Nephritic Syndrome - MPGN Flashcards
What are the three basic components of Nephritic syndrome?
- Hematuria
- Renal insufficiency
- Hypertension
Where is the localization of immune complexes in IgA Nephropathy?
Mesangial deposits
Where is the localization of immune deposits in Lupus nephritis?
Subendothelial
Where is the localization of immune deposits in post-infectious GN?
Subepithelial
What do the immune complexes in MPGN, IgA nephropathy and Lupus Nephritis have in common?
The complexes in these diseases are thought to be pre-formed outside the glomeruli and trapped there in the process of filtration.
What effect do subendothelial deposits have on the glomerular capillaries?
Subendothelial immune complex deposition is injurious to endothelial cells which can lead to thrombus formation in glomerular capillaries.
What is MPGN?
A heterogenous group of uncommon diseases with a shared light microscopic appearance combined thickened glomerular basement with a proliferation of glomerular cells and infiltration of inflammatory cells.
What is the characteristic appearance of the GBM in MPGN?
Thickening and splitting causes a Tram Track appearance on Silver stain
What is the most common type of MPGN?
Type I MPGN
What are some of the causes of secondary MPGN.
- HCV (most common)
- HBV
- Cryoglobulinemia
How does MPGN affect the different age groups?
Usually primary in children and secondary in adults.
What is the predominant age range affected by MPGN?
7-30
What mediates (causes) type I MPGN?
Immune complex deposition causing complement activation by the Classical pathway.
What damages the capillary wall in MPGN Type I?
Cytokines and Proteases
What happens to the endothelial cells in MPGN Type I?
Loss of fenestration
What would microscopy show in MPGN Type I?
- Subendothelial deposits
2. Granular deposits of C3 and IgG
What would generally be the end result of MPGN?
End-stage renal disease
What is another name for MPGN Type II?
Dense Deposit disease
In what subset of patients is type II MPGN most likely to present?
Older children and young adults.
What usually precedes Type II MPGN?
URI
Is Type II MPGN / Dense deposit disease caused by immune complexes? d
NO NO NO
What is the cause of Type II MPGN / Dense deposit disease?
Dysregulation of the complement system
What pathway is inappropriately and excessively activated in Type II MPGN?
The alternative pathway due to congenital mutations of complement regulating proteins or acquired antibodies to them
What leads to the injury phase in Type II MPGN?
Deposition of complement factors of the alternative pathway and terminal complement complex
What are other etiologies of Type II MPGN?
- Autoantibodies against Complement factor H
- Autoantibodies against Complement factor I
- Autoantibodies against Complement factor B
- Autoantibodies against C3 convertase (C3 nephritic factor.
What is the difference on immunoflurescence between Type I and Type II
In type II usually there is only granular deposits of C3 along the GBM and in the mesangium but no IgG C1q or C4
What differentiates type I from type II on electronmicroscopy?
Dense deposits in the basement membrane. Type II features ribbons of dense dark material deposited within the GBM
Where else may dense deposits occure in Type II?
1.Bruch membrane of eye (drusen)
What else differentiates Type II from type I?
1.In type II there may b Partial lipodystrophy with loss of subQ fat in the upper half of the body.
What is the treatment for MPGN?
Prognosis is poor.
