PATH: Nephritic Syndrome

Question 1

What is nephritic syndrome?

Answer 1

Acute onset of hematuria, renal insufficiency (olguria/azotemia), and HTN (with some degree of proteinuria and edema)

Question 2

What is the most common form of MPGN?

Answer 2

Type I (80%)
Type 2 (~20%)
Type 3 (very rare)

Question 3

What is type I MPGN associated with?

Answer 3

Hepatitis C and Hepatitis B

Question 4

What is the pathogenesis of type I MPGN?

Answer 4

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)

Question 5

What complement component is low in type I MPGN?

Answer 5

C3

Question 6

What is the pathology of Type 1 MPGN?

Answer 6

LM: enlarged glomeruli, tram tracks (GBM thick and split), abundant mesangial matrix, proliferation of cells
IF: granular deposits of C3 and IgG

Question 7

What is the underlying cause of Type II MPGN?

Answer 7

C3 nephritic factor is found in 80% of patients (leading to dysregulation of complement system)–> nothing to do with immune complexes

Question 8

How does IF differ between Type I and Type II MPGN?

Answer 8

Type II is not likely to have IgG, C1q, or C4 present! It has C3 deposits along the GBM and mesangial matrix

Question 9

What does EM look like with Type II MPGN?

Answer 9

Dense ribbons of intramembranous deposits

Question 10

What are two unique symptoms seen with Type II MPGN that are NOT seen with Type I?

Answer 10

1) Drusen (decreased vision)

2) Partial lipodsytrophy

Question 11

What is the action of C3 nephritic factor?

Answer 11

inappropriately and excessively activate the alternative pathway because it stabilizes C3 convertase

Question 12

Familial forms of dense deposit disease may have what mutation?

Answer 12

decreased complement factor H

Question 13

What is another name for IgA nephropathy?

Answer 13

Berger’s disease

Question 14

What is the systemic form of IgA nephropathy?

Answer 14

Henoch-schonlein purpura

Question 15

How does IgA nephropathy occur?

Answer 15

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.

Question 16

Who gets IgA nephropathy?

Answer 16

young, East Asian male children with genetic predisposition or secondary to celiac disease, IBS, etc.

Question 17

When do you see symptoms of IgA nephropathy?

Answer 17

1-2 days after a GI infection or URI

Question 18

How can you distinguish IgA nephropathy from the other forms of glomerulonephritis?

Answer 18

Immunofluorescence shows IgA deposits with C3 and properdin

Question 19

How do you treat IgA nephropathy?

Answer 19

steroids, ACE inhibitors, ARBs

Question 20

What are anti-GBM antibodies targeted against?

Answer 20

NC-domain of alpha3 chain of type IV collagen

Question 21

What triggers anti-GBM or Goodpastrue’s disease?

Answer 21

smoking, hydrocarbons, tumors, etc.

Question 22

How can you differentiate Goodpasture’s from anti-GBM?

Answer 22

Goodpasture’s will have hemoptysis and pulmonary infiltrates most likely

Question 23

What is the characteristic light microscope finding of rapidly progressive GN?

Answer 23

crescents (made up of proliferating parietal epithelial cells, macrophages, and fibrin) in Bowman’s space

Question 24

What are the 3 classifications of RPGN?

Answer 24

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)

Question 25

True or False: RPGN is a medical emergency.

Answer 25

FALSE: but it does need prompt diagnosis and treatment to prevent severe and permanent renal damage and failure.

Question 26

What is Alport Syndrome?

Answer 26

Hereditary Nephritis caused by X-linked defect in alpha-5 collagen type IV that leads to defective assembly of the GBM

Question 27

What does the EM of Alport syndrome look like?

Answer 27

“basket weave”–> thin GBM with splintering of lamina densa with complete focal effacement

Question 28

What s/s are associated with Alport Syndrome?

Answer 28

Deafness, lens abnormalities, platelet defects, rare esophageal problems