Glomerulus and nephrotic & nephritic syndrome


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Glomerulus and nephrotic & nephritic syndrome

  1. 1. Presented By Prof. Dr. Nabil Tadros Mikhail MBBS, MS Pathol., PhD Pathol. Prof. of Pathology Alexandria University - Egypt Consultant & Chief Pathologist King Fahad Central Hospital Gizan - KSA
  2. 2. Kidney diseases Glomerulonephritis , nephritic & nephrotic syndromes
  3. 3. The kidney can be divided into four morphologic components, 1. Glomeruli 2. Tubules 3. Interstitium 4. Blood vessels.
  4. 4. Left: General organization of the kidney. Right: Parts of a juxtamedullary nephron and its collecting duct and tubule
  5. 5. 1 2 Portal circulation of the kidney 2 arterial capillaries
  6. 6. The small spaces between adjacent processes constitute the filtration slits
  7. 7. subendothelium intramembranous subepithelium
  8. 8.  Glomerular diseases are often immunologically mediated  Whereas tubular and interstitium are more likely caused by toxic or infectious agents
  9. 9.  Damage to one component almost always secondarily affect others. 1. Severe damage to glomeruli affect peritubular blood flow, 2. Tubular destruction, by increasing intraglomerular pressure may induce glomerular atrophy. 3. All forms of chronic renal disease will ultimately destroy all kidney components and lead to CRF.
  10. 10. Endless triangle
  11. 11. Glomerular diseases  Glomerular diseases are a major problem in nephrology,  Chronic glomerulonephritis (GN) is one of the most common cause of CRF in human .
  12. 12. Glomerular diseases Glomerular diseases Glomerular diseases
  13. 13. Glomerular structure
  14. 14. Glomerular structure  The glomerulus consists of a network of capillaries invested by epithelium.
  15. 15. Structure of glomerular wall   The glomerular capillary wall is the filtering area Consists of four basic structure: 1. 2. 3. 4. Thin layer of fenestrated endothelial cells. Glomerular basement membrane (GBM): Visceral epithelium: (podocytes) Mesangial cells and mesangial matrix:
  16. 16. Structure of glomerular wall  1- Thin layer of fenestrated endothelial cells.  2- Glomerular basement membrane (GBM): It consists of 1. Collagen 2. Laminin 3. Fibronectin 4. Other proteins.
  17. 17. Structure of glomerular wall 3- Visceral epithelium: (podocytes)  It shows a characteristic foot processes (pedicles) embedded and adherent to GBM.  These foot processes are  separated by 20-30 nm filtration slit  which are bridged by a thin diaphragm composed of nephrin molecules.
  18. 18. Structure of glomerular wall 3- Visceral epithelium: (podocytes)  Visceral epithelium is critical to maintain glomerular barrier function.  It is the cell type that is largely responsible for synthesis of GBM.
  19. 19. Structure of glomerular wall 4- Mesangial cells and mesangial matrix :  It serve as a support of glomerular tuft.  These cells is capable for proliferation.  The whole glomerulus is surrounded by parietal epithelium, which lines the bowman’s space (urinary space), the cavity in which plasma filtrate first collect.
  20. 20.  15% of glomerular filtration through the mesangium,  85% of glomerular filtration through the fenestrated epithelium.
  21. 21. PAS to highlight basement membranes. The capillary loops of the glomerulus are well-defined and thin.
  22. 22. Glomerular barrier function  The major characteristic of glomerular filtration are 1. High permeability to water and small molecules 2. Almost impermeable to molecules of the size of albumin (70KD).
  23. 23. Glomerular barrier function  The latter characteristic is called glomerular barrier function,  Discriminates among protein depending on their size (the larger, the less permeable).  Also the charge affect the permeability (The more cationic the more permeable).
  24. 24. Glomerular diseases
  25. 25. Glomerular diseases  Glomerular diseases may be  Primary ,where the kidney is the main or the only organ affected.  Secondary to other disease as 1. SLE, 2. DM, 3. Amyloidosis. , 4. Polyarteritis nodosa 5. others.
  26. 26. Here amyloid deposits are seen in glomeruli at the left and arteries at the right.
