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all right nine nerds in this video we're
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going to talk about hemostasis first off
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what is hemostasis hemostasis well first
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off we can kind of break apart this term
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here hemo is blood stasis means stop so
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it's a localized blood stoppage right so
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that's what we're trying to do usually
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this occurs whenever there's some type
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of damage to our blood vessels right
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whenever they're either ruptured or
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lacerated and blood is actually leaking
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out and our desire is to be able to stop
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that from happening so there's a a
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sequence of five steps that we're going
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to go over throughout this entire length
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of the blood vessel in order to
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understand how this hemostasis is
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occurring before we do that we really
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need to understand what is keeping the
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blood naturally thin what's keeping it
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from coagulating on its own naturally so
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now we need to go over that before we go
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into understanding how this coagulation
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how these actual platelet plug
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formations and all that stuff is
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occurring so let's come over here and
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let's understand exactly how the blood
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is keeping itself naturally thin and
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pring it from becoming thrombotic in
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other words trying to form a clot all
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right first thing we have here our
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endothelial cells right so here's here's
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our endothelia cells here we have
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underneath it our subendothelial layer
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and you know the subendothelial layer is
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made up of connective tissue
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specifically collagen it's rich in rich
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in collagen and then down here we have
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some smooth muscle cells with some
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specific types of receptors and then
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over here these orange cells are going
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to be our no receptors or our pain
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receptors right all right so first thing
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our endothel I cells they secrete
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chemicals two really important chemicals
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one is called
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nitric
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oxide and the other chemical that it
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secretes also is going to be
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pg2 which is prostacyclin all right so
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it secretes these two chemicals
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prostacyclin and nitric oxide what is
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the purpose of these chemicals well you
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know if with inside of our blood we have
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two things plasma and cells are form
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elements right and those formed elements
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are platelets when we're going to care
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about white blood cells and red blood
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cells so circulating through this area
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what are we going to have we're going to
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have these little tiny microscopic
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cytoplasmic fragments which are called
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platelets and what happens is this
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nitric oxide and
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pgi2 it naturally inhibits the platelet
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and keeps the platelet inactive and
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prevents the platelet from being able to
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bind on to the endothelial lining
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that's what it's naturally doing so what
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is this whole purpose of this it's
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inactivating the
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platelet okay so you can think about
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these platelets as though they're
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sleeping right so they're sleeping
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they're catching some z's over here
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right so again that's the whole purpose
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of this nitric oxide prostoy inactivate
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the platet and prevent the plat from
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binding onto the surface that's one
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thing to prevent the blood from clotting
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natur on naturally right
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next thing there's another Protein
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that's present on the membrane actually
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it's not a protein it's a proteoglycan
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or glycos aminoglycan I should be more
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specific it's a glycos aminoglycan and
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this glycos aminoglycan is called Hein
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Hein sulfate it's called Heparin sulfate
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and Hein sulfate is a natural
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anti-coagulant right so here's our
