Disorders of arteries I Flashcards
Where do arterial thrombotic disorders originate in?
The atherosclerotic plaque
How does the plaque affect the lumen?
Narrows the lumen of the artery & triggers thrombus formation -> occlusion
What can the plaque lead to?
Myocardial infarction
stroke
peripheral vascular disease
What are 4 main risk factors of atherosclerosis?
Age
Male sex
Diabetes
Hypercolesterolaemia
What are common heart attack symptoms?
Chest pain
Fatigue
Heartburn
Nausea
Why does thrombosis in human coronary arteries causes infarction?
As they are functional end arteries
Where does thrombosis oftern occur?
Branch of left coronary artery
What is the main cause of MI?
Local atherosclerosis of coronary arteries
What are 2 methods to achieve reperfusion?
Fibrinolytic therapy (recombinant tPA)
Mechanical/surgical approaches (implant stent)
What are 3 antiplatelet therapies?
Aspirin
Clopidogrel
Integrin alpha IIb beta 3 antagonists
What is the MoA of aspirin?
Irreversible inhibition of COX-1 at a single aa -> blocks thromboxane A2 synthesis
What is the MoA of clopidogrel?
inhibit ADP binding
What is the MoA of Integrin alpha IIb beta 3 antagonists?
block fibrinogen binding & aggregation eg. monoclonal antibody abciximab
What are 3 anticoagulant therapies for MI?
Heparin
Direct thrombin inhibitors
Direct FXa inhibitors
What is an example of dual pathway inhibition?
Combination of FXa inhibitors with aspirin or clopidogrel
What are the 3 layers of the normal arterial wall?
Tunica intima
Tunica media
Adventitia
What does the tunica intima contain?
Endothelial cells & SMCs
What does the tunica media contain?
SMCs embedded in a complex ECM
What does the adventitia contain?
Fibroblasts, mast cells, nerve endings & microvessels
What are characteristics of the initiation phase in atherosclerotic plaques?
Changes in properties of ECs -> expression of adhesion molecules -> increased permeability -> monocytes adhere & transmigrate -> macrophages -> lipid uptake -> foam cells
What 2 cells contribute to plaque developement?
Lymphocytes & activated platelets
What is familial hypercholesterolaemia caused by?
Defect in LDL receptor -> reduced LDL uptake -> elevated plasma LDL & cholesterol
What are LDL and cholesterol taken up by?
Macrophages via scavenger receptors leading to foam cell formation
What is FH associated with in childhood?
MI
What are the stages in lesion progression in plaque development?
SMCs migrate from media to intima -> SMCs proliferate -> ECM increased -> fibrous cap formation -> extracellular lipid from dead cells accumulate -> cholesterol crystals form
What does the disruption of the plaque lead to?
Thrombosis
What factor do plaque cells express?
Tissue factor
