Clinical syndromes related to renal disease. Acute nephritis. Hematuria, proteinuria, hypertension. Nephrotic synd. Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria. Asymptomatic hemat / proteinuria. Due to subtle glomerular abnormalities. Ac renal failure.
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Hematuria, proteinuria, hypertension
Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria
Asymptomatic hemat / proteinuria
Due to subtle glomerular abnormalities
Ac renal failure
Oliguria / anuria, azotemia,
(Anuria <100 ml; oliguria 100-400 ml)
Chr renal failure
Tubular defects, Urinary infections, Nephrolithiasis, Obstruction, Tumors
Clinical syndromes related to renal disease
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.
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.
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
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
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
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