logging in or signing up lab diagnosis of nephrotic syndrome cyto786 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 681 Category: Science & Tech.. License: All Rights Reserved Like it (3) Dislike it (0) Added: February 26, 2011 This Presentation is Public Favorites: 0 Presentation Description nephrotic syndrome is diagnosed using urine, serum & renal biopsy specimens Comments Posting comment... By: vishalvanani (13 month(s) ago) good one. keep it up Saving..... Post Reply Close Saving..... Edit Comment Close By: sitinur (14 month(s) ago) great! Saving..... Post Reply Close Saving..... Edit Comment Close By: cyto786 (14 month(s) ago) yes . Saving..... Post Reply Close Saving..... Edit Comment Close By: mari_kapiko (14 month(s) ago) can i download this slide show?? Saving..... Post Reply Close Saving..... Edit Comment Close By: sathee12345 (14 month(s) ago) very useful slide show thank you for your wonderful contribution Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript LAB DIAGNOSIS OF NEPHROTIC SYNDROME: LAB DIAGNOSIS OF NEPHROTIC SYNDROME MODERATOR : DR SANJEEV NARANG SPEAKER : DR RAVI JAINNEPHROTIC SYNDROME: NEPHROTIC SYNDROME DEFINITION : the nephrotic syndrome is a clinical complex characterized by a no of renal & extra renal features, the most prominent of which are Proteinuria of > 3.5 g/1.73 m 2 /24 hr Hypoalbuminemia Edema Hyperlipidemia Lipiduria HypercoagulabilityGLOMERULUS: GLOMERULUS Glomerulus is an anastomosing network of capillaries lined by fenestrated endothelium invested by two layers of epithelium. The glomerular capillary wall is the filtering membrane consisting of : Thin layer of endothelial cells Glomerular basement membrane Visceral epithelial cells Mesangial cellsENDOTHELIAL CELLS: ENDOTHELIAL CELLS A thin layer of endothelial cells which are fenestrated, are responsible for high permeability of water & solutes. Size of fenestrum varies from 70 to 100 nm in diameter.GLOMERULAR BASEMENT MEMBRANE: GLOMERULAR BASEMENT MEMBRANE Glomerular basement membrane has two layers : Thick electron dense central layer – Lamina densa Thinner electron lucent peripheral layers – Lamina rara interna & externa GBM consists of type IV collagen, laminin, polyanionic proteoglycans, fibronectin, entactin & other glycoproteinsGLOMERULAR BASEMENT MEMBRANE: GLOMERULAR BASEMENT MEMBRANE These charged proteins & fenestrations in endothelium are responsible for impermeability to proteins like albumin & permeability to water & solutes. These charged proteins are anionic & block the passage of anionic proteins like albumin.PODOCYTES: PODOCYTES Also K/as visceral epithelial cells, are important for maintainence of glomerular barrier function. Its slit diaphragm presents a size selective distal diffusion barrier to the filtration of proteins. Podocin & nephrin are two proteins that control glomerular permeabilityPODOCYTES: PODOCYTES Nephrin is trans membrane protein with large extra cellular portion made up of Ig like domains These proteins dimerize across the slit diaphragm Within the cytoplasm of foot processes of podocytes, nephrin forms molecular connections with podocin, CD2 associated protein & actin cytoskeletonMESANGIAL CELLS: MESANGIAL CELLS These are supporting cells of glomerulus, lying between the capillaries. These cells are of mesodermal origin. Contractile Phagocytic Capable of proliferation Laying down both matrix & collagen Secreting no of active mediatorsSlide 11: CAUSES OF THE NEPHROTIC SYNDROME IN ADULTSNEPHROTIC SYNDROME: NEPHROTIC SYNDROME PATHOGENESIS: Derangement in glomerular capillary walls Increased permeability to plasma proteins Massive proteinuria + increased renal catabolism of albumin Depletion of serum albumin & reversal of A:G ratio Generalized edema abnormal transport of lipids + decreased catabolism HyperlipidemiaSlide 14: Figure 3.NEPHROTIC SYNDROME: NEPHROTIC SYNDROME CLINICAL FEATURES: Massive proteinuria Hypoalbuminemia Generalized edema Hyperlipidemia & lipiduriaSlide 16: Figure 1. Nephrotic edema.Slide 17: Figure 2. Nephrotic edema.LAB DIAGNOSIS OF NEPHROTIC SYNDROME: LAB DIAGNOSIS OF NEPHROTIC SYNDROME Specimen Urine Serum Renal biopsyURINE EXAMINATION: URINE EXAMINATION Physical examination Chemical examination Microscopic examinationPHYSICAL EXAMINATION: PHYSICAL EXAMINATION Volume- increased in Diabetes mellitus Color – Milky due to lipiduria in nephrotic syndrome Appearance Sediment formation Odor Specific gravity (Sp. Gr.) – High due to proteinuria Osmolality – increased in nephrotic syndromeSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) At constant temperature weight of volume of urine weight of same volume of distilled water Measure the diluting and concentrating power of kidneys Reliable indicator of body hydration statusSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Depends upon the number and weight of particles in urine Normal value - 1.003 to 1.035 (For random sample) - 1.015 – 1.030 (For 24 hr sample) Normal contributors 1. Urea (20%) 2. Sodium chloride ( 25%) 3. Sulfate 4. PhosphatesSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Hypersthenuria – High specific gravity 1 . Diabetes mellitus 2. Dehydration 3. Eclampsia 4. Proteinuria 5. Nephrotic syndrome 6. Fever 7. Acute nephritisSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Hyposthenuria – Low specific gravity (<1.007) 1. Pyelonephritis 2. Hypertension 3. Diabetes insipidus 4. Protein malnutrition 5. Glomerulonephritis 5. Diuretics drugsURINE