L24. Thrombosis and Embolism Flashcards
What is normal haemostasis
Haemostasis is the physiological response of a blood vessel to injury. It helps to prevent blood loss by plugging leaks in injured vessels. It sets the vessels up for future repair.
What actively switches off haemostasis in non-damaged vessels to maintain the blood in a fluid state
Endothelial cells physically insulate tissues from blood.-> stops the switch to turn on when blood contacts CT proteins underneath endothelial cells.
- Produce enzymatic and chemical inhibitors of platelet activation: NO, prostacyclins
- Produce anti-thrombin on endothelial cells which binds and inactivates coagulation enzyme thrombin
What do endothelial cells do to turn on haemostasis in damaged vessels
- Produce endothelin which causes vasoconstriction-> allows repair to get started
- Loss of endothelial barrier which activates platelets and coagulation by contact
- Produce von Willebrand factor which helps platelets to stick together and prevents platelet adhesion to ECM proteins
- They produce tissue factor = thromboplastin which activates coagulation cascade
What do platelets (Made by megakaryocytes, week alive, chocolate chips) do to amplify haemostasis in damaged vessels
- Become activated by touching ECM proteins:
- Secrete Thromoxane A2, vasoactive amines and ADP
- Causes vasoconstriction and platelet aggregation
What does the clotting cascade (coagulation) do in haemostasis
- Using precursor proteins (inactivated) activated by cleaving, originally from tissue factor by endothelial cells (extrinsic pathway because tissue injury).
- Eventually activate thrombin which catalyses fibrinogen into fibrin monomers.
- These can then polymerise into fibrin strands which make a mesh with platelets to make a plug
- It can also activate platelets and turn on endothelial cells
What are the 7 stages of haemostasis
After initial injury brief period of arteriolar vasoconstriction – reflex & local factors
• Endothelial injury exposes highly thrombogenic sub-endothelial extra-cellular matrix –>
platelets adhere and activated
• Platelets release secretory granules -> aggregation to form platelet plug. This is know as
primary haemostasis
• Tissue factor – secreted by endothelium, activates the coagulation cascade to activate
thrombin – conversion soluble fibrinogen to insoluble fibrin -> local fibrin deposition
• Thrombin induces further platelet aggregation & granule release. This is know as secondary
haemostasis.
• Fibrin & platelet aggregates form solid permanent plug
• Counter-regulatory mechanisms activated to limit haemostatic plug to site of injury
What is thrombosis and a thrombus and what does it do
Pathological process where haemostasis is activated inappropriately. A thrombus can form in arteries or veins, made of fibrin, platelets, and entrapped WBC/RBC. If not dissolved it can propogate in veins, narrow or occlude vessels, organise and recanalisation or embolise
What are the Virchows triad = features that predispose thrombosis
-Changes in vessel wall due to endothelial cell injury or activation- eg inflammation, atherosclerosis, hypoxia.
- Abnormal blood flow: in arteries/cardiac chambers this is turbulence by narrowing/necrosis.
in veins it is stasis: compressed veins, right heart failure
-Hypercoagulability: change to blood constituents to favour clotting- acute phase response from liver
What is embolism
Intravascular mass (solid, liquid or gas) carried by blood flow from its point of origin to a distant site.
What is the effect of emboli from the from leg or pelvis veins
It will lodge in pulmonary artery (pulmonary embolus). This
causes pulmonary infarction (death of lung tissue due to inadequate blood supply), reduced
cardiac output, right heart failure and in the worst case death
What is the effect of emboli from the from the left side of the heart/ aorta
It will enter the systemic arterial system and may pass to the brain, spleen, kidney, gut, legs, etc
