Transcript Slide 1
Pathology of Kidney Part II Dr. Sachin Kale, MD. Asso. Professor, Dept of Pathology. Nephrotic syndrome Massive proteinuria (>3.5 gm/24 hrs) Hypoalbuminemia Generalised edema Hyperlipidemia Why? – derangement in glomerular capillary wall – Increased permeability 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 NS: pathophysiology Largest proportion of protein lost is albumin Highly selective proteinuria – low molecular wt proteins Poorly selective proteinuria : HMW in addition to albumin 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 Vulnerability towards infection Staph, peumococci, why? Loss of Immunoglobulins, LMW complement Thrombotic/thomboembolic complications – loss of anticoagulant factors Renal vein thrombosis 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) 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 Secondary MGN Malignant epithelial tumors, carcinoma lung, colon and melanoma SLE Exposure to inorganic salts (Gold, mercury) Drugs (Penicillamine, Captopril) Infections (Chr Hep B), syphilis, thyroiditis Met. Disorders (GM, thyroidis) 85% Idiopathic 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 Morphology Early stages: normal Uniform, diffuse thickening of capillary wall 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 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 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 Increased incidence in HD Recurrence of proteinuria after transplantation Minimal Change Disease: Loss of Foot processes Clinical features Proteinuria Renal function good No HT or Hematuria 90% rapid response to steroids May recur Steroid dependent Long term prognosis: excellant 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) FSG.. 10 - 15 % cases of NS Hematuria, GFR, HT Proteinuria: Non-selective Poor response to steroids Progress to Chr GN IgM, C3 deposits 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 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 Membranoproliferative GN Alteration in BM & proliferation of glomerular cells Mesangiocapillary GN 5 – 10% idiopathic NS Hematuria/proteinuria Asso with systemic disorders, Primary or secondary MPGN Glomeruli: large, Hypercellular Proliferation of mesangial cells, Leukocytic infiltrate, parietal epithelial crescents Lobular appearance of glomeruli GBM thickened 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 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 Membranoproliferative “tram-tracking” MPGN 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 Secondary MPGN Usually of Type I SLE, Hepatitis B, C Cryoglobulinemia Chronic liver disease Certain malignancies Schistosomiasis Chronic Glomerulonephritis End stage pool of gomerular disease RPGN Membranous GN Focal Glomerulosclerosis MPGN IgA nephropathy Poststreptococcal is rare, others Morphology Symmetrically contracted kidneys Diffuse granular cortical surface Cortex is thinned Peripelvic fat is increased Hyaline obliteration of glomeruli Acellular, eosinophilic PAS-positive masses Arterial arteriolar sclerosis: HT Atrophy of tubules Interstitial fibrosis Lymphocytic infiltrate Stigmata of uremia: pericarditis, gastroenteritis, renal osteodystrophy, LVH due to HT, Uremic pneumonitis Clinical features Develops insidiously Nonspecific GI complaints Finding of azotemia, proteinuria, HT on routine check up Edema HT – CNS, CVS problems Dialysis or transplantation False about NS Proteinuria results from deranged capillary walls In selective proteinuria Albumin is lost Hyperlipidemia Vulnerability to infection Bleeding complications 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. FSGS: True or False Seen in Heroin abuse and HIV True Selective proteinuria False Respond well to steroids False Many Progress to chronic GN True Sclerotic segments show hyalinosis and lipoid droplets True There is no podocyte fusion False Represents evolution of MCD True 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 Following commonaly leads to Chronic Glomerulonephritis except RPGN Membranous GN MPGN Post-streptococcal GN in children False about CGN Asymmetrically contracted kidneys Thinned cortex Hyaline obliteration of glomeruli Hypertension Atrophy of tubules Uremia Which of the following is a clinical feature of CGN Loss of appetite, nausea, Proteinuria, HT Edema All of the above Spot the diagnosis… FSGS Spot the diagnosis… CGN Spot the diagnosis… MGN Spot the diagnosis… MCD Spot the diagnosis… MPGN Thought for the day… Life is like lemon & spoon race, if you drop the lemon there is no use coming first.. Same is with life, where health and family are your lemon! Thank you! Contact: http://sachinkale1.tripod.com