Pathology of Glomerulonephritis

1. Pathology of Glomerulonephritis CPC4.1-2008: <ul><li>Miss G.M. is a 37 year old woman with longstanding Type 1 Diabetes . </li></ul><ul><li>Dysuria (36h), Urinary Frequency, Fatigue , backache(T11,12) – few months. </li></ul><ul><li>BSL – 9-11 , Pedal edema – few weeks. </li></ul><ul><li>Diarrhea, anorexia, bloating – year. </li></ul><ul><li>Microalbuminuria – 1998, </li></ul><ul><li>Urine: nitrate positive; ketones:+; glucose ++ wbc+++; protein++++ ; blood : trace ; </li></ul><ul><li>Urine MC+S : leucocytes 10^8 ; E Coli Sensitive to trimethoprim - ? </li></ul><ul><li>Post micturation bladder volume : 180 ml - ? </li></ul><ul><li>Anti tissue transglutaminase antibody: 12(normal < 2) - ? </li></ul>

2. CPC4.4.1 – Clinical Cases <ul><li>The patient is a 35y Italian female who works as a shop assistant, Tired for years , but has always been able to carry out her work. Over the past two months, however, her fatigue has worsened , and she has noted swelling of her legs and puffiness around eyelids. MGN </li></ul><ul><li>2 year old boy presents with sudden onset polyuria , proteinuria mild fever. MCD </li></ul><ul><li>8 year old girl presents with fever, oliguria , smoke coloured urine & hypertension following upper respiratory tract infection. PGN </li></ul> CPC4.4.1 – Clinical Cases <ul><li>The patient is a 35y Italian female who works as a shop assistant, Tired for years , but has always been able to carry out her work. Over the past two months, however, her fatigue has worsened , and she has noted swelling of her legs and puffiness around eyelids. MGN </li></ul><ul><li>2 year old boy presents with sudden onset polyuria , proteinuria mild fever. MCD </li></ul><ul><li>8 year old girl presents with fever, oliguria , smoke coloured urine & hypertension following upper respiratory tract infection. PGN </li></ul>

3. Investigations: Nephrotic <ul><li>Urine: 4+ proteinuria, granular casts, RBC +. </li></ul><ul><li>24h urine: 6g protein in 24h </li></ul><ul><li>Serum: creatinine = 0.14 (slightly elevated) </li></ul><ul><li>LFT, electrolytes, Full blood counts – Normal. </li></ul><ul><li>Serum albumin is 28 g/l (low); </li></ul><ul><li>Cholesterol (6.5mmol/l) </li></ul><ul><li>Triglycerides (2.8mmol/l) </li></ul><ul><li>Antinuclear antibody (SLE) - Negative </li></ul><ul><li>Ultrasound of kidneys: normal </li></ul><ul><li>Renal biopsy – Glomerulonephritis* </li></ul> Investigations: Nephrotic <ul><li>Urine: 4+ proteinuria, granular casts, RBC +. </li></ul><ul><li>24h urine: 6g protein in 24h </li></ul><ul><li>Serum: creatinine = 0.14 (slightly elevated) </li></ul><ul><li>LFT, electrolytes, Full blood counts – Normal. </li></ul><ul><li>Serum albumin is 28 g/l (low); </li></ul><ul><li>Cholesterol (6.5mmol/l) </li></ul><ul><li>Triglycerides (2.8mmol/l) </li></ul><ul><li>Antinuclear antibody (SLE) - Negative </li></ul><ul><li>Ultrasound of kidneys: normal </li></ul><ul><li>Renal biopsy – Glomerulonephritis* </li></ul>

4. Investigations: Nephritic <ul><li>Urine: Oliguria, 2+ protein, RBC ++++, RBC & WBC casts. </li></ul><ul><li>24h urine: 0.5 g protein in 24h </li></ul><ul><li>Serum: creatinine = 0.14 (slightly elevated) </li></ul><ul><li>LFT, electrolytes, Full blood counts – Normal. </li></ul><ul><li>Serum albumin – normal ; </li></ul><ul><li>Antinuclear antibody (SLE) - Negative </li></ul><ul><li>Ultrasound of kidneys: normal </li></ul><ul><li>Renal biopsy – Glomerulonephritis* </li></ul> Investigations: Nephritic <ul><li>Urine: Oliguria, 2+ protein, RBC ++++, RBC & WBC casts. </li></ul><ul><li>24h urine: 0.5 g protein in 24h </li></ul><ul><li>Serum: creatinine = 0.14 (slightly elevated) </li></ul><ul><li>LFT, electrolytes, Full blood counts – Normal. </li></ul><ul><li>Serum albumin – normal ; </li></ul><ul><li>Antinuclear antibody (SLE) - Negative </li></ul><ul><li>Ultrasound of kidneys: normal </li></ul><ul><li>Renal biopsy – Glomerulonephritis* </li></ul>

