1. Clinical syndromes related to renal disease

2. Clinical syndromes related to renal disease
Tubular defects, Urinary infections, Nephrolithiasis, Obstruction, Tumors
Uremia
Chr renal failure
Oliguria / anuria, azotemia,
(Anuria <100 ml; oliguria ml)
Ac renal failure
Due to subtle glomerular abnormalities
Asymptomatic hemat / proteinuria
Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria
Nephrotic synd
Hematuria, proteinuria, hypertension
Acute nephritis

4. Renal failure - Acute
Syndrome characterized by acute suppression of renal function with oliguria / anuria, azotemia.
Major causes are - Vascular obstruction, Severe glomerular disease, Acute tubulo-interstitial nephritis, Severe pyelonephritis with papillary necrosis, Urinary obstruction, Acute tubular necrosis.

5. End result is a decrease of GFR
Renal failure - Acute
Pathogenesis..
Failure of glomerular filtration due to hypo-perfusion
Renal causes
Post-renal causes
End result is a decrease of GFR

6. Renal failure - Chronic
End result of various renal diseases. Four stages:
Diminished renal reserve: GFR > 50%. Asymptomatic but susceptible
Renal insufficiency: GFR 20-50%. Azotemia, anemia, hypertension, polyuria. Sudden stress Uremia
Renal failure: GFR < 20%. Edema, metabolic acidosis, hypocalcemia, uremia with systemic complications.
End-stage renal disease: GFR < 5%. Terminal stage of uremia.

7. Pathogenesis of Glomerulonephritis

8. Pathogenesis of glomerulonephritis
Immune mechanisms underlie majority of the primary glomerulonephritis
1. In situ immune complex deposition
a. Intrinsic (fixed) glomerular antigens
Anti GBM, Heymann nephritis, membranous nephropathy
b. Planted antigens (proteins, bacterial, viral)
2. Circulating immune complexes
Others: cytotoxic antibodies, chemical mediators, cell mediated injury, non-immune mechanisms.
Ag-Ab deposition is the major pathway of glomerular injury. Interaction of in-situ and trapped immune complexes and local hemodynamic factors and structural determinants contribute to morphological and functional alterations in GN.
Majority of diseases produce granular deposits.
Heymann nephritis is animal model produced by injection of proximal tubular brush border induced antibodies.
Non-immune mechanisms - Diabetes, lipoid nephrosis

9. Pathogenesis of glomerulonephritis
Intrinsic (fixed) glomerular antigens - Anti GBM
Antibodies directed against non-collagenous domain of type IV collagen.
Linear pattern of fluorescence for IgG
Underlying cause in Goodpasture’s
syndrome
Ag-Ab deposition is the major pathway of glomerular injury. Interaction of in-situ and trapped immune complexes and local hemodynamic factors and structural determinants contribute to morphological and functional alterations in GN.
Majority of diseases produce granular deposits.
Heymann nephritis is animal model produced by injection of proximal tubular brush border induced antibodies.
Non-immune mechanisms - Diabetes, lipoid nephrosis

10. Pathogenesis of glomerulonephritis
Intrinsic (fixed) glomerular antigens
Heymann nephritis, membranous nephropathy
Animal model - rats immunized with preparations of PCT brush border developed antibodies. Manifested as membranous glomerulonephritis closely resembling human MGN.
Sub-epithelial granular deposits of immunoglobulin.
Heymann antigen is a 30 kd protein located in pits on the basal surface of podocyte.
Nature of antigen in man is unknown
Ag-Ab deposition is the major pathway of glomerular injury. Interaction of in-situ and trapped immune complexes and local hemodynamic factors and structural determinants contribute to morphological and functional alterations in GN.
Majority of diseases produce granular deposits.
Heymann nephritis is animal model produced by injection of proximal tubular brush border induced antibodies.
Non-immune mechanisms - Diabetes, lipoid nephrosis

11. Pathogenesis of glomerulonephritis
Circulating immune complexes -
Localize in glomeruli due to physicochemical and hemodynamic factors
Evocative antigen may be endogenous (SLE) or exogenous (PSGN, malaria etc)
Immune complexes lie in mesangium and sub-endothelial region of glomerulus or in sub-epithelial region. Deposits are granular.
Localization of complexes is dependant on:
- Molecular charge: Cationic particles pass through GBM
- Molecular size
Ag-Ab deposition is the major pathway of glomerular injury. Interaction of in-situ and trapped immune complexes and local hemodynamic factors and structural determinants contribute to morphological and functional alterations in GN.
Majority of diseases produce granular deposits.
Heymann nephritis is animal model produced by injection of proximal tubular brush border induced antibodies.
Non-immune mechanisms - Diabetes, lipoid nephrosis

16. Immunological studies in glomerulonephritis.
Immunofuorescence on biopsy
Complement levels
Circulating antibodies (ANA, GBM, ANCA)

17. Pathogenesis of glomerulonephritis
Cell mediated glomerular injury:
By activated T cells, monocytes and macrophages
- Delayed hypersensitivity by ag specific T cells
- Direct action by cytotoxic T cells
- Cytokine mediation
Tubulointerstitial nephritis
? Pauci-immune crescentic nephritis
Minimal change nephropathy
Focal segmental glomerulosclerosis