3 Flashcards
4 components of articular cartilage
Type 2 collagenProteoglycan (aggrecan)Glycoproteins (fibronectin, link protein)Water
Major proteoglycan in articular cartilage
Aggrecan Know components!!!!Chondrotin sulfate head (3b3, 7D4)Keratan sulfate (5D4)Interglobular domainHyaluronan
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
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)
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
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
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
Biological properties of alpha 1 acid glycoprotein
Decreases inflammationImmunomodulatory
Biological properties of alpha 1 acid glycoprotein
Decreases inflammationImmunomodulatoryMAIN + acute phase protein in cats! (increases with FIP)
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
4 ways biomarkers can be used in clinical medicine
- Diagnostic2. Staging3. Prognostic4. Monitoring clinical response to tx
what is chondroitin sulfate
glycosaminoglycan (GAG) with repeating disaccharide sequenceFound in Chondroitin Sulfate head of aggrecan (proteoglycan molecule)
types of glycosaminoglycans
Chondroitin sulfateKeratan sulfateBoth found on aggrecan proteoglycan molecule
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
What metal ion is present at the active site of MMP
Matrix metalloproteinasesZINC
type II collagen molecular structure
triple folded helix Folded extracellularly
types of noncollagenous glycoproteins within the cartilage matrix
Fibronectin (role in matrix organization and interaction with chondrocytes)Link Protein (links aggrecan to hyaluronan)
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)
Major negative acute phase protein in dogs and cats
Albuminnot SN or SP
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
Biological variation in acute phase proteins may be due to….
- 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)
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)
Disadvantages of using acute phase proteins for monitoring disease/response to therapy
- 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
key stimuli for TNF alpha synthesis by macrophages
LPS and IL-1
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
White fat as an endocrine organ released what factor
adipokines including TNF alpha, IL 6, leptin–PROINFLMAdiponectin–ANTIINFLM
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
Major source of adipokines in joints
SynoviumInfrapatellar fat padOsteophytes
