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GLOMERULAR DISEASES

GLOMERULAR DISEASES. Antonio V. Cayco, MD Section of Nephrology. OBJECTIVES. Introduction Approach to Glomerular Diseases Syndrome Diagnosis Clinical Diagnosis Histologic Diagnosis Clinicopathologic Correlation General Principles of Management.

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GLOMERULAR DISEASES

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  1. GLOMERULAR DISEASES Antonio V. Cayco, MD Section of Nephrology

  2. OBJECTIVES Introduction Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation General Principles of Management

  3. CAUSES OF ESRD IN THE PHILIPPINES: Renal Registry Data, PSN, 2003

  4. Afferent arteriole Parietal EC Capillary loop Endothelium Macula densa Mesangium JG cells Urinary space Visceral EC Efferent arteriole

  5. Mesangium Normal Glomerulus

  6. Normal glomerulus

  7. PATHOLOGY Definition of Terms • Glomerulopathy vs. Glomerulonephritis • Primary vs. Secondary • Diffuse vs. Focal • Global vs. Segmental • Fibrosis vs. Sclerosis • Membranous vs. Proliferative • Endocapillary vs. Extracapillary

  8. Fibrosis – increase in the deposition of collagen fibers Sclerosis – increase in the amount of homo-genous nonfibrillar extracellular material Sclerosis

  9. Segmental – lesion involves < 50% of the glomerulus Sclerosis Global – lesion involves > 50% of the glomerulus Sclerosis

  10. Diffuse Global Glomerulosclerosis Focal – lesion seen in less than 50% of glomeruli Diffuse – lesion seen in more than 50% of glomeruli

  11. Mesangial cells Normal glomerulus Mesangial cells Proliferation – increase in the glomerular cell number Mesangial proliferativeGN

  12. Endocapillary proliferation Extracapillary proliferation

  13. Normal glomerulus Membranous – expansion and thickening of the glomerular basement membrane (GBM) by immune deposits

  14. Primary Mechanisms of Glomerular Injury

  15. Primary Mechanisms of Glomerular Injury

  16. Immunologic Glomerular Injury Humoral Antibody-Mediated Injury • Autoantibodies against intrinsic antigens (example: Goodpasture’s syndrome) • Autoantibodies against extrinsic “trapped antigens (example: Postinfectious GN) • Trapping of circulating immune complexes (example: Cryoglobulinemic GN) Cellular Mediated Injury

  17. GN Loss of nephrons Glomerular hyperfiltration Glomerular HTN Non-selective prtoteinuria Glomerular sclerosis Tubulointerstitial inflammation Ischemia Tubulointerstitial atrophy/fibrosis Two Final Common Pathways in Glomerular Injury

  18. OBJECTIVES Introduction Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation General Principles of Management

  19. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

  20. Syndrome Diagnosis History Physical Examination Ancillary Laboratory Tests • Chemistry • Serology • Urinalysis

  21. Syndromes inGlomerular Diseases

  22. Syndromes inGlomerular Diseases

  23. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

  24. C-ANCA: Cytoplasmic Antineutrophil Cytoplasmic Antibodies • C-ANCA • Antibodies against • Proteinase 3 • Associated with • Wegener’s ggranulomatosis

  25. P-ANCA: Perinuclear Antineutrophil Cytoplasmic Antibody • P-ANCA • Antibodies against • myeloperoxidase • Associated with a • variety of vasculitides • Non-specific for • Wegener’s granulomatosis

  26. Clinical Diagnosis

  27. Clinical Diagnosis

  28. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

  29. Indications for a Kidney Biopsy • Unexplained ARF • Unexplained RPRF • Adult nephrotic syndrome w/out systemic disease • Proteinuria < 2 g/d w/ deterioration of renal function • Proteinuria > 2 g/d • DM w/ acute onset of proteinuria and renal failure • DM with proteinuria but w/out retinopathy • Selected cases of Lupus nephritis

  30. Crescent

  31. Membrane thickening Mesangial expansion Cellular proliferation MPGN

  32. Deposits Splitting MPGN

  33. Normal glomerulus

  34. Fusion of foot processes Minimal Change Disease

  35. Sclerosis FSGS

  36. Foot process fusion FSGS

  37. Membranous Nephropathy

  38. Deposits Membranous GN

  39. Mesangial proliferation

  40. Mesangial IgA Deposits

  41. IgA Nephritis

  42. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

  43. Clinicopathologic Correlation * SLE, Postinfectious GN, IE, Cryoglobulinemia ** Wegener’s granulomatosis, Microscopic PAN

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