular epithelial cells exhibit degenerative and hydropic changes. Interstitial edema and focal collections of lymphocytes may be present. Electron microscopy confirms the normal structure of the glomeruli and reveals subcellular degenerative changes of organelles. There is a progressive decrease in urine output and a progressive increase in azotemia, metabolic acidosis, and serum potassium levels. Renal function returns if the underlying disease process is contained and the renal-induced metabolic and electrolyte abnormalities are treated successfully.
Chronic renal failure (CRF) is a marked impairment in renal homeostatic function coupled with abnormalities in composition of body fluids. The most common causes of CRF are various types of glomerulonephritis and other nephritides. The functional and structural consequences of ischemia—obstruction with increased intra-pelvic pressure, infection with microorganisms, or deposition of antigen-antibody-complement complexes—may also result in CRF. Renal insufficiency is characterized by impaired renal adaptive function without major alterations in body fluid composition. Further loss in function results in CRF and culminates in uremia. Changes induced by CRF include secondary hyperparathyroidism and metabolic bone disease. In humans, the common structural basis for renal failure is thought to be a progressive reduction in the number of functioning nephrons, while the remaining nephrons develop hypertrophy and increased work per nephron, until these nephrons also are lost.
Uremia is characterized by multiple clinical and laboratory findings resulting from severe renal failure. Azotemia, a hallmark of renal failure, which is characterized by increased concentration of nonprotein nitrogenous compounds in blood, is measured with the blood urea nitrogen (BUN) test. Reduction in glomerular filtration can be measured by the diminution of creatine clearance and resulting increase of creatinine in the blood.
Nephrotic syndrome may be induced by noninflammatory or inflammatory (glomerulonephritic) conditions. The resultant damage, which may be subtle, produces increased permeability of the glomerular capillaries leading to proteinuria. Clinically, nephrotic syndrome is characterized by proteinuria in excess of 3.5 g/d/1.73 m2 body surface area, edema, hypoalbuminemia, and hyperlipidemia. Prolonged massive proteinuria and resultant hypoproteinemia are the common denominators for all consequent metabolic and nutritional defects. Glomerular inflammation also may lead to a decrease in renal blood flow, which may activate the renin-angiotensin system, increasing production of angiotensin II and causing hypertension.
A spectrum of glomerular lesions can produce nephrotic syndrome. Minimal change disease (lipoid nephrosis) shows little or no change by light microscopy. Fused epithelial foot processes and occasional immunoglobulin (Ig) M deposits are seen by electron microscopy. If the disease is complicated by focal and segmental sclerosis, fused epithelial foot processes, capillary collapse, or mesangial expansion with γ-globulin deposits, response to immunosuppressive therapy deteriorates. Membranous nephropathy is characterized by thickened capillary walls, spikes in the basement membrane due to antigen-antibody complexes beneath the epithelial cells (membranous disease), and diffuse granular deposits of IgG and C3 (complement). Mesangioproliferative glomerulonephritis shows thickening of glomerular capillary walls complicated by mesangial proliferation and sclerosis with subendothelial deposits of C3 and IgG in a lumpy, nonlinear pattern. Focal segmental inflammatory necrosis and crescent formation signals a poor response to immunosuppressive therapy.
In anti–glomerular basement membrane (GBM) disease, the antibody is directed against the GBM, the antigen being a normal component of the glomerulus. Anti-GBM disease, whether produced by heterologous antibodies or autoantibodies, has the following features: (1) it is produced by circulating antibodies; (2) the antibodies (γ globulins) and complement are readily detected by immunofluorescence with a distribution along the basement membrane of every glomerulus in a highly distinctive, continuous, linear pattern; and (3) electron microscopy reveals inconspicuous deposits along the endothelial side of the basement membrane. Leukocytes recruited by locally produced chemotactic factors contribute to the glomerular damage. Forms of anti-GBM disease in humans include rapidly progressive, subacute glomerulonephritis and Goodpasture syndrome, which is characterized by lung hemorrhage and severe and rapidly progressive glomerulonephritis.
Acute glomerular injury results when large amounts of immune complexes are delivered to the glomerular capillaries over a short period of time; examples are poststreptococcal glomerulonephritis and the glomerulonephritis associated with subacute bacterial endocarditis. The immune complexes form large deposits on the epithelial side of the basement membranes, which are detected by immunofluorescence as irregular lumpy deposits and by electron microscopy as subepithelial humps in the basement membranes. The immune complexes stimulate an inflammatory response that leads to acute glomerulonephritis. Chronic glomerular injury also results when small amounts of immune complexes are delivered to the glomerular capillaries over a prolonged period, as seen in systemic lupus erythematosus. Electron microscopy and immunofluorescence show extensive deposits of immune complexes along the epithelial side of the basement membrane. The glomerular injury may progress to include proliferative and sclerosing changes.
The kidneys in acute diffuse (poststreptococcal) glomerulonephritis show enlargement and pallor. Abnormally large and cellular glomeruli are seen microscopically; the capillary walls are swollen, and the lumens are narrowed. The hypercellularity is caused by proliferation of mesangial cells with associated increased mesangial matrix. A variable amount of infiltration by polymorphonuclear leukocytes is seen early in the disease. Other changes include casts and erythrocytes in the tubules and interstitial edema and focal inflammation. Electron microscopy reveals swelling of epithelial and endothelial cells and increased numbers of mesangial cells. The presence of semicircular or triangular “humps” (protein deposits) between the basement membrane and epithelial cells are considered to be diagnostic. Rapidly progressive (extracapillary) glomerulonephritis is characterized by the presence of many large cellular crescents consisting of proliferated epithelial cells of Bowman capsules, macrophages, and matrix.
Chronic glomerulonephritis is characterized pathologically by sclerosis of many glomeruli and clinically by manifestations of renal insufficiency. The disease progresses because of inflammation leading to sclerosis of glomeruli and scarring. The kidney may be normal or slightly increased or decreased in size and is often pale yellow with smooth or slightly granular surfaces. On cut section, the cortex is often pale and swollen as a result of lipid in the tubules and interstitial edema. In proliferative and sclerosing glomerulonephritis, the glomeruli typically exhibit cellular proliferation and deposition of intercellular material with an approximate balance between proliferation of cells and sclerosis. In contrast, in membranous glomerulonephritis, cell proliferation and sclerosis are absent, and the histologic changes are limited to the capillary walls, at least in the early stages.
