L13 - Blood formation and clotting

Question 1

Where is there a high / low blood pressure in terms of blood vessels?

Answer 1

High blood pressure - arteries
Low blood pressure - veins

Question 2

What happens when blood vessels become damaged?

Answer 2

Blood can leak out into surrounding tissues
- (haematoma (vs bruise))

Question 3

What is the bodies immediate response to a damages vessel?

Answer 3

To constrict
- opposing endothelial surfaces can temporarily glue together

Question 4

What can blood clotting dysfunction lead to?

Answer 4

Bleeding disorders

Question 5

What 2 phases can blood clotting be broken down into?

Answer 5

• primary haemostasis: platelet plug formation
• secondary haemostasis: blood clotting mech to transform and stabilise weak platelet plug into clot by fibrin network

Question 6

What can damage to endothelial cells expose?

Answer 6

The subendothelial layers consisting of connective collages fibres

Question 7

How do platelets adhere to these collagen fibres via?

Answer 7

Intermediate protein called von Willebrand factor (vWF)

Question 8

What does platelet binding cause?

Answer 8

Release of ADP and serotonin from their secretory vesicles
= platelet activation

Question 9

What is platelet activation?

Answer 9

Release of ADP and serotonin from electron dense granules
- causes change in shape and surface protein expression

Question 10

What is platelet aggregation?

Answer 10

When platelets adhere to each other to form a plug

Question 11

What enhances activation and aggregation?

Answer 11

Synthesis and release of thromboxane A2

Question 12

What is the plub stabilised by?

Answer 12

Fibrinogen bridges
- receptors on platelet surface become exposed during activation

Question 13

What causes contraction of plug?

Answer 13

Actin and myosin
- binding it tightly together

Smoothe muscle in vessels
- mediated by TxA2 + other chems from platelet granules

Question 14

What do healthy endothelial cells synthesise? (For restriction of platelet plug spreading)

Answer 14

• prostacyclin (prostaglandin I2, PGI2)
• Nitric oxide (vasodilator

Both potent inhibitors of platelet activation

Question 15

What is a clot?

Answer 15

(Thrombus)
The transformation of blood into a gel consisting of fibrin polymers
- occurs arounf the platelet plug

Question 16

What do damaged vessels activate?

Answer 16

Cascade of enzymes that result in the activation of an enzyme called thrombin

Question 17

What does thrombin cleave?

Answer 17

Protein called fibrinogen into fibrin molcules that bind together to form a loose meshwork

Question 18

What are the steps that take place after a blood vessel is damaged?

Answer 18

• damaged blood vessel
• formation of platelet plug
• development of clot

Question 19

What happens at each step of blood clotting?

Answer 19

Inactive plasma protein is cleaved to become an active enzyme or cofactor activating the next step of the pathway

Question 20

What is a key step in blood clotting?

Answer 20

Activation of prothrombin to thrombin which then cleaves and activated fibrinogen to fibrin

Question 21

What happens once thrombin activates?

Answer 21

Has a positive feedback on other factors which lead to more thrombin activation

Question 22

Where is the extrinsic pathway of the clotting cascade initiated

Answer 22

by tissue factor located on the outer leaflet of the plasma membrane of cells found in sub endothelial tissue

Question 23

What does the extrinsic pathway activate?

Answer 23

FVII and FX

Question 24

What is the normal way to activate clotting in the body?

Answer 24

Extrinsic pathway via tissue
- generates small amounts of thrombin
- feeds back to intrinsic pathway to activate components and generate more

Question 25

Where is everything require to activate intrinsic cascade found?

Answer 25

In the blood

Question 26

What does intrinsic pathway start with? And what does it acts as?

Answer 26

Activation of FXII by contact with collagen
- essential cofactor

Question 27

What is intrinsic pathway triggered like in vivo?

Answer 27

Sequentially after extrinsic pathway

Question 28

What is the role of the liver?

Answer 28

The site of many clotting factors
- produces bile salts require for absorption of vit K for the production of prothrombin

Question 29

What do patients with liver disease often have?

Answer 29

Bleeding problems

Question 30

What is thrombin?

Answer 30

Enzyme
- recruits the intrinsic pathway, enhances prothrombin conversion to thrombin by activating factor V and platelets

Question 31

What do platelets express?

Answer 31

A receptor called the Protease activated receptor (PAR)

Question 32

What are the 4 anti-clotting mechanisms?

Answer 32

1. PGI2, NO, endogenous anti-coagulants (inhibition of platelet activation)
2. Endothelial cell production of tissue factor inhibitor
3. Thrombin binds to endothelial cell receptor thrombomodulin (activates protein C = inactivates FV and VII)
4. Plasma protein antithrombin II (inactivate thrombin, other clotting factors

Question 33

How is the clot dissolved?

Answer 33

Fibrinolytics
- tissue plasminogen activator (t-PA) released by EC
- binds to fibirin clot and is stabilised to activate plasmin

Question 34

Examples of clotting disorders and treatments

Answer 34

Damage to endothelium: myocardial infacrtion, atherosclerosis
Clots: deep vein thrombosis, pulmonary embolism
Clotting disorders: haemophilia

Aspirin, heparin, warfarin, recombinant t-PA