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Renal pathology

Renal pathology

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PSGN, MPGN,Membranous nephropathy, Lupus nephritis, Physiology of nephrons, Diuretics, alport syndrome, loop diuretics, normal glomerulus, minimal change disease, nephrotic syndrome, nephritic syndrome, FSGS

PSGN, MPGN,Membranous nephropathy, Lupus nephritis, Physiology of nephrons, Diuretics, alport syndrome, loop diuretics, normal glomerulus, minimal change disease, nephrotic syndrome, nephritic syndrome, FSGS

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Renal pathology

  1. 1. - DR.AKIF A.B STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  2. 2. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  3. 3. -100% Glucose -100% amino acids and Proteins -90% of Bicarbonate -60-70% of water -60-70% of all other solutes -40% of urea Reabsorption STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  4. 4. - Highly permeable to water -Relatively impermeable to solutes. Hence concentration of filtrate increases STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  5. 5. -Less permeable to water - But highly permeable to NaCl STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  6. 6. -Almost totally impermeable to water -Na+/K+/2Cl- channel is present here.It reabsorbs Na,K and Cl. -Mg and Ca is also reabsorbed - Loop diuretics acts by inhibiting this channel. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  7. 7. Furosemide Diuretic of choice in patients with Renal Failure. Torsemide Longest acting Ethacrynic acid Most ototoxic Loop Diuretic -All have weak carbonic anhydrase activity except Ethacrynic acid. Bumetanide Most potent loop diuretic Indacrinone It is used in Gout as it decerases reabsorption of Uric acid in nephron. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  8. 8. -They have weak Carbonic anhydrase action except Ethacrynic Acid -Uses : 1) Pulmonary edema STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  9. 9. -Similar to Thick Ascending Loop of Henle -water is less reabsorbed - 7% of total NaCl is reabsorbed via Na+/Cl- channel STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  10. 10. -It has 2 types of cells: 1) Principal cell 2) Intercalated cell Principal cell is responsible for Intercalated cell - Na+ reabsorption - H+-K+ channel - K+ secretion Secretes H+ - H20 absorption Reabsorbs K+ STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  11. 11. PCT Collecting Duct Brush border present No brush border Carbonic anhydrase (type4) is present at luminal membrane No Carbonic anhydrase (type4) is present at luminal membrane Cytoplasmic carbonic anhydrase (type2) present Cytoplasmic carbonic anhydrase (type2) present Leaky tight junction present Tight tight junctions present Paracellular transport is possible via leakt ‘TJ’ Paracellular transport is not possible Gap junctions present at lateral cell membrane Gap junctions absent - Acetazolamide acts on both type2 and type4 cell membrane. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  12. 12. Cortical nephrons Juxtamedullary nephrons 85% of all nephrons 15% Short Loop of Henle Long loop of henle (Responsible for counter current multiplier) Peritubular capillary network is short Peritubular capillary network forms vasa recta : responsible for counter current exchanger Blood flow is large (5ml/gm/min) Less (0.6ml/gm/min) O2 consumption is high (9ml/gm/min) Low (0.4ml/gm/min) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  13. 13. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  14. 14. Total 1250 ml/min Cortex 5ml/gm/min Outer medulla 2.5ml/gm/min Inner medulla 0.6ml/gm/min -Renal plasma flow = 700ml/min -Effective Renal Plasma flow = 625ml/min = Measured via Para Amino Hippuric Acid (PAH) clearance STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  15. 15. Total 18ml/gm/min Cortex 9ml/min/kg Medulla 0.4ml/min/kg -Arterio venous O2 difference =14ml/L STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  16. 16. Glomerular endothelial cell layer + Basement membrane + Podocyte (Visceral epithelial layer of Bowman capsule) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  17. 17. -Slit diaphragm consists of proteins : NPHS-1(Nephrin) , NPHS-2(podocin),actinin etc. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  18. 18. Gene Protein Disease Inheritance NPHS-1 Nephrin Finnish type of nephrotic Sx AR NPHS-2 Podocin Congenital nephrotic Sx AR LAMB2 Laminin Beta2 Pierson Sx AR ACTN4 Alpha actinin 4 FSGS AD COL4A5,3,4 Collagen IV alpha 5 Alport’s Sx XR STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  19. 19. -Depends on : 1) Size of particle 2) Charge of particle Size Charge <4nm Freely permeable Glomerular basement membrane is negatively charged. >8nm Not permeable So +ve charged particles are easily filtrable 4-8nm Depends on charge -ve charge particle are difficult for filtration STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  20. 20. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  21. 21. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  22. 22. TYPE 2 HYPERSENSITIVITY TYPE 3 HYPERSENSITIVITY TYPE 4 HYPERSENSITIVITY Good-Pasture Sx PSGN Granulomatous MGN MPGN IgA Nephropathy FSGS Lupus nephritis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  23. 23. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  24. 24. Sub-epithelial Sub endothelial Membranous Mesangial PSGN MPGN-I MPGN-II IgA Nephropathy MGN RPGN-II STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  25. 