Transcript for:
Cardiac Cycle and Heart Function

in this lecture we're going to finish up our discussion about the heart and look at cardiac function so up until this point we've been discussing how the heart generates its own beat from looking at the electrophysiology where the signal starts in the sa node and spreads over the atria through the av node down to the ventricles and all of that is spread through gap junctions and then from the nodal cells and from the fibers those ions are being passed to cardiomyocytes and that's going to then coordinate a contraction in the respective chambers so we've talked about the action potentials and we talked about how an action potential in the cardiomyocyte leads to calcium coming in which then induces the release of calcium from the sarcoplasmic reticulum and then you get the cross-bridging cycle because calcium is present so now we're going to take our understanding of those concepts and then look at it from a larger scale and looking at the actual mechanical events that take place in response to the electrophysiology and contraction of the cardiomyocytes so what we're going to be covering is what we call the cardiac cycle so this is the mechanical events that take place throughout one beat of the heart so we're going to walk through each one of the stages of the cardiac cycle so there's five basic stages now for each stage we're going to be looking at the state of contraction or relaxation of the atria or ventricles we're looking at the movement of blood we'll be looking at the opening and closure of valves now for the sake of ease what i've done here is just drawn out one side of the heart so we're just going to look at the left side of the heart here just knowing that the right side is doing the same thing at the same time but just for the sake of east we're just going to look at one side of the heart so in this case we're going to be looking at the left atrium here at the top we'll be looking at the left ventricle and then remembering that we have the bicuspid valve between or the mitral valve between and the semilunar valve on the left side here is the aortic valve and that leads out into the aorta so again this is just the left side but the right side is doing the same thing at the same time so we'd have the right atrium right ventricle we'd have the blood moving past the tricuspid valve and then eventually of the pulmonary valve into the pulmonary trunk and so the same thing's going to happen but just for the sake of these here's the left side so this first stage is between beats so it's already gone through a cardiac cycle we've gone through the peqrst and now we're sitting between the beats so as as soon as the ventricles start to relax in the previous beat once the pressure drops enough where the mitral valve opens then the blood just falls in so this stage we call passive filling because there's nothing going on so if we're just kind of keeping it running tally here through the stages i just want to make sure that we understand the terminology so in this case both the atria and the ventricles are going to be in a state of relaxation and remember in that phase is called diastole so if we just kind of keep a note here that this is atrial diastole and ventricular diastole as well okay so in this stage blood is just falling into the ventricles now i introduced this concept a little bit earlier when we're talking about the idea of atrial fibrillation's not leading to death because the atria are not contributing all the blood down into the ventricles so in this state of passive filling so this is before we get into the next beat before the atria contract 80 percent of the volume of blood that's going to enter the ventricle just falls in so again this is passive there's no action required here to get the blood in there all the requirement is is the pressure is low enough in the ventricle for the mitral valve to be open and the blood just falls in we'll see as we go the the once the ventricular contraction starts and closes the mitral valve there's blood in circulation that's going to be delivered back to the atrium and that will start building up in the atrium so there will be some blood that kind of pools there before the valve opens that will fall in and the blood continuously returning to the heart will also fall in okay so this is a stage of passive filling so the next stage then is atrial systole so passive feeling has occurred 80 percent of the volume that is going to enter the the ventricles already just fallen in now if we're just following this along on the ekg just bearing that mind because we have to be able to overlap these concepts well now this is a point where the p wave has already started right so the electrical events that are taking place at the sa node that is spread over the atria and now it's driving contraction so at this point we're we're in the p wave or just after the p wave starts where the atria are starting to contract now they are going to push in the extra or the last 20 percent of the volume that's going to fill up in that area okay so at the end of the stage here after atrial contraction that is going to be the final volume because once the ventricles start contracting they're going to close the mitral valve so no more blood can enter so at this point this is all of the volume that's going to be in the ventricle so when we look at giving these volumes terms here because it's going to be important to look at cardiac function we got to know the names of these volumes that this when we look at the ventricles this is the end of diastole for the ventricles so we're following this along this is atrial systole because they are contracting but it's ventricular diastole but this is the end stage of ventricular diastole the next stage we're going to move into the ventricle starting to contract right that signal is going to go down through the av node av bundle bundle branches and then it's going to coordinate a contraction in the ventricle so that's the next stage so this is the end of diastole for the ventricles so the volume that fills up in the ventricles we call the end diastolic volume now this is the load of blood that's going to get into the ventricles before that valve is going to