01-09 PATH: Glomerular Dzs

Question 1

charges on glomerulus

Answer 1

endothelium - neg charge from polyanionic GPs

podocyte - neg charged glycocalyx

Question 2

major components of GBM

Answer 2

Type IV collagen
proteoglycans (esp. heparan sulfate)
laminin

Question 3

1. Anti-GBM nephritis

Answer 3

IN SITU IMM CMPLX DEPOSITION (like membranous GN)
Abs-against intrinsic BM Ags (alpha chain of Type IV collagen)
—IF: linear
—in Goodpasture’s synd, anti-GBM Abs cross-react with alveolar BMs in the lung.

Question 4

2. Membranous GN

Answer 4

IN SITU IMM CMPLX DEPOSITION (like anti-GBM)
—Abs against M-type phospholipase A2 receptor on foot processes of visc epithelial cells
—Ab binds —> activates complement —> sheds imm aggregates —> subendo deposits

Question 5

3. Circulating immune complex nephritis

Answer 5

CIRCULATING IMM CMPLX DEPOSITION
—Cmplxs not specific to nephron, just get stuck there
—depositions in the mesangium and subendoethelial areas in a GRANULAR pattern

Question 6

terms to describe extent/regionality of renal damage?

Answer 6

@ kidney level: diffuse, focal

@ glomerular level: global, segmental

Question 7

I.F. linear pattern ddx

Answer 7

– anti-GBM disease if intense (should be confirmed)
– light chain deposition disease
—membranoproliferative GN (MPGN) type II

Question 8

I.F. granular pattern ddx

Answer 8

granular pattern = immune complexes
– mesangial: IgA and lupus nephropathy
– cap. wall: membranous
– combined: lupus, acute post-infectious GN

Question 9

nephrotic syndrome

Answer 9

cytokines damage neg charge of BM —> leaks protein
—proteinuria >3.0g/d
—hyperlipidemia b/c liver make lipoprot to try and maintain oncotic pressure
—hypoalbuminemia
—peripheral edema (2° to hypoalb. and Na+ ret)
—hypercoag b/c anti-thrombin 3 peaces out

Question 10

nephritic syndrome

Answer 10

neutrophils attack BM —> hematuria
—hematuria w/ red cell casts in the urine
—azotemia
—oliguria
—mild to moderate HTN

Question 11

Most common nephrotic syndrome DDX

Answer 11

1. minimal ∆dz
2. FSGS: focal segmental glomerulosclerosis
3. membranous GN
4. amyloidosis
5. DM

Question 12

Most common nephritic syndrome DDX

Answer 12

1. post-streptococcal GN
2. MPGN: membranoproliferative GN
3. lupus nephritis

Question 13

4. Minimal ∆ Dz

Answer 13

commonest NEPHROTIC syndrome in kids
—rapid onset
—90% 1°
—2° to NSAIDs, food rxn, bee stings, lymphoma
—normal light microscopy
—normal IF
—complete podocyte foot effacement on EM
—respond well to steroids

Question 14

5. FSGS

Answer 14

Focal Segmental Glomerulosclerosis
—Commonest NEPHROTIC syndrome in adults
—segmental cap collapse/scarring
—thickened BM, effacement of podocytes (but not as bad as MCD)
—bad news: progressive, poor tx response
—80% 1°; 20% 2° drugs, virus, genetics, small kidneys, obestity

Question 15

6. Membranous Glomerulopathy

Answer 15

• one of the commonest causes of NEPHROTIC syndrome in adults
• 1° and 2° forms (drugs, tumors, lupus, infections) • subepithelial immune deposits in capillary wall, which evolve over time
• may see spikes and holes in the GBM with special
stains
• IF: diffuse, granular pattern along the GBM (esp. IgG, C3)
• EM: subepithelial deposits with spike-like projections of the GBM between deposits

Question 16

7. Diabetes Mellitus

Answer 16

Causes a NEPHROTIC syndrome

EARLY Light micros
—glomerular hypertrophy
—thicker GBM
—wider mesangium
ADVANCED STAGE Light micr.:
—progressive thickening of GBM
—diffuse glomerulosclerosis
—nodular glomerulosclerosis (Kimmelstiel-Wilson
nodules) [can call this "KW Disease"]
—microaneurysms
—arteriolar hyalinization
IF: negative for deposits
EM: thick GBM, mesangial sclerosis

