Renal Pathology PDF

Renal pathology I Dr Mazen Abood Bin Thabit Associate professor of Pathology Senior lecturer of Oral pathology Classification of renal disease  Glomerular disease  Disease affecting tubules and interstitium  Disease involving the blood vessels  Cystic disease of the kideny  Urinary outflo...

Renal pathology I Dr Mazen Abood Bin Thabit Associate professor of Pathology Senior lecturer of Oral pathology Classification of renal disease  Glomerular disease  Disease affecting tubules and interstitium  Disease involving the blood vessels  Cystic disease of the kideny  Urinary outflow obstruction  Tumors  Medical nephropathology  Glomerular disease  Histology Is a group of disorder  Function characterized by destruction of the glomerular  Pathophysiology components and constitute one of the most common causes of chronic renal failure ( ESRD) Glomerular structure and function Bodocyte  Mechanism  Immune mediated I. Immune Complex – glomerular injury associated injury  Characterized by Ag-Ab 1. Circulating : complex formation 2. In Situ : whitish precipitated in a) Glommerular the glomerulous GBM nephritis Heymann’s nephritis a) Non glomerular DNA Bacterial products Large aggrgate of proteien Pathogenesis  Pathogenesis ii. Cytotoxic antibodies : VI. Hyperfilteration Ab directed to glomerular Ag and cause direct lysis of cells Injury occur during ( Mesangiolysis) hemodynamic changes III. Activation of classic Glomerular Blood Flow and alternative Glomerular pressure pathway IV. Cell mediated immunity Single nephron glomular V. Loss of polyanion filtration Effectively destroy part of the charge –selective barrier vii. Podocyst injury: that essential to glomular filtertaion  Pattern of glomerular response to injury 1. Cellular proliferation 2. Leukocyte infilteration 3. Thickenning of glumerular capillary loop Deposition of immune complex Increase in GBM material An in filtration of abnormal material Factor affecting localization of deposit Pattern of glomerular response to injury  BM reaction : Membranous Projection ( Spikes ) Splitting of BM ( Double counter )  Hyalinosis :  Fibrosis  Epithelial cell injury Pattern or extent of glomerular injury  Diffuse : All glomeruli affected  Focal : Some glomeruli affected  Segmental : Part of glomeruli affected  Global : The entire glomeruli affected  Classification  WHO classification: I. Proliferative GN II. Non Proliferative GN Classification  GN associated with  Clinical nephrotic syndrome classification I. Primary : Minimal change disease Membranous GN Membranoproliferative GN Focal Segmental glomeruosclerosis II. Secondary: DM Amyloidosis SLE and IgA nephropathy Drugs Infection Malignancy Hereditary Classification  GN associated with  Clinical nephritic syndrome classification I. Primary : Post-streptococcal GN Rapid progressive GN Good Pasture's syndrome II. Secondary: SLE Essential cryoglobulinemia Wegener’s granuloma Henoch –Schonlein purpura Classification  Clinical classification  Clinical manifestation of GN  Asymptomatic hematuria: Continuous or intermittent Micro to macro without significant proteinurea Dose not cause renal failure  Asymptomatic proteinurea Proteinurea› 0.3 gm/24/hr without hematura Continuous or transiant  Clinical manifestation of GN  Acute nephritic syndrome Sudden Hematuria Mild proterinurea Oligurea and uremia Flank pain Hypertention No edema  Acute nephrotic synderome Heavy proteinurea ›3.5gm /day Hypoproteinemia Hyperlipidemia Odema  Clinical manifestation of GN  Chronic renal failure Uremia Anemia Metabolic bone disesae Acidosis neuropathy Endocrine abnormalities GN Associated with Nephritis syndrome  Acute Post infectious GN:  Common cause  Immune complex deposit disease  2 wk after streptococcal infection  More in children  Cause by type 12,4 and 1 group Aβ hemolytic streptococci  Non streptococcal less common of either bacterial , viral and parasite GN Associated with Nephritis syndrome  Microscopic:  Glomeruli enlarged and hyper-cellular  Infiltration by leukocytes  Diffuse proliferative pattern  Electron microscope:  Large immune complex deposit ( subendothelial , intra-membranous and most often sub-epithelial ) Hump  Immuno-flurosecence  Scattered granular deposit of IgG, Igm and C3 GN