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Flashcards in 3 Deck (28):
1

4 components of articular cartilage

Type 2 collagenProteoglycan (aggrecan)Glycoproteins (fibronectin, link protein)Water

2

Major proteoglycan in articular cartilage

Aggrecan Know components!!!!Chondrotin sulfate head (3b3, 7D4)Keratan sulfate (5D4)Interglobular domainHyaluronan

3

What enzyme is responsible for cartilage collagen breakdown

Matrix metalloproteinases MMPMMP 1, 8, 13, 14 (membrane bound)13 is the most important collagenase and prefers type 2 collagen

4

Pathophysiology of collagen breakdown

Mediated by MMPsBrks into 1/4 fragments and 3/4 fragmentsOnly 3/4 fragments go into circulation (MMP 9 further breaks down)

5

What are the major Positive acute phase proteins in the dog

Major -- c reactive protein (increases in pyometra and steroid responsive meningitis)Moderate-- alpha 1 acid glycoprotein, ceruloplasmin, haptoglobin, serum amyloid A

6

What are the major Positive acute phase proteins in the cat

Major -- serum amyloid A, alpha 1 acid glycoprotein (increases w FIP)Moderate-- haptoglobin, ceruloplasmin

7

Biological properties of serum amyloid A

Increases chemotaxisDecreases inflammationFx w lipid metabolism and transport MAIN + acute phase protein in cats! Responds the quickest to an inflammatory stimulus

8

Biological properties of alpha 1 acid glycoprotein

Decreases inflammationImmunomodulatory

9

Biological properties of alpha 1 acid glycoprotein

Decreases inflammationImmunomodulatoryMAIN + acute phase protein in cats! (increases with FIP)

10

many IL and Acute phase proteins increase w obesity EXCEPT....

AdiponectinDoes not increase with obesityINVERSELY related to body weightObesity= chronic inflammation = increases in TNF alpha, IL6, C-reactive protein

11

4 ways biomarkers can be used in clinical medicine

1. Diagnostic2. Staging3. Prognostic4. Monitoring clinical response to tx

12

what is chondroitin sulfate

glycosaminoglycan (GAG) with repeating disaccharide sequenceFound in Chondroitin Sulfate head of aggrecan (proteoglycan molecule)

13

types of glycosaminoglycans

Chondroitin sulfateKeratan sulfateBoth found on aggrecan proteoglycan molecule

14

5D4 biomarker in keratan sulfate

found to be elevated follow CCL transection and MPLINVERSELY correlated with increasing duration of lameness(higher concentration for acute disease)NOT affected by recent TPLO surgery

15

What metal ion is present at the active site of MMP

Matrix metalloproteinasesZINC

16

type II collagen molecular structure

triple folded helix Folded extracellularly

17

types of noncollagenous glycoproteins within the cartilage matrix

Fibronectin (role in matrix organization and interaction with chondrocytes)Link Protein (links aggrecan to hyaluronan)

18

Difference of C reactive protein dog vs cat

C reactive Protein is MAJOR positive acute phase protein in DOG NOT CAT (not affected by inflammation)

19

Major negative acute phase protein in dogs and cats

Albuminnot SN or SP

20

increased C reactive protein in dogs has been associated with...

Bacterial Infection (PYOMETRA)Recent surgery (100x within 4 hr)ObesitySteroid responsive meningitisCorrelated with severity of inflammation

21

Biological variation in acute phase proteins may be due to....

1. SIGNALMENT (adult dogs respond more dramatically, though age does NOT appear to affect concentrations in healthy animals)2. PREGNANCY (incr during pregnancy in dogs)3. ENVIRONMENT (private kept dogs have higher)4. GCC admin (incr proteins--haptoglobin)

22

Disadvantage for using acute phase proteins

HIGH SN and respond rapidly to inflammationBUT LACK SPECIFICITYMay be more helpful in monitoring response to therapy (ie. steroid responsive meningitis)

23

Disadvantages of using acute phase proteins for monitoring disease/response to therapy

1. Changes in concentrations may not represent natural history of disease2. TX (W GCC) may interfere w concentrations3. unknown "normal" reference ranges for some individuals4. Not affected by NSAID therapy (NSAIDS do not decr IL 6 which induces acute phase proteins)5. Surgery can influence concentrations

24

key stimuli for TNF alpha synthesis by macrophages

LPS and IL-1

25

6 specific functions of TNF alpha

PROINFLAMMATORY1. Incr PMN function2. Incr macrophage function3. Endogenous pyrogen (hypothalamus fx)4. Liver production of acute phase proteins5. Insulin resistance6. Antiviral/antineoplastic

26

White fat as an endocrine organ released what factor

adipokines including TNF alpha, IL 6, leptin--PROINFLMAdiponectin--ANTIINFLM

27

How do adipokines relate to insulin resistance

Adipokines include TNF alpha which functions as adown regulator of GLUT 4 receptors in adipocytes leading to decreased glucose uptake and resistance in insulin signaling pathway

28

Major source of adipokines in joints

SynoviumInfrapatellar fat padOsteophytes