1. Urinary System Tutorial Glomerulonephritis

2. The renal biopsy Glomeruli Renal tubules and Interstitium Vasculature
Glomerulonephritis
Renal tubules and Interstitium
Acute tubular necrosis
Acute interstitial nephritis
Chronic tubulointerstitial nephritis
Vasculature
Nephrosclerosis
Renal artery sclerosis

3. Normal structure of the glomerulus

4. Presentation of glomerular disease
Nephrotic syndrome / Proteinuria
Proteinuria (> 3.5g protein / day)
Hypoproteinaemia
Oedema
Hyperlipidaemia
Nephritic syndrome / Haematuria
Haematuria
Lesser amounts of proteinuria
Hypertension
Progressive renal failure

5. Pathogenesis of glomerular disease
Immune mediated
Immune complex formation/deposition
Intrinsic glomerular antigens (anti-GBM)
Circulating antigens deposited in glomerulus (Membranous)
Circulating immune complexes deposited in glomerulus
Activation of complement
Cytokine release
Neutrophil / macrophage recruitment and activation
Activation of coagulation system

6. Pathogenesis of glomerular disease
Immune mediated
Subepithelial immune complexes
less inflammation
BM alterations +/- podocyte damage
Proteinuria
Subendothelial immune complexes “inflammatory GN”
more inflammation and cellular proliferation
Vessel damage
Haematuria
BM complexes
Either presentation, usually haematuria

7. Pathogenesis of glomerular disease
Non-immune mediated
Activation of complement
“inflammatory GN” like picture but no immune deposits
Epithelial cell injury
Toxins / cytokines / unknown factors
Loss of foot processes
Detachment from BM
Proteinuria

8. Glomerular response to injury
Increased cells (Hypercellularity)
Seen in “inflammatory diseases”
Proliferation of mesangial and endothelial cells
Inflammatory cells
Proliferation of epithelial cells +/- crescent formation
Increased matrix / connective tissue (Hyalinization / Fibrosis)
Hyalinization = accumulation of pink homogenous material
Plasma protein/BM/Mesangial matrix
Eventually leads to Fibrosis
Increased basement membrane
Thickened capillary loops
Increased BM / immune deposits

9. Investigation of glomerular disease
Histopathology / Light microscopy
Glomeruli
Hypercellularity
Increased matrix / Hyalinization / Fibrosis)
Thickened basement membrane
Secondary changes in tubules/interstitium
Amount of tubular atrophy and fibrosis is a sensitive indicator of prognosis
Associated large vessel disease

10. Investigation of glomerular disease
Immunofluorescence
Formation of immune complexes with deposition of antibodies in glomerulus
IgG, IgA, IgM
Basement membrane, mesangium
Linear or granular pattern
Electron microscopy
Changes in podocytes, basement membranes and mesangium
Location and presence of immune deposits (subepithelial, subendothelial, basement membrane)

11. Classification of glomerular disease
How many glomeruli?
Focal = only some glomeruli
Diffuse = all glomeruli affected
How much of a single glomerulus?
Segmental = only part of the glomerulus
Global = the entire glomerulus
Primary vs Secondary
primarily renal disease vs renal complication of systemic disease

12. Glomerular diseases associated with nephrotic syndrome
Primary
Minimal change disease
Membranous GN
Focal segmental glomerulosclerosis (FSGS)
Secondary
Diabetic nephropathy
Amyloidosis

13. Glomerular diseases associated with nephritic syndrome
Primary
Postinfectious / Diffuse proliferative GN
Membranoproliferative GN
IgA nephropathy (Mesangioproliferative GN)
Crescentic GN
Secondary
HSP
Systemic vasculitis
SLE
Systemic sclerosis

14. Causes of the nephrotic syndrome
(Minimal change disease)

15. Minimal change disease
Commonest cause of nephrotic syndrome in children
Can occur in adults
Characterised by
Lack of glomerular changes on light microscopy
Lack of immune deposits
Good response to steroids
Pathogenesis
Circulating factor causing damage to podocytes (glomerular epithelial cells)

16. Minimal change disease
Light microscopy (LM) – Normal
Immunofluorescence (IF) – Normal (no immune deposits)
Electron microscopy (EM) – Fusion of podocyte foot processes

