Ischaemic cascade, blood clotting and injury

Question 1

blood clotting

Answer 1

coagulation

Question 2

ischaemia

Answer 2

restriction in blood supply

Question 3

hypoxia

Answer 3

low O2

Question 4

ROS

Answer 4

reactive oxygen species

Question 5

reperfusion

Answer 5

return of blood supply

Question 6

atherosclerosis

Answer 6

arterial thickening and hardening

Question 7

atheroma

Answer 7

accumulation of plaques

Question 8

stenosis

Answer 8

narrowing of blood vessels

Question 9

atheromatous plaque formation : simple

Answer 9

1) endothelia dysfunction -fatty streak
2) stable plaque formation
3) T-cell activation
4) plaque rupture and blood coagulation

Question 10

two types of artery

Answer 10

elastic artery

muscular artery

Question 11

lumen is much wider in

Answer 11

elastic artery

Question 12

tunica media (muscle)

Answer 12

is much wider in muscular artery

Question 13

atheromas are common at

Answer 13

aortic branching (aortic burification)

Question 14

risk factors for atheroma formation

Answer 14

ROS, hyperglycaemia, hypercholesterolaemia, hypertension

Question 15

stage 1 of atheroma formations

Answer 15

Endothelial dysfunction

• monocytes adhere to endothelium via VCAM-1 and infiltrate
• monocytes become macrophages n intimate
• macrophages oxidate LDL - OxLDL
• macrophage becomes foam cells

Question 16

foam cells

Answer 16

fatty streak

Question 17

stage 2 of atheroma formation

Answer 17

Formation of stable plaque

• many foam cells in intimate
• vascular smooth muscle cells migrate from tunica media, proliferate and act like mofibroblasts to produce collagen
• fibrous cap containing cppllagen fibres form

Question 18

stage 3 of atheroma formation

Answer 18

T-cell activation

• Th1 and Th2 recruited and activated
• MMps produced by foam cells and pro inflammatory cytokines begin to breakdown the fibrous cap

Question 19

MMPs

Answer 19

metric metalloproteinases

Question 20

stage 4 of atheroma formation

Answer 20

Ulceration and thrombus formation

• MMPs and cytokines break down fibrous cap
• tissue factor released from endothelium
• start of extrinsic coagulation cascade
• TF binds to factor V11a (serine protease) and activates (coagulation factors are inactive zymogens)
• catalyses conversion of factor X- factor Xa
• initiates common pathway
• blood clotting prothrombin- thrombin –> fibrinogen –> fibrin
• blood vessels tenses, occlusion or thrombi release

Question 21

basic blood clotting .

Answer 21

common pathway activates prothrombin- activates thrombin.

Thrombin converts fibrinogen to fibrin–> platelet cross bridge- clots

Question 22

two clotting cascade

Answer 22

intrinsic and extrinsic

Question 23

both the intrinsic and extrinsic lead to

Answer 23

the common pathway

Question 24

intrinsic

Answer 24

surface contact

- more important for amplification of cascade

Question 25

extrinsic

Answer 25

trauma | -faster to produce factor X

Question 26

Intrinsic cascade (slower)

Answer 26

Contact phase-blood and negative charged surfaces come to contact Hamgen factor (XII) binds to sub endothelial surface, Binding of HK & PK activates XII. Activates prekallikrein, kaillikren can also cleave factor XII Further cascade of proteolytic conversions: inactive clotting factors -> active forms

Question 27

Extrinsic cascade

Answer 27

Factor III binds to VII, activating it to form a complex | This then activates factor X

Question 28

fibrinolysis is mediated by

Answer 28

Protein C is involved in fibrinolysis - a process to break down the fibrin clot after haemostasis has been restored.

Question 29

if lacking in vitamin K

Answer 29

Deficiency in vitamin K can result in excessive bleeding due to an increased time for the clotting cascade to occur. Vitamin K is important co-factor for the synthesis of factors II, VII, IX, and X.

Question 30

if lacking in vitamin K

Answer 30

Deficiency in vitamin K can result in excessive bleeding due to an increased time for the clotting cascade to occur. Vitamin K is important co-factor for the synthesis of factors II, VII, IX, and X.

Question 31

more specific intrinsic

Answer 31

1) damaged surface 2) calcium and PL activated XII --> XIIa (12) 3) XIIa activates XI to XIa (11) 4) XIa activates IX (9) to IXa 5) which activates VIIIa (8) 6) VIIIa activates factor X

Question 32

more specific extrinsic

Answer 32

1) trauma 2) converts VII (7) to VIIa 3) tissue factors released 4) X converted to Xa

Question 33

common pathway

Answer 33

1) X to Xa 2) Xa causes prothrombin to become thrombin (11a) 3) thrombin activates fibrinogen to become fibbing (Ia) 4) paltletes clot

Question 34

common pathway

Answer 34

1) X to Xa 2) Xa causes prothrombin to become thrombin (11a) 3) thrombin activates fibrinogen to become fibbing (Ia) 4) platelets clot

Question 35

excitoxiticity is caused by

Answer 35

increase in intracellular Ca2_ and increase in ROS --> causing neuronal death

Question 36

low oxygen mean

Answer 36

reduced ATP and H+ gradient not maintained- ROS generation and calcium release

Question 37

increased calcium mean more vesicle transport of Glu

Answer 37

therefore increase in calcium intracellularly

Question 38

high conc of calcium activated

Answer 38

- nNOS - increase in ROS - calpains and lipase activates - vesicles transport increases glutamate release - activates RyR- open channels on ER- increase in intracellular calcium