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Nephrotic Syndrome Symptoms
- Hyperproteinuria (> 3.5g/ day)
- Hyperlipidemia
- Hypercoaguability (due to loss of ATIII in urine)
- Edema
- Hypoalbuminemia
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Nephritic Syndrome (Acute Nephritis) Symptoms
- Hematuria, RBC casts in urine
- Azotemia
- Oliguria (decreased urine output)
- Mild-to-moderate HTN
- Proteinuria and edema (less severe than in nephrotic syndrome)
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IF deposits:
FSGS?
MG?
MCD?
MPGN Type I?
MPGN Type II?
Post-infectious Glomerulonephropathy?
Lupus Nephritis?
IgA Nephropathy?
Alport?
Anti-GBM?
- FSGS: IgM, C3
- MG: IgG (granular), IgA (in 25%)
- MCD: Negative
- MPGN Type I: IgG, C3 (+/- IgM)
- MPGN Type II: C3, irregular/granular capillary wall and mesangium
- PIG: IgG, IgM, C3 (granular)
- Lupus Nephritis: Full House! IgG, IgM, IgA, C3, C1q, C4
- IgA Nephropathy: IgA in mesangium, C3 (NOT C1q, C4)
- Alport: None
- Anti-GBM: IgG (linear)
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Crescents
- MPGN (some)
- Anti-GBM: Goodpastures
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Serologic findings of p- or c-ANCA
Pauci-immune glomerulonephritis
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RPGN associated w/
- Lupus
- Membranoproliferative glomerulonephritis
- IgA nephritis
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Sclerosis of some, but not all glomeruli (focal)
Only a portion of the capillary tuft is involved (segmental)
Focal Segmental Glomerular Sclerosis
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Most common cause of nephrotic syndrome in the US
Focal Segmental Glomerular Sclerosis
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Hallmark of FSGS
Visceral epithelial damage
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Response to corticosteroid therapy:
FSGS?
MCD?
- FSGS- poor response
- MCD- great response
- MG- variable response
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FSGS: LM
Sclerosis and collapse of glomerular capillary segments; hypercellularity of affected glomeruli; Hyalinosis
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FSGS: IF
Granular IgM and C3 deposits
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FSGS: EM
- Effacement of foot processes
- Vacuolization of visceral epithelial cells
- Widening of lamina rara externa
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Focal cystic dilation of tubule segments and tubuloreticular inclusions (in endothelial cells via EM)
FSGS HIV-associated nephropathy
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Nephrotic syndrome w/ thromboembolic episodes
Membranous Glomerulonephropathy
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MG: LM
- Thickened capillary walls
- Spikes (silver stain)
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MG: IF
Granular IgG (IgA in 25%)
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MG: EM
Subepithelial dense deposits
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Common in children, often follows respiratory infxn or immunization
Minimal Change Disease
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Minimal Change Disease is associated w/
Hodgkin Lymphoma
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MCD: EM
- Effacement of podocytes
- Lipid droplets in the interstitial and tubular cells
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2 Nephrotic Syndromes w/ effacement of foot processes
- Focal Segmental Glomerular Sclerosis
- Minimal Change Disease
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Occurs in myeloma patients
Amyloidosis
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Two types of Amyloidosis
- AL (light chain)
- AA types (SAA protein)
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Amyloidosis: LM
Thickened vessels, expanded glomerular matrix
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Amyloidosis: IF
Light chains (AL, kappa or lambda monoclonality)
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Amyloidosis: EM
Straight, non-branching fibrils
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Characteristic stain of Amyloidosis
Apple green birefringence w/ Congo Red stain
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3 Types of Membranoproliferative Glomerulonephritis (MPGN)
- Type I: Immune complex mediated; classical and alternative
- Type II: Circulating C3 nephritic factor; alternative
- Type III: Features Type I and membranous glomerulopathy
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Nephrotic Syndrome, often w/ a nephritic component (hematuria), that affects adolescents and young adults
MPGN
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Immune complex mediated, activates classical and alternative complement pathways
MPGN (Type I)
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MPGN Type I: LM
- Hypercellular glomeruli
- Tram track on PAS/silver stain
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Tram Track (silver stain) on LM
MPGN Type I
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MPGN Type I: IF
C3, IgG (+/- IgM) in capillary loops and mesangium
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MPGN Type I: EM
