Pathology of Kidney Dr Sachin Kale MD Associate

Pathology of Kidney Dr. Sachin Kale, MD. Associate Professor, Dept of Pathology.

Anatomy of Kidney Note the positions of Glomerulus PCT, DCT, CT Cortex, Medulla, Pelvis.

Glomerular diseases: n Primary – Acute diffuse post streptococcal – RPGN – Membranous GN – FSGS – MPGN – Lipoid nephrosis or minimal change – Ig. A nephropathy n Secondary – SLE, Diabetes, Amyloidosis, Goodpasture’s syndrome, PAN, WG, HSP, Hypertension etc.

Clinical Syndromes: n Nephritic syndrome. – Oliguria, Haematuria, Proteinuria, Oedema, Azotemmia, Hypertension. n Nephrotic syndrome. – >3. 5 gm proteinuria, Hypoalbuminemia hyperlipidemia, Lipiduria n RPGN. – Nephritis, loss of Kidney function - within weeks n Chronic renal failure. – Azotemia/uremia progressing over months and years q Asymptomatic Hematuria or proteinuria

CHRONIC RENAL FAILURE Fluid and Electrolytes: Dehydration, Edema, Hyperkalemia, Metabolic acidosis Calcium Phosphate and Bone: Hyperphosphatemia, Hypocalcemia, Secondary hyperparathyroidism, Renal osteodystrophy Hematologic: Anemia, Bleeding diathesis Cardiopulmonary: Hypertension, Congestive heart failure, Pulmonary edema, Uremic pericarditis Gastrointestinal: Nausea and vomiting, Bleeding, Esophagitis, gastritis, colitis Neuromuscular: Myopathy, Peripheral neuropathy, Encephalopathy Dermatologic: Sallow (greenish-yellow) color, Pruritus, Dermatitis

ACUTE TUBULAR NECROSIS • • Destruction of renal TUBULAR epithelium Loss of renal function 50% of ACUTE renal failure Two types: ISCHEMIC NEPHROTOXIC -AMINOGLYCOSIDES -AMPHOTERICIN B -CONTRAST AGENTS

NORMAL

ATN

ATN PATHOGENESIS • BLOOD FLOW DISTURBANCES (ISCHEMIC) • TUBULAR INJURY (NEPHROTOXIC)

CLINICAL COURSE • INITIATION (36 hours) – Mild OLIGURIA – Mild AZOTEMIA • MAINTENANCE – More OLIGURIA – More AZOTEMIA – DIALYSIS NEEDED • RECOVERY – HYPOKALEMIA main problem – BUN, CREATININE return to normal

Immune Mechanisms of Glomerular injury: n Antibody mediated: In-Situ immune complex deposition n Circulating immune complex deposition. n n n – Tissue antigens - Goodpasture anti GBM Ag – Planted antigens - infections, toxins, drugs. – – Endogenous - DNA as in SLE Exogenous – infections – HBs. Ag, Syphilis, Streptococcal, Falciparum, Cell mediated Immune injury Activation of alternate complement pathway

Immune Glomerulonephritis: 1. 2. 3. 4. 5. 6. Antigen or Antibody - Immune reaction Activation of complements, Neutrophils… destruction of glomerular structure Inflammation, exudation swelling. ↓ blood flow, GFR, Oliguria, Proteinuria, Hematuria, Hypertension.

Neutrophil Activity Proteases – GBM degradation n Reactive oxygen metabolites – cell damage n Arachidonic acid metabolites – Reduction in GFR n

Other Mediators Cytotoxic antibodies n Macrophages n Platelets n Resident glomerular cells n Fibrin related products n

Nephritic Syndromes : n Diffuse Proliferative GN – Post Streptococcal. n Rapidly Progressive GN (or Crescentic) – Post Streptococcal, Goodpasture’s, n Focal Glomerulonephritis – Primary: Bergers disease (Ig. A Nephritis) – Secondary Ig. A nephritis, Henoch Schonlein purpura, SBE, Coeliac Disease etc.

