Lecture 2-3 Flashcards
What is hemostasis?
The prevention of blood loss when a vessel is severed or ruptured
What are several mechanisms to limit blood loss in hemostasis?
- Vascular constriction
- Formation of a platelet plug
- Formation of a blood clot
- Clot retraction
- Removal of the clot (dissolved after repair)
Local factors released from damaged tissues causes platelets to release ___________ which contributes to ____________.
- Thromboxane A2 (TXA2), [synthesized from arachidonic acid formed by PLA2]
- Vasoconstriction, (nervous reflexes initiated principally by pain receptors also contributes)
What releases prostaglandin I2 (aka PGI2 or prostacyclin)?
Adjacent undamaged endothelium and platelets
What is the purpose of prostacyclin (aka PGI2 or prostaglandin)?
Inhibits platelet aggregation from spreading inappropriately and vasodilator.
What are thrombocytes?
platelets
Thrombocytes contain contractile proteins including _____, ______ and __________ which allow the platelets to rapidly release intracellular granules as necessary.
actin, myosin, and thrombosthenin
What do platelets contain that stimulates endothelial cells, vascular smooth muscle cells and fibroblasts to multiply and grow?
Prostaglandins, fibrin-stabilizing factor, and a growth factor. (Necessary for repair)
________ is on the external face of the platelet cell membrane which prevents them from adhering to the normal undamaged endothelial surface.
Glycoproteins
Platelets contain high concentration of __________ that are involved in blood clotting.
phospholipids
T or F? Platelets has a short half-life of 8-12 days and are removed by macrophages in the liver.
False, spleen
T or F? Platelets begin to swell and assume irregular shapes and radiating pseudopodia as they come in contact with damaged endothelium or exposed collagen.
True
During the formation of the platelet plug, the platelets become “sticky” and adhere to _____ and a protein called __________ from the blood.
damaged endothelium and/or collagen; von Willebrand factor
During the formation of the platelet plug, platelet secrete large amounts of _______ and ______ which activate nearby platelets which themselves adhere to the original ones in a positive feedback loop.
ADP; TXA2
How quickly can a blood clot form?
15-20 seconds if trauma is significant
1-2 minutes if minor.
After 3-6 minutes most reasonable holes are plugged by the clot.
(After 20-60 mins the clot retracts due to platelets and close the hole even more/more tightly)
What are the 2 options after a clot has formed?
- It can be invaded by fibroblasts (which form fibrous connective tissue throughout the clot)
- It can be dissolved
T or F? There are more than 50 substances found to affect or cause clotting.
True. (Anticoagulants dominate but when there is damage procoagulants dominate at the site)
What are the 3 simplified essential steps to clotting/coagulation?
- Trauma stimulating either of 2 enzyme cascades resulting in formation complex called Prothrombin activator.
- Conversion of Prothrombin into the active enzyme Thrombin.
- Conversion of soluble plasma protein Fibrinogen into insoluble Fibrin.
T or F? Fibrinogen enmesh platelets, RBC’s and plasma to form the clot.
False, Fibrin fibers not Fibrinogen.
What are the 2 different enzyme cascades?
Extrinsic pathway; initiated by trauma to the endothelium and surrounding/supporting tissues.
Intrinsic pathway; originates in the blood itself or exposure to collagen.
T or F? During the intrinsic pathway, platelets are activated and release phospholipids including Tissue factor III, and factor XII is activated
False, lipoprotein platelet factor III not tissue factor III
Intrinsic pathway: factor XIIa together with ____ ____ ___ ____, (accelerated by Prekallikrein), activates XI.
High Molecular Weight Kininogen
Intrinsic pathway could be blocked by deficiency in either factor VIII or platelets, what are these conditions called?
Deficiency in factor VIII is the primary cause of “classic” hemophilia.
Deficiency in number of platelets is termed Thrombocytopenia.
Which enzyme cascade is faster?
Extrinsic (as fast as 15 seconds, intrinsic taking 1-6 mins to clot)
What protein is expressed on the endothelial surface which binds to Thrombin and inhibits its function as a procoagulant?
Thrombomodulin
What acts as an anticoagulant by inactivating factors Va and VIIIa?
Activated Protein C (activated by Thrombomodulin + Thrombin)
Name 2 important anticoagulants found in blood itself.
Fibrin fibers (absorbs Thrombin) Antithrombin III (alpha-globulin) (combines and inactivates thrombin)
Heparin + Antithrombin III complex removes which activated factors?
IIa, IXa, Xa, XIa, and XIIa
Heparin is secreted by many cell types but especially by _____ cells in connective tissues and _____ in blood.
Mast ; basophils
How are prothrombin levels estimated?
By measuring the clotting time in the presence of excess Ca2+ and tissue factor.
What are 3 conditions that are particularly significant in excessive bleeding?
- Vitamin K defciency
- Hemophilia (deficiency of factor XIII)
- Thrombocytopenia (low platelet counts)
Vitamin K (synthesized by symbiotic gut bacteria) is important in the production of which clotting factors?
II, VII, IX, X.