physiological thrombosis

Question 1

define haemostasis

Answer 1

stopping you bleeding (platelet and clotting factor)

Question 2

normal artery structure

Answer 2

• Endothelial cells line the lumen, the lining is made up from several endothelial cells (anticoagulant surface to prevent thrombosis)
  
  • Endothelial cells make basal lamina to sit on (usually made from connective tissue proteins)
  • Around the BL are smooth muscle cells
    Around smooth muscle cells are interstitial collagen fibres - small, thin, rope-like fibres that mesh together

Question 3

what is inside the lumen of a blood vessel

Answer 3

• The lumen contains RBCs (5 micrometres across) and WBCs(white in colour), as well as platelets (also white in colour, very small) and plasma (consists of water and numerous proteins and other molecules)
  ○ Platelets aren’t normally exposed to interstitial collagen fibres around the vessel
  Plasma contains proteins, clotting factors and other molecules (e.g. albumin is the most abundant plasma protein)

Question 4

where are most clotting factors produced

Answer 4

liver

Question 5

clotting factors

Answer 5

• Many clotting factors are named with roman numerals
• They are an amplification system, resulting in thrombin production
  Thrombin in turn converts soluble fibrinogen into insoluble fibrin which produces a mesh of strands

Question 6

the clotting cascade is an …

Answer 6

amplification system - many more molecules of fibrin are produced compared to (for instance) TF

Question 7

what are the 3 steps that lead to the clotting cascade beginning

Answer 7

1. INITIAL DAMAGE (anything that alters blood vessel structure) - one obvious way is trauma, trauma leads to:
2. Exposure of interstitial collagens (collagens in connective tissue between structures)
3. Exposure of TF molecule

Question 8

trauma results in …

Answer 8

defects in vessel walls
blood leaks out
plasma comes into contact with interstitial collagen fibres
clotting factors are activated

Question 9

what happens when plasma comes into contact with interstitial fibres

Answer 9

• TF is also released from smooth muscle cells (TF molecule is present on muscle cells - and other cells)
• Trauma exposes and released TF
  TF can now bind a particular clotting factor and initiate the clotting cascade in the area

Question 10

many clotting factors are …

Answer 10

serine proteases

cleave other clotting factors to form the active molecule

Question 11

prothrombin is produced from

Answer 11

thrombin

Question 12

thrombin converts

Answer 12

soluble fibrinogen to insoluble fibrin

Question 13

what is the endpoint of the clotting cascade

Answer 13

production of insoluble fibrin strands that form a network

Question 14

platelets are produced in the

Answer 14

bone marrow from megakaryocytes

Question 15

what are megakaryocytes

Answer 15

large cells with many nu

Question 16

how are platelets formed from megakaryocytes

Answer 16

they undergo nu division but not cell division

platelets bud off as fragments from cytoplasmic extensions

Question 17

how are platelets exposed to interstitial collagen

Answer 17

trauma to the vessels

Question 18

define coagulation

Answer 18

solidification of blood

Question 19

what are the 2 types of coagulation

Answer 19

thrombus formation

clot formation

Question 20

thrombus formation

Answer 20

occurs in flowing blood
A pure thrombus is pale cream coloured; consists of platelets and a mesh like network of fibrin strands.
Platelets have molecules on their surfaces which allow adherence to interstitial collagen; even when the blood is flowing past them - the clotting cascade deposits factor VIII which enhances this further

Question 21

clot formation

Answer 21

blood leaks out of the vessel and becomes stationary or stagnant
○ Within the stagnant blood, sitting next to the interstitial collagen, the clotting cascade is activated
A clot consists of a network of fibrin strands and RBC meaning it is red in colour

Question 22

haemostasis process

Answer 22

• A cut is made in the skin, trauma to skin disrupts one side of the vessel
• Blood, including RBC, leaks out
The clotting system is activated by interstitial collagen and by the stagnant blood, forming a clot - blood can extend to the surface and form the clot
• This may not work perfectly and the wound may continue to bleed
• The vessel vasoconstricts to decrease blood loss
A platelet and fibrin thrombus forms to bridge the gap between the ends of the vessel adjacent to flowing blood
The skin has now stopped bleeding and haemostasis has been achieved

Question 23

granulation tissue

Answer 23

New vessels can grow into the area of the wound - these new vessels are called granulation tissue. The capillaries that grow in can oxygenate the area of the wound and keep it alive

Question 24

plasminogen and thrombus removal

Answer 24

Blood protein plasminogen converts to plasmin and plasmin cuts up fibrin into smaller fragments (way of removing fibrin in both clots and thrombi). In a thrombus this is sometimes called thrombolysis

Question 25

fibrinolytic system

Answer 25

removes the fibrin and stops thrombi from propagating, allowing blood flow to continue

Question 26

fibrinolytic system depends on

Answer 26

• Plasma protein called plasminogen being converted to plasmin
• Plasmin cuts up fibrin in a thrombus into fibrin degradation products
- Fibrinolytic system is normally in balance with clotting system, plasmin generation at the site of injury limits the extent of the evolving thrombus

Question 27

3 main causes of thrombosis

Answer 27

• Changes in the intimal surface of a vessel
• Changes in the pattern of blood flow
Changes in the blood constituents