EXAMINATION: URINE EXAMINATION CHEMICAL EXAMINATIONURINE EXAMINATION: URINE EXAMINATION Urine : Protein estimation Qualitative Quantitative – 24 hr protein estimationPROTEIN DETERMINATION IN URINE : PROTEIN DETERMINATION IN URINE - Normal kidney secretes only small amount of low molecular weight proteins filtered, most of which are reabsorbed by tubules. - Normal protein excretion <150 mg/day in adult. - Daily physiological protein contain :- (i) Mucoprotein (Tamm Horsfall glycoprotein 70 mg) (ii) Blood group related antigen 35 mg (iii) Albumin 15 mg (iv) Mucopolysaccharide 15 mg (v) Immunoglobulin 5 mg - Abnormal amount of protein in urine – ProteinuriaPATHOPHYSIOLOGICAL CLASSIFICATION OF PROTEINURIA : PATHOPHYSIOLOGICAL CLASSIFICATION OF PROTEINURIA Physiological Proteinuria Glomerular proteinuria Tubular proteniuria Other types (i) Benign orthostatic proteinuria (ii) Transient proteinuria (iii) Microalbuminuria (iv) Bence jones ProteinuriaDifference between glomerular and Tubular proteinuria : Difference between glomerular and Tubular proteinuria Glomerular Tubular Due to injury of Renal glomerulus Due to Injury Involving Tubulointerstitial region Comprises predominantly albumin Comprises low molecular wt protein ( 2 microglobilin Protein excretion >3 – 3.5 gm/dl < 2 gm/dl. Urinary protein electrophoresis More albumin than globulin More globulin Albumin micro globulin ratio > 1000 : 1 100:1 (N – 50-200:1) Cause - Glomerulonephritis - - Hypertension - Lipoid Nephrosis - - Pyelonephritis - - Interstitial Nephritis - Rejection of kidney allograftQualitative tests for protein : Qualitative tests for protein Reagent strip method Precipitation method (a) Heat and acetic acid test (b) Sulphosalicylic acid test (c) Heller’s nitric acid testPrecipitation method : Precipitation method Urine Protein: SSAChemical Tests on Urine: (Reagent Strip/Dipstick Analysis): Procedure : Chemical Tests on Urine: (Reagent Strip/Dipstick Analysis): Procedure Reagent strip method : Reagent strip method Dipstick more sensitive to albumin than globulin, mucoproteins, Bence-Jones protein False Positives: - Chlorhexidine, quartenary ammonium antispetic or detergent residual left in container - Vaginal secretions - Highly buffered urine with pH >6.5PROTEIN - URINE: PROTEIN - URINE Normal : < 20 mg % Reagent strip/ stick Negative : 0 – 5 mg/dl Trace : 5 – 20 mg/dl 1+ : 30 mg/dl 2+ : 100 mg/dl 3+ : 300 mg/dl 4+ : 1000 mg/dlPROTEIN - URINE: PROTEIN - URINE False +ve results: Incorrect matching of reagent strip to the color chart Prolonged exposure of the strip or stick to the urine Hematuria Drugs Acetazolamide Amino salicylic acid Chlorpromazine PenicillinPROTEIN - URINE: PROTEIN - URINE False -ve results: Very dilute urine Highly buffered alkaline urine Urine high in sodium Urea splitting organismsPROTEIN- URINE: PROTEIN- URINE Increased in : Amyloidosis Collagen disease Cryoglobulinemia Nephrotic syndrome Diabetes24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION This test is indicated when a random urine sample is positive for more than a trace of protein. Protein substances are excreted at different rates & at varying times in a 24 hr period 24 hr protein estimation provides the most accurate reflection of kidney function24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION Early morning is the preferred time for 24 hr urine collection Discard the first morning urine specimen Save all the urine voided for 24 hr in a clean refrigerated container Include the urine voided at the end of the 24 hour period24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION Quantitative norms : Adults : 30 – 150 mg/ 24 hrs Children < 10 years : < 100 mg/ 24 hrs New born : increased protein in urine for 3 days after delivery24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION False +ve quantitative test : Drugs Acetazolamide Amino salicylic acid Aspirin Barbiturates Cephalosporins Penicillin False -ve quantitative test : Urine accidently discarded during 24 hr collection Urine lost during defecationPROTEIN ELECTROPHORESIS - URINE : PROTEIN ELECTROPHORESIS - URINE Principle -The term electrophoresis describes the migration of a charged particle under the influence of an electric field. Many important biologic molecules, such as amino acids, peptides, proteins, nucleotides and nucleic acids, possess ionizable groups and, therefore, at any given pH, in solution as electrically charged species either as cations(+) or anions(-) Under the influence of an electric field these charged particles will migrate either to the cathode or to the anode, depending on the nature of their net charge.PROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE Normal urine electrophoretograms show individual variance & show a globulin pattern that is generally diffuse . The dominant protein is albumin. Normal pattern seen : Albumin : 37.9 % ά 1 globulin : 27.3 % ά 2 globulin : 19.5 % β globulin : 8.8 % γ globulin : 3.3 %PROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE INTERPRETATION: Proteinuria associated with increased glomerular permeability exhibits an electrophoretic pattern that is dominated by albumin, with moderate β globulin , some ά globulin & trace γ globulinPROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE Factors that affect result: Contamination of the specimen with the stool invalidates the test. Drugs Amikacin Amphotericin B Penicillin PhenylbutazoneMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Casts - Formed in lumen of the tubules of kidney - Tamm-Horsfall protein - Secreted by thick part of ascending loop of henle - Forms the matrix of all casts - Casts can form as the result of- A. Precipitation of gelatin of Tamm-Horsfall mucoprotein B. Clumping/adherence of cells or cellular material to the matrix C. Coagulation of material within the lumenMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE - Cast formation take place in the distal and collecting tubules ( requires high solute concentration and acidic pH) - Dissolves in alkaline pH - Nearly parallel sides and rounded or blunted ends - Convoluted, straight or curved.MICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE A. According To Matrix: a. Hyaline cast - Most frequently observed cas- Colorless, transparent, homogenous with rounded ends - Normally - 0-2 hyaline casts/hpfMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE b. Waxy casts - High refractive index - Yellow gray or colorless and homogenous, smooth sharp margins and blunted endsMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Renal failure casts - Unusually broad waxy castsMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE a. Granular casts - Granules large or small Increased in Pyelonephritis Viral infection Chronic lead poisoning Renal papillary necrosis Hyperparathyroidism Extreme stressMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Causes : Nephrotic syndrome Chronic glomerulonephritisCREATININE - URINE: CREATININE - URINE Urine creatinine(mg/dl) = O.D Test/O.D Std X 100 For determination of 24 hrs creatinine excretion, measure the urine volume & calculate using following formula Creatinine excretion (mg/24 hrs) = urine creatinine, mg/dl X ml, 24 hrs urine/100CREATININE - URINE: CREATININE - URINE NORMS : Adult : 14 – 26 mg/kg/24 hrs Female : 600 – 1800 mg/24 hrs Male : 800 – 2000 mg/24 hrs Child : 8 – 22 mg/kg/24 hrsCREATININE - URINE: CREATININE - URINE INTERPRETATION : It is decreased in nephrotic syndromeCREATININE - URINE: CREATININE - URINE INCREASED IN : Fever Hypothyroidism Tissue catabolism DECREASED IN : Decreased renal perfusion Glomerulonephritis Cystic kidney disease Polymyositis Pyelonephritis Hypovolemic shockPROTEIN - SERUM: PROTEIN - SERUM Normal values : Adults : 6.0 – 8.0 g/dl Children : 4.3 – 7.6 g/dl Premature : 4.6 – 7.4 g/dl Newborn : 6.0 – 6.7 g/dl Infant : 6.2 – 8.0 g/dlPROTEIN - SERUM: PROTEIN - SERUM Factors that affect result: Hemolysed or lipemic specimen Falsely elevated value occur upto 48 hr after use of sulfo- bromopthalein contrast dye Recent dialysis Hyperglycemia Bed ridden patients – lower valuesPROTEIN SERUM: PROTEIN SERUM INCREASED IN : Amyloidosis Addison’s disease Macroglobulinemia Multiple myeloma Sarcoidosis Chronic infection DECREASED IN : Analbuminemia Burns Chronic glomerulonephritis Diarrhea Edema Hyperthyroidism Nephrotic syndrome MalabsorptionPROTEIN ELECTROPHORESIS - SERUM: PROTEIN ELECTROPHORESIS - SERUM Norms : Total protein : 100 % Albumin : 58 – 74 % ά 1 globulin : 2.0 – 3.5 % ά 2 globulin : 5.4 – 10.6 % β globulin : 7.0 – 14.0 % γ globulin : 8.0 – 18.0 %PROTEIN ELECTROPHORESIS – SERUM in NEPHROTIC SYNDROME: PROTEIN ELECTROPHORESIS – SERUM in NEPHROTIC SYNDROME Increased ά globulin zone intensity ( ά 2 globulin ) Increased ά 2 - β 1 globulin interzone intensity Increased β globulin zone intensity Decreased albumin zone intensity Decreased γ globulin zone intensityLIPID PROFILE TESTS for HYPERLIPIDEMIA: LIPID PROFILE TESTS for HYPERLIPIDEMIA TOTAL LIPIDS SERUM TOTAL CHOLESTEROL SERUM H.D.L – C SERUM TRIGLYCERIDES SERUM VLDL SERUM LDLNORMAL LEVELS: NORMAL LEVELS S.No Lipid level 1 TOTAL LIPIDS 400-800 MG/DL 2 TOTAL CHOLESTEROL < 200 MG/DL 3 HDL 30-60 MG/DL 4 TRIGLYCERIDES 10-90 MG/DL 5 LDL <100 MG/DL 6 VLDL < 80 MG/DLLIPID PROFILE IN NEPHROTIC SYNDROME: LIPID PROFILE IN NEPHROTIC SYNDROME Increased LDL – C Increased Total Cholesterol(usually > 350 mg/dl) Increased VLDL Increased TGUREA NITROGEN - SERUM: UREA NITROGEN - SERUM NORMS : Young adult : 5 – 18 mg/dl Adult : 5 – 20 mg/dl Elderly > 60 yrs : 8 – 21 mg/dl Mild azotemia : 20 – 50 mg/dl Children : Cord blood : 21 – 40 mg/dl Full term newborn : 3 – 25 mg/dl Infant : 5 – 18 mg/dl Child : 5 – 18 mg/dlUREA NITROGEN - SERUM: UREA NITROGEN - SERUM Urea N 2 increased in : Addison’s disease Amyloidosis Diabetes mellitus Glomerulonephritis Nephropathy Nephrosclerosis Good pasture syndrome Urea N 2 decreased in : Acromegaly Alcohol abuse Hemodialysis Malnutrition Celiac disease CirrhosisCREATININE - SERUM: CREATININE - SERUM NORMS: Adults : 0.6 – 1.2 mg/dl Elderly – may be lower Children (< 2 years) – 0.3 – 0.6 mg/dlCREATININE - SERUM: CREATININE - SERUM INTERPRETATION: It is increased in nephrotic syndrome especially if the etiology is nephrosclerosisCREATININE - SERUM: CREATININE - SERUM INCREASED IN : Acromegaly Amyloidosis Azotemia CHF Diabetes mellitus Nephritis Nephrosclerosis Drugs DECREASED IN : Muscular dystrophy DrugsCREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE PRINCIPLE :the clearance of any substance is defined as volume of plasma from which a substance is removed in a fixed period of time. Clearance = (UV/S or P) X (1.73/A) In case of creatinine clearance U = mg/ml urine creatinine S or P = Serum or Plasma creatinine V = ml of urine excreted / minute 1.73 = std average surface area of normal individual A = surface area of patientCREATININE CLEARANCE – SERUM & URINE norms: CREATININE CLEARANCE – SERUM & URINE norms AGE ADULT FEMALE ( mL /Min) ADULT FEMALE ( mL /Min) < 20 YEARS 75 80 21-30 YEARS 90 96 31-40 YEARS 96 102 41-50 YEARS 102 108 51-60 YEARS 108 114 61-70 YEARS 114 120 71-80 YEARS 120 126 81-90 YEARS 126 132 91-100 YEARS 132 138CREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE INTERPRETATION: It is decreased in Nephrotic syndromeCREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE INCREASED IN : Acute stroke Drugs Herbal remedies DECREASED IN : Acute coronary syndrome ATN CHF Dehydration Glomerulonephritis Nephrosclerosis B/L renal malignancyTESTS WHICH ARE HELPFUL IN DIAGNOSIS BUT ARE NOT MANDATORY: TESTS WHICH ARE HELPFUL IN DIAGNOSIS BUT ARE NOT MANDATORY SERUM C3 LEVEL SERUM CALCIUM SERUM CERULOP[LASMIN SERUM FIBRINOGEN ESRRENAL BIOPSY : RENAL BIOPSY Renal biopsy is a valuable tool in adults with nephrotic syndrome for establishing a definitive diagnosis, guiding therapy & assessing prognosis Renal biopsy is not required in majority of children with nephrotic syndrome as most cases are due to MCD & respond to empirical T/t with corticosteroidsLESIONS THAT PRESENT AS NEPHROTIC SYNDROME: LESIONS THAT PRESENT AS NEPHROTIC SYNDROME Minimal Change Disease Focal Segmental GS Membranous Glomerulopathy Membranoproliferative GN Diabetic nephropathy AmyloidosisMINIMAL CHANGE GLOM. (LIPOID NEPHROSIS or NIL LESION or FOOT PROCESS DISEASE): MINIMAL CHANGE GLOM. (LIPOID NEPHROSIS or NIL LESION or FOOT PROCESS DISEASE) NORMAL LIGHT MICROSCOPY MOST COMMON CAUSE of NEPHROTIC SYNDROME in CHILDREN EFFACEMENT of FOOT PROCESSESLIPOID NEPHROSIS: LIPOID NEPHROSIS Numerous albumin positive resorption lipid droplets in proximal tubular epithelial cellsMINIMAL CHANGE DISEASE: MINIMAL CHANGE DISEASE Most common cause of paediatric NS. Normal by light microscopy Patent capillary loops Basement membrane normal in thickness No tubular atrophy No interstitial scarring.MINIMAL CHANGE DISEASE: MINIMAL CHANGE DISEASE Lipid & protein droplets accumulate in cell cytoplasm of convoluted tubules. LIPOID CELLS . Masson’s trichrome stain. Tubular BM is light blue, cells rusty.FOCAL & SEGMENTAL GLOMERULOSCLEROSIS: FOCAL & SEGMENTAL GLOMERULOSCLEROSIS Typical -Segmental sclerosis in one or more lobules of the glomerular tuft near axial region. Pronounced hyalinosis & thickening of afferent arteriolesFOCAL & SEGMENTAL GLOMERULOSCLEROSIS: FOCAL & SEGMENTAL GLOMERULOSCLEROSIS Segmental deposition of IgMMEMBRANOUS GN: MEMBRANOUS GN MC cause of adult NS. Diffuse thickening of the basement membrane The change is diffuse, affecting all capillaries in the glomerulus equally No proliferation of endothelial cells or measngial cellsMEMBRANOUS GN: MEMBRANOUS GN Generalized, peripheral granular pattern of IgG & C3, sometimes with C1q, C4, IgM & IgAMEMBRANOPROLIFERATIVE GN: MEMBRANOPROLIFERATIVE GN Mesangiocapillary GN. The glomeruli are enlarged & show a diffuse proliferative change Increase in no & size of endothelial & measngial cells Lobular structure of glomerulus is more obviousMEMBRANOPROLIFERATIVE GN: MEMBRANOPROLIFERATIVE GN Granular reaction for C3 & IgG along the capillary walls & mesangiumDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY Deposition of hyaline material in the mesangium of the lobules of glomerulus Deposition may be diffuse & more or less evenly through out glomerulus Afferent arteriole showinh hyaline changeDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY KIMMELSTIEL- WILSON LESION. Hyaline material deposited in round, acellular nodules in the glomerular tuft. The cuff of RBC’s is greatly dilated capillary. There is also deposition of hyaline material in bowman’s capsule Arterioles showing eosinophillic hyaline thickeningDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY Diffuse linear localization of IgG along glomerular & tubular basement membranes & bowman’s capsuleRENAL AMYLOIDOSIS: RENAL AMYLOIDOSIS Extracellular deposition of fibrillar proteins, β pleated sheet configuration on diffraction analysis On L/M,amorphous, eosiniphilc, PAS negative or scanty positive extracellular material.RENAL AMYLOIDOSIS: RENAL AMYLOIDOSIS Fluorescence of amyloid under UV light (Thioflavin T stain)NEPHROTIC SYNDROME: NEPHROTIC SYNDROME COMPLICATIONS: EDEMA HYPERLIPIDEMIA THROMBO EMBOLIC COMPLICATIONS – renal vein thrombosisCONGENITAL NEPHROTIC SYNDROME: CONGENITAL NEPHROTIC SYNDROME Due to mutations in certain genes Congenital nephrotic syndrome of finnish type – mutation in NPHS 1 which encode protein nephrin. Steroid resistant nephrotic syndrome – mutation in NPHS 2 which encode protein podocin.Slide 95: Lesion LM IFM EM LAB FEATURES Minimal change Normal or very mild proliferation -ve trace IgM Foot process fusion, no deposits Highly selective Proteinuria, normal C3 Focal sclerosis Focal & segmental sclerosis Focal & segmental IgM, C3 Foot process fusion, sclerosis, hyaline Hematuria, leukocyturia, poorly selective Proteinuria Membranous GN Thick capillary wall, spikes of BM material Diffuse granular capillary wall IgG Sub epithelial deposits Variable protein selectivity, normal C3, RVT Mesangio Capillary GN type I Mesangial interposition, lobular change Diffuse C3; variable IgG, IgM Sub endothelial deposits Hematuria, reduced C3(intermittent) Mesangio Capillary GN type II Mesangial interposition C3 capillary wall & Mesangial nodules Intra membranous deposits Hematuria, reduced C3(persistent) by : dr ravi jain : by : dr ravi jain THANK YOU….. 