1. Department of Nephrology, the First Affiliated Hospital Sun Yat-sun University Qiongqiong Yang 杨琼琼 Glomerular disease

3. outline Anatomy and function General pathogenesis Clinical syndromes and presentation Specific glomerular diseases

4. Anatomy and function

6. Anatomy Renal Function Remove wastes Maintain homeostasis Secrete EPO Diagram of a bisected kidney

8. Three-dimensional schematic drawing of the glomerulus Afferent arteriole Efferent arteriole Bowman’s Capsule Basement membrane Visceral Epithelium(Podocyte) Parietal Epithelium Capillary loops Bowman’s Space Endothelial cells Stucture of renal glomerulus Mesangial matrix and cell

9. Ultramicroscopic Stucture of glomerullar Capillaries Filtration Mem

11. Glomerular Anatomy Capillary Lumen Endothelial cell Glomerular basement membrane Epithelial cell Podocytes Electron micrograph Capillary Lumen 毛细血管腔 Endothelial cell 内皮细胞

12. Ultrastructure of normal glomerular capillary 系膜细胞 系膜基质 内皮细胞 上皮细胞足突

15. General pathogenesis

17. Antibody mediated GN - Circulating Immune complex Location: Mesangial and sub-endothelial

19. Antibody mediated GN - In-situ Immune complex (trapped Ag) Location: GBM sub-epithelial Extrinsic antigens planted within the glomerulus

20. Pathogenesis In situ immune complex Circulating immune complex Activation of T lymphocytes Acitvation of complements cytokines C5b-9 C5a,C3a Epithelial, mesangial, Endothelial cells Macrophage polynuclear leucocyte, platelets Mesangial cells oxidative stress, protease, matrix accumulations Glomerular Disease

21. Characterizations of glomerular disease ？

22. Glomerular Filtration Barrier

24. Characteristics of Glomerular Diseases Parameter Glomerular Tubulointerstitial Proteinuria MW of Protein Renal morphology RBC Morphology Massive>++ >1.5~2.0g/d Large/Medium/Small Symmetry dysmorphic Small amount<2+ <1.0g/d Small Asymmetry normal

25. Hematuria Isomorphic nonglomerular erythrocytes. The arrows indicate the so-called crenated erythrocytes 皱缩红细胞 , which are a frequent finding in nonglomerular hematuria. Dysmorphic glomerular erythrocytes . The dysmorphism consists mainly in irregularities of the cell membrane. Inset , Acanthocytes 棘红细胞 with their typical ring-formed cell bodies with one or more blebs 水泡 of different sizes and shapes. Examination of the urine sediment by a phase constrast microscope Dysmorphic glomerular erythrocytes>8000/ml,Acanthocytes>5%

26. Classification of Glomerular Disease Etiology Pathology Clinical Features

27. Clinical syndromes and presentation

29. How are glomurular diseases diagnosed ? Usually by history, physical findings, Urinalysis and other laboratory data. Occasionally a renal biopsy must be performed !

34. Pathology PAS MASSON H&E PASM

39. Dysmorphic glomerular erythrocytes

43. Light microscopy: diffuse mesangial hypercellularity H&E

44. mesangial hypercellularity PAS

45. Immunofluorescence microscopy: diffuse mesangial IgA IgA

46. Electron microscopy: mesangial electron-dense deposits.

47. The Patient Has IgA nephropathy!

56. Electron Microscopy: effacement and fusion of foot processes

57. The patient has Minimal change disease!

58. Introduction Incidence: Etiology: Clinical Features: Clinical Course: Loss of net negative charge on capillary basement membrane. Nephrotic syndrome. Prominent proteinuria & edema No hypertension Sensitive to steroid, relapse may occur. 80% of nephrotic syndrome in children Minimal Change Disease

60. Why is a thorough Clinical evaluation important in patients with the nephrotic syndrome ! Many such patients have an occult malignancy !

61. CASE III Lung Carcinoma

62. Silver PAS

63. CASE III LM-PASM:”spikes” along the GBM

64. CASE III IF: IgG deposition along GBM

65. CASE III EM: subepithelial electron dense material

66. It’s Clearly a case Of carcinoma related Membranous nephropathy !

68. Introduction Membranous Nephropathy Incidence: Etiology: Path: Clinical Course: Immune complex disease. May associated with carcinomas, infections, drugs, and heavy metals. Some adults develop ESRD. Diffuse, uniform basement membrane thickening with subepithelial projections (“spikes”). Commonly occurred in middle&old-aged people

69. How to treat the Nephrotic Syndrome?

70. Pathogenesis/Complication Liver Edema Hypoalbuminemia Glom inflammation Proteinuria ↑ Permeability↑ Lipoprotein Synthesis↑ Blood Lipid↑ Primary Secondary Causes Blood volume↓ Thrombosis CV disease↑ ARF Infection vitD deficiency Protein malnutrition Development↓

71. Treatment of NS Liver Edema Hypoalbuminemia Glom inflammation Proteinuria ↑ Permeability↑ Lipoprotein Synthesis↑ Blood Lipid↑ Primary Secondary Causes Causative Therapy Steroid/CTX/CsA ACEI/ARB Diuretics

72. Treatment of Complication Liver Edema Hypoalbuminemia Glom inflammation Proteinuria ↑ Permeability↑ Lipoprotein Synthesis↑ Blood Lipid↑ Primary Secondary Causes Blood volume↓ Thrombosis CV disease↑ ARF Infection Antithrombotic Anti-infection Diuretics/Dialysis Statins

73. How to use glucosteroids(1) 0.25mg/kg.d Slow the speed of tapering 1mg/kg.d×8w 0.5mg/kg.d Taper 5mg per 1-2week Maintenance for 1 year

74. How to use glucosteroids(1) 0.25mg/kg.d Slow the speed of tapering 1mg/kg.d×8w 0.5mg/kg.d Taper 5mg per week Maintenance for 1 year Sufficient initial dose

75. How to use glucosteroids(3) 0.25mg/kg.d Slow the speed of tapering 1mg/kg.d×8w 0.5mg/kg.d Taper 5mg per week Maintenance for 1 year Sufficient initial dose Slow tapering

76. How to use glucosteroids 0.25mg/kg.d Slow the speed of tapering 1mg/kg.d×8w 0.5mg/kg.d Taper 5mg per week Maintenance for 1 year Sufficient initial dose Slow tapering Long maintenance

79. 急性肾小球肾炎 Acute GN Endocapillary proliferation:A diffuse proliferative and exudative glomerulonephritis :infiltration of the glomerular tuft by neutrophils and monocyte

83. Rapid progressive GN Crescent

89. THANKS ！ [email_address]