be force shut and then that's the volume that you have to play with to eject into circulation so this is the load before the contraction so the other term for this is preload okay so this is the load in the ventricle before contraction so this is preload sometimes we also refer to preload as venus returned so that's the amount of the venous blood because all these are the pulmonary veins leading into the left atrium that's the amount of blood that's coming back through venous return to the heart and that ends up in the ventricle if we added more we would say that the venous return has been increased and so we get more blood to the heart which would increase the preload which means that the end diastolic volume goes up so you should be able to use these terms interchangeably so the next step now is the ventricles are going to start to contract so signals traveling through the av node right now and then will be quickly sent to the base of the heart to start a contraction in the ventricles so when the ventricles start to contract okay so we follow this along here this is going to be atrial diastole so the p wave has occurred now the atria are going to be starting to go through relaxation so this is on the ekg we are starting the qrs complex because that is leading to ventricular contraction so at this point now we've moved into ventricular systole okay so at this point the ventricles start to contract now there's a little bit of a phase before this is kind of between these as soon as it starts when we look at the actual pressure inside of the ventricle before the contraction heart before the contraction of the the ventricles start the pressure is essentially zero so when the contraction starts it doesn't take very much to get up to five millimeters in mercury and at about five millimeters of mercury that's when the valve closes okay so that's where we'll hear the first heart sound remember the valves are shutting and it's the valves closing that creates the heart sound so this is the lub so the first little bit of pressure will close the mitral valve we'll hear the first heart sound okay so at that point then as soon as it's above five millimeters of mercury so the valve is closed the mitral valve in this case the tricuspid on the right that is going to be closed okay but we have to consider here that the semi-lunar valve has blood on the other side of it right you always have blood in your arteries and that's why you have a diastolic pressure right that every time we use the term siciliar diastole to describe a lot of things that we're really referring to the ventricles so your diastolic pressure in your arteries that's the lower number of your blood pressure is what's sitting on the valve right we discussed that earlier so there's a load of blood that is sitting on the semilunar valve holding it shut okay so this term we give to that load that's keeping that valve closed that's fallen back on the valve and closed it this is the afterload okay that's the term for it so whatever the pressure may be here i'm just using the example of the normal blood pressure 120 over 80. so your lower number your diastolic pressure is that value in the aorta so that's 80 millimeters of mercury pressure that is forcing this valve shut so that means that if we're looking at opening up this valve the pressure inside the ventricle has to exceed 80 for it to open right this is in terms of the valve being open or closed this is really just a pressure difference across that valve to whatever's higher right the mitral valve is closed because the pressure inside the ventricle once it gets beyond about five millimeters of mercury pressure that's higher than what it what it is in the atria and so they close so just a pressure difference so when we look at the semilunar valve that anywhere between 5 and 80 millimeters of mercury pressure so anything below 80 that is not a sufficient amount of pressure built within the ventricle in that chamber to overcome the afterload so the valve stays shut so if you're looking at this the early part we're going to get the first heart sound and then all of a sudden from the point of five millimeters of mercury pressure up to just below 80 millimeters of mercury pressure a contraction is taking place but when we look at the amount of volume if we look at that volume inside the ventricle there is no more addition of blood and there's no blood escaping right the mitral valve and the aortic valve in this case on the left side is shut so when we look at the name of this phase it makes sense iso means the same right so we have an iso volumetric contraction so this is suggesting it's the same volume inside of the ventricle when it's contracting so when we say iso volumetric you automatically know that all valves in the heart have to be closed there's no more blood entering there's none escaping so this is isovolumetric contraction so this contraction in the ventricles again we're in the qrs complex that contraction is going to keep going that's not the end of it this is just the beginning of the contraction so there's this small little phase before you overcome the afterload that we call the isovolumetric contraction so that contraction is going to keep going and we're going to generate more pressure the pressure inside the ventricle is going to continue to rise and so we're still in the qrs complex or slightly after because of delay with calcium coming in so as soon as you overcome the after load so once you're beyond 80 remember 80 was the pressure that was inside of this beforehand so once you exceed the afterload once you're over 80 millimeters of mercury pressure then that semilunar valve right this aortic valve on this side is going to open up and you're going to eject the blood so this point we call ventricular ejection so if there's ejection of blood you know that the pressure has been raised higher than the pressure that was against the valve so we know the afterload has been overcome by the pressure built up inside of the ventricle so that contraction is going to continue going and raising the pressure up to whatever the systolic pressure is so in the case of the 120 over 80 normal blood pressure that that pressure is going to raise up to 120 millimeter