Disorders of arteries I

Question 1

Where do arterial thrombotic disorders originate in?

Answer 1

The atherosclerotic plaque

Question 2

How does the plaque affect the lumen?

Answer 2

Narrows the lumen of the artery & triggers thrombus formation -> occlusion

Question 3

What can the plaque lead to?

Answer 3

Myocardial infarction
stroke
peripheral vascular disease

Question 4

What are 4 main risk factors of atherosclerosis?

Answer 4

Age
Male sex
Diabetes
Hypercolesterolaemia

Question 5

What are common heart attack symptoms?

Answer 5

Chest pain
Fatigue
Heartburn
Nausea

Question 6

Why does thrombosis in human coronary arteries causes infarction?

Answer 6

As they are functional end arteries

Question 7

Where does thrombosis oftern occur?

Answer 7

Branch of left coronary artery

Question 8

What is the main cause of MI?

Answer 8

Local atherosclerosis of coronary arteries

Question 9

What are 2 methods to achieve reperfusion?

Answer 9

Fibrinolytic therapy (recombinant tPA)
Mechanical/surgical approaches (implant stent)

Question 10

What are 3 antiplatelet therapies?

Answer 10

Aspirin
Clopidogrel
Integrin alpha IIb beta 3 antagonists

Question 11

What is the MoA of aspirin?

Answer 11

Irreversible inhibition of COX-1 at a single aa -> blocks thromboxane A2 synthesis

Question 12

What is the MoA of clopidogrel?

Answer 12

inhibit ADP binding

Question 13

What is the MoA of Integrin alpha IIb beta 3 antagonists?

Answer 13

block fibrinogen binding & aggregation eg. monoclonal antibody abciximab

Question 14

What are 3 anticoagulant therapies for MI?

Answer 14

Heparin
Direct thrombin inhibitors
Direct FXa inhibitors

Question 15

What is an example of dual pathway inhibition?

Answer 15

Combination of FXa inhibitors with aspirin or clopidogrel

Question 16

What are the 3 layers of the normal arterial wall?

Answer 16

Tunica intima
Tunica media
Adventitia

Question 17

What does the tunica intima contain?

Answer 17

Endothelial cells & SMCs

Question 18

What does the tunica media contain?

Answer 18

SMCs embedded in a complex ECM

Question 19

What does the adventitia contain?

Answer 19

Fibroblasts, mast cells, nerve endings & microvessels

Question 20

What are characteristics of the initiation phase in atherosclerotic plaques?

Answer 20

Changes in properties of ECs -> expression of adhesion molecules -> increased permeability -> monocytes adhere & transmigrate -> macrophages -> lipid uptake -> foam cells

Question 21

What 2 cells contribute to plaque developement?

Answer 21

Lymphocytes & activated platelets

Question 22

What is familial hypercholesterolaemia caused by?

Answer 22

Defect in LDL receptor -> reduced LDL uptake -> elevated plasma LDL & cholesterol

Question 23

What are LDL and cholesterol taken up by?

Answer 23

Macrophages via scavenger receptors leading to foam cell formation

Question 24

What is FH associated with in childhood?

Answer 24

MI

Question 25

What are the stages in lesion progression in plaque development?

Answer 25

SMCs migrate from media to intima -> SMCs proliferate -> ECM increased -> fibrous cap formation -> extracellular lipid from dead cells accumulate -> cholesterol crystals form

Question 26

What does the disruption of the plaque lead to?

Answer 26

Thrombosis

Question 27

What factor do plaque cells express?

Answer 27

Tissue factor