Hemostasis& the coagulation cascade

Question 1

2 pathways that damage can stimulate

Answer 1

1) Intrinsic
2) Extrinsic

But two systems are almost always working concurrently

Question 2

What is special about endothelial lining

Answer 2

Only surface that blood can flow through without clotting (covered with anticoagulant proteins that prevent initiation of anticoagulant system)

Question 3

How platelets in blood get activated + formation of plug

Answer 3

1. Damaged endothelial cell
2. Injured cell secretes Von Willabran factor
3. This factor activates platelets and make them sticky
4. Platelets form a plug (proteins on surface of platelets are actively binding with fibrinogen so get linkage between platelets via fibrinogen)

Question 4

Fibrinogen (+ state in platelet plug)

Answer 4

A inactive clotting protein in the body
Will be activated later on to become fibrin
When binding platelets together still in fibrinogen form (only working because proteins on platelet surface bind with fibrinogen)

Question 5

Initiation of the intrinsic pathway (all the way to formation of fibrin)

Answer 5

1. Significant injury exposes blood to basement membrane below endothelial cells (free ends of collagen proteins exposed to lumen of blood vessel)
   2) Collagen binds with proteins in blood stream - coagulation Factor XII (hageman factor) and causes it to change conformation
   3) Hageman changes from factor XII to factor XIIa –> has active binding site.
   4) Factor XII a binds with factor XI and causes XI to change to its active form XIa
   5) XIa activates IX –> IXa
   6) IXa activates X –> Xa
   7) Xa activates Prothrombin (PT) –> thrombin
   8) Thrombin causes fibrinogen to turn into fibrin

Question 6

Function of fibrin

Answer 6

• fibrin monomers come together to form fibrin polymer

- fibrin polymer cross-linked by FXIIIa –> to create fibrin mesh

Question 7

Nature of many factors in clotting cascade

Answer 7

Alot of these factors are proteases –> cleaving proteins such that when cleaved produces an active form with receptors on it that are now active
-prior to this receptors had been bound in matrix of large protein

Question 8

Why so many steps??

Answer 8

• system of amplification

- each step amplifys the prior step by a significant facctor

Question 9

Extrinsic pathway

Answer 9

1) Tissue factor (TF, aka factor III) -in inactive form
2) TF activated (3 sources)
3) active TF (IIIa) causes VII –> VIIa
4) VIIa causes X –> Xa (common step with intrinsic pathway)
5) After this is just the intrinsic pathway to produce fibrin = common pathway

Question 10

3 places TF is found

Answer 10

1) inside cells
2) on some cell membranes
3) in extracellular fluid

Question 11

What can activate TF

Answer 11

1) Inflammatory cytokines
2) Cell injury
3) Vessel injury/disruption (blood in the tissue)

Question 12

Nature of thrombin

Answer 12

• protease
• activates fibrinogen (long strand with globulin at the end) by cleaving fibrinogen into two -what is exposed is receptor where fibrin can bind to itself
• end up with long strands of fibrin (fibrin polymers)
• lots of fibrin polymers are cross linked by XIIIa (binds fibrin polymers together)

Question 13

Strength of fibrin polymers

Answer 13

-as strong as collagen strands