Atlas of pathophysiology, 2 Edition

Part II - Disorders

Glomerulonephritis

Glomerulonephritis is a bilateral inflammation of the glomeruli, commonly following a streptococcal infection. Acute glomerulonephritis is also called acute poststreptococcal glomerulonephritis.

Age Alert

Acute glomerulonephritis is most common in boys ages 3 to 7 but can occur at any age. Rapidly progressive glomerulonephritis most commonly occurs between ages 50 and 60. Up to 95% of children and 70% of adults recover fully. Elderly patients may progress to chronic renal failure within months.

Rapidly progressive glomerulonephritis—also called subacute, crescentic, or extracapillary glomerulonephritis—may be idiopathic or associated with a proliferative glomerular disease such as poststreptococcal glomerulonephritis.

Chronic glomerulonephritis is a slowly progressive disease characterized by inflammation, sclerosis, scarring and, eventually, renal failure. It usually remains undetected until the progressive (irreversible) phase.

Causes

Acute or rapidly progressive glomerulonephritis

·   Streptococcal infection of the respiratory tract

·   Immunoglobulin A nephropathy (Berger's disease)

·   Impetigo

·   Lipoid nephrosis

Chronic glomerulonephritis

·   Membranoproliferative glomerulonephritis

·   Membranous glomerulopathy

·   Focal glomerulosclerosis

·   Rapidly progressive glomerulonephritis, poststreptococcal glomerulonephritis

·   Systemic lupus erythematosus, Goodpasture's syndrome

·   Hemolytic uremic syndrome

Pathophysiology

In nearly all types of glomerulonephritis, the epithelial or podocyte layer of the glomerular membrane is damaged.

Acute poststreptococcal glomerulonephritis results from the entrapment and collection of antigen-antibody complexes, also known as immune complexes, in the glomerular capillary membranes, after infection with a group A beta-hemolytic streptococcus. The antigens, which are endogenous or exogenous, stimulate the formation of antibodies, which form immune complexes. Circulating immune complexes become lodged in the glomerular capillaries. The severity of glomerular damage and consequent renal insufficiency is related to the size, number, location (focal or diffuse), duration of exposure, and type of immune complexes.

In the glomerular capillary wall, immune complexes activate biochemical mediators of inflammation—complement, leukocytes, and fibrin. Activated complement attracts neutrophils and monocytes, which release lysosomal enzymes that damage the cell walls and cause a proliferation of the extracellular matrix, affecting glomerular blood flow. Those events increase membrane permeability, which causes a loss of negative charge across the glomerular membrane and enhanced protein filtration. Membrane damage also leads to platelet aggregation, and platelet degranulation releases substances that increase glomerular permeability.

Protein molecules and red blood cells (RBCs) can now pass into the urine, resulting in proteinuria or hematuria. Activation of the coagulation system leads to fibrin deposits in Bowman's space. The result is formation of crescent-shaped blood cells and diminished renal blood flow and glomerular filtration rate. The presence of crescents signifies severe, often irreversible kidney damage. Glomerular bleeding acidifies the urine and thereby transforms hemoglobin to methemoglobin; the result is brown urine without clots.

Signs and symptoms

·   Decreased urination; smoky or coffee-colored urine

·   Shortness of breath, dyspnea, orthopnea, bibasilar crackles

·   Periorbital and peripheral edema

·   Mild to severe hypertension

Diagnostic test results

·   Blood studies reveal elevated blood urea nitrogen and creatinine levels; decreased serum protein levels; decreased hemoglobin; elevated antistreptolysin-O titers in 80% of patients; elevated streptozyme (a hemagglutination test that detects antibodies to several streptococcal antigens) and anti-DNase B (a test to determine a previous infection of group A beta-hemolytic streptococcus) titers; and low serum complement levels indicate recent streptococcal infection.

·   Urinalysis reveals RBCs, white blood cells, mixed cells casts, and protein.

·   Throat culture detects group A beta-hemolytic streptococcus.

·   Kidney-ureter-bladder X-ray shows bilateral kidney enlargement (acute glomerulonephritis).

·   Renal biopsy confirms the diagnosis or assesses renal tissue status.

Treatment

·   Treatment for primary disease, antibiotics for infections

·   Bed rest to reduce metabolic demands

·   Fluid and dietary sodium restriction, correction of electrolyte imbalances

·   Loop diuretics (metolazone or furosemide) for extracellular fluid overload

·   Vasodilators (hydralazine or nifedipine) for hypertension

·   Corticosteroids to decrease antibody synthesis and suppress inflammatory response

·   In rapidly progressive glomerulonephritis, plasmapheresis to suppress rebound antibody production, possibly combined with corticosteroids and cyclophosphamide

·   In chronic glomerulonephritis, dialysis or kidney transplantation

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IMMUNE COMPLEX DEPOSITS ON GLOMERULUS

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