Nephrotic Syndrome Flashcards Preview

CVPR: Renal > Nephrotic Syndrome > Flashcards

Flashcards in Nephrotic Syndrome Deck (28)
Loading flashcards...
1

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

2

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

3

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

4

Nephritic syndrome definition

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

5

Pathophysiology of nephrotic syndrome: proteinuria + hypoalbuminemia

  • proteinuria <== disruption of slit diaphragm
  • hypoalbuminemia <== proteinuria 

6

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

7

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

8

Common additional features in nephrotic syndrom

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

9

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 

10

Renal nephritic diseases

Post Infectious (post strep)

IgA Nephropathy

Rapidly Progressive GN (RPGN)

   Anti-GBM Nephritic

   Idiopathic RPGN

11

Systemic nephritic diseases

Vasculitis (esp Wegener’s)

Large Vessel

Small Vessel

Hypersensitivity

Systemic Lupus

Henoch-Schonlein Purpura

Cryoglobulinemia

Wegener’s Granulomatosis

12

Renal nephrotic syndromes

Hereditary Nephrotic Syndromes

Minimal Change Disease

Focal Glomerular Sclerosis

Membranous Nephropathy

Membranoproliferative GN (MPGN)

13

Systemic disease w/nephrotic syndrome

Diabetes

Amyloid

Light Chain Deposition Disease

Lupus (SLE) Membranous Type

14

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

15

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

16

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

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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

25

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

26

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

27

Characteristics of SLE

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

28

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)