24 glomerular disease

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  • 24 glomerular disease

    1. 1. Department of Nephrology, the First Affiliated Hospital Sun Yat-sun University Qiongqiong Yang 杨琼琼 Glomerular disease
    2. 2. Glomerular disease <ul><li>a group of diseases characterized by </li></ul><ul><li>similar clincal manifestations : </li></ul><ul><li>Proteinuria Hematuria Edema Hypertension </li></ul><ul><li>Etiology Pathogenesis Prognosis : Different </li></ul>
    3. 3. outline Anatomy and function General pathogenesis Clinical syndromes and presentation Specific glomerular diseases
    4. 4. Anatomy and function
    5. 5. Anatomy <ul><li>Retroperitoneally posterior part of the abdomen </li></ul><ul><li>Either side of the vertebral column </li></ul><ul><li>Right kidney is one vertebral body lower than the left. </li></ul>
    6. 6. Anatomy Renal Function Remove wastes Maintain homeostasis Secrete EPO Diagram of a bisected kidney
    7. 7. Anatomy-nephron <ul><li>Functional unit of kidney </li></ul><ul><li>Renal corpuscle ( 肾小体 ): Glomerulus , Bowman’s Capsule </li></ul><ul><li>Renal tubule (Proximal tubule, Loop of Henle, Distal tubule, Collecting duct) </li></ul>
    8. 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. 9. Ultramicroscopic Stucture of glomerullar Capillaries Filtration Mem
    10. 10. Light micrograph of glomerulus <ul><li>Normal celluarity; </li></ul><ul><li>Patent capillary lumens </li></ul>
    11. 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. 12. Ultrastructure of normal glomerular capillary 系膜细胞 系膜基质 内皮细胞 上皮细胞足突
    13. 15. General pathogenesis
    14. 16. What causes glomerular disease ? Most are of immunologic origin, and caused by immune complexes ! <ul><li>metabolic stress: DN </li></ul><ul><li>mechanical stress: </li></ul><ul><li>hypertension </li></ul>
    15. 17. Antibody mediated GN - Circulating Immune complex Location: Mesangial and sub-endothelial
    16. 18. Antibody mediated GN - In-situ Immune complex Location: GBM sub-epithelial <ul><li>circulating auto antibodies with intrinsic autoantigens (component of normal parenchyma) </li></ul>
    17. 19. Antibody mediated GN - In-situ Immune complex (trapped Ag) Location: GBM sub-epithelial Extrinsic antigens planted within the glomerulus
    18. 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
    19. 21. Characterizations of glomerular disease ?
    20. 22. Glomerular Filtration Barrier
    21. 23. Glomerular Filtration Barrier Injury <ul><li>Fusion of foot process : Proteinuria </li></ul><ul><li>GBM Injury : Hematuria/ Proteinuria </li></ul>
    22. 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
    23. 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%
    24. 26. Classification of Glomerular Disease Etiology Pathology Clinical Features
    25. 27. Clinical syndromes and presentation
    26. 28. Clinical syndromes and presentation Latent GN (asymptomatic urinary abnormalities) Nephrotic syndrome Acute GN RPGN Chronic GN microscopic or Macroscopic hematuria Proteinuria Dysmorphic Glomerular erythrocytes Proteinuria>3.5g/d Hypoalbuminemia Hyperlipidemia Edema Hematuria Proteinuria (1-3g/d) ARF Edema Hypertension Red cell casts <ul><li>Rapidly deterioration of renal function </li></ul><ul><li>Hematuria, Proteinuria </li></ul><ul><li>oliguria or anuria </li></ul><ul><li>Red cell casts </li></ul><ul><li>With or without systemic symptom </li></ul><ul><li>Hematuria, Proteinuria </li></ul><ul><li>Hypertension </li></ul><ul><li>Reduced GFR </li></ul>
    27. 29. How are glomurular diseases diagnosed ? Usually by history, physical findings, Urinalysis and other laboratory data. Occasionally a renal biopsy must be performed !
