PATH: Nephritic Syndrome Flashcards
What is nephritic syndrome?
Acute onset of hematuria, renal insufficiency (olguria/azotemia), and HTN (with some degree of proteinuria and edema)
What is the most common form of MPGN?
Type I (80%) Type 2 (~20%) Type 3 (very rare)
What is type I MPGN associated with?
Hepatitis C and Hepatitis B
What is the pathogenesis of type I MPGN?
1) Immune complexes form outside glomerulus
2) Deposition in subendothelium
3) Endothelial cells injured (capillary lumen thrombus formation and influx of leukocytes)
4) proliferation of luekocytes and release of cytokines (activate complement via classical pathway)
5) Glomerular capillary rupture–> hematuria
6) Repair (mesangial cell proliferation forms tram tracks)
What complement component is low in type I MPGN?
C3
What is the pathology of Type 1 MPGN?
LM: enlarged glomeruli, tram tracks (GBM thick and split), abundant mesangial matrix, proliferation of cells
IF: granular deposits of C3 and IgG
What is the underlying cause of Type II MPGN?
C3 nephritic factor is found in 80% of patients (leading to dysregulation of complement system)–> nothing to do with immune complexes
How does IF differ between Type I and Type II MPGN?
Type II is not likely to have IgG, C1q, or C4 present! It has C3 deposits along the GBM and mesangial matrix
What does EM look like with Type II MPGN?
Dense ribbons of intramembranous deposits
What are two unique symptoms seen with Type II MPGN that are NOT seen with Type I?
1) Drusen (decreased vision)
2) Partial lipodsytrophy
What is the action of C3 nephritic factor?
inappropriately and excessively activate the alternative pathway because it stabilizes C3 convertase
Familial forms of dense deposit disease may have what mutation?
decreased complement factor H
What is another name for IgA nephropathy?
Berger’s disease
What is the systemic form of IgA nephropathy?
Henoch-schonlein purpura
How does IgA nephropathy occur?
Aberrant galactosylation of O-linked glycans in the hinge region of IgA2 so that they terminate with N-acetlygalactosamine (rather than galactose). Get recognized by IgG or IgA1 antibodies. These IC’s circulate and deposit int he mesangium of glomeruli.
Who gets IgA nephropathy?
young, East Asian male children with genetic predisposition or secondary to celiac disease, IBS, etc.
When do you see symptoms of IgA nephropathy?
1-2 days after a GI infection or URI
How can you distinguish IgA nephropathy from the other forms of glomerulonephritis?
Immunofluorescence shows IgA deposits with C3 and properdin
How do you treat IgA nephropathy?
steroids, ACE inhibitors, ARBs
What are anti-GBM antibodies targeted against?
NC-domain of alpha3 chain of type IV collagen
What triggers anti-GBM or Goodpastrue’s disease?
smoking, hydrocarbons, tumors, etc.
How can you differentiate Goodpasture’s from anti-GBM?
Goodpasture’s will have hemoptysis and pulmonary infiltrates most likely
What is the characteristic light microscope finding of rapidly progressive GN?
crescents (made up of proliferating parietal epithelial cells, macrophages, and fibrin) in Bowman’s space
What are the 3 classifications of RPGN?
Type 1: Linear Glomerular Deposits (anti-GBM)
Type 2: Granular Immune Complex Deposits (SLE, post-strep GN, IgA nephropathy).
Type 3: Pauci-immune (ex. ANCA vasculitis)
True or False: RPGN is a medical emergency.
FALSE: but it does need prompt diagnosis and treatment to prevent severe and permanent renal damage and failure.
What is Alport Syndrome?
Hereditary Nephritis caused by X-linked defect in alpha-5 collagen type IV that leads to defective assembly of the GBM
What does the EM of Alport syndrome look like?
“basket weave”–> thin GBM with splintering of lamina densa with complete focal effacement
What s/s are associated with Alport Syndrome?
Deafness, lens abnormalities, platelet defects, rare esophageal problems
