Question | Answer |
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 |