    28. 30. Renal Biopsy Processing <ul><li>performed by nephrologists using real-time ultrasound guidance and disposable automated biopsy needles. </li></ul><ul><li>16-gauge needles </li></ul><ul><li>lower pole of the kidney </li></ul>
    29. 31. Renal Biopsy Processing <ul><li>Ultrasound scan demonstrating the deepness of needle entering the lower pole of the left kidney (centimeter) </li></ul>
    30. 32. Renal Biopsy Processing <ul><li>Needle is guided into the probe pore </li></ul><ul><li>passed under ultrasonic guidance to kidney capsule. </li></ul>
    31. 33. Renal Biopsy Processing <ul><li>The trigger mechanism is released with the pt stopping the breath </li></ul><ul><li>firing the needle into the kidney </li></ul><ul><li>Needle is immediately withdrawn </li></ul>renal biopsy material
    32. 34. Pathology PAS MASSON H&E PASM
    33. 35. Pathological classification of GN <ul><li>minimal change glomerulonephritis 轻微病变性肾小球肾炎 </li></ul><ul><li>focal segmental lesions 局灶节段性病变 </li></ul><ul><li>diffuse glomerulonephritis 弥漫性肾小球肾炎 </li></ul><ul><ul><ul><li>membranous nephropathy 膜性肾病 </li></ul></ul></ul><ul><ul><ul><li>proliferative glomerulonephritis 增生性肾炎 </li></ul></ul></ul><ul><li>sclerosing glomerulonephritis 硬化性肾炎 </li></ul><ul><li>unclassified glomerulonephritis 未分类性肾小球肾炎 </li></ul>
    34. 36. <ul><li>proliferative glomerulone-phritis 增生性肾炎 </li></ul><ul><li>mesangial proliferative GN 系膜增生性肾小球肾炎 </li></ul><ul><li>endocapillary proliferative GN 毛细血管内增生性肾小球肾炎 </li></ul><ul><li>mesangial capillary GN 系膜毛细血管内增生性肾小球肾炎 </li></ul><ul><li>crecentic GN 新月体肾炎 </li></ul><ul><ul><ul><ul><li>Dense deposit glomerulonephritis </li></ul></ul></ul></ul>Pathological classification of GN
    35. 37. Clinical syndromes of glomerular diseases <ul><li>Asymptomatic hematuria/ or proteinuria </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Acute glomerular nephritis </li></ul><ul><li>Rapidly progressive glomerular nephritis </li></ul><ul><li>Chronic glomerular nephritis </li></ul>
    36. 39. Dysmorphic glomerular erythrocytes
    37. 41. Asymptomatic hematuria/ or proteinuria Latent nephritis <ul><li>Mild chronic GN or recovery phase of acute GN </li></ul><ul><li>Isolated microscopic hematuria (Dysmorphic RBC) </li></ul><ul><li>Isolated proteinuria </li></ul><ul><li>No HBP, edema or Azotemia </li></ul><ul><li>Treatment is similar to chronic GN </li></ul>
    38. 42. CASE I <ul><li>11 year-old male </li></ul><ul><li>History: Intermittent hematuria x 1 year </li></ul><ul><li>Hx of recurrent pharyngitis </li></ul><ul><li>Physical: tonsillitis </li></ul><ul><li>Urinalysis: 15 RBC/HPF </li></ul><ul><li>1  protein </li></ul><ul><li> RBC casts </li></ul><ul><li>Lab Data: dysmorphic RBC </li></ul>red blood cells per high-power field
    39. 43. Light microscopy: diffuse mesangial hypercellularity H&E
    40. 44. mesangial hypercellularity PAS
    41. 45. Immunofluorescence microscopy: diffuse mesangial IgA IgA
    42. 46. Electron microscopy: mesangial electron-dense deposits.
    43. 47. The Patient Has IgA nephropathy!
