Psl301 Lec5 Blood Clotting

Front 1

1) What are the precursors to platelets in haematopoiesis?

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Back 1

1) Megakaryocytes

Front 2

1) What is the structure of megakaryocytes? Where are they and how to they form platelets? Do the granules have repair process

2) What is the factor called that increases platelet number?

3) What is the half life of platelets?

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Back 2

1) Large polyploid cells, have multiple copies of DNA in nucleus. Nucleus itself doesnt divide, they dont have actual nucleus, only have mitochondria, ER, granules They are in the bone marrow. They pass their cytoplasm in cytosols, and break off to make platelets. No repair process or anything, it just releases as granules.

2) Thrombopoietin

3) 10 days

Front 3

1) What is the process that regulates blood clotting called? Describe the 3 phases in summary.

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Back 3

1) Haemostasis

-Vascular phase: Shuts down the blood vessel after injury (as collagen is exposed) so that next phase can occur

-Platelete phase: Shores up the hole from injury. Platelets aggregate there; they just blot it, not too strong.

-Coagulation phase: Create environment for tissue to repair. Also reinforces platelets.

Front 4

Vascular phase

1) What happens?

2) What are the 2 types of controls?

3) What are the main 3 factors released by damaged cells e.g. endothelial cells?

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Back 4

1) Vasoconstriction, so that tissue can respond to growth factor

2) Neurogenic, Myogenic (in muscles)

3) Serotonin, Endothelin-1, Thromoboxane A2

Front 5

Platelets phase steps

1) Initial exposure

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Back 5

1) -Endothelial barrier broken, blood components exposed to underlying collagen. The platelets use vonWillebrand factor released from damaged tissue to bind to collagen.

Front 6

2) Released factors

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Back 6

2) Platelets release vesicles with factors.

-ADP released: Enhances release of Platelet activating factor (PAF), serotonin, Thromboxan A2. PAF also amplified building of Thromboxan from phospholipid bilayer of cells that are there.

ADP also makes platelets more sticky, holding onto each other; building on the base.

-Some factors (Serotonin and Thromboxan A2) also involved in vasoconstriction.

Front 7

3) Attraction

4) Plugging

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Back 7

3) Platelets attracted and stick.

4) Platelets aggregate and form a weak plug in the cut area

Front 8

1) Describe Structure of non activated vs activated platelets

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Back 8

1) Non activates ones are small fragments. Activated ones develop spiky outer surface, becomes stickier, adhere to each other.

Front 9

1) Why are platelets not activate without injury? What two factors involved?

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Back 9

1) Prostacyclin (Prostaglandin I2, PGI2), and nitric oxide (O2) are made from intact endothelial cells. Once platelets come near, ADP released and influences the intact cells to release the factors to prevent platelet adhesion, and also cause vasodilation.

Front 10

Case study 1

1) Guy had heart attack, they gave him baby aspiring, why?

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Back 10

11) Arachidonic acid is essential in plasma membrane, under influence of Cyclooxygenase (COX2), It gets converted to Prostoglandin H2, Thromboxane H2, Prostacyclin.

Baby Aspirin inhibits COX1 and in turn inhibits production of platelets and aggregation.

but normal aspirin blocks COX-2, which is what making prostaglandin.

Front 11

1) What are the 3 pathways in the coagulation phase and what activates them?

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Back 11

1) Intrinsic pathway: Contact activation e.g. damage to barrier, exposure to collagen, negative surface.

Extrinsic pathway: Tissue factor pathway. Activated by material from damaged tissue outside blood vessels

Common pathway: Both of the last 2 pathways converge into this, leading to blood clot.

Front 12

1) What is fibrinogen and what is it activated by to form what?

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Back 12

1) circulates blood, activated by thrombin, to form fibrin (insoluble polymers) that eventually get cross-linked to form stable blood clot.

Front 13

1) Describe the steps of the common pathway, the factors and the products.

2) What can Calcium chelators (EDTA) cause? what are they used for.