5. CPC4.4.1 – Diff. Diag: <ul><li>Low serum albumin </li></ul><ul><ul><li>Renal disease – nephrotic syndrome </li></ul></ul><ul><ul><li>Liver disease (cirrhosis) </li></ul></ul><ul><ul><li>Gastrointestinal disease: malabsorption or protein-losing enteropathy, starvation. </li></ul></ul><ul><li>Normal serum albumin </li></ul><ul><ul><li>Renal disease – Nephritic syndrome </li></ul></ul><ul><ul><li>acute/chronic GN - diabetic, hypertensive. </li></ul></ul><ul><ul><li>Acute/Chronic renal failure. </li></ul></ul><ul><li>Fluid overload </li></ul><ul><ul><li>Congestive cardiac failure </li></ul></ul><ul><li>Endocrine : Hypothyroidism. </li></ul> CPC4.4.1 – Diff. Diag: <ul><li>Low serum albumin </li></ul><ul><ul><li>Renal disease – nephrotic syndrome </li></ul></ul><ul><ul><li>Liver disease (cirrhosis) </li></ul></ul><ul><ul><li>Gastrointestinal disease: malabsorption or protein-losing enteropathy, starvation. </li></ul></ul><ul><li>Normal serum albumin </li></ul><ul><ul><li>Renal disease – Nephritic syndrome </li></ul></ul><ul><ul><li>acute/chronic GN - diabetic, hypertensive. </li></ul></ul><ul><ul><li>Acute/Chronic renal failure. </li></ul></ul><ul><li>Fluid overload </li></ul><ul><ul><li>Congestive cardiac failure </li></ul></ul><ul><li>Endocrine : Hypothyroidism. </li></ul>

6. Pathogenesis of Renal Symptoms / Signs: Body_ID: TI021001 Proteinuria GBM Damage – Selective (albumin)-nephrotic, non selective nephritic syndrome. Oliguria or anuria Dehydration, GN-Nephritic Sy , renal failure, obstruction. Polyuria Excessive fluid, Osmotic (DM), GN-Nephrotic Sy , Tubule dysfunction (D.Insipidus) Dysuria Inflammation, Obstruction, stone, tumor, stricture. Renal colic Calculus, blood clot or tumour in ureter Uraemia (Fatigue, Nausea, vomiting, encephalopathy) Renal failure Haematuria Infection, stones, tumor, Glomerulonephritis (red cell casts) Casts: Coagulation of proteins in renal tubules. • Hyaline/Gr. casts Protein loss from glomeruli or necrotic cells • RBC, WBC, Ep. Protein with cell loss from glomeruli/tubules. • Waxy casts Degenerated cast following prolonged retention (chronic RF) Hypertension Renal ischaemia, decreased GFR  Renin  Angiotensin. Oedema periorbital* Hypoalbuminaemia due to albumin loss in urine (glomerulonephritis) Aldosterone. Pathogenesis of Renal Symptoms / Signs: Body_ID: TI021001 Proteinuria GBM Damage – Selective (albumin)-nephrotic, non selective nephritic syndrome. Oliguria or anuria Dehydration, GN-Nephritic Sy , renal failure, obstruction. Polyuria Excessive fluid, Osmotic (DM), GN-Nephrotic Sy , Tubule dysfunction (D.Insipidus) Dysuria Inflammation, Obstruction, stone, tumor, stricture. Renal colic Calculus, blood clot or tumour in ureter Uraemia (Fatigue, Nausea, vomiting, encephalopathy) Renal failure Haematuria Infection, stones, tumor, Glomerulonephritis (red cell casts) Casts: Coagulation of proteins in renal tubules. • Hyaline/Gr. casts Protein loss from glomeruli or necrotic cells • RBC, WBC, Ep. Protein with cell loss from glomeruli/tubules. • Waxy casts Degenerated cast following prolonged retention (chronic RF) Hypertension Renal ischaemia, decreased GFR  Renin  Angiotensin. Oedema periorbital* Hypoalbuminaemia due to albumin loss in urine (glomerulonephritis) Aldosterone.

