Circulation 1 -physical thrombosis and clotting in wound healing Flashcards
What does the arterial system do?
takes blood away from the heart
oxygenated blood to distal organs and tissues in the body so that they can survive
Describe the arterial system?
Goes from the heart and straight into the aorta, which is a large or wide diameter, wide calibre vessel.
As it propagates through the body, it gets smaller and smaller as it branches.
Keeps getting smaller till you get to capillaries and oxygenation occurs here.
What cell lines the lumen?
endothelial cell
What do endothelial cells sit on?
basal lamina or connective tissue layer
What surrounds the basal lamina?
smooth muscle cells
What is around smooth muscle cells?
interstitial collagen fibres
What does lumen consist of?
red blood cells - carry oxygen
white blood cells - comprise immune mediated cells
platelets
plasma - fluid mixed up of water and numerous proteins other than WBC and RBC …. main constituent of that is clotting factors
What is haemostasis?
the cessation of flow of blood either within a lumen or if there’s defect in lumen stopping the flow of blood outside the lumen into the surrounding soft tissues
What are the three main steps in haemostasis?
Vasoconstriction- reduces the diameter of the lumen
-reduces blood flow
-limits blood loss
Primary haemostatic process
(initial process of trying to stop blood actually getting through the defect)
-platelet plug formation
Secondary haemostatic process
-Activation of the coagulation cascade
-fibrin meshwork
What is the parent cell of platelets?
megakaryocyte
Describe the physical appearance of a megakaryocyte?
large cell with many nuclei
What kind of division do megakaryocytes go through?
nuclear division but not cell division
How do platelets via megakaryocytes enter circulation?
megakaryocytes then produce platelets, which form little clusters on the membrane of the megakaryocytes.
Megakaryocytes in bone marrow sit over the sinusoids of bone marrow and deposit platelets into sinusoids.
-which then enters the circulation
Describe primary haemostasis?
when lumen is intact -> inactive and circulate around body
when defect in vessel- contents of vessel gets exposed to tissues and immediately body recognizes that as an abnormal event
Body reacts and platelets bind with collagen fibres and smooth muscle - become activated. Producing diff glycoproteins and molecules.
Platelets start to become sticky and they start to aggregate and stick together.
What happens in secondary haemostasia?
activation or the initiation of the coagulation cascade + the activation of clotting factors within that cascade.
Where are most clotting factors produced?
in the liver
What is the main aim of the coagulation cascade?
convert prothrombin into thrombin- which then converts water soluble molecule , fibrinogen, into an insoluble molecule called fibrin. Fibrin is the ultimate haemostatic endpoint.
Describe Extrinsic pathway?
quickest pathway
initial damage to the vessel lumen produces a mol called tissue factor. Tissue factor becomes joined to factor 7 to create a tissue factor 7A complex - which then directly acts on factor 10 , factor 5 to activate their co factors to produce thrombin, fibrin and meshwork.
Describe the intrinsic pathway?
initiated by damage to sub endothelial tissue
thrombin can act back into pathway to propagate more conversion of inactive clotting factors to active clotting factors.
How is the clotting cascade an amplification system?
so many more molecules of fibrin are produced compared to no. tissue factor mols
What is meant by initial damage?
One obvious way is trauma
Trauma leads to 1. Exposure of interstitial collagens (collagens in connective tissue between structures) and 2. Exposure of a molecule called Tissue Factor (=TF)
blood leaks out and plasma comes into contact with interstitial collagen fibres
Contact between plasma clotting factors and interstitial collagen initiates activation
tissue factor produced by smooth muscle and endothelial and initiates secondary phase of haemostasis
How do clotting factors become activated?
when come into contact with activator, activates them by allowing them to bind to co factor (12A).
When bound, becomes active complex. Can do the same in next stage of pathway
What happens when clotting factor is activated?
Many clotting factors are serine proteases
the serine mol in them is cleaved and allows co factor to bind and that active complex does same thing in next stage of pathway
Describe the endpoint of the clotting cascade?
insoluble fibrin strands form a network
Difference between thrombus formation and clot formation?
thrombus:
-Occurs in flowing blood
-A pure thrombus is pale cream coloured
-A thrombus consists of platelets and a mesh like network of fibrin strands (although usually also layers of RBCs)
-adherent to the blood vessel wall
clot:
Blood leaks out of a vessel and becomes stationary
within the stagnant blood, next to interstitial collagen- clotting cascade activated
- a clot consists of a network of fibrin strands and red blood cells
Why does a thrombus of platelets and fibrin occur in flowing blood?
Platelets have molecules on their surfaces which allow adherence to interstitial collagen, even when blood is flowing past them – the clotting cascade deposits Factor VIII which enhances this further
What happens when there is trauma to the skin?
vasoconstriction - limit flow of blood
clotting system- activated by collagen and by stagnant blood- forms clot
May not work v well
activation of platelets
activation of coagulation cascade
to ultimately produce fibrin mesh across vessel
What happens after flowing blood has stopped?
production of vascular endothelial growth factors to allow new vessels to be formed into wound area
with production of fibroblasts and oxygen
get granulation tissue (scar tissue formation) — mature fibrous tissue
How to removed thrombus?
A blood protein called Plasminogen converts to plasmin, and plasmin cuts up fibrin into smaller fragments, as a way of removing fibrin (in both clots and thrombi). In a thrombus this is sometimes called thrombolysis
What is the fibrinolytic system which removes fibrin and stops thrombi from propagating?
In blood there is a fibrinolytic system which removes fibrin and stops thrombi from propagating