Associated with Nephritis syndrome  Rapid progressive ( Crescent ) GN  It is clinical syndrome rather than specific form  Accompanied by rapid and progressive decline of renal function  Characterized histologically by accumulation of cells in the Bowman's space in the form of crescent GN Associated with Nephritis syndrome  Classification 1. Post infectious 2. Systemic disease SLE Good Pasture syndrome Wegener’s granulomatosis Essential cryoglobulinemia 3. Idiopathic I. Anti GBM crescent GN II. Immune complex crescent GN III. Pauci-immune Crescent GN  GN Associated with Nephritis syndrome  Anti GBM crescent GN  Renal faiular and when accompanied with heamoptysis ( Goodpasture syndrome)  Classic example of in situ immune complex anti-GBM nephritis  Ag is noncollagenous protein of 3 chain of collagen type IV  Linear deposit of IgG and C3 along the GBM.  Anti-GBN antibodies in the serum  Plasmapheresis  GN Associated with Nephritis syndrome  Immune complex crescent GN  Rapid progressive Renal failure.  Granular ( Lumpy –bumpy) pattern of staining of GBM or mesengeum & C3  Not responds to Plasmapheresis  GN Associated with Nephritis syndrome  Pauci- Immune crescent GN  Rapid progressive Renal failure.  the patient have no or minimal immune complex ( Pauci –immune crescent GN)  Produced by anti-neutrophilic cystoplasmic antibodies ( ANCA) 1. Antimyeloperosidase 2. Antiprotease 3  Idiopathic RPGN may be ( Immune complex , antiGBM or ANCA GN Associated with Nephritis syndrome  Macro:  Kidney enlarged , pale with petechial hemorrhage  Micro:  Diffuse or focal proliferation of endothelial cells and mesengium  Segmental necrosis  Crescent formation  Electron microscope:  Rupture of BM or subendothelail deposit  Immunofluorescent :  Linear , granular or no GN associated with nephritic syndrome  IgA Nephropathy:  Isolated disease  Berger’s disease ( Primary )  Prominent IgA deposit in  Secondary the mesangium  Affect children and young Henoch Schőnlein purpura adult Liver disease  The most frequent cause of Intestinal disease recurrent gross or microscopic hematuria  Mild proteinurea  Initial course is benign  Renal failure occur over 20 years GN associated with nephritic syndrome  Light microscope:  Normal or widening and proliferation of mesangium Focal Diffuse.  Electron microscope:  Dense deposit in the mesangium  Immunofluorescent  Mesangial deposit of IgA , C3 and Properdin and less amount of IgM and IgG Hereditary nephritis  A group of hereditary  Alport syndrome glomerular disease  X linked disease caused by mutation in  Nephritis gene encoding GBM proteins  Nerve deafness  Various eye disorder  Congenital nephrotic syndrome  AR disease  Nephrotic syndrome in the 1st weeks of life  GN associated with nephrotic syndrome  Minimal change disease ( MCD)  Lipoid nephrosis  The most common cause of nephrotic syndrome  Diffuse loss of foot process  Appears normal by light microscope  May follow respiratory infection or vaccination  GN associated with nephrotic syndrome  Pathogenesis : The role of immune mechanism supported by :  Associated with respiratory infection and immunization  Respond for coticosteroids  Associated with allergic disease  Increase the prevalence with certain HLA  Increase incidence with Hodgkin disease  Recurrence of proteinurea after transplantation  Report of proteinurea –inducing factor in the plasma  Light microscope:  Normal glomeruli  Electron mcroscope:  Normal BM  No electron dense deposit  Uniform and diffuse effacment of foot process  Proximal tubules laden with lipid ( Lipoid nephrosis )  Immuno-fluorescence :  No immunoglobulin or complements  GN associated with nephrotic syndrome  Focal segmental  Idiopathic glomerulosclerosis :  FSG superimposed on another  Chracterized by sclerosis of primary glomerular disease some , but not all the ( e.g IgA nephropathy) glomeruli ( Focal ) and in the in  FSG associated with loss of the affected glomeruli only renal mass ( Renal ablation portion of the capillary tuft is FSG) involved ( Segmental ) e.g. Reflux nephropathy Analgesic nephropathy Unilateral renal agenesis  Secondary Heroin abuse HIV infection  Inherited or congenital form GN associated with nephrotic syndrome  Idiopathic FSG:  Account 20-30 % of nephrotic syndrome  