Homeostasis Flashcards
What are the main functions of homeostasis regarding haematology?
- blood in fluid state
- confine blood to vascular bed.
- arrest bleeding (haemostatic plug)
What does normal haemostasis involve?
Normal haemostasis physiology constitutes a delicate balance where any deficit or exaggeration could lead to either thrombosis or hemorrhage.
What are the 5 components of normal haemostasis?
- blood vessels (vascular system)
- Platelets
- Plasma coagulation factors
- Plasma coagulation inhibitors.
- Fibrinolytic system
What is the general role of the endothelium cell?
The prevention of blood clotting in vivo
What is the endothelium cell?
This is a single layer of cells on the lumen of vascular tissue.
blood clotting is controlled by the vascular endothelial cells and some of the substances present on these cells.
What are some of the substances on the endothelium cell which promote an anticoagulant environment?
Thrombomodulin and heparan sulphate.
What are some of the natural anticoagulants in the blood?
Antithrombin, protein C , protein S
Which enzyme inhibits platelet aggregation?
ADPase - breaks down ADP which is a platelet agonist.
Which two substances are platelet inhibitors?
Prostacyclin and nitric oxide.
Why is ADPase effective as an inhibitor of platelet aggregation?
As when platelets are activated aka coagulation, to be kept neutral (coagulation not needed) ADPase prevents the platelets from using ADP for aggregation.
Name a vasoconstrictor:
Serotonin
What is the first factor which is released from the exposure of the sub endothelial after vessel damage?
Tissue factor is released from the blood vessel into the area that is damaged
How is the physiological coagulation cascade activated?
When the tissue factor released by the damaged vessel is in the presence of phospholipid released from platelets this leads to the formation of the physiological blood coagulation cascade.
What is the role of thrombin and when is it released?
When the blood coagulation cascade begins, a large amount of it is produced. It has mainly enzymatic functions including converting soluble fibrin to insoluble fibrinogen which can aid and reinforce the development of the primary haemostatic plug = leading to a stable hemostatic plug.
What is the role of vasoconstrictors?
To minimise the blood going to a site of injury.
How to platelets adhere to the damaged vessel?
They adhere to the glycoprotein receptors in the sub endothelial cells of the damaged vessel. Join to collagen.
What does the aggregation of platelets lead to?
Primary haemostatic plug.
How do the coagulation factors from the tissue factor cascade interact with the platlets?
Coagulation factors use the laid down platelets as a membrane to lay down fibrin.
What is the role of the physiological coagulation cascade?
Their role involves activated coagulation factors that function in the generation of thrombin and formation of the fibrin clot. This is coagulation
What type of muscle do muscular arteries have?
Smooth muscle.
What type of muscle do elastic arteries have?
Collagen and elastic fibres.
What are vessels with muscular coats able to do after injury?
Contract, helping to arrest bleeding.
Release vasoconstrictores such as angiotensin II, this ensures that there is reduced blood flow which will assist in the eventual formation of a stable haemostatic plug.
What do endothelial cells contain that that helps in attempting to arrest bleeding?
Procoagulants and anticoagulant proteins that when released will play a balancing act in attempting to arrest bleeding.
What do the endothelial cells synthesis upon damage to the their vessel?
Tissue factor - which initiates coagulation.
Protein S and C
What are protein S and C examples of?
These are natural anticoagulants.
What is heparin sulphate and which cells synthesis it?
Endothelial cells synthesis it, it is a natural anticoagulant/antithrombin.
Which factor does the endothelial tissue produce?
Von Willebrand Factor.
What is Von Willebrand Factor?
It is essential for platelets for adhesion to the sub endothelial glycoprotein receptors.
What is the sub endothelium consisting of?
Connective tissue, collage, elastic tissues, proteoglycans, non collagenous glycoproteins and VWF - after damage = exposed ….. available to enable platelet adherence.
What are platelets made up of?
They are produced in the marrow by fragmentation of the cytoplasm of megakaryocytes.
Which precursor did thrombocytes arise from in thrombopoiesis? How long does differentiation take?
CFU - GEMM
10 days
How many platelets does one megakaryocyte give rise to?