25. NEPHRITIC Sx NEPHROTIC Sx Proteinuria <3.5gm/dl (usually <1.5gm/dl) >3.5gm/dl Edema Mild ( Due to Na+ and water retention) Severe ( Due to loss of Proteins) Hypertension Severe Mild Hematuria +++ + Uremia +++ + Etiology PSGN ( MC in Children) Minimal Change Disease( MC in Children) MPGN MGN RPGN FSGS( MC in adults) IgA Nephropathy( MC in adults) MPGN IgA Nephropathy STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  26. 26. Etiology Clinical Features Prognosis Unknown No prior history Excellent prognosis 99% - Recovers 1% - Progress to chronic glomerulonephritis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  27. 27. Light Microscopy (L.M) Electron Microscopy (E.M) Fluorecent Microscopy (F.M) No changes Effacement of foot process (Podocytopathy) No changes - Selective Proteinuria STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  28. 28. Effaced foot Process of Podocyte basement membrane Fenestrated endothelium STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  29. 29. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS). collagenous sclerosis To focal and segmental Proliferation of Visceral epithelial cells STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  30. 30. An area of collagenous sclerosis runs across the middle of this glomerulus. Focal : <50% of Glomeruli are involved Segmental : Part of glomerulus involved In contrast to minimal change disease, patients with FSGS are more likely to have non-selective proteinuria, hematuria, progression to chronic renal failure, and poor response to corticosteroid therapy. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  31. 31. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS). ETIOLOGY 1) Reflux Nephropathy (MC) 2) HIV 3) Sickle cell anemia 4) I.V Drug abuse 5) Massive obesity 6) Congenital Nephrotic Sx STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  32. 32. Minimal change disease FSGS Selective proteinuria Non selective proteinuria Hematuria –ve +ve Low chances of progression to Chronic Glomerulonephritis (<!%) High chances of progression Good response to steroids Poor response FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  33. 33. This trichrome stain of a glomerulus in a patient with focal segmental glomerulosclerosis (FSGS) demonstrates blue collagen deposition. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  34. 34. This glomerulus is hypercellular and capillary loops are poorly defined. This is a type of proliferative glomerulonephritis known as post-infectious glomerulonephritis. This case followed a group A beta hemolytic streptococcal infection of the pharynx 3 weeks earlier, and thus it could be termed 'post-streptococcal gomerulonephritis'. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  35. 35. The hypercellularity of post-infectious glomerulonephritis is due to increased numbers of epithelial, endothelial, and mesangial cells as well as neutrophils in and around the glomerular capillary loops. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  36. 36. Etiology C/F Prognosis Beta hemolytic Streptococci Nephritic Sx Hematuria after 7- 21days after Sore throat/Pyoderma Very good 95% - Resolves Antibiotic prophylaxis has no role in preventing PSGN 5% -Chronic glomerulonephritis <1% - RPGN STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  37. 37. L.M F.M E.M Endo and exo capillary proliferation Granular deposit (Lumpy bumpy deposit) Sub epithelial deposits STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  38. 38. Question: What 3 serologic tests have high sensitivity for post-streptococcal GN? Answer : 1) The anti-streptolysin O (ASO), 2) anti-hyaluronidase, and 3) anti-DNase B test STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  39. 39. Post-infectious glomerulonephritis is immunologically mediated, and the immune deposits are widely distributed within the capillary loops. The deposits are seen here with bright breen fluorescence in a granular, bumpy pattern because of the focal nature of the immune complex deposition process. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  40. 40. Subepithelial humps basement membrane epithelial cell STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  41. 41. Here is the light microscopic appearance of membranous nephropathy in which the capillary loops are thickened and prominent, but the cellularity is not increased. Membranous GN is the most common cause for nephrotic syndrome in adults. In most cases there is no underlying condition present (idiopathic). However, some cases of membranous GN can be linked to a chronic infectious disease such as hepatitis B, a carcinoma, or SLE. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  42. 42. Etiology 1) Infections : Hepatitis B> C , HIV,Leprosy, Syphilis 2) Autoimmune : SLE, RA 3) Drugs : Gold, Penicillamine, NSAIDs 4) Malignancy : Ca. colon, Melanoma STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  43. 43. Light Microscopy F.M E.M Sub epithelial deposits On PAS Stain : Spike and Dome appearance Granular deposits Podocytopathy STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  44. 44. Spike and Dome appearance STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  45. 45. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  46. 46. By electron microscopy in membranous nephropathy, the darker electron dense immune deposits are seen scattered within the thickened basement membrane. The "spikes" seen with the silver stain represent the intervening matrix of basement membrane between the deposits. Spike and Dome appearance STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  47. 47. -H/O progression to renal failure within 4 weeks. -Microscopic Examination = Crescents -Gross = Flea Bitten Kidney Type I RPGN Type II RPGN Type III RPGN Anti Glomerular Basement membrane antibodies Immune complex Pauci Immune or no immune complex Good Pasture Sx MGN Wegener’s Granulomatosis MPGN Microscopic Polyangitis PSGN Churg Strauss Sx IgA nephropathy ANCA associated Lupus Nephritis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  48. 