L13 - blood formation & clotting Flashcards
what do pluripotent stem cells give rise to?
haematopoietic progenitors (precursors) of the blood cells
what are thrombopoietin and erythropoietin?
haematopoietic growth factors (cytokines)
what happens if a blood vessel becomes damaged?
blood can leak out into surrounding tissues (haematoma)
what is endothelium?
surrounds blood vessels
what is epithelium?
outside tissues
what is a bruise?
blood leaked out of capillary
would blood loss be greatest in artery, vein or capillary?
artery - higher blood pressure
why is raising a damaged limb where a blood vessel has been cut beneficial?
lowers blood pressure and blood flow, so less blood loss
what is the immediate response of a damaged vessel?
to constrict. 2 endothelial surfaces can temporarily glue together to stop blood flow, gives time for vessel to wound and form a clot
what happens if vessels glue for too long?
starving other downstream tissues from oxygen
another name for blood clotting?
haemostasis
what can dysfunction in blood clotting lead to?
haemophilia
2 stages of blood clotting
- primary haemostasis: platelet plug formation
- secondary haemostasis: weak platelet plug is transformed into clot by fibrin network
describe primary haemostasis: adhesion
- damage of endothelial cells exposes the subendothelial layers which consist of connective tissues and collagen fibres
- collagen activates platelets via von Willebrand factor (vWF)
- platelets adhere to the collagen
- platelet binding causes release of ADP + seratonin (5HT) from secretory vesicles leading to platelet activation
- then platelet aggregation occurs
platelet activation (primary haemostasis)
- seratonin and ADP released from granules
- causes change in shape and surface protein expression
platelet aggregation
platelets start to adhere to each other to form a plug. this causes synthesis of and release of thromboxane A2 (TxA2) from arachidonic acid which enhances activation + aggregation
what happens once plug is made?
- plug is stabilised by fibrinogen bridges
- actin and myosin cause contraction of plug to bind it tightly together
- smooth muscle is vessels also contracts via TxA2 + chemicals from platelet granules
how does the body restrict the platelet plug from spreading?
- healthy endothelial cells synthesise prostacyclin (prostaglandin, PG12) and nitric oxide which are both potent inhibitors of platelet activation
- PG12 also secreted by thromboxane/ arachidonic acids
what is nitric oxide?
vasodilator
what is a clot/thrombus?
transformation of blood into a gel which is made up of fibrinogen polymers
where does clotting occur?
around the platelet plug
what does vessel damage activate?
cascade of enzymes that result in activation of enzyme THROMBIN
what does thrombin do?
cleaves protein fibrinogen into fibrin molecules that bind together to form a loose meshwork
general principles of blood clotting
- vessel is damaged + exposes subendothelial layers consisting of collagen which binds to platelets
- activation of prothrombin to thrombin which cleaves + activates fibrinogen to fibrin
- thrombin has positive feedback mechanism so it leads to more thrombin production
clotting cascade in extrinsic pathway (outside the blood vessels - the usual one)
- initiated by tissue factor (located on collagen)
- this initates factor 7 and 10
- this is normal way to activate clotting mechanism
- generates small amounts of thrombin
- thrombin has positive feedback mechanism
intrinsic pathway (everything in blood)
- initiated by factor 12 by contact from collagen
- factor 8 is a cofactor
what causes haemophilia?
not having factor 8
role of liver in clotting
- many clotting factors made in liver
- liver makes bile salts which absorb vitamin K needed for production of prothrombin
- this is why ppl with liver disease often having bleeding problems
describe thrombin
- enzyme
- initiated in instrinsic pathway
- enhances prothrombin conversion to thrombin by activating factor 5
- activates platelets
- ligand so binds to receptor called protease activated receptors (PARs) + activates it
anti clotting mechanisms
- PGI2 and NO are anticoagulants as they inhibit platelet activation
- endothelial cell production of tissue factor inhibitor
- thrombin binds to endothelial cell receptor thrombomodulin to activate protein C which inactivates FV and FVIII
- antithrombin III synergies with heparin to inactivate thrombin + other clotting factors
how is the clot dissolved?
fibrinolytics.
- activate plasminogen which can digest fibrin back to soluble fibrin fragments + dissolve the clot
