nephritic and nephrotic syndrome

pathological approach

1. Nephritic and nephrotic syndrome PBL 6 8 sept 2017 1

2. objectives Nephritic and nephrotic syndrome - pathophysiology - clinical features 2

3. Kidney disease Affect four basic morphologic components Glomeruli Tubules Interstitium Blood vessels 3

4. Glomerulus 4

5. Nephritic syndrome Glomerular diseases presenting with a nephritic syndrome are often characterized by inflammation in the glomeruli succeeding presentation with : Hematuria Red cell casts in the urine Azotemia Oliguria Mild to moderate hypertension Proteinuria and edema are common, but not as severe as those confronted in the nephrotic syndrome 5

6. Acute Proliferative ( poststreptococcal , Postinfectious ) Glomerulonephritis Rapidly progressive (Crescentic ) Glomerulonephritis 6

7. Acute Proliferative Glomerulonephritis Characterized histologically by diffuse proliferation of glomerular cells associated with influx of leukocytes # Pathophysiology Deposition of immune complexes (in situ) containing streptococcal antigens and specific antibodies leading to complement activation and inflammation . Begins after 2-6 weeks of Nephritogenic Streptococcal Infection - Throat(M type : 1,3,4,3,25,49,12) or - Skin(M type: 47,49,55,2,60,57) 7

8. Morphology 8 Normal glomerulus Glomerular hypercellularity (Leukocyte and glomerular cells) c. Electron dense sub-epithelial Hump d. Coarse granular deposits of C3

9. Clinical features Frequently seen in children Present with peripheral and periorbital edema Cola-color urine Hypertension Positive strep. t itres Decrease C3 complement level due consumption 9

10. Rapidly progressive (crescentic) glomerulonephritis It is a syndrome associated with severe glomerular injury , but does not denote a specific etiologic form of glomerulonephritis Most common histologic picture is the presence of crescents in most of the glomeruli 10

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12. # Pathophysiology Several distinct pathogenic mechanism 1. Anti-GBM antibody mediated diseases (immunologic basis) Characterized by linear deposits of IgG and, in many cases, C3 in GBM Anti GBM when cross-react with pulmonary alveolar basement membrane produces clinical picture of pulmonary hemorrhage with renal failure ( Goodpasture syndrome ) 2. Disease caused by immune complex deposition RPGN as a complication of any of immune nephritides : eg . Lupus nephritis, PSGN Granular pattern of staining (shows immune complex deposition) 3. Pauci - immune RPGN Defined as lack of detectable anti-GBM antibodies or immune complex by immunofluorescence and electron microscopy 12

13. Morphology Fig. Endothelial and mesangial proliferation (PAS stain ) Fig. glomerulus in immunofluorescence (crescent) 13 Crescent : proliferation of parietal layer and migration of monocyte , macrophage and fibrin strand between cellular layer Collapsed glomerular tuft, Leukocytes in bowman's capsule

14. Clinical features Rbc cast , Rapidly deteriorating renal function (days to weeks) Hematuria/hemoptysis Pulmonary hemorrhage(GPS) 14

15. Nephrotic syndrome Caused by a derangement in glomerular capillary walls resulting increased permeability to plasma proteins Clinical Syndrome Characterized by : Massive proteinuria, >3.5 gm/day Hypoalbuminemia (<3gm/dl) Generalized edema Hyperlipidemia and lipiduria 15

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17. Minimal change disease Characterized by diffuse effacement of foot process of podocytes , detectable only by electron microscopy, in glomeruli that appear virtually normal by light microscopy Absence of immune complex deposit in the glomerulus, but immunologic basis as : - clinical association with respiratory infection and prophylactic immunization - response to corticosteroids - Increase incidence in Hodgkin lymphoma 17

18. Morphology 18 A. Normal appearance in LM B. Effacement of foot processes (arrows) and no deposits in EM

19. Membranous Nephropathy Characterized by diffuse thickening of glomerular capillary wall due to the accumulation of Ig deposits along the sub-epithelial side of basement membrane Caused by auto Abs that cross react with Ag express by podocytes . 75% cases are primary, secondarily due to : Drugs Malignant Tumors SLE Infections 19

20. Morphology 20 Diffuse thickening of capillary wall, spikes on silver stain (arrow) Electron dense sub-epithelial deposit on epithelial BM side C. Granular immunofluorescent deposits of IgG D. Diagrammatic representation

21. Focal Segmental Glomerulosclerosis (FSGN) Characterized by sclerosis of some, but not all glomeruli (focal); and in the affected glomeruli, only a portion of capillary tuft is involved (segmental) Epidemiology: Most common cause of nephrotic syndrome in African American Primarily :idiopathic Secondarily as: HIV nephropathy, Heroin nephropathy IgA nephropathy Maladaptation after nephron loss Inherited congenital forms 21

22. pathophysiology Characteristic degeneration and focal disruption of podocyte with effacement of foot processes resembling diffuse epithelial cell change Epithelial damage as hallmark of FSGS Genetic basis of pathology : - Mutation in NPHS 1 ( Nephrin ) - Mutation in NPHS2 gene ( Podocin ) - defect in alfa-actinin4 - mutation in TRPC6 22

23. Morphology 23 Fig. Trichome stain and PAS stain Collagen deposition on vascular side

24. Clinical features Basic features of nephrotic syndrome which may also lead to the renal insufficiency and chronic renal disease 24

25. Membranoproliferative glomerulonephritis (MPGN) Either may be combined with nephrotic-nephritic picture and with proteinuria or hematuria Two types Type I : Deposition of immune complex containing IgG and complement Type II (Dense deposit disease) : Activation of complement (C3) appears to be of significance Characterized by alternation in GBM, proliferation of glomerular cell, leukocyte infiltration and presence of deposits in mesangial regions and glomerular capillary walls 25

26. Morphology 26 - Accentuated lobular appearance due to proliferation of mesangial cells and increase mesangial matrix - GBM thickened and shows a tram-track appearance (due to duplication of basement membrane ), in jones silver stain

27. Isolated glomerular nephritis IgA nephropathy ( berger disease) : Characterized by IgA-containing complex mesangial deposit Most common cause of glomerulonephritis worldwide Alport syndrome : a form of hereditary nephritis caused by mutation in genes encoding GBM type IV collagen Hematuria and proteinuria 27

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29. References Robbins and Cotran Pathologic basis of disease,9e,vol2 Robbins and Cotran atlas of pathology, 3e 29

30. Thank you 30