Pathology of Glomerulonephritis.

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.

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.

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

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)

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

23. Filtration Membrane: Endothelium Basement Mem Epithelium

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.

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.

32. Gross: Acute Nephritis:

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

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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).

49. IgA Nephropathy:

50. IgA Nephropathy:

51. IgA Nephropathy:

52. Acute Post Strept, Diff, Prol GN: Synonyms: Incidence : Etiology : Clinical : Lab: Path: Clinical Course: Acute proliferative glomerulonephritis, acute post-infectious GN. Glomerular trapping of circulating immune complexes. (Group A, Beta-hemolytic streptococci, type 12). Acute nephritic following strep. pharyngitis or pyoderma. (Other infections rare) Nephritic urine (little, dark, smoky) RBC casts, non selective proteinuria. Decreased serum complement. Evidence of strep inf. Children - Excellent prognosis. Adults - Worse prognosis, some develop progressive disease. Enlarged, hypercellular glomeruli with endothelial and mesangial cell proliferation, neutrophils, IgG and C3 in very coarsely granular pattern along GBMs. Discrete, subepithelial “hump-like” deposits. children (3-14). Sporatic, mostly winter and spring.

53. Post.Strep Proliferative GN: Normal PGN Ig+C3 Ig+C3

54. Post.Strep Proliferative GN: Hypercellularity, narrow capillary lumen, pleomorphic population of neutrophils, mesangial cells and granular sub. Epithelial deposits of IgG and C3. Neutrophils. Narrow cap.

55. Acute PGN (neutrophils)

57. RPGN (large, pale, edema)

58. RPGN Epithelial Crescent Collapsed capillary

59. RPGN Prot. Cast

60. Progression of GN

62. Diabetic Glomerulosclerosis

64. Acute Nephritis & Papillary necrosis - DM

66. Benign Nephrosclerosis: HPTN

67. Arteriosclerosis & Nephrosclerosis in HPTN Arteriolosclerosis Kidney: Leathery Granularity Benign Nephrosclerosis

73. Acute Tubular Necrosis: Glom. Norm Necrotic PCT (no nuclei) Normal DCT (Pro. cast inside) PCT early necrosis

75. Acute Pyelonephritis Abscesses Congestion

76. Pyelonephritis Inflammatory cells WBC Cast in DCT PCT BV

77. Pyelonephritis - Abscess WBC Cast in DCT PCT Glom.

79. Chronic Renal Failure: ESKD Small atrophic kidney – Irregular pitted surface (due to scarring). Prominent loss of Cortical tissue.

80. Chronic Renal Failure: ESKD

81. Chronic Glomerulosclerosis :

82. Chronic Glomerulosclerosis :

83. Chronic Glomerulonephritis: Advanced tubular atrophy with "thyroidization” inspisated secretions within tubules.

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108. Video tutorials on Digital Pathology Slides on Acknowledgements: You Tube WashingtonDeceit: Dedicated to the greatest pathologist of all time - Martin A. Swerdlow , MD "Build it and they will come."

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112. Altruism……!

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115. Urine specimens: 1. Random clean catch or mid-stream collection 2. First morning specimen 3. Second-voided specimen 4. Post prandial collection 5. Day specimen 6. Night specimen 7. Twenty-four hour collection 8. Catheterized collection

116. Normal Urine Crystals Acid Urine pH Neutral Urine pH Alkaline Urine pH Calcium Oxalate Ammonium Biurate Triple Phosphates Uric Acid Calcium Carbonate Ammonium Biurate Calcium Oxalate Calcium Carbonate Triple Phosphate Calcium Phosphate Amorphous urates Amorphous Phosphates

123. A 27-year-old white man Urinalysis: protein - 2+ blood - 4+ glucose - neg Micro: > 40 RBCs/HPF (0-2 RBCs/HPF) 10 WBCs/HPF (0-2 WBCs/HPF) 5-10 RBC casts/LPF (0 casts/LPF) Hematocrit 38% Creatinine 3.9 mg/dL BUN 102 mg/dL Liver serology normal ANCA, ANA, HIV negative

124. Renal Artery stenosis - Atrophy Leathery Granularity Benign Nephrosclerosis Atrophy

125. Septicemia: pinpoint micro abscesses with hyperaemic borders. (Flea bitten kidney)