Lecture 20: Hemostasis Flashcards
4 steps of hemostasis?
1) Vascular spasm
2) Formation of a platelet plug
3) Formation of a blood clot
4) Repair of damage
What is hemostasis?
Steps taken by the body to limit blood loss
*Not confined only to the production of a blood clot!
Primary cause of vascular spasm?
Myogenic response to injury, no neurons or reflexes involved
Platelets release what that contributes to the vascular spasm?
Platelet factors
- Serotonin
- Thromboxane A2
*Both vasoconstrictors
What is a small component/contributor to vascular spasm, but is not necessary?
Neural reflex initiated by mechanical injury and pain
Purpose of vascular spasm?
Reduce blood loss by slowing/stopping blood flow out
Damage to vessel wall exposes?
Collagen
What will bind to exposed collagen?
Platelets
Step I of formation of platelet plug involves, its function?
Von Willebrand Factor (plasma protein) serves as anchor binding collagen and platelet (receptor)
What occurs during step II of formation of platelet plug?
Binding of platelet receptor (integrin) to collagen
What 2 things occur during activation of platelet bound to its receptor which has bound collagen?
1) Platelets swell
2) Extend podocytes
After the platelet swells what occurs?
Contraction
What does the platelet release after contraction?
Granules
What is found within granules that cause platelets to stick to vessel wall and eachother?
ADP and thromboxane A2
Platelet plug will stop what kind of bleeding?
Small breaks - nose, skin
3 major steps of clot formation?
1) Activation of prothrombin activator (Xa)
2) Activation of thrombin
3) Creation of fibrin from fibrinogen
What is clot retraction and function?
- Get rid of excess fluid
- Solidify clot
What is required for clot retraction?
Platelets
Platelets express what for clot retraction, function?
Express Fibrin receptor, binds fibrin polymer together
What pulls the fibrin together?
Platelets contain actin and myosin, which causes a contraction
What do platelets secret for repair of damage?
Platelet-derived Growth Factor
What does platelet-derived growth factor do?
Stimulates fibroblasts to grow into area
Fibroblasts differentiate into?
Smooth muscle to close hole
Where is plasminogen made?
Liver
How is plasminogen activated?
Tissue plasminogen activator (tPA)
Where does tPA come from?
Damaged tissue
Activation of tPA is inhibited by?
tPA inhibitor which is always circulating in the blood
What is found on an intact endothelial cell and is necessary for steps to produce plasmin?
Protein receptor called thrombomodulin
Binding of thrombin to thrombomodulin causes?
Activation of Protein C, which is able to inactivate the t-PA inhibitor
Inactivation of the t-PA inhibitor allows for?
Plasminogen (inactive) —-> Plasmin (active)
Function of plasmin?
Lysis of fibrin (breaks down clot)
What part of blood vessel prevents platelet from rupturing?
Smooth surface
Function of glycocalyx?
Repels platelets
Thrombomodulin changes activity of?
Thrombin
How does fibrin limit clotting?
“Binds” thrombin and prevents it from working
How does prostacyclin (PGI2) limit clotting?
Causes vasodilation and limits platelet aggregation
How does Antithrombin III limit clotting?
When thrombin binds to it, works as an anticoagulant?
Where is heparin derived from and how does it limit clotting?
Mast cells; increases antithrombin efficacy
How does ProteinC limit clotting?
When activated, inactivates factors V and VII, which inhibits further fibrin creation
Leidan mutation?
Protein C is unable to inactivate factor V
Leidan mutation commonly seen in and becomes a problem when?
Usually women who will have multiple miscarriages