Lecture 13- vascular disorders 1

Question 1

Explain the role of haeomstasis (blood coagulation)

Answer 1

role of haeomstasis
defence mechanism to maintain the integrity of the circulatory system which is under high pressure
causes blood clots
dependent on platelets and circulating plasma proteins
it ensues the blood remains in a fluid state, within the vasculature
haemostats results in a stable plug (blood clot) @ the sight of injuries blood vessel

Question 2

Explain the 3 phases of haemostasis

Answer 2

3 phases of haemostasis
-primary haemostasis
formation of the primary plug @ site of endothelial damage
-secondary haemostasis
activation of coagulation cascade to produce fibrin which stabilises the platelet plug (forms a mesh over the clot making it hard to break down)
-fibrinolysis
breakdown of the fibrin in the plug (stops clot from getting too big)

Question 3

For the endothelial cell explain how it works to maintain haemostasis (7)

Answer 3

Endothelial cells 
lines the vascular system 
injury/activation; produce or respond to mediators that induce vasoconstriction, enhanced platelet adhesion and aggregation & coagulation 
forms a physical barrier 
help to mediate/regulate inflammation 
fluid distribution 
haemostasis 
regulation of angiogenesis

Question 4

For the anithrombotic properties explain the types

• Anti-platelet effects
• anticoagulant effects;
• fibrinolytic effects;

Answer 4

Antithrombotic properties of endothelium

• Anti-platelet effects; physical barrier bw platelets & plasma coagulation factors & highly thrombotic subendotheial ECM
• anticoagulant effects; heparin and thrombomodulin act indirectly to inactive clotting factors
• fibrinolytic effects; promotes fibrinolytic activity to clear fibrin from endothelial surfaces

Question 5

For prothrombotic properties of endothelium explain

• Platelet effects
• Procoagulant effects
• Antifibrinoltic effects

Answer 5

Prothrombotic properties of endothelium
-Platelet effects; von wilebrands factor [roduced by endothelial cells facilitates the binding of platelets to collagen surfaces
-procoagulant effects IL-1 synthesise tissue factor, major activator of extrinsic clotting cascade
-Antifibrinoltic effects;
endothelial cells secrete inhibitors of plasminogen activators which limit fibrinolysis and favour thrombosis

Question 6

For platelets explain the following
main regulator of production
what granules are present and what do they contain
how activation occurs

Answer 6

Platelets
-thrombopoietin is main regulatory production
intracytoplasmic granules contain;
fibrinogen
fibronectin
factors V & VII
-activation
platelet adhesion; von wilebrands factor acts as a resilient bridge bw surface receptors and exposed collagen
secretion; release of alpha and dense bodies
aggregation; ADP and thromboxane secreted by platelets is the stimulus for platelet aggregation which makes the plug

Question 7

Explain the function of the following

• prostacyclin
• Thromboxane TxA2

Answer 7

• prostacyclin; vasodilator and inhibits platelet aggregation
• Thromboxane TxA2; vasoconstrictor and activates platelet aggregation

Question 8

For the fibrinolysis explain how it works to maintain haemostasis

Answer 8

fibrinolysis explain how it works to maintain haemostasis
breakdown of fibrin in clot
last stage in the coagulation process
causes less fo fibrin and degrades the haemostats clot
produces soluble fibrin degradation products

Question 9

For the primary phase of haemostasis and list what occurs

Answer 9

Primary haeomstasis
-damage to vessel wall (endothelium)
transient (short) vasoconstriction
-platelets adhere to exposed subendothelia ECM (collagen)
platelets aggregate and form a primary haemostatic (platelet) plug

Question 10

For the secondary phase of haemostasis and list what occurs and list the coagulation factors

Answer 10

Secondary haeomostasis 
-exposed tissue factor (extrinsic)
-activation of the coagulation cascade 
-thrombin- fibrin 
deposition of fibrin strengths platelet plug to form a secondary haemostats plug 
coagulation factors; 
-fibrinogen
-prothrombin 
-tissue factor

Question 11

For the third phase of haemostasis and list what occurs

Answer 11

3 phases of haemostasis; fibrinolysis
breakdown of fibrin in the haeomstatic plug
activation of plasminogen to plasmin, causes less of fibrin and degrades the clot
thrombomodulin binds to thrombin which blocks the coagulation cascade
this limits haemostats to the site of injury

Question 12

What makes up the primary and secondary haemostatic plug

Answer 12

• Primary haemostatic plug; damaged endothelium, exposed collagen, platelet adhesion, activation, secretion
• secondary haemostatic plug primary haemostat plug + sub endothelial collagen + vWF + platelets its stable

Question 13

What is the main substance assist adherence of platelets to damaged blood vessel walls?

Answer 13

platelet adhesion; Von Wilebrands factor act as a resilient bridge bw platelet surface receptors and exposed collagen

Question 14

Give examples of how coagulation is controlled

Answer 14

Give examples of how coagulation is controlled
Coagulation control; restrictions/limitations
once activated, coagulation must be limited to local site of vascular injury to prevent widespread clotting;
intact healthy endothelial cells stop platelet adherence and stop blood clotting
coagulation factor activation is restricted to sites of exposed phospholipids
anticoagulant proteins regulate the coagulation cascade
fibrinolysis is activated after coagulation
procoagulant and anticoagulation pathways are regulated @ multiple levels to maintain balance