  27. 27. Amyloidosis may be  "AL" type in patients with plasma cell dyscrasias (multiple myeloma) in which the amyloid is associated with excess immunoglobulin light chain production,  "AA" type or "amyloid associated" in which the cause is often chronic inflammatory diseases.
  28. 28. Pathogenesis of glomerular diseases   Immune mechanisms underlie most cases of primary glomerular diseases . It may be 1. Antibody mediated 2. Cell mediated.
  29. 29. Pathogenesis of glomerular diseases  1- Antibody mediated glomerular injury:
  30. 30. Pathogenesis of glomerular diseases  1- Antibody mediated glomerular injury:  Two forms are recognized: A- Injury resulting from deposition of circulating immune complexes. (IC)  B- Injury by antibody reacting in situ within the glomerulus  (antiglomerular basement membrane antibodies) & (the Heymann’s model)
  31. 31. Immunofluorescence microscopy patterns Granular Linear
  32. 32. A- Circulating immune complexes  The antigen may be 1. Endogenous as in SLE or 2. Exogenous as acute glomerulonephritis follow certain  bacteria (Streptococci) or  viral (HBV).
  33. 33. A- Circulating immune complexes     Antigen antibody complexes are formed in the circulation and then trapped in the glomeruli, where they produce injury through binding of complement .
  34. 34. A- Circulating immune complexes These IC are seen either by  Electron microscopy as dense deposits Immunofluorescence microscopy, as granular deposits  
  35. 35. granular immune deposits
  36. 36. Post-streptococcal glomerulonephritis is immunologically mediated, The immune deposits are distributed in the capillary loops in A granular, bumpy pattern because of the focal nature of the deposition process (granular immune deposits)
  37. 37. B- nephritis in situ  The best example is anti glomerular basement membrane disease.  In this type antibody are directed against fixed antigen in the GBM.  Also can react to planted non-glomerular antigens interacting with intrinsic component (Heymann’s model)
  38. 38. B- nephritis in situ  Some times the anti GBM antibodies cross react with basement membrane of alveoli resulting in simultaneous lung and kidney disease (Good Pasture syndrome).  The antibody can be visualized along GBM by indirect immunofluorescence microscopy, giving a characteristic linear pattern.
  39. 39.  Antibody to IgG, has a smooth, diffuse, linear pattern that is characteristic for glomerular basement membrane antibody with Goodpasture's syndrome.
  40. 40. Clinical findings of good pasture syndrome  There is picture of RPGN with haematuria and may end in renal failure.  Haemorraghic interstitial pneumonitis with haemoptysis, dyspnea,..  Iron ↓ anemia from recurrent hemorrahge.
  41. 41. Good Pasture Syndrome  It is an example of type II hypersensitivity with cytotoxic antibodies  Circulating anti GBM antibodies can be detected in serum (by EIA). Renal biopsy:  shows a characteristic linear immunofluorescence deposits of IgG and C3.
  42. 42. Good Pasture Syndrome Renal biopsy:  shows a characteristic linear immunofluorescence deposits of IgG and C3.
  43. 43. 2- Cell mediated immunity
  44. 44. 2- Cell mediated immunity  There is increasing evidence that sensitized T cells can cause glomerular injury .  These may be the case in some forms of rapidly progressive glomerulonephritis.
  45. 45. Mediators of immune injury  Glomerular damage is reflected physiologically by  loss of barrier function   manifested by proteinuria and   reduction of glomerular filtration rate (GFR).
  46. 46. Mediators of immune injury  Many mechanisms are described:  Complement-leukocyte mechanism  C5-9 complement components  Cytotoxic antibodies  Monocytes and macrophage.  Platelets
  47. 47. Mediators of immune injury 1- Complement-leukocyte mechanism :  Activation of complement   Generation of chemotactic factors (C5a)   Attract neutrophils  1. Produce Proteases which degrade GBM, 2. O2 free radicals which cause tissue damage 3. Arachidonic acid metabolites (as TXA2) and which lead to reduction of GFR.
  48. 48. Mediators of immune injury  Endothelin & other vasoconstrictors also contribute to reduction of GFR.  In addition GFR is also ↓ as a result of obstruction of glomerular lumen by 1. infiltrating inflammatory cells and 2. proliferating mesangial cells.
