6a GLOMERULAR DISEASES Year 4 Internal Medicine Notes

6a GLOMERULAR DISEASES Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 GLOMERULAR DISEASES Dr. Alex Mogere Consultant Physician Slide 2 Glomerular disease Glomerular diseases account for a significant proportion of acute and chronic kidney disease. Immunologically mediated Metabolic diseases Hereditary eg Alport’s syndrome(hematuria) May be primary or secondary Slide 5 Spectrum of glomerular disease Slide 6 Primary glomerular disease Minimal change glomerular disease Membranous GN Membranoproliferative GN Acute diffuse proliferative GN IgA nephropathy Slide 7 Secondary glomerular disease HIVAN Polyarteritis nodosa (PAN) DM SLE Amyloid Malaria RA, Sarcoidosis HUS Drugs eg Gold, penicillamine, Mercury allergies Slide 8 Pathogenesis Circulating immune complex deposition(Ag/ab deposition on glomeruli, interaction with complement, inflammation, glomerular injury) Abs directed against Ag on glomerular capillary membrane: eg goodpasture syndrome Slide 9 Nephrotic syndrome Characterized by: Severe proteinuria(≥3.5g/d) Hypoalbuminemia-from proteinuria Edema- from hypoalbumineamia(low colloid Pa) Hyperlipidemia- due to hypoalbuminemia-increased prot synth including lipoproteins hyperlipiduria-increased permeability Slide 10 Aetiology of NS Due to: Primary Glomerular disease Secondary GN Slide 11 Clinical presentation of NS Edema Malnutrition-infections, proteinuria, muscle wasting Hypercoagulability-arterial/venous thrombosis Slide 12 Invxs Urinalysis Serum albumin-<3g/dl,, Total serum prot <6mg/dL Renal biopsy LDL-raised,\nESR high—increased serum fibrinogen ANA Serum glc Slide 13 MX of NS Antihypertensive-ACE Is, ARBs Diuretics Lipid-lowering meds Anticoagulants\nImmunosuppresants(to induce remission)-corticosteroids,\nOther immunosuppresants(reserved for steroid-resistant pts with persistent edema, or for steroid-dependent pts with significant steroid-related A/Es.):rituximab, cyclosporine, cyclophosphamide Cyclosporine is indicated when relapses occur after cyclophosphamide treatment Slide 14 Minimal change GN Accounts for nephrotic syndrome in most children and about 25% of adults.\ncaused by reversible dysfunction of podocytes Presents with proteinuria/Nephrotic syndrome Good response to corticosteroids Pathogenesis unknown Slide 15 Focal segmental glomerulosclerosis Segmental scars in some glomeruli\nNo acute inflammation\nPodocyte foot process fusion seen in primary FSGS with nephrotic syndrome Primary FSGS presents as idiopathic nephrotic syndrome but is less responsive to Tx than minimal change; Secondary FSGS presents with variable proteinuria and outcome Associations: Healing of previous local glomerular injury\nHIV infection\nHeroin misuse\nMorbid obesity Slide 16 Ct.Focal segmental GN Segmental inflammation and/or necrosis in some glomeruli ± crescent formation Small-vessel vasculitis Often occurs in systemic disease Responds to Tx with corticosteroids and immunosuppressants\nCheck ANCA, ANA Slide 17 Membranous GN Slowly progressive(Is a form of chronic immune complex nephritis) Commoner btwn 30-50 yrs Diffuse thickening of GBM Deposition of immune complex on the epithelial side of the GBM\ncommon cause of adult idiopathic nephrotic syndrome Associations: HLA-DR3 (for idiopathic)\nDrugs\nMercury,\nheavy metals\nHepatitis B virus\nMalignancy Slide 18 Aetiology:Membranous GN(MGN) Primary:85% from autoabs that cross react with Ags expressed by podocytes Secondary: Infections- malaria, syphilis, chronic hep B SLE Malignancies, ca lung, colon, melanoma Drugs-NSAIDs, penicillamine Exposure to inorganic salts-Au, Hg Slide 19 Clinical presentation of MGN Insidious devt of NS No response to corticosteroids About 40 % lead to Renal failure after2-40 yrs Unlike minimal change disease, the proteinuria is non selective- both albumin and globulin are excreted Slide 20 IgA nephropathy Increased mesangial matrix and cells\nFocal segmental nephritis in acute disease Common disease with a range of presentations, usually including haematuria and hypertension Haematuria is the earliest sign\nProteinuria can also occur but is usually a later feature hallmark in young adults -acute self-limiting exacerbations, often with gross haematuria, in association with minor respiratory infections.\nthe latency from clinical infection to nephritis is short: a few days or less.\nPoor response to immunosuppressive therapy Slide 21 Membranoproliferative GN(MPGN) Also called Mesangiocapillary glomerulonephritis (MCGN) increase in mesangial cellularity with thickening of glomerular capillary walls and subendothelial deposition of immune complexes and/or components of the complement pathway The typical presentation is with proteinuria and haematuria. Tx –underlying cause,immunosuppressive drugs Slide 22 Post infectious GN The most cmn histological pattern in bacterial infection is mesangiocapillary glomerulonephritis serum concentrations of C3 and C4 are typically reduced, reflecting complement