mercury pressure so that far exceeds the afterload and that's going to help to push blood out and get it into circulation okay so the pressure inside of the aorta is going to rise similarly right so as soon as we overcome the pressure that pressure is going to raise up to a 120 millimeters of mercury pressure inside of the aorta that's why we can measure it in the major arteries as 120 for the systolic value so that ejection is going to raise the pressure inside of the arteries so just keeping this in mind again just knowing the stages well the atria are relaxing right so we're in atrial diastole and we're still in ventricular systole so as i've kind of drawn out here though the blood that has gone out into circulation is starting to build up in the atria after the mitral valve shuts so you get a little bit of blood starting to pool in the atria on the other side of the valve but again that valve stays closed because the pressure inside the pressure is much higher on the inside of the ventricle than it is in the atria so that will remain shut so now we're getting to the point of ventricular diastole so we're still in atrial diastole and now we've gone back into ventricular diastole so we're past the qrs complex and if you think on the ekg where are we well we're at the t wave right those cardiomyocytes in the ventricle the potassium is moving out they're starting to move the calcium back into the stores or outside of the cell and so they're beginning to relax so they have raised the pressure the ventricles have raised the pressure up to 120 but they start to relax that ventricle starts to expand back out during relaxation and so the pressure starts to drop inside the ventricle but remember that the valves here are closed and that diastolic pressure remains so what has happened with ventricular ejection you push it out and then all of a sudden the ventricle is not forcing any blood out anymore that pressure drops there's no more force behind that and so the blood goes out and falls back down and closes the valve so right around the t wave you're gonna hear the second heart sound or what we call s2 so that second heart sounds going to happen because the semilunar valves we're just looking at the left here so this is the aortic valve but the pulmonary valve will be closing as well and so we have second heart sound occurring now the pressure which was raised up to 120 is dropping down and if we look in the atria the blood building up in that area it's building up about five millimeters of mercury pressure so anything when this is relaxing and coming down from 120 down anything that is above five if we're just looking at the mitral valve right we're looking at it across here anything that's above five in terms of pressure inside the ventricle will not allow the mitral valve to open there's still pressure difference forcing it shut so there is a case where it's dropping down from the higher pressure down it's still over what's in the atria and so it's in a state of relaxation the ventricles right this is ventricular diastole but now we're seeing the same case all valves are closed the blood has fallen back down on the semilunar valves close those and you haven't dropped the pressure enough inside the ventricle to have the mitral and tricuspid valves open and so if we're looking at that if all valves are closed just like we mentioned before that there cannot be any additional blood and there's no removal of blood from the ventricles so it's the same volume so this is isovolumetric but now the ventricles are in a state of relaxation okay so this is isovolumetric relaxation now there will be some volume of blood left over we have some reserve that stays in the ventricle we don't eject all of the blood so there's a little bit of volume that remains after ventricular systole so at the end of systole in the ventricle there is a volume left over so we call this end systolic volume right so now if you start thinking ahead like if we can calculate how much is actually ejected from heart because there's an end diastolic volume and now we have this n-systolic volume and so we can calculate the difference between the two and we know how much has been ejected okay so that's going to help us try to interpret actual cardiac function because that's what we call stroke volume how much is released in one stroke of the heart now as soon as the pressure in the ventricle drops below five remember at the beginning you had about five millimeters of mercury pressure when that mitral valve was shut and as soon as the ventricle drops below five so this will drop down to about zero so once it gets below five the mitral valve opens and then we get the passive filling stage start again right so we're now we're right back to the start and we go through those five steps over and over again and if you take the average number of eights that this happens 72 times per minute on average so this is the cardiac cycle right so when we take this you should be able to tell me at each stage what this heart looks like you should be able to tell me in each one of those stages whether the atria and systole are diastole you should be able to tell me whether the ventricles are in systole or diastole you should be able to tell me which valves are closed in each of those stages you should be able to tell me uh how much volume should be there at least the terms of the volumes that should be there you should be able to tell me what preload means you should be able to tell me after load and so you take those concepts of the cardiac cycle and then the the challenge is bringing it back to what we know already you should be able to overlap these steps with the ekg right atrial contraction is going to be p wave so we have two stages we have isovolumetric and ventricular ejection those are qrs complexes right we get into isovolumetric relaxation that's going to be created by the the onset of the t wave and then between beats we have passive filling okay there's lots of times between beats this doesn't take very long to do and so when we look at the timing of it there's lots of time for passive filling and then we get into the next beat so here's a figure that will help you assess your understanding of how these concepts