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223 Cards in this Set
- Front
- Back
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1c is in Yellow - hemostasis thrombosis
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1C is in Yellow - hemostasis thrombosis
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What distinguishes normal from pathologic hemostasis
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Pathologic is not temporally nor geographically restricted
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How is coagulation initiated
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Exposure of constitutively synthesized TF to plasma via endothelial cell damage
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list five stages of clot formation
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1. platelet deposition (weak) 2. fibrin production 3. control of fibrin production 4. fibrinolysis 5. control of fibrinolysis
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What are two ways platelets accelerate coagulation
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1. platelets provide binding sites for clotting proteins 2. anionic phospholipids relocate to outside of platelets causing this
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what phenotype might you see in pts with depleted platelets
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menorrghagia epistaxis- petechiae soon after trauma
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what two mechanisms might produce TF and which is the shorter one
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de-encryptation is fast route- postulate constitutively available and go from inactive dimer to active monomer on vascular injury or itassociates with phospholipids giving it anticoag activity. Synthesis is the other route and takes 1-3 hours but is not longlasting without outside stimulus beyond trauma
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Which five proteins are direct members of the extrinsic pathway
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TF- 7- 10- 2-->thrombin- fibrinogen-->fibrin are members of this pathway
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how is factor 7 activated
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TF binds to this factor and activtes it
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What two proteins are activated by TF-7a
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X and 9 are activated by this - X is believed to be the main pathway
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What's required for optimal Xa (prothrombinase) activity
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activated platelets bind to Xa- secrete Ca- express phospholipids- and bind FVa in order to optimize THIS enzyme's activity
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What does Xa cleave
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Prothrombin (2) into thrombin is done by this enzyme
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what does thrombin cleave
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Fibrinogen to fibrin is made by this
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what are four functions of thrombin
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1. to cleave a and b peptides off fibrinogen to produce the fibrin monomer 2. it increases TF production 3. It activates platelets 4. it activates V to Va which in turn helps stabilize Xa to make more thrombin
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why do you need 9 and 10?
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because there usually isn't enough TF-7a to sustain production of Xa. 9a is also activated by TF7a which ALSO makes more Xa from X
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what factor are hemophelia B patients defective in and how does this explain their phenotype
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these pts are deficient in 9 and suffer from delayed bleeding in joint spaces or elsewhere that TF is low signaling the importance of 9 in production of addtl 10a
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what are two "chairs" activated by thrombin and what do they do?
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factors V and VIII are both activated by this. factor Va helps produce more thrombin and factor 8a assists 9a in making more Xa
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which two proteins in the extrinsic pathway amplify their own production?
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Xa (acts on 7) and thrombin (acts on 5- 8- and indirectly on 9 via 11)
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why is factor 11 (XI) deficiency usually mild
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this factor deficiency is mild because factor 9a production usually depends more on activated factor 7a than on help from 11a
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if you have prolonged aPTT only and pt asymptomatic what 4 factors could be deficient
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HK- PK- XI or XII
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if you have prolonged aPTT only and pt symptomatic what factors could be deficient
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8- 9- XI
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what is a normal PTT
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22-32 seconds
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what are three required components for PT measurement
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citrated plasma containing all coagulation proteins- TF- and Ca++ (activates)
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what does the PT time measure
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function of 7- 5- 8- prothrombin (ii) and fibrinogen tested by this one
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why do you add a LOT of TF in a PT test
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because there is no tissue to regenerate it
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what are the contact factors
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clinically unimportant to clotting but they are prekallikrein-->kallikrein- 12- and the enzyme HMK. they show up in the aPTT
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what is lacking when you do an aPTT
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no TF- use partial thromboplastin instead in this test
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what protein is NOT tested by an aPTT
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7 not tested in this one
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what if you only have long pT and aPTT normal
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7 is abnormal showing these results
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what if BOTH aPTT and PT are abnormal
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5- 10- prothrombin- fibrinogen abnormalities produce this
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what protein is affected in hempphelia A
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XIII
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What protein is affected in hemophelia B
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9a
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how do hemphelias manifest differently from platelet disorders
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hemophelias often result in delayed internal bleeding rather than mucocutaneous due to weak clot formation
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How can you identify an inhibitor vs. a deficiency?
