[Music] so this is our second video in this first week of 228 where we're getting into the topic of blood and in this particular video what we're going to talk about is hemostasis so this is a term that's new to most people hemostasis means the stoppage of bleeding so when you start bleeding when you have a cup something like that and you're bleeding hemostasis is the process that your body goes through in order to stop that bleeding this believe it or not is one of the most complex if we wanted to make it that way one of the most complex topics in the entire anatomy and physiology Series so if you remember our 227 class okay and when we did muscle contraction and when we did nerve impulse conduction it's on that level possibly worse if we want to make it that way and I don't want to make it that way so here's what we're going to do I'm going to give you kind of an overview to this topic and we're going to go through the overview and then we'll break it down okay and look at each of the steps in a little bit more detail and kind of simplify that way so that okay if you start feeling like you're getting bogged down into this particular topic you can come back to this overview remind you there's yourself there's these three basic steps that are going on and think about the topic from that particular standpoint so hemostasis again stoppage of bleeding um the first thing that happens in this particular process is what's known as a vascular spasm so if you think about a blood vessel right here's a cross section of a blood vessel it's got blood moving through the center of it if you get a Nick or a cut in a blood vessel that blood vessel is open and that allows blood to be able to flow out of it and you're bleeding right and the very first thing that happens in order to try and stop that so that you're not losing blood is what's known as a vascular or spasm and when you have a vascular spasm what happens is this reflexively that blood vessel that's been cut is going to constrict and just doing that in and of itself is going to decrease the diameter of the blood vessel allow less blood therefore to be able to enter into the blood vessel and that's going to limit the blood that's leaving the blood vessel so that in and of itself just an immediate response is really going to slow down blood flow when you have a wound that is bleeding the second thing that happens is we get formation of what's known as the platelet plug so we talked about platelets or thrombocytes in our last video they are those cells right cell fragments really that are kind of floating around in the bloodstream and I mentioned that they play this role in clotting so we've got this blood vessel it's been cut we've had this constriction this vascular spasm but we've still got a hole right we've still got a hole that's in that blood vessel that is going to allow some bleeding to occur so the next thing that happens is we get those little cell fragments those platelets they start collecting over that hole in the blood vessel and they kind of form a soft Band-Aid over it if you will and that's going to also help along with the vascular spasm to slow down the bleeding both of those first two steps so the vascular spasm which happens immediately the platelet plug formation which happens very quickly after that they cannot stop bleeding completely but they're there to kind of slow down the loss of blood as much as possible wow we initiate coagulation so coagulation is where this process starts to get complicated but basically what happens in coagulation is the blood which is normally a liquid right it's normally that liquid plasma which is mostly just water with some cells that are dissolved in it okay floating around that liquid blood actually changes into a solid so if you've seen a blood clot that's what's happened that blood has coagulated and the liquid or the previously liquid blood has now become a solid so that's what coagulation is so that's kind of the big picture that's what I want you to keep in mind if you start getting kind of bog down in the details of what's going on with this particular process so now that we've looked at kind of the big picture maybe simplified it a little bit giving you an overview what I want to do now is talk about each of those steps in a little bit more detail and you'll remember that the first thing that happens when you have a blood vessel that's been cut that's losing blood is we get a vascular spasm so that's that blood vessel constricting down right so that we're going to limit blood blast as much as possible through it and that's going to happen immediately there's a few things that are actually going to trigger this and in order to be able to talk about what triggers this I really probably need to give you some background in blood vessel anatomy and the layers of a blood vessel wall in order to be able to understand that so in order to understand how this vascular spasm is initiated it's really important that you understand what a blood vessel actually looks like anatomically and the walls that make it up so most of the blood vessels in the body have three layers to their wall we have an outermost layer okay which I'm going to represent here and kind of this blackish color and this outermost layer is made up of connective tissue so it is almost entirely collagen fibers that protein collagen that you've heard about before and then inside of that we have a second middle layer to the blood vessels wall which I'm going to represent in red and this layer is composed of smooth muscle so we've got kind of a circular muscular layer inside of those blood vessels