Nephrotic Syndrome Flashcards

1
Q

Review of glomerular anatomy

A
  • 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
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2
Q

Glomerular impermeability to protein mechanism

A
  • charge barrier ==> GBM + epithelial are negatively charged ==> repels negatively charged proteins
  • size barrier ==> slit pore diaphragm ==> nephrin helps interlock pores
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3
Q

Nephrotic syndrome definition

A
  • =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
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4
Q

Nephritic syndrome definition

A
  • active inflammation w/in glomerulus ++. damage w/loss of filtration + reduced GFR
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5
Q

Pathophysiology of nephrotic syndrome: proteinuria + hypoalbuminemia

A
  • proteinuria <== disruption of slit diaphragm
  • hypoalbuminemia <== proteinuria
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6
Q

Pathophysiology of nephrotic syndrome: Edema

A
  • decrease in serum albumin ==> decreased oncotic pressure ==> fluid passes into interstitium ==> decreased intravascular volume ==> renin-ag-ald ==> water/salt retention
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7
Q

Pathophysiology of nephrotic syndrome: Hyperlipidemia/lipiduria

A
  • increased lipoprotein synthesis (VLDL, LDL) @ liver + decreased VLDL removal ==> increase in serum cholesterol
  • increased cap wall permeability + hyperlipidemia ==> lipiduria
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8
Q

Common additional features in nephrotic syndrom

A
  • increased risk for infections
  • increased risk for thrombosis
  • poor growth in children + osteomalacia
  • protein malnutrition
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9
Q

Classifications of glomerular disease

A
  • nephrotic syndrome = severe proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria, pitting edema
  • nephritic sydrome = hematuria, RBC casts, some proteinuria, decreased GFR, HTN, edema
  • asymptomatic proteinuria/hematuria
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10
Q

Renal nephritic diseases

A

Post Infectious (post strep)

IgA Nephropathy

Rapidly Progressive GN (RPGN)

Anti-GBM Nephritic

Idiopathic RPGN

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11
Q

Systemic nephritic diseases

A

Vasculitis (esp Wegener’s)

Large Vessel

Small Vessel

Hypersensitivity

Systemic Lupus

Henoch-Schonlein Purpura

Cryoglobulinemia

Wegener’s Granulomatosis

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12
Q

Renal nephrotic syndromes

A

Hereditary Nephrotic Syndromes

Minimal Change Disease

Focal Glomerular Sclerosis

Membranous Nephropathy

Membranoproliferative GN (MPGN)

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13
Q

Systemic disease w/nephrotic syndrome

A

Diabetes

Amyloid

Light Chain Deposition Disease

Lupus (SLE) Membranous Type

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14
Q

Etiology/pathology of Minimal Change Disease

A
  • 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
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15
Q

Clinical presentation/treatment of Minimal Change Disease

A
  • common sx: edema w/normal renal fxn and w/out HTN
    • ​Labs: normal complement, severe hypoalbuminemia
    • some cases w/Hodgkin’s disease
  • Tx: steroids
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16
Q

Etiology/pathology of Focal Segmental Glomerulosclerosis (FSGS)

A
  • 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
17
Q

Clinical presentation/treatment of Focal Segmental Glomerulosclerosis (FSGS)

A
  • 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
18
Q

Etiology/pathology of Membranous nephropathy

A
  • 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
19
Q

Clinical presentation/treatment of Membranous nephropathy

A
  • 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
20
Q

Clinical presentation/treatment of MPGN

A
  • 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
21
Q

Etiology/pathology of Membranoproligerative glomerulonephropathy

A
  • 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
22
Q

MPGN definition

A
  • Membranoproliferative glomerulonephritis=
  • proliferation @ mesangium + thick GBM
  • MPGN type 1 = immune complex defnition
  • MPGN type 2 = complement activation @ cap wall w/out immune deposits
23
Q

Summary: Prevalence, Age/Sex in MCD, FGSG, MN, MPGN Type I

A
24
Q

Summary: Acute nephritis, HTN, Serum complement in MCD, FGSG, MN, MPGN Type I

A
25
Q

Summary: LM, IF, EM, Associations in MCD, FGSG, MN, MPGN Type I

A
26
Q

Characteristics of Diabetic Nephropathy

A
  • most common cause of nephrotic syndrome in adults
  • nephrotic proteinuria +/- microhematuria
  • renal biopsy=glomerulosclerosis + thick GBM
  • tx: glucose/BP control + ACE-inhibitors
27
Q

Characteristics of SLE

A
  • lupus usually ==> nephritic glomerular disease
  • can present w/membranous histologic pattern ==> proteinuria + nephrotic syndrome
  • tx: prednisone + mycophenolate
28
Q

Characteristics of Amyloidosis or plasma cell dyscrasia

A
  • 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)