    44. 48. IgA Nephropathy <ul><li>Most common GN </li></ul><ul><li>Mesangioproliferative or other pathological types </li></ul><ul><li>Predominent mesangial IgA deposit </li></ul><ul><li>Persistent or episode of hematuria </li></ul><ul><li>Exacerbate on infection </li></ul><ul><li>1/3 have elevated serum IgA </li></ul>
    45. 49. Clinical syndromes of glomerular diseases <ul><li>Asymptomatic hematuria/ or proteinuria </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Acute glomerular nephritis </li></ul><ul><li>Rapidly progressive glomerular nephritis </li></ul><ul><li>Chronic glomerular nephritis </li></ul>
    46. 50. Nephrotic Syndrome <ul><li>Insidious onset </li></ul><ul><li>Manifestations </li></ul><ul><ul><li>Proteinuria > 3.5g/d </li></ul></ul><ul><ul><li>Hypoalbuminemia a lb < 30 g/l </li></ul></ul><ul><ul><li>Edema </li></ul></ul><ul><ul><li>Hyperlipidemia </li></ul></ul>
    47. 51. Nephrotic syndrom-etiology(1) <ul><li>Primary Nephrotic syndrom </li></ul><ul><ul><li>minimal change disease </li></ul></ul><ul><ul><li>FSGS(focal segemental glomerular disease) </li></ul></ul><ul><ul><li>membranous nephropathy </li></ul></ul><ul><ul><li>membranoproliferative GN </li></ul></ul><ul><ul><li>IgAN </li></ul></ul>
    48. 52. Nephrotic syndrom-etiology(2) <ul><li>Secondary Nephrotic syndrom </li></ul><ul><li>Autoimmunity:SLE, </li></ul><ul><li>Infection: Hepatitis B or C,HIV </li></ul><ul><li>Tumor: solid carcinoma, lymphoma </li></ul><ul><li>Metabolic: DM, Amyloidosis </li></ul><ul><li>Drugs: NSAIDS </li></ul>
    49. 53. Nephrotic syndrom-epidemiology <ul><li>Children Yong people Old people </li></ul><ul><li>Primary MCD FSGS,MsGN MN </li></ul><ul><li>MPGN </li></ul><ul><li>Secondary HSP SLE DN </li></ul><ul><li>Hepatitis B HSP Tumor </li></ul><ul><li>Inherited NS Hepatitis B MM , AL </li></ul><ul><li>Henoch-Schönlein Nephritis </li></ul><ul><li>Multiple myeloma , Amylosis </li></ul>
    50. 54. <ul><li>14 year-old, male, high-school student </li></ul><ul><li>History: No significant medical history </li></ul><ul><li>Fatigue x 3 weeks </li></ul><ul><ul><li>Edema x 1 week </li></ul></ul><ul><li>Physical: Mild generalized edema </li></ul><ul><li>Urinalysis: 4  protein </li></ul><ul><ul><li>Many hyaline casts </li></ul></ul><ul><ul><li>Few granular casts No RBCs or RBC casts </li></ul></ul><ul><li>Lab Data: proteinuria 4g/d , alb 20g/l,normal renal function, Hepatitis (-), Auto-immunity Ab (-) </li></ul><ul><li>Renal biopsy </li></ul>CASE II
    51. 56. Electron Microscopy: effacement and fusion of foot processes
    52. 57. The patient has Minimal change disease!
    53. 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
    54. 59. CASE III <ul><li>65 year-old, male, Smoke for 40 years </li></ul><ul><li>History: Fatigue x 3 months </li></ul><ul><li>Cough and chest pain x 2 months </li></ul><ul><li>Facial edema x 1 week </li></ul><ul><li>Physical: edema, </li></ul><ul><li>Urinalysis: protein ++++ </li></ul><ul><li>Lab Data: proteinuria 8g/d , </li></ul><ul><li>alb 24g/l, normal renal function, </li></ul><ul><ul><li>Hepatitis (-), </li></ul></ul><ul><li>Auto-immunity Ab (-) </li></ul>
    55. 60. Why is a thorough Clinical evaluation important in patients with the nephrotic syndrome ! Many such patients have an occult malignancy !
    56. 61. CASE III Lung Carcinoma
    57. 62. Silver PAS
    58. 63. CASE III LM-PASM:”spikes” along the GBM
    59. 64. CASE III IF: IgG deposition along GBM
    60. 65. CASE III EM: subepithelial electron dense material
    61. 66. It’s Clearly a case Of carcinoma related Membranous nephropathy !
    62. 67. CASE II-MN <ul><li>Commonly occurred in middle&old-aged </li></ul><ul><li>people </li></ul><ul><li>Etiology : Primary </li></ul><ul><li>Secondary : Tumor-related, </li></ul><ul><li>Hepatitis B related , Drugs - related </li></ul><ul><li>Presentation: HT & Renal failure, </li></ul><ul><li>Thrombosis </li></ul>
    63. 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
    64. 69. How to treat the Nephrotic Syndrome?