1000-5000
What is thrombopoietin?
It is a platelet growth factor and is a major growth regulator of platelet production and is mainly found in the liver and kidneys.
What do platelets contain?
- granules (pro coagulant and anticoagulant factors)
- thromboxane A2 = powerful vasoconstrictor.
- glycoprotein receptors (activated coagulation factors bind - thrombin )
What is thromboxane A2?
A powerful vasoconstrictor.
What does platelet function consist of?
Adhesion, activation and aggregation (triple a)
What two components lead to normal circulatory platelet function?
Nitric oxide, prostacylin
What is step one of platelet function in homeostasis?
adhesion - platelets adhere to collagen fires at the site of injury
What is the second step of platelet function in homeostasis?
activation - change in platelet shape - activation, release of procoagulant molecules from granules
What are some examples of procoagulant granule molecules?
TXA2, ADP, VWF, serotonin, phospholipid, platelet factor 3
What do the procoagulant granules provide for the platelets?
A surface for the reactions of the coagulation factors in the physiological coagulation cascade
What is step three of the platelet function in homeostasis?
Platelet aggregation - this is where a primary aggregation (reversible) and secondary aggregation (irreversible) take place
What is the product of the platelet aggregation step?
A primary haemostatic plug.
What do activated platelets produce and what is its function?
Thromboxane A2 which is a powerful vasoconstrictor.
What reduces the level of platelet aggregation?
Aspirin and clonotril
Upon vessel injury and exposure of the sub endotherlium, circulating platelets bind to which blood vessel surface glycoproteins?
Gp 1a
Gp 1b
What happens to platelets when they bind to the blood vessel surface glycoproteins?
They undergo shape change, become spherical, extending pseudopods.
Intracellular granules are moved to surface and release of content into microenvironment.
Mediated by mobilization of calcium and activation of platelets.
What helps binding of the surface glycoproteins, present on the platelet membrane ?
- collagen
- VWF
- fibrinogen
What is the function of VWF?
- binds platelets to sub endothelial
- carries coagulation factor 8 (haemophilia A)
What does soluble fibrinogen convert to?
Fibrin.
What are the advantages to the platelet surface membrane being invaginated?
- increases surface area for release of contents of intracellular granules.
What do alpha granules contain?
A variety of haemostatic proteins including PDGF, vWF, fibrinogen and fibrinolytic proteins.
What is PDGF?
Platelet derived growth factor
Which glycoprotein binds directly to collagen?
Glycoprotein 1a.
Permits direct adhesion.
What are the glycoproteins which when attached to the vWF adhere to the subendothelium?
1b, 2b, 3a
Where is vWF synthesised and stored?
It is synthesised in the endothelial cells and megakaryocytes.
Stored in Weibel Palade bodies and platelet alpha granules.
Who discovered the blood coagulation factors?
Morawitz
What is the simple equation of blood clot development?
Prothrombin + calcium + tissue thromboplastin = Thrombin, Thrombin + fibrinogen = fibrin clot.
What is the role of thrombin?
Converts fibrinogen to fibrin.
What is the coagulation pathway dependent on ?
Activated coagulation factors (enzymes), some are known as serine proteases or serine endopeptidases.
What are serine proteases or serine endopeptidases?
These are a class of peptidase enzymes that cleave peptide bonds in proteins, they are characterized by the presence of a serine residue in the active centre o f the enzyme.
What are some examples of serine proteases in coagulation?
Factor: II, IX, X
What is factor III?
Calcium
What is the lacking factor in haemophilia B?
Factor 9 or the Christmas Factor.
What is factor 15?
Fibrin Stabilising factor.
What stages are involved in the generation of thrombin following vascular injury?
Initiation
Amplification
Propagation
IAP
What happens during the initiation phase of post thrombin formation?
Small amounts of thrombin are generated which prepares the coagulation cascade for the amplification and propagation phases which sees a thrombin burst and conversion of fibrinogen to fibrin.
Which factor strengthens the thrombin?
By the transamidase which crosslinks fibrin clot = action of factor 13, fibrin stabilising factor - reinforces the clot
What activated factor 15?
Thrombin.
