Inflammatory Glomerular Disease

Question 0

5 histologic-ish stages of the response to glomerular capillary injury?

Answer 0

1. Injury.
2. Proliferation.
3. Acellular crescent formation.
4. Cellular crescent formation.
5. Scarring (glomerular and interstitial).

Question 1

4 aspects of nephritic clinical syndrome?

Answer 1

Microscopic hematuria.
Proteinuria.
Hypertension.
Edema.

Question 2

3 mechanisms for glomerular capillary injury?

Answer 2

Auto-antibodies.
Immune complexes.
…Mechanism X…

Question 3

When glomerular capillaries are affecting by autoantibodies, what specific structure do they target? (what antigen?)

Answer 3

The glomerular basement membrane (GBM).

Type IV collagen.

Question 4

How do both auto-antibodies and immune complexes in the glomerulus cause inflammation?

Answer 4

Via complement fixation.

Question 5

Is Rapidly Progressing Glomerular Nephritis (RPGN) a specific disease process?

Answer 5

No. It’s a syndrome of a combined subacute rise in serum Cr and a nephritic syndrome.
(i.e. there are multiple potential underlying causes)

Question 6

What other organ can be affected when there are auto-Abs against the GBM?

Answer 6

Lungs.

If both happen, this is called Goodpasture’s Syndrome.

Question 7

How do anti-GBM vs. immune complexes appear differently on immunofluorescence?

Answer 7

Anti-GBM: linear (I think a better word would be “continuous”)
Immune complexes: granular

Question 8

What’s the mechanism, usually, behind a glomerulonephritis that doesn’t stain for immune elements (antibodies or complement)?

Answer 8

Vasculitis.

Question 9

Clinical presentation of Goodpasture’s syndrome? (2 main features)

Answer 9

Hemoptysis.
RPGN (rapidly progressive GN)
(These 2 features define a “pulmonary-renal syndrome”)

Question 10

3 diseases in the DDx of renal-pulmonary syndrome?

Answer 10

Goodpasture’s (Abs against GBM).
SLE.
ANCA-positive small vessel vasculitis.

Question 11

Light microscopy features of Goodpasture’s?

Answer 11

Hypercellular glomeruli with crescents and fibrin in Bowman’s space.

Question 12

EM findings in Goodpasture’s?

Answer 12

Mainly useful for the negatives: no electron-dense deposits.

Question 13

Treatment for Goodpasture’s?

Answer 13

Immune suppression.
Plasmapheresis.
Rituximab - anti-CD20 (probably).

Question 14

3 types of GN caused immune complex deposition?

Answer 14

Post-infectious (esp. post-Strep) GN.
Lupus Nephritis.
IgA nephropathy / Henoch-Schoenlein Purpura

Question 15

What does post-infectious GN look like by light microscopy?

Answer 15

Proliferation with PMN infiltration

Question 16

On what side of the GBM are the immune deposits in post-infectious GN?

Answer 16

On the epithelial, Bowman’s space side.
So these are “subepithelial” deposits.
(one can imagine that this is because the immune complexes form after their constituent parts have filtered through the GBM)

Question 17

What should you do to confirm the diagnosis of post-Strep GN?

Answer 17

Get confirmation from the patient’s PCP that they genuinely had Strep pharyngitis a few weeks ago.
Can also test for anti-Streptolysin O Abs.

Question 18

Treatment / prognosis of post-Strep GN?

Answer 18

It’ll go away on its own.

Question 19

Renal presentation of SLE?

Answer 19

RPGN

Question 20

3 serological findings in lupus nephritis?

Answer 20

Positive ANA
Positive anti-DNA Abs.
Hypocomplementemia.

Question 21

How does lupus nephritis look by H&E?

Answer 21

Proliferation limited to mesangium… or like post-infectious GN but with fewer PMNs.
(but the exam wouldn’t ever ask you distinguish lupus nephritis from post-infectious GN this way)

Question 22

On what side of the GBM are immune complexes deposited in lupus nephritis?

Answer 22

On the endothelial side - “subendothelial deposits”.
(one can imagine that lupus-associated immune complexes are pre-formed in the blood, and thus get stuck on the blood side of the GBM –whether or not that’s accurate)

Question 23

Thickening of glomerular capillary loops was an H&E finding associated with what disease process?

Answer 23

Lupus nephritis (not sure how specific this is, though)

Question 24

Which immune elements are seen in lupus nephritis immune complexes? (eg. IgG vs. IgA vs. complement)

Answer 24

All of them - a “full house” pattern.

IgG, IgA, IgM, C1q, C3, C4

Question 25

In IgA nephropathy, what are typical H&E findings? (2 things)

Answer 25

Mesangial hypercellularity.

Focal crescents.

Question 26

Where are the immune complexes deposited in IgA nephropathy?

Answer 26

In the mesangium.

Question 27

What’s a variant of IgA nephropathy that affects the skin?

Answer 27

Henoch-Schoelein Purpura

Question 28

4 aspects of Henoch-Schoenlein Purpura?

Answer 28

RPGN.
Purpura.
Arthritis.
Colitis.

Question 29

In “small vessel vasculitis” what vessels are affected?

Answer 29

Small arteries -> veins.

Question 30

What’s a common cause of pauci-immune GN?

Answer 30

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Question 31

Light microscopy findings in ANCA-associated small vessel vasculitis -> GN?

Answer 31

Vasculitis with fibrinoid necrosis (but this is hard to find).
Crescents with segmental necrosis.