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Heparin
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Hein sulfate and what does Hein sulfate
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do Hein sulfate binds another protein
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which is called anti-th
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3 so this is called anti-
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thrombin three not and tensin three
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antithrombin three okay so again Hein
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sulfate is bound bound to the plasma
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membrane it activates antithrombin 3 and
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imagine antithrombin 3 having like a
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specific type of uh hand out here
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imagine it having like a specific type
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of cutter look at this it's got a little
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cutter here a little like blade or
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radula and there's specific clotting
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factors that are constantly circulating
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throughout your bloodstream naturally
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what are those clotting factors that
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this one degrades it degrades clotting
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Factor
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two it also degrades clotting Factor
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n and clotting Factor 10 so imagine
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these guys running through this this
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little grinder what does it do it
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inactivates these these proteins so what
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proteins are inactivated then you
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inactivate two so two is
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inactivated all right nine is
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inactivated and 10 is inactivated so now
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these guys are inactive all right one
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more mechanism this one right here look
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at this protein right
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here this protein right here is called
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thrombo
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modulin this protein is called
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thrombomodulin so what does thrombo
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modulin do thrombomodulin binds another
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protein and this protein is
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called
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thrombin or we can also call it Factor
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two right so you can also call it Factor
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two and then what does thrombin do
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imagine thrombin having its hand out
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here so imagine it has a hand right and
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what it does is there's a protein that's
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kind of circulating by in this area and
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just so happens to run into this guy so
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look at this protein right here
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this protein this green protein is
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called protein C and what happens is
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when protein C moves across the thrombin
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it becomes active so now we have
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activated protein C and then what does
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protein C
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do protein C degrades so again what is
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this protein
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protein C protein C degrades two factors
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one is going to be Factor five and the
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other one is Factor
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eight okay so these guys are going to be
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degraded or inhibited so these are kept
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inactive okay so again what happens with
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these guys these are all the three
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natural mechanisms that are trying to be
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able to keep the blood naturally thin
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and preventing it from un undesirable
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clotting now that we know that let's go
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into the first mechanism so
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now well first off let's actually number
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them real quickly what are the what are
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the five mechanisms right here we're
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going to go one is the first one we're
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going to go into is called
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vascular
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spasm the second mechanism is called
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platelet
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plug
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formation and the third is going to be
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the bear of it all which is coagulation
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this is a beast and then the fourth one
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is
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clot
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retraction and repair
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and then we'll finish up with
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fibrinolysis these are the five steps of
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hemostasis and that's what we're going
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to go into in specific order so first
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one we have to go into is vascular
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spasm well how do you classify vascular
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spasm whenever there's damage to the
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blood vessel lining so look here let's
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say that we damage these endothelial
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cells right here they're damaged so look
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at them they're damaged and maybe we