7. Pathogenesis of Renal Symptoms / Signs: Body_ID: TI021001 Fatigue/Malaise Renal failure – Azotemia / Uremia. Headache Fluid retention, acidosis, uremia. Flank pain Ureteric Colic – stones. SOB, pallor Anemia – decreased erythropoietin Nausea / Vom. Renal Osteodystrophy – renal failure. Pruritis Uremia / neuropathy. Pigmentation Endocrine abnormality in uremia Smoky urine Microscopic hematuria at glomerular level – RBC casts. Nephritic syndrome. Hematuria UTI, Glomerulonephritis, tumor Painless Hematu. DM, IgA Nephropathy, TB. Pathogenesis of Renal Symptoms / Signs: Body_ID: TI021001 Fatigue/Malaise Renal failure – Azotemia / Uremia. Headache Fluid retention, acidosis, uremia. Flank pain Ureteric Colic – stones. SOB, pallor Anemia – decreased erythropoietin Nausea / Vom. Renal Osteodystrophy – renal failure. Pruritis Uremia / neuropathy. Pigmentation Endocrine abnormality in uremia Smoky urine Microscopic hematuria at glomerular level – RBC casts. Nephritic syndrome. Hematuria UTI, Glomerulonephritis, tumor Painless Hematu. DM, IgA Nephropathy, TB.

8. <ul><li>Whenever you see someone who is sick, dispirited, disconsolate, or diseased, there is a field of service. Every blood cell, every nerve must tingle with love, When love fills the heart, it transforms into Divinity. ( Genesis 20:13 ) </li></ul>Medicine is the Noble Profession <ul><li>Whenever you see someone who is sick, dispirited, disconsolate, or diseased, there is a field of service. Every blood cell, every nerve must tingle with love, When love fills the heart, it transforms into Divinity. ( Genesis 20:13 ) </li></ul>Medicine is the Noble Profession

9. Pathology of Glomerulonephritis: Dr. Shashidhar V. Murthy A/Prof. & Head of Pathology Pathology of Glomerulonephritis: Dr. Shashidhar V. Murthy A/Prof. & Head of Pathology

10. . CPC4.4.1 – CLI <ul><li>Pathology Major CLI: </li></ul><ul><ul><li>Overview & classification Disorders of Kidney. </li></ul></ul><ul><ul><li>Pathogenesis & Clinical features of Nephrotic, Nephritic Syndromes and Renal Failure. </li></ul></ul><ul><ul><li>Pathology of common types of Glomerulonephritis. </li></ul></ul><ul><ul><li>PGN, MGN, MPGN, FSGS, RPGN, CGN. </li></ul></ul><ul><ul><li>Pathology of Disorders of Tubules, Interstitium & Blood vessels. </li></ul></ul><ul><ul><li>Pathology of Renal failure both acute & Chronic. </li></ul></ul><ul><li>Pathology Minor CLI: </li></ul><ul><ul><li>Interpretation of Common Renal function tests. </li></ul></ul><ul><ul><li>Pathogenesis of Renal artery stenosis & other Nephrogenic Hypertension. </li></ul></ul><ul><ul><li>IgA nephropathy. </li></ul></ul><ul><ul><li>Renal involvement in SLE </li></ul></ul><ul><ul><li>Analgesic nephropathy. </li></ul></ul><ul><ul><li>Amyloid nephropathy. </li></ul></ul><ul><ul><li>Hypertensive nephropathy. </li></ul></ul><ul><ul><li>Acute tubular necrosis. </li></ul></ul>

11. . Anatomy-Kidney L R

12. . Normal Kidney * note: Lobulations are prominent in fetal kidney Less common in adult kidney.

13. . Anatomy of Renal System Cortex Medulla - pyramid Renal Papilla

14. . Blood supply of Kidney. Brödel's 1901 artist rendition of a human left kidney anterior view, following celloidin injection with tissue digestion, demonstrating details of the lush venous return. For the sake of clarity, he omitted the small veins of the cortex (Brödel M. Johns Hopkins Hospital Bulletin 1901; 118 :10–13). Arcuate BV Note arcuate large vessels in medulla, But, small straight vessels in cortex. (revise physiology of urine production, counter current mechansim)

15. . <ul><li>Note the positions of </li></ul><ul><li>Glom, PCT, Loop, DCT, CT </li></ul>Anatomy of Kidney

16. . Normal Kidney: Histology DCT PCT Gl.Cap Mesang. Aff.Art JGA * Remember: JGA, Renin, Angiotensin, Blood pressure control….