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Incubate with normal plasma missing any factor but the one that is deficient- and the PTT should correct
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which factors are vitmain K dependent
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2- 7- 9- 10- C and S proteins require this for posttranslational y-carboxylation
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post-translational y-carboxylation occuring in the liver mediated by vitamin K allows..
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2-7-9-10 localize to the membrane of the platelets once they have these
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How does coumadin affect clottin
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when coumadin is present- this stops regeneration of active vitamin K- causing decreased activation of these clotting proteins
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what does TFPI do>
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This protein associates with excess Xa- then with Xa-VIIa- inhibiting VIIa-TF activity
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which protein might be expected to step up when there is a lot of TFPI activity
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Factor 9a activated by factor 8
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what generates activated protein C
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thrombin and vitamin K are required to make this- along with a thrombomodulin substrate
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what might deficiencies in protein C or S cause?
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increased thrombosis due to decreased inactivation of V- 8 by C and S
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What does APC do?
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inactivate factors V and 8
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what does Anti-thrombin III do and where is it made
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This protein is made in the liver and competitively binds to serine residues on activated coagulation proteins which stops clotting
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what does heparin do
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this dug prevents AT3 from interacting with its targets
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what if there were no AT3
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lifethreatening risk of thrombosis
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what are three steps in fibrinolysis
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initation- propagation- and control of this process stop clots from getting too big
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what is plasmin produced from
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plasminogen activated by tissue plasminogen activator (tPA)
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where is tPA stored and when is it released
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this is stored in endothelial cless and released under hypoxia or mechanical stress
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which domains of tPA mediate its binding?
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The 2nd kringle and finger domains allow tPA to bind to fibrin- allowing this protein to cleave plasminogen to plasmin
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what does plasmin do?
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this protein cleaves fibrin into FDPs to stop clot formation (helped form by tPA)
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what are five ways to stop fibrinolysis
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1. loss of fibrin surface ( down tPA) 2. genereation of 13a which is a glue holding clot together preventing entry of plasmin and TAFI 4. generate plasminogen activator inhibitors 5. generate an inhibitor of plasmin (a2 antiplasmin)
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what does 13a do
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this protein crosslinks fibrin preventing physical access by plasmin
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what does TAFI do?
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thrombin activates this protein causing it to remove binding sites for plasminogen on the endothelium
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what does PAI do?
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binds up tPA preventing it from interacting with plasminogen to make plasmin
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what does a2 anti-plasmin do?
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duh it prevents interaction of plasmin with fibrin (kind of like how factor 13 physically prevented plasmin from getting to fibrin)
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1D phatology of thrombi
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1D pathology of thrombi
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What are two food related terms describing postmortem clots but NOT thrombi?
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red currant jelly and chicken fat are characteristic of clots that form at these times
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Which types of clots are gelatinous- not friable
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Post mortem clots' texture may be described this way
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What two main features identify thrombi as opposed to post-mortem clots
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Lines of Zahn and a site of attachemnet to the vessel wall are signs of this
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What composes the pink layer of line of zahn
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platelets and fibrin
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What's a mural thrombus
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a thrombus that forms on the inside wall fo the heart
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1e Pathology of cell injury
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1e pathology of cell injury
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List a few ways in which cells are injured
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mech- temp trauma- virus- nutritional- genetic can do this
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Identify the major cell organelles that are injured
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mitochondria- any membrane bound organelle as Ca breaks them open
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How are free radicals generated (four)
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UV light- Xray- CCl4- iron- normal redox rxns
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How are free radicals controlled?
