3. Pathogenesis of glomerular diseases
Genetic –
• Mutations in exons of DNA
• Mutations in the regulatory genes controlling DNA transcription
• Abnormal post transcriptional modification of RNA transcripts
• Abnormal post translational modifications of proteins
Immunological injury –
• AG – Ab – Glomerulus – complement activation – chemtactic and
anaphylatoxin-like factors
Coaglation system activation –
• Direct or indirect
• Activation of kinin system- chemtactic and anaphylatoxin-like factors
4. Pathology
• Proliferation of glomerular cells –
Generalized – all glomeruli
Focal – some glomeruli
Diffuse – all parts of glomeruli
Segmental – some parts of glomeruli
Endothelial, mesangial cells, mesangial matrix proliferation
Increased glomerular size – norrow the lumens of glomerular
capillaries – renal insufficiency
• Crescent formation in bowman capsule –
Proliferation of parietal epithelial cells
Composition – Fibrin, epithelial cells, BM-like material
macrophages
Fibroepithelial crescent – invasion of connective tissue
Crescent – glomerular cell death – eosinophilic appearance
5. • Exudation of blood cells –
Neutrophils, eosinophils, basophils, mononuclear cells
• Increase in the width of the BM
• Tubulo interstitial fibrosis –
Injury to the renal tubules – MNC infiltration – soluble factors –
fibrosis – destruction of renal tubules and peritubular capillaries
Pathology
6. Acute poststreptococcal GN
It is characterized by sudden onset of gross hematuria, edema,
hypertension and renal insufficiency
Etiology and epidemiology –
• Nephritogenic strains of group-A β hemolytic streptococci –
• Throat serotype – 1,3, 4, 12,25
• Skin serotype – 2, 49, 55, 57, 60
•
• Pharyngitis - ( cold weather )
• Pyoderma - (warm weather )
7. Pathogenesis & Pathology
Pathogenesis –
Immune complex mediated injury
Alternate pathway activation
Pathology -
• Light microscopy –
All glomeruli enlarged,
Bloodless
Mesanchymal cell proliferation
Mesanchymal matrix proliferation
PMN cell infiltration
Crescent formation
• Immunofluorescence microscopy –
Lumpy-bumpy deposits of Ig and complements in BM & mesangium
• Electrone microscopy –
Electrone dense deposits or ‘humps’ on epithelial side of BM
8. Clinical manifestations
• Age – 5-12 yrs, uncommon before 3 yrs
• Pharyngitis – 1-2 wks
• Pyoderma – 3-6 wks
• Asymptomatic microscopic hematuria, normal RFT to
ARF
• Edema, HT, oliguria, encephalopathy, CHF,nephrotic
syndrome(10 20%)
• Malaise, lethargy, abdominal pain, fever, acute subglottic
edema, air way obstruction
• Acute phase – 6-8 wks
• Proteinuria and HT – 4-6 wks
• Microscopic hematuria – 1-2 yrs
9. Diagnosis
Normal urine examination -
No cast,except hyaline 1/hpf
RBC – 1-2/hpf
WBC – Male – 0-3/hpf
Female -0-5/ hpf
Epithelial cell few
Bacteria – no organism/oif : unspun
<20/hpf : spun
Urine in AGN –
RBC,
RBC cast,
proteinuria,
PMN cells
10. Diagnosis
Blood –
Normochromic anemia
C3 level decreased
ASLO – throat infections
2-5 yrs – 120-160 todds unit
6-9 yrs – 240 todds unit
10-12 – 320 todds unit
> 13 yrs - 320 todds unit
DNase B – skin infection
Positive throat culture
11. Diagnosis
Streptozyme test –
( SLO, DNase B, Hyaluronidase, Streptokinase, NADase )
Renal biopsy –
- ARF
- Nephrotic syndrome
- Absence of evidence of streptococcal infection
- Normal complement level
- Hematuria, proteinuria and low C3 >2 months
14. Membranous Glomerulonephritis
Etiology –
SLE, chronic ITP, neuroblastoma, gonadoblastoma,
syphilis,HBV infection, gold .penicillamine.
Pathology –
LMC – Diffuse thickening of GBM without significant proliferative
changes.
Deposition of membrane-like material by visceral epithelial
cells
Resembles ‘spikes’ on epithelial side of GBM.
IFM – Granular deposits of IgG & C3 on epithelial side.
EMC – Linear staining of IgG,IgA,C3 on tubular BM
15. Clinical features –
Most common in 2nd
decade, nephrotic syndrome (2-6%),
microscopic or gross hematuria, HT (20%).