overlap right so we've walked through the five steps on the bottom of the cardiac cycle and so if you take things like atrial systole for example right if we draw this up to overlap it with the ekg we know that the onset of it's going to happen just after the p wave starts because it takes a little bit of time for the calcium to get in and then spread throughout the atria so contraction kind of follows briefly after the electrical events as we discussed in the previous lecture and then with the isovolumetric contraction and ventricular ejection that's going to overlap with the qrs complex or slightly after right so those stages are going to last throughout this timeline now when we look at the iso volumetric relaxation well that's going to happen after t because t is going to be the indicator that potassium is moving out we're getting this wave of repolarization and then relaxation follows as soon as calcium is pumped back in sarcoplasmic reticulum and out of the cell so even then we can look at the uh heart sounds when those were occur so we know a little bit of pressure has to build up in the ventricles to shut the valve the the av valves and so you hear s1 just after the qrs complex had started right because the contraction is going to follow that and then s2 where we get the semilunar valves closing that's going to happen slightly after t has begun because it takes a little bit time for relaxation then you're not forcing blood out into the order of the pulmonary trunk and that blood falls back down and shuts the valve creating the second heart sound right so s1 is lub s2 is dub so you should be able to take that and draw it out and then especially looking at the pressures up here this should all make sense when you walk through it now there's a couple things i want to focus on with the pressures so we just take that part of the graph we'll just follow a few things along here now just to illustrate some of the pressures that we see outside of the heart i want to focus on the aorta just a little bit but first let's look at the pressure in the ventricles so at this point we're getting between beats right so the pressure in the ventricles will be close to zero right they were relaxing there's there's plenty of compliance there meaning that when the blunt falls in it kind of just stretches out there's really no pressure that builds up now we actually see just a little bit of blip of a pressure because if you remember back from the previous slide this area here is atrial systole so this little blip and pressure that you get is because the atria of contraction has pushed blood down into the ventricle so it builds up a little pressure on the wall so once we start seeing this rise in pressure now you know that the ventricles have to be generating the pressure themselves and so this is ventricular systole so this first little stage is isovolumetric contraction and then when we overlap this with the aortic pressure right if we just follow this aortic pressure we'll describe this process of slowly going down in a moment but look at the the pressures well if we're looking at blood pressure it's in the taking the average example it's 120 over 80 and so we can draw this line across here and so that's the diastolic pressure and then we're going to see it rise up to 120 that's systolic pressure so you see that this junction right here when we're looking at these two tracings that anything between the points where the ventricles are starting to contract up to the point of your diastolic pressure remember we also called that the afterload that's the pressure on the valve that the aorta is experiencing no increase in pressure because no volume has been ejected right so if we follow the pressure in the ventricle yes that rises up to your systolic and then starts to drop back down well the aortic pressure will rise as soon as the ventricles overcome the afterload and so you start seeing this increase in pressure in the aorta so the ventricles will will push and hold remember in the ekg we have the st segment which we said was complete depolarization so all the cardiomyocytes and the ventricles have contracted and then they're just kind of holding there for a brief moment before the t wave starts and then starts to repolarize the cell and so the pressure in in both the ventricle and the aorta start to drop so the pressure in the aorta starts dropping and then what happens is you see this little blip and that's the valve closing there's a little pressure in the aorta because the valve closes at that point and what i want to focus on now and describe is independent of the ventricles you see the ventricles here they're relaxing and this is isovolumetric relaxation and then we get passive filling start again but let's focus on the aorta well the valve has closed right here so there's no more blood being ejected so whatever the pressure is in the aorta is not influenced by anything from the ventricle because the ventricles now shut off from the aorta because the aortic valve has closed so what i want you to look at is well if there's no blood being forced out into the aorta why doesn't the pressure just automatically drop off back to diastolic pressure and then stay at that value until the next beat because what you see if we follow the real tracing is that this slowly declines back to your diastolic pressure until the next beat and then then it's forced back up so we need to describe this because this is one of the reasons why blood is not just this kind of rapid just movement of blood that there's a smoothing out of the blood flow that's coming through the major arteries because of what the aorta and those big vessels around the heart are doing so let's try to describe why that goes down slowly so the first thing you need to understand is that this is the this is the heart so we're just drawing again the left side the same thing that happened the right side but we're looking at the aorta so this was a stage where we've shut the mitral valve and now this ventricle is going through a bit of contraction here closes the mitral valve and then we're waiting for a rapid ejection so let's look at this the point of rapid ejection because the stages that we talked about before in the cardiac