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antioxidants (A and E)- superoxide dismutase & cataase- as well as GSSG
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What can result from free radical damage
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DNA damage- modification of proteins- modification of lipids
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What is the main difference between hypoxia and ischemia
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ischemia deprives tissues of glucose in addition to oxygen (stops blood flow entirely whereas CO poisoning or something)
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What are four ways that cells can adapt to non-lethal stimuli
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hyperplasia hypertrophy atrophy metaplasia
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name the adaptation that results in increased cell number and the adaptation that results in expression of a different cell type than normal
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hyperplasia and metaplasia
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What are a few differences between apoptosis and necrosis
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How does the bulding of colloid lakes in the thyroid of Graves' disease illustrate an adaptation
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There is hyperplasia in Graves' disease die to continual stim of TSH resulting in too many cells impingining on the lakes
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What two muscle types commonly show hypertrphy
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skeletal and heart muscle show this because they are non-dividing
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Which cell type adaptations are reversble
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all ____ are reversible
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What is SMA and associated denervation an example of
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Atrophy of babies' muscles - due to denervation
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describe an adaptive cell response to smoking that is a metaplasia
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transformation of pseudo columnar ciliated epithelium into squamus in smokers
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Which cell types are most susceptible to ischemia? Least?
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most-neurons least-skin (epidermis fibroblast- skeletal muscle)
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Why does the heart stop contracting in 60s after ischemic onset
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depletion of ATP leads to slowdown of oxphos due to no pump- [cell swells] rapid depletion of glycogen stores- protein synthesis decreases
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membrane blebs signal what
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these signal prolonged ischemia
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What does Ca influz into cell signal
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irreversible process of cell death is triggered by this
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How does acetaminophen and CCl4 cause toxicity
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both interact with the cytochrome P450 system in the liver
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What's a lewy body
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misformed aggregates of a synuclein protein that aggregate to cause degeneration of the substantia negra
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mutations in the E3 protein (parkin) can cause PD how?
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by preventing ubiquitnation and misfolded a synuclein accumulates
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List the trhee main patterns of necrosis
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caseous- liquefactive- coagulative
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what is coagulative necrosis
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ischemia as with a clot- MAINTAINS tissue architecture are characteristic fo this type of necrosis
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what is liqufactive necrosis
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example of cardiac abcess (near valve- drug user infetion)- predominant hydrolytic enzymes- pus and neutrophil infiltrate with secondarry inflammation
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what type of necrosis predominates in the brain
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liquefactive is most common in this organ
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what are two histologic signs of apoptosis
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shrink away from neighbors and chromatin condense
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What does hyperactivation of PARP cause and what process does it favor
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This compound is hyperactivated to rapidly deplete ATP and thus tends to favor necrosis
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IN which type of cell death do you see only small cell groups and cell shrinkage
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apoptosis displays these histo findings (also no inflammation)
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what are BCL2 proteins
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antiapoptotic- their ratio to the BH3 and Bak- Bax are important
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What does BH3-only BCl2 proteins do
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proapoptotic
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What do Bax and Bak do
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pro-apoptotic- multimerize to puncture mitochondial membrane
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What does cytochrome C play in apoptosis
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this protein is part of the apoptosome and also requires APAF1 and ADP
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ROle of apaf1 in apoptosis
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this protein is part of the apoptosome and also requires cytochrome C
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What are initiator caspases
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receive signals form the apoptosome and activate the iexecutor caspases
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what are executioner caspases
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they cause the morphological changes seen in apoptosis eg chromatin condense- membrane bleb
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what is the difference between the intrinsic and extrinsic apoptotic pathways
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intrinsic is from mitochondrial explosion while extrinsic can be from death signals or lack of GFs- but both meet at initiator caspases
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where is bcl2 found and what does this mean for its function
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it's found in the outer mitochondrial membrane so it is antiapoptotic
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which mitochondrial membrane must be permeable for apoptosis and why
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The outer membrane in order to release cyt c
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Name two diseases associated with too much apoptosis
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PD- AD- lots of neurodegen
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Name two diseases associated with too little apoptosis
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p53 mutation cancers- lupus- herpesvirsus- estrogen dependent carcinoma- follicular lymphoma
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would you expect follicular lymphoma to express too much or too little BCl2
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too much
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What does the Fenton rxn produce and what disease is associated
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Friedrich's ataxia is a neurodegen disease that kills neurons due to oxidative radicals produced in the iron fenton reaction
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If you increase mitochondrial mutations what happens to mouse age
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mice age prematurely if you screw this up
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Pink1 is another mitochondrial protein which may link WHAT to parkin and alpha synuclein folding
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Pink1 may associate mitochondrial error with this pathology in parkinson's
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1E platelets
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1E platelets
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How do activated and resting platelets differ in morphology?
