Hemostasis and the Clotting Cascade (Why Vitamin K & Calcium are important!)
hi every R Dr Mike here in this video. we're taking a look at how the body can. stop itself from bleeding a process. known as hemostasis and we're going to. focus on an aspect that students tend to. have a lot of difficulty with which is. the clotting Cascade and how all those. various factors 1 to 13 fit in today. we're going to make it. easy so to begin with we need to talk. about blood clotting and the fact that. if you were to cut a blood vessel so we. got a blood vessel right here if you.
were to damage that blood vessel in some. particular way and what you've now done. by damaging that blood vessel is you've. now exposed the internal aspects of the. blood vessel so the blood itself this is. going to be the fact that we've got red. blood cells we got white blood cells. we're going to have all of these ions. and solutes and nutrients and wastes and. gases and blood. plasma it can leave that blood vessel. that's obviously not a good thing. because once the contents of the the.
blood leaves if the plasma leaves our. blood volume drops the tissues don't get. fed we can die if our red blood cells. leave we no longer have that oxygen. carrying capacity we can die this is. something we need to fix quickly and we. do this by creating what we call a clot. now that's the end stage of this process. but a couple of things happen before the. clot and so I want to talk about that. and this whole process together is. called hemostasis let's write this. down.
hemostasis now there's actually three. steps to hemostasis and it's quite. simple to be honest the first step of. hemostasis is something that we call. vascular. [Music]. spasm vascular spasm well I want you to. think about this you've damaged a blood. vessel right we don't want any of these. contents to leave what does the blood. vessel do reflexively to try and. mitigate the blood loss straight away.
well it spasms what it does is it tells. itself to constrict to narrow so if this. blood vessel told itself to narrow that. means the blood the incoming. blood is not going to be able to get. past and that means it can't leave the. blood vessel brilliant now this vascular. spasm which in actual fact is Vaso. constriction it happens because of a. number of different factors that are Rel.
so when this tissue is damaged remember. that your blood vessel is made up of. endothelia this is epithelia right these. squish cells it's made up of endothelia. and then underneath that endothelia we. have connective tissue that we call the. basement membrane so when you damage. this blood vessel couple things happen. you damage the cells of the area and. they're going to release their various. cellular components some of these. cellular components include things like.
prostaglandins prostaglandins now. prostaglandins are really important. particularly one that's released during. this process which is called thromboxane. A2. thromboxane A2 and what thromboxane A2. does is it Vasa constricts what it also. does is it promotes one of the later. phases called platelet aggregation but. we'll get there in a sec another. chemical that's released in this process.
is. serotonin and you've heard of Serotonin. as a neurotransmitter but what serotonin. can do is Vasa constrict another one. is. noradrenaline another one is. ellin there's a whole bunch of chemicals. that are released that basically Vasa. constrict in the immediate moment so. that's the first thing that happens is. that vascular SP spasm mitigating any. blood loss the second thing that.
happens is what we call the platelet. plug platelet. plug all right think about this once. you've damaged this blood vessel you've. now damaged the endothelial cells but. you've also now. exposed the underlying connective tissue. that b membrane and this tissue is made.
up of a lot of collagen so you've got. all of this collagen now that's. exposed right now the thing about. collagen is it's negatively. charged right so we've got all of this. negatively charged. collagen exposed now the thing about. collagen apart from it being negatively. charged is it's sticky and as the blood. that's moving past remember blood. doesn't just have red blood cells white. blood cells and the various solutes that.
are sitting within the plasma it also. has some cell products like platelets. what we call thrombos sites and so. you've got these platelets that are. coming past I'm going to draw them as. little squares and as the platelets come. past they get. stuck to the collagen beautiful and when. one platelet gets stuck it starts to. release factors that promote more. platelets to get stuck but here's the. thing when you damage endothelia.
and you've got platelets coming in both. endothelia and let's write this down. both. endothelia and. platelets release something really. important releases this. protein. called Von. willbrand. Factor Von willbrand Factor now what. this Von Willer brand Factor does is.