17. . Normal Glomerulus (PAS stain for BM) DCT PCT Gl.Cap Mesang.

18. . Normal Glomerulus DCT PCT Gl.Cap Mesang.

19. . Glomeruli: ScanEM showing Outside view of Glom Podocyte foot processes (Epithelium) Scan EM showing View from inside capillary Endothelial Fenestrations

20. . A B C D E F F Juxta Glomerular Apparatus JGA  GFR  Renin  Aldosterone Angiotensin BP, Na/K/H+

21. . Review Physiology: Urine, Hormones & Homeostasis Renin Hypertonic

22. . Renal Filtration Unit: <ul><li>IMPORTANT IN UNDERSTANDING GLOMERULONEPHRITIS: </li></ul><ul><li>Permeability to solutes & water, but Impermeable to </li></ul><ul><ul><li>Cells (endothelium) </li></ul></ul><ul><ul><li>larger molecules (BM) </li></ul></ul><ul><ul><li>small proteins (podocytes). </li></ul></ul>

23. . Filtration Membrane: Endothelium Basement Mem Epithelium

24. . Glom. Nephritis : Pathogenesis <ul><li>Large quantity blood filtration…. </li></ul><ul><ul><li>1.2 L/min = 1,728 L/day (25% Cardiac output) </li></ul></ul><ul><ul><li>Glomerular filtrate 180 L / day, Urine 1-2 L / day. </li></ul></ul><ul><li>Trap large proteins – Ag, Ab, Ig.complex, toxins. </li></ul><ul><li>Activation of complement system </li></ul><ul><li>Inflammation – cytokines & inflammatory cells. </li></ul><ul><li>Damage filtration membrane: </li></ul><ul><ul><li>Incomplete/podocyte damage Nephrotic Sy : no swelling, selective albuminuria. </li></ul></ul><ul><ul><li>Complete filter damage: Nephritic Sy : inflam swelling, ↓ blood flow, ↓ GFR  Oliguria, hypertension, hematuria. </li></ul></ul><ul><li>Systemic effects: </li></ul><ul><ul><li>JGA  BP, water, electrolyte imbalance. </li></ul></ul><ul><ul><li>Erythropoietin – anemia. </li></ul></ul><ul><ul><li>Vit-D – Bone metabolism. </li></ul></ul>

25. . Pathogenesis of GN: Blood GBM Podocyte GLOM. FILT. MEM: 1. Endothelium 2. GBM 3. Podocyte Slit membrane Endothelium Cells Glom.Filt Glob. Alb. Nephrotic Sy – No Infl. - Polyuria Nephritic Sy – Inflam - oliguria

26. . Glom. Immunoflourescence Granular Smooth Circulating Ig. Complexes, C3 Anti GBM Ab. disease/. Planted antigens & Ab. Infections, Autoimmune dis.

27. . <ul><li>Nephritic </li></ul><ul><li>Oliguria </li></ul><ul><li>Hematuria </li></ul><ul><li>Non selective Proteinuria. </li></ul><ul><li>GFR  , Cr  , BUN  </li></ul><ul><li>Edema (salt and water retention) </li></ul><ul><li>Hypertension </li></ul><ul><li>RBC & Protein casts. </li></ul><ul><li>Nephrotic </li></ul><ul><li>Polyuria </li></ul><ul><li>Proteinuria (“nephrotic range” >3.5g/24h) </li></ul><ul><li>Edema (Hypoalbuminemia) </li></ul><ul><li>Hyperlipidemia </li></ul><ul><li>Lipiduria </li></ul><ul><li>Protein casts. </li></ul>urine urine

28. . Be content with what you have; rejoice in the way things are. When you realize there is nothing lacking, the whole world belongs to you. Lao Tzu

29. . Causes of Renal Disease: Hypovolemia Diarrhoea, vomiting Bleeding, Burns, CCF Ascitis, Anasarca Renal A / V thrombosis Autoimmune disorders Vasculitis, anti GBM dis Diabetes, tubular dis. Toxins, infections, metabolic. Ureteral, urethral obstruction. Stone, papillary necrosis, bladder dis, prostate, drugs, cancer.