Diffuse Proliferative GN: Post streptococcal* common – n Primary infection - Pharynx, skin, ear etc. . n Kidney damage – 1 -4 weeks after infection. n Malaise, fever, nausea, edema*, ↑ASO, ↓C 3 n Resolution in 6 -8 weeks. n

Post Streptococcal GN (Prol. GN): 1 -4 weeks following streptococcal infection by nephritogenic strains (time for Ab formation) n Immune mediated n Granular deposits of Ig. G, Ig. M & C 3 in GBM, (subepithelial location common) n Humps in GBM on EM or IF Microscopy n

• Normal • Inflammation • Proliferation • Swelling. • Narrow capillary • ↓GFR-Renin-BP • Post Strepto GN

Diffuse Proliferative GN: n n Enlarged hypercellular glomeruli. Hyperplasia of epithelium & endothelium. Cell Swelling. Inflammatory cells. Collapsed capillaries. Obstruction to blood flow.

IF- Diffuse Proliferative GN

Pathogenesis of Diffuse PGN: Streptococcal infection – Antibody attack GBM - inflammation & proliferation. n Glomerular capillary obstruction: n – J. G. A stimulation – Renin – high blood pressure – Reduced filtration – raised blood urea – Fluid retention – Oedema n Damage to GBM: – Unselective proteinuria (form Pr. casts in tubule) – Haematuria (form RBC casts in tubule)

Progression of DPGN: Poststreptococ cal DPGN Rapidly Progressive GN Complete Healing CGN Cardiac Failure or Uremia; death in acute phase

RPGN Clinicopathologic syndrome n Glomerular damage n Rapid progressive decline in renal function n Histology: accumulation of cells in Bowman’s space in the form of “Crescents” n

RPGN: Classification & Pathogenesis Postinfectious n GN associated with systemic diseases n Idiopathic RPGN n Glomerular injury is immunologically mediated. n Goodpasture’s syndrome – classic anti. GBM nephritis n

RPGN classification Post-infectious RPGN n Systemic diseases – n – SLE, Goodpasture’s, Vasculitis (PAN), Wegener’s granulomatosus, HSP, Essential cryoglobulinemia n Idiopathic RPGN

RPGN cont. . Idiopathic : ½ the cases, n Linear, Granular or minimal to none immune deposits n Gross: Enlarged pale kidneys Large white kidney n Petechial hemorrhages in cortex n M/E: Glomeruli: focal necrosis, endothelial proliferation n

RPGN… Formation of crescents: n Proliferation of parietal cells, migration of monocytes and macrophages into Bowman’s space n Crescents obliterate Bowman’s space, compression capillary tuft n Crescents undergo sclerosis n

RPGN: Clinical features Goodpasture’s Syndrome: recurrent hemoptasis & renal manifestations n Hematuria, Red cell casts, Moderate proteinuria, n Variable HT and edema n Oliguria n

Which of the following presents with hematuria, proteinuria and hypertension Nephrotic syndrome n Nephritic Syndrome n UTI n Renal Tubular Acidosis n

All of the following are seen in renal failure except Hypercalcemia n Hyperkalemia n Bone lesions n Metobolic Acidosis n

Anemia in renal failure is generally Microcytic hypochromic n Normocytic normochromic n Dimorphic n megaloblastic n

Which of the following is not a primary GN Minimal Change disease n Membranous GN n Diabetes mellitus n RPGN n

Which of the following is not part of nephrotic syndrome Lipiduria n Hypertension n Proteinuria n Edema n

True about Post-strepto GN Occurs 1 – 4 months after infection n Occurs 1 – 4 days after infection n Occurs 1 – 4 weeks after infection n Non of the above n

False about RPGN. . Formation of crescents n Small contracted kidneys n Hematuria n Oliguria n

Spot the diagnosis RPGN

Spot the diagnosis ATN

Spot the diagnosis Post streptoco ccal GN

Thought for the day… n Ours is a world where people don't know what they want and are willing to go through hell to get it.

Thanks… n http: //sachinkale 1. tripod. com