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Pathology of Glomerulonephritis
Dr. Venkatesh Murthy Shashidhar
Senior Lecturer in Pathology
Normal Kidney:
Normal Glomerulus (PAS)
Anatomy:
Cap. loops
J.G.App. DCT
Afferent.A
DCT
Efferent.A
Filtration Unit:
1. Fenestrated Endothelium 2. Lamina Rara Interna 3. Lamina Rara Densa 4. Lamina Rara Externa 5. Podocytes + Slit membrane
Capillary Lumen
Glomerular Filtration:
BLOOD
Proteins
3.6nm/70,000MW
Glomerular Capillary Lumen
L.R.I L.D. L.R.E
GBM
Plasma Proteins
FILTRATE
Foot Process Podocyte
(Visceral epithelium)
Bowman’s Capsule Space
Pathogenesis:
Immune mechanisms – Most common
Autoimmune
Planted Antigen Immune complex.
Toxins Metabolic
Glomerular diseases:
Primary GN: • Acute Diffuse Prol. Poststrept & other Inf. • Crescentic (Rapidly Progressive) • Membranous GN. • Lipoid / Minimal Change . • Focal segmental G.sclerosis. • Membranoproliferative GN. • IgA nephropathy. • Chronic Idiopathic GN. Associated with Systemic Diseases: • SLE, DiabetesMellitus. • Goodpasture's Syndrome. • Polyarteritis Nodosa. • Wegener's Granulomatosis. • Henoch-Schonlein Purpura. • Bacterial Endocarditis. • Amyloidosis
• Hereditary Disorders: • Alport's Syndrome. • Fabry's Disease
Pathogenesis of Immune GN:
1. Ab, Ag/Ab or Immune complex deposition. 2. Immune reaction 3. Inflammation Activation of complement 4. destruction of glomerular structure 5. Renal dysfunction, Proteinuria, Hematuria
Immune Glomerulonephritis:
Glomerular damage - patterns:
Immune Glomerulonephritis:
In-Situ immune complex formation:
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
Immune Glomerulonephritis:
C.Immune Complex ANTI-GBM HEYMANN
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
Nephritic Syndromes :
Diffuse Proliferative GN
Post Streptococcal.
Rapidly Progressive GN (or Crescentic)
Post Streptococcal, Goodpasture’s,
Focal Glomerulonephritis
Primary: Bergers disease (IgA Nephritis)
Secondary IgA nephritis, Henoch Schonlein purpura, SBE, Coeliac Disease etc.
Post Streptococcal GN (Prol.GN):
1-4 weeks following streptococcal infection (nephritogenic strains) Immune mediated (time for Ab formation) Granular deposits of IgG,IgM & C3 in GBM, (subepithelial location common) Humps in GBM on EM or IF Microscopy
Pathogenesis of Diffuse PGN:
Streptococcal infection - Immune complex deposition, 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)
Progression of DPGN:
Poststreptococcal DPGN
Complete Healing
Focal segmental glomerulo sclerosis
CGN
Tubulo – Interstitial Damage
Clinical Features: G.Nephritis
•Hypertension •Skin Infections •Congestive Cardiac Failure
Laboratory Features: G.Nephritis
•Inflammation •Decreased filtration •Damage to filtration unit
Diffuse Proliferative GN:
Hyperplasia of epithelium & endothelium.
Cell Swelling.
Inflammatory cells. Obstruction to flow. Enlarged hypercellular glomeruli.
•Normal
•Proliferative •Post strepto
IF- Diffuse Proliferative GN
Complications:
Glomerular diseases:
Chronic Glomerulonephritis:
Urine Microscopy :
Cells Casts Crystals. Casts are formed within nephron.
Casts Suggest Kidney pathology.
Casts can be made up of Protein, lipid, cells or mixed.
Crystals suggest high concentration or altered solubility.
Formation of Casts:
Red cell Casts in Urine:
The greatest test of courage is to bear defeat without losing heart…!
Robert G. Ingersoll
Glomerular diseases:
Minimal Change/Lipoid :
Minimal Change Disease:
Loss of Foot processes
Membranous GN :
Crescentic GN - (RPGN)
Crescentic GN - (Trichrome Stain)
Goodpasture Syndrome:
Membranous GN :
Focal Segmental Gl. Sclerosis:
Mesangiocapillary GN: (MPGN)