Kidneys, Ureters, and Urinary Bladder



Kidneys, Ureters, and Urinary Bladder


The organ system examined in this chapter is the site of numerous diverse conditions, including congenital and hereditary diseases of the kidney, primary disease of the kidney, systemic diseases affecting the kidney, and diseases of the urinary system.


The kidneys are the primary regulators of the internal environment, particularly the volume, tonicity, and compartmental distribution of body fluids. They perform this function by exchanging and excreting water, minerals, and nonmetabolized solutes from the daily diet and end products of nitrogen metabolism (urea and creatinine). To accomplish this task, the kidneys produce an ultrafiltrate of plasma amounting to 180 L per day, reabsorbing more than 99% of it to produce an average of 1.5 L urine per day. Normal kidney function requires well-regulated blood flow through the kidneys, amounting to approximately 20% of the cardiac output, even though both kidneys comprise only approximately 1% of total body weight. Thus, even minor changes in renal structure can cause major functional disturbances and diseases. Consequently, microscopic investigations of the kidneys (e.g., by biopsy) are valuable for the diagnosis and classification of renal diseases.



Primary Diseases of the Kidney


Acute renal failure (ARF), which occurs in approximately 5% of hospitalized patients, is defined as an increase in serum creatinine of 0.5 to 1.0 mg/dL. Chronic renal failure (CRF) is a long-standing and usually irreversible impairment of renal function with reduction of the filtration rate, azotemia, and uremia. Common causes of ARF and CRF, as discussed in this chapter, are diverse, and both renal and extrarenal diseases must be considered in differential diagnosis.


The etiopathogenesis of glomerular and tubuloglomerular diseases (e.g., glomerulonephritis and nephrotic syndrome) is also highly diverse, as reflected in the difficulty in their classification. Many cases follow an autoimmune disorder; therefore, it is necessary to supplement the usual biopsy histology for staging and grading of the disease with immunohistologic procedures, occasionally including serology. Consequently, although the primary manifestation of an autoimmune renal disease may be the kidney, virtually all these conditions should be considered systemic processes (as in postinfectious autoimmune glomerulonephritis). Some, such as anaphylactoid purpura, lupus nephritis, and Wegener syndrome (see below), show systemic organ involvement from the beginning.



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.




Diseases of the Urinary System


Common diseases of the urinary system include pyelonephritis, obstructive uropathy, infections (e.g., tuberculosis, parasitic infections, cystitis) nephrolithiasis, some malformations (cystic disease, diverticula), neurogenic bladder, and neoplastic diseases. Obstructive nephropathy and hydronephrosis result from mechanical impediment of urine flow with renal dysfunction, dilatation of the collecting system, and frequent infections. Causes include intraluminal calculi (urolithiasis) and tumors (papilloma), compression (prostatic hypertrophy, pregnancy, retroperitoneal fibromatosis or tumors) and ureteral dysfunctions (amyloidosis, malformations, neurogenic conditions). Infections resulting from such functional disturbances are frequent causes of pyelonephritis, a bacterial infection of the renal parenchyma calyces and pelvis.


Other frequent and important diseases discussed in this chapter are malignant tumors such as adenocarcinoma and nephroblastoma of the kidney and transitional carcinoma of the urinary tract and bladder. Adenocarcinoma (renal cell carcinoma [RCC]) constitutes approximately 90% of renal malignancies; it occurs in more than 10,000 persons per year in the United States, and its annual incidence is increasing. A few cases occur as hereditary tumors and may be part of a cancer syndrome (e.g., von Hippel-Lindau syndrome). Clinical features are hematuria, pain, and an abdominal mass, which may lead to diagnosis and treatment by surgical resection. The 5-year survival rate of RCC is 40%. Urothelial cell (transitional cell) carcinoma (UCC) of the renal pelvis represents 5% to 10% of all kidney tumors. UCCs are more frequent in the urinary tract and account for 80% of neoplasms in the bladder. As long as the disease is confined to the bladder, as it is in approximately 85% of cases at initial presentation, survival after surgery amounts to 57% and 35% for low-grade and high-grade malignancy tumors, respectively. Nephroblastoma (Wilms tumor [WT]) constitutes the most frequent solid abdominal tumor in children. WTs may develop bilaterally and may accompany various congenital syndromes (e.g., Beckwith-Wiedemann syndrome). Karyotypic analysis reveals characteristic chromosomal changes in sporadic and congenital WTs such as alterations of the tumor suppressor gene WT1 or the susceptibility gene WT2. These changes apparently support the unrestricted growth of the nephrogenic blastoma, resulting in a tumor composed of blastemal, stromal, and epithelial elements. Early diagnosis before the age of 2 years with surgical removal of the tumor, radiation therapy, and chemotherapy may result in long-term survival of up to 90%.


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Figure 6-1 Acute Renal Failure I
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.

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Figure 6-2 Acute Renal Failure II
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.

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Figure 6-3 Chronic Renal Failure
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.

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Figure 6-4 Uremia
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.

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Figure 6-5 Nephrotic Syndrome: Pathophysiology
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.

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Figure 6-6 Nephrotic Syndrome: Pathology
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.

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Figure 6-7 Anti–Glomerular Basement Membrane Disease
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.

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Figure 6-8 Acute and Chronic Glomerular Injury Produced by Circulating Immune Complexes
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.

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Figure 6-9 Acute Glomerulonephritis
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.

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Figure 6-10 Chronic Glomerulonephritis: Early Stage
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.

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Figure 6-11 Chronic Glomerulonephritis: Mesangiocapillary Glomerulonephritis
Mesangiocapillary glomerulonephritis (membranoproliferative, lobular, or hypocomplementemic glomerulonephritis) occurs most often in children and young adults. Patients present with components of the nephrotic syndrome and, usually, depression of serum complement. Typically, the disease progresses slowly. Histologically, the glomeruli are enlarged and moderately cellular, and the lobular centers are expanded as a result of proliferation of the mesangial cells and matrix. Ingrowth of the mesangium into the capillary wall causes capillary wall thickening, separates the endothelium from the basement membrane, and narrows the lumen. Immunofluorescence reveals deposits of complement (C3) and small amounts of γ globulin (IgG, IgM) within the mesangial matrix.

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Jun 28, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Kidneys, Ureters, and Urinary Bladder

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