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Pathology of Glomerular Disease
334-341
14
Biology
Professional
10/01/2012

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Term
What are the 3 functions of mesangial cells within the mesangial matrix (contiguous with the lamina rara interna of the BM)
Definition
1) Tether BM to mesangium, creating central mesangial unit connected to many glomerular segments.

2) Phagocytosis of debris

3) Cytokine production for glomerular proliferation in response to injury
Term
What glomerular disease is described by each of the following sets of signs/symptoms?

1) Hematuria, azotemia, proteinuria, oliguria, edema, HTN

2) Acute nephritic syndrome with acute renal failure

3) >3.5 gm/24 proteinuria, hypoalbuminemia, hyperlipidemia, hyperlipiduria, edema

4) Azotemia progressing to renal failure

5) Non-progressive, subclinial hematuria or proteinuria
Definition
1) Acute nephritic syndrome
2) Rapidly progressive glomerulonephritis
3) Nephrotic syndrome
4) Chronic renal failure
5) Asymptomatic
Term
How do you correctly describe the Distribution of glomerular injury on light microscopic investigation?
Definition
1) Diffuse (>50% of glomeruli) vs. Focal (<50 %)
- Can be random, subscapular or juxtamedullary

2) Global (entire glomerulus) vs. segmental vs. mesangial
- Segmental is peripheral + mesangial
- Peripheral is podocyte + GBM
- Central mesangial is just mesangium
Term
What distributions of ECM "sclerosis" are seen in glomerular disease under the light microscope?
Definition
1) Mesangial
- nodular vs. non-nodular expansion

2) Capillary wall
3) Bowman's space
Term
What patterns of "hypercellularity" are seen in glomerular disease under the light microscope?
Definition
1) Intraglomerular
- Mesangium= mesangioproliferation

- Mesangium + capillary= mesangiocapillary
** can be membranoproliferative or exudative (PMNs)

2) Extraglomerular
- Crescentic
Term
What would you see in the following on light microscopy.

1) Focal segmental glomerulosclerosis with hyalinosis

2) Focal segmental endocapillary proliferative and necrotizing glomerulonephritis with focal cellular cescents.
Definition
1)
- Few glomeruli (focal) with mesangial and capillary involvement in sub-regions of those glomeruli (segmental).
- There would be increased plasma protein (eosinophillic)

2)
- Focal, segmental is the same.
- Endocapillary proliferative means there is increased mesangial & capillary cellularity
- Necrotizing means that there should be inflammation and fibrosis.
- Focal crescents are epithelial/fibrin/inflammatory cell/fibroblast/collagen entities.
Term
What are the different distributions and patterns of staining that you should look for on IF evaluation of glomerular disease?
Definition
1) Distribution
- Glomerular (diffuse vs. focal, global vs. segmental, mesangial vs. peripheral loop).

- Extraglomerular (tubules, interstitium, blood vessels)

2) Pattern
- Granular
- Linear
- Homogenous or irregular
- Intracellular droplet staining
Term
What is the IF staining profile for each of the following glomerular diseases?

1) Focal segmental glomerulosclerosis

2) IgA nephropathy

3) Lupus
Definition
1) homogenous, segmental IgM and C3

2) Granular mesangial IgA, C3

3) Granular mesangial and/or peripheral loop IgG, IgM, IgA, C3, C1q, C4 (full house)
Term
What types of glomerular disease lend themselves to EM analysis?
Definition
Diffuse disorders

**Focal processes may be missed in small section**
Term
What changes are assessed in EM analysis?
Definition
1) Cellular changes (docyte fusion, intracellular inclusion)

2) Extracellular matrix changes
- BM (duplications, increase, thinning, interruption)
- Mesangium

3) Electron dense deposits.
- Location
- Substructual detail (immune complex?)
-
Term
What are the 2 primary mechanisms of glomerular immune deposition?
Definition
1) Injury mediated by circulating antibodies binding in-situ to intrinsic glomerular antigens.

** Example is anti-BM (Goodpastures) with linear IF and necrotizing glomeruloneprhitis**

- Type II

2) Injury resulting from deposition of preformed soluble circulating antibody-antigen ICs.

- Type III
Term
True or False:

Cellular proliferation correlates with the presence of IC deposits in the mesangial-subendothelial space, but not the subepithelial space.
Definition
True
Term
What pathological changes cause Hematuria and/or Proteinuria?
Definition
1) Hematuria occurs with glomerular capillary rupture
2) Proteinuria occurs with damage to BM and/or podocytes without capillary break
Term
What types of glomerulopathy produce norma vs. decreased renal function?
Definition
1) Normal
- Focal +/- proliferation
- Diffuse without proliferation

2) Decreased
- Diffuse + proliferation +/- crescentic/necrosis (acute)
- Diffuse glomerulosclerosis (chronic)
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