cycle i didn't include this so i want i wanted to specifically focus on it here while we're seeing the pressures in the aorta because the reality is that when there is rapid ejection of the blood so when we have that ventricular ejection phase that what happens is that aorta is being forced upon by more blood being ejected by the heart there's already blood in there so the ventricle is trying to push blood into a container into this vessel that already has blood in it and so the pressure builds up in the aorta and we will discuss this in more detail when we get to the blood vessels but what you should recognize is all the blood of all the blood vessels around the heart that are close to the heart that are under a lot of pressure they have elastic tissue in them so they will expand so the reality here is that these major blood vessels around the heart when they get when they get that blood ejected from the ventricle they are pushed outwards right so you kind of see this ballooning of the aorta and that helps withstand the pressure so how we describe again this part up in the pressures why this is a slow decrease up here is because of the stretching you're taking this vessel and you're stretching the elastic that's built on into it right that's helpful when the blood is being ejected so that the aortic wall will take up some of that pressure and then once it relaxes so once you get an isovolumetric relaxation and passive filling those stages you have stretched the elastic out here and now if we're looking at what's going on between beats that aorta which was once stretched out to here then recoils it comes back to its normal state so imagine that you have blood inside of there though so the pressure is built up inside of there you stretch it out the valve closes no more blood's coming out and that elastic comes back it recoils and so that blood vessel gets smaller again to its normal state and while it's doing that it is squeezing more blood down so this kind of helps to smooth out the blood flow away from the heart so it's not just this rapid little spurt of blood that we've forced it out into this vessel it stretches out and then between beats that will come back and kind of squeeze more blood forward so that's describing why we see this slow decline in the pressure in the aorta so that helps to smooth out blood flow so if we are trying to look at the efficiency of the heart and how the heart is functioning it is not enough to talk about the circulation of blood or how that how well that heart is working as a pump if we're just looking at the heart rate right because the heart rate could be really high and if you just you know think about that conceptually well it sounds like you might be able to eject a lot of blood in a minute if you have a really high heart rate but then you think about ventricular fibrillations right we get the heart rate up to like 350 beats a minute and no blood is leaving so heart rate can't really tell you everything about how the heart is functioning so similarly if we just took the stroke volume which we just defined stroke volume this was again this is just the end diastolic volume how much falls in and then how much remains after the ventricles have contracted well if you just look at that that's not enough to tell you how the heart is functioning over time right that independently well you could have you could have you know 100 milliliters of blood being ejected was quite a bit then if you just look at that it sounds like lots is leaving a lot of blood is leaving the heart but if you only have one beat in a minute that's not a lot right so that independently can't tell you everything about how the heart is actually working as a pump and so how we look at cardiac function is really a measure of cardiac output so this is giving it a rate because we're looking over time so now we can use these two variables that we've been discussing and put them together because this tells us a lot stroke volume is how much is is being ejected from the heart and then heart rate is how many times you're releasing that volume in a given minute so that's cardiac output now if you look at just the normal average kind of heart function in terms of cardiac output these are the normal volume so end diastolic volume is about 120 milliliters per beat it's not a lot of volume and then we left we leave about 50 mils of blood for end systolic volume so that means for every beat you're releasing about 70 milliliters of blood on average right and then you you take that for every beat that's normal systolic volume and then you're gonna times that by your heart rate and if it's average then you get a 72 beats per minute right so we get that times 70. so this is a measure of cardiac function this is a more appropriate one because now we're taking account how much is leaving and how many times we're actually pushing that volume out so to understand cardiac function and the physiology you have to understand the factors that are influencing stroke volume and heart rate so we're going to look at a few here i'm going to be scratching the surface there's a lot of things that are going to be contributing to this but we're going to look at some of the major contributors generally speaking so first starting out with stroke volume so how much is going to be released now we can have a difference in the amount of volume that's released based on the strength of the contraction right that seems fairly intuitive that if we increase the contractile strength of the ventricles you would expect that we'd eject more so if i somehow increase the strength of the contraction i can get more released and so we're going to increase cardiac output because stroke volume will be going up with every beat so contractility we're going to look at the sarcomere and i'm going to describe this a little bit more when we talk about preload which is upcoming but what is driving contractility just think about the components that are important for contraction what is needed well in the cardiomyocytes what's the one particular ion that influences more directly contraction well it's calcium right we talked about this with the action potentials and the cardiomyocytes that the level of calcium that is present