Physiology + pathophysiology of clotting

Question 1

What is the blood?

Answer 1

A complex fluid of cellular components suspended in water ECF (plasma)

Question 2

What are 3 components of blood?

Answer 2

-erythrocytes - red blood cells
-leukocytes - white blood cells
-platelets - involved in clotting

Question 3

What is plasma?

Answer 3

A pale, watery solution of electrolytes, plasma, proteins, carbohydrates + lipids

Question 4

What are the principle proteins in plasma?

Answer 4

-albumin
-fibrinogen
-immunoglobulins
-other plasma proteins in blood coagulation cascades

Question 5

What are erythrocytes?

Answer 5

-most abundant cell (haematocrit)
-mainly composed of haemoglobin

Question 6

What are the functions of erythrocytes?

Answer 6

-O2 carriage from lungs to systemic system
-CO2 carriage from tissues to lungs
-buffering of acids/bases

Question 7

Describe the feedback mechanism for platelets

Answer 7

-platelets have receptor for thrombopoietin (TPO)
-abundant platelets bind TPO
-megakaryocytes not generated
-platelets not made
-receptors don’t bind to TPO
-TPO stimulates megakaryocyte production
-platelets generated

Question 8

What is haemostasis?

Answer 8

The prevention of haemorrhage

Question 9

How is haemostasis achieved?

Answer 9

-vasoconstriction
-increased tissue pressure
-platelet plug - primary haemostasis
-clot formation - secondary haemostasis

Question 10

What do platelets contain?

Answer 10

-mitochondria
-lysosomes
-peroxisomes
-alpha granules (VWF, fibrinogen, clotting factor, platelet derived growth factor)
-dense-core granules

Question 11

What is the outer coat of platelets rich in?

Answer 11

Platelet receptors

Question 12

What are the steps of platelet plug formation?

Answer 12

1. platelet adhesion
2. platelet activation
3. platelet aggregation
4. blood clot formation

Question 13

Describe platelet adhesion

Answer 13

-a rapid temporary seal to prevent further blood loss
-plasma von Willebrand factor (VWF) binds to exposed collagen + platelet receptors
-binding of platelet receptors –> cascade of IC events –> activation

Question 14

What does damage to the endothelium expose?

Answer 14

Subendothelial collagen (most thrombogenic)

Question 15

Describe platelet activation

Answer 15

-secretion/exocytosis of dense and alpha granules
-secretion of platelet derived growth factor (PDGF)
-cytoskeletal changes
-expression of fibrinogen receptors

Question 16

Describe platelet aggregation

Answer 16

-platelet fibrinogen receptors bind to plasma fibrinogen
-forms molecular bridges between platelets (aggregation)
-eventually actin + myosin contract (more compact platelet plug)

Question 17

Describe blood clot formation

Answer 17

-slower, complex process involving cascade of clotting factors
-makes more permanent fibrin mesh

Question 18

What are the 2 pathways for clotting?

Answer 18

-intrinsic pathway (slower)
-extrinsic pathway

Question 19

When is the intrinsic pathway used for blood clotting?

Answer 19

Contact activation or surface damage

Question 20

When is the extrinsic pathway used for blood clotting?

Answer 20

Trauma or inflammation

Question 21

How is the intrinsic pathway for clotting initiated and describe the process

Answer 21

-initiated by factors in blood in contact with -ively charged membrane surface of activated platelets
-cascade of protease reactions
-end with activated factor Xa

Question 22

How is the intrinsic pathway for clotting initiated and describe the process

Answer 22

-injury to endothelium allows tissue factor in subendothelial cells to become activated when blood factor VII in contact
-results in activated factor Xa

Question 23

What is the common pathway from the 2 pathways for blood clotting?

Answer 23

-activated factor Xa
-enters common pathway to generate thrombin (enzyme) + produce stable fibrin

Question 24

What happens as a result of the promotion of anti-thrombotic state?

Answer 24

-normal endothelial cells maintain normal blood fluidity
-paracrine factors inhibit platelet adhesion + aggregation
-many anti-coagulant factors

Question 25

What is the promotion of pro-thrombotic state via?

Answer 25

-event of vascular damage
-hypoxia - expression of procoagulants

Question 26

What does normal blood flow lead to injury of?

Answer 26

Turbulent blood flow leads to endothelial injury

Question 27

What is turbulent flow caused by?

Answer 27

-local stenosis
-large radius
-high velocity

Question 28

What can thrombus lead to?

Answer 28

Pathological conditions