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What are the 3 layers of the normal vessel wall??
- 1. intima
- 2. media
- 3. adventitia
The intima is the _____ layer.
What is the function of the intima layer of a vessel?
Separates the blood from the vessel
- Notes from book
- *forms a barrier separating the fluid contents within the BV from the highly thrombogenic material in the subendothelial space
- *repels blood contents from vessel wall preventing activation of clotting mechanism
- *when damage occurs.. this process does not occur
What is the intima made up of??
Name 5 things that are synthesized and secreted by endothelial cells...
- 1. Von Willebrand factor
- 2. Tissue factor
- 3. ADP
- 4. NO
- 5. Prostacyclin
What does Von Willebrand factor do within the intima layer??
it is a cofactor for the adherence of platelets to the vessel wall
What does tissue factor do within the intima layer?
activates the clotting cascade
What does ADP do within the intima layer?
controls blood flow by vasoconstriction
What does NO and prostacyclin do within the intima layer??
controls blood flow by vasodilation
What is the 2nd layer of the vessel wall called?? what is another name for it??
- Thombogenic layer
What does the media layer of the vessel wall contain?? and what does it do?
collagen --- which stimulates platelet attachment to the vessel wall
- notes from book
- this layer if very active.. it facilitates the anchoring of fibrin during the formation of a plug
What is the 3rd layer of the blood vessel called? and what is it responsible for?
controls blood flow and influences vessel contraction
What influences the adventitia layer and where do these influences come from??
NO and prostacyclin
these are produced by endothelial cells
Within the adventitia layer, what does NO do??
- 1. inhibits platelet adhesion
- 2. inhibits aggregation
- 3. inhibits binding of fibrinogen between glycoprotein IIb/IIIa complex
- 4. promotes smooth muscle relaxation resulting in vascular vasodilation
- from book --- this vasodilation causes increased blood flow which allows for procoagulant mediators to be washed away
NO causes a metabolic reaction to occur within the endothelial lining of the vessel... what exactly happens??
L-arginine is converted into NO which activates guanylate cyclase producing cyclic GMP which causes muscle relaxation
What is prostacyclin synthesized from??
Prostacyclin is a powerful ________.
What does prostacyclin do??
interferes with platelet formation and aggregation
What are platelets formed from??
formed in bone marrow from megakaryocytes
Where are platelets typically located within the vessel???
they tend to be pushed against the lining of the vessel
- from book
- they are smaller than other constituents of blood, therefore they are strategically pushed away to the vessel edge to be available to react to injuries
Platelets contain contractile proteins..what are these proteins in charge of??
storing large amounts of calcium and enzymes
Platelets contain alpha and dense granules..what do each of these granules do??
alpha --- store proteins such as vWf, fibrinogen, fibronectin, platelet factors4, platelet growth factor
dense --- store nonproteins such as serotonin, ADP, ATP, histamine, epi
What do platelet granules synthesize??
these help to promote vascular and local tissue reactions
What do platelets produce during the initial portion of vessel injury?? and what does this do??
activates some of the coagulation factors, recruits platelets to the site of injury
Platelets are typically unactivated... what activates them???
What occurs in response to injury the vessel???
the formation of a clot
What are the steps of hemostasis when vessel injury occurs?
- 1. vessel spasm
- 2. formation of the platelet plug
- 3. blood coagulation
- 4. clot retraction
- 5. clot dissolution
What initiates the constriction of the vessel during injury??
vessel wall will immediately contract to decrease blood flow via ANS
When the vessel spasms to constrict the tissue what is released??
thromboxane A2, ADP and prostacyclin
What does Prostacyclin do when released during vessel spasm after injury??
dilates the surrounding tissue to prevent further bleeding, sends blood to surrounding organs and tissues instead of site of injury
The outer coating of a platelet is covered by _____.
GPIIb/IIIa binds fibrinogen and bridges one platelet to another.
After the vessel contracts, then what occurs??