there the concentration inside of the cell that's released from the sarcoplasmic reticulum and comes in from the outside the concentration of calcium is correlated to the strength of the contraction because more calcium binds to more troponin that means more tropomyosins out of the way that means there's more binding sites for myosin heads on actin and so calcium concentrations really relate to the strength of the contraction so there's other things that we can add in here to increase the strength and we're really talking about it the strength being a measure of calcium concentrations that we'll see in in a moment especially when we look at heart rate that'll come back to this we'll table for a moment but we can look at the sympathetic nervous system right that's your fight or flight response you know your heart rate will go up so we'll talk about it more there but this also changes the cardiomyocytes and can change the amount of calcium that gets into the cells and released from the sarcoplasmic reticulum so the contractility can go up with the sympathetic nervous system signal so there's other chemicals that we can add in we have pharmaceuticals that we can use and all of this is is talking about changing these cells to lead to more depolarization and increasing calcium concentrations so for your purposes and your understanding you should be relating contractility with the amount of calcium present the second thing on the list here is afterload so remember what afterload is well that's the pressure on the semilunar valve so that's the diastolic pressure in those circuits that's the pressure forcing that valve shut and then that is the pressure that needs to be overcome by the ventricular contraction inside the chamber of the ventricle that pressure has to raise above after load before it gets out right before we can have ejection of the blood so think about how that can influence it though right so if you take a valve so if we have a semilunar valve and we have 80 millimeters of mercury of pressure and so what do you have to do to overcome this and open the valve well you have to be greater than 80. right so you can have a contraction that will generate greater than 80 millimeters of mercury pressure and we're going to eject blood once that pressure raises above the afterload now let's take a case where we raise the afterload what if we raise it up to 90. now think about this conceptually that i want you to imagine that we're going to have two beats of the ventricle that are going to be exactly the same so they're going to generate the same amount of pressure so they're just going to raise up to 120 millimeters of mercury pressure so what do you have to overcome in this second case well it has to be greater than 90. right so if we have a contraction in a ventricle leading into into building a pressure to overcome this afterload it takes less effort to open up the valve on the left here because it's less pressure forcing that valve shut where it takes more of a contraction here but if you have the same contraction then more effort would be put in in that one contraction to overcome the afterload than would be to eject the blood and so the stroke volume would go down okay so generally speaking when we look at after load if you have an increase in afterload we have an increase in afterload that means that we could have a decrease in stroke volume because instead of the that effort that contraction going towards ejecting the blood we need more of that contraction just to overcome the afterload so that's how it can influence stroke volume the last point we'll discuss is how the preload affects stroke volume this is a really important concept in terms of regulating stroke volume but it's also a really important concept in cardiac physiology so if you remember preload is related to the end diastolic volume that's how much ended up in the ventricles before ventricular systole started and that av valves closed so we also termed this venous return how much blood is returning to the venous system and ends up in the ventricles so we have to think about this concept in terms of the nature of the wall of the ventricles now what i want you to picture is that the ventricle is a balloon okay so we're filling it up with water for example right if we're making a water balloon you add more water it stretches out right there's no no pressure at the beginning we add some water into this balloon and it starts to stretch out and there'll be a little bit of pressure that's that's generated but i want you to consider that that if we're just looking at the ventricle the more blood that's falling into it just like a balloon it's going to expand out okay so there's some compliance in the wall meaning it has some give that if we add more it stretches now think about what's in the wall what's in the wall well primarily these are cardiomyocytes so you're taking the cardiomyocytes and you're stretching them out so what is that going to do well now we have to go back and see how that relates to the contractile units inside of the ventricle because a really cool part about the heart is that if we increase preload if we put more volume into the ventricle it stretches out and just by the nature of its physical makeup it contracts harder so you get an increase in stroke volume when you get an increase in preload automatically there is nothing else done other than just stretching it out to understand this really cool feature of the heart we have to go back to our understanding of the sarcomere so on the right here we have four sarcomeres at varying lengths now i'm going to first just describe a couple features of here that are important in our understanding so these diagrams here we just have that's myosin with the mice and heads these things coming off of that filament and then we have actin and then these would be the z lines okay so that's what the actin is anchored to and for a contraction then the myosin heads would be grabbing onto actin pulling and these z lines will get shorter in terms of distance apart right that's a contraction that's going to be able to squeeze and get the blood out of the ventricles so now that we know what we're looking at over here let's let's describe a couple features