Pathology of Kidney Part II

1. Pathology of Kidney Part II Dr. Sachin Kale, MD. Asso. Professor, Dept of Pathology.

2. Nephrotic syndrome • Massive proteinuria (>3.5 gm/24 hrs) • Hypoalbuminemia • Generalised edema • Hyperlipidemia • Why? – derangement in glomerular capillary wall – Increased permeability

3. NS: pathophysiology • Proteinuria –depletion of serum albumin • Edema – results from loss of colloid pressure of blood – accumulation of fluid in interstitial tissue • Sodium/ H2O retention – • Aldosterone, ADH, decreased ANP • Edema: soft and pitting – periorbital region

4. NS: pathophysiology • Largest proportion of protein lost is albumin • Highly selective proteinuria – low molecular wt proteins • Poorly selective proteinuria : HMW in addition to albumin

5. Genesis of Hyperlipidemia • Increased levels of Cholesterol, TG, VLDL, LDL, LP(a), apolipoproteins • Increased synthesis of Lipoproteins in liver, abnormal transport of lipids, decreased catabolism. • Lipiduria: lipoproteins leak across glomerular capillary wall. • Oval fat bodies

6. Vulnerability towards infection • Staph, peumococci, why? Loss of Immunoglobulins, LMW complement • Thrombotic/thomboembolic complications – loss of anticoagulant factors • Renal vein thrombosis

7. Causes of NS • Primary glomerular diseases: Membranous GN (5, 40%), Lipoid Nephrosis (65, 15%), FSGS (10, 15%), MPGN (10, 7%), IgA nephropathy • Systemic diseases: Diabetes, amyloidosis, SLE, Drugs (Gold, penicillamine, heroin), Infections (malaria, syphilis, Hepatitis B, AIDS), Malignancy (carcinoma, melanoma), Misc (bee sting, hereditary nephritis)

8. Membranous GN • Major cause of NS in adults • Presence of electron dense, Ig containing deposits subepithelial side of BM • Early: normal by light microscopy Diffuse: thickening of capillary wall

9. Secondary MGN • Malignant epithelial tumors, carcinoma lung, colon and melanoma • SLE • Exposure to inorganic salts (Gold, mercury) • Drugs (Penicillamine, Captopril) • Infections (ChrHep B), syphilis, thyroiditis • Met. Disorders (GM, thyroidis) • 85% Idiopathic

10. Etiology/Pathogenesis • Chr antigen-antibody mediated disease • Secondary forms – specific antigens implicated – Exogenous/Endogenous (thyroglobulin) • Majority of patients antigens unknown • Genetic susceptibility • In situ immune reaction – glomerular or planted antigens • Heymann’s nephritis • Why capillaries are leaky? Membrane attack complex complent

11. Morphology • Early stages: normal • Uniform, diffuse thickening of capillary wall

14. Clinical features • Insidious NS, 15% non-nephrotic proteinuria • Hematuria/Mild HT – (15 – 35%) • Course: indolent • Progression: increasing sclerosis, rising BUN, reduction of proteinuria, HT. • Proteinuria persists 60%, 10% die, 40% develop renal insufficiency

15. Minimal change disease • Relatively benign disorder • Most frequent cause in children • Diffuse loss of foot processes of epithelial cells • Glomeruli virtually normal by light microscopy • Peak incidence: 2 – 6 yrs

16. Etiology/ pathogenesis • Immunologic basis – • Clinical asso with respiratory infections and immunizations • Response to steroid and immunosuppressive therapy • Asso with other atopic disorders • Increased prevalence of certain HLA haplotypes

17. Increased incidence in HD • Recurrence of proteinuria after transplantation

19. Minimal Change Disease: Loss of Foot processes

20. Clinical features • Proteinuria • Renal function good • No HT or Hematuria • 90% rapid response to steroids • May recur • Steroid dependent • Long term prognosis: excellant

21. Focal segmental glomerulosclerosis • Sclerosis of some (focal) but not all, glomeruli • Only a portion of capillary tuft (segmental) is involved. • A) Idiopathic • B) FSG superimposed on other primary GN (IgA nephropathy) • C) Renal ablation FSG • Secondary FSG (HIV, Heroin)

22. FSG.. • 10 - 15 % cases of NS • Hematuria, GFR, HT • Proteinuria: Non-selective • Poor response to steroids • Progress to Chr GN • IgM, C3 deposits