  49. 49. Mediators of immune injury 2- C5-9 complement component: This component causes epithelial damage. It also up regulates the transforming growth factor receptors on epithelial cells , and  lead to excessive synthesis of extra cellular matrix and GBM thickening.   
  50. 50. Mediators of immune injury  3- Cytotoxic antibodies:  antibodies directed against glomerular structure and produce cytotoxicity (even if IC is absent)
  51. 51. Mediators of immune injury  4- Monocytes and macrophage:  They secrete a number of biologically active mediators which contribute to glomerular damage.  5- Platelet:  It aggregates in the glomerulus and release PG and growth factors.
  52. 52. Mediators of immune injury    Epithelial injury: is the most important factor in glomerular damage. This can be induced by 1. Antibody to visceral epithelium or by 2. Toxins or others.  Such injury is reflected 1. Morphologically by loss of foot processes 2. Functionally by proteinuria.
  53. 53. Nephrotic syndrome
  54. 54. Nephrotic syndrome  Nephrotic syndrome refers to clinical condition that include five main features; 1. 2. 3. 4. 5.  Massive proteinuria (more than 3.5 gm/day) Hypo-albuminaemia (less than 3 gm/dl) Generalized edema Hyper-lipidaemia (increase cholesterol & triglycerides) Lipiduria (Lipid casts in urine ). At the onset renal function is normal (BUN, creatinine) but later on it is impaired.
  55. 55. Pathogenesis of Nephrotic syndrome  The initial event is damage to capillary wall  resulting in increase permeability to plasma protein.  With long standing heavy proteinuria serum albumin tend to become depleted and decreased.  The drop of osmotic pressure will lead to generalized edema .
  56. 56. Pathogenesis of Nephrotic syndrome  1. 2. 3. 4.  As fluid escape from vessels to tissues, there is decrease of plasma volume with compensatory secretion of aldosterone resulting in salt and water retention and further aggravate the edema. Hypo-albuminaemia trigger increased synthesis of lipids in the liver.
  57. 57. Causes of Nephrotic syndrome Nephrotic syndrome may be 1.Primary or 2.Secondary.
  58. 58. Causes of Nephrotic syndrome  Secondary nephrotic syndrome: Many disease can lead to Nephrotic changes in the kidney as 1. DM, 2. SLE, 3. Amyloidosis, 4. Drugs (gold, penicillamine), 5. Infection (malaria, syphilis, HBV, HIV, ..)
  59. 59. Causes of nephrotic syndrome  Primary nephrotic syndrome: It is encountered in primary glomerular diseases as : 1. 2. 3. 4. Lipoid nephrosis (minimal change disease) Membranous glomerulonephritis Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis
  60. 60. 1 Minimal change disease lipoid nephrosis
  61. 61. Minimal change disease  This disease is also called lipoid nephrosis. It is the most frequent cause of nephrotic syndrome in children.  It is characterized by normal appearance of glomeruli under light microscope,  but it show loss of visceral foot processes when viewed under electron microscope.
  62. 62. Lipoid nephrosis Pathogenesis:  The current evidence suggest that minimal change disease results from disorder in T cells.  It is postulated that T cells elaborate a factor that affect nephrin synthesis.
  63. 63. Morphology of minimal change disease Light microscopy  With light microscopy the glomeruli appear nearly normal.  The cells of proximal convoluted tubules are heavily laden with lipids and this is the basis of the name lipoid nephrosis.
  64. 64. The cells of proximal convoluted tubules are heavily laden with lipids (lipoid nephrosis). Slide 21.30
  65. 65. Diffuse loss of the foot processes of podocytes The cells of proximal convoluted tubules are heavily laden with lipids (lipoid nephrosis).
  66. 66. Morphology of minimal change disease Electron microscopy  With electron microscopy,  The only obvious abnormality is the uniform & diffuse loss of the foot processes of podocytes
  67. 67. This is minimal change disease (MCD) loss of the epithelial cell (podocyte) foot processes .
  68. 68. Clinical course      Gradual onset of nephrotic syndrome . It affect only children. Renal function is preserved in most cases. Hypertension is absent. Protein loss is usually confined to small molecular proteins (selective proteinuria).
