Pathophysiology of Glomerular Disease (Cianciolo) Flashcards
What are the three components of the glomerular filtration barrier?
- Capillary endothelium
- Fenestrated
- Covered by glycocalyx (negatively charged) - Glomerular Basement Membrane (GBM)
- Mostly composed of Type IV Collagen
- Also glycosaminoglycans - Podocytes
- very rarely able to replace themselves
- Production of VEGF to maintain endothelial cell health
Maintains structural integrity of the glomerular tuft
Mesangial Cell
(T/F) Mesangial lesions are always clinically significant
False
What is a hallmark of glomerular disease?
Proteinuria
What might be seen in nephrotic syndrome?
- Proteinuria
- Hypoalbuminemia / Hypoproteinemia
- Edema/ascites
- Hypercholesterolemia / hyperlipidemia
(T/F) Azotemia is not a criterion for diagnosis of nephrotic syndrome
True
What should a kidney report describe?
- Hypercellularity
- Mesangium
- Sclerosis or Hyalinosis
- Immune deposits
- Capillary wall
- Synechia
What are the two hypercellularity?
- Mesangial
- Endocapillary
- These are not mutually exclusive
Plasma was pushed into the mesangium or GBM
Hyalinosis
Same extracellular matrix components but MORE
Segmental sclerosis (Scarring of the glomerulus)
Adhesions between the glomerular tuft and Bowman’s capsule
Synechiae (podocytes have been damaged)
(T/F) We know that GBM is normal when we see some remodeling
False, when it has a normal smooth contour
Occurs when the GBM ruptures and the material in circulation pours into Bowman’s space
Crescents
(T/F) Crescents are common in small animals
False, rare in small animals and seen more often in pigs
What are the 2 large categories of Glomerular Disease in animals?
- Immune complex-mediated glomerulonephritis (ICGN)
- Non- ICGN
(T/F) Immunosuppression of non-ICGN is not recommended
True
(T/F) You can try to treat ICGN with immunosuppressive agents
True
- Immune complexes are aggregates of antigens and antibodies which can be deposited in glomeruli
- Location in which it is trapped depends on size and charge
ICGN
- Is an immune complex
- Complement pathway is activated on the OUTSIDE of the capillary lumen (inflammatory cells are not attracted to tuft)
- Complexes likely contain antigens released by
- Infections
- Drugs
- Neoplasia - We almost never ID the antigen in small animals
Membranous Glomerulonephritis (MGN)
- Endocapillary hypercellularity due to subendothelial deposits
- Mesangial hypercellularity
- GBM remodeling
Membranoproliferative GN (ICGN)
What are 2 common examples of Non-ICGN?
- Amyloidosis
- fibrils get deposited in glomeruli
- irreversible process
- generated from Serum Amyloid A protein (in the liver) in states of systemic inflammation - Focal segmental glomerulosclerosis
- Due to podocyte injury
- Diagnosed in about 1/4 biopsies from proteinuric dogs
- Primary
- Assumed to be due to abnormal podocyte genes/proteins
Focal Segmental Glomerulosclerosis
- Secondary (or Adaptive) due to podocyte injury
- Systemic hypertension
- Obesity
- decreased nephron mass -> increased single nephron GFR
- Drugs or viruses - Significant tuft scarring in immune-mediated GN, it is called “sclerosing ICGN”
Focal Segmental Glomerulosclerosis
Compression and effacement of peripheral capillary loops
Sclerosis
- Is thought to be hereditary
- Most don’t know the mutation/pattern of inheritance except for Alport syndrome
- Alport is due to a mutation in Type IV collagen
Glomerular Basement Membrane Lesions
Multifocal embolic nephritis in young foals due to _____________________
Actinobacillus equuili