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lab diagnosis of nephrotic syndrome cyto786 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 681 Category: Science & Tech.. License: All Rights Reserved Like it (3) Dislike it (0) Added: February 26, 2011 This Presentation is Public Favorites: 0 Presentation Description nephrotic syndrome is diagnosed using urine, serum & renal biopsy specimens Comments Posting comment... By: vishalvanani (13 month(s) ago) good one. keep it up Saving..... Post Reply Close Saving..... Edit Comment Close By: sitinur (14 month(s) ago) great! Saving..... Post Reply Close Saving..... Edit Comment Close By: cyto786 (14 month(s) ago) yes . Saving..... Post Reply Close Saving..... Edit Comment Close By: mari_kapiko (14 month(s) ago) can i download this slide show?? Saving..... Post Reply Close Saving..... Edit Comment Close By: sathee12345 (14 month(s) ago) very useful slide show thank you for your wonderful contribution Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript LAB DIAGNOSIS OF NEPHROTIC SYNDROME: LAB DIAGNOSIS OF NEPHROTIC SYNDROME MODERATOR : DR SANJEEV NARANG SPEAKER : DR RAVI JAINNEPHROTIC SYNDROME: NEPHROTIC SYNDROME DEFINITION : the nephrotic syndrome is a clinical complex characterized by a no of renal & extra renal features, the most prominent of which are Proteinuria of > 3.5 g/1.73 m 2 /24 hr Hypoalbuminemia Edema Hyperlipidemia Lipiduria HypercoagulabilityGLOMERULUS: GLOMERULUS Glomerulus is an anastomosing network of capillaries lined by fenestrated endothelium invested by two layers of epithelium. The glomerular capillary wall is the filtering membrane consisting of : Thin layer of endothelial cells Glomerular basement membrane Visceral epithelial cells Mesangial cellsENDOTHELIAL CELLS: ENDOTHELIAL CELLS A thin layer of endothelial cells which are fenestrated, are responsible for high permeability of water & solutes. Size of fenestrum varies from 70 to 100 nm in diameter.GLOMERULAR BASEMENT MEMBRANE: GLOMERULAR BASEMENT MEMBRANE Glomerular basement membrane has two layers : Thick electron dense central layer – Lamina densa Thinner electron lucent peripheral layers – Lamina rara interna & externa GBM consists of type IV collagen, laminin, polyanionic proteoglycans, fibronectin, entactin & other glycoproteinsGLOMERULAR BASEMENT MEMBRANE: GLOMERULAR BASEMENT MEMBRANE These charged proteins & fenestrations in endothelium are responsible for impermeability to proteins like albumin & permeability to water & solutes. These charged proteins are anionic & block the passage of anionic proteins like albumin.PODOCYTES: PODOCYTES Also K/as visceral epithelial cells, are important for maintainence of glomerular barrier function. Its slit diaphragm presents a size selective distal diffusion barrier to the filtration of proteins. Podocin & nephrin are two proteins that control glomerular permeabilityPODOCYTES: PODOCYTES Nephrin is trans membrane protein with large extra cellular portion made up of Ig like domains These proteins dimerize across the slit diaphragm Within the cytoplasm of foot processes of podocytes, nephrin forms molecular connections with podocin, CD2 associated protein & actin cytoskeletonMESANGIAL CELLS: MESANGIAL CELLS These are supporting cells of glomerulus, lying between the capillaries. These cells are of mesodermal origin. Contractile Phagocytic Capable of proliferation Laying down both matrix & collagen Secreting no of active mediatorsSlide 11: CAUSES OF THE NEPHROTIC SYNDROME IN ADULTSNEPHROTIC SYNDROME: NEPHROTIC SYNDROME PATHOGENESIS: Derangement in glomerular capillary walls Increased permeability to plasma proteins Massive proteinuria + increased renal catabolism of albumin Depletion of serum albumin & reversal of A:G ratio Generalized edema abnormal transport of lipids + decreased catabolism HyperlipidemiaSlide 14: Figure 3.NEPHROTIC SYNDROME: NEPHROTIC SYNDROME CLINICAL FEATURES: Massive proteinuria Hypoalbuminemia Generalized edema Hyperlipidemia & lipiduriaSlide 16: Figure 1. Nephrotic edema.Slide 17: Figure 2. Nephrotic edema.LAB DIAGNOSIS OF NEPHROTIC SYNDROME: LAB DIAGNOSIS OF NEPHROTIC SYNDROME Specimen Urine Serum Renal biopsyURINE EXAMINATION: URINE EXAMINATION Physical examination Chemical examination Microscopic examinationPHYSICAL EXAMINATION: PHYSICAL EXAMINATION Volume- increased in Diabetes mellitus Color – Milky due to lipiduria in nephrotic syndrome Appearance Sediment formation Odor Specific gravity (Sp. Gr.) – High due to proteinuria Osmolality – increased in nephrotic syndromeSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) At constant temperature weight of volume of urine weight of same volume of distilled water Measure the diluting and concentrating power of kidneys Reliable indicator of body hydration statusSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Depends upon the number and weight of particles in urine Normal value - 1.003 to 1.035 (For random sample) - 1.015 – 1.030 (For 24 hr sample) Normal contributors 1. Urea (20%) 2. Sodium chloride ( 25%) 3. Sulfate 4. PhosphatesSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Hypersthenuria – High specific gravity 1 . Diabetes mellitus 2. Dehydration 3. Eclampsia 4. Proteinuria 5. Nephrotic syndrome 6. Fever 7. Acute nephritisSPECIFIC GRAVITY (Sp. Gr.): SPECIFIC GRAVITY (Sp. Gr.) Hyposthenuria – Low specific gravity (<1.007) 1. Pyelonephritis 2. Hypertension 3. Diabetes insipidus 4. Protein malnutrition 5. Glomerulonephritis 5. Diuretics