    65. 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↓
    66. 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
    67. 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
    68. 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
    69. 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
    70. 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
    71. 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
    72. 77. Clinical syndromes of glomerular diseases <ul><li>Asymptomatic hematuria/ or proteinuria </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Acute glomerular nephritis </li></ul><ul><li>Rapidly progressive glomerular nephritis </li></ul><ul><li>Chronic glomerular nephritis </li></ul>
    73. 78. 急性肾小球肾炎 Acute GN <ul><li>History of streptococcus infection 2 weeks ago </li></ul><ul><li>Acute onset </li></ul><ul><li>Prominent hematuria and RBC casts </li></ul><ul><li>ARF & HT </li></ul><ul><li>Low C3 , for 8weeks </li></ul><ul><li>ESR increased , Anti-DNAseB (+) </li></ul>
    74. 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
    75. 80. cute GN <ul><li>Treatment : eliminating the streptococcal infection with antibiotics; supportive therapy </li></ul><ul><li>Prognosis: Spontaneous resolution(for children within 6-8 wks). Excellent prognosis, and rarely causes ESRD. </li></ul>
    76. 81. Clinical syndromes of glomerular diseases <ul><li>Asymptomatic hematuria/ or proteinuria </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Acute glomerular nephritis </li></ul><ul><li>Rapidly progressive glomerular nephritis </li></ul><ul><li>Chronic glomerular nephritis </li></ul>
    77. 82. Rapid progressive GN <ul><li>Similar to acute GN on onset </li></ul><ul><li>Rapid deterioration of renal function </li></ul><ul><li>Cr↑ , Oliguria and obvious macroscopic hematuria </li></ul><ul><li>Crescent formation>50% </li></ul><ul><li>Need aggressive therapy(Large dose of steroid pulse therapy + CTX ; Plasmaphoresis) </li></ul><ul><li>Prognosis: poor, most require dialysis. </li></ul>
    78. 83. Rapid progressive GN Crescent
    79. 84. <ul><li>Idiopathic crescentic GN(RPGN) : </li></ul><ul><li>Type I : with linear deposits of Ig anti - GBM antibody + </li></ul><ul><li>Type II: with granular deposits of Ig immune complex-mediated </li></ul><ul><li>Type III: with few or no immune deposits of Ig Pauci-immne ,ANCA + </li></ul><ul><li>Type IV: anti - GBM antibody + & ANCA + </li></ul><ul><li>Type V: Pauci-immne , ANCA - </li></ul>Rapid progressive GN
    80. 85. Clinical syndromes of glomerular diseases <ul><li>Asymptomatic hematuria/ or proteinuria </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Acute glomerular nephritis </li></ul><ul><li>Rapidly progressive glomerular nephritis </li></ul><ul><li>Chronic glomerular nephritis </li></ul>
    81. 86. Chronic glomerulonephritis <ul><li>Clinical presentations: Proteinuria(<3.5g/d);Hematuria; Hypertension;Edema;Azotema(BUN/Cr↑) </li></ul><ul><li>Pathological manifestations of all of major glomerulopathies. </li></ul><ul><li>Exclusion of secondary cause :SLE etc. </li></ul><ul><li>To correct the reversible factors: hypertension, infection, drug toxicity </li></ul>
    82. 87. Treatment of Chronic GN <ul><li>Reduce proteinuria </li></ul><ul><li>Control hypertension </li></ul><ul><ul><ul><li>ACE-I or AT II receptor blocker/ antagonist (ARB): reducing proteinuria in addition to lowing of blood pressure </li></ul></ul></ul><ul><li>Low protein diet for azotemia </li></ul><ul><li>Avoid nephrotoxic agents </li></ul><ul><li>Anti-platelet aggregation </li></ul>
    83. 88. TAKE HOME MESSAGE ! <ul><li>One important clinic syndrome of glomerular disease: Nephrotic syndrome ! </li></ul><ul><li>Diagnosis is based on thorough clinic evaluation ! </li></ul><ul><li>Renal biopsy is critical for diagnosis ! </li></ul>
    84. 89. THANKS ! [email_address]

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