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Activated are all spiky looking
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What three compounds keep platelets flowing
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PGI2 NO and CD39 from endothelium (especially PGI2 does this)
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What causes tumbling- adhesion and activation of platelets
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exposure of collagen and VWF due to endothelial injury stimulate this
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What usually activates platelets?
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collagen thrombin TxA2 ADP
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How do platelets encourage clotting reactions?
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Platelets usually support factor five and eight (phospholipids and Calcium)
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How does aspirin affect platelets
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Aspirin inhibits COX2 in platelets which prevents formation of TxA2 which platelets normally need to be recruited into a plug
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what two hormones regulate platelet count
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TPO and MPL (the latter is competed for by platelets and megakaryocytes to
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how long do platelets normally survive
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10days and then either cleared in clot or spleen
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14.0 - 17.5
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Male hemoglobin
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12.3 - 15.3
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Female hemoglobin
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42-50%
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hematocrit
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36-45%
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hematorcrit
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4-11000
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white cell count
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150-400k
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platelet normal
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what is an ecchymosis
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bruise
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what are petechiae
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littler brusises
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why don't you see hemearthrosis in thrombocytopenia
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it's more of a hemophelia thing- slow vs fast
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What Which bleed type is characterized by delayed bleeding into retroperioneum- joints
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hemophelia (defects in clotting factors)
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name two diseases resultings from inappropriatesly activated platelets
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heart attack and stroke- can be consequences of too many of these
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what are bleed thresholds for any and gross bleeding
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100k any gross 15k
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name three ways thrombocytopenia may develop
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increased destruction (- decreased production- or MALdistribution including spleomegaly due to portal hypertension)
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list a few causes of thrombocytopenia from decreased produciton
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low megakaryocytes=chloramphenical- leukemia or aplastic anemia- b12 and folate deficiency
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what are four immune causes of thrombocytopenia
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ITP PTP CVD HEP: ITP (immune or idiopathic) post-transfusion- collagen-vascular disease (lupus)- quinidine and heparin
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what are four non-immune causes of thrombocytopenia
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DIC sepsis TTP and bypass pumps
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kid with ITP preceded by several weeks of viral illness. rest of CBC normal. think?
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ITP is diagnosed by these clinical features and exclusion
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Why are steroids and rituxan appropriate therapy for ITP? What about Nplate? Why might splenectomy be a last resort
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steroid immunosuppress. rituxan suppress CD20 B cell- Nplate is TPO to increase production- and splenectomy
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are drug induced cytopenias more likely to result in damage to megakaryocyte or platelet?
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platelet because drug may bind to platelet glycoprotein and then trigger antibody removal (so more potent the next time)
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how can liver disease resilt in thrombocytopenia
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portal hypertension leading to splenomegaly and 80-100k platelets
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how is thrombocytosis different from thrombocytothemia
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thrombocytothemia is neoplastic and results in increased but abnormal platelet count- still leading to bleeds. thrombocytosis is often secondary to iron deficiency or splenectomy put is udually asymptomatic.