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damage some underlying tissue also so
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these guys are damaged now
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whenever these tissues are damaged what
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can happen blood can leak out right well
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we don't want the blood to leak out into
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this area because then if we start
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losing blood volume that can lead to a
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lot of problems right so we don't want
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to lose a lot of that blood so what we
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want to do is we want to be able to
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prevent this blood loss from occurring
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so we want to contract or constrict the
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blood vessels and by constricting the
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blood vessels we decrease the amount of
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blood that's being lost that's what we
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want to do that's vascular spasm what
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causes these smooth muscles here to
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contract let's go into that first thing
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whenever these smooth muscles are
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injured I mean whenever these
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endothelial cells are injured they
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secrete a chemical and this chemical is
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called I'm going to put it with an
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E Endo thylin so what is this chemical
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called it's called
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Endo thin and what does endothil do you
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see this purple receptor down here in
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the smooth muscle look what he
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does he comes over here and he binds
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onto that purple receptor and he
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activates an inter cellular mechanism
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and that intracellular pip2 calcium
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signaling mechanism will cause
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contraction and whenever that smooth
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muscle contract so again what's
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happening here there's going to be
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contraction that's the overall effect
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and what is contraction going to do it's
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going to cause vasil constriction which
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is going to decrease the diameter of the
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blood vessel and try to prevent the
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blood loss that's one
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mechanism second mechanism so again
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what's the first mechanism here for
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vascular spasm so we have vascular SP
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spasm this is our first
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event the first event
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is
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endoth while we're at the muscles let's
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do one more mechanism so endoth um
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effect right the second thing is there's
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what's called a myogenic mechanism so
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whenever you have direct contact or
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injury to the blood vessel wall and it
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it actually causes direct injury to the
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smooth muscle whenever there's direct
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injury or contact with the smooth muscle
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there's a protective mechanism in
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response to that and it's called a
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myogenic mechanism so if there's direct
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injury or contact the smooth muscle will
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contract so again what's the second
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mechanism this is called a
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myogenic
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mechanism okay so it's whenever there's
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direct injury or contact with the smooth
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muscle it contracts third
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event you see these orange receptors
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here these orange neurons whenever
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there's inflammation you release
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specific types of inflammatory chemicals
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so there's a lot of inflammatory
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chemicals within this area area a lot of
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INF inflammatory chemicals like maybe
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some histamines and some lucrin and some
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prostaglandins what are they going to do
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they're going to stimulate these actual
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orange orange uh neurons right these
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noio spors and whenever they're
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stimulated they're going to initiate
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pain but that pain reflex can cause Vaso
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constriction so whenever these neurons
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are stimulated these no acceptors due to
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local inflammatory chemicals or
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mechanical trauma so other words you
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they're direct injury to them as well
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they're going to initiate a reflex that
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causes contraction so so again what will
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happen here he can
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initiate contraction onto this actual
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smooth muscle cell and whenever there's