  69. 69. Prognosis:  More than 90% of cases respond to corticosteroids.  Recurrence may occur and CRF may develop in less than 5% of cases after about 25 years
  70. 70. 2 Membranous glomerulonephritis (MGN)
  71. 71. Membranous glomerulonephritis (MGN) It is a slowly progressive disease Affect adults between 30-50 years. It is characterized by the presence of subepithelial immunoglobulin containing deposits along the GBM.  Diffuse thickening of GBM is shown under light microscopy in well developed cases.   
  72. 72. Causes of MGN Primary  As a primary kidney involvement in 85 % of cases (idiopathic) .  It results from antibodies that react in situ to endogenous glomerular antigen.  The glomerular damage is due to the action of C5-9 lytic components of complement.
  73. 73. Causes of MGN Secondary: MGN may occur secondary to  Many known disorders as 1. 2. 3. 4.  HBV, Syphilis Malaria SLE Exposure to inorganic salts as 1. Gold 2. Mercury  Exposure to drugs as 1. Penicillamin captopril 2. Non-steroidal anti-inflammatory drugs.
  74. 74. Morphology of MGN  The basic change seen by light microscope is diffuse thickening of GBM.  By electron microscopy ,there is subepithelial deposits along GBM as well as loss of foot processes.
  75. 75. Subepithelial deposits along GBM as well as loss of foot processes. Diffuse thickening of GBM.
  76. 76. Morphology of MGN  With further progression glomeruli become sclerosed and hyalinized.  Immunoflurescence staining of patient glomerulus show typical granular deposition of immunoglobulin and complement along GBM.
  77. 77.  Membranous glomerulonephritis in which the capillary loops are thickened & prominent, but the cellularity is not increased.
  78. 78. silver stain of the glomerulus highlights the proteinaceous basement membranes in black. There are characteristic "spikes" seen with membranous glomerulonephritis in which the black basement membrane material appears as projections around the capillary loops.
  79. 79. By electron microscopy in membranous glomerulonephritis,  the darker electron dense immune subepithelial deposits are seen scattered within the thickened basement membrane.
  80. 80. Membranous glomerulonephritis appear in a diffuse granular pattern by immunofluorescence.
  81. 81. Clinical picture of MGN    Gradual onset of nephrotic syndrome. It affect only adults, In contrast to lipoid nephrosis, proteinuria is not selective (i.e. ↑permeability also to large size proteins as globulins)  Does not respond to corticosteroids.
  82. 82. Clinical picture of MGN  40% of patients suffer from progressive disease terminating in renal failure after 2 - 20 years.  It is necessary to rule out secondary causes.
  83. 83. Compare lipoid nephrosis A & C with membranous GN B & D
  84. 84. (FSG)
  85. 85. 3 Focal segmental glomerulosclerosis (FSG)
  86. 86. Focal segmental glomerulosclerosis (FSG)  FSG is characterized histologically by sclerosis affecting 1. Some but not all glomeruli (focal) 2. Involving only segments of each glomerulus (segmental).
  87. 87. Causes of FSG Primary or idiopathic:  FSG account for about 10% of all cases of nephrotic syndrome.  It affect both children and adult.  In children it is important to be differentiated from minimal change disease.
  88. 88. Causes of FSG  The following aspects are found in FSG only not found in minimal change disease;  Hypertension,  Non-selective proteinuria,  Haematuria,  Poor response to corticosteroid.  Poor prognosis , 50% develop CRF within 10 years
  89. 89. Causes of FSG  Secondary FSG: occur in  HIV nephropathy,  IgA nephropathy ,….
  90. 90. Morphology of FSG    The disease affect only some of glomeruli (focal) initially the juxtamedullary glomeruli. It affect only some tufts within the glomerulus and sparing the others (segmental). The lesion exhibit 1. Increased mesangial matrix and 2. Deposition of hyaline masses and lipid droplets.
  91. 91. FSG morphology  On electron microscopy , 1. Visceral epithelium show loss of foot processes as in lipoid nephrosis and also 2. Greater degree of epithelial detachment  On progression 1. Glomeruli are completely sclerosed (global sclerosis) 2. With tubular atrophy.
  92. 92. This is focal segmental glomerulosclerosis (FSGS). An area of collagenous sclerosis runs across the middle of this glomerulus.