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what might you expect to see in a pt with CML
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thrombocytothemia may result in this type of marrow cancer
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polycythemia vera - what is it and how might it lead to increaed bleeds
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increases in number of all marrow output but not cancer- bluish skin with red spots- it can perturb bone marrow so much that platelet counts actually drop (termed myelofibrosis)
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what is TTP
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immune reaction to platelets in transfused blood. a wait and see.
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What effects does heparin induced thrombocytopenia have
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Actually this causes THROMBOSIS not bleeds because pts generate antibodies to heparin plus platelet. plus remains longer
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what are a few usually asymptomatic causes of thrombocytosis/thrombocythemia?
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osetomyelitis- splenectomy. these are REACTIVE to another insult.
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1T Anticoag and antiplatelet therapy
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1T Anticoag and antiplatelet therapy
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Which agent inhibits thrombin or the conversion of 2 into thrombin (Xa inhib)
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heparin!
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What do antiplatelet agents do as opposed to fibrinolytic agents
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antiplatelets prevent platelet activation while fibrinolytic agents break up clots
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List 4 proteins that are naturally antithrombotic
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AT3-
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What three small molecules can inhibit platelet activation
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NO- PGi2- CD39
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why might serine proteases be good candidates for anticoagulants
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There are several serine proteases which try to cleave AT3 but get STUCK and suicide- turning off coagulation
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what factors are inhibited by heparin and how?
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Because thet are 2-9-10-11 so it has many targets in coag cascase. It has a LONG GAG side chain to allow it to bind both of them
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with what 2 protein does heparin associate to have its anticoag effect?
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heparin inhibits 2 by binding to AT3 and thrombin (2) and stabilizing their interaction
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how is heparin administed and how long does it last
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It can be IV or subQ and short half life- but can be given at home. variable half life
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what are risks of heparin and why might you consider it for CABG?
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Could get bleeding and oseteoporosis over long term use- but it prevents further clot formation so might use it post CABG or people who have a blood clot. Can also cause low platelets!
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How do excess antibodies produced in HATT result from heparin administration
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heparin associated thrombocytopenia- because ppl with clot have circulating activated platelets. Heparin binds to PF4 which is secreted by activated platelets. This complex binds platelets- causing immune response to platelets. In some cases these Abs activate Fc receptors on platelets to crosslink- erroneously activating platelets to clot- embolism- TISSUE DAMAGE.
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What are some symptoms of HATT and what does HATT do to platelet count
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heparin induced skin necrosis due to fall in platelet count. do not screen for Abs unless person has had problem before- just monitor platelets.
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What is LMWH
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Heparin but ONLY with small side chain. Eg- fondaparinux. This inhibits Xa preferentially to thrombin. Given SQ. dosed by weight.
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For which factor is LMWH most sensitive
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10 NOT thrombin because it's shorter
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Why can't you follow LMWH patients with a PTT?
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Because LMWH prefers to inactivate 10a over thrombin. If 10a is inactivated- the PTT will be long but not as long as if both thrombin and 10a were inactivated. So in the tt it's not a big enough difference but in the pt it's therapeutic
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How do you monitor heparin therapy
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aPTT. It measures contact- 9- 10- prothrombin- PT isn't as sensitive to heparin because TF drives so fast. Both aPTT and PT should increase- however. You should prolong the PTT but 1.5-2x baseline.
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List three indications for LMWH
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DVT PE-
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What are some preexisting conditions which might require prophylaxis for VTE?
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afib- previous vte
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What are some DTIs and why might you choose to use them over heparin?
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only IV - lepirudin- and argatroban. Use these types of molecules ac
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What are the sites of excretion and mechanisms of lepirudin and argatraban
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lepirudin is renal- leech protein like- and binds to thrombin to inhibit it. and argatroben is liver- inhibits active site.
