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Acute Proliferative Glomerulonephritis Lecture 45Acute Poststreptococcal Glomerulonephritis

Acute Poststreptococcal GlomerulonephritisAcute glomerulonephritis is a disease characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension.

APSGNIt is a representative disease of acute nephritic syndrome in which inflammation of the glomerulus is manifested by proliferation of cellular elements secondary to an immunologic mechanism.

Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis

Characterized histologically by diffuse proliferation of glomerular cells, associated with influx of leukocytes.Occurs predominantly in males 97 percent occur in developing countries

Acute Poststreptococcal GlomerulonephritisThese lesions are typically caused by immune complexes. The inciting antigen may be exogenous (Postinfectious glomerulonephritis) or endogenous (SLE).

Acute Proliferative GlomerulonephritisThe most common underlying infections are streptococcal, but the disorder also has been associated with other infections.

APSGN

It usually appears 1 to 4 weeks after a streptococcal infection of the pharynx or skin. It occurs most frequently in children 6 to 10 years of age, but adults of any age can also be affected.

Etiology and Pathogenesis.

Only certain strains of group A -hemolytic streptococci are nephritogenic, more than 90% of cases being traced to types 12, 4, and 1, which can be identified by typing of M protein of the cell wall.

The M and T proteins in the bacterial wall have been used for characterizing streptococci. Nephritogenicity is mainly restricted to certain M protein serotypes (ie, 1, 2, 4, 12, 18, 25, 49, 55, 57, and 60) that have shown nephritogenic potential.

Etiology & Pathogenesis of Ac Prolif. GPoststreptococcal glomerulonephritis is an immunologically mediated disease. Elevated titers of antibodies against one or more streptococcal antigens are present in a great majority of patients.

Etiology & Pathogenesis of Ac Prolif. GSerum complement levels are low, There are granular immune deposits in the glomeruli, supporting an immune complexmediated mechanism. The resulting glomerular immune complex disease triggers complement activation and inflammation.

PathogenesisThe 2 most widely proposed theories include (1) glomerular trapping of circulating immune complexes and (2) in situ immune antigen-antibody complex formation resulting from antibodies reacting with either streptococcal components deposited in the glomerulus or with components of the glomerulus itself, which has been termed molecular mimicry.

Etiology & PathogenesisSeveral cationic antigens, including a nephritis-associated streptococcal plasmin receptor (NAPlr), unique to nephritogenic strains of streptococci, can be found in affected glomeruli.

Etiology & PathogenesisStreptococcal pyogenic exotoxin B (SpeB) and its zymogen precursor (zSpeB), are the principal antigenic determinants in most cases of poststreptococcal glomerulonephritis.

MorphologyLight microscopyIt shows a diffuse proliferative glomerulonephritis with prominent endocapillary proliferation and numerous neutrophils. Trichrome stain may show small subepithelial hump-shaped deposits. Crescent formation is uncommon and is associated with a poor prognosis.

Light microscopic findingsEarly stage glomerular hypercellularity Later stage Proliferation of intrinsic endothelial & mesangial cells

Immunofluorescence microscopyShows a characteristic pattern of deposits of immunoglobulin (IgG) and C3 distributed in a diffuse granular pattern within the mesangium, and glomerular capillary walls.Other immune reactants (eg, IgM, IgA, fibrin, and other complement components) may also be detected.

Electron microscopy

The dome-shaped subepithelial electron-dense deposits that are referred to as humps.Subendothelial immune deposits and subsequent complement activation are responsible for the local influx of inflammatory cells, leading to a proliferative glomerulonephritis, an active urine sediment, and a variable decline in glomerular filtration rate.Subepithelial "humps" are responsible for epithelial cell damage and proteinuria, similar to that seen in membranous nephropathy

Clinical Features Of APGHistory:

In the classic case, a young child abruptly develops malaise, fever, nausea, oliguria, and hematuria 1 to 2 weeks after recovery from a sore throat.

Clinical features of Acute Proliferative GlomerulonephritisThe patients have red cell casts in the urine, mild proteinuria (usually less than 1 gm/day), periorbital edema, and mild to moderate hypertension.

Clinical features of Acute Proliferative GlomerulonephritisIn adults the onset is more likely to be atypical, such as the sudden appearance of hypertension or edema, frequently with elevation of BUN.

Clinical features of Acute Proliferative GlomerulonephritisDuring epidemics caused by nephritogenic streptococcal infections, glomerulonephritis may be asymptomatic, discovered only on screening for microscopic hematuria.

Laboratory FindingsElevations of antistreptococcal antibody titers and a decline in the serum concentration of C3 and other components of the complement cascade.

PrognosisMore than 95% of affected children eventually recover totally with conservative therapy aimed at maintaining sodium and water balance. A small minority of children (perhaps fewer than 1%) do not improve, become severely oliguric, and develop a rapidly progressive form of glomerulonephritis.

Nonstreptococcal Acute Glomerulonephritis (Postinfectious Glomerulonephritis)

Glomerulonephritis occurs sporadically in association with other infections, including bacterial viral and parasitic. Granular immunofluorescent deposits and subepithelial humps are present.

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