  93. 93. 4 Membranoproliferative glomerulonephritis (MPGN)
  94. 94. Membranoproliferative glomerulonephritis (MPGN)  MPGN is manifested histologically by 1. Alterations of basement membrane & mesangium 2. Proliferation of glomerular cells.   It affect both children and adult. It account for 10-15 % of cases of nephrotic syndrome
  95. 95. Pathogenesis of MPGN     Two types are recognized. Most cases of type I MPGN appear to be caused by circulating IC. It could be also secondary to SLE, HBV, and other conditions . The pathogenesis of type II MPGN is not clear . It could result from activation of alternative complement pathway through C3 nephritic factor.
  96. 96. Morphology of MPGN  By light microscope both types of MPGN are similar.  The glomeruli are 1. large 2. Proliferation of mesangium, 3. Infiltrating leucocytes 4. lobular appearance.
  97. 97. Morphology of MPGN  The GBM is thickened and show double contour appearance.  This splitting of GBM is caused by mesangial cells inclusion between GBM laminae.  It is not easily seen by ordinary microscope.  EM or special stain is required.
  98. 98. Membranoproliferative glomerulonephritis (MPGN). Glomerulus has increased overall cellularity, mainly mesangial
  99. 99. Morphology of MPGN  Immunofluorescence and electron microscopy differentiate between the two types of MPGN;  type I MPGN is characterized by subendothelial deposits(C3 and IgG).  Type II MPGN is characterized by intramembranous dense deposits of C3 mainly (dense deposit disease)
  100. 100. Subendothelial deposit TYPE I Interposed mesangial cell process Intramembranous deposit TYPE II
  101. 101.   A mesangial cell at the lower left that is interposing its cytoplasm at the arrow into the basement membrane, leading to splitting and reduplication of basement membrane. This is MPGN type I. These are characteristic subendothelial immune deposits.
  102. 102. This EM demonstrates the dense deposits in the basement membrane of MPGN type II. There are dark electron dense deposits within the basement membrane that often coalesce to form a ribbon-like mass of deposits
  103. 103. Clinical picture of MPGN  Nephrotic syndrome is present in 50% of cases.  40% progress to CRF.  Type II has a worse prognosis.
  104. 104. Clinical picture of MPGN However MPGN may begin with  Acute nephritic syndrome  With haematuria & mild proteinuria  Others has a combined nephritic- nephrotic picture.
  105. 105. Nephritic Syndrome
  106. 106. Nephritic Syndrome  It is a clinical complex usually of acute onset  characterized by five criteria: 1. 2. 3. 4. 5. Haematuria with diagnostic red cell casts. Oliguria and impairment of kidney function. Hypertension. Mild proteinuria. Mild edema (localized to face)
  107. 107. Pathogenesis  GFR is decreased due to obstruction of glomerular lumen by  The proliferating glomerular cells  Infiltrating inflammatory cells  Due to haemodynamic changes (vasoconstriction).  The inflammatory reactions injure the capillary wall and produce hematuria.
  108. 108. pathogenesis   Reduced GFR is manifested clinically by oliguria. Hypertension is the result of both 1. Fluid retention and 2. Renin release from ischemic kidney.  Acute nephritic syndrome may be produced   Secondary to other disorders as SLE or may as a result of Primary glomerular disease.
  109. 109. Kidney Diseases Associated With Nephritic Syndrome 1. Acute diffuse proliferative post streptococcal glomerulonephritis The commonest type 2. Rapidly progressive glomerulonephritis (Crescentic) 3. IgA nephropathy (Berger Disease) 4. Hereditary nephritis 5. Chronic glomerulonephritis
  110. 110. Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)
  111. 111. 1 Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)
  112. 112. Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)    It is one of the more common glomerular disease typically caused by Immune complex. The commonest organism is streptococci, however it can be caused by 1. Pneumococci. 2. Staphylococci, 3. Viruses as  Measles  Mumps.
  113. 113. Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)    PGN is an IC disease . IC are deposited as granular pattern on GBM there is also blood decrease of complement (due to increase consumption).