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How do factor Xa inhibitors compare to heparins? (list their names too)
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ORAL - rivaroxaban- apixaban- fondaparinux (SQ) which is short but can still inhibit Xa
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What's thrombin inhibitor
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dabigatran inhibits what??- oral- LONG half life- fixed dose and no monitoring.
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Which proteins are affected by warfarin?
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warfarin inhibits K..thus inhibiting 2-7-9-10 strongly- and decreases post-trans modification of C and S
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which process does warfarin inhibit and what vitmain is necessary
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vitamin K activation is inhibited by warfarin- causing an inhibition of clotting proteins
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what can happen when you take broad spectrum ABs and don't eat
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you have to eat it and it is synthesized by gut flora. If you have vitamin K deficiency.
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What two drug interactions are potentially harmful for warfarin users?
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Other drugs can displace warfarin from albumin- increasing effective dose. OR other drugs can rev up P450 and excrete warfarin quicker. Diffiuclt to control therapeutic window
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How is warfarin metabolized
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it is oral- into the bloodstream- some is free and some bound to albumin. Free warfarin in the liver is the active site for Vit K antagonist. P450 cytochrome system excretes warfarin
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Do steroids potentiate or attenuate warfarin levels?
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Attenuate warfarin levels.
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Which coagulation factors are broken down most quickly? Slowly?
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Short halflife: 7 long halflife: platelets
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How is coumadin administered?
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oral. monitor frequently at first and then monthyl
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What does coumadin do to PT? PTT?
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PT increases greatly due to extrinsic pathway inhibition/factor 7 inhibition by warfarin. PTT can also increase.
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What is an INR and if it is high what does it mean?
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The INR is a measure of how a patient's PT compares to control PT. Therapeutic if usually 2-3
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what is a target INR for PE?
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between 2 and 3
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What three side effects are possible?
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Bleeding (stop with FFP- vit K)
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how mgiht skin necrosis arise?
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potential for transient procoagulative state if protein c levels fall first (so usu start heparin first)
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what is a sign of fibrin degradation in the blood? (and what condition does this diagnose if high)
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D-dimers (DIC)
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what two things does plasmin cleave?
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x-linked fibrin OR fibringogen. these are stimulated by streptokinase to urokinase to tPA.
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List a few indications for plasminogen activators
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active MI- PE- proximal DVT- catheter occulusion
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What does tpa do to fibrinogen levels
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Fibrinogen levels decrease with thsi drug
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Which plasminogen activator is assoc with alelrgic reactions?
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streptokinase (it activates tPA)
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Should you give a plasminogen activator to someone with uncontrolled severe hypertension or cranial neoplasm? why or why not?
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High bleed risk- allergic reactions- high cost. Risks of massive hemhorrage in the brain
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what does PAI-1 do?
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It decrases tPA
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what is done immediately- and long term for venous thrombus management
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Immediate VT management: can give TPA. Then put on heparin LMWH- and put them on coumadin for 3-6 mos
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what three sites of action are there for antiplatelet agents?
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Receptor antagonists (prevent turn on)- signaling blockers (prevent turn on )- and Integrin a2B3 blockers (prevents platelets form sticking to each other)
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Name two antiplatelet RECEPTOR blockers
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clopidogrel (plavix)- ticoldipine. Bind to GPCR P2Y12 and prevent ADP from binding and activating platelets
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what are two antiplatelet signaling vblockers and how do they work
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aspirin and dipyramidole. aspirin prevents formation of TxA2 inside one platelet- preventing recruitment of other platelets/activation of other platelets. Aspirin inhibits COX1 in all platelets- causing decreased recruitment of platelets
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why do integrin blockers work
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They prevent activated platelet from binding to fibrinogen and sticking to each other. Glanzmann's is an example of this disease. Examples: ReoPro- Integrilin- Tirofiban.All IV.
