I- Overview :
The N.G correspond to inflammatory lesions whose starting point is located in the capillary network of the glomeruli. This individualized reached the morphologically gloméruk "nephritis.
II- PATHOGENESIS glomerulonephritis :
The causes are diverse G.N :
- immunological mechanisms.
- metabolic, vascular, thrombotiques, hereditary or unknown.
But the immune phenomena, are the most important and intervene according 2 key terms :
1° – Fixing at the glomerular capillary walls, antigen complex- circulating antibody, related supplement.
2° – Fixing at the glomerular basement membrane antibodies against it.
III- DAMAGE BASIC glomerular :
1- Deposits :
Depending on their nature are distinguished :
- Non immune deposits (hyalins).
- The immune deposits. L’immuno fluorescence les classes : in granular deposits (immune complexes) very common, linear deposits (AC anti membrane glomérulaire).
According to their headquarters :
They are in the mesangium :
mesangial deposits or inter capillaries or with respect to the basement membrane (MB), we can then observe :
- On the external side of the M.B (between podocytes and M.B) : deposit- extra membraneux.
- Within the M.B : deposits intra membranous.
- on i<; internal side of M.B (between M.B and endothelial cell) : endomembraneux deposits or under endothelial.
2- Cell proliferation :
The glomerulus contains 3 different types of cells :
- The epithelial cell of the parietal layer of Bowman's capsule, the visceral layer : les podocytes.
- The c glomerular capillary endothelial Mule.
- Mesangial cell or endocapillary.
The proliferating cells : it is mainly mesangial cell and epithelial cell. The proliferation of the latter type is serious : in that case, the cells of the two layers is "rejoignei it" and form a "crescent" that bridges cell urinary space.
3- Topography :
Lesions may interest all or part of the glomeruli. The whole of each glomerulus or the latter sector :
1°- pm compared to all glomeruli :
- If all glomeruli are affected : G.N diffuse ;
- If some glomeruli are affected : focal G.N.
2°- I V’ir relation to each glomerulus :
- If all of the glomerulus is hit : overall achievement.
- If part of the glomerulus is affected : segmental reached.
IV- CLASSIFICATION :
2 groups :
- apparently primitive GN (pathological classification)
- secondary GN (etiological classification).
V- Glomerulonephritis APPARENTLY PRIMITIVE :
They are complex, both morphologically and clinical qu'immunopathologique.
A- G.N WITH MINIMAL DAMAGE glomerular :
C’is the case of pure nephrotic syndrome in children or lipoid nephrosis. It combines syndrome :
- Selective massive proteinuria without hematuria.
- Hypoproteinemia with hypoalbuminemia.
- Hyperlipidemia and edema.
- Renal function and BP are normal.
- In urine, observed many hyaline and granular casts containing lipid droplets refractive : are the refractile bodies.
- The glomeruli are substantially normal to the optical microscope.
- L’glomerular involvement n’is visible only thanks to the study in electron microscopy : it consists of a fusion of the pedicels of podocytes, thus forming a continuous cytoplasmic tongue lining the outer side of the glomerular capillary M.B. No deposit n’is visible and the immunofluorescence tests are negative.
Before the steroids era, the death was common and usually secondary to infection. The first treatment by steroids, and now by immuno depressants changed the prognosis is good.
B- G.N DIFFUSES :
a- non-proliferative :
It's the extra membranous G.N (gnem) , about 15% primitive G.N .
→ clinically : It is characterized by the insidious onset of proteinuria and nephrotic syndrome.
C’is the most important cause of adult nephrotic syndrome, it is idiopathic in most cases but reported a large number of antigens involved.
- Extrinsic antigens of diverse nature :
– infectious : Hepatitis B, filariose, malaria.
– drug or toxic : mercure, or, penicillamine,
- intrinsic antigens :
– tumor antigen : For G.N extra membranous colic cancer or Hodgkin's disease.
– G.N extra membraneuse du lupus.
→ on the pathological plane :
1° – Optical microscope : diffuse wall thickening of the glomerular capillary MB, related to the existence of deposits on its outer side.
2° – Electron microscope : for deposits on the external side of the MB, situated under the feet of podocytes.
3°- En immuno fluorescence : granular deposits of I g G and C3 along the capillary walls.
→ evolutionarily :
The complete spontaneous remission is the rule, but it is followed by frequent recurrences, leading to kidney failure. Treatment with corticosteroids and anti- inflammatory gives little or no results. The prognosis is unfavorable. We must remove the cause when it's . possiole.
b- Prolifératives :
1° – G.N capillary pure endo (acute G.N) :
- Usually occurs, A recent streptococcal infection of the upper airways.
- More common in children than in children’adult.
- gross hematuria.
- Frequently hypertension.
- In this case there is no nephrotic syndrome.
- Complement Decrease (C3).
- Sometimes kidney failure.
- The piotéinurie is abundant.
- Renal biopsy (unnecessary in the typical form).
→ In the optical microscope :
at low magnification, she shows :
Glomeruli "big" hyper inflated- cell because there is a proliferation of glomerular cells (especially mesangial cells) and swelling of endothelial cells associated with a tuft of infiltration by polymorphonuclear.
A high magnification :
we sometimes see peui deposits or "humps" ; they sit on the outer side of M.B, are rare, scattered, bulky, triangular, color red or green trichrome.
→ En immuno fluorescence : These deposits contain some of IgG and especially C3 +++ → La M.E : Confirms topography "humpus" between podocytes and M.B
- Evolution : Usually toward healing or clinical remission.
– For kids : Excellent evolution 90% cases.
– For adults : Good evolution in 50 at 70 % cases.
– Very rarely, adverse developments : deaths during the acute phase (exceptional) uremia infection and cardiovascular complications- vascular.
2° – Glomérulonéphrite membrane- proliferative :
- Represented 10% of G.N. primitives,
- clinical Reminder :
- In 1/3 cases : as acute glomerulonephritis.
- In other cases : nephrotic syndrome (frequent) with microscopic hematuria, asymptomatic proteinuria.
- Dam blood serum complement (You C3 +++) and anemia (inconstant).
→ Renal biopsy :
All glomeruli are big, characterized by thickening of the capillary walls and pai a capillary cell proliferation with endo deposits under – endothéliaux (type I) or dense deposits intra membranous (type II).
- In type I : deposits analysis in immunofluorescence shows immunoglobulins (IG1 and the fraction complement C3.
- In type II : their analysis by immunofluorescence only shows the fraction complement C3.
- Evolution : frequently (despite various therapeutic attempts) towards’IRC in a few months or years.
3° – Glomerulonephritis endo and extra hair ( 5% primitive GN) :
→ Clinical Reminder :
- Symptoms depend on the etiology and % croissants.
- sudden onset, gross hematuria, proteinuria, kidney failure within a few weeks or months.
- Sometimes nephrotic syndrome occurs during various affections : PAN – Wegener's granulomatosis – Good Pasture's syndrome +++ (GN + pulmonary hemorrhage) – the HSP- bacterial endocarditis- la G.N post streptococcique.
→ Renal biopsy, on observe :
- a diffuse involvement of all glomeruli.
- a proliferation of mesangial cells and epithelial cells of Bowman's capsule, which will form proliferating cell growing obliterating Bowman's space.
- these growing, beginning in cell, become after fibro- cellular and fibrous .
- There is also a diffuse tubular atrophy of’variable intensity.
→ In immuno- fluorescence
- Deposits depend on the’etiology.
- Most often in the growing fibrin.
- Sometimes deposits C3jau level of "humps", IgA deposits (HSP), deposits of’Linear IgG and C3 with exceptional anti-glomerular M.B. (particularly in Good pasture syndrome).
→ Change :
- Rapid and severe despite treatment (heparin, platelet dispersants) to renal insufficiency 3 at 12 month.
- Prognosis depends on the etiology, the number of glomeruli with crescents and the growing area.
C- GLOMERULONEPHRITES FOCALES :
a- The focal segmental : is about 10% primitive GN.
→ Clinical Reminder :
- Hematuria or proteinuria isolated.
- Often nephrotic syndrome steroid- resistant.
→ Renal biopsy : Focal segmental reached :
- There are healthy and pathological glomeruli glomeruli.
- At the latter part of the glomerulus is injured.
- Lesion : hyaline membrane endo deposits, segmentaires.
→ En immuno fluorescence : deposits of IgM or C3.
→ Change : Despite corticosteroid treatment (corticorésistance, the disease progresses to IRC.
b- Glomerulonephritis focal segmental must be distinguished :
→ The G.N focal segmental itself :
The lesions are similar to cells described in G.N endo and extra hair, but they are Focal and segmental :
- focus : healthy glomeruli alternate with pathologic glomeruli.
- Segmentaires : at each glomerulus, mesangial proliferation interested in a glomerulus sector, it is accompanied by a proliferation extra- capillaries (croissants).
- En immuno fluorescence : deposits are diffuse, variable and depend on the etiology, same causes as for G.N endo and extra hair, especially :
– The bread.
– The HSP.
– Bacterial endocarditis.
- clinically : same symptoms that also G.N endo and extra hair but less "noisy".
- The evolution : is quick enough to kidney failure .
→ Berger's disease or mesangial deposits G.N IgA :
Very frequented, about 20% primitive G.N, which defines : mesangial deposits of IgA, So the immunofluorescence is required to make the diagnosis. These deposits are diffuse.
- clinically :
– recurrent hematuria +.+ (macroscopic or microscopic)
– sometimes proteinuria.
– Rarely an infection site.
– Sometimes elevated serum IgA.
- renal biopsy :
– In light microscope :
normal kidney or increased mesangial axes, or focal segmental reached :
- focus : healthy glomeruli alternate with pathologic glomeruli.
- segmentaire : moderate mesangial cell proliferation affecting only secteui the glomerulus.
– In immunofluorescence and M.E :
diffuse mesangial deposits of IgA interesting the +++, optionally IgG, C3.
- Evolution :
– Good in general.
– In 20% cases, evolution to IRC, with hypertension.
D- G.N INCLASSEES :
- fairly frequent : 10% about primitive GN.
- This framework includes the advanced too primitive GN or not within a framework defined : deposits, cell proliferation, do not allow the store in the types described above.
Course of Dr Madoui – Faculty of Constantine