Download ppt - Rapidly progressive glomerulonephritis (1)

RAPIDLY PROGRESSIVE GLOMERULONEPHRITISCharacterized clinically by rapid and progressive loss of renal

function.Severe oilguria and signs of nephritic syndrome.If untreated ,death due to renal failure occurs from weeks to months.The most common histological picture is the presence of crescent in

most of the glomeruli hence called crescent glomerulonephritis.On the basis of immunological findings RPGN can be divide into

three groups: Type I - Anti GBM antibody-induced disease

Type II - Immune complex deposition

Type III- Pauci immune type

Anti-GBM antibody induced disease

Accounts for 20% of RPGN. Characterized by linear deposition of IgG.In some of these patients,the anti-GBM antibody cross reacts

with pulmonary alveolar basement membrane to produce the clinical picture of pulmonary hemorrhage associated with renal failure(Goodpasture syndrome).

The Goodpasture antigen is a peptide within the non-collagenous portion of the α-3 chain of collagen type IV

The majority of type I , disease however features anti-GBM antibody alone ,these cases are considered idiopathic.

Plasmapheresis to remove the pathogenic circulating antibodies is usually part of the treatment.

Immune complex depostition

Accounts for 25% of RPGN.It can be a complication of any of the immune complex

nephritides including : post infectious glomerulonephritis,lupus nephritis ,IgA nephropathy,Henoch-Schonlein purpura.

This type of RPGN frequently demonstrate cellular profusion within the glomerular tuft ,in addition to crescent formation.

These patients cannot usuly be helped by plasmapheresis.

Pauci-immune type

Accounts for 55% of RPGN.Defined by the lack of anti-GBM antibodies or immune complexesMost ptients with this type of RPGN have circulating antineutrophil

cytoplasmic antibodies (ANCAs). In some cases this type of RPGN is a component of a systemic vasculitis

such as :Wegener granulomatosis or microscopic polyangiitis. In many cases however,pauci-immune crescentric glomerulonephritis is

uisolated and hence idiopathic.More than 90% of such idiopathic cases have c-ANCAs or p-ANCAs in the

serum.The presence of circulating ANCAs in both idiopathic crescent

glomerulonephritis and cases of crescent glomerulonephritis that occur as a component of systemic vasculitis and the similar pathologic feature in either setting have led to the idea that these disorders are pathogenetically related.

The common denominator in all types of RPGN is severe glomerular injury and formation of crescent.

The common denominator in

all types of RPGN is severe

glomerular injury

SUMMARY OF CLASSIFICATION

MORPHOLOGY

The kidney are enlarged and pale often with petechial hemorrhages on the cortical surfaces.

Light microscopy can provide useful information to help distinguish which subclass (RPGN I, II, III) of crescentic glomerulonephritis is present.

RPGN type II have more segmental hypercellularity than types I and III.

Necrotizing changes of glomerular tufts are more common in RPGN types I and III. In particular, comparing RPGN Type I to RPGN type III, the pauci-immune disease is more often associated with necrotizing arteritis

Enlarged ,pale kidney with petechial hemorrhage on cortical surface

GROSS

Crescentric glomerulonephritis. Collapsed glomerular tuft and crescent-shaped mass of proliferating

parietal epithelial cells.

Glomeruli may show focal necrosis, diffuse or

focal endothelial

proliferation and

mesengial proliferation.

The histological picture is

dominated by distinctive crescents.

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

LIGHT MICROSCOP

Y

Direct immunofluorescence shows smooth, linear staining of the glomerular capillary basement membranes for IgG. Similar staining pattern would also

be seen for C3.

•Anti GBM disease

•Good pasture syndrome


Type I RPGN

IMMUNOFLUORESCENCE

Immunofluorescence reveals the granular pattern of staining characteristic of immune

complex deposition


Type II RPGN

IMMUNOFLUORESCENCE

It has weak or no demonstrable immunoglobulin / complement deposition,


Type III RPGN

IMMUNOFLUORESCENCE

Crescentric glomerulonephritis showing characteristic wrinkling of GBM with focal

disruptions (arrows)


ELECTRON MICROSCOP

Y