Session 5 Flashcards
What is haemostasis and what does it involve?
- Stopping of a haemorrhage to prevent blood loss
- Involves vasoconstriction and platelet plug formation
What is clotting?*
The process of blood becoming a solid mass when it makes contact with connective tissue
What controls clotting?
- Activation and release of different clotting factors
- Production of thrombin which acts on fibrinogen and produces insoluble fibrin filaments that trap RBCs
When will blood clot?
- As soon as spilled from a vessels
- Only cells that will not clot then are endothelial cells, RBCs and WBCs
What are the 3 steps of haemostasis?
1) Severed artery contracts to decrease pressure downstream
2) Primary haemostatic plug of activated platelets forms at the hole in the vessel to control bleeding
3) Secondary haemostatic plug as fibrin filaments stabilise the blood clot (30 mins)
What activates platelets?
- Collagen surfaces
- ADP released by activated platelets and RBCs
- Thromboxane A2 (platelet aggregator)
- Thrombin (informs platelets that clotting is activated)
What happens when platelets are activated?
- Stick to the exposed endothelium (von Willebrand factor) on basement membrane
- Aggregate with other platelets to form platelet plug
- Fibrinogen sticks platelets together
- Platelets swell and change shape
- Secrete factors from platelet granules that help aid clotting (Thromboxane A2/fibrinogen)
How does aspirin decrease platelet aggregation?
Irreversibly inactivates cyclooxygenase which is responsible for producing thromboxane A2
Why must thrombin be activated and how is that done?
- Must be activated as blood would otherwise be solid
- Activated by proenzymes known as clotting factors
Which clotting factors need vitamin K for synthesis?
II, VII, IX, X + protein C and protein 5
What are proenzymes?
Biologically inactive enzyme precursors that must be activated to function as enzymes
What is the intrinsic clotting pathway?*
Pathway that involves factors, all of which are in the blood. Vessel break not needed to occur as triggered by a negatively charged surface.
What is the extrinsic clotting pathway?*
A pathway that needs a clotting factor (thromboplastin) which is present outside the blood, and is triggered by thromboplastin release from damaged cells that are adjacent to area of haemorrhage.
How does the vascular wall contribute to haemostasis?
- Arterial tunica media contracts
- Subendothelium traps platelets
- Secretes plasminogen activator and thrombomodulin that oppose clotting as well as von Willebrand factor which favours it when there is damage
- Exposure collagen and initiate clotting factor activation
What are the main natural anticoagulants?
- Antithrombin III
- Protein C
- Protein S
What happens when someone is deficient in natural anticoagulants?
More prone to repeated thrombosis
How does the clot retract?
- Platelets in clot die and cling to fibrin
- Pull by actin-myosin filaments similar to muscle contractions to retract the clot
- Toughened by squeezing out fluid
What is fibrinolysis?
The process of dissolving the clot once the hole in the vessel is repaired
How is the clot broken down?
- Recognised by macrophages
- Broken down by plasmin
How is plasmin activated?
- Circulates as plasminogen made in liver
- Activated by tissue plasminogen factor (blood), urokinase (urine) and streptokinase (bacteria, not in body)
Why are plasminogen activators used therapeutically?
Dissolving fibrin (thrombi and thromboemboli)
Why is tPA preferred over streptokinase ?
- Streptokinase can only be given once as it is antigenic
- tPA has a higher affinity for fibrinogen, is not antigenic and can be given multiple times
Where can bleeding occur from treatment with plasminogen activators?
Gums, nose, (serious) brain
What activates fibrinolysis?*
- Fibrin increasing activity of tPA
- tPA produces plasmin
- Plasmin breaks fibrin down to the fibrin degradation products (FDPs)