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Question 1

4 components of articular cartilage

Answer 1

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

Question 2

Major proteoglycan in articular cartilage

Answer 2

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

Question 3

What enzyme is responsible for cartilage collagen breakdown

Answer 3

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

Question 4

Pathophysiology of collagen breakdown

Answer 4

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

Question 5

What are the major Positive acute phase proteins in the dog

Answer 5

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

Question 6

What are the major Positive acute phase proteins in the cat

Answer 6

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

Question 7

Biological properties of serum amyloid A

Answer 7

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

Question 8

Biological properties of alpha 1 acid glycoprotein

Answer 8

Decreases inflammationImmunomodulatory

Question 9

Biological properties of alpha 1 acid glycoprotein

Answer 9

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

Question 10

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

Answer 10

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

Question 11

4 ways biomarkers can be used in clinical medicine

Answer 11

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

Question 12

what is chondroitin sulfate

Answer 12

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

Question 13

types of glycosaminoglycans

Answer 13

Chondroitin sulfateKeratan sulfateBoth found on aggrecan proteoglycan molecule

Question 14

5D4 biomarker in keratan sulfate

Answer 14

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

Question 15

What metal ion is present at the active site of MMP

Answer 15

Matrix metalloproteinasesZINC

Question 16

type II collagen molecular structure

Answer 16

triple folded helix Folded extracellularly

Question 17

types of noncollagenous glycoproteins within the cartilage matrix

Answer 17

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

Question 18

Difference of C reactive protein dog vs cat

Answer 18

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

Question 19

Major negative acute phase protein in dogs and cats

Answer 19

Albuminnot SN or SP

Question 20

increased C reactive protein in dogs has been associated with…

Answer 20

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

Question 21

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

Answer 21

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)

Question 22

Disadvantage for using acute phase proteins

Answer 22

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

Question 23

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

Answer 23

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

Question 24

key stimuli for TNF alpha synthesis by macrophages

Answer 24

LPS and IL-1

Question 25

6 specific functions of TNF alpha

Answer 25

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

Question 26

White fat as an endocrine organ released what factor

Answer 26

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

Question 27

How do adipokines relate to insulin resistance

Answer 27

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

Question 28

Major source of adipokines in joints

Answer 28

SynoviumInfrapatellar fat padOsteophytes