Blood 3 Flashcards
Define Haemostatsis
the process that maintains the flowing blood in a fluid state and confined to the circulatory system.
Define haemorrhage
The process if bleeding
Define Thrombosis
The process of clotting
Define embolism
A blocked artery caused by a foreign body, such as a blood clot or an air bubble
Define fibrinolysis
The process of clot dissociation
What is stemming of bleeding?
Placing pressure on the wound constricts the blood vessels manually, helping to stem blood flow.
What is the difference between primary and secondary haemostasis?
The primary response is driven by blood platelets and mediated by fibrinogen. If there is a defect in this response you bleed immediately. Fibrinogen enables platelets to aggregate in the primary response. This can be early washed away.
The secondary response are driven by circulating enzymes mediated by fibrin. A defect in this response will lead to delayed bleeding e..g haemophilia. Over time the clot breaks down and you bleed.
What is the trigger for primary haemostatsis?
When there is an injury, the collagen in the connective tissue is exposed. collagen is highly thrombogenic. This causes platelets to be activated and so accumulate and aggregate.
Describe the main structural and functional characteristics of the platelet
- Platelets are anucleate
- Platelets have a large number of receptors on their surface e.g. a large number of fibrinogen receptors for agglutination
- Platelets have many granules rich in signalling molecules. They have dense and alpha granules.
- There are able to accumulate in the primary response
- Have both an autocrine and paracrine capability - they can therefore activate themselves and there platelets
Describe, in detail, the primary response.
- There is injury to the blood vessel causing the collagen in the extracellular matrix of the endothelium to be exposed. The binding to collagen activates the platelets.
- When platelets reach the site of injury, they roll on the endothelium and eventually stop.
- The platelets adheres to the collagen. They change shape in order to stick to the collagen.
- The platelets secrete granules containing chemical messengers that cause other platelets nearby to accumulate at the site of injury. These include ADP and thromboxane. This helps to amplify the response.
- Fibrinogen binds to the receptors on platelets and enable them to aggregate.
- This forms a primary clot.
What is the neural response to injury?
Immediate vasoconstriction
What are the types of granules? What are their differences?
Dense granules: Secrete ATP, ADP, Serotonin and calcium ions. The secretion of dense granules helps platelets activate other proteins and thereby enable them to accumulate (positive feedback).
Alpha granules: Secrete many different factors. The secretion of alpha granules helps coagulation and drive wound healing.
What drugs are used to treat an MI?
Aspirin: Blocks Thromboxane A2
Clopidogrel: Blocks ADP
Many other receptors on platelets are targeted to prevent another MI. A favourite at the moment is GpVI. This blocks collagen receptors.
How is coagulation kept localised?
- Platelets are only activated when collagen is exposed. This only occurs at the site of injury.
- Only activated platelets can secrete chemical messengers to gather other platelets.
- Only activated platelets can bind to fibrinogen.
- The coagulation cascade can only be imitated by activated platelets.
- Thrombin is produced on the surface of activated platelets.
What are the main platelet receptors involved in collagen adhesion and platelet aggregation?
Adhesion:
- α2β1 receptor for adhesion of collagen
- Gp1b-IX-V for adhesion of the Von Willebrand factor
Platelet activation:
- GpVI for Collagen
- PAR1 and 4 for Thrombin
- P2Y1 and P2Y12 for ADP
Platelet aggregation:
- αIIbβ3 (GPIIb/IIIa) for Fibrinogen
Discuss the principle of limited proteolysis and its role in coagulation
There are many stages in the coagulation pathway - each step activating an enzyme. Limited proteolytic processing of blood coagulation enables zymogens to become functionally active. The principle of limited proteolysis is that a protein is incubated with a relatively low concentration of different proteases, which cut at recognition sites throughout the protein, normally at exposed regions such as loops and other flexible regions
Discuss the extrinsic pathway involved in activating coagulation.
Extrinsic pathway:
Normally cells keep tissue factor outside inside the cell - they normally do not come into contact with the blood. When there is an injury, the cells push the protein up through the plasma membrane into the blood. The tissue fluid will then combine with factor VII. This activates Factor VII to form a large complex. This complex can then activate Factor X.
Discuss the common pathway in coagulation
Factor IXa can then activate Factor X along with Factor VIIIa. TF:FcVII (a complex of tissue factor and factor VII) combines with Factor Xa to produce a greater complex on the surface of the platelets.
Factor X can then convert prothrombin to thrombin. Thrombin can convert Fibrinogen to form insoluble Fibrin, This consolidate the pug, making it stronger and less susceptible to being washed away. Thrombin activate Factor XIII. Factor XIIIa helps to further stabilise the plug. Thrombin also helps to further stimulate the intrinsic pathway, producing more thrombin in positive feedback (this includes the activation of Factor VIII).
What is the Von Willebrand factor?
Adhesive and multimeric glycoprotein. Von Willebrand Factor’s primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. It is not an enzyme and, thus, has no catalytic activity.