48. -Experimentally induced MGN -Megalin antigen -Inserted in Rat -Immune complex deposited -Biopsy : Similar to MGN STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  49. 49. FLEA BITTEN KIDNEY More is the no. of Crescents = Poorer is the Prognosis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  50. 50. Type I Type II Type III Linear deposits (Ribbon like) Granular deposits No deposits STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  51. 51. Seen here within the glomeruli are crescents composed of proliferating epithelial cells. Crescentic glomerulonephritis is known as rapidly progressive glomerulonephritis (RPGN) because this disease is very progressive. Note in the lower left glomerulus that the capillary loops are markedly thickened (the so-called "wire loop" lesion of lupus nephritis). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  52. 52. Here is another glomerulus with an epithelial crescent squashi ng the glomerular tufts from all sides. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  53. 53. This immunofluorescence micrograph of a glomerulus demonstrates positivity with antibody to fibrinogen. With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen leaks into Bowman's space, leading to proliferation of the epithelial cells and formation of the bright crescent shown here. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  54. 54. This immunofluorescence pattern shows positivity with antibody to IgG and has a smooth, diffuse, linear pattern that is characteristic for deposition of glomerular basement membrane antibody with Goodpasture syndrome. Serologic testing for anti- GBM in patient serum is often positive. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  55. 55. -MC type of Nephritic Sx in adult -Raised IgA -IgA deposits in Mesangium, Hence also known as Mesangiocapillary Glomerilonephritis Secondary IgA Nephropathy 1) Severe Liver Disease 2) Celiac disease Poor Prognosis 15-40% : Nephrotic Sx 15% : End stage renal disease 15% : Recur in post Renal transplantation STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  56. 56. Granular deposits STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  57. 57. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). ETIOLOGY 1) Infection : Hep.C +/- Cryoglobulinemia, Hep. B, HIV, Kala Azar 2) Autoimmune 3) Drugs 4) Malignancy : CLL 5) Partial Lipodystrophy STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  58. 58. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). Type I Type II Classical complement Alternate complement All complements : Decreased C1,C2,C4 : Normal Sub endothelial deposits ( Tram track appearance) Membranous deposits Measngial proliferation + -ve Poor Prognosis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  59. 59. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  60. 60. The pathologic findings shown here include increased glomerular overall cellularity, mainly increased mesangial cellularity. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  61. 61. This silver stain demonstrates a double contour to many basement membranes, or the "tram-tracking" that is characteristic of membranoprolifera tive glomerulonephritis (MPGN) that results from basement membrane reduplication. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  62. 62. The bright deposits scattered along capillary walls and in the mesangium by immunofluorescence microscopy with antibody to complement component C3 are typical for dense deposit disease (formerly called membranoproliferative glomerulonephritis, type II). Dense deposit disease produces a nephritic syndrome. Most patients have detectable circulating C3 nephritic factor, an IgG autoantibody. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN). STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  63. 63. Glomerular disease with systemic lupus erythematosus (SLE) is common, and lupus nephritis can have many morphologic manifestations as seen on renal biopsy. In general, the more immune complex deposition and the more cellular proliferation, the worse the disease. In this case, there is extensive immune complex deposition in the thickened glomerular capillary loops, giving a so-called wire loop appearance. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  64. 64. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  65. 65. -MC Type = FSGS ( MC : Collapsing variety) - Collapsing type : Masangial necrosis + Proliferation of visceral epitheluial cells Collapsing variety STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  66. 66. -X-Linked dominant -Hereditary nephritis -Defect = collagen 4@5 (MC) > 4@3, 4@4 Hematuria + Sensorineural deafness + Eye defects ( Anterior Lenticonus) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  67. 67. LM FM EM Diffuse thickening of Glomerular basement membrane Decreased staining with Col 4@5 Alternate thick and thin layer ( Basket weave appearanec) STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  68. 68. 1) Diabetic nephropathy 2)Analgesic nephropathy 3)Sickle cell anemia 4)Chronic Alcoholism 5)Complication of acute pyelonephritis STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  69. 69. SYMMETRIC ASSYMETRIC Chronic Glomerulonephritis Chronic pyelonephritis Diabetes Benign HTN STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  70. 70. STEP TO PG-MD/MS/DNB - DR.AKIF A.B
  71. 71. STEP TO PG-MD/MS/DNB - DR.AKIF A.B

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