Blood Production & Clotting part 1

Question 1

1. The Production of Blood Cells

Answer 1

Bone marrow of adult weighs as much as liver

Pluripotent stem cells give rise to progenitors (precursors) of any of the blood cells

Multiple proteins are responsible for the differentiation of precursor cells into mature blood cells

Question 2

Thrombopoietin (TPO) and erythropoietin (EPO) are hematopoietic growth factors (sometimes termed cytokines)

Answer 2

Thrombopoietin stimulates the production of platelets from megakaryocytes

Erythopoietin stimulates the production of erythrocytes

Other proteins (cytokines) are involved in blood cell production e.g. interleukins

Question 3

Blood clotting

Answer 3

Essential part of the healthy body
Dysfunction leads to bleeding disorders e.g. hemophilia
Clotting can be broken down into 2 phases:
Primary hemostasis: Platelet Plug formation
Secondary hemostasis: Transform and stabilize the weak platelet plug into a clot by a fibrin network

Hemotoma: accumulation of blood in tissues

Question 4

Platelet Plug Formation: Adhesion

Answer 4

Endothelial Cells coat the inside of blood vessels and in direct contact with blood
Damage of endothelial cells exposes the subendothelial proteins formed by connective tissues collagen fibres
Platelets adhere to these collagen fibres via an intermediate protein called von Willebrand factor (vWF)

Question 5

Platelet Activation and Secretion step

Answer 5

Platelets bind to the sub-endothelial layer and become activated
Activated platelets release the contents of secretory vesicles
Secretory vesicles (electron dense granules) contain the signalling molecules adenosine diphosphate (ADP) and serotonin that activated nearby platelets
Also generate thromboxane A2, a member of the eicosanoid family, from arachadonic acid
Platelets change shape and stick together (aggregate)

Question 6

Platelet Plug Formation

Answer 6

Adhesion of platelets to damaged surface
Platelet activation, platelet Aggregation, platelet plug formation
Platelets contain high levels actin/myosin, a cytoskeleton that contract in activated to platelets to enhance plug formation.
Smooth muscle in the blood vessel wall also contracts and decreases blood flow to the site of damage

Question 7

What stops the platelet plug spreading beyond the site of injury?

Answer 7

Healthy endothelial cells synthesize Prostacyclin (prostaglandin I2, PGI2) and Nitric oxide – both are potent inhibitors of platelet activation.

Question 8

Clot Formation

Answer 8

A clot is the transformation of blood into a gel

Clotting occurs around the platelet plug

Vessel damage activates a cascade of enzymes that result in the activation of an enzyme called Thrombin

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

Prothrombinase complex forms on the surface of the activated platelet and leads to activation of prothrombin

Prothrombin is cleaved into active thrombin

Thrombin is a protease enzyme that cleaves proteins

Thrombin cleaves fibrinogen to form fibrin

Question 9

Thrombin

Answer 9

Thrombin is an enzyme

It recruits the intrinsic pathways, enhances the prothrombin conversion to thrombin by activating factor V and also activates platelets

Platelets express a receptor called the ‘Protease activated receptor’ PAR