Pathology of Kidney Disorders

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Pathology of Glomerulonephritis
Dr. Venkatesh Murthy Shashidhar Associate
Professor of Pathology Fiji School of Medicine.
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Anatomy-Kidney
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Anatomy of Kidney
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Anatomy of Kidney

• Note the positions of
• Glomerulus
• Loop of Henley
• PCT, DCT, CT
• Cortex, Medulla, Pelvis.

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(No Transcript)
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Ultrastructure Glom. capillary
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Filtration Membrane Electron Micro.
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Glomerular Filtration
Collagen IV Laminin Fibronectin Entactin etc.
Blood Cells Proteins 3.6nm/70,000MW
Glomerular Capillary Lumen
L.R.I L.D. L.R.E Foot Process Podocyte (Viscera
l epithelium)
GBM

Plasma - Proteins FILTRATE
Bowmans Capsule Space
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Filtration Membrane
1. Fenestrated Endothelium 2. Lamina Rara
Interna 3. Lamina Rara Densa 4. Lamina Rara
Externa 5. Podocyte Slit membrane
Capillary Lumen
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Normal Kidney
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Normal Glomerulus (PAS)
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Disorders of Kidney

• Congenital
• Malformations, ectopic, cysts, dysplasia.
• Acquired
• Glomerular diseases
• Tubulointerstitial diseases,
• Renal calculi.
• Neoplasms carcinoma.

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Glomerular diseases

• Primary
• Acute diffuse post streptococcal
• Lipoid nephrosis or minimal change
• IgA nephropathy
• Secondary
• SLE, Diabetes, Hypertension etc.
• Immune, Toxins, Metabolic

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Immune Glomerulonephritis

• In-Situ immune complex deposition
• Tissue antigens - Goodpasture anti GBM Ag
• Planted antigens - infections, toxins, drugs.
• Circulating immune complex deposition.
• Endogenous - DNA as in SLE
• Exogenous - infections.
• Cell mediated Immune injury

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Diffuse Proliferative GN

• Post streptococcal common (even others)
• Primary infection - Pharynx, skin, ear etc..
• Kidney damage 1-4 weeks after infection.
• Malaise, fever, nausea, edema, ?ASO, ?C3
• Resolution in 6-8 weeks.

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Immune Glomerulonephritis

• Antigen or Antibody - Immune reaction
• Activation of complements, Neutrophils
• destruction of glomerular structure
• Inflammation, exudation ? swelling.
• ? blood flow, GFR, -
• Oliguria, Proteinuria, Hematuria, Hypertension.

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Neutrophil Activity

• Proteases
• Reactive oxygen metabolites
• Arachidonic acid metabolites

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Other Mediators

• Cytotoxic antibodies
• Macrophages
• Platelets
• Resident glomerular cells
• Fibrin related products

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Clinical Syndromes

• Nephritic syndrome.
• Oliguria, Haematuria, Proteinuria, Oedema.
• Nephrotic syndrome.
• Gross proteinuria, hyperlipidemia,
• Acute renal failure (RPGN).
• Oliguria, loss of Kidney function - within weeks
• Chronic renal failure.
• Over months and years - Uremia

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Nephritic Syndromes

• Diffuse Proliferative GN
• Post Streptococcal.
• Rapidly Progressive GN (or Crescentic)
• Post Streptococcal, Goodpastures,
• Focal Glomerulonephritis
• Primary Bergers disease (IgA Nephritis)
• Secondary IgA nephritis, Henoch Schonlein
  purpura, SBE, Coeliac Disease etc.

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Post Streptococcal GN (Prol.GN)

• 1-4 weeks following streptococcal infection by
  nephritogenic strains (time for Ab formation)
• Immune mediated
• Granular deposits of IgG,IgM C3 in GBM,
  (subepithelial location common)
• Humps in GBM on EM or IF Microscopy

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• Normal
• Post Strepto GN

• Inflammation
• Proliferation
• Swelling.
• Narrow capillary
• ?GFR-Renin-BP

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Diffuse Proliferative GN

• Enlarged hypercellular glomeruli.
• Hyperplasia of epithelium endothelium. Cell
  Swelling.
• Inflammatory cells.
• Collapsed capillaries. Obstruction to blood flow.

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IF- Diffuse Proliferative GN
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Pathogenesis of Diffuse PGN

• Streptococcal infection Antibody attack GBM -
  inflammation proliferation.
• Glomerular capillary obstruction
• J.G.A stimulation Renin high blood pressure
• Reduced filtration raised blood urea
• Fluid retention Oedema
• Damage to GBM
• Unselective proteinuria (form Pr. casts in
  tubule)
• Haematuria (form RBC casts in tubule)

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Progression of DPGN
Focal segmental glomerulo sclerosis

• Poststreptococcal DPGN

Complete Healing
Tubulo Interstitial Damage
CGN
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Diseases of Kidney summary

• Glomerulonephritis Glomerular diseases
  Destruction of glomeruli by immune or infections.
  
• Acute tubular necrosis Tubular diseases Necrosis
  of tubules by toxins or infections.
• Pyelonephritis Interstitial disease - Infections
• Nephrosclerosis Vascular diseases thickening
  of blood vessels Hypertension leading to micro
  infarctions.

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Clinical SyndromesSummary

• Nephritic syndrome.
• Oliguria, Haematuria, Proteinuria, Oedema.
• Nephrotic syndrome.
• Gross proteinuria, hyperlipidemia,
• Acute renal failure
• Oliguria, loss of Kidney function - within weeks
• Chronic renal failure.
• Over months and years - Uremia

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"It is our attitude at the beginning of a
difficult task which, more than anything else,
will affect its successful outcome."William
James1842-1910, Psychologist and Author
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Urine Microscopy

• Cells Casts Crystals.
• Cells - epithelial, inflammatory, malignant.
• Casts Protein cast of nephron DCT/CT
• Suggest Kidney pathology not URT.
• Protein, lipid, cells or mixed.
• Crystals suggest high concentration or altered
  solubility.

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WBC in Urine
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Urine Oxalate Crystals
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Granular Cast
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Epithelial Casts in Urine
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WBC Cast Urine
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Formation of Casts
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Red cell Casts in Urine
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What is an RBC cast?
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Nephrolithiasis stones.
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Urolithiasis Hydronephrosis
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Gordon
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Minimal Change Disease
Loss of Foot processes
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Membranous GN
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Crescentic GN - (RPGN)
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Crescentic GN - (Trichrome Stain)
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Goodpasture Syndrome
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Membranous GN
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Chronic Glomerulonephritis
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Urolithiasis
Ooouuuch!