what are the mechanisms of the immune reaction of glomerulonephritis
in situ deposition of antibodies or immune complexes against antigens that are intrinsic to the glomerulus or planted antigens
or circulating immune complex formation which then deposits into the glomerulus
what has to happen with the immune complexes to cause infiltrating hypercellular GNs
the deposits have to be subendothelial so that there is access to teh blood stream and complement factors C5a and C3a can recruit leukocytes to the site
what are the antigens incriminated in post-streptococcal GN?
SpeB and GAPDH
what are the symptoms of nephritic syndrome
oliguria - due to the fall in GFR
haematuria - due to leakage of RBC
hypertension - due to the volume retention
what is our light microscopy appearance of post-strep GN
enlarged, hypercellular glomerulus, obliterated capillary lumens with proliferation and leukocyte infiltration
what is our electron microscopy in post-strep GN
sub-epithelial electron dense immune complexes
they were initially sub endothelial however they move in this disease process
whats the immunofluorescence of post strep GN
granular deposits of IgG, IgM and C3
what are the three causes of crescentic glomerulonephritis
type 1
- anti GBM
type 2
- immune complex mediate - essentially a consequence of post-strep GN
type 3
- pauci-immune
what is goodpasture syndrome
anti-GBM antibodies cross react with pulmonary alveolar BM leading to pulmonary haemorrhage as well as the renal failure
whats the pathogenesis of why anti-GBM causes cresentic
the anti-gbm disrupts the basement membrane allowing the leakage of fibrinogen into the urinary space, forming the cresents of fibrin
what does light microscopy of anti-gbm GN look like
collapsed capillary tufts, crescents of proliferated epithelial cells, monocytes and fibrin are seen against the bowmans capsule
overtime these crescents become fibrosed
what does electron microscopy look like for antigbm
wrinkled, focally disrupted glomerular basement membrane
has holes in the basement membrane as this is needed to allow the fibrin passage as part of disease process
what does the immunofluorscence look like in anti-GBM
linear pattern of IgG positivity along the basement membrane. the tuft is compressed due to the fibrin crescent
what are the symptoms of nephrotic syndrome
massive proteinuria, hypoalbuminaemia, generalised oedema, hyperlipidaemia
whats the pathophysiology of membranous nephropathy
the IgG immune complexes are against the PLA2R antigen on podocyte cells
the immune complexes deposit subepithelially and become incorporated into the basement membrane causing it to thicken. the immune complex also activates the MAC which causes proteolytic enzyme release in the podocytes - causing effacement of their foot processes. this damaged the filtration barrier leading to the protein leakage.
what does light microscopy look like in membranous nephropathy
thickened basement membane with a spike appearance due to the incorporate immune complexes. no increase in the cellularity of course due to the subepithelial nature of the immune reaction
what does electron microscopy look like in membranous nephropathy
BM is thickened with electron dense immune deposits subepithelially
podocyte foot processes overlying the deposits are effaced causing protein leakage
What’s the immunofluorscence of membranous nephropathy
granular IgG as the podocytes arent along the whole way like anti-GBM - it may look linear but its not.
why do we get red cell casts in the urine in glomerulonephritis
the blood in the urine reacts with the tamm-horsfall protein thus forming a aggregation of red blood cells