19. Membranous GN Commonest cause of nephrotic syndrome in adults
Idiopathic (85%) or secondary (15%) to:
Neoplasms (lung, colon, melanoma)
Autoimmune disease (SLE, thyroiditis)
Infections (Hep B, syphilis, malaria)
Drugs (Penicillamine, gold)
40% progress to chronic renal failure (CRF)
Pathogenesis
Subepithelial immune deposits
Thickening of BM between deposits – eventually envelopes and covers the deposits

20. Membranous GN Light microscopy (LM)
Thickened capillary BM
BM spikes on silver stain
Immunofluorescence (IF) – diffuse granular GBM staining
Electron microscopy (EM) – subepithelial deposits

25. FSGS Idiopathic or secondary to: Characterised by:
Other glomerular disease (IgA)
Other renal disease (chronic reflux / pyelonephritis / interstitial nephritis)
Systemic disorder (HIV)
Drugs (Heroin)
Characterised by:
Sclerosis of portions of some, not all glomeruli
Often progresses to chronic renal failure (CRF)
Recurs in 25-50% renal transplants

26. FSGS Light microscopy (LM) Immunofluorescence (IF)
Focal segmental sclerosis
Some normal glomeruli
Immunofluorescence (IF)
IgM and C3 deposition in sclerotic areas
Electron microscopy (EM)
Fusion of podocyte foot processes

28. Postinfectious / Diffuse proliferative GN
Characterised by
Onset 1 – 4 weeks after upper respiratory / cutaneous infection with Group A -haemolytic streptococci
Can occur after a number of other bacterial, viral and parasitic infections
Elevated antistreptococcal antibody and decreased C3
Secondary to anti-strep antibodies binding to glomerular components
Usually resolves within 6 weeks

29. Postinfectious / Diffuse proliferative GN
Light microscopy (LM)
Diffuse glomerular proliferation
Immunofluorescence (IF)
Granular BM IgG, IgM, C3
Electron microscopy (EM)
Subepithelial deposits

32. Membranoproliferative GN
Type I:
Immune complex disease
Idiopathic or secondary to Neoplasm, Autoimmune disease, Infections, Drugs
Subendothelial immune complexes
Type II:
Complement activation
BM deposits (dense deposit disease)
50% progress to chronic renal failure (CRF)
High recurrence rate in renal transplants
Characterised by
Thickened capillary loops
Glomerular hypercellularity due to mesangial proliferation
Mesangial interposition – double GBM’s (Type I)

33. Membranoproliferative GN
Light microscopy (LM)
Mesangial proliferation
Thickened capillary BM
Double BM’s on silver stain (Type I)
Immunofluorescence (IF)
Type I: Granular BM and mesangial IgG, IgM, C3
Type II: Granular BM C3
Electron microscopy (EM)
Type I: Subendothelial deposits and mesangial interposition
Type II: Dense deposits in GBM

37. IgA Nephropathy Mesangioproliferative GN
Pathogenesis
Increased mucosal IgA secretion in response to inhaled/ingested antigens
Glomerular (mesangial) deposition of IgA
Characterised by episodic haematuria following respiratory tract infections
50% progress to chronic renal failure (CRF)
Recurs in 20-60% of transplants
Varying histology

38. Mesangioproliferative GN
Light microscopy (LM)
Increased mesangial matrix
Mesangial proliferation
Focal sclerosis (FSGS)
Immunofluorescence (IF) – mesangial IgA
Electron microscopy (EM) – mesangial deposits

41. Crescentic GN Rapidly progressive GN
Characterised by
Glomerular crescents
Accumulation of cells in Bowman’s space
Inflammatory cells, fibrin and epithelial cell proliferation
Compression of glomerulus
Rapidly progressive clinical course
Pathogenesis
Damage to glomerular vessels
Egress of inflammatory cells and fibrin into Bowman’s space
Proliferation of epithelial cells

42. Crescentic GN Rapidly progressive GN
Pathogenesis
Type I – anti-GBM antibodies
linear deposition of IgG
May bind to alveolar BM in lung = Goodpasture’s disease
Type II – immune complexes
Idiopathic or secondary to autoimmune disease or other GN
SLE
HSP
IgA nephropathy
Postinfectious GN
Type III – pauci-immune
Idiopathic or secondary to systemic vasculitis
Wegeners
PAN

43. Crescentic GN Light microscopy (LM) Immunofluorescence (IF)
Cellular crescents of epithelium and inflammatory cells
Fibrotic crescents
Immunofluorescence (IF)
Type I: linear IgG
Type II: granular IgG
Type III: no deposits
Electron microscopy (EM)
Type II: subendo, mesangial and subepi deposits