Pathophysiology of glomerular disease

Question 1

3 signs of glomerular disease

Answer 1

hematuria
proteinuria
reduced GFR

Question 2

Immune mechanism of glomerular disease

Answer 2

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

Question 3

Hematologic mechanism of glomerular disease

Answer 3

Hyperfiltration/hyperperfusion - mechanical dmg to podocytes

Ischemia - collagen deposition in glomerulus

Question 4

Other mechanisms of glomerular disease

Answer 4

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)

Question 5

Nephrotic syndrome

Answer 5

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

Question 6

Causes of nephrotic syndrome

Answer 6

1) Primary glomerulonephritis
MCD

2) Focal segmental glomerulosclerosis
- most common cause in adults

3) Membranoproliferative glomerulonephritis
4) Membranous nephropathy

Question 7

MCD

Answer 7

• 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

Question 8

Focal segmental glomerulosclerosis

Answer 8

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

Question 9

Membranous nephropathy

Answer 9

• 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

Question 10

Nephritic syndrome

Answer 10

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)

Question 11

Differentiating nephrotic vs nephritic

Answer 11

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

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

Question 12

Corticosteroids in Tx of nephrotic syndrome

Answer 12

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