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Flashcards in Pathophysiology of glomerular disease Deck (12):
1

3 signs of glomerular disease

hematuria
proteinuria
reduced GFR

2

Immune mechanism of glomerular disease

1) Ab-mediated
- immune complexes (post-infectious)
- Ab against basement membrane (Goodpasture's disease, rapidly progressing glomerulonephritis)
- Ab on subendothelial/mesangial (BV side) produce inflammation
--> deposition leads to complement activation and chemoattraction of inflammatory cells, causes leukocyte recruitment, fibrin production, damage to glomerular barrier, increased ECM production
- Ab on subepithelial (podocyte side) do not produce inflammation

Cell-mediated: T-cells in minimal change disease

3

Hematologic mechanism of glomerular disease

Hyperfiltration/hyperperfusion - mechanical dmg to podocytes
Ischemia - collagen deposition in glomerulus

4

Other mechanisms of glomerular disease

Podocyte injury
Polyanion loss - loss of -ve charge in BM, allows proteins to cross (MCC)
Metabolic: familial - Fabry's disease, cystinosis, DB (glycosylation of BM proteins prevents degradation, inhibits turnover - more ECM)

5

Nephrotic syndrome

Non-specific, increased permeability of glomerulus
Primary signs: proteinuria, edema, hypoalbuminemia
Can also see hyperlipidemia and predisposition for coagulation
Cutoff of proteinuria: >3.5 g/day

6

Causes of nephrotic syndrome

1) Primary glomerulonephritis
MCD

2) Focal segmental glomerulosclerosis
- most common cause in adults

3) Membranoproliferative glomerulonephritis

4) Membranous nephropathy

7

MCD

- most common cause in children
- histology: nephron normal under light microscopy, lesions seen under EM (diffuse effacement/fusion of foot processes), loss of polyanion charge, detachment of epithelium, principal lesion in visceral epithelium - diffuse effacement of foot processes
- Etiology: secondary to prophylactic immunizations, RTIs, NSAIDs
- Treatment: usually highly responsive to corticosteroids and immunosuppression

8

Focal segmental glomerulosclerosis

Hematuria, HTN

Causes: idiopathic, HIV, advanced renal disease, decreased GFR

EM/LM: scars contain Ig and complement, diffuse effacement of foot proesses in sclerotic areas
focal detachment of epithelium
denudation of underlying BM

Tx: steroids
Prognosis: can develop renal disease

9

Membranous nephropathy

- most common nephrotic in old peole
- can occur with chronic glomerulonephritis
- proteinuria, renal impairment

Causes; idiopathic, malignancy, hep B, lupus, gold, penicillamine drugs

LM/EM: thickening of BM, subendothelial deposits

Tx: some response to steroids

10

Nephritic syndrome

Intraglomerular inflammation and renal dysfunction
Intrinsic renal disease or 2ndary to systemic process
Most common presentations:
- post-infectious glomerulonephritis (post-strep)
- IgA nephropathy - most common worldwide
- Lupus nephritis
- Rapidly progressive glomerulonephritis (Goodpasture's disease)

11

Differentiating nephrotic vs nephritic

Nephritic:
Proteinuria (mild-moderate)
HTN
Azotemia
RBC casts
Oliguria
Hematuria

Nephrotic:
Proteinuria (>3.5 g/day)
Edema
Cholesteremia
Hypoproteinemia

12

Corticosteroids in Tx of nephrotic syndrome

1st step in idiopathic nephrotic syndrome where renal biopsy is not indicated
reduce inflammation
help reduce proteinuria
help alleviate edema
Prednisone 4-8 weeks
If relapses: use cyclophosphamide

Adverse effects:
hyperglycemia
infection
weight gain, swelling
fat redistribution
psychiatric
muscular wasting/myopathy
osteoporosis
development suppression