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contraction that will cause the vascular
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spasm also so again what's the third
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effect noio
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sceptor
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Activation so three
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mechanisms that trigger this vascular
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spasm event right so that's that's that
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part now let's go into the second event
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because we've already gone over how
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we're trying to prevent this from
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happening let's go over here and do the
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second event what's the second event now
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all right so now when there's damage to
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these endothelial cells right damage to
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the endothelial cells maybe damage to
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the collagen maybe damage to the smooth
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muscle what happens is there's a protein
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there's a protein produced by the
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endothelial cells look at this see this
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protein right here this protein is
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called Von Wilder bronze Factor Von
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Wilder bronze Factor so again what is
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this protein called it's called
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vau will debron
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Factor so this protein it's secreted by
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the injured endothelial cells right and
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what happens is normally the platelets
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love to bind to the collagen because it
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is Von Wilder Bron's Factor if these
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cells are injured can they release
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nitric oxide can they release
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prostacyclin no so then the plet is not
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kept inactivated so that plet is
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actually going to bind and on top of
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that if we don't have Hein sulfate
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because maybe it's damaged and there's
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Hein sulfate right here can we keep some
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of those CLA factors inactive no and if
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we have thrombomodulin right there and
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that was damaged can we actually keep
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the blood thin from Factor five and
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factor 8 no so this would trigger that
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coagulation Cascade right but but first
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we need to do playlet plug so again
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nitric oxide and prosy is inhibited and
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then the platelets will come and bind
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here so look here's a platelet right
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here and here's a platelet right there
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they'll bind but on the Von W bronze
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Factor so let's say here's the Von
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Wilder bronze Factor there's a specific
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receptor on the platelet that binds with
00:12:30
the Von Wilder Bron's
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Factor what is this glycoprotein called
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and the only reason I mention it is
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because it's important because we have
00:12:39
to understand certain diseases and drugs
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that protein right there is
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called that black protein is called
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glycoprotein
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1B so again what is that protein called
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right there it's called glycoprotein 1B
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and it binds with the Von wild Bron's
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Factor so the playlets bind here right
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and then what happens once the platelets
00:13:01
are actually going to be like activated
00:13:03
because of this binding their granules
00:13:05
start actually releasing specific
00:13:07
chemicals what are those chemicals that
00:13:09
it secretes three chemicals it secretes
00:13:13
one of these chemicals is called a
00:13:17
DP right that's one really really
00:13:19
important one another chemical is called
00:13:22
thromboxane
00:13:25
A2 and another chemical that secretes is
00:13:27
called Sarah
00:13:29
tonin or five hydroxy
00:13:33
tryptamine what do these chemicals
00:13:35
do well I told you before that there's
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platelets just kind of naturally
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circulating within this area right here
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right so maybe here's a platelet Maybe
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here's a platelet Maybe here's a
00:13:45
platelet here's a platelet right these
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platelets are just tiny little
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cytoplasmic fragments they're super
00:13:50
super tiny they're derived from a mega
00:13:51
Cario site right so what happens is ADP
00:13:55
and thromboxane A2 these guys work to be
00:13:58
able to stimulate this these actual uh
00:14:01
platelets so they have receptors on
00:14:03
their
00:14:04
membrane that specifically bind the ADP
00:14:07
and the thrombo A2 so when ADP and
00:14:10
thrombo A2 bind on to these playlets it
00:14:12
activates the playlets and causes these
00:14:14
playlets to want to come to that site of
00:14:16
injury so then what's going to happen
00:14:19
these plets are going to start
00:14:20
aggregating to that site of injury so
00:14:23
they're going to undergo what's What's
00:14:24
this called whenever they come here it's
00:14:25
called platelet
00:14:31
aggregation that's the first step all
00:14:33
right so now the playlets are going to
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start binding here so look at what's
00:14:36
happening here so playlist bind here
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they bind here they bind here and they
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start forming this nice plug right here
00:14:44
but then there's one more thing that we
00:14:45
