Pathology of the Urinary System, Nephritic Syndrome (PDF)

Pathology of the urinary system NEPHRITIC SYNDROME Prof Dr. Amany Abdel-Bary Pathology Department  Clinical manifestations of renal/urinary diseases 1. Azotemia: elevation of blood urea nitrogen (BUN) and serum creatinine levels without significant clinical effects, related to...

Pathology of the urinary system NEPHRITIC SYNDROME Prof Dr. Amany Abdel-Bary Pathology Department  Clinical manifestations of renal/urinary diseases 1. Azotemia: elevation of blood urea nitrogen (BUN) and serum creatinine levels without significant clinical effects, related to a decrease (GFR) 2. Uremia: clinically manifested azotemia, characterized by failure of renal excretory and metabolic functions. 3. Acute nephritic syndrome 4. Rapidly progressive glomerulonephritis (RPGN) 5. Nephrotic syndrome 6. Asymptomatic proteinuria and/or hematuria Kidney 7. Acute renal failure Ureters 8. Chronic renal failure Bladder 9. Urinary tract infections Urethra 10. Obstructive diseases and renal stones. 11. Neoplastic diseases. Pathology of Glomerular diseases Glomerulopathy Glomerular nephritis (GN)  Glomerular nephritis (GN): Glomerulonephritis (GN) are diseases that primarily involve renal glomeruli. 1. Primary glomerulonephritis: the glomeruli are the predominant site of involvement. 2. Secondary glomerulonephritis: is due to systemic diseases (diabetes mellitus, systemic lupus erythematosus, amyloidosis) and hereditary diseases.  Pathogenesis of glomerulonephritis Immunologically mediated GN Non-immunologically mediated GN 1. Metabolic glomerular injury as in DM Antibody Cell mediated GN 2. Hemodynamic: systemic hypertension. mediated GN (IV, T-cell mediated) 3. Glomerular ablation: any renal disease reduces (GFR) to 30-40% of normal. 4. Deposition of foreign material: amyloidosis Immune complex 5. Inherited glomerular diseases. Direct antibody mediated mediated (intrinsic or extrinsic) visceral epithelium Circulating Insitu endothelium immune immune neutrophils. complexes complexes  Fate of immune deposits: Transient Persistent exposure exposure Degradation of immune Repeated formation of complexes by mesangial immune complexes cells and monocytes Continuous glomerular injury Acute GN Chronic/Progressive Then regression of GN inflammation  How to study glomerular changes? Renal biopsy Should be subjected to examination by: Light microscopic examination Florescence microscopy Electron microscopy I. Light microscopy (LM) Glomerular lesions: Pattern of affection of the glomeruli may be: Diffuse: affection of the whole glomeruli. Focal: affection of < 50% of the glomeruli. Global: affection of the entire glomerulus. Segmental: affection of one segment within the affected glomerulus. Focal segmental GN. I. Light microscopic glomerular changes include: 1. Glomerular hypercellularity which may be due to: Proliferative Increase in endocapillary cellularity (mesangial and endothelial cells) Infiltration by inflammatory cells (neutrophils and monocytes) Crescentic: Proliferation of parietal cells leading to crescent formation 2. Thickening of GBM due to splitting of GBM or immune deposits. 3. Glomerular hyalinization or sclerosis. 4. Deposition of fibrin or abnormal material as amyloid Patterns of glomerular diseases by LM 1. Normal glomeruli 2. Glomerular hypercellularity (proliferative) 2. Glomerular hypercellularity (Crescentic) 2. Thickening of GBM 3. Glomerular hyalinization or sclerosis 4. Deposition of fibrin abnormal material as amyloid  II- Fluorescence microscopy: Fluorescein labeled antibodies. Against IgG, IgA, IgM and complements. Granular Linear Deposits have: Granular pattern; (most common). Linear pattern: (limited to GBM) III- Electron microscopy: It Plays an important role in: a. visualizing changes not seen by LM. b. site of immune complex deposition. Nephritic Syndrome Nephritic Syndrome It is a clinical complex, usually acute characterized by: 1- Hematuria with RBCs cast. 2- Proteinuria (90%) Only 10% RPGN (crescent), CRD. Adult: (15-50%) chronic GN.  Rapid progressive GN (Crescentic GN) Rapidly Progressive GN Definition: It is a clinicopathological syndrome characterized by rapid and progressive loss of renal function associated with severe oliguria, leading to acute renal failure. Characterized histologically by crescent formation in 50%-80% of the glomeruli (Crescent formed by proliferation of parietal cells of Bowman's capsule). Clinical picture: Rapid deterioration of renal functions. Prognosis and fate: If not rapidly treated patient progress to renal failure. Pathogenesis of RPGN: ❑ RPGN is induced by different diseases (glomerular and systemic). ❑ Glomerular injury is immunologically mediated by autoantibodies against endogenous GBM antigen. ❑ Goodpasture syndrome. ❑ Anti-GBM antibodies may bind to pulmonary alveolar capillary BM inducing hemoptysis associated with renal failure. ❑ Anti-GBM antibodies are present in the serum so, patients get benefit from plasmapheresis. Morphology of-RPGN: LM: - FM: linear deposition of immunoglobulins and C3 along the GBM. EM: non-specific. LM RPGN (Crescentic GN): Proliferation of partial cells within Bowman’s capsule which may obliterates and compresses the glomerular capillaries. FM RPGN (linear pattern) Linear deposition of Igs (IgG, IgM) and C3. EM: Non specific. THANK YOU