30. . Disorders of Kidney: <ul><li>Congenital </li></ul><ul><ul><li>Malformations-Horseshoe </li></ul></ul><ul><ul><li>ectopic, cysts, dysplasia. </li></ul></ul><ul><li>Acquired </li></ul><ul><ul><li>Glomerulonephritis – Acute/Chronic </li></ul></ul><ul><ul><li>Tubulointerstitial diseases – toxins, drugs, Infect. </li></ul></ul><ul><ul><li>Vascular diseases. – vasculitis. </li></ul></ul><ul><ul><li>Obstructive uropathy. hydronephrosis… </li></ul></ul><ul><ul><li>Renal calculi. </li></ul></ul><ul><ul><li>Neoplasms – carcinoma. </li></ul></ul><ul><li>End stage renal disease. </li></ul>

31. . GN -Clinical Presentations: <ul><li>Asymptomatic Proteinuria: </li></ul><ul><ul><li>Many types of early GN, MCD & FSGS </li></ul></ul><ul><li>Painless hematuria: </li></ul><ul><ul><li>Bergers (IgA), SLE, SBE, </li></ul></ul><ul><li>Nephr itic Syndrome: </li></ul><ul><ul><li>Posts Strep PGN , RPGN , antiGBM, SLE. </li></ul></ul><ul><li>Nephr otic Syndrome: </li></ul><ul><ul><li>Pri: MCD, MPGN, FSGS , MGN , IgA Neph </li></ul></ul><ul><ul><li>Sec: DM, drugs, SLE, Amyloidosis. </li></ul></ul><ul><li>Renal Failure: Acute/Chronic & endstage. </li></ul><ul><ul><li>Common end result, Drugs, infections, ischemic, metabolic. </li></ul></ul><ul><ul><li>ATN-Acute tubular necrosis. </li></ul></ul><ul><ul><li>Sec: Hypertension, DM , GN, </li></ul></ul><ul><ul><li>Pri: CRF. </li></ul></ul>

32. . Gross: Acute Nephritis:

33. . Glom. Dis. Classification: <ul><li>Aetiological </li></ul><ul><ul><li>Primary & Secondary </li></ul></ul><ul><li>Immunological </li></ul><ul><ul><li>Glomerular Ag (anti GBM) </li></ul></ul><ul><ul><li>Non-glomerular Ag. (immune complex) </li></ul></ul><ul><li>Morphological . </li></ul><ul><ul><li>diffuse : all glomeruli </li></ul></ul><ul><ul><li>focal : some glomeruli. </li></ul></ul><ul><ul><li>global : whole of glom. </li></ul></ul><ul><ul><li>segmental : part of glom. </li></ul></ul><ul><li>Morphologic: </li></ul><ul><ul><li>proliferative : increased cells </li></ul></ul><ul><ul><li>membranous : thickening of BM </li></ul></ul><ul><ul><li>membrano-proliferative : combination </li></ul></ul><ul><ul><li>crescentic : epithelial proliferation, florid / severe. </li></ul></ul>

34. . Morphologic types of GN: Diffuse Focal Global Segmental FSGS

35. . Casts = Glomerular pathology: Kidney Biopsy: Showing RBC, protein & mixed casts within tubules Glomerulus

36. . Red cell Casts in Urine:

37. . Casts in Urine: WBC Epithelial RBC Mixed Granular Hyaline Online Urinalysis tutorial : http:// library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html

38. . Great achievements can start right where you stand, by applying the habit of going the extra mile, by rendering more service and better service than you are now being paid for. Napoleon Hill

39. . AGN: Neph ro tic Sy: Polyuria, Proteinuria, hypoalbum hyperlipidemia. <ul><li>Primary glomerular diseases </li></ul><ul><ul><li>minimal change disease </li></ul></ul><ul><ul><li>membranous glomerulonephritis </li></ul></ul><ul><ul><li>membrano-proliferative GN (mesangiocapillary GN) </li></ul></ul><ul><ul><li>focal glomerulosclerosis </li></ul></ul><ul><ul><li>mesangial IgA nephropathy </li></ul></ul><ul><ul><li>bacterial endocarditis </li></ul></ul><ul><ul><li>shunt nephritis </li></ul></ul><ul><li>Secondary glomerular disease </li></ul><ul><ul><li>SLE </li></ul></ul><ul><ul><li>Henoch-Schönlein purpura </li></ul></ul><ul><ul><li>immune complex disease related to tumours, infections drugs (gold, penicillamine, phenytoin etc) etc.. </li></ul></ul><ul><ul><li>diabetes mellitus </li></ul></ul><ul><ul><li>amyloidosis </li></ul></ul><ul><ul><li>bee sting allergy </li></ul></ul><ul><li>Inherited disease </li></ul><ul><ul><li>congenital nephrotic sy. </li></ul></ul>