and that's what allows blood vessels to be able to constrict down okay because they've got that muscle there or be able to relax and open up because that muscle is present and then we also have a third layer within blood vessels I'm going to draw that third layer in this is the innermost layer I'm going to represent it in blue this layer is known as the endothelium it's really thin it's a single layer of cells typically and they are squamous shaped cells so the most thin type of cell there is but the role of this endothelium inside of blood vessels is to make the inside of blood vessels really slick because remember we've got 60 000 miles of blood vessels that go throughout the body and blood has to move through that and the heart has to pump that blood through all of those sixty Thousand Miles and so we don't want friction and we don't want resistance to blood flow so we've got this innermost layer this endothelium that's really slick inside of the blood vessel so now that you've got this introduction to blood vessel Anatomy okay the layers of the wall it's going to make more sense to talk about some of these things that actually initiate the vascular spasm so if you look at this diagram here you can see a blood vessel right it's been cut here's some red blood cells inside of it that now potentially are going to be leaking out you're going to be bleeding and you'll notice that the first thing according to the slide that initiates that vascular spasm is injury to the vascular smooth muscle so we talked about that middle layer of smooth muscle and it is going to reflexively contract down immediately upon injury to decrease the diameter of that blood vessel we also talked about the endothelium right that innermost layer that's really slick it's helping to decrease friction as the blood is moving through the blood vessel and the cells that make up the endothelium they are going to start when they're damaged right because they've been cut as well they're going to start releasing chemicals that are going to help to hold that vascular spasm and kind of keep it in place platelets so the clotting cells that we talked about previously the thrombocytes that are present in the blood they're also going to be producing chemicals that are helping to hold that vascular spasm and then the last thing is if you've got a cut to a blood vessel you've got damage to tissue right you've got skin that's been cut potentially other tissues that have been cut as well and we've got pain receptors that are embedded in those tissues that are also going to initiate a reflex that causes that vascular spasm and helps that vascular spasm to hold in place so if you look at this picture down here okay we've we've had our vascular spasm occurs we're kind of holding the diameter of that blood vessel a little bit tighter and then the next thing that happens is we get formation of the platelet plug so remember this is when those thrombocytes those platelets that are floating around in the blood start to migrate into the area of the injury and they start to stick to the broken area and they form kind of a soft Band-Aid over it we talked about the endothelium earlier with the picture that I drew on the board and I talked about how it's really slick and that's super important because we don't normally want platelets to stick to that endothelium when you get platelets sticking to the endothelium when it's not damaged and you get fatty plaques that are building up on an endothelium when it's not damaged those are the situations that lead to heart attacks and strokes right so normally when the endothelium is intact it's super slick and platelets if you're healthy don't attach to it because that forms a blood clot or it initiates the classes the process of cladding if you look at this picture down here though the endothelium has been cut through smooth muscles cut through and we've got that collagen layer so that most external layer connective tissue on the outside of the blood vessel and it's exposed right and so that's what the platelets actually start to adhere to is that outermost layer of the blood vessel and once you get one platelet in there a Deering it releases chemicals that call in more platelets and those platelets release chemicals that call in even more platelets so you get basically this positive feedback mechanism occurring that's going to lead to platelets congregating in that specific area and forming kind of this soft tissue bandage over the cut that has happened to the blood vessel so we've looked at basal constriction and we've talked about platelet plug formation and those first two steps of hemostasis are that just there to bias time like that's what they're doing they don't stop the blood flow they limit the blood flow and they give us time for coagulation to occur so coagulation is where this starts to get complicated and the reason that I say that is there are a whole bunch of chemical reactions that allow for coagulation to occur and because there's a whole bunch of them even though they're initiated as soon as damage to a blood vessel occurs it takes some time it takes 30 60 seconds for all of those chemical reactions to complete in order to change the blood from a liquid to a solid which is what coagulation actually is so coagulation is the last step of hemostasis because it takes the longest to complete it's also the last step because it's the final thing that needs to happen once coagulation has occurred and you've changed that blood from a liquid into a solid the bleeding should stop if you look at this picture over here so that's showing you a blood clot under a microscope