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Urinary System Tutorial Glomerulonephritis

Urinary System Tutorial Glomerulonephritis. 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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Urinary System Tutorial Glomerulonephritis

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  1. Urinary System TutorialGlomerulonephritis

  2. The renal biopsy • Glomeruli • 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

  17. 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

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

  19. 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

  20. 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

  21. 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

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

  23. 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)

  24. 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

  25. 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

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

  27. 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

  28. 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

  29. 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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