something important platelets are also. negatively. charged now if you've got negatively. charged platelets but you've also got. negatively charged collagen they're not. going to really want to stick together. very much so luckily what we have is. something called Von Willer Brands. factor and what Von willbrand Factor. does is it creates this intermediate it. basically tethers it holds on to. platelets on one end and it holds on to. the collagen on the other end and holds. them together so if we were to zoom in.
at this point. here let's take a quick look we've got. all this free collagen. now that's sticking out we've now got. this Von Willer brand. Factor that's been released from the. endothelia and the platelets and then it. allows for the platelets to stick so now. we've got all all these sticky platelets.
and what these platelets are. doing once the Von willbrand. Factor has been released is it starts to. form a. plug so now we've got this platelet plug. that's formed beautiful because of Von. willbrand Factor now think about this. what if Von Willer brand Factor wasn't. produced what if somebody had a mutation. and that mutation didn't Express Von. willbrand Factor well somebody would. bleed far more easily and that can.
happen when somebody has Von willbrand. disease sometimes you can express too. much Von willbrand factor and you. unfortunately clot when you shouldn't. clot because now you've got Von. willbrand Factor floating through. pulling all these platelets together so. that's an important clinical factor to. understand about Von willbrand Factor. but this is the thing this platelet plug. that's formed isn't the clot this is. phase three of hemostasis phase three of. H stasis is clotting and this is where.
students start to have difficulties is. what we call the clotting. Cascade so what I want to do is I want. to draw up the clotting Cascade and the. clotting Cascade is really important and. students tend to lose their minds. because there's all of these various. factors associated with the clotting. Cascade now because it's biology we love. to make things difficult so instead of. just numbering all of these various. factors 1 to 13 we use Roman numerals we.
use a way of counting that hasn't been. used for 2,000 years cuz that's what we. love to do so let's write down all of. the factors the clotting factors. involved in this process because we want. to form a clot right ultimately so these. factors let's write these down are. one. 2. 3 4. 5. 6. 7 8.
9. 10. 11. 12. and 13 oh how good we have to talk about. 13 factors well we don't actually have. to talk talk about 13 factors I'll tell. you why because there's basically no. such thing as factor three there's no. such thing as factor four and there's no. such thing as factor six so we don't. really have to talk about those some. times in some textbooks they do refer to.
factor 3 and four I'll talk about that. in a second all right so let's start the. thing about clotting is this at the end. of the day we want to create a clot so. remember we've got all those platelets. aggregating together what we want to do. is take these fibers and these fibers. are really important they're called. fibron and we want to embed these fibron. fibers and mesh them together and this. is the clot that we form this allows for. the blood to stop leaking out but also. facilitates the healing process so how.
do we start this firstly the clotting. Cascade has two major Pathways let's. draw them. up all right you've got the. intrinsic. pathway and you've got the. extrinsic. pathway of the and Cascade right now.
what's the difference between these two. all right think about this the intrinsic. pathway is when you have damage to the. blood vessel so when that blood vessel. is damaged so. damaged blood vessel that's when you. stimulate the intrinsic pathway and in. actual fact when you damage the blood. vessel you release stuff or certain. things happen I should say when you. damage a blood vessel you're going to. have damaged.
endothelia you're going to. have. collagen available right you're going to. have that collagen sticking out and. you're going to have the presence of. platelets that's what happens in the. intrinsic pathway that makes sense we. drew it up before right what about the. extrinsic pathway What's Happening Here. extrinsic is from without intrinsic is. from within makes total sense damage. blood vessel you damage the endothelia.
which is the epithelia you've now got. exposed collagen and you've now got. platelets accumulating because of that. platelet plug right extrinsic from. without this is odd so what this is. referring to is anytime you have tissue. damage but the blood vessel itself isn't. damaged now it can include damaged blood. vessel but basically this is when you. have tissue damage so not damage blood. vessel necessarily but tissue damage now. your your argument might be well a.
damaged blood vessel is tissue damage. true which means anytime you do damage. the blood vessel both Pathways get. activated but let me delineate what this. is referring to they did a study where. they took a I think it was a mouse and. they took I think part of its brain and. just mushed it up so damaged that tissue. and just introduced that damaged tissue. into an intact blood vessel and this. damaged tissue released factors that. stimul ated clotting in the intact blood.
