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Urinary System Tutorial
Glomerulonephritis
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The renal biopsy
• Glomeruli– Glomerulonephritis
• Renal tubules and Interstitium– Acute tubular necrosis– Acute interstitial nephritis– Chronic tubulointerstitial nephritis
• Vasculature– Nephrosclerosis– Renal artery sclerosis
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Normal structure of the glomerulus
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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
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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
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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
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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
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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
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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
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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)
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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
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Glomerular diseases associated with nephrotic syndrome
• Primary– Minimal change disease– Membranous GN– Focal segmental glomerulosclerosis (FSGS)
• Secondary– Diabetic nephropathy– Amyloidosis
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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
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Causes of the nephrotic syndrome
(Minimal change disease)
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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)
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Minimal change disease
• Light microscopy (LM) – Normal
• Immunofluorescence (IF) – Normal (no immune deposits)
• Electron microscopy (EM) – Fusion of podocyte foot processes
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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
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Membranous GN
• Light microscopy (LM)– Thickened capillary BM– BM spikes on silver stain
• Immunofluorescence (IF) – diffuse granular GBM staining
• Electron microscopy (EM) – subepithelial deposits
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FSGS
• Idiopathic or secondary to:– 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
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FSGS
• Light microscopy (LM) – Focal segmental sclerosis– Some normal glomeruli
• Immunofluorescence (IF)– IgM and C3 deposition in sclerotic areas
• Electron microscopy (EM)– Fusion of podocyte foot processes
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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
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Postinfectious / Diffuse proliferative GN
• Light microscopy (LM)– Diffuse glomerular proliferation
• Immunofluorescence (IF) – Granular BM IgG, IgM, C3
• Electron microscopy (EM)– Subepithelial deposits
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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)
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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
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IgA NephropathyMesangioproliferative 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
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Mesangioproliferative GN
• Light microscopy (LM)– Increased mesangial matrix– Mesangial proliferation– Focal sclerosis (FSGS)
• Immunofluorescence (IF) – mesangial IgA
• Electron microscopy (EM) – mesangial deposits
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Crescentic GNRapidly 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
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Crescentic GNRapidly 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
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Crescentic GN
• Light microscopy (LM)– 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
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