L13 - blood formation & clotting

Question 1

what do pluripotent stem cells give rise to?

Answer 1

haematopoietic progenitors (precursors) of the blood cells

Question 2

what are thrombopoietin and erythropoietin?

Answer 2

haematopoietic growth factors (cytokines)

Question 3

what happens if a blood vessel becomes damaged?

Answer 3

blood can leak out into surrounding tissues (haematoma)

Question 4

what is endothelium?

Answer 4

surrounds blood vessels

Question 5

what is epithelium?

Answer 5

outside tissues

Question 6

what is a bruise?

Answer 6

blood leaked out of capillary

Question 7

would blood loss be greatest in artery, vein or capillary?

Answer 7

artery - higher blood pressure

Question 8

why is raising a damaged limb where a blood vessel has been cut beneficial?

Answer 8

lowers blood pressure and blood flow, so less blood loss

Question 9

what is the immediate response of a damaged vessel?

Answer 9

to constrict. 2 endothelial surfaces can temporarily glue together to stop blood flow, gives time for vessel to wound and form a clot

Question 10

what happens if vessels glue for too long?

Answer 10

starving other downstream tissues from oxygen

Question 11

another name for blood clotting?

Answer 11

haemostasis

Question 12

what can dysfunction in blood clotting lead to?

Answer 12

haemophilia

Question 13

2 stages of blood clotting

Answer 13

1. primary haemostasis: platelet plug formation
2. secondary haemostasis: weak platelet plug is transformed into clot by fibrin network

Question 14

describe primary haemostasis: adhesion

Answer 14

1. damage of endothelial cells exposes the subendothelial layers which consist of connective tissues and collagen fibres
2. collagen activates platelets via von Willebrand factor (vWF)
3. platelets adhere to the collagen
4. platelet binding causes release of ADP + seratonin (5HT) from secretory vesicles leading to platelet activation
5. then platelet aggregation occurs

Question 15

platelet activation (primary haemostasis)

Answer 15

1. seratonin and ADP released from granules
2. causes change in shape and surface protein expression

Question 16

platelet aggregation

Answer 16

platelets start to adhere to each other to form a plug. this causes synthesis of and release of thromboxane A2 (TxA2) from arachidonic acid which enhances activation + aggregation

Question 17

what happens once plug is made?

Answer 17

1. plug is stabilised by fibrinogen bridges
2. actin and myosin cause contraction of plug to bind it tightly together
3. smooth muscle is vessels also contracts via TxA2 + chemicals from platelet granules

Question 18

how does the body restrict the platelet plug from spreading?

Answer 18

1. healthy endothelial cells synthesise prostacyclin (prostaglandin, PG12) and nitric oxide which are both potent inhibitors of platelet activation
2. PG12 also secreted by thromboxane/ arachidonic acids

Question 19

what is nitric oxide?

Answer 19

vasodilator

Question 20

what is a clot/thrombus?

Answer 20

transformation of blood into a gel which is made up of fibrinogen polymers

Question 21

where does clotting occur?

Answer 21

around the platelet plug

Question 22

what does vessel damage activate?

Answer 22

cascade of enzymes that result in activation of enzyme THROMBIN

Question 23

what does thrombin do?

Answer 23

cleaves protein fibrinogen into fibrin molecules that bind together to form a loose meshwork

Question 24

general principles of blood clotting

Answer 24

• vessel is damaged + exposes subendothelial layers consisting of collagen which binds to platelets
• activation of prothrombin to thrombin which cleaves + activates fibrinogen to fibrin
• thrombin has positive feedback mechanism so it leads to more thrombin production

Question 25

clotting cascade in extrinsic pathway (outside the blood vessels - the usual one)

Answer 25

- initiated by tissue factor (located on collagen) - this initates factor 7 and 10 - this is normal way to activate clotting mechanism - generates small amounts of thrombin - thrombin has positive feedback mechanism

Question 26

intrinsic pathway (everything in blood)

Answer 26

- initiated by factor 12 by contact from collagen - factor 8 is a cofactor

Question 27

what causes haemophilia?

Answer 27

not having factor 8

Question 28

role of liver in clotting

Answer 28

- many clotting factors made in liver - liver makes bile salts which absorb vitamin K needed for production of prothrombin - this is why ppl with liver disease often having bleeding problems

Question 29

describe thrombin

Answer 29

- enzyme - initiated in instrinsic pathway - enhances prothrombin conversion to thrombin by activating factor 5 - activates platelets - ligand so binds to receptor called protease activated receptors (PARs) + activates it

Question 30

anti clotting mechanisms

Answer 30

1. PGI2 and NO are anticoagulants as they inhibit platelet activation 2. endothelial cell production of tissue factor inhibitor 3. thrombin binds to endothelial cell receptor thrombomodulin to activate protein C which inactivates FV and FVIII 4. antithrombin III synergies with heparin to inactivate thrombin + other clotting factors

Question 31

how is the clot dissolved?

Answer 31

fibrinolytics. - activate plasminogen which can digest fibrin back to soluble fibrin fragments + dissolve the clot