vessel but it was through a different. pathway that's what's called the. extrinsic all right so what happens in. this case is the release. of what's. called. tissue. factors or specifically a tissue Factor. called. thromboplastin so let's write thrombo. plastin down. thrombo plastin.
that's the tissue Factor that's released. let's start with the intrinsic so this. is how we work it right this is how to. make it. easy we want to let's make this a little. bit bigger cuz I think. it'll throw in pens all over the place. I'm all goofy today all right that's. better so let's start here at the very. end and we're going to work our way. backwards but we're not going to start. at 13 we're going to start at 12 just to. make things easy let's start at 12 so. what happens is this you've got Factor.
12 floating through the system when. Factor 12 comes into contact with. damaged endothelia exposed collagen or. platelets that have aggregated they all. activate clotting Factor 12 now all of. these factors here are proteins that are. produced in the. liver right they're proteins that are. produced in the liver and this is. important because if you have liver.
damage or problems with the liver you. might have issues with your ability to. clot again another important clinical. point so we've got this Factor 12 and. like I said Factor 12 is inactive it. needs to get activated all of them are. actually inactivated and need to be. activated how does this happen well. Factor 12 when it comes across these uh. various things like I said it will. activate. it into an active form of 12 now we. denote a little a there to highlight.
that it's the active form now what. happens well we've just spoken about 12. so we can cross that off what's the next. one as we move back 11 so you've got. Factor 11 floating through the. system it needs to be activated when it. comes across activated Factor 12 what do. you think it makes activated. Factor 11 okay cool let's cross that one. off now the thing is this is really.
important Point as you can see both the. intrinsic and extrinsic clotting. Pathways they Converge on a common. pathway they Converge on a common. pathway now this is where we need to. meet this is where they meet and so what. do we say there x marks the spot right x. marks the spot where the two Pathways. meet and this is where we start talking. about X now again X needs to be. activated or I should say 10 needs to be. activated but I'm not going to talk.
about what activates it yet let's just. know that x marks the spot number 10. Factor 10 is where they converge so. we've spoken briefly about 10 the next. is nine so we need to talk about nine. this is where you've got nine floating. through the. system and it comes across. 11 and. becomes. activated all right what does nine do. what nine does is. it activates.
10 nine activates 10 isn't that. beautiful all right but importantly nine. cannot do this unless it has a couple of. additional factors associated with it so. nine Cann not activate Factor 10 unless. it has three things right three things. let's draw these three things up and. I'll discuss them later first thing is. it needs vitamin. K second thing it needs is. calcium and the third thing it.
needs is factor eight the next. one so without that now what factor 8. does is it forms a complex and the. complex that it forms. is active 9. a 8 that's the. complex I'll discuss shortly What. vitamin K and calcium do why they're. important in this process now I've got. 10 all right let's now talk about the.
extrinsic pathway and how it converges. here what are we up to now we've done. eight right we just spoke about eight. because it forms a complex with nine. we're up to seven and so number seven. the clotting Factor seven this is where. we begin so when clotting Factor. 7 comes into contact with tissue Factor. also known as. thromboplastin it turns into the active. form of seven and what does the active. form of seven do well it activates.
10 look at that converging but just like. the last one of the intrinsic the last. clotting factor of the intrinsic pathway. needed three things the last factor of. the extrinsic pathway also needs three. three things those three things. are 1. 2 3 it needs vitamin K. just like Factor 9 did calcium okay and.
what else do you think we need here. where are we up to so we've spoken about. seven. right we don't need a factor here we. just needed to form a complex with. tissue factor or thromboplastin let's. just write TF for tissue Factor so what. we have just like here we have a complex. that's. formed like that okay things are. starting to make sense we've only got a.
couple left right so 10 goes to 10 a the. thing is 10 a cannot do what it needs to. do unless it has a couple of things what. does it need well it needs three things. what do you think those three things are. it needs vitamin K it needs. calcium and it needs what do you. think Factor. five.