have to do before we keep going on with
00:14:47
this right so the playes are binding but
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how are they binding to each other we
00:14:50
know how they bind with Von Wilder
00:14:52
Bron's Factor let me draw a platelet
00:14:54
right here so here's one
00:14:56
platelet and here's another platelet
00:15:00
so we know that they can join with the
00:15:02
Von Wilder bronze Factor right so here's
00:15:03
the let's say here's a Von Wilder bronze
00:15:04
Factor protein they bind with that with
00:15:07
the glycoprotein 1B right so here's our
00:15:09
glycoprotein 1B that's how they bind
00:15:12
this but how do they bind to each other
00:15:16
well here's another there's these
00:15:17
proteins here on each one's surface and
00:15:19
then there's a thing called fibrinogen
00:15:21
that actually leaks links them together
00:15:23
this protein right there is called get
00:15:26
ready glycoprotein 2
00:15:29
B 3 a holy goodness right so that's a
00:15:34
it's a crazy name right there but it's
00:15:36
important because we have to know these
00:15:37
proteins because they're drug targets
00:15:40
okay so again glycoprotein 2B and 3A
00:15:43
with fibrinogen between them link the
00:15:45
platelets together so that's what you'll
00:15:46
see linking them together but now look
00:15:49
we got a nice platelet plug okay we're
00:15:50
not done yet what is thron box2 and what
00:15:53
else does serotonin do well you see
00:15:56
these actual pink these purple receptors
00:15:57
down here thr oxan na2 and serotonin
00:16:01
love to bind to the smooth
00:16:04
muscle and when they bind onto the
00:16:06
smooth muscle they cause contraction so
00:16:09
again what would they cause let's come
00:16:10
down here they
00:16:12
cause contraction right and what does
00:16:16
contraction cause contraction leads to
00:16:19
Vaso constriction and then again what
00:16:21
will that Vaso constriction do enhance
00:16:22
the vascular spasm effect so again ADP
00:16:25
and throx na2 cause platelet aggregation
00:16:28
which leades plet plug but throx A2 and
00:16:32
serotonin cause vasal constriction to
00:16:35
enhance the vascular spasm response that
00:16:37
is the second step so what is this
00:16:39
second step right here that we've done
00:16:41
it's
00:16:42
called
00:16:45
platelet
00:16:47
plug
00:16:49
formation not bad right all right so
00:16:53
again we've done the Second Step so we
00:16:54
done first step second step now let's go
00:16:56
on to the third step
00:16:59
okay so now real quick recap this this
00:17:02
will be right so again there's damage to
00:17:04
this endothelial lining we already know
00:17:06
what
00:17:07
happens Von water bronze factor is going
00:17:09
to be right here right and it's going to
00:17:12
have its specific proteins there what's
00:17:14
going to bind platelets and they're
00:17:16
going to bind with their glycoprotein 1
00:17:18
B they're going to bind to each other
00:17:20
through their glycoprotein 2 B 3A with
00:17:23
the fibrinogen in between them they're
00:17:26
going to start becoming activated and
00:17:28
secreting ADP and thrombo and A2 which
00:17:31
causes platelet aggregation and then
00:17:33
they're going to secrete serotonin and
00:17:35
then throx and A2 also will cause vasil
00:17:38
constriction to enhance vascular
00:17:41
spasm
00:17:43
right so now we got this beautiful
00:17:46
platelet plug here now we go into the be
00:17:48
of it all all right now we're going to
00:17:50
go into
00:17:52
coagulation okay so now we're talking
00:17:53
about the coagulation Cascade so first
00:17:56
off these playlets so they've already
00:17:58
undergone a aggregation and the plug
00:18:00
formation and they just continue to keep
00:18:02
pulling more playlists at that site but
00:18:05
once this has happened we go into this
00:18:07
next step right so there's these things
00:18:10
called phospho tialing groups that are
00:18:12
going to be on present on the platelet's
00:18:14
membrane and it creates these negative
00:18:16
charges right here so these negative
00:18:18
charges on the actual platelet cell
00:18:19
membrane and this is again caused by
00:18:21
phospho talerine there's going to be
00:18:24
proteins you know your liver your here's
00:18:26
your liver right here so your liver is
00:18:28
const stantly making tons of clotting
00:18:31
proteins tons of clotting proteins and
00:18:33
these clotting proteins are normally
00:18:35
circulating within the blood plasma
00:18:37
right but they're kept inactive but now
00:18:40
we're going to activate them so the
00:18:42
first clotting protein that just so
00:18:44
happens to be walking through this area
00:18:46
and then boom interacts with a playlet
00:18:48
is called Factor 12 so what is the first
00:18:50
protein called it's called Factor
00:18:53
12 or hegan's factor right so there is
00:18:56
Factor 12 Factor 12 will interact with
00:19:00
those negative charges on the playlet
00:19:02
and then convert itself into an active
00:19:04
form so it's a precursor or a pro-enzyme
00:19:08
we can call it a pro-enzyme right or
00:19:11
even we can call them zymogens they're
00:19:12
just inactivated right well we're going
00:19:13
to activate them now so now here's
00:19:16
Factor 12 he's activated what happens
00:19:18
next is Factor 12 activates Factor
00:19:21
11 so here we have Factor
00:19:26
11 Factor 11 is going to get activated
00:19:28
ated by Factor 12 so now he's
00:19:33
activated and then Factor 11 is going to
00:19:36
go and activate factor nine so here's
00:19:38
another one so here's going to be factor
00:19:41
nine so factor
00:19:44
nine right here is going to interact
00:19:46
with Factor 11 and he'll be
00:19:51
activated and then what happens factor
00:19:54
nine interacts with another protein that
00:19:55
just happens to be walking by all right
00:19:58
and that is going to be be called
00:19:59
factor8 so over here is actually going
00:20:01
to be
00:20:03
factor8 and factor8 is going to interact
00:20:06
with factor nine and they're going to
00:20:09
form a complex right but they're going
00:20:11
to need two other things present for
00:20:13
this to happen they're going to need
00:20:15
what's called platelet Factor 3 and
00:20:19
calcium so they need calcium as a
00:20:22
co-factor and then need they need the
00:20:23
membrane of the platelets or platelet
00:20:25
factor three in order for this complex
00:20:27
to occur then there's another protein
00:20:29
here and this protein is called Factor
00:20:33
10 and Factor 10 so these guys are
00:20:36
actually going to combine together and
00:20:38
they'll form
00:20:39
one complexing pathway right
00:20:42
here that will drive the conversion of
00:20:45
the inactive form of 10 into active form
00:20:48
of
00:20:50
10 and now the active form of 10 is
00:20:53
going to react with another protein I
00:20:57
know this is a lot of proteins here but
00:20:59
it's going to react with Factor five so
00:21:02
Factor five will actually react here
00:21:05
you'll also have platelet Factor
00:21:09
3 and calcium driving the step also and
00:21:14
what this will do is this will activate
00:21:15
another protein and this protein is
00:21:18
called
00:21:19
the
00:21:21
pro thrombin activator so this is called
00:21:24
the
00:21:26
pro thrombin
00:21:31
activator okay now what the proin
00:21:33
activator does is it has look at these
00:21:40
ears look at these
00:21:42
ears what it does is there's another
00:21:45
molecule kind of circulating within that
00:21:47
area and that molecule is called Factor
00:21:50
2 but in this form it's called
00:21:53
prothrombin it's in the inactive form so
00:21:56
what the prothrombin does is look it
00:21:59
reacts with the ear of pro thrombin
00:22:00
activator reacts with him and when it
00:22:02
does it converts the prothombin into
00:22:06
thrombin the activated form so Factor
00:22:08
two is also called thrombin okay know
00:22:10
that factor two is also called
00:22:12
thrombin thrombin then does what okay
