Renal Pathology - Nephrotic Syndromes

Question 1

Nephrotic syndrome pathology (2):

Answer 1

• Increased GBM permeability

- Urinary loss of plasma protein

Question 2

Nephrotic syndrome clinical findings (4):

Answer 2

• Proteinuria (> 3.5 gm/day)
• Hypoalbuminemia
• Edema
• Hyperlipidemia and lipiduria

Question 3

Diseases primarily nephrotic (4):

Answer 3

• Membranous nephropathy
• Minimal-change disease
• Focal segmental glomerulosclerosis (FSGS)
• Membranoproliferative glomerulonephritis (MPGN)

Question 4

Membranous nephropathy - pathogenesis:

Answer 4

Chronic, immune-complex mediated

Question 5

Membranous nephropathy - light microscopy:

Answer 5

Diffuse thickening of glomerular capillary wall

Question 6

Membranous nephropathy - IF:

Answer 6

Granular, IgG and C3

Question 7

Membranous nephropathy - EM (3):

Answer 7

• Irregular dense immune-complex deposits between GBM and epithelial cells
• “Spikes and domes”
• Effaced foot processes on epithelial cells

Question 8

Membranous nephropathy - clinical features (4):

Answer 8

• Mild proteinuria, not selective
• Hematuria
• Mild HTN
• Course is indolent

Question 9

Most common cause of nephrotic disease in children:

Answer 9

Minimal-change disease

Question 10

Minimal-change disease - light microscopy:

Answer 10

No change

Question 11

MInimal-change disease - IF:

Answer 11

No Ig or complement deposits

Question 12

Minimal-change disease - EM (2):

Answer 12

• No electron-dense deposits

- Effacement of foot processes of visceral epithelial cells

Question 13

Minimal-change disease - clinical feature:

Answer 13

Highly selective, massive proteinuria (mostly albumin)

Question 14

Minimal-change disease - treatment:

Answer 14

Corticosteroids

Question 15

Most common cause of nephrotic syndrome:

Answer 15

Focal segmental glomerulosclerosis (FSGS)

Question 16

FSGS is associated with (4):

Answer 16

• HIV
• Heroin addiction
• Sickle-cell disease
• Morbid obesity

Question 17

FSGS - pathogenesis of visceral epithelial damage (3):

Answer 17

• Cytokines
• Genetically determined factors
• Affect components of slit diaphragm complex

Question 18

FSGS - pathogenesis of hyalinosis and sclerosis:

Answer 18

Plasma proteins exuding through hyperpermeable areas

Question 19

FSGS - light microscopy (4):

Answer 19

• Sclerosing of some but not all glomeruli (focal)
• Partial glomerular scarring/sclerosis (segmental)
• Affected capillary loops collapse
• Segmental hyalinosis in affected capillary walls

Question 20

FSGS - IF:

Answer 20

IgM and C3 in sclerotic areas +/- mesangium

Question 21

FSGS - EM (2):

Answer 21

• Diffuse effacement of foot processes in both sclerotic and nonsclerotic areas
• Focal detachment of epithelial cells and denudation of GBM

Question 22

Difference from minimal-change disease (3):

Answer 22

• Higher incidence of hematuria, reduced GFR and HTN
• Proteinuria more often nonselective
• Poor response to corticosteroid treatment

Question 23

MPGN type I - pathogenesis (2):

Answer 23

• Immune complexes in the glomerulus (Ags unknown)

- Activation of classical and alternative complement pathways

Question 24

MPGN type II - pathogenesis:

Answer 24

Activation of alternative complement pathway

Question 25

MPGN hypercellular glomerulus (3):

Answer 25

• Proliferation of mesangial cells
• Proliferation of capillary endothelium and influx of WBCs
• Crescents may be present

Question 26

MPGN - light microscopy (3):

Answer 26

• Hypercellular
• Thickened GBM
• Glomerular capillary wall has “tram-track” appearance

Question 27

MPGN type I - IF (2):

Answer 27

• C3 deposited in granular pattern

- IgG, C1q and C4 may also be present

Question 28

MPGN type II - IF:

Answer 28

C3 deposited in an irregular granular pattern or linear foci in BMs but not in dense deposits
- No IgG, C1q or C4

Question 29

MPGN type I - EM (2):

Answer 29

• Subendothelial electron-dense deposits

- May also be mesangial and subepithelial deposits

Question 30

MPGN type II - EM (2):

Answer 30

• Deposition of dense material into GBM

- Results in lamina densa becoming an irregular “ribbon-like” extremely electron-dense structure

Question 31

MPGN - clinical features (3):

Answer 31

• Children, adolescents and young adults
• Combined nephrotic-nephritic picture
• Slowly progressive, unremitting