Differ from MCD by:  Higher incidence of hematuria , decrease GFR and hypertension  Protienurea more selective  Poorly respond to corticosteroid  50% of cases progress to End Stage Renal Disease ( ESRD)  Immunofluorscent shows immune depots of Igm and C3 GN associated with nephrotic syndrome  Light microscope:  Initially involves the juxtmedullary glomeruli  The sclerotic segment shows collapse of BM with obliteration of calpillary lumen , increase of mesangeal matrix, deposition of hyaline masses ( Hyalinosis ) and lipid droplets  Non sclerotic glomeruli appears normal or may shows increase of mesangeal matrix and mesangeal proliferation  Electron microscope:  Non sclerotic area shows diffuse loss of foot process with pronounced focal detachment of B.M  Immunofluorescent :  Igm and C3 present in the hyaline masses GN associated with nephrotic syndrome  Membranous GN :  Secondary :  Membranous nephropathy. 1. Malignant epithelial tumors  Prototype of Heymann 2. SLE nepheritis 3. Inorganic salt  Sub-epithelial immuno- 4. Infection globulin deposit 5. Metabolic  Slowly progressive disease  Idiopathic:  Is a major cause of 1. 85% nephrotic syndrome in adult. 2. Unknown cause  Early disease Glomeruli normal  Diffuse thickening of capillary wall.  85% auto-antibodies to foot process antigen  In situ immune complex  Diffuse thickening of GBM and mesengeal proliferation  Sub-epithelial granular deposits  Spikes formation ( Spikes and dome formation )  Effacement of foot process GN associated with nephrotic syndrome  Membranoproliferative GN  Secondary :  5-10% of nephrotic 1. Malignant epithelial tumors syndrome in children and 2. SLE adult. 3. Inorganic salt  Alteration of BM and 4. Infection mesangium and proliferation of glomerular cells 5. Metabolic  Diffuse thickening of capillary  Idiopathic: wall. 1. 85%  Classified into ; 2. Unknown cause 1. Type I MPGN 3. 15-25% caused by in situ 2. Dense deposit disease (Type II) immune complex caused Ab 3.Type III MPGN to intrinsic tissue Ag  Light microscope:  Normal at early stage  Later uniform and diffuse thickening of the capillary wall  Absence of inflammtion  Electeron microscope:  Irregular dense deopsit between BM and epithelial cells  B.M material between deposit appears as irregular spikes  Later immue deposit fuse with B.M material  Mild increase of mesangium GN associated with nephrotic syndrome GN associated with nephrotic syndrome  Immunofluorescence  Garnular deposit contains both IgG and complements  Diabetic glomerulosclerosis  D.M is the major of renal  Clinical feature : morbidity and mortality  Occur after 10-20 years of  Renal failure occur in 30% clincal disease accompained of insulin dependent D.M with :  3 glomerular syndromes 1. Microangiopathy: Ratinopathy 1. Non nephrotic proteinurea CHD 2. Nephrotic proteinurea Peripheral vascular 3. Chronic renal failure insifficincy  Arteriosclerosis 2. Renal symptoms accelerated in DM Proteinurea  Pyelonephritis and Glucosurea papillary necrosis are more Progressive decrease in common in D.M renal function :  Pathogenesis  Linked with generalized  Hemodynamic changes : micro-angiopathy : Uncontrollaed hyperglycemia associated with increase of  Metabolic defect which cause GFR and increase of GF area hyperglycemia with an increase of glomerular  Biochemical alteration in diabetic capillary pressure and GBM with an increase the glomerular hypertrophy which amount and synthesis of collagen type IV and fibronection and accelerate the sclerosis decrease the synthesis of proteoglycans  Non anzymatic glycosylation may give arise of advance glycosylation end product which may cause micro-angiopathy and increase permeability  Pathology I. Capillary BM Thickening  Occur early as few years of clinical onst of D.M  Associated with thickening of tubular BM II. Diffuse glomerulosclerosis  Overall widening of the mesangium and increase of mesangeal matrix  Associated with thickening of glomerular capillary BM  Immunofluorescent may shows weak linear staining with Ig, albumin and plasma protein bind to GBM III. Nodular glomerulosclerosis  Kimmelstiel Wilson disease  Nodular accentuation or expansion mesangium with increase matrix material  Micro-aneurysm dilatation of the adjacent capillary loop