now what it can do. is activated Factor 10 what it does. beautifully is it takes what we call Pro. thrombin again protein made in the liver. and turns it to. thrombin now the thing is prothombin has. another name it's Factor two.
what thrombin. does is it come comes across fibrinogen. fibrinogen H fibrinogen again made in. the liver if it ends in Ogen it tells. you it's inactive it needs to be. activated it gets activated by thrombin. and turns into. fibrin beautiful fibrin fibrinogen is. also known as Factor one there's Factor. one have we gone through it all no we. haven't we're missing one which is 13.
now let's look at fibrin what does. fibrin do fibron forms the clot right. these are fibers these are strands that. can be embedded between all of these. platelets they can adhere to the. platelets but it needs to be cross- L to. hold it strongly together that's what 13. does 13 Factor 13 is required. here.
and what factor 13 does is it allows for. the clot to cross. link beautiful so we've now just covered. all of those various factors and how. they fit together and cross link but. what we haven't spoken about is What. vitamin K and calcium do this is what. they do right and you've probably heard. of babies when they're born needing a. vitamin K injection this is the reason. why all right think about it like this I. said before that if you've got a blood. vessel and it's.
damaged right that you've got all of. this negatively charged collagen that's. exposed right got all this exposed. negative. collagen all right What vitamin k does. is it takes these various factors so it. takes factors n factors. 10 uh factors seven and in actual fact. we need Vitamin K.
and calcium here for thrombin too so. number two so it takes two let's write. it down right What vitamin k does I've. got no space let's write it down here so. vitamin K and calcium are needed. together right and they affect factors 2. they affect factors n they affect. factors 10 and they affect factors. 7 and what it does is this it takes. those factors so if the factor looked.
like this. right right they're proteins so they got. these amino acids that are sort of bound. together it adds a it adds carboxy. groups to them it carox them what's that. mean it gives them carbon dioxide and so. when you give them carbon dioxide you. give them a. c negative you make them negative. basically vitamin K carboxilate these. factors making them negatively charged. now you might think wait a minute why do.
we want to do that well ultimately we. want these to be negatively charged so. calcium can bind to them so if that's. negatively charged calcium can come. along and say hey I'm positive you're. negative let me come along and bind to. you right why do we want to do that. because then the calcium can be just. like the Von willbrand Factor right a. tether and the calcium combined to the. collagen and the calcium combined to the. platelets all of these negatively.
charged things which allows for these. factors now like Factor two and Factor. 10 uh 10 and Factor 9 and Factor 7 it. allows for them all to go to this area. otherwise they're just going to float. past right you don't want these factors. to move past because then it can't clot. they need to be adherent to the side of. the clot and that's What vitamin k does. it makes them negative so calcium can. then bind and then they can bind to the. area that needs to be clotted and then.
they can start to do this process and. this then allows for the clot to form. brilliant which is the reason why when. bubs are born newborn bubs this process. isn't mature enough they don't have. enough vitamin K in their body for this. process to occur so they need a vitamin. K injection it's also important because. without calcium you can't clot either. and so when you take your blood if you. go to a fotus and they take your blood. and they put it into a tube like a. plastic or glass tube if that tube is. not coated your blood will clot in the.
tube and often they tend to coat it with. something like citrate citrate is. negatively charged if they coat that. tube right if you've got a tube here. that you want to put your blood in and. you coat it with a negatively charged. thing hm what do you think that means it. means that when you put your blood in it. steals all the calcium from it it binds. all the calcium up to the walls of the. tube which means these factors. Float On by and you can't clot and so.
your blood doesn't clot in those tubes. and there's not just citrate but they. line it with other things as well that. basically perform the exact same. function so hopefully all of this makes. sense this is hemostasis and this is the. clotting Cascade and I'm Dr. Mike hi everyone Dr Mike here if you. enjoyed this video please hit like And. subscribe we've got hundreds of others. just like this if you want to contact us. please do so on social media we are on. Instagram Twitter and Tik Tok at Dr Mike.
todorovich at d m i to o o r o v i speak. to you. soon.