40. . Minimal Change GN: Introduction Synonyms: Incidence: Etiology: Clinical Features: Lab Features: Pathology: Clinical Course: Nil disease, lipoid nephrosis, foot process disease Idiopathic. Loss of net negative charge destruction of podocyte foot processes. Nephrotic syndrome. History of recent URI in 30%. Association with Hodgkin’s lymphoma. Overlap with FSGS patients. Nephrotic urine (polyuria, Selective proteinuria. (albuminuria). Spontaneous remission in 25-40%. Complete remission in 65-70% of patients. Steroid resistant patients may progress to FSGS. LM - Normal. IF - Negative. EM - Focal fusion/loss of foot processes. 80% of nephrotic syndrome in children (1-8 yrs.), mostly male. Adults in 2nd-3rd decade.

41. . Minimal Change Disease: Loss of Foot processes Normal

42. . Focal Segmental GN: Adults Synonyms: Incidence: Etiology: Clinical Features: Lab Features: Pathology: Clinical Course: Focal segmental Sclerosis Idiopathic - ? Auto Immune. No deposits. (Similar to minimal change). Nephrotic syndrome. History of recent URI in 30%. Association with Hodgkin’s lymphoma. Overlap with MCD patients. Nephrotic urine (more, clear) Selective proteinuria. No specific laboratory findings. Spontaneous remission 30% , 50% progression to chronic renal failure, 20% rapid progression. Podocyte damage, Segmental collapse of glom. increase in matrix (pink). 10 - 35% of nephrotic syndrome in adults.

43. . Membranous GN: Synonyms: Incidence: Etiology: Clinical: Lab: Path: Clinical Course: Epimembranous, extramembranous GN Immune complex deposition. Idiopathic in most patients, associated with infections, drugs, carcinomas, and heavy metals. Nephrotic syndrome in 80%, asymptomatic proteinuria in 20%. Microscopic hematuria. Non-selective proteinuria ± hematuria. Excellent prognosis in children. Some adults develop ESRD. Exclusion of other diseases is required. Diffuse, uniform BM thickening with subepithelial projections (“spikes”). Diffuse, coarsely granular IgG and C3 deposits along basement membranes. Electron-dense subepithelial deposits. 40-60 Years, 50% of adult nephrotic syndrome. Wireloop

44. . Mem.GN: Wireloop. Sub ep. dep.- Spikes IgG & C3.

45. . Membranoproliferative GN: Etiology: Chronic immune complex GN. Associated with chronic infections, SLE, cancer, cirrhosis, heroin abuse, etc. Clinical: Nephrotic syndrome in 50%, acute nephritic syndrome in 20%. Recent history of URI in 50%. Hypertension and/or renal insufficiency. Lab: Hypocomplementemia of classic and alternate pathways. C3 nephritic factor (C3NEF). Circulating immune complexes. Clinical Course: Progressive deterioration of renal function ± short remissions. ESRD within 10 years in 50% of children and 80% of adults. Path: Diffuse proliferative GN with thickening of the glomerular capillary walls,, and GBM splitting (“tram-tracking”). Diffuse, coarsely granular C3 and IgG deposits along GBMs. Electron-dense subendothelial deposits. Incidence: Children and young adults (5-25 years).

46. . MPGN-Tram tracking Arrow: Mesangial cell proliferation, basement membrane thickening, leukocyte infiltration, and accentuation of lobular architecture. Type 1 – Most common 80% Type 2 – Dense deposit disease (C3)

47. . MPGN-Tram tracking Glomerulus PAS stain to highlight the glomerular basement membranes. Observe the glomerular capillary loops showing two basements membranes giving the loops a tram track appearance (arrow).

48. . IgA Nephropathy (Berger’s) <ul><li>Commonest form of GN – Nephritic. </li></ul><ul><li>Young 15-30y, males, Asia-Pacific. </li></ul><ul><li>IgA deposits in mesangium, High serum IgA, varied severity </li></ul><ul><li>Episodic asymptomatic hematuria </li></ul><ul><li>microscopic hematuria (40%) </li></ul><ul><li>Bouts of macro hematuria (40%) </li></ul><ul><li>Nephritic or Nephrotic. </li></ul><ul><li>Renal failure (10%) </li></ul><ul><li>Slowly progressive CRF in 1/3 patients. </li></ul>IgA dep.  Normal IgA dep.

49. . IgA Nephropathy:

50. . IgA Nephropathy: