atherosclerosis and coagulation

Question 1

what is haemostasis

Answer 1

arrest of blood from damaged tissues

Question 2

what is thrombosis

Answer 2

pathological formation of a clot in vasculature in absence of bleeding

Question 3

how are atherosclerotic plaques formed

Answer 3

1. LDL accumulates on endothelium
2. endothelial cells release chemokines to attract immune cells
3. immune cells eat LDL and some cells
4. macrophages –> foam cells
5. migration and proliferation of smooth muscle
6. fibrous cap
7. smooth muscle cell death = break down - debris released

Question 4

how does coagulation occur

Answer 4

1. platelets attach to endothelium
2. platelets release fibrin and seal endothelium
3. fibrin network traps red blood cells
4. fibrin clot formation

Question 5

what are the two pathways of the coagulation cascade

Answer 5

intrinsic - all components present in blood
extrinsic - switched on in presence of tissue damage

Question 6

what is the key step in the coagulation cascade

Answer 6

10a cleaves prothrombin to thrombin
thrombin cleaves thrombinogen to fibrin

Question 7

what do thrombin/fibrinogen cause

Answer 7

platelet aggregation

Question 8

what does thrombin do

Answer 8

cleaves fibrinogen to fibrin
platelet aggregation
cell proliferation
regulates smooth muscle contraction

Question 9

what role does the liver play in coagulation

Answer 9

synthesises clotting factors
synthesises vitamin K

Question 10

what is vitamin K

Answer 10

coagulation vitamin
lipid soluble
required for synthesis of coagulation cascade proteins II, VII, IX, X

Question 11

which medicines can be used to inhibit the production of white thrombi

Answer 11

aspirin

Question 12

which medicines can be used to prevent the production of red thrombi

Answer 12

heparins and warfarin

Question 13

what is heparin

Answer 13

antiplatelet present in mast cells, that activates antithrombin III which inactivates thrombin and 10a

Question 14

what are the two types of heparin

Answer 14

unfractionated
low molecular weight

Question 15

what are unfractionated heparins

Answer 15

inhibit thrombin and 10a
only used in hospital - heavily monitored and unpredictable

Question 16

what are low molecular weight heparins

Answer 16

only inhibit 10a, more predictable so can be taken at home, binds less to endothelium, greater bioavilability

Question 17

pharmacokinetics of heparin

Answer 17

not orally absorbed
partially metabolised in the liver by heparinase to uroheparin
1/2 life of 40-90 mins

Question 18

what is warfarin

Answer 18

competitive vitamin K reductase inhibitor

Question 19

how does warfarin stop coagulation

Answer 19

stops production of vitamin K which is essential for the production of coagulation proteins

Question 20

pharmacokinetics of warfarin

Answer 20

lipophilic so absorbed via GIT, extensively plasma bound, CYP450 metabolised