00:22:16
here's where we get to the good
00:22:18
stuff
00:22:19
thrombin reacts in two ways one there's
00:22:23
a molecule which is called look I'm
00:22:24
going to draw it like a circle here
00:22:26
they're kind of just hanging out in this
00:22:27
area these little circle circles what
00:22:29
are these little circles called these
00:22:31
little circles are called fibrinogen so
00:22:34
this is called
00:22:36
fi brinogen and fibrinogen is a plasma
00:22:40
protein if you remember from the
00:22:42
hematocrite that is actually counting
00:22:44
for some of the the 4% of the plasma
00:22:46
proteins right and it's circulating
00:22:48
through the blood soluble Wise It's
00:22:50
soluble within the blood plasma but then
00:22:53
what happens is Factor 2 or thrombin
00:22:55
polymerizes them starts linking them
00:22:57
together and if you starts linking them
00:22:59
together look at what they're going to
00:23:00
look like now so now how many do I have
00:23:02
1 2 3 4 5 six seven so I have to have
00:23:05
seven of these together over here so
00:23:06
three four five 6 7 what is this
00:23:11
molecule here called This is called
00:23:15
fibrin and fibrin is insoluble in the
00:23:19
blood plasma so this is going to help to
00:23:21
turn the blood for more of a liquid into
00:23:23
a jelly-like substance that's the
00:23:24
purpose of coagulation because we want
00:23:26
it to be more jelly like so that it will
00:23:28
slow down the blood flow beyond that
00:23:30
area because we don't want to keep
00:23:31
losing our red blood cells so it slows
00:23:34
that flow of the red blood cells through
00:23:35
there and turns it into more of a
00:23:36
jelly-like substance all right so now
00:23:38
it's insoluble one more thing it reacts
00:23:42
with another protein over here and this
00:23:44
protein is called
00:23:45
Factor 13 also called the fibrin
00:23:48
stabilizing factor and look what he does
00:23:51
he becomes
00:23:55
activated and you need calcium also for
00:23:57
this step to occur so what else do you
00:23:58
need for this step to occur you need
00:24:03
calcium Factor 13 will then take these
00:24:06
fibrin strands and cross link them
00:24:08
together so then it'll take another
00:24:10
fibrin strand that it might have over
00:24:11
here somewhere that thrombin's
00:24:13
polymerized and look what it's going to
00:24:14
do it's going to cross link them so it's
00:24:16
going to take this one cross link it
00:24:18
this
00:24:19
way and then it might cross link another
00:24:21
one over here what's the purpose of
00:24:23
crosslinking this the purpose of
00:24:26
crosslinking it is to create a nice
00:24:27
fiber mesh so that when we lay this over
00:24:30
the platelets it prevents the platelet
00:24:33
thrombus from dislodging and going into
00:24:35
an area and causing animalism right we
00:24:36
want to keep this taught nice and held
00:24:38
down so that we don't have any blood
00:24:41
loss from here but we also don't let it
00:24:42
break off that's important so again
00:24:46
fiber and stabilizing Factor will cause
00:24:48
this crosslinking so again what will it
00:24:49
cause here it'll lead to
00:24:54
cross-linking of fibrin
00:24:58
and this produces the fibrin mesh so
00:25:00
what is this molecule now called it's a
00:25:03
fibrin mesh Network
00:25:07
right now what does this fi mesh do this
00:25:11
fibr mesh is going to be laid over this
00:25:14
so now imagine here I'm just going to
00:25:16
draw it as lines now look look at this
00:25:18
we're
00:25:19
holding this down now and here's our
00:25:22
cross
00:25:23
linking there's our fiber and mesh and
00:25:25
that's holding that platelet plug in
00:25:28
place place so that it doesn't dislodge
00:25:29
and go somewhere else right and also
00:25:31
it's keeping the blood as it's
00:25:32
circulating through this area right here
00:25:34
more jelly-like more thick more viscous
00:25:36
so that slows the blood flow down so we
00:25:38
don't continuously have blood loss right
00:25:41
all right so what have we gone over then
00:25:42
so basically let me let me tell you real
00:25:44
quick here we have two Pathways an
00:25:47
intrinsic
00:25:49
pathway and an extrinsic pathway I
00:25:51
haven't talked about the extrinsic but I
00:25:53
will it's a very quick pathway but
00:25:55
intrinsic is the ones that we just
00:25:56
talked about where we started with 12
00:25:59
right and we went from 12 down to 11 and
00:26:02
then 11 down to 9 and then nine with
00:26:06
eight and then eight combined with nine
00:26:09
to activate another one which is that
00:26:11
factor 10 right and here let me tell you
00:26:13
one more thing Factor 10 getting
00:26:14
activated this is the common pathway so
00:26:18
now what we just went over here is the
00:26:20
intrinsic pathway right in the intrinsic
00:26:22
pathway is the pathway that's occurring
00:26:24
inside of the blood independent of the
00:26:26
extrinsic pathway what do I mean if you
00:26:29
take someone's blood out of their you
00:26:31
take someone's blood and you put it in a
00:26:33
tube that's not heparinized so it
00:26:35
doesn't have heper coding it right the
00:26:38
the glass has a roughen surface and
00:26:40
charged surface so what does that do it
00:26:42
activates Factor 12 so the intrinsic
00:26:45
pathway can occur inside of a test tube
00:26:48
independent of the extrinsic pathway
00:26:51
however the extrinsic pathway which
00:26:52
you're going to talk about does depend
00:26:53
on some of the factors and proteins
00:26:55
within the intrinsic pathway all right
00:26:58
but before we do that again know that
00:27:00
what we covered intrinsic is 12 11 9 8
00:27:04
and then activating the common pathway
00:27:06
which is 10 that's going to be super
00:27:08
important because now you see how there
00:27:10
was tissue damage here whenever there's
00:27:12
damage to any of our tissues our tissues
00:27:15
release a protein which is
00:27:18
called tissue factor or
00:27:22
factor
00:27:26
three factor three now factor three will
00:27:30
come over here and look what it will
00:27:33
react with it will react with another
00:27:35
protein over here and this protein is
00:27:38
called Factor 7 so this protein is
00:27:41
called Factor 7 when Factor 7 reacts
00:27:45
with this factor three it becomes
00:27:48
active and look what it can do now it
00:27:51
can do two things one thing is it can
00:27:53
stimulate this step you see how it can
00:27:55
actually push factor nine into becoming
00:27:58
activated well look what else it can do
00:28:01
it can also
00:28:03
converge right here onto the common
00:28:07
pathway it can converge right onto the
00:28:09
common pathway right so now what do we
00:28:12
know out of this then so what do we know
00:28:14
is we know that factor three can be
00:28:16
secreted by damaged tissue cells and
00:28:19
those tissue cells will then actually
00:28:21
activate they produce tissue factor
00:28:23
factor three factor three will react
00:28:25
with react with Factor 7 and then Factor
00:28:27
7 can activate Factor 9 and it can come
00:28:30
into this common pathway that is the
00:28:34
extrinsic pathway so what is this
00:28:36
pathway here again let's write it up
00:28:37
over here so again what is this pathway
00:28:39
called This is the extrinsic pathway and
00:28:43
again how does this pathway occur what
00:28:45
is the protein produced by the damaged
00:28:46
tissue cells this is factor three factor
00:28:49
three will react with Factor
00:28:52
7 Factor 7 will be activated and Factor
00:28:56
7 can drive the activation of
00:29:01
factor
00:29:03
9 as well as he can also Drive the
00:29:07
activation of the common pathway so what
00:29:10
is the big what's the big thing about
00:29:11
this look how much longer it takes for
00:29:13
the intrinsic Pathway to occur versus
00:29:15
the extrinsic pathway the extrinsic
00:29:17
pathway can occur in about 30
00:29:20
seconds it's very fast whereas the
00:29:23
intrinsic pathway might take about four
00:29:25