23. FSG.. • Sclerotic segments: collapse of BM • Increased mesangial matrix • Deposition of Hyaline masses (Hyalinosis) • Lipoid droplets • Diffuse loss of foot processes • Pronounced, focal detachment of epithelial cells • Denudation of underlying GBM • Hyaline thickening of afferent arterioles • Global sclerosis • Tubular atrophy and interstial fibrosis

26. FSG: Clinical features • No spontaneous remissions • Children : better prognosis. • Malignant focal sclerosis: 20% unusually rapid course • HIV: Idiopathic FSG, focal cystic dilation of tubule segments, tubuloreticular inclusions

27. Membranoproliferative GN • Alteration in BM & proliferation of glomerular cells • Mesangiocapillary GN • 5 – 10% idiopathic NS • Hematuria/proteinuria • Asso with systemic disorders, Primary or secondary

28. MPGN • Glomeruli: large, Hypercellular • Proliferation of mesangial cells, • Leukocytic infiltrate, parietal epithelial crescents • Lobular appearance of glomeruli • GBM thickened

29. MPGN • Gomerular capillary wall shows ‘double contour’ or ‘Tram track apperence” • Splitting of BM due to extension of processes of mesangial cells : Mesangial interposition • Type I: Subendothelial electron dense deposits

30. MPGN • Type II: Deposition of dense material of unknown composition in GBM proper • C3 is present in granular linear foci and as mesangial rings. • IgG absent • Type III: Subendothelial and subepithelial deposits

31. Membranoproliferative“tram-tracking”

32. MPGN

33. Type I: Immune complexes, activation of classic and alternate pathway of complement • Type II: Activation of alternate pathway of complement • C3 Nephrtic Factor (C3NeF) in blood • Presents as NS • Progresses slowly but unremittingly • Some develop RPGN • 50% develop CRF in 10 years

34. Secondary MPGN • Usually of Type I • SLE, Hepatitis B, C • Cryoglobulinemia • Chronic liver disease • Certain malignancies • Schistosomiasis

35. Chronic Glomerulonephritis • End stage pool of gomerular disease - • RPGN • Membranous GN • Focal Glomerulosclerosis • MPGN • IgA nephropathy • Poststreptococcal is rare, others

36. Morphology • Symmetrically contracted kidneys • Diffuse granular cortical surface • Cortex is thinned • Peripelvic fat is increased • Hyaline obliteration of glomeruli • Acellular, eosinophilic PAS-positive masses

38. Arterial arteriolar sclerosis: HT • Atrophy of tubules • Interstitial fibrosis • Lymphocytic infiltrate • Stigmata of uremia: pericarditis, gastroenteritis, renal osteodystrophy, LVH due to HT, Uremic pneumonitis

39. Clinical features • Develops insidiously • Nonspecific GI complaints • Finding of azotemia, proteinuria, HT on routine check up • Edema • HT – CNS, CVS problems • Dialysis or transplantation

40. False about NS • Proteinuria results from deranged capillary walls • In selective proteinuria Albumin is lost • Hyperlipidemia • Vulnerability to infection • Bleeding complications

41. False about MCD.. • Frequent cause of NS between 2 – 6 yrs • Glomeruli show thickening of GBM by light microscopy • Immune deposits are not seen • Tubules are ladden with lipids.

42. FSGS: True or False True • Seen in Heroin abuse and HIV • Selective proteinuria • Respond well to steroids • Many Progress to chronic GN • Sclerotic segments show hyalinosis and lipoid droplets • There is no podocyte fusion • Represents evolution of MCD False False True True False True

43. False about MPGN.. • Type I is common • Type I shows subendothelial electron dense deposits • Type I is called dense deposit disease • In type II GBM is, irregular, ribbon-like structure • Type I shows Immune complexes • Type II has activation of alternate complement pathway • Secondary MPGN is usually type I

44. Following commonaly leads to Chronic Glomerulonephritis except • RPGN • Membranous GN • MPGN • Post-streptococcal GN in children

45. False about CGN • Asymmetrically contracted kidneys • Thinned cortex • Hyaline obliteration of glomeruli • Hypertension • Atrophy of tubules • Uremia

46. Which of the following is a clinical feature of CGN • Loss of appetite, nausea, • Proteinuria, HT • Edema • All of the above

47. Spot the diagnosis… FSGS

48. Spot the diagnosis… CGN

49. Spot the diagnosis… MGN

50. Spot the diagnosis… MCD