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Back 13

1)

-Start with inactive factor X, activated in presence of Ca2+ and phospholipids (PL)

- Prothrombin into thrombin in presence of Ca2+, PL, Factor V

- Fibrinogen into Fibrin by factor I (thrombin) Fibrin in presence of Ca2+ and Factor 13 (activated by thrombin), gets actively cross linked.

2) Can inhibit coagulation. Stop clotting in blood bags.

Front 14

1) Describe the steps of the intrinsic pathway, the factors and the products.

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Back 14

1)

-Initiated by exposure to collagen activated factor XII

-Factor XII activates Factor XI in presence of Ca2+

-Factor XI activated Factor IX (9) in presence of Ca2+

-Active IX activates Factor X in presence of Ca2+ and PL, leading to common pathways

-> von Willebrand factor regulates VIII, which is needed for factor X activation.

Front 15

1) What is kininogen, what is it modified by and into what? What role does the product have?

2) What is the role of Vitamin K in the intrinsic pathway?

3) What does anticoagulant Coumadin (Warfarin) do and how?

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Back 15

1) By Factor XII into kallikrein, which is then changed to kinins. One type, bradykinin has role in inflammation process and pain reception.

2) Needed for synthesis of IX, X

3) Block action of vitamin K, messing up coagulation pathway

Front 16

1) Describe the steps of the extrinsic pathway, the factors and the products.

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Back 16

1)

-Initiated by factors from damaged cells from outside blood vessels. The factor is tissue factors, factor III (also called thromboplastin)

-Exposure to factor III allows binding of factor VII, activating it

-The factor III-factor VII complex then activates active X in presence of PL and Ca2+, can also activate factor IX in intrinsic pathway

Front 17

1) What is the role of Vitamin K in extrinsic pathway?

2) What are the 2 mechanisms in the coagulation cascades that reinforce positive feedback and what factors are involved?

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Back 17

1) Needed for synthesis of thrombin, VII, X

2) -Active X on activating VII

-Thrombin on activating V and XI

Front 18

1) What is von Willebrand disease, where does it affect and why worry?

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Back 18

1) Most common coagulation disorder, affects areas with small capillaries, e.g. gut skin.

-Important for vWf for linking platelets, and binding to VIII in order to increase its half life (VIII needed for activating X)

Front 19

1) What is haemophilia A and what does it cause? how to counter?

2) What does haemophilia B cause?

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Back 19

1) Its an X linked recessive disease, causes deficiency in factor VIII.

-Severe forms essentially eliminate activity.

-Susceptible to internal and external bleedings

-infused with factor VIII

2) deficiency in factor IX

Front 20

1) How is the clot removed? what is the enzyme involved, how is it activated and what is the process caused?

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Back 20

1) Plasminogen, found in blood, activated by Tissue plasminogen activator (tPA) released by damaged endothelium and also by by low levels of thrombin (allowing plasminogen activity to go on). When activated, turns to plasmin. Plasmin turns the fibrin polymer to fibrin fragments.

-This is the fibrinolysis process.

Front 21

1) What are the 3 main anticoagulants and how do they work and where?

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Back 21

1) -TFPI (tissue factor [extrinsic] pathway inhibitor): inhibiting activation of factor VII

-Antithrombin: self-explanatory. This would stop activation of many factors. Antithrombin III released by heparin from liver, blocks IX, X, XI, XII, thrombin.

-Active protein C: Thrombin binds to thrombomodulin (component of cells in area), this activates protein C, which is then able to inhibit coagulation. Protein S also mildly increases protein C activity.

Front 22

1) What is ischemic stroke and what are the 2 types

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Back 22

1) Obstruction in blood vessels leading to brain

-Thrombotic stroke: Due to thrombus (blood clot or fatty deposit attached to vessel wall)

-Embolic stroke: due to embolus (floating blood clot or fatty deposit)

Front 23

1) What happens if someone has ischemic stroke, what do they administer and why is imaging important?

2) What are the signs of stroke?

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Back 23

1) Administer tPA to break up the clot, and reduce tissue damage, within 4.5-6 hours after first signs of stroke.

-> brain imaging important in order to see if stroke is hemorrhagic in the brain. If we reduce clotting in brain, we could get bleeding in the brain.

2) sudden weakness, vision problems, dizziness