drugsURINE EXAMINATION: URINE EXAMINATION CHEMICAL EXAMINATIONURINE EXAMINATION: URINE EXAMINATION Urine : Protein estimation Qualitative Quantitative – 24 hr protein estimationPROTEIN DETERMINATION IN URINE : PROTEIN DETERMINATION IN URINE - Normal kidney secretes only small amount of low molecular weight proteins filtered, most of which are reabsorbed by tubules. - Normal protein excretion <150 mg/day in adult. - Daily physiological protein contain :- (i) Mucoprotein (Tamm Horsfall glycoprotein 70 mg) (ii) Blood group related antigen 35 mg (iii) Albumin 15 mg (iv) Mucopolysaccharide 15 mg (v) Immunoglobulin 5 mg - Abnormal amount of protein in urine – ProteinuriaPATHOPHYSIOLOGICAL CLASSIFICATION OF PROTEINURIA : PATHOPHYSIOLOGICAL CLASSIFICATION OF PROTEINURIA Physiological Proteinuria Glomerular proteinuria Tubular proteniuria Other types (i) Benign orthostatic proteinuria (ii) Transient proteinuria (iii) Microalbuminuria (iv) Bence jones ProteinuriaDifference between glomerular and Tubular proteinuria : Difference between glomerular and Tubular proteinuria Glomerular Tubular Due to injury of Renal glomerulus Due to Injury Involving Tubulointerstitial region Comprises predominantly albumin Comprises low molecular wt protein ( 2 microglobilin Protein excretion >3 – 3.5 gm/dl < 2 gm/dl. Urinary protein electrophoresis More albumin than globulin More globulin Albumin micro globulin ratio > 1000 : 1 100:1 (N – 50-200:1) Cause - Glomerulonephritis - - Hypertension - Lipoid Nephrosis - - Pyelonephritis - - Interstitial Nephritis - Rejection of kidney allograftQualitative tests for protein : Qualitative tests for protein Reagent strip method Precipitation method (a) Heat and acetic acid test (b) Sulphosalicylic acid test (c) Heller’s nitric acid testPrecipitation method : Precipitation method Urine Protein: SSAChemical Tests on Urine: (Reagent Strip/Dipstick Analysis): Procedure : Chemical Tests on Urine: (Reagent Strip/Dipstick Analysis): Procedure Reagent strip method : Reagent strip method Dipstick more sensitive to albumin than globulin, mucoproteins, Bence-Jones protein False Positives: - Chlorhexidine, quartenary ammonium antispetic or detergent residual left in container - Vaginal secretions - Highly buffered urine with pH >6.5PROTEIN - URINE: PROTEIN - URINE Normal : < 20 mg % Reagent strip/ stick Negative : 0 – 5 mg/dl Trace : 5 – 20 mg/dl 1+ : 30 mg/dl 2+ : 100 mg/dl 3+ : 300 mg/dl 4+ : 1000 mg/dlPROTEIN - URINE: PROTEIN - URINE False +ve results: Incorrect matching of reagent strip to the color chart Prolonged exposure of the strip or stick to the urine Hematuria Drugs Acetazolamide Amino salicylic acid Chlorpromazine PenicillinPROTEIN - URINE: PROTEIN - URINE False -ve results: Very dilute urine Highly buffered alkaline urine Urine high in sodium Urea splitting organismsPROTEIN- URINE: PROTEIN- URINE Increased in : Amyloidosis Collagen disease Cryoglobulinemia Nephrotic syndrome Diabetes24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION This test is indicated when a random urine sample is positive for more than a trace of protein. Protein substances are excreted at different rates & at varying times in a 24 hr period 24 hr protein estimation provides the most accurate reflection of kidney function24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION Early morning is the preferred time for 24 hr urine collection Discard the first morning urine specimen Save all the urine voided for 24 hr in a clean refrigerated container Include the urine voided at the end of the 24 hour period24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION Quantitative norms : Adults : 30 – 150 mg/ 24 hrs Children < 10 years : < 100 mg/ 24 hrs New born : increased protein in urine for 3 days after delivery24 HOUR PROTEIN ESTIMATION: 24 HOUR PROTEIN ESTIMATION False +ve quantitative test : Drugs Acetazolamide Amino salicylic acid Aspirin Barbiturates Cephalosporins Penicillin False -ve quantitative test : Urine accidently discarded during 24 hr collection Urine lost during defecationPROTEIN ELECTROPHORESIS - URINE : PROTEIN ELECTROPHORESIS - URINE Principle -The term electrophoresis describes the migration of a charged particle under the influence of an electric field. Many important biologic molecules, such as amino acids, peptides, proteins, nucleotides and nucleic acids, possess ionizable groups and, therefore, at any given pH, in solution as electrically charged species either as cations(+) or anions(-) Under the influence of an electric field these charged particles will migrate either to the cathode or to the anode, depending on the nature of their net charge.PROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE Normal urine electrophoretograms show individual variance & show a globulin pattern that is generally diffuse . The dominant protein is albumin. Normal pattern seen : Albumin : 37.9 % ά 1 globulin : 27.3 % ά 2 globulin : 19.5 % β globulin : 8.8 % γ globulin : 3.3 %PROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE INTERPRETATION: Proteinuria associated with increased glomerular permeability exhibits an electrophoretic pattern that is dominated by albumin, with moderate β globulin , some ά globulin & trace γ globulinPROTEIN ELECTROPHORESIS - URINE: PROTEIN ELECTROPHORESIS - URINE Factors that affect result: Contamination of the specimen with the stool invalidates the test. Drugs Amikacin Amphotericin B Penicillin PhenylbutazoneMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Casts - Formed in lumen of the tubules of kidney - Tamm-Horsfall protein - Secreted by thick part of ascending loop of henle - Forms the matrix of all casts - Casts can form as the result of- A. Precipitation of gelatin of Tamm-Horsfall mucoprotein B. Clumping/adherence of cells or cellular material to the matrix C. Coagulation of material within the lumenMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE - Cast formation take place in the distal and collecting tubules ( requires high solute concentration and acidic pH) - Dissolves in alkaline pH - Nearly parallel sides and rounded or blunted ends - Convoluted, straight or curved.MICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE A. According To Matrix: a. Hyaline cast - Most frequently observed cas- Colorless, transparent, homogenous with rounded ends - Normally - 0-2 hyaline casts/hpfMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE b. Waxy casts - High refractive index - Yellow gray or colorless and homogenous, smooth sharp margins and blunted endsMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Renal failure casts - Unusually broad waxy castsMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE a. Granular casts - Granules large or small Increased in Pyelonephritis Viral infection Chronic lead poisoning Renal papillary necrosis Hyperparathyroidism Extreme stressMICROSCOPIC EXAMINATION - URINE: MICROSCOPIC EXAMINATION - URINE Causes : Nephrotic syndrome Chronic glomerulonephritisCREATININE - URINE: CREATININE - URINE Urine creatinine(mg/dl) = O.D Test/O.D Std X 100 For determination of 24 hrs creatinine excretion, measure the urine volume & calculate using following formula Creatinine excretion (mg/24 hrs) = urine creatinine, mg/dl X ml, 24 hrs urine/100CREATININE - URINE: CREATININE - URINE NORMS : Adult : 14 – 26 mg/kg/24 hrs Female : 600 – 1800 mg/24 hrs Male : 800 – 2000 mg/24 hrs Child : 8 – 22 mg/kg/24 hrsCREATININE - URINE: CREATININE - URINE INTERPRETATION : It is decreased in nephrotic syndromeCREATININE - URINE: CREATININE - URINE INCREASED IN : Fever Hypothyroidism Tissue catabolism DECREASED IN : Decreased renal perfusion Glomerulonephritis Cystic kidney disease Polymyositis Pyelonephritis Hypovolemic shockPROTEIN - SERUM: PROTEIN - SERUM Normal values : Adults : 6.0 – 8.0 g/dl Children : 4.3 – 7.6 g/dl Premature : 4.6 – 7.4 g/dl Newborn : 6.0 – 6.7 g/dl Infant : 6.2 – 8.0 g/dlPROTEIN - SERUM: PROTEIN - SERUM Factors that affect result: Hemolysed or lipemic specimen Falsely elevated value occur upto 48 hr after use of sulfo- bromopthalein contrast dye Recent dialysis Hyperglycemia Bed ridden patients – lower valuesPROTEIN SERUM: PROTEIN SERUM INCREASED IN : Amyloidosis Addison’s disease Macroglobulinemia Multiple myeloma Sarcoidosis Chronic infection DECREASED IN : Analbuminemia Burns Chronic glomerulonephritis Diarrhea Edema Hyperthyroidism Nephrotic syndrome MalabsorptionPROTEIN ELECTROPHORESIS - SERUM: PROTEIN ELECTROPHORESIS - SERUM Norms : Total protein : 100 % Albumin : 58 – 74 % ά 1 globulin : 2.0 – 3.5 % ά 2 globulin : 5.4 – 10.6 % β globulin : 7.0 – 14.0 % γ globulin : 8.0 – 18.0 %PROTEIN ELECTROPHORESIS – SERUM in NEPHROTIC SYNDROME: PROTEIN ELECTROPHORESIS – SERUM in NEPHROTIC SYNDROME Increased ά globulin zone intensity ( ά 2 globulin ) Increased ά 2 - β 1 globulin interzone intensity Increased β globulin zone intensity Decreased albumin zone intensity Decreased γ globulin zone intensityLIPID PROFILE TESTS for HYPERLIPIDEMIA: LIPID PROFILE TESTS for HYPERLIPIDEMIA TOTAL LIPIDS SERUM TOTAL CHOLESTEROL SERUM H.D.L – C SERUM TRIGLYCERIDES SERUM VLDL SERUM LDLNORMAL LEVELS: NORMAL LEVELS S.No Lipid level 1 TOTAL LIPIDS 400-800 MG/DL 2 TOTAL CHOLESTEROL < 200 MG/DL 3 HDL 30-60 MG/DL 4 TRIGLYCERIDES 10-90 MG/DL 5 LDL <100 MG/DL 6 VLDL < 80 MG/DLLIPID PROFILE IN NEPHROTIC SYNDROME: LIPID PROFILE IN NEPHROTIC SYNDROME Increased LDL – C Increased Total Cholesterol(usually > 350 mg/dl) Increased VLDL Increased TGUREA NITROGEN - SERUM: UREA NITROGEN - SERUM NORMS : Young adult : 5 – 18 mg/dl Adult : 5 – 20 mg/dl Elderly > 60 yrs : 8 – 21 mg/dl Mild azotemia : 20 – 50 mg/dl Children : Cord blood : 21 – 40 mg/dl Full term newborn : 3 – 25 mg/dl Infant : 5 – 18 mg/dl Child : 5 – 18 mg/dlUREA NITROGEN - SERUM: UREA NITROGEN - SERUM Urea N 2 increased in : Addison’s disease Amyloidosis Diabetes mellitus Glomerulonephritis Nephropathy Nephrosclerosis Good pasture syndrome Urea N 2 decreased in : Acromegaly Alcohol abuse Hemodialysis Malnutrition Celiac disease CirrhosisCREATININE - SERUM: CREATININE - SERUM NORMS: Adults : 0.6 – 1.2 mg/dl Elderly – may be lower Children (< 2 years) – 0.3 – 0.6 mg/dlCREATININE - SERUM: CREATININE - SERUM INTERPRETATION: It is increased in nephrotic syndrome especially if the etiology is nephrosclerosisCREATININE - SERUM: CREATININE - SERUM INCREASED IN : Acromegaly Amyloidosis Azotemia CHF Diabetes mellitus Nephritis Nephrosclerosis Drugs DECREASED IN : Muscular dystrophy DrugsCREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE PRINCIPLE :the clearance of any substance is defined as volume of plasma from which a substance is removed in a fixed period of time. Clearance = (UV/S or P) X (1.73/A) In case of creatinine clearance U = mg/ml urine creatinine S or P = Serum or Plasma creatinine V = ml of urine excreted / minute 1.73 = std average surface area of normal individual A = surface area of patientCREATININE CLEARANCE – SERUM & URINE norms: CREATININE CLEARANCE – SERUM & URINE norms AGE ADULT FEMALE ( mL /Min) ADULT FEMALE ( mL /Min) < 20 YEARS 75 80 21-30 YEARS 90 96 31-40 YEARS 96 102 41-50 YEARS 102 108 51-60 YEARS 108 114 61-70 YEARS 114 120 71-80 YEARS 120 126 81-90 YEARS 126 132 91-100 YEARS 132 138CREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE INTERPRETATION: It is decreased in Nephrotic syndromeCREATININE CLEARANCE – SERUM & URINE: CREATININE CLEARANCE – SERUM & URINE INCREASED IN : Acute stroke Drugs Herbal remedies DECREASED IN : Acute coronary syndrome ATN CHF Dehydration Glomerulonephritis Nephrosclerosis B/L renal malignancyTESTS WHICH ARE HELPFUL IN DIAGNOSIS BUT ARE NOT MANDATORY: TESTS WHICH ARE HELPFUL IN DIAGNOSIS BUT ARE NOT MANDATORY SERUM C3 LEVEL SERUM CALCIUM SERUM CERULOP[LASMIN SERUM FIBRINOGEN ESRRENAL BIOPSY : RENAL BIOPSY Renal biopsy is a valuable tool in adults with nephrotic syndrome for establishing a definitive diagnosis, guiding therapy & assessing prognosis Renal biopsy is not required in majority of children with nephrotic syndrome as most cases are due to MCD & respond to empirical T/t with corticosteroidsLESIONS THAT PRESENT AS NEPHROTIC SYNDROME: LESIONS THAT PRESENT AS NEPHROTIC SYNDROME Minimal Change Disease Focal Segmental GS Membranous Glomerulopathy Membranoproliferative GN Diabetic nephropathy AmyloidosisMINIMAL CHANGE GLOM. (LIPOID NEPHROSIS or NIL LESION or FOOT PROCESS DISEASE): MINIMAL CHANGE GLOM. (LIPOID NEPHROSIS or NIL LESION or FOOT PROCESS DISEASE) NORMAL LIGHT MICROSCOPY MOST COMMON CAUSE of NEPHROTIC SYNDROME in CHILDREN EFFACEMENT of FOOT PROCESSESLIPOID NEPHROSIS: LIPOID NEPHROSIS Numerous albumin positive resorption lipid droplets in proximal tubular epithelial cellsMINIMAL CHANGE DISEASE: MINIMAL CHANGE DISEASE Most common cause of paediatric NS. Normal by light microscopy Patent capillary loops Basement membrane normal in thickness No tubular atrophy No interstitial scarring.MINIMAL CHANGE DISEASE: MINIMAL CHANGE DISEASE Lipid & protein droplets accumulate in cell cytoplasm of convoluted tubules. LIPOID CELLS . Masson’s trichrome stain. Tubular BM is light blue, cells rusty.FOCAL & SEGMENTAL GLOMERULOSCLEROSIS: FOCAL & SEGMENTAL GLOMERULOSCLEROSIS Typical -Segmental sclerosis in one or more lobules of the glomerular tuft near axial region. Pronounced hyalinosis & thickening of afferent arteriolesFOCAL & SEGMENTAL GLOMERULOSCLEROSIS: FOCAL & SEGMENTAL GLOMERULOSCLEROSIS Segmental deposition of IgMMEMBRANOUS GN: MEMBRANOUS GN MC cause of adult NS. Diffuse thickening of the basement membrane The change is diffuse, affecting all capillaries in the glomerulus equally No proliferation of endothelial cells or measngial cellsMEMBRANOUS GN: MEMBRANOUS GN Generalized, peripheral granular pattern of IgG & C3, sometimes with C1q, C4, IgM & IgAMEMBRANOPROLIFERATIVE GN: MEMBRANOPROLIFERATIVE GN Mesangiocapillary GN. The glomeruli are enlarged & show a diffuse proliferative change Increase in no & size of endothelial & measngial cells Lobular structure of glomerulus is more obviousMEMBRANOPROLIFERATIVE GN: MEMBRANOPROLIFERATIVE GN Granular reaction for C3 & IgG along the capillary walls & mesangiumDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY Deposition of hyaline material in the mesangium of the lobules of glomerulus Deposition may be diffuse & more or less evenly through out glomerulus Afferent arteriole showinh hyaline changeDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY KIMMELSTIEL- WILSON LESION. Hyaline material deposited in round, acellular nodules in the glomerular tuft. The cuff of RBC’s is greatly dilated capillary. There is also deposition of hyaline material in bowman’s capsule Arterioles showing eosinophillic hyaline thickeningDIABETIC NEPHROPATHY: DIABETIC NEPHROPATHY Diffuse linear localization of IgG along glomerular & tubular basement membranes & bowman’s capsuleRENAL AMYLOIDOSIS: RENAL AMYLOIDOSIS Extracellular deposition of fibrillar proteins, β pleated sheet configuration on diffraction analysis On L/M,amorphous, eosiniphilc, PAS negative or scanty positive extracellular material.RENAL AMYLOIDOSIS: RENAL AMYLOIDOSIS Fluorescence of amyloid under UV light (Thioflavin T stain)NEPHROTIC SYNDROME: NEPHROTIC SYNDROME COMPLICATIONS: EDEMA HYPERLIPIDEMIA THROMBO EMBOLIC COMPLICATIONS – renal vein thrombosisCONGENITAL NEPHROTIC SYNDROME: CONGENITAL NEPHROTIC SYNDROME Due to mutations in certain genes Congenital nephrotic syndrome of finnish type – mutation in NPHS 1 which encode protein nephrin. Steroid resistant nephrotic syndrome – mutation in NPHS 2 which encode protein podocin.Slide 95: Lesion LM IFM EM LAB FEATURES Minimal change Normal or very mild proliferation -ve trace IgM Foot process fusion, no deposits Highly selective Proteinuria, normal C3 Focal sclerosis Focal & segmental sclerosis Focal & segmental IgM, C3 Foot process fusion, sclerosis, hyaline Hematuria, leukocyturia, poorly selective Proteinuria Membranous GN Thick capillary wall, spikes of BM material Diffuse granular capillary wall IgG Sub epithelial deposits Variable protein selectivity, normal C3, RVT Mesangio Capillary GN type I Mesangial interposition, lobular change Diffuse C3; variable IgG, IgM Sub endothelial deposits Hematuria, reduced C3(intermittent) Mesangio Capillary GN type II Mesangial interposition C3 capillary wall & Mesangial nodules Intra membranous deposits Hematuria, reduced C3(persistent) by : dr ravi jain : by : dr ravi jain THANK YOU…..