to six minutes to occur so it's a little
00:29:27
long
00:29:29
right so now now that we understand that
00:29:32
we understand the activity of the
00:29:34
intrinsic and extrinsic pathway how the
00:29:37
ex transic tries to drive either Factor
00:29:39
9 activation or it can act try to
00:29:42
activate Factor 10 and then the
00:29:44
intrinsic pathway is the sequence of
00:29:45
cascade that also desires to activate
00:29:47
Factor 10 which is again the common
00:29:50
pathway all right so I know coagulation
00:29:52
is a is a pretty big beast it takes a
00:29:54
lot to remember all these proteins so I
00:29:56
wanted to give you a little trick to
00:29:57
help you you to remember it all right so
00:29:59
here on the left we're going to have the
00:30:00
intrinsic pathway here on the right
00:30:02
we're going to have the extrinsic
00:30:04
pathway it's just a little trick you can
00:30:05
take it if you want it so what I do is x
00:30:08
marks the spot so I put that it's the
00:30:09
first thing I do I put it right in the
00:30:10
middle then after that I count downwards
00:30:15
starting with 12 skipping 10 so in other
00:30:18
words I I put x x marks a spot that's 10
00:30:21
and I work backwards from 12 12 11 skip
00:30:24
10 9 8 and then I go to 10 right so look
00:30:27
here 12 to 11 11 to 9 9 to 8 and then 8
00:30:31
to 10 guess what pathway this is this is
00:30:33
the intrinsic pathway right so this is
00:30:36
the
00:30:38
intrinsic pathway again what do I do x
00:30:41
marks the spot so 10 and then again I
00:30:43
count backwards from 12 just skipping 10
00:30:46
12 11 skip 10 9 8 and then I get to 10
00:30:52
how do I remember the extrinsic
00:30:54
pathway
00:30:56
extrinsic you can remember 3 + 7 = 10
00:31:01
that's easy right so again count
00:31:04
backwards from 12 and then 3 + 7 equals
00:31:06
10 now how do I remember the common
00:31:08
pathway and then the formation of throm
00:31:10
and the fiber mesh so in order to make
00:31:13
10 right because this this is going to
00:31:14
go downwards but in order for me to
00:31:16
remember this I remember 5 * 2 * 1 = 10
00:31:22
so what is we have Factor five right
00:31:24
that activ uh reacts with 10 and then 10
00:31:28
and five activate two which is thrombin
00:31:30
right so two is
00:31:33
thrombin and then two activates one what
00:31:35
is one
00:31:39
fibrinogen so again how do I do it x
00:31:41
marks the spot 10 count backwards
00:31:44
starting with 12 skipping 10 so TW 10 12
00:31:47
sorry 12 11 9 8 and then he had
00:31:52
10 how do you remember the x transic 3 +
00:31:54
7 = 10 and then how do you remember the
00:31:57
formation of uh the the thrombin so you
00:32:00
have remember 5 * 2 * 1 equals 10 right
00:32:05
so five is going to be who Factor five
00:32:08
two is going to be thrombin and then
00:32:10
thrombin is going to be activating
00:32:11
fibrin so you can remember that again 10
00:32:13
with five activates two two activates
00:32:18
one so that's a very quick easy little
00:32:20
trick to be able to remember the
00:32:21
coagulation Cascade okay so again what
00:32:24
have we done then we finished this third
00:32:26
step which is coagulation Cascade so we
00:32:28
finished the third step coagulation
00:32:31
Cascade now let's go to the fourth step
00:32:33
so again what do we have over
00:32:36
here we had damage to the endothelial
00:32:38
lining right it's just a constant review
00:32:42
of this guys so again damage
00:32:45
here then what do we have on Wilder
00:32:48
bronze Factor
00:32:49
here then we have our platelets
00:32:55
here here's our plet plug the platelet
00:32:58
plug is releasing tons of different
00:33:00
chemicals right causing the platelet
00:33:03
aggregation causing the plet plug
00:33:04
formation vascular spasm then we have
00:33:06
the coagulation
00:33:08
Cascade which is leading to the
00:33:10
production of the fibrin
00:33:12
mesh with the intrinsic and the
00:33:14
extrinsic pathway now we go to our
00:33:15
fourth step what is the fourth step the
00:33:19
fourth step is
00:33:21
called
00:33:22
clot
00:33:25
retraction and repair
00:33:28
hair so you see these plets they have
00:33:31
contractile proteins within them it's
00:33:33
called actin and myosin so what they do
00:33:35
is
00:33:36
Imagine imagine my arms are the
00:33:38
platelets right so imagine I'm the
00:33:40
platelet right here what I'm going to do
00:33:42
is I'm going to take one arm over here
00:33:44
and I'm going to grab I'm going to grab
00:33:46
the endothelial cell on this side and
00:33:48
then I'm going to grab the endothelial
00:33:49
cell on this side what I'm going to do
00:33:50
is I'm going to pull the edges of the
00:33:52
endothelial cells closer together right
00:33:56
by doing that I'm bringing those
00:33:58
ruptured edges of the blood vessel
00:33:59
closer together so again what does the
00:34:01
platelet do within this step the first
00:34:03
thing that's going to happen is
00:34:07
platet
00:34:10
contraction and that will pull the
00:34:12
ruptured edges of the blood vessel
00:34:14
closer together second thing that's
00:34:16
going to
00:34:17
happen it's going to secrete a chemical
00:34:19
these platelets nearby are going to
00:34:21
secrete a chemical which is
00:34:24
called platelet
00:34:28
derived growth factor so this chemical
00:34:30
is called platelet derived growth
00:34:35
factor what does this PL deriv growth
00:34:37
factor do the pl derived growth factor
00:34:39
comes down here and if these smooth
00:34:42
muscle cells were damaged so let's say
00:34:43
that the smooth muscle cells were
00:34:44
damaged right here there was damage to
00:34:46
these smooth muscle cells the plet
00:34:48
derived growth factor is going to
00:34:50
trigger trigger the mitosis or
00:34:52
proliferation of the smooth muscle
00:34:54
lining and on top of that if there was
00:34:56
any damage to these connective tissues
00:34:57
here it's going to cause connective
00:34:59
tissue patches to be formed to
00:35:00
regenerate those collagen fibers so it's
00:35:03
going to help to produce connective
00:35:04
tissue patches to repair the collagen
00:35:06
maybe even produce connective tissue
00:35:08
patches over this endothelial cell
00:35:10
area and it's going to help to
00:35:12
proliferate the smooth muscle to renew
00:35:14
that lining so again what is this
00:35:16
chemical here called This is called
00:35:17
platelet
00:35:19
derived growth factor what is the third
00:35:22
thing that happens there's one more
00:35:24
chemical and that chemical is called
00:35:26
vascular endothel
00:35:28
growth
00:35:29
factor and again the pl will secrete
00:35:32
that chemical so again what is this
00:35:33
chemical
00:35:34
called This is called vascular
00:35:37
endothelial growth factor what do you
00:35:40
think it does it says it within its name
00:35:42
the vascular endothelial growth factor
00:35:44
is going to regenerate the new
00:35:46
endothelial lining so any of the
00:35:48
endothelial lining that we damage it's
00:35:49
going to help to regenerate that okay so
00:35:52
again CLA retraction repair it's going
00:35:53
to contract pull the pl ruptured edges
00:35:55
closer to one another secrete p dgf to
00:35:58
proliferate the smooth muscle and
00:36:00
produce connective tissue patches here
00:36:02
and then it's going to release vascular
00:36:03
endothelial growth factor which is going
00:36:05
to replenish the new endothelial lining
00:36:07
and it can lead to what's called
00:36:09
canalization but we're not going to do
00:36:10
that here that's the fourth step all
00:36:13
right so this last step here this last
00:36:15
step the fifth and final step for this
00:36:17
process is called
00:36:19
fi
00:36:21
breno
00:36:22
Lis so you remember here that we had
00:36:26
that clot right
00:36:28
now this area can get pretty big and
00:36:30
sometimes it can get so big that it can
00:36:32
actually olude the blood vessel flow
00:36:33
beyond that area and lead to aeia right
00:36:35
so we don't want that so what we want to