  114. 114. Morphology of PGN Light microscopy Increased cellularity of glomerular tuft  Affect all glomeruli and hence it is termed diffuse.  This is caused mainly by three cells: 1. 2. 3. Proliferation and swelling of endothelial cells Proliferation of mesangial cells Infiltration by neutrophils and macrophages
  115. 115. Morphology of PGN  In few cases there may be also crescent inside bowman capsule.  Electron Microscopy:  Show immune complex deposits  Arranged subepithelial along GBM (called humps)
  116. 116. Morphology of PGN Immuno fluorescence microscopy  Characteristic granular deposits of IgG & complement.
  117. 117. This glomerulus is hypercellular and capillary loops are poorly defined.
  118. 118.  The hypercellularity of post-streptococcal glomerulonephritis is due to increased numbers of epithelial, endothelial, and mesangial cells as well as neutrophils in and around the capillary loops.. (high power)
  119. 119.  By electron microscopy, the electron dense immune deposits of poststreptococcal glomerulonephritis are predominantly subepithelial, as seen here with a large subepithelial "hump" at the right of the basement membrane (BM).
  120. 120. Clinical picture of PGN    History of previous streptococcal infection 2-3 weeks before. Onset is sudden with fever ,and malaise. There is picture of nephritic syndrome 1. Oliguria , 2. Haematuria, 3. Hypertension
  121. 121. Laboratory finding of PGN 1- urine :  Smoky in color,  Many RBCs are found,  Diagnostic red cell casts
  122. 122. Laboratory finding of PGN  2- Evidence of recent streptococcal infection: 1. Increased ASOT 2. Anti DNAse   3- Mild elevation of urea and creatinine. 4- Decreased serum complement.
  123. 123. Prognosis of PGN  Recovery occur in most children.  Few cases develop RPGN. (Rapidly progressive glomerulonephritis)  In adult 15-50% develop ESRD (End stage renal disease) over few years
  124. 124. Rapidly progressive glomerulonephritis (RPGN) (Crescentic),
  125. 125. 2 Rapidly progressive glomerulonephritis (RPGN) (Crescentic),
  126. 126. 2-Rapidly progressive ,(Crescentic), glomerulonephritis (RPGN)  RPGN is characterized by 1. Rapid and progressive loss of renal function 2. Associated with severe oliguria and 3. Death from renal failure within weeks if not treated.  RPGN may be caused by many diseases, 1. Some are Restricted to the kidney 2. Others are systemic.
  127. 127. Types of RPGN Three types are recognized: Type I  It is due to anti GBM antibody. The typical example is good pasture syndrome.  Diagnosis of this type is important because the patient improve from treatment by plasmapheresis which remove pathological antibodies
  128. 128. Types OF RPGN Type II  It is an immune complex mediated disorder.  It can be a complication of any IC nephritis as     post streptococcal GN, IgA nephropathy, henoch-schonlien purpura, and SLE. In some cases the underlying cause is unknown.  Immunofluorescence studies reveal granular deposition of IC
  129. 129. Types of RPGN     Type III: It is also called pauci-immune type . There is no anti GBM or IC by immunofluorescence or even by EM. Most of these patients have Anti Neutrophil Cytoplasmic Antibodies in serum. (ANCA) These antibodies play a role in some vasculitis .
  130. 130. Types of RPGN   Type III: This type may be associated with disorders of systemic vasculitis as 1. PAN 2. wegener granulomatosis. However in many cases this type is 1. Limited to the kidney & 2. Idiopathic.
  131. 131. Morphology of RPGN   Histological picture is characterized by the presence of crescents in most of the glomeruli. (Crescentic GN). Crescents are formed by 1. Proliferation of parietal cells of the bowman capsule 2. Infiltration of mononuclear cells and 3. Deposition of fibrin within bowman space.
  132. 132. Morphology of RPGN  The crescents eventually obliterate bowman space and compress the glomeruli.  EM may reveal subepithelial deposits in some cases
  133. 133. Seen here within the glomeruli are crescents composed of proliferating epithelial cells. Note in the lower left glomerulus that the capillary loops are markedly thickened (the so-called "wire loop" lesion of lupus nephritis.
  134. 134. Another glomerulus with epithelial crescents  squashing the glomerular tufts from all sides.
  135. 135.   RPGN may be idiopathic or may result from 1. SLE, 2. Post-infectious GN (some cases of post-streptococcal GN), 3. Various types of vasculitis, and 4. Goodpasture's syndrome.