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what does dipyramidole do
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it increases cAMP by preventing its degradation in platelets- making them less responsive to activation
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what are two system indications for platelet inactivators use?
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Heart disease- stroke- cancer
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How do antiplatelet agents and anticoagulant agents DIFFER??
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Antiplatelets prevent platelet activation or binding of platelets- while anticoagulants stop coagulant proteins
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1V pathology of leukocyte trafficking
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1V pathology of leukocyte trafficking
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Name the four leukocyte subpopulations
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Neutrtophils- monocytes- eosinophils (parasite)- and lymphocytes (eg ARDS)
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Why might dyregulated integrin expression lead to inflammatory disease
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Excessive white cell recruitment may result ininflammation (integrin overexpression or something)
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Cadherins and selectins are 2/4 of these-.what are the otehr 2
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cell adhesion molecules or CAMS- immunoglobulins and integrins also
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what two functions are cadherins normally responsible for
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NOT used in WBC recruitment - but mediate homophilic adhesion hold cells of one tissue together. They link epithelial cells all together.
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what family's members are expressed on the endothelium and include ICAM- PECAM? What do they do?
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Immunoglobulin superfamily includes these - expressed ON endothelium and involved in WBC traficking
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where do you find selectins and what do they bind?
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these are on cells associated with vascular endothelium only and they bind carbohydrate motifs on leukocytes- platelets- and vascular endothelium
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which adhesion molecule is a dimer?
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the integrins!
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which adhesion molecule is NOT involved in leukocyte/endothelium recruitment
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the cadherins
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what molecule is important in leukocyte rolling
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L-selectin!! it is important in capture
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what do integrins participate in
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diapedesis
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Where is P selectin stored
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in weibel palade bodies of platelets
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does igSF have a strong orweak hold and when would it because active in the recruitment process
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it has a strong hold so it bind durign the stopping process
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P selectin is expressed where
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in the endothelium- important in capture of fast roll
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which selectin mediates slow rolling and why?
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E selectin mediates slow rolling because it's synthesized SLOWLY and comes up slowly
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what ligand is upregulated in the leukocyte after it is slow rolling and what is shed?
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B integrin is upregulated in response to chemokines while concurrently L selectin is shed- causing a stop in leukocyte rolling
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What is expressed on the endothelium and what on the WBC to cause firm binding of leukocytes
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The integrins on the WBC bind to Ig superfamilar on the endothelium
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what are the two routes for diapedesis to occur?
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paracellular transendothelial migration OR transcellular transendothelial migration
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What are four factors involved in leukocytes traversing the endothelial layer
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PECAM1 --> CD99 JAMA--> neutrophil elastase (makes sense because PECAM is an immunoglobulin- there's also a and B integrins from the WBC involved)
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What process requires a podosome?
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transcellular transendothelial migration while preserving vessel integrity
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If patient deficient in B integrin what process defective? What clinical signs?
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The slow rolling and transition to stop will not be involved- pt will be immunodeficient
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How do type I and type II leukocyte adhesion deficinecy differ? Proteins- explain the chemical phenotype?
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Type 1 is absence of B integrins. High blood neutrophil low pus- recurrent infection. Type II is NO E and P selectin on the WBC- compromising WBC trafficking. Same phenotype as blood neutrophil
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Why is the phenotype the most severe if you delete E and P selectin?
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They are redundant similar function. HOWEVER it is tissue dependent
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Why might cell adhesion molecules represent attractive targets for drugs? What types of diseases?
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They could be suppressed to decrease recruitment- decreasing inflammatory response in disease Ex: MS- crohn's arthritis
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Why might Tysabri work in MS? What are its risks (bc what molecule does it inhibit?)
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Risk of immunosuppression - getting PML but on other immunosuppression so drug reintroduced. It tartgets a4 integrin
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What does Factor V leiden cause?
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Inability of activated protein C to shut off factor V=hypercoagulability
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