Renal Week 1 - Nephrotic/nephritic Flashcards
2 protein components of podocyte slit diaphragm
Nephrin
Podocin
Classic and common mechanisms of pitting edema in nephrotic syndrome
Classic (low V, low P): low serum albumin -> low oncotic pressure -> fluid leaks out -> increased ADH/Na retention -> more fluid out
Common (high V, high P): primary defect in Na excretion -> retention
Complications of nephrotic syndrome
Hypercoagulable state: protein deficiency, increased ATIII production and renal vein thrombosis Infection (loss of Ig and complement) Decreased vitamin D Hypercholesterolemia HypoNa/K
Management of nephrotic syndrome
Low salt diet Diuretics BP control Decrease GFR (ACEI) Replace Vit D binding proteins
Hereditary Nephrotic Syndrome
Mostly kids
Mutation in nephrin or podocin
Foot process fusion on EM
Minimal change dz: age, UA, cell markers/pathogenesis
2-8 years old UA: 4+ protein, hyaline casts CD-80 expression on podocytes (usually on APCs) Foot process fusion on EM Circulating factor damaging podocyte
Associations of minimal change dz
Allergy
Hodgkin’s Lymphoma
NSAIDs
Treatment of minimal change dz
Steroids
Course of oral cytoxan for frequent relapsers
FSGS: age, UA, pathogenesis
20-40 years
UA: 4+ protein, hyaline casts, micro hem
Viral factor: HIV infecting podocyte
Genetic factor: APOL1 polymorphism (AA, sleeping sickness protection)
FSGS associations
Idiopathic HIV associated Sickle cell Obesity Heroin nephropathy
FSGS treatment
Steroids
Calcineurin inhibitors or other immunosuppresion
Anti-viral for HIV
HIV Nephropathy
FSGS
Tubular dilation
Reticulo-endothelial inclusions
Membranous nephropathy associations
Idiopathic CA (Lung esp) Lupus Hep B (tx interferon) Heavy metals
Membranous nephropathy: age, pathogenesis
Adults Immune complex disease Thickened BM Subepithelial deposits on podocyte side of BM (granular deposits on IF) Ab binding to PL A2 podocyte receptor
Membranoproliferative GN type I associations
Hep C (autoimmune, palpable purpura)
Low grade systemic infection
Neoplasm
CT disease (lupus)
MPGN type I presentation, pathogenesis
Endothelial deposits (WBC)
Complement is low due to activation (C3 and C4)
GBM thickening and hypercellularity
MPGN type II
Same presentation at type I
Low C3, nml C4 -> alternative pathway activation
Nephrotic syndromes: primary renal dz
Hereditary MCD FSGS MN MPGN (I and II)
Nephrotic syndromes: systemic
Diabetes
Amyloid and Light chain dz
SLE (membranous)
Nephritic syndromes: primary renal
Post strep GN
IgA nephropathy
RPGN (anti-GBM, idiopathic)
Nephritic syndromes: systemic
Vasculitis (ANCA associated) Immune complex (SLE, HSP)
Nephrotic syndrome: overall theme and major criteria
Increased glomerular permeability
- Albuminuria
- Hypoalbuminemia
- Edema
- Hyperlipidemia
Nephrotic mechanisms of injury
Non-inflammatory
Podocyte injury and retraction: loss of size selectivity and loss of polyanion
Injury to clathrin pit, absorbed and secreted as deposit
Progress into CRF
Renal amyloidosis: types, path, stain
Kidney involved in 85% Different LC types: AA/AL Fluffy pink in glomeruli and vessels Red congo stain/polarized light/granny apple green Spilled uncooked spaghetti
Causes of chronic renal failure
Most common: diabetes
Next: vascular/HTN dz
DM in CRF
Hyaline arteriolar disease (increased thickness)
Diabetic GS: hypercellularity, diffuse/nodular mesangial expansion, BM thickening
Uremia definition
Group of manifestations with severe loss of all renal functions
Nephritic syndrome: major criteria
Hematuria (RBC and casts)
Signs of aggressive disease and usual association
RPGN (2x Scr or 50%
Treatment of nephritic syndrome
Treat symptoms
Immunosuppression
Plasma exchange
4 examples of glomerulonephritis
IgA nephropathy (HSP = systemic,
IgA nephropathy: deposition, prognosis, type
Mesangial immune complex deposition
Focal
30% regress, 30% to ESRD, 40% chronic renal dz
Nephritic or nephrotic
Lupus nephritis: deposition, presentation, type, pathoneumonic finding
Mesangial (hematuria)
Subendothelial (hematuria, nephritic syndrome)
Subepithelial (proteinuria)
>90% scarring -> nephritic and progressive failure
Nephritic or nephrotic or both
Pathoneumonic = tubuloreticular body
Anti-GBM disease: deposition, presentation
Antibody to glomerular antigen (linear)
Usually bad: pulmonary-renal, crescents, RPGN
Big treatment
ANCA associated vasculitis: deposition, presentation, unique treatment
ANCA but few immune complexes seen
Usually bad: pulmonary-renal, RPGN
Normal treatment + B cell targeted therapy
ANCA vasculitis examples
Granulomatosis with polyangiitis (C-ANCA, PR3)
Microscopic polyangiitis (P-ANCA, MPO)
Eosinophilc granulomatosis (Churg-Strauss)(more P-ANCA)
Renal limited vasculitis (usually P-ANCA)
Two diseases that mimic nephritic dz
Benign Familial Hemauria (thin BM dz)
Alport’s dz (nephritis, deaf, ocular lesions)
Collagen IV mutation, basket-weave pattern on microscopy
Proliferative glomerulonephritis: types and consequences
Endocapillary: occlusion of capillary loops
Mesangial: >3 nuclei in space
Epithelial: crescents, fill Bowman’s space
Post-infectious GN: etiology, morphology, stain, tx
Post strep, acute nephritic
Diffuse proliferative
Starry sky on IF
Supportive therapy
IF Staining and diseases
Linear: Goodpasture’s, Anti-GBM
Granular: IgA, SLE, endocarditis, idiopathic
None: vasculitis, idiopathic
Renal lupus WHO classes
I = no change II = mesagnial glomerulitis III = Focal, segmental IV = Diffuse (>55%) V = membranous