here that are important so the first thing is tension so when you learn about skeletal muscles which the concept that should have been presented was the fact that when myosin heads grab on to actin you can develop tension in the muscle right so calcium has to be present tropomyosin has to be out of the way the myosin heads can bind on to the actin sites and grab and as soon as they grab you can develop tension right not all contractions get shorter so we can have these isotonic contractions or isometric contractions if you remember from the skeletal muscles that the isometric means the same distance right if you just grab a weight and hold it out with your your bicep partially contracted you can hold it there that's an isometric contraction you have tension in the muscle because myosin has a binding to actin but you're not shortening the sarcomeres if you can overcome the load and you decide to then that's an isotonic contraction where you're shortening the sarcomeres so we can develop tension and it doesn't always have to be shortening the sarcomere but that in the case of the heart if we want to push things out yes the sarcomeres have to get shorter so the two things that we need to pay attention to is that tension is related to how many myosin heads are grabbing on to actin so the prerequisite to actually develop tension is those filaments have to be overlapped and the myosin heads have to be able to bind on have to be able to grab onto the actin the second thing is how far i can actually make this move right so that what i'm talking about here is the myosin is going to pull and we're talking about this distance here so how far can i actually get this to move to shorten because the shortening is the squeezing right that's going to help squeeze the blood out of the ventricle now to try to picture this in your head imagine grabbing a five pound weight and then curling it all the way to the top where you can't move that bicep anymore so when we look at the contraction you can have a contraction you have tension in the muscle but you can't move that bicep very far so you can't because it's already contracted you've already pulled that bicep in this example where it's moving all the way up then your sarcomeres look like this at the top yes you can develop tension but you can't generate any movement so that's great that you can have tension but you can't squeeze something you can't move the blood in that case if they are fully contracted where the myosins now is now bumping into the z lines or z discs okay so those are the two concepts to keep in mind the distance that we can travel and how much how many myosin heads can bind now we've already talked about the relationship to calcium so the more calcium out there the more myosin heads combine to actin because more of those binding sites are open so this is all independent of calcium so we're going to leave that aside and just look at these two other concepts now if we're looking at optimal stages here well the first one here is not optimal for the reasons i mentioned yes with this current arrangement we can have all the myosin heads binding onto actin but i can't move it very far that's a little sub-optimal because i want to be able to squeeze the blood now let's go to the opposite end let's go to this last one here okay now we have a ton of distance here but there's no overlap of actin and myosin so there's lots of distance but you are unable to generate any tension because myosin heads cannot grab on to any site on actin this is what happens when you hyper extend a muscle and if you were to take your arm and bend it backwards you can't contract your bicep because you've stretched the sarcomeres out so much that the mice is not overlapping with actin and you can't develop any tension you have all the room in the world to do it in terms of the length of the sarcomere but you can't because the filaments are no longer overlapping so this is sub-optimal because it can't move it very far and this is sub-optimal because you can't generate any tension so the optimal state are in between now the optimal state is the one that's second on the list here so in this case we have the maximum amount of heads that combined and we have the maximum amount of distance right as soon as you move it closer now we're back to this initial suboptimal phase or state and if we move the z lines farther apart now we're losing some ability to generate some tension so we have more room but less tension can develop and so this is the optimal state okay so let's take this and look at this in terms of the sarcomere length and the amount of tension we can develop because now we know that the length does tell us something about how much tension can develop so let's look at at this graph here and try to understand how the preload would affect the contraction because they said it goes up within limits it goes up if we add more blood so these states so b is right here so this is the optimal state to be in that's where we can generate the most amount of movement with the most amount of tension okay so that's that's the sarcomere length here the reality is at rest our our heart is not filling up so much that it is getting to that optimal state what we are sitting at is a so we are sitting in the sub-optimal state at rest so this is more what it looks like at the top here right we can generate some contractions not as dramatic as what that suggests there so we're sitting a little bit sub-optimal in that arrangement at rest and so think about what's going to happen if i increase preload think about the balloon example if i increase the amount of volume that i'm putting into the balloon the balloon stretches out right and what's happening to the sarcomere so you're stretching so now you're taking the state of going from a to b so now we're increasing the sarcomere length by stretching it out with more volume falling into the ventricle and look what happens to the amount of tension i can develop more tension and more of a contraction so we're sitting in a sub-optimal state an increase in preload again within limits but these are normal physiological limits that if we increase the load in the heart it actually contracts harder because of the sarcomere