Subendothelial dense deposits
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MPGN Type 2: LM
- Thickening of GBM
- Dense deposits in segmental fashion "string of sausages"
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MPGN Type II: EM
Intramembranous dense deposits in lamina densa
*FSGS has widening of lamina rara externa
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Circulating C3 nephritic factor
MPGN Type II
This causes persistent C3 activation and hypocomplementemia
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Diabetic Nephropathy 5 Stages
- 1: Increased GFR, microalbuminuria
- 2: GFR and albumin excretion normalizes
- 3: HTN develops, microalbuminemia returns
- 4: Persistent proteinuria and HTN
- 5: ESRD
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Microangiopathy
Glycosylation of proteins --> thickened basement membrane
Diabetic Nephropathy
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Diabetic Nephropathy: LM
- Thickening of basement membrane
- Kimmelstiel-Wilson lesion
- Capsular "drop" lesions- eosinophili mass btw Bowman's capsule and parietal epithelium
- "Fibrin Cap Lesion"- eosinophilic lipid-rich structure found within glomerular capillary lamina
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Kimmelstiel-Wilson lesion
Diabetic Nephropathy
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Capsular drop lesions
Diabetic Nephropathy
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Fibrin cap lesion
Diabetic Nephropathy
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1-4 weeks after a strep infxn (Grp. A Beta-hemolytic) in children
Post-infectious Glomerulonephritis
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Symptom of Post-infectious Glomerulonephritis
Periorbital Edema
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PIG: LM
Glomerular Hypercellularity
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PIG: IF
Granular IgG, IgM, C3
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PIG: EM
Subepithelial "humps"- lumpy bumpy
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DNA and anti-DNA Abs to histones
Lupus Nephritis
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Lupus Nephritis Classes
- •Class I: Negative or minimal mesangial
- deposits
•Class II: More extensive mesangial deposits than class I
- •Class III: Diffuse mesangial deposits and widely scattered irregular
- deposits in capillary loops
•Class IV: Extensive immune complex deposits in capillaries and mesangium
•Class V: Uniform subepithelial deposits (especially IgG) in capillaries
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IgA deposits in mesangium (often w/ C3)
IgA Nephropathy (Berger's Disease)
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IgA Nephropathy (Berger's Disease) is seen w/ increased frequency in pts. w/
Gluten enteropathy (Celiac Disease)
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IgA Nephropathy: LM
Mesangial proliferation
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IgA Nephropathy: IF
- IgA deposits in mesangium
- C3 (NOT C1q, C4)
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IgA Nephropathy: EM
- Large dense depostis in the mesangium
- Subendothelial, subepithelial and intramembranous deposits
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Non-thrombycytopenic palpable purpura of the lower extremities; renal disease w/ hematuria
Henoch-Schonlein Purpura
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HSP occurs in
Children 3-8 (can occur in adults) often after onset of URTI
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HSP is associated w/
IgA Nephropathy (same microscopic findings)
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Hereditary Nephritis (Alport Syndrome): Defect in what
Type IV collagen (basement membrane)
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Mutation of Hereditary Nephritis (Alport Syndrome)
Sex-linked mutations of alpha-5 chain
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Presents w/ hematuria, gradual renal failure, neurosensory hearing loss, anterior lenticonus
Hereditary Nephritis (Alport Syndrome)
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Alport Syndrome: LM
- Gradual global sclerosis
- Interstitial foam cells
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Interstitial foam cells on LM
Hereditary Nephritis (Alport Syndrome)
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Alport: EM
Laminated, frayed, irregular basement membranes
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Attenuation of basement membrane 150-250 nm (normal 300-400 nm)
Thin Basement Membrane Lesion
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Mutations of Thin Basement Membrane Lesion
COL4A3, COL4A4 genes that encode alpha chains of type IV collagen
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Antibodies to NC1 domain of a3(IV) chain of type IV collagen
Anti-GBM
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Anti-GBM + Pulmonary involvement w/ hemorrhage
Goodpasture syndrome
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Prominent cellular crescents and linear IgG deposits
Anti-GBM Disease
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