  136. 136. 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 a crescent
  137. 137. Clinical picture of RPGN  Onset is rapid with marked oliguria and azotemia (Increase urea and creatinine).  Anuria may occur in some cases (require dialysis).  Prognosis is not good, renal failure occur within weeks if proper treatment in not done rapidly.
  138. 138. 3 IgA nephropathy (Berger disease)
  139. 139. IgA nephropathy (Berger disease)  It is one of the most common causes of recurrent gross or microscopic hematuria.  Pathogenesis:  Increase IgA concentration is found in more than 50% of cases.  Patients with IgA nephropathy have increased production of IgA in bone marrow.  Also there is abnormalities in IgA clearance.
  140. 140. Pathogenesis of IgA nephropathy  It may be genetic and associated with HLA types  It could also be acquired due to increase IgA synthesis in response to respiratory or GIT infection.
  141. 141. Pathogenesis of IgA nephropathy  IgA nephropathy occur also in increased frequency in patients with celiac disease (intestinal mucosal defect).  IgA and IgA complexes are then entrapped in mesangium where they activate alternative complement pathway and initiate glomerular injury.
  142. 142. Morphology of Berger disease  The lesions vary considerably.  The glomeruli may show focal and segmental mesangial proliferation or diffuse proliferation.  Immunofluorescence staining show a characteristic mesangial deposition of IgA often with C3 and properdin.  EM demonstrate electron dense deposits in the mesangium.
  143. 143. Slide 21.38
  144. 144. This is Berger's disease, or IgA nephropathy. The IgA is deposited mainly in mesangium, which then  increases mesangial cellularity as shown at the arrow.
  145. 145. This immunofluorescence micrograph demonstrates positivity with antibody to IgA. Note that the pattern is that of mesangial staining. This is IgA nephropathy. (Berger Disease)
  146. 146. Clinical picture of Berger disease  The disease often present with gross hematuria after infection of respiratory tract or GIT.  It affects children or young adults  30-40% has only microscopic hematuria.
  147. 147. Clinical picture of Berger disease  Diagnosis depend on renal biopsy with immunofluorescence mesangial IgA deposition.  It is usually recurrent.  Many patients maintain normal renal function,  CRF occur in 25% of cases after many years.
  148. 148. 4 Hereditary nephritis
  149. 149. Hereditary nephritis  The most important disease is Alport’s syndrome .  It is hereditary nephritis associated with nerve deafness and eye disorders (cataract,…).  It is due to gene abnormalities which encode collagen production and so interfere with GBM structure  It affect male more frequently between 5-20 years.
  150. 150. Hereditary nephritis  Morphology  A characteristic foam cells is present due to accumulation of fat.  There is glomerular proliferation.
  151. 151. Hereditary nephritis Clinical picture Patients present with   1. 2. 3. 4.  Haematuria, Proteinuria Nerve deafness and Eye problems. CRF may develop within years
  152. 152. Alport's syndrome The renal tubular cells appear foamy because of the accumulation of neutral fats and mucopolysaccharides. The glomeruli show irregular thickening and splitting of basement membranes
  153. 153. Chronic glomerulonephritis (CGN)
  154. 154. 5 Chronic glomerulonephritis (CGN)
  155. 155. Chronic glomerulonephritis (CGN)  CGN is a most important cause of ESRD (end stage renal disease) presenting as CRF.  It probably represents the end stage of many disease as RPGN, FSG,MGN and MPGN.  However 20% of cases arise with no history of symptomatic renal disease
  156. 156. Slide 21.42
  157. 157. Morphology of CGN  Gross: the kidneys are symmetrically contracted with diffuse granular surface.  Microscopically: There is wide spread replacement of glomerular tuft by avascular acellular hyaline materials (hyalinization) with complete glomerular obliteration.  There is also marked interstitial fibrosis and tubular atrophy (due to impact on its blood flow)
  158. 158. •Chronic glomerulonephritis •Complete replacement of glomeruli by blue stained collagen (Masson trichrome) Slide 21.43
  159. 159. Clinical picture of CGN  Gradual onset ,usually discovered late in its course after the onset of renal insufficiency.  First manifestations include hypertension ,proteinuria ,haematuria, azotemia  Progression to CRF and death unless renal dialysis or transplantation is done.
  160. 160. Thank you