01-09 PATH: Glomerular Dzs Flashcards
Alport syndrome mechanism
charges on glomerulus
endothelium - neg charge from polyanionic GPs
podocyte - neg charged glycocalyx
major components of GBM
Type IV collagen
proteoglycans (esp. heparan sulfate)
laminin
- Anti-GBM nephritis
IN SITU IMM CMPLX DEPOSITION (like membranous GN)
Abs-against intrinsic BM Ags (alpha chain of Type IV collagen)
—IF: linear
—in Goodpasture’s synd, anti-GBM Abs cross-react with alveolar BMs in the lung.
- Membranous GN
IN SITU IMM CMPLX DEPOSITION (like anti-GBM)
—Abs against M-type phospholipase A2 receptor on foot processes of visc epithelial cells
—Ab binds —> activates complement —> sheds imm aggregates —> subendo deposits
- Circulating immune complex nephritis
CIRCULATING IMM CMPLX DEPOSITION
—Cmplxs not specific to nephron, just get stuck there
—depositions in the mesangium and subendoethelial areas in a GRANULAR pattern
terms to describe extent/regionality of renal damage?
@ kidney level: diffuse, focal
@ glomerular level: global, segmental
I.F. linear pattern ddx
– anti-GBM disease if intense (should be confirmed)
– light chain deposition disease
—membranoproliferative GN (MPGN) type II
I.F. granular pattern ddx
granular pattern = immune complexes
– mesangial: IgA and lupus nephropathy
– cap. wall: membranous
– combined: lupus, acute post-infectious GN
nephrotic syndrome
cytokines damage neg charge of BM —> leaks protein
—proteinuria >3.0g/d
—hyperlipidemia b/c liver make lipoprot to try and maintain oncotic pressure
—hypoalbuminemia
—peripheral edema (2° to hypoalb. and Na+ ret)
—hypercoag b/c anti-thrombin 3 peaces out
nephritic syndrome
neutrophils attack BM —> hematuria —hematuria w/ red cell casts in the urine —azotemia —oliguria —mild to moderate HTN
Most common nephrotic syndrome DDX
- minimal ∆dz
- FSGS: focal segmental glomerulosclerosis
- membranous GN
- amyloidosis
- DM
Most common nephritic syndrome DDX
- post-streptococcal GN
- MPGN: membranoproliferative GN
- lupus nephritis
- Minimal ∆ Dz
commonest NEPHROTIC syndrome in kids —rapid onset —90% 1° —2° to NSAIDs, food rxn, bee stings, lymphoma —normal light microscopy —normal IF —complete podocyte foot effacement on EM —respond well to steroids
- FSGS
Focal Segmental Glomerulosclerosis
—Commonest NEPHROTIC syndrome in adults
—segmental cap collapse/scarring
—thickened BM, effacement of podocytes (but not as bad as MCD)
—bad news: progressive, poor tx response
—80% 1°; 20% 2° drugs, virus, genetics, small kidneys, obestity
- Membranous Glomerulopathy
• one of the commonest causes of NEPHROTIC syndrome in adults
• 1° and 2° forms (drugs, tumors, lupus, infections) • subepithelial immune deposits in capillary wall, which evolve over time
• may see spikes and holes in the GBM with special
stains
• IF: diffuse, granular pattern along the GBM (esp. IgG, C3)
• EM: subepithelial deposits with spike-like projections of the GBM between deposits
- Diabetes Mellitus
Causes a NEPHROTIC syndrome
EARLY Light micros —glomerular hypertrophy —thicker GBM —wider mesangium ADVANCED STAGE Light micr.: —progressive thickening of GBM —diffuse glomerulosclerosis —nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) [can call this "KW Disease"] —microaneurysms —arteriolar hyalinization IF: negative for deposits EM: thick GBM, mesangial sclerosis
- amyloidosis
Causes a NEPHROTIC syndrome
- variable mesangial & GBM deposition of beta-pleated amyloid fibrils
- Congo Red positive, with apple green birefringence under polarized light
- EM: 8-12 nm random fibrils
- most common amyloid proteins are light chains
- other amyloid proteins include amyloid A, transthyretin, beta2-microglobulin, lysozyme, apolipoprotein AI or AII, others
- acute post-infection GN
Causes a NEPHRITIC syndrome
• prototype: post-streptococcal (uncertain Ag)
• LIGHT: diffuse prolif. (i.e. exudative) GN
—diffuse endocap prolif w/ WBC —> swollen, hypercellular glomerulus
• IF: granular deposits along GBM (esp. C3)
• EM: classic subepithelial “hump-like” deposits
- MPGN: Memebranoproliferative glomeulonephritis
Causes a NEPHRITIC syndrome
- a general pattern of injury as well as a particular disease
- 1° idiopathic forms but often 2° forms (the most common GN assoc w/ Hep B and C)
- may present with nephrotic and/or nephritic syndrome
- hypercellular glomeruli with leukocytes
- glomeruli are often hyperlobulated
- “tram-track” appearance due to duplication of GBMs, w/ subendothelial deposits, esp. C3
- vast majority progress to ESRD regardless of Rx
- lupus nephritis
Causes a NEPHRITIC syndrome
- 60-70% of SLE pts get it, w/ wide spectrum of disease
- WHO Classification: 6 classes
- LIGHT: wire loops, hyaline thrombi, fibrinoid necrosis
- IF: “full house” pattern of staining (everything stains positive, all 3 Ig’s, C3a, C1q and light chains)
- EM: mesangial deposits in all subtypes + peripheral deposits
- Alport syndrome
Causes a HEMATURIC Syndrome
- nephritis w/ hematuria accomp. by nerve deafness & ocular abnormalities
- caused by hetero group of mutations involved in collagen IV (α3 or α5) chain synth
- EM: fragmentation & splitting of the GBM (“basketweave” pattern)
- progresses to renal failure =(
- Thin basement membrane dz
Causes a HEMATURIC Syndrome
a.k.a. Benign familial hematuria
• persistent or intermittent microhematuria (non-progressive)
• ? atypical or variant form of Alport syndrome (similar mutations in some cases)
• EM: generalized thinning of GBM
- IgA Nephropathy (Berger’s)
Causes a HEMATURIC Syndrome
- commonest cause of GN worldwide (esp. in Asians)
- most pts present w/ gross or microscopic hematuria, buta few w/ nephrotic syndrome or renal failure
- most classically, a mesangioproliferative appearance, but variable
- IF & EM: IgA + deposits primarily in the mesangium
- same renal pathology is seen in Henoch-Schönlein syndrome, a systemic vasculitic disease with GI, joint, and skin manifestations
- Crescentic Glomerulonephritis
Causes a Rapidly-Progressing Renal Disease
—3 subtypes based on IF: granular, linear and pauci-immune
• crescent = sign of SEVERE glomerular injury
• cellular prolif along inside of B’s capsule and filling a part of B’s space.
– comprised of parietal epithelial cells, inflamm cells, and fibrin
– lesions evolve: cellular→fibrocellular→fibrous
• >50% glomerular involvement = “crescentic GN”
• fibrocellular or fibrous crescents indicate a probable poor response to Rx
