clinical syndromes related to renal disease
DESCRIPTION
Clinical syndromes related to renal disease. Acute nephritis. Hematuria, proteinuria, hypertension. Nephrotic synd. Proteinuria > 3.5 g/day, hypoalbuminemiaTRANSCRIPT
Clinical syndromes related to renal disease
Tubular defects, Urinary infections, Nephrolithiasis, Obstruction, Tumors
UremiaChr renal failure
Oliguria / anuria, azotemia, (Anuria <100 ml; oliguria 100-400 ml)
Ac renal failure
Due to subtle glomerular abnormalitiesAsymptomatic hemat / proteinuria
Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria
Nephrotic synd
Hematuria, proteinuria, hypertensionAcute nephritis
Clinical syndromes related to renal disease
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.
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 glomerulonephritis1. In situ immune complex deposition
a. Intrinsic (fixed) glomerular antigensAnti GBM, Heymann nephritis, membranous nephropathyb. Planted antigens (proteins, bacterial, viral)
2. Circulating immune complexes
Others: cytotoxic antibodies, chemical mediators, cell mediated injury, non-immune mechanisms.
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
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
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
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