Clinical syndromes related to renal disease

Clinical syndromes related to renal disease Tubular defects, Urinary infections, Nephrolithiasis, Obstruction, Tumors Uremia Chr renal failure Oliguria / anuria, azotemia, (Anuria <100 ml; oliguria 100-400 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

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.

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

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.

Pathogenesis of Glomerulonephritis

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

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

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

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

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

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