PHS 3342 Lecture Notes - Lecture 4: Von Willebrand Factor, Vascular Smooth Muscle, Vasospasm
28 Apr 2018
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January 16, 2018
Platelets
Platelets
Cytoplasmic fragments of megakaryocytes
Anucleuate, but have organelles and cytosolic enzymes required for generating energy and synthesizing secretary
products
Lifespan: ~10 days
Have granules that contain factors and enzymes involved in blood clotting
-Have 2 types of granules:
•Alpha granules: contain clotting factors and PDGF (proliferation of vascular endothelial cells, vascular smooth
muscle, and fibroblasts to repair damaged walls)
•Dense granules: ADP, ATP, Ca2+, serotonin
-Contain enzymes to make thromboxane A2 (PG that stimulates platelet release of ADP, serotonin) and fibrin-
stabilizing factor
Platelet formation regulated by hormone thrombopoietin
-Network of membranes from plasma membrane divides cytoplasm into compartments
-Cell processes break off membrane-enclosed fragments (2-4 μm; aka thrombocyte)
Hemostasis
Hemostasis response must be quick, localized to the region of damage, and carefully controlled
-Clot formation
-3 phases:
•Vascular spasms
•Platelet plug formation
•Blood clotting (coagulation)
Vascular spasms: vasoconstriction of vessel in response to damage (due to smooth muscles, pain receptors)
-Allows time for platelet plug formation
-Slows blood flow and minimizes blood loss
Platelet plug formation:
-Exposure to collagen stimulates platelets to swell, become spiky and sticky
-Causes them to adhere to exposed collagen (via von Willebrand factor) - leads to degranulation
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January 16, 2018
-Platelet release reaction:
•Activated platelets release ADP and thromboxane A2
•The released chemical messengers work together to activate other platelets passing by
-ADP: enhances aggregation and degranulation
-Serotonin and thromboxane A2: induce vasoconstriction (enhance vascular spasm and aggregation)
-Newly activated platelets aggregate onto growing platelet plug and release even more platelet-attracting chemicals
-NB: normal (uninjured) endothelium releases prostacyclin and nitric oxide to inhibit platelet formation in response to
the released ADP and other chemicals
•Allows platelet plug to be confined to the site of injury
-The newly formed platelet plug forms three important roles (other than physically sealing the break in the vessel):
•Actin-myosin complexes within the platelets contract to compact and strengthen the plug
•The plug releases powerful vasoconstrictors, which induces vasoconstriction and reinforces the initial vascular
spasm
•The plug releases other chemicals that enhance blood coagulation
Coagulation (formation of a blood clot): platelet plug becomes much more solid and is resistant to being pushed away
by blood flowing nearby
-Blood transformed from a liquid into a gel
-Formation of a clot on top of the platelet plug strengthens and supports the plug, reinforcing the seal of a break in
the vessel
-Clotting is the body’s most powerful hemostatic mechanism - required to stop bleeding for all but the most minute
defects
-3 phases:
•Prothrombin activator (prothrombinase) is formed
•Prothrombin activator converts prothrombin to thrombin
•Thrombin catalyzes joining of fibrinogen molecules - forms a fibrin mesh
-Fibrinogen is a soluble plasma protein that is always present in the plasma
-Fibrin is an insoluble, thread-like molecule
-Fibrin molecules will adhere to the damaged vessel surface, forming a loose, net-like meshwork that traps
blood cells (including aggregating platelets) - forms a clot
-The fibrin strands will rapidly form chemical linkages in order to strengthen and stabilize the clot
-NB: requires Ca2+ in order to occur
Role of vitamin K in clotting: needed for synthesis for 4 clotting factors (II [prothrombin], VII, IX, and X [prothrombin
activator]) by hepatocytes
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Document Summary
Anucleuate, but have organelles and cytosolic enzymes required for generating energy and synthesizing secretary products. Have granules that contain factors and enzymes involved in blood clotting. Have 2 types of granules: alpha granules: contain clotting factors and pdgf (proliferation of vascular endothelial cells, vascular smooth muscle, and broblasts to repair damaged walls, dense granules: adp, atp, ca2+, serotonin. Contain enzymes to make thromboxane a2 (pg that stimulates platelet release of adp, serotonin) and brin- stabilizing factor. Network of membranes from plasma membrane divides cytoplasm into compartments. Cell processes break off membrane-enclosed fragments (2-4 m; aka thrombocyte) Hemostasis response must be quick, localized to the region of damage, and carefully controlled. 3 phases: vascular spasms, platelet plug formation, blood clotting (coagulation) Vascular spasms: vasoconstriction of vessel in response to damage (due to smooth muscles, pain receptors) Slows blood ow and minimizes blood loss. Exposure to collagen stimulates platelets to swell, become spiky and sticky.
