Nephrotic Syndrome Flashcards
Review of glomerular anatomy
- glomerular filtration barrier = endothelial cells, GBM, glomerular epithelial cells
- endothelial cells w/fenestrations
- mesangial cell = centrally located cell
- GBM = type IV collagen + glycoproteins + proteoglycan ==> negative charge
- epithelial cells = podocytes separated by slit diaphragms <== most important filtration barrier
Glomerular impermeability to protein mechanism
- charge barrier ==> GBM + epithelial are negatively charged ==> repels negatively charged proteins
- size barrier ==> slit pore diaphragm ==> nephrin helps interlock pores
Nephrotic syndrome definition
- =excessive leak of of protein through glomerulus
- albumin > 3 - 3.5 g/day = defect in glomerular permeability = “nephrotic-range proteinuria”
- proteinuria
- hypoalbuminemia
- edema
- hyperlipidemia (elevated serum cholesterol)
- lipiduria
Nephritic syndrome definition
- active inflammation w/in glomerulus ++. damage w/loss of filtration + reduced GFR
Pathophysiology of nephrotic syndrome: proteinuria + hypoalbuminemia
- proteinuria <== disruption of slit diaphragm
- hypoalbuminemia <== proteinuria
Pathophysiology of nephrotic syndrome: Edema
- decrease in serum albumin ==> decreased oncotic pressure ==> fluid passes into interstitium ==> decreased intravascular volume ==> renin-ag-ald ==> water/salt retention
Pathophysiology of nephrotic syndrome: Hyperlipidemia/lipiduria
- increased lipoprotein synthesis (VLDL, LDL) @ liver + decreased VLDL removal ==> increase in serum cholesterol
- increased cap wall permeability + hyperlipidemia ==> lipiduria
Common additional features in nephrotic syndrom
- increased risk for infections
- increased risk for thrombosis
- poor growth in children + osteomalacia
- protein malnutrition
Classifications of glomerular disease
- nephrotic syndrome = severe proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria, pitting edema
- nephritic sydrome = hematuria, RBC casts, some proteinuria, decreased GFR, HTN, edema
- asymptomatic proteinuria/hematuria
Renal nephritic diseases
Post Infectious (post strep)
IgA Nephropathy
Rapidly Progressive GN (RPGN)
Anti-GBM Nephritic
Idiopathic RPGN
Systemic nephritic diseases
Vasculitis (esp Wegener’s)
Large Vessel
Small Vessel
Hypersensitivity
Systemic Lupus
Henoch-Schonlein Purpura
Cryoglobulinemia
Wegener’s Granulomatosis
Renal nephrotic syndromes
Hereditary Nephrotic Syndromes
Minimal Change Disease
Focal Glomerular Sclerosis
Membranous Nephropathy
Membranoproliferative GN (MPGN)
Systemic disease w/nephrotic syndrome
Diabetes
Amyloid
Light Chain Deposition Disease
Lupus (SLE) Membranous Type
Etiology/pathology of Minimal Change Disease
- common cause of idiopathic nephrotic syndrome, esp. in children 2-4 (male>female)
- light microscopy ==> normal glomeruli
- EM ==> foot process fusion
- possibly mediated by T cell-derived circulating permeability factor
- expression of CD80 antigen in podocytes
Clinical presentation/treatment of Minimal Change Disease
- common sx: edema w/normal renal fxn and w/out HTN
- Labs: normal complement, severe hypoalbuminemia
- some cases w/Hodgkin’s disease
- Tx: steroids
Etiology/pathology of Focal Segmental Glomerulosclerosis (FSGS)
- most common in younger adults + African Americans
- LM = segmental scarring (sclerosis) in only some glomeruli (focal)
- IF=negative
- EM = diffuse foot process fusion
- FSGS <== circulating factor that affects podocytes
Clinical presentation/treatment of Focal Segmental Glomerulosclerosis (FSGS)
- Associated w/: prior MCD, heroin use, HIV infection or idiopathic
- Clinical:
- nephrotic syndrome +
- may be hypertensive w/microhematuria
- Tx:
- prolonged steroids
- sometimes cyclosporine
- HIV: antiretroviral + ACE-inhibitors
Etiology/pathology of Membranous nephropathy
- most common in older adults
- pathology:
- LM = thickening of GBM
- IF = granular deposits of immunoglobulin + complement along GBM
- EM = dense subepithelial deposits = immune complexes
- etiology:
- autoimmune: Ab against podocyte ==> immune complex ==> shed into subepithelial space
Clinical presentation/treatment of Membranous nephropathy
- Associated w/:
- Hep B
- drugs (gold, penicillamine)
- lupus
- cancer (lung, breast, GI)
- post-transplant
- 2/3 cases = idiopathic
- Clinical:
- nephrotic syndrome + edema
- normal complement
- may ==> HTN/renal fail over time
- Tx:
- steroids + cytotoxic (e.g. cyclophosphamide)
- ACE-inhibitors
Clinical presentation/treatment of MPGN
- Clinical:
- most = nephrotic but some = acute nephritis
- HTN
- adults commonly Hep C positive + cryoglobulins + RF + low complement
- Type I = low C4 + low C3
- Type II = normal C4 + low C3
- Tx:
- poor prognosis
Etiology/pathology of Membranoproligerative glomerulonephropathy
- idiopathic or Hep C infection
- idiopathic = @ older children/adolescents (females>males)
- type II = @ adolescents
- Path:
- LM (type I/II)= thick GBM + mesangial cell proliferation + lobulated appearance
- EM (type I) = subendothelial + mesangial deposits
- IF (type II) = only C3; no IgG
- Type I <== traping of circulating immune complexes
- Type II <== circulating nephritic factor
MPGN definition
- Membranoproliferative glomerulonephritis=
- proliferation @ mesangium + thick GBM
- MPGN type 1 = immune complex defnition
- MPGN type 2 = complement activation @ cap wall w/out immune deposits
Summary: Prevalence, Age/Sex in MCD, FGSG, MN, MPGN Type I
Summary: Acute nephritis, HTN, Serum complement in MCD, FGSG, MN, MPGN Type I
Summary: LM, IF, EM, Associations in MCD, FGSG, MN, MPGN Type I
Characteristics of Diabetic Nephropathy
- most common cause of nephrotic syndrome in adults
- nephrotic proteinuria +/- microhematuria
- renal biopsy=glomerulosclerosis + thick GBM
- tx: glucose/BP control + ACE-inhibitors
Characteristics of SLE
- lupus usually ==> nephritic glomerular disease
- can present w/membranous histologic pattern ==> proteinuria + nephrotic syndrome
- tx: prednisone + mycophenolate
Characteristics of Amyloidosis or plasma cell dyscrasia
- older patients could have multiple myeloma/plasma cell dyscrasia
- renal sx vs. systemic presentation
- common: free plasma light chains or monoclonal light chains @ urine
- renal biopsy: amyloid deposits (in amyloidosis) vs. nodular glomerulosclerosis (light chain disease)