and you've seen some pictures already of blood right and we've talked about the red blood cells and the white blood cells and you can see those in this picture what you're seeing with this particular picture in coagulated blood that wasn't present before is a net right there's like this net that has been woven in the blood and that net is actually trapping these formed elements right the white blood cells the red blood cells and it's holding them in place and that net trapping those blood cells and kind of holding them in place is literally what's forming the clot so the entire reason that the blood coagulates believe it or not is just to form this net-like structure inside of the blood which doesn't exist prior to coagulation so that that net-like structure can trap those blood cells and we can convert that blood from a liquid into a solid so I mentioned previously those chemical reactions the whole series of chemical reactions that has to occur in order for us to coagulate the blood to change it from a solid or from a liquid sorry into a solid so if you look at this diagram here okay this is a graph that represents all of these chemical reactions the coagulation Cascade if you go online even if you look in your textbooks you're going to find representations of the coagulation Cascade that are much more complicated than this because this is a complicated process unless you are becoming a doctor and specifically you're going into hematology so you're a blood specialist you do not need to know the coagulation Cascade on that level so this much more simplified graph is much better for the purposes of our class and I would suggest as you're studying this material for art class that you use this graph even above the graph that's in the textbook which is more complicated okay so with that being said um still some complication here right and so I want to talk through this and kind of walk you through this so we have this whole series of chemical reactions that's represented okay and I'll talk about the shorthand way in which it's represented in just a second but these chemical reactions start up here okay and over here in this chemical reaction causes another chemical reaction causes another chemical reaction causes another chemical reaction and so we've got this Cascade right if you will this waterfall of reactions that are occurring and because of that we refer to this as the coagulation Cascade but the whole idea behind the coagulation Cascade is when we get down to here when we get to the very end of it we're actually using these chemical reactions to weave that net in the blood from substances that are within the blood all the time but not normally in the shape of a nut and so that we can capture those blood cells okay and that's what's going to convert our blood from a liquid to a solid all of these chemical reactions take time so they start when the vascular spasm starts and when the platelet plug starts but those are pretty immediate responses and meanwhile all of these chemical reactions are occurring and eventually okay 30 60 seconds later we get that blood clot actually being formed so here's some more stuff just kind of background information before we get into the coagulation Cascade specifically that's important for you to know to be able to understand it you'll notice we have all of these Roman numerals so these Roman numerals are actually the shorthand names for chemicals that are found in the blood these chemicals are known as clotting factors you'll also sometimes hear them referred to as pro-coagulants okay so these are just our shorthand names that are used usually in graphs because these guys have some really weird long names like one of them is called Christmas Factor okay so it's just easier to say clotting Factor five than to write out all these long weird names but the clotting factors have so that's the reason for the Roman numerals there are 12 clotting factors okay they are normally in the blood all the time we all have them they're floating around in our blood in an inactive form um oddly enough and I'm going to explain why this is I mentioned that we have 12 clotting factors or 12 Pro coagulants and they are numbered 1 through 13 okay so the reason that they are numbered 1 through 13 is they were assigned Roman numerals in the order that they were discovered so the first one that was discovered is this chemical right here which has the name of fibrinogen it's clotting Factor number one the next one that was discovered is prothrombin which was clotting Factor two clotting factor three is tissue Factor okay so it's up here and then there was clotting factor four and five and six and seven and eight nine ten eleven twelve thirteen that were all discovered and once we had them all discovered and all named and they all had these Roman numerals assigned to them the scientists realized that clotting factor six and clotting Factor five were the same thing so clotting factor six no longer exists we've got 12 clotting factors we didn't renumber 7 8 9 10 11 12 and 13 we just let them be okay so 12 clotting factor is numbered 12 through 13. so you look at this I mentioned before that this coagulation Cascade starts up here so we've got clotting Factor 12 okay and clotting Factor 12. when there's damage to a blood vessel it physically changes that chemical in the blood and it activates it basically so when there's damage to a blood vessel clotting Factor 12 or Pro coagulant 12 this chemical that's always in the blood converts into its active form so then we call it 12a a just means it's become active when we have 12a in the blood it converts