Formation of the platelet plug
What occurs during the formation of a platelet plug??
vWF moves from endothelial cells and adheres to the damaged vessel
Platelets change their shape once activated..what is this shape and why do they do this???
change from round disc like shape to an odd shaped form (oval and irregular) to create a block and prevent bleeding
when they change shape they also release their contents
What are the parts called that stick out from the platelet??
glycoproteins...these parts help the platelets stick together
they also help in promoting healing
Platelet adhesion can not occur without??
What activates the platelet??
Thrombin (factor IIa)
also vascular injury starts the whole process
When they platelet is activated what is released from the platelet??
thromboxane A2 and ADP
**at different parts through the repair of the vessel, they also release thrombin and growth factors
What does P-selection have to do with the platelet plug formation??
it participates in aggregation
Defective platelet plug formation occurs in patients who are deficient in ___ or ____ ____ ____.
platelets or Von Willebrand's Factor
Platelets also release growth hormones during the formation of the platelet plug..why is this??
they are released for endothelial and arterial smooth muscle cells...they help maintain normal vascular integrity.
Name a few drugs that inhibit platelet function??
What does ASA block to inhibit platelet function?? How long does ASA work??
blocks cycloxgenase --- blocks enzyme TXA2
works for the life of the platelet
What does Plavix and ticlid inhibit to block platelet function??
What do integrilen, aggrostat and reopro block??
What are 3 requirements for the blood clotting process???
- 1. presence of platelets
- 2. vWF
- 3. clotting factors synthesized
What is the platelet plug reinforced by??
Name these clotting factors:
- 1. fibrinogen
- 2. prothombin
- 3. tissue thromboplastin
- 4. ionized calcium
- 8. antihemophilic factors
- 9. plasma thromboplastic component or Christmas factor
- 13. fibrin stabilizing factor
What does the "a" after a factor mean??
it has been activated
Once these factors are activated..what are they called??
- 1. fibrin
- 2. thrombin
- 8. hemophilia A
- 9. hemophilia B
List the clotting factors in the INTRINSIC pathway...
- 12 ----> 12a
- 11 ----> 11a
- 9 ---->9a
then combines with extrinsic to make the common pathway
List the clotting factors in the EXTRINSIC pathway...
factor 3 and 7
combine with 10 to complete the common pathway
List what happens in the common pathway
- factor 10 ---- 10a
- prothrombin (2)--->thrombin (2a)
- fibrinogen (1) ----> fibrin (13)
What is the result of the common pathway?
What does proteolysis mean??
breaking down the precursor to release the active form of a clotting factor
What part of the pathway does heparin work on?? and how can heparin be measured???
What part of the pathway does Coumadin work on?? and how can you measure it??
LMWH inhibits which clotting factor??
has no real other effects on other factors
Once the vessel is sealed thrombin will act like an _____.
Once the vessel is sealed how does thrombin work???
- releases TPA---tissue plasminogen activator
- stimulates proteins C&S
- works with antithombin III
Coagulation proteins are made where??
in the liver
What factors are depending on vit k?
2, 7, 9, 10
When does the clot retract and what exactly does this mean?
20 to 60 mins after the clot is formed
this means that the clot is pulled together using actin and myosin
The clot will start to break down short after retraction once the vessel is sealed...how does plasminogen act here???
- plasminogen activates to plasmin
- plasmin digests fibrin strands causing the clot to dissolve
What are two activators of plasminogen??
tissue plasminogen activator and Urokinase type plasminogen activator
What does antithrombin III do??
inactivates clotting factors and neutralizers thrombin
What does protein C do?
inactivates factors 5 and 8
What does protein S do??
accelerates the action of protein C
What is the normal bleeding time??
*this is not a routine test
What is the normal platelet count?
150,000 to 300,000 mm3
What is the normal PT? what is this value altered by?
What is the normal INR??
What is the normal PTT? What alters this level??
What is the normal fibrogen level??
what is the normal value of fibrinogen degradation products??
measures by products of clot dissolution
What is the normal D dimer?
degradation products secondary to fibrinolysis
What is the normal value for antithrombin III???
if this is decrease---can explain reason for heparin not working well