GLOMERULONEPHRITIS

Dr S Chakradhar

Relatively uniform, involve most or all glomeruli Focal lesions: Diffuse lesions: Relatively uniform, involve most or all glomeruli Focal lesions: Involve only some glomeruli; others normal Segmental: Involve only one part of the glomerulus Mesangial: Deposits of immunoglobulins in mesangial matrix Membranous: Thickening of BM Proliferative lesions: Increased number of glomerular cells Sclerotic lesions: Glomerular scarring from previous glomerular injury Crescent lesions: Accumulation of proliferating cells in Bowman's space Dr S Chakradhar

Glomerulonephritis / Glomerulopathy / Glomerular Diseases Group of disease in which the disease affects the Glomerulus and is often inflammatory in nature. The disease is Immunologically mediated and involves both kidneys symmetrically. Classification A. Primary - When major problem starts in the Glomerulus Secondary - when involvement is part of systemic disease. B. Inherited Acquired Proliferative Non proliferative Dr S Chakradhar

Non Proliferative Characterized by numbers of cells (lack of hypercellularity) in the Glomerulus They usually cause nephrotic syndrome. Proliferative Characterized by increased number of cells in the Glomerulus (hypercellular). Usually present as a nephritic syndrome and usually progress to end- stage renal failure (ESRF) over weeks to years

Inherited Glomerular Disease Alport’s Syndrome Classification: Inherited Glomerular Disease Alport’s Syndrome Thin Basement Membrane Disease Acquired Glomerular Disease Non Proliferative Minimal change GN Focal Segmental Glomerulosclerosis (FSGS) Membranous glomerulonephritis Proliferative IgA nephropathy (Berger's disease) Henoch-Schönlein purpura Post-infectious Membranoproliferative/mesangiocapillary GN Rapidly progressive glomerulonephritis Dr S Chakradhar

Pathogenesis of glomerular injury Circulating Immune Complex Deposition Injury resulting from deposition of antigen-antibody complex in the glomerulus Endogenous antigens (e.g. DNA in SLE, tumor antigens) Exogenous antigens (e.g. infectious products - streptococci) There is type III hypersensitivity reaction Dr S Chakradhar

2. In Situ Immune Complex Deposition Injury by antibodies reacting in situ within the glomerulus either with Insoluble fixed (intrinsic) glomerular antigens Glomerular basement membrane/anti-GBM nephritis - Goodpasture syndrome Heymann antigen - Membranous glomerulopathy Mesangial antigens Others – unknown antigen Planted antigen within the glomerulus Exogenous – drugs, infectious agents Endogenous – DNA, IG A Dr S Chakradhar

Secondary mechanisms / Mediators of Glomerular injury Cells Chemical mediators Dr S Chakradhar

Clinical presentations (Glomerulo syndromes) Nephrotic syndrome Acute nephritic syndrome Renal failure – Acute or Chronic renal failure Asymptomatic hematuria or proteinuria, or a combination of these two, Is usually a manifestation of subtle or mild glomerular abnormalities. Hypertension It may be the first findings in some pt with certain glomerular disease Dr S Chakradhar

Alport syndrome Arise from a mutation or deletion of the COL4A5 gene on the X chromosome Defect in the synthesis of collagen (important structural component of basement membranes in the kidney, inner ear, and eye) Accumulation of abnormal collagen results in a progressive degeneration of the GBM Dr S Chakradhar

Thin Basement Membrane Disease (benign familial hematuria) Is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent Microscopic haematuria, Without associated HTN, Proteinuria or reduced GFR. Dr S Chakradhar

ACUTE Nephritic Syndrome It is a clinical manifestation in which several different renal diseases giving rise to a group of specific symptoms It is an immune mediated inflammatory bilateral disease of the kidney which affects almost all the Glomeruli, characterized by: Haematuria – RBC casts or dysmorphic RBC Proteinuria – usually less than 1gm HTN Edema Renal impairment – Oliguria, uremia, raised urea & creatinine Dr S Chakradhar

Post-infectious / Acute glomerulonephritis (Acute diffuse proliferative glomerulonephritis) Occur essentially after any infection, but classically occurs after infection with Streptococcus pyogenes Post Streptococcal Non-Post Streptococcal Normal Dr S Chakradhar

Pathogenesis Ag – Ab Immune Complex  Immune Injuries GBM fracture Haematuria, Proteinuria Cells proliferation  capillary lumen narrowed Glomerular blood flow↓  ↓ GFR Oliguria, AzotemiaARF Retention of water & sodium ↑ Blood Volume a. Oedema b. hypertension c. Hypertensive Encephalopathy  Circulatory Congestion  Cardiac Failure Dr S Chakradhar

Pathology Dr S Chakradhar

Patient is usually a child of 5-10 years age Clinical features Symptoms: Patient is usually a child of 5-10 years age History of streptococcal infection (e.g. pharyngitis) 1-3 weeks before may present Puffy face & swelling of the whole body gradually. Scanty & smoky colored urine. Dull aching pain at renal angle. Low grade fever. Systemic symptoms: Anorexia, nausea, vomiting, constipation & sore throat may be Dr S Chakradhar

Signs: 1. Puffiness of face. 2. Temperature is raised. 3 Signs: 1. Puffiness of face. 2. Temperature is raised. 3. Periorbital & ankle oedema present. 4. Tenderness over renal angle. 5. BP is normal or raised in 50% cases. Dr S Chakradhar

4. Acute or chronic renal failure 5. Nephrotic syndrome Encephalopathy Complication: 1. Hypertension 2. Pulmonary oedema 3. Heart failure 4. Acute or chronic renal failure 5. Nephrotic syndrome Encephalopathy Causes of death in AGN: 1. Acute circulatory congestion with pulmonary Oedema (LVF). 2. Hypertensive encephalopathy. 3. Acute renal failure. Dr S Chakradhar

Total output: decreased. Colour: Smoky. Specific Gravity: Raised Investigation 1.Urine: Total output: decreased. Colour: Smoky. Specific Gravity: Raised Proteinuria: Mild (usually <2 gm/dl). Microscopic: RBC & RBC cast, WBC  2. Blood: TC and DC: leucocytosis with increased Polymorphs ESR: often High Blood urea and Creatinine : High. Serum electrolyte: K & Na. Dr S Chakradhar

Cardiomegally & pulmonary oedema (if complication). 3. X-ray of chest: Cardiomegally & pulmonary oedema (if complication). 4. Throat swab C/S. 5. ASO titer (anti DNAase) - elevated 6. Serum C3 level is low (returns to normal 6 12 weeks) 6. Renal biopsy: confirmatory Dr S Chakradhar

Protein restriction in renal failure Low sodium in presence of oedema Treatment Bed rest : Is indicated as long as there are clinical manifestations of active disease, such as Oedema, Hypertension, or Gross Haematuria. Diet Protein restriction in renal failure Low sodium in presence of oedema Fluid Restriction of fluid Diuretics Frusemide 40 – 80 mg/day Dr S Chakradhar

Dose adjusted according to BP Pulmonary Oedema Propped up position Hypertension Drug of choice: Nifedipine Methydopa Prazosin Dose adjusted according to BP Pulmonary Oedema Propped up position O2 inhalation Diuretics – Frusemide Morphine 2.5 mg + Phenargan 25 mg IV or IM Specific treatment : Inj. Benzyl Penicillin 10 lakhs units IM 6 hourly for 10 days   Dr S Chakradhar