clotting Factor 11 into its active Factor okay so it becomes activated when 11 is activated it converts nine okay into its active form and so you're probably like ah stop why isn't this going in order right like it would be really nice if it was 12 11 10 9 8 7 6. and that goes back to the fact that these things were named and assigned Roman numerals based on when they were discovered so this was our 12th one discovered this was our 11th this was our ninth right they were discovered in that order but that's not the order that they activate themselves okay so we get these activating nine or eleven when it becomes active activates nine nine activates eight eight activates ten ten activates five five activates two two activates one one is this little small Protein that's in the blood and when one becomes active that little small protein within the Blood starts to join with other little small proteins in the blood and you get these long strands of proteins being formed and once you have those long strands of proteins being formed in the blood we get clotting Factor 13. So Pro coagulant 13 it becomes activated and what it does is it cross-links all those long strands so we have these long strands right floating around in the blood and 13 is going to cross link them all so that we form this kind of net like structure within the blood itself okay so I mentioned previously that we all have these clotting factors these Pro coagulants they're floating around in the bloodstream at all times when there's damage to a blood vessel they become activated and that's going to initiate this pathway that leads to our net right our net of protein being formed within the blood so that we can start trapping these blood vessels so we've got this coagulation Cascade that occurs and when I see this honestly the most simple way to think about it is dominoes so I used to play with dominoes when I was a kid my Grandma had them at her house and if you've ever played with dominoes you know you can like stack them up right and if you knock one down it knocks down the next one which knocks down the next one which knocks down the next one and you get this Cascade of falling dominoes all the way down here okay this is the exact same thing and I think if you can think about it in that way it can really help you right like all of these chemicals are present in the blood all the time all of these dominoes are there but we have to activate one of them to activate the next to activate the next to eventually get down here to where we have this cross-linked clap in the activity that you guys are working with for this particular folder you are going to be looking at hemophilia which is a condition where a person is missing one or more of these clotting factors so very very often it's either clotting factor eight or its clotting factor nine that they are actually missing if you can imagine this again kind of using that Domino idea if you are a hemophiliac and you are missing clotting factor eight and you have damage to a blood vessel okay 12 is going to activate it's going to activate 11 which is going to activate nine and now we have a missing Domino right there's a gap there's no 8 to activate and that means for a hemophiliac this coagulation Cascade stops right here they can't activate 10 which means they can't activate five which means they can't activate any of these and they are not able to clot their blood for that particular reason with this activity another thing that you're going to be working with is looking at different snake Venoms so snake Venoms believe it or not at least way back in the 30s the Venoms of some snakes were looked at as a treatment for hemophilia and the reason for this is snake Venoms kind of across the board do one of two things to the coagulation Cascade so some snake Venoms are activators of the coagulation Cascade and what that means is they are an activator of one of these Pro coagulants so you're going to be working with a snake specifically in this activate in this activity that's a factor five activator okay so if you think about a snake that is a factor 5 activator you get bit by that snake it puts that Venom into your body okay you don't need any of this that's actually like hitting this Domino which is going to make these other dominoes fall and you're going to get a clot forming right and you're going to get a platforming extremely rapidly because you started the process down here as opposed to up here if you haven't before I would suggest going to YouTube and looking at some of the videos of what snake venom does to blood and test tubes it's like immediate chunky coagulation because of that okay there are other snakes that have Venoms that actually inhibit a factor in the coagulation Cascade so you're going to be looking for example at spitting cobras which inhibit I believe factor three that's tissue Factor here what that means is it prevents factor three from being able to become active if you cannot active activate a clotting Factor because it's inhibited by a snake venom that has been introduced into your body now you can't get clotting to occur right it's just like removing that clotting factor from this equation and you're never going to get a clot forming and and you're probably going to have some bleeding issues because this Venom is causing this particular situation all throughout your body so you're going to be working with those two things right snake bites hemophilia looking at how they affect this coagulation Cascade in the activity that you're doing this week and that in a nutshell is the coagulation Cascade and the process of hemostasis