“To be a great champion you must believe you are the best. If you’re not, pretend you are….!” – Muhammad Ali The only place success comes before work is in a dictionary…! Pathology of Glomerulonephritis Dr. Venkatesh Murthy Shashidhar Associate Professor of Pathology Fiji School of Medicine. Anatomy-Kidney Anatomy of Kidney Anatomy of Kidney Note the positions of Glomerulus Loop of Henley PCT, DCT, CT Cortex, Medulla, Pelvis. ↓GFR Renin Angiotensin Blood Pressure JGA Ultrastructure – Glom. capillary Filtration Membrane – Electron Micro. Capillary Space GBM Endothelium Urinary Space Podocyte Glomerular Filtration: Blood Cells Proteins 3.6nm/70,000MW Glomerular Capillary Lumen Collagen IV Laminin Fibronectin Entactin etc. L.R.I L.D. L.R.E + GBM Plasma Proteins FILTRATE Foot Process Podocyte (Visceral epithelium) Bowman’s Capsule Space Filtration Membrane 1. Fenestrated Endothelium 2. Lamina Rara Interna 3. Lamina Rara Densa 4. Lamina Rara Externa 5. Podocyte Slit membrane Capillary Lumen Normal Kidney: Normal Glomerulus (PAS) “The worst times in your life may contain seeds of the best. When you can see crisis as an opportunity, your life becomes not only easier, but more satisfying.” –Joe Kogel Disorders of Kidney: Congenital Malformations, ectopic, cysts, dysplasia. Acquired Glomerular diseases Tubulointerstitial diseases, Renal calculi. Neoplasms – carcinoma. Glomerular diseases: Primary Acute diffuse post streptococcal Lipoid nephrosis or minimal change IgA nephropathy Secondary SLE, Diabetes, Hypertension etc. Immune, Toxins, Metabolic Immune Glomerulonephritis: In-Situ immune complex deposition Tissue antigens - Goodpasture anti GBM Ag Planted antigens - infections, toxins, drugs. Circulating immune complex deposition. Endogenous - DNA as in SLE Exogenous - infections. Cell mediated Immune injury Diffuse Proliferative GN: Post streptococcal* common – (even others) Primary infection - Pharynx, skin, ear etc.. Kidney damage – 1-4 weeks after infection. Malaise, fever, nausea, edema*, ↑ASO, ↓C3 Resolution in 6-8 weeks. Immune Glomerulonephritis: 1. Antigen or Antibody - Immune reaction 2. Activation of complements, Neutrophils… 3. destruction of glomerular structure 4. Inflammation, exudation swelling. 5. ↓ blood flow, GFR, - 6. Oliguria, Proteinuria, Hematuria, Hypertension. Neutrophil Activity Proteases Reactive oxygen metabolites Arachidonic acid metabolites Other Mediators Cytotoxic antibodies Macrophages Platelets Resident glomerular cells Fibrin related products Clinical Syndromes: Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. Nephrotic syndrome. Gross proteinuria, hyperlipidemia, Acute renal failure (RPGN). Oliguria, loss of Kidney function - within weeks Chronic renal failure. Over months and years - Uremia Nephritic Syndromes : Diffuse Proliferative GN Post Streptococcal. Rapidly Progressive GN (or Crescentic) Post Streptococcal, Goodpasture’s, Focal Glomerulonephritis Primary: Bergers disease (IgA Nephritis) Secondary IgA nephritis, Henoch Schonlein purpura, SBE, Coeliac Disease etc. Post Streptococcal GN (Prol.GN): 1-4 weeks following streptococcal infection by nephritogenic strains (time for Ab formation) Immune mediated Granular deposits of IgG,IgM & C3 in GBM, (subepithelial location common) Humps in GBM on EM or IF Microscopy •Normal •Post Strepto GN •Inflammation •Proliferation •Swelling. •Narrow capillary •↓GFR-Renin-BP Diffuse Proliferative GN: Enlarged hypercellular glomeruli. Hyperplasia of epithelium & endothelium. Cell Swelling. Inflammatory cells. Collapsed capillaries. Obstruction to blood flow. IF- Diffuse Proliferative GN Pathogenesis of Diffuse PGN: Streptococcal infection – Antibody attack GBM - inflammation & proliferation. Glomerular capillary obstruction: J.G.A stimulation – Renin – high blood pressure Reduced filtration – raised blood urea Fluid retention – Oedema Damage to GBM: Unselective proteinuria (form Pr. casts in tubule) Haematuria (form RBC casts in tubule) Progression of DPGN: Poststreptococcal DPGN Complete Healing Focal segmental glomerulo sclerosis CGN Tubulo – Interstitial Damage Diseases of Kidney: summary Glomerulonephritis Glomerular diseases Destruction of glomeruli by immune or infections. Acute tubular necrosis Tubular diseases Necrosis of tubules by toxins or infections. Pyelonephritis Interstitial disease Infections Nephrosclerosis Vascular diseases –– thickening of blood vessels Hypertension leading to micro infarctions. Clinical Syndromes:Summary Nephritic syndrome. Oliguria, Haematuria, Proteinuria, Oedema. Nephrotic syndrome. Gross proteinuria, hyperlipidemia, Acute renal failure Oliguria, loss of Kidney function - within weeks Chronic renal failure. Over months and years - Uremia "It is our attitude at the beginning of a difficult task which, more than anything else, will affect its successful outcome." William James 1842-1910, Psychologist and Author Urine Microscopy : Cells Casts Crystals. Cells - epithelial, inflammatory, malignant. Casts – Protein cast of nephron – DCT/CT Suggest Kidney pathology – not URT. Protein, lipid, cells or mixed. Crystals suggest high concentration or altered solubility. WBC in Urine : Urine Oxalate Crystals: Granular Cast: Epithelial Casts in Urine: WBC Cast Urine: Formation of Casts: Red cell Casts in Urine: What is an RBC cast? Nephrolithiasis: stones. Urolithiasis Hydronephrosis: "If you tell the truth, you have infinite power supporting you; but if not, you have infinite power against you." --Charles Gordon Minimal Change Disease: Loss of Foot processes Membranous GN : Crescentic GN - (RPGN) Crescentic GN - (Trichrome Stain) Goodpasture Syndrome: Membranous GN : Chronic Glomerulonephritis: Urolithiasis: Ooouuuch…!
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