Hemostasis Word Scramble
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| Question | Answer |
| Physiological challenges | Do not harm when all is normal - do not obstruct Automatically seal vascular punctures Prevent loss of blood Recruit healing helpers Resolve when healed |
| Stages of hemostasis | Vascular spasm in response to injury Primary - platelet plug formation Secondary - blood clotting (coagulation) Removing clots (fibrinolysis) |
| Arteriolar vasoconstriction | Damaged endothelium initiates sympathetic reflex (noradrenaline and neuropeptides) releases endothelin-1, a vasoconstrictor Arteriolar smooth muscle contraction restricts flow |
| The platelet | Small cytoplasmic fragments of megakaryocytes Life span of 8-10 days Abundant in blood Packed with granules |
| Platelet aggregation reaction | Adhesion to vessel wall - platelet GPIa/IIa binds collagen and GPIIb/IIIa binds fibronectin Activating platelet changes shape releasing granule contents Aggregation of platelets Release of ADP and TxA2 GPIb binds vWF to induce further aggregation |
| Platelet granule functions | Further activation Leukocyte recruitment Endothelial repair Secondary hemostasis Further aggregation Defence protein |
| Thrombopoiesis | TPO produced by liver and kidneys acts at every stage HSC - MPP - CMP - EMk - MkP All have CD110 receptors Negative feedback - platelets internalise TPO to reduce production |
| Platelet disorders | Hereditary thrombocytopenia Small platelets e.g. Wiskott-Aldrich syndrome Large platelets e.g. Bernard-Soulier syndrome Extreme folate/Vit B12 deficiency Infections Drugs Autoimmunity |
| The coagulation cascade | Signal amplification by a series of protease reactions Initiated by exposed charged surface and release of tissue factor and phospholipid from endothelium Generates insoluble fibrin mesh Regulated |
| Fibrinogen | Present in plasma at high concentrations High molecular weight Made in the liver 6 polypeptides - 2 alpha, 2 beta and 2 gamma Fibrinopeptides cleaved by thrombin to allow aggregation |
| Fibrin polymerization | Thrombin cleaves fibrinopeptides in fibrinogen Exposed regions spontaneously aggregate Meshwork traps platelets, rbc etc to stabilise plug Further crosslinking GLN-LYS by factor XIIIa to form gamma dimers |
| Vitamin K dependent zymogens | Signal peptide Gla domain - gamma carboxylated glutamate Kringle domains for regulation - cleaved off by prothrombinase Catalytic domain - serine protease |
| Vitamin K deficiency | Needed for gamma carboxyglutamate Gla residues bind 7 calciums to orientate hydrophobic residues into the membrane Epoxide reductase needed for VitK reduction inhibited by warfarin |
| The common pathway | Prothrombin Activated by FXa Also by FVa Requires phospholipid Restricts reaction to surface of activated platelets Serine protease that activates factors I V VIII XI XIII |
| Inhibitors of clotting | Endothelial glycosaminoglycans e.g. heparan sulphate Activated Protein C Thrombomodulin EPI Anti thrombin III |
| Antithrombin III | A serine protease inhibitor encoded in the human genome Also alpha 1 anti trypsin, Complement C1q inhibitor, PLA-1 ATIII-thrombin interaction enhanced 1000 fold by hepSO4 GAG and heparin |
| Haemophilia | X linked Often a recent mutation due to elderly spermatogenesis Cannot produce tenase complex Treated with clotting factors May be able to recombinantly produce these from DNA clones in mammalian cells |
| Fibrinolysis | Breakdown clots - used in treatment of clotting e.g. in strokes Plasminogen broken down to plasmin which is a serine protease - converts fibrin to fibrin degradation products |
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