00:36:37
do is is we want to be able to get rid
00:36:39
of that clot we want to bust that clot
00:36:41
up
00:36:42
so there's natural proteins present here
00:36:45
on the cell membrane here so what is
00:36:47
this protein called right
00:36:50
here this protein right here is called
00:36:53
they have two names for you can call
00:36:54
them tissue plasminogen activator
00:36:56
sometimes they even call it strepto
00:36:58
but we're going to just call it tissue
00:37:01
plasminogen
00:37:03
activator so what is the tissue
00:37:05
plasminogen activator do there's a
00:37:07
protein naturally present within your
00:37:09
bloodstream again and this protein is
00:37:11
called
00:37:13
plasminogen it's called
00:37:16
plasminogen and plasminogen will react
00:37:19
with the tissue plasminogen activator
00:37:21
and get converted into what's
00:37:24
called
00:37:25
plasmin and imagine plasman as though
00:37:29
he's like a hungry little eater here so
00:37:33
look he's got nice little teeth in here
00:37:35
right and he's ready to eat what he's
00:37:38
going to do is he loves to eat
00:37:40
fibin okay so he loves to eat
00:37:44
fibrin all right I love fibrin right so
00:37:47
what he does is he's going to come over
00:37:49
here and he's going to start digesting
00:37:51
that fibr mesh he's going to start
00:37:53
cutting that fiin mesh up and what is he
00:37:56
going to do then by degrading the fibrin
00:37:58
mesh he might release a little bit of
00:37:59
fibrinogen out here which remember was
00:38:02
the
00:38:03
precursor and he also might release a
00:38:05
very very important chemical called a d
00:38:08
peptide or a
00:38:09
d
00:38:12
dier why is this
00:38:14
important when they run specific blood
00:38:16
tests to determine if someone's had some
00:38:18
type of clot formation they run a d dier
00:38:21
it's really important because we run a d
00:38:22
dier and we see elevated D dier levels
00:38:24
that can help us to understand maybe
00:38:25
this person has had some type of clot
00:38:27
form
00:38:28
so dmer is very important for Diagnostic
00:38:30
uh procedures within differential
00:38:32
diagnoses right so again what is this
00:38:34
going to do plasma into plasma it's
00:38:36
going to digest the fibrine and bust
00:38:38
that clot up right and by busting up
00:38:41
that clot that helps to be able to
00:38:42
prevent uh e clusion to the blood
00:38:44
vessels right one more thing why is this
00:38:47
TPA important we give this to people who
00:38:49
have some type of a a stroke so if they
00:38:52
have some type of transin es schic
00:38:53
attack that's blocking the uding the
00:38:55
blood flow to the cerebral vessels the
00:38:57
TPA we're going to give that to them in
00:38:59
the acute response within hours you
00:39:01
needan you need to give it within hours
00:39:03
because they also give aspirin in
00:39:04
response to this too but TPA what is it
00:39:06
going to do when you give it to them
00:39:07
it's going to make plasmine what's
00:39:08
plasma going to do it's going to start
00:39:10
breaking down that fiin mesh to get rid
00:39:13
of that blood clot right and that's
00:39:14
important because we don't want to have
00:39:16
too much blood blood loss to a specific
00:39:18
area within the brain because it can
00:39:19
lead to
00:39:20
cytotoxicity and that what leads to the
00:39:22
the damage to some of the neurons within
00:39:24
that area and it can lead to limb
00:39:25
weakness and problems with that right
00:39:27
all right so that covers our fifth step
00:39:28
which is fibron analyis let's come back
00:39:29
over here do a quick recap of everything
00:39:32
and talk just really really briefly
00:39:34
about a couple drugs all right so again
00:39:36
what was that first thing that we wanted
00:39:37
to go over again what keeps the blood
00:39:39
naturally thin the nitric oxide the
00:39:41
prostacyclin and activates the platet
00:39:43
the Heparin sulfate the anti-thrombin 3
00:39:45
and activate some of these coagulating
00:39:47
proteins Pro coagulating proteins and
00:39:49
then thrombomodulin thrombin and protein
00:39:51
C and activate other procoagulants so
00:39:53
again this is all our step one but it's
00:39:55
again it's what keeps the blood
00:39:57
naturally thin
00:40:00
now what kind of drug could we use here
00:40:03
to enhance this process if someone needs
00:40:05
to be able to prevent themselves from
00:40:06
having a cloth well you know
00:40:07
antithrombin 3 we can give a molecule
00:40:11
called Hein and what does Hein do if we
00:40:15
give more Hein it's going to enhance
00:40:19
antithrombin reactivity if you enhance
00:40:21
antithrombin re activity what are you
00:40:22
going to do you're going to destroy a
00:40:23
lot of these procoagulants keeping the
00:40:25
blood naturally thin
00:40:28
all right what's this first step here
00:40:29
that we went over vascular spasm what's
00:40:31
the whole purpose of it just to be able
00:40:33
to keep blood from uh prevent blood from
00:40:35
continuously being lost right by how
00:40:37
vasoconstricting the blood vessel and
00:40:39
preventing as little blood as possible
00:40:41
from leaking out into the tissue spaces
00:40:43
right and causing hematomas and other
00:40:44
damage severe blood loss right that's
00:40:47
important there Second Step plet plug
00:40:50
formation again what was the whole
00:40:52
purpose here the plets love to bind with
00:40:53
the Von Wilder Bron's Factor there okay
00:40:56
now one more thing here when these
00:40:57
playlets aggregate right how can we
00:40:59
prevent the
00:41:00
aggregation well you remember
00:41:03
ADP ADP there is a a drug that can
00:41:06
actually block ADP this drug is called
00:41:13
cigil so what does it do it inhibits
00:41:17
ADP that's one drug that you can give
00:41:20
another drug that you can give inhibits
00:41:22
the formation of thromboxane A2 which
00:41:24
it's a Cox 2 inhibitor and this is
00:41:26
called everybody usually knows this one
00:41:27
this is called
00:41:30
aspirin and an aspirin inhibits thromb
00:41:32
boxy A2 you can also give a drug to
00:41:35
block this glycoprotein 2 b3a protein
00:41:38
right and this is
00:41:40
called ab6
00:41:43
aab and ab six amab inhibits the
00:41:46
activation of the glycoprotein 2b3a
00:41:47
connection so a lot of things that you
00:41:49
can do you can also give direct uh
00:41:52
proteins in here you can actually give
00:41:53
some some specific Inhibitors you can
00:41:56
actually give a direct bromen Inhibitors
00:41:58
you can give uh I'm sorry direct Factor
00:42:00
10 Inhibitors and you can give Factor 2
00:42:02
Inhibitors uh common factor 2 Inhibitors
00:42:04
are like the botran or praxa as the
00:42:07
brand praxa or deigan
00:42:10
etexilate that can inhibit this enzyme
00:42:12
right
00:42:13
there okay so there's a lot of different
00:42:15
drugs that you can give here to be able
00:42:16
to treat some of these conditions right
00:42:18
you can also give warrin and what is the
00:42:19
purpose of warrin
00:42:22
warrin is a vitamin K oxide reductase
00:42:25
inhibitor what the heck does that even
00:42:27
mean you know there's specific proteins
00:42:29
like Factor
00:42:31
2 Factor uh
00:42:35
seven factor nine Factor 10 protein C
00:42:39
protein s whole bunch of different
00:42:40
proteins they require vitamin k What
00:42:44
warrin does is it inhibits the enzyme
00:42:46
that actually uh pushes that vitamin K
00:42:48
into these enzymes making them
00:42:49
functional so if you don't have vitamin
00:42:52
K what's going to happen to these
00:42:54
procoagulants they're going to be
00:42:55
inhibited and not functional that's
00:42:57
another drug that you can give someone
00:42:58
to be able to inhibit the clot formation
00:43:01
so again that's in a nutshell everything
00:43:04
we're going to need to know about
00:43:04
hemostasis and just a very basic amount
00:43:07
of drug information that we can go to
00:43:10
understand a little bit more about that
00:43:11
pathway