arrangement so this is the frank starling law of the heart that the contraction of the ventricles are going to increase with preload so the more load we put in the heart the stronger the contraction is going to be so this is independent again of anything else we're not talking about sympathetic nervous system we're not talking about chemicals in circulation that are aiding in this no you just stretch out the ventricles more puts the sarcomeres in a more optimal position and we get a stronger contraction normally so that is the influence of preload and this is the frank starling law of the heart let's move on to the factors regulating heart rate so we're going to talk about a few things but the most important thing we're going to discuss is how the nervous system influences the heart and specifically looking at the autonomic nervous system because both the sympathetic and parasympathetic nervous system will go to the heart and influence heart rate and we'll see that the sympathetic as we mentioned earlier also affects uh contractility so we have to understand how both of these divisions can have an effect on overall cardiac function both stroke volume and heart rate so again these are the sympathetic and parasympathetic nervous systems so if we look at these systems so these are autonomics where you don't have conscious control of these now the first one we'll talk about is the sympathetic nervous system so we're going to look at the sympathetic nervous system now let's follow this along and see where it goes to the heart because where it goes to the heart will tell you how it's going to influence the heart now we follow the sympathetic nervous system it's coming out from the major control that's actually in the brainstem that's where the autonomic controls are largely regulated from and i want you to follow this along to see where it's going well those nerves are going out the neurons are then going to connect with the sa node and if we follow this along it's also going to the av node and also with this division only this is out going out to the cardiomyocytes so we're going to affect muscle as well so the important thing to remember is that with the sympathetic nervous system because it's going to the nodes it's going to increase the pace of the nodes so all of these in terms of increasing the pacing that means we're just adding in positive charge quicker when the system is activated we're not going to look at the specific mechanisms of how it's doing that but i want you to remember that that the sympathetic nervous system is going to help depolarize the cell and add more calcium in so that we get more contraction so the sympathetic nervous system because it goes to the nodes it will increase the rate of those autonomic cells and so this will change the heart rate so this will increase the heart rate but because it's also going to the cardiomyocytes it's going to help to get more calcium out into the cytoplasm so that it can bind to troponin and so this can increase stroke volume as well by increasing contractility so you have to follow where these go so that you know the effect the sympathetic nervous system goes to both the nodes and cardiomyocytes so it can affect heart rate and stroke volume okay so this is the fight-or-flight system so if you get anxious or stressed your heart rate is going to go up contractility is going to go up if you start to exercise that's going to activate the sympathetic nervous system heart rate is going to go up contractility is going to go up and so both of these factors here will increase cardiac output you think about in those cases yeah i want more blood to go in circulation blood pressure is going to go up for the sympathetic or sorry for the parasympathetic nervous system this is coming away again from the brain stem initially and let's just follow this along and where does it go well it only goes to the sa node and the av node so the parasympathetic nervous system is only going to the nodes so what can it only affect well it can only affect the pacing of the heart right the heart rate and so this once you activate it this is rest and digest so if your parasympathetic is more active then your heart rate is going to go down blood pressure goes down so this is going to decrease heart rate this won't affect stroke volume because it doesn't go to the cardiomyocytes it only goes to the nodes okay so it only affects heart rate now i want to go back to a concept that we talked about in terms of pacing do you remember the beats per minute when we look at the autorhythmic cells in the sa node in the av node and then purkinje fibers but we'll focus on the nodes only remember the av node was about 40 to 60 beats per minute and the sa node was the normal range of heart rate that we look for is between 60 and 100. but remember when i was talking about that that point that i wanted you to remember those closer to a hundred okay so there's a couple things i want to talk about here so if the sa node pace is closer to a hundred what is the average number again well it is 72 beats per minute right so if i have 72 beats per minute but the sa node is normally firing closer to 100 what does that mean about a normal heart at rest which system is a little more active well it's got to be the parasympathetic because it's decreasing the heart rate right so the parasympathetic normally has a break on the heart okay so when we look at the note the the nerve sorry that is taking the parasympathetic nervous system signal down to the heart this is called the vagus nerve and so when we look at giving this a name of why the heart at rest this kind of has this break on it this normal condition that we call this vagal tone so that's normal tone the signals that are going to the heart is more driven by the parasympathetic nervous system that keeps our heart rate down a little bit from the normal pacing of the assay node now let's apply that then to situations where we have individuals with lower heart rates remember we talked about the difference between an average individual and then an elite athlete remember the difference well the normal average is going to be 72 beats per minute and then we look at an elite athlete and they can have somewhere between 40 and