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Lecture 1

PATH 310 Lecture Notes - Lecture 1: Gpvi, Thromboxane A2, Zymogen


Department
Pathology and Molecular Medicine
Course Code
PATH 310
Professor
Christine Hough
Lecture
1

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Lecture 1. Hemostasis
Hemostasis: The stopping of a flow of blood
This is the process which stops bleeding after injury to a blood vessel
Normally, our bodies want to make sure that the blood that flows through our
blood vessels stays in our bodies. If we have an injury that allows our blood to
leak out of the blood vessel and out of our body, we want to make sure we can
stop that. We do this through a process called hemostasis.
It’s through heostasis that we reate a lot, ad the lot allows the leeding to
stop.
It stabilizes the injury in the blood vessel, and gives the blood vessel time to heal.
Hemostasis vs. Thrombosis
Hemostasis is a normal process that stops bleeding in an injured vessel through
the formation of a hemostatic plug
o It is rapid, controlled, site specific, and removed when no longer needed
Thrombosis is a pathological process with formation of a blood clot (thrombus)
in an uninjured vessel
o It is a cause of sudden death
Components of Blood
4-6 liters
Erythrocytes: red blood cells that carry oxygen around the body
Leukocytes: white blood cells to fight invaders
Platelets: carry sacs or granules that carry molecules necessary for hemostasis
Plasma: has lots of different proteins, including coagulation factors
Coagulation
Also known as clotting
The process by which blood changes from a liquid to a solid or semi-solid state,
forming a blood clot
Blood Vessels
Vessel wall
Fibroblasts
Smooth muscle cells
Endothelial cells: lines the interior surface of blood vessels,
allows blood to flow smoothly, communicates with blood
during injury; it regulates vascular tone, vascular smooth
muscle cell proliferation, transendothelial leukocyte
migration, thrombosis and thrombolysis
Lumen: hollow passageway through which blood flows
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Vascular Endothelium Functions
1. The monolayer of endothelial cells separates blood from prothrombotic
components
o The prothrombotic components are tissue factor, von Willebrand factor,
and collagen
2. Plays an important role in hemostasis
3. Plays an important role in thrombolysis (as well as thrombosis)
Components of Hemostatic System
Vascular endothelium
Platelets
Coagulation System
Fibrinolytic System
Keeping blood in a fluid state depends on:
Intact vascular endothelium: no injury to blood vessel
Platelets in a quiescent state: keeping platelets inactive
Regulation of coagulation: regulation of clotting
Regulation of fibrinolysis: breakdown of fibrin in blood clots to prevent blood
clots from growing and becoming problematic
Resting Endothelium
In a healthy blood vessel, our endothelium is secreting:
o Nitric oxide and prostacyclin: vasodilators to ensure good blood flow,
inhibits platelets from sticking to endothelial cells
o Thrombomodulin: anticoagulant protein that, in cooperation with protein
C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the
endothelial microenvironment in an anti-inflammatory and anticoagulant
state
o t-PA + UK: plasminogen activator and urokinase helps to break down
fibrin clots
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Three Reactions of Hemostasis
1. Primary Hemostasis
o Vasoconstriction
o Platelet plug formation
2. Secondary Hemostasis
o Clot Formation
3. Fibrinolysis
o Breakdown of fibrin clot
Primary Hemostasis
Vasoconstriction:
o We want to constrict the smooth muscle cells to make the hole that the
blood is flowing though smaller, in order to decrease the amount of
blood we lose
o Vasoconstriction occurs in two ways:
Reflex vasoconstriction: during injury our nerves suddenly tell our
smooth muscle cells to contract
Endothelin secretion: during injury we lose some of the nitric
oxide and prostacyclin and instead secrete endothelin, which
causes vasoconstriction.
Platelet plug formation:
o Platelet adhesion
Upon endothelial injury, platelets bind to exposed subendothelial
matrix proteins with the aid of adhesion molecules or receptors
on their surfaces.
GP6 ad Itegri αβ: Binds directly to collagen
GP1b95: Binds to vWf
Collagen: a substance that provides structure to the blood
vessels, and it normally doesn't have contact to blood or to
platelets
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