Lecture 16- Haematology Lecture 4 Flashcards
What happens if you cut yourself?
immediate: bleeding
-activates the dormant coagulation factors
Delayed:
- steps to prevent infections-> recrutment of bacterial and fungal decenfes
-to reduce blood loss:
-initiation of a blood clot forming
-contraction of the blood vessel
When you have a tissue injury what inflammatory mediators are released and why? What happens to capillary permeability? And what other things are triggered to counter the damage?
- Release of inflammatory mediators:
- Mast cells = histamine
- Monocytes = cytokines
- Complement activation
- ↑ capillary permeability
- Neutrophils, monocytes and lymphocytes
attracted to the area - Phagocytosis of pathogens & dead cells
- Activation of blood coagulation to:
- Prevent blood loss
- Seal off wound site & prevent spread of the
pathogen
What is haemostasis?
the process by which blood coagulation is initiated and terminated, together with the removal (fibrinolysis) of the clot as part of vascular remodelling
Why is haemostasis important?
Preserve the integrity of the vascular system in response to injury
Prevents microbes from gaining entry to the body
The body is high pressure vascular system therefore response must be
rapid. Also has to be regulated to prevent inappropriate clot
formation and localised to prevent loss of blood flow through the
blood vessels.
Inappropriate blood coagulation may block vessels
through formation of a thrombus, which
Restricts blood flow
Starves tissues of oxygen
Leads to cell death
Failure to achieve blood coagulation (haemophilia) is life threatening
What is haemostasis dependent on?
-vessel wall integrity
-adequate numbers of platelets
-proper functioning platelets
-adequate levels of clotting factors
-proper function of fibrinolytic pathway
Define all the terms
-Adhered
-aggregation
-filopdia
-granules
-phospholipid
-protease
-vasoconstriction
Summarise the steps of haemostasis
vessel injury
1. platelet adhesion
2. platelet activation
3. platelet aggregation
4. stable haemostatic plug
What happens to coagulation at rest?
Coagulation – at rest
The clotting factors are pre-synthesized
and circulate in inactive forms
Platelets circulate in large numbers
Tissue factor (TF) is the trigger for blood
coagulation. This is a cell surface
protein expressed on cells not in
contact with blood; expression pattern
generates the ’haemostatic envelope’
Endothelial cells present an
anticoagulant surface through
expression of cell surface molecules
What happens if blood begins to escape a vessel following injury?
- vascular phase- vasoconstriction to reduce blood flow
- platelet phase- platelet plug forms (von willebrand factor bind to damaged vessel and platelets)
- coagulation phase- activation of clottinf cascade with generation of fibrin clot formation
- fibrinolytic phase- fibrinolysis (clot breakdown)
What is vascular spasm- detail step 1
When arteries or arterioles are damaged circularly arranged smooth
muscle contracts immediately
* Function: Reduces blood loss
* Effective for several minutes to several hours
* Controlled by:
* Likely initiated by damage to the smooth muscle itself
* Enhanced by substances released from activated platelets
* reflexes initiated by pain receptors.
Detail step 2- plug formation
1) PLATELET ADHESION: Platelets are attracted to
damaged blood vessel by collagen fibres of the
connective tissue underlying the damaged
endothelial cells.
2) PLATELET RELEASE REACTION: Adhered
platelets become activated → change in
properties. Extension of projections enabling
contact & interaction with each another →
release of granules.
* ADP and thromboxane A2 (TXA2) activate nearby
platelets.
* Serotonin and TXA2 = vasoconstrictors
3) PLATELET AGGREGATION: Release of ADP → local
platelets become sticky → recruitment of new activated
platelets to adhere to original activated platelets.
Accumulation & attachment of many platelets
form a mass called a platelet plug.
Describe what activated platelets do.
- Shape change - generation of filopodia
- Spread and attach around injury
- Granules are release
- ADP
- Thromboxane (TXA2)
- Von Willebrand factor (vWF)
- Fibrinogen (precursor to fibrin)
- P-selectin
- Phospholipid composition
- Exposure of phosphotidylserine (PS) negatively charged surface that
promotes thrombin generation and fibrin deposition
Describe step 3- coagulation
- Series of (proteolytic) reactions that culminates
in formation of fibrin threads. - Each step many molecules of the next target
are activated – amplifying the signal - A blood clot is a gel that contains formed
elements of the blood entangled in fibrin
threads. - Clotting involves several substances known as coagulation factors.
- These include calcium ions (Ca2+), several inactive enzymes which are
released into the bloodstream by the liver and molecules associated with
platelets or released by damaged tissues.
Why is fibrin important? Why is thrombin important?
Conversion of Fibrinogen to Fibrin: Thrombin cleaves fibrinogen, a soluble plasma protein produced by the liver, into insoluble fibrin strands. Fibrin forms the structural framework of a blood clot, providing stability and strength.
Activation of Platelets: Thrombin activates platelets, blood cell fragments involved in hemostasis, by binding to specific receptors on their surface. Activated platelets undergo shape change, aggregation, and release of clotting factors to promote clot formation.
Positive Feedback Amplification: Thrombin activates factors V and VIII, which are cofactors that further enhance the coagulation cascade, leading to amplification of thrombin generation and blood clot formation.
Mechanical Support: Fibrin provides structural support and stability to the blood clot, preventing it from dislodging or breaking apart prematurely.
Hemostasis: Fibrin meshwork acts as a barrier to seal off the site of injury and stop bleeding, preventing further blood loss.
Wound Healing: Fibrin clot serves as a scaffold for tissue repair and regeneration, facilitating the healing process at the site of injury
Where are blood clotting factors synthesised?
in the liver