Diagnosis –
C3 normal except SLE.
Kidney biopsy –
Nephrotic syndrome > 10yrs, Unexplained hematuria and
proteinuria, increased risk of RVT.
Treatment –
Salt restriction, diuretic, prednisone+cyclophosphamide or
chlorombucil
Prognosis –
CRF (20%), Active disease (40%)
Membranous Glomerulonephritis
16. Pathogenesis –
C3 nephritic factors- activates alternative complement pathway
Pathology –
Type 1 –
LMC - most common
- Accentuation of lobular pattern
- Generalized increased in mesangial cells & matrix
- GBM splitting from interposition of mesangial cytoplasm & matrix b/w
- endothelial cell and GBM
- Formation of crescent
IFMC – C3 & lesser amount of Ig in mesangium and along the peripheral
capillary in a lobular pattern
EMC – immune complex-like deposits in mesangial and subendothelial
regions
Type 2 –
-less common, irregular ribbon-like thickening of GBM,
crescent common, splitting rare.
Membranoproliferative (mesangiocapillary)
Glomerulonephritis (MPGN)
17. Type 3 –
Similar to type 1 in LMC & IFMC
EMC – subepithelial and subendothelial
Clinical features –
Most common in 3rd decade, nephrotic syndrome, acute
nephritic syndrome, RFT-normal to decreased, HT.
Diagnosis –
C3 decreased
Renal biopsy – Nephrotic syndrome >10yrs, significant proteinuria
with microscopic hematuria, decreased C3 >8wks.
Treatment –
Long term prednisone EOD
Prognosis –
ESRD (50%), type 2 worst prognosis, recurrent MPGN in kidney
transplant, type 1(13%), type 2(90%)
Membranoproliferative (mesangiocapillary)
Glomerulonephritis (MPGN)
18. SLE Nephritis
Immune complex mediated injury, both T cell and B cell function alteration
WHO classification –
Type 1 – No abnormality
Type 2 – Mesangial lupus nephritis
2a – mild deposit
2b – moderate deposit
Type 3 – FSGN, subendothelial & mesangeal deposits,
necrosis,crescent, sclerosis.
Type 4 – Most common, most severe, diffuse proliferative lupus
nephritis, subendothelial & mesangeal deposits, ‘wire loop
lesions’ necrosis,crescent, sclerosis.
Type 5 – Membranuous lupus nephritis, least common, resembles
membranuous GN except mild to moderate mesangial
proliferation, decreased C3 level.
19. Clinical features –
• Adolescence , female
• All type 2 and some type 3 – hematuria, normal RFT, proteinuria <1g/day.
• Some type 3 and all type 4 - hematuria, decreased RFT, proteinuria,
nephrotic syndrome, ARF
• Type 5 – nephrotic syndrome.
Diagnosis –
ANA, antibody to double stranded DNA, C3-C4 level decreased.
Treatment –
• All patients – prednisone 4-6 months
• Type 3 & 4 – 6 monthly IV cyclophosphamide 500-1000mg/m2
followed by
every 3 monthly dosing for 18-36 months.
• Type 1 & 2 – azathioprine single dose daily, 1.5-2mg/kg/day
Prognosis –
Highest risk of progression in type 4
SLE Nephritis
20. Henoch-schonlein purpura nephritis
Pathology and pathogenesis –
• Immune complexes containing IgA1 deposition within the capillaries of the
skin, intestine and glomerulus.
• Crescent formation more common and extensive
Clinical manifestations –
• 1-3 wks after URI
• Gross hematuria (20-30%),
• Isolated microscopic hematuria
• Hematuria and proteinuria
• Acute nephritic syndrome
• Nephrotic syndrome
• Renal insufficiency
• Ureteritis
Prognosis –
Best - Isolated microscopic hematuria
Poor - Acute nephritic syndrome, Nephrotic syndrome
21. Rapidly Progressive (crescentic) GN
Classification –
1. Immune comlex mediated GN – PSGN, MPGN, lupus, HSP and IgA
nephritis.
2. Anti-GBM mediated GN – Goodpasture disease.
3. ANCA mediated GN –Microscopic PAN, Wegner granulomatosis.
Crescent formation.
Goodpasture disease –
-Pulmonary hemorrage and GN with antibody against type 4
collagen of alveolar BM and GBM.
-Continuous linear pattern of IgG along the GBM.
Diagnosis –
ANA, Normal C3, anti DNase B,
ANCA to MPO or proteinase-3
Treatment -
According to cause