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26 Cards in this Set
- Front
- Back
Phases of haemostasis
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1. Vascular
2. Platelet 3. Coagulation |
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Vascular phase: vasospasm
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Cutting the wall of a blood vessels, triggers smooth muscle contraction.
- Vasospasm, lasting around 30 mins to slow or even stop the flow of blood |
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Vascular phase: endothelium
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- Endothelial cells contract and expose underlying BM to blood stream
- Endothelial cells release local factors and hormones e.g. ADP, tissue factor, prostacyclin, endothelins - Endothelial plasma membranes become "sticky", facilitating the attachment of platelets and even sticking to the opposite endothelial wall |
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Endothelins
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Peptide hormones that:
- stimulate smooth muscle contraction and promote vascular spasm - stimulate the division of endothelial cells, smooth muscle cells and fibroblasts to accelerate the repair process |
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Platelet phase
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Begins with the attachment of platelets to endothelial surfaces, BM and exposed collagen fibres
Platelet adhesion > platetlet aggregation > platelet plug |
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Activation of platelets
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First sign of activation: become more spherical, develop cytoplasmic processes to link with other platelets. Release a variety of compounds:
1. ADP stimulates platelet aggregation and secretion 2. Thromoxane A2 and serotonin stimulate vascular spasm 3. Clotting factors are proteins 4. PDGF is a peptide that promotes vessel repair 5. Calcium ions are required for platelet aggregation and in the clotting process |
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Progression of platelet phase
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ADP, thomboxane and calcium are released from each arriving platelet, stimulating further aggregation
- this is a positive feedback loop |
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Role of prostacyclin
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A prostaglandin that inhibits platelet aggregation and is released by endothelial cells. Controls and restricts platelet aggregation to the injury site.
- This is reinforced by inhibitory compounds released by WBCs |
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Role of plasma enzyme
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Circulating plasma enzymes break down ADP near the plug, restricting the response
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Inhibition of plug formation
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- Serotonin blocks the action of ADP at high concentrations
- Circulating plasma enzymes - Inhibitory WBC compounds - Prostacyclin inhibits platelet aggregation - development of a blood clot isolates the plug |
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Coagulation phase
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A complex sequence of steps leading to the conversion of circulating fibrinogen into the insoluble protein fibrin.
- As the fibrin network grows, blood cells and additional platelets are trapped in the fibrous tangle, forming a blood clot. |
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TImings of phases
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Vascular and platelet phases begin with a few seconds of injury
Coagulation does not start until 30 seconds later |
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Clotting factors
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- Normal clotting depends on procoagulants in the blood: Ca2+ and 11 proteins
- Many of the proteins are proenzymes, which are converted to active enzymes and direct essential reactions in the clotting response |
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Pathways initiating clotting cascade
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Extrinsic: begins outside the blood stream in the vessel wall (appropriate activation)
Intrinsic: begins in the blood vessel with the activation of a circulating proenzyme These two pathways converge at the common pathway |
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Draw clottting cascade
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Extrinsic pathway
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Appropriate activation:
- TF/FIII is released by damaged endothelial cells or peripheral tissues - The more damage, the more TF released |
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Intrinsic pathway
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Inappropriate activation:
- activation of proenzymes exposed to collagen at the site of insult |
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The common pathway
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Enzymes from either pathway activate FX, forming the enzyme prothrombinase.
- Prothrombinase converts prothrombin into thrombin - Thrombin completes the clotting cascade by converting fibrinogen to insoluble fibrin |
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Clot retraction
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One the fibrin mesh-work has formed, platelets and RBCs stick to the fibrin strands.
- The platelets then contract, and the entire clot undergoes clot retraction - This process continues over 30-60mins |
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Feedback control of coagulation
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Thrombin generated in the common pathway stimulates clotting by:
- Stimulating the formation of TF 2. Stimulating the release od PF-3 by platelets This is a positive feedback loop, stimulating intrinsic and extrinsic pathways |
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Restriction of coagulation: antithrombin-III
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- Normal plasma includes several anticoagulants e.g. antithrombin-III inhibits several factors, including thrombin
- Heparin is released by basophils and mast cells, and accelerates the activation of antithrombin-III |
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Restriction of coagulation: aspirin
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- Aspirin inhibits the production of thombozane-A2 and prostaglandins.
- Prevents platelet aggregation and so clot formation - Prolongs bleeding time |
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Restriction of coagulation: thrombomodulin
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- Thombomodulin is released by endothelial cells and binds to thrombin
- Activated thrombin then activates protein C - Protein C is a plasma protein that inactivates several clotting factors and stimulates the formation of plasmin - Plasmin gradually breaks down fibrin strands |
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Restriction of coagulation: prostacyclin
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Prostacyclin released during the platelet phase inhibits platelet aggregation and opposes the stimulatory action of thrombin and ADP
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Restriction of coagulation: Vitamin K
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Sufficient vitamin K is needed in the liver to synthesise 4 of the clotting factors
- long term lack of Vit K causes breakdown of the common pathway and eventual destruction of the clotting cascade |
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Fibrinolysis
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Activation of proenzyme plasminogen by thrombin and tissue plasminogen activator (t-PA) released by damaged tissues
- produces the enzyme plasmin which begins digesting the clot |