Question 17

8. amyloidosis

Answer 17

Causes a NEPHROTIC syndrome

• variable mesangial & GBM deposition of beta-pleated amyloid fibrils
• Congo Red positive, with apple green birefringence under polarized light
• EM: 8-12 nm random fibrils
• most common amyloid proteins are light chains
• other amyloid proteins include amyloid A, transthyretin, beta2-microglobulin, lysozyme, apolipoprotein AI or AII, others

Question 18

9. acute post-infection GN

Answer 18

Causes a NEPHRITIC syndrome

• prototype: post-streptococcal (uncertain Ag)
• LIGHT: diffuse prolif. (i.e. exudative) GN
—diffuse endocap prolif w/ WBC —> swollen, hypercellular glomerulus
• IF: granular deposits along GBM (esp. C3)
• EM: classic subepithelial “hump-like” deposits

Question 19

10. MPGN: Memebranoproliferative glomeulonephritis

Answer 19

Causes a NEPHRITIC syndrome

• a general pattern of injury as well as a particular disease
• 1° idiopathic forms but often 2° forms (the most common GN assoc w/ Hep B and C)
• may present with nephrotic and/or nephritic syndrome
• hypercellular glomeruli with leukocytes
• glomeruli are often hyperlobulated
• “tram-track” appearance due to duplication of GBMs, w/ subendothelial deposits, esp. C3
• vast majority progress to ESRD regardless of Rx

Question 20

11. lupus nephritis

Answer 20

Causes a NEPHRITIC syndrome

• 60-70% of SLE pts get it, w/ wide spectrum of disease
• WHO Classification: 6 classes
• LIGHT: wire loops, hyaline thrombi, fibrinoid necrosis
• IF: “full house” pattern of staining (everything stains positive, all 3 Ig’s, C3a, C1q and light chains)
• EM: mesangial deposits in all subtypes + peripheral deposits

Question 21

12. Alport syndrome

Answer 21

Causes a HEMATURIC Syndrome

• nephritis w/ hematuria accomp. by nerve deafness & ocular abnormalities
• caused by hetero group of mutations involved in collagen IV (α3 or α5) chain synth
• EM: fragmentation & splitting of the GBM (“basketweave” pattern)
• progresses to renal failure =(

Question 22

13. Thin basement membrane dz

Answer 22

Causes a HEMATURIC Syndrome

a.k.a. Benign familial hematuria
• persistent or intermittent microhematuria (non-progressive)
• ? atypical or variant form of Alport syndrome (similar mutations in some cases)
• EM: generalized thinning of GBM

Question 23

14. IgA Nephropathy (Berger’s)

Answer 23

Causes a HEMATURIC Syndrome

• commonest cause of GN worldwide (esp. in Asians)
• most pts present w/ gross or microscopic hematuria, buta few w/ nephrotic syndrome or renal failure
• most classically, a mesangioproliferative appearance, but variable
• IF & EM: IgA + deposits primarily in the mesangium
• same renal pathology is seen in Henoch-Schönlein syndrome, a systemic vasculitic disease with GI, joint, and skin manifestations

Question 24

15. Crescentic Glomerulonephritis

Answer 24

Causes a Rapidly-Progressing Renal Disease
—3 subtypes based on IF: granular, linear and pauci-immune
• crescent = sign of SEVERE glomerular injury
• cellular prolif along inside of B’s capsule and filling a part of B’s space.
– comprised of parietal epithelial cells, inflamm cells, and fibrin
– lesions evolve: cellular→fibrocellular→fibrous
• >50% glomerular involvement = “crescentic GN”
• fibrocellular or fibrous crescents indicate a probable poor response to Rx

Question 25

15a. Crescentic Glomerulonephritis w/ Linear IF

Answer 25

a. Linear = anti-GBM disease • IF: linear deposits of IgG + C3 • anti-GBM Abs may cross-react w/ pulm alve BM → hemorrhage (= Goodpasture’s)

Question 26

15b. Crescentic Glomerulonephritis w/ Granular IF

Answer 26

Granular = immune complex-mediated disease • may be a complication of almost any of the immune complex nephritides • IF: granular (“lumpy bumpy”) deposits

Question 27

15c. Crescentic Glomerulonephritis w/ Negative IF

Answer 27

IF negative = "pacui-immune" a. ANCA- b. ANCA+ (~80%) • often associated with a systemic vasculitis, such as Wegener’s granulomatosis, Churg-Strauss, or microscopic polyangiitis