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Renal 09 Glom. Dz

Dickinson: Glomerular disease - introduction

Most glomerular diseases are... Immune mediated
Which immune systems mediate glomerular injury? Innate and adaptive
Immune-mediated injury occurs through... Inflammatory and non-inflammatory mechanisms
Classification of glomerular disease 1. Nephrotic/Nephritic 2. Proliferative, sclerotic or membranous 3. Primary or secondary
Classification of glomerular disease: Proliferative Increase in cellular components of the glomerulus regardless of origin
Classification of glomerular disease: Sclerotic Increase in the non-cellular components of the glomerulus
Classification of glomerular disease: Membranous Increase in the thickness of the glomerular capillary wall Often caused by immune complex deposition
Classification of glomerular disease: Primary V Secondary Primary -Kidneys are directly affected Secondary -Kidneys are damaged as a result of systemic disease, toxin or medication
Nephrotic Syndrome Increased permeability Protein loss Proteinuria >3.5 g/day Non-inflammatory
Nephritic syndrome Inflammatory process Hematuria Low proteinuria Decreases permeability of the GCW
Glomerular capillary wall (4 layers) Mesangial cells Endothelium GBM Podocytes
Immune complexes can be found in.. Mesangium Subendothelium Basement membrane Subepithelium
Immune complexes of antibodies form with ____ or ____ Fixed glomerular antigens Exogenous non-renal antigens
Type of glomerular lesion depends on.. Site of immune complex deposition
Site of deposition determines... What mediators of tissue injury are activated
In situ immune complex deposition: Ab binding to... Endogenous renal antigen Endogenous non-renal antigen Exogenous antigen
Preformed circulating immune complex deposition Preformed complexes re transported directly to kidney tissue via the circulation and trapped -Lupus -Post-group A strep infxn
Nephrotic syndrome: Target of injury and site of complex depostion Podocytes Subepithelial complexes
Nephrotic syndrome: Activates... Membrane attack complex
Which complement pathway is initiated by IgG? Classical
Classical complement pathway Recruits neutrophils, monocytes, macrphages Produces MAC which damages podocytes
Non-inflammatory mechanism of classical pathway Does not recruit cells MAC damages podocytes
Non-inflammatory mechanism for subendothelial immune complex deposition Phagocytes can't cross GBM Chemoattractants can't establish a gradient
Nephritic syndrome Immune complex deposition in mesangium and subendothelium Immune cells cause tissue damage MAC produced
Inflammatory classical pathway Recruits neutrophils, monocytes, macrphages Produces MAC which damages membranes
What serum proteins accumulate in tissues during an inflammatory response? Growth factors Albumin Chemokines
How do complexes cause glomerular injury? 1. Activate complement 2. Chemokines recruit macrophages and neutrophils 3. MAC injures plasma membranes 4. phagocytes activated
How do complexes cause glomerular injury? (cont.) 5. Phagocytes produce pro-inflammatory mediators, ROS, lysosomal enzymes and proteases
IgA Nephropathy Most frequent form of idiopathic glomerularnephritis worldwide Deposition of IgA in mesangium Induces inflammation
IgA nephropathy: Pathogenesis Abnormal gylcosylation of IgA Induces self aggregation
IgA nephropathy: Nephritic syndrome Glycosylated dimeric IgA activates the Lectin complement pathway Induces MAC production Microscopic hematuria in the absence of sustained proteinuria
IgA nephropathy: Dx Made by immunofluorescence of IgA
Created by: bcriss