Health and Disease Week 5 Flashcards
What is blood production controlled by?
multiple protein cytokines (release by WB cells) and growth factors
What detects blood vessel damage?
platelet surface receptors
What do platelets secrete? Why?
soluble factors to activate neighbouring platelets
What is required for a clotting cascade?
multiple blood proteins
What does thrombopoietin do?
regulate production of platelets
What does erythropoietin do?
regulate production of erythrocytes
What are the major precursors of platelets?
megakaryocytes
What kind of cells give rise to haematopoietic precursors of blood cells?
pluripotent stem cells
What creates a bruise?
when blood vessel endotheliums become damaged and blood leaks into surrouding tissues
What is the scientific name for blood clotting?
haemostasis
What 2 stages can clotting be broken down into?
- primary haemostasis
- secondary haemostasis
What happens in primary haemostasis?
platelets form a plug and are attracted to site of damage
What happens in secondary haemostasis?
a blood clotting mechanism is used to transform and stabilise the weak platelet plug into a clot by a fibrin network
What is the 1st step of platelet plug formation?
adhesion
What are the steps of adhesion in platelet plug formation?
- damage to endothelium cells exposes subendothelial tissue which is made up of collagen fibres
- collagen activates platelets and they adhere to these collagen fibres via an intermediate protein called von Willebrand factor (vWF)
- platelets binding to collagen causes a release of ADP and serotonin from their secretory vesicles, resulting in more platelet activation
What is the 2nd step of platelet plug formation?
platelet activation
What are the steps of platelet activation?
- release of ADP and serotonin from vesicles
- this causes change in shape and surface protein expression of platelets
What is the 3rd step of platelet plug formation?
platelet aggregation
What are the steps of platelet aggregation?
- platelets adhere to each other to form a plug
- synthesis and release of thromboxane A2 from arachidonic acid enhances more activation and aggregation
What stabilises the platelet plug?
fibrinogen bridges that form when receptors in the platelet surface become exposed during activation
What causes contraction of the plug?
actin and myosin
What do healthy endothelial cells do?
synthesis and release of Prostacyclin (PGI2) and nitric oxide, which both inhibit platelet activation
What is the scientific name for a clot?
a thrombus
What is a clot?
the transformation of blood into a gel consisting of fibrin polymers that occurs around the platelet plug
What does vessel damage and collagen exposure activate?
a cascade of enzyme that results in the activation of an enzyme called thrombin
What happens at each step of the clotting cascade?
an inactive plasma protein (factor) is cleaved to become an active enzyme or cofactor to activate the next step of the pathway
define zymogen
an inactive substance which is converted to an active enzyme when activated by another enzyme
What does the enzyme thrombin do?
cleaves a protein called fibrinogen into fibrin molecules that create the fibrin network
Absence of which clotting factor causes haemophilia?
factor 8
How is plasmin activated?
tissue-plasminogen activator (t-PA) is released and binds to fibrin clot and activates plasmin from plasminogen
How is the clot dissolved?
by the enzyme plasmin, which is activated by t-PA from plasminogen
Sequence of events
clotting factors -> prothrombin -> thrombin -> fibrinogen -> fibrin -> blood clot
What are the overall steps of blood clotting?
- damage to blood vessel lining triggers the release of clotting factors
- formation of the platelet plug and vasoconstriction limits blood flow
- development of the clot and fibrin strands adhere to form an insoluble clot
How is thrombin activated?
activated from prothrombin which then cleaves fibrinogen to fibrin (which is stabilised by activation of factor 8 by thrombin)
What are the steps in activating the clotting cascade for the extrinsic pathway?
- initiated by a tissue factor, not blood protein, on the outside of plasma membrane of cells in the sub-endothelial tissue
- tissue factors activates factor 7 and they both activate factor 10
- generates small amounts of thrombin
- thrombin then feeds back onto the intrinsic pathway to activate components and generate more thrombin
What are the steps of beginning the enzyme cascade in the intrinsic pathway of the clotting cascade?
- clotting factor 12 is activated by contact with collagen
What is the role of the liver in blood clotting?
- produces many clotting factors
- produces bile salts which are required for absorption of vitamin K needed for production of prothrombin
What does thrombin do?
it is an enzyme that recruits the intrinsic pathway and activates factor 5 and activates platelets
How does the protease activated receptor on platelets activate them?
- the enzyme thrombin binds and cleaves the thrombin receptor at a specific site on the N terminus on a platelet
- the cleaved N terminus can then bind and activate the receptor on the platelet
What are examples of clotting disorders?
damage to endothelium (myocardial infarction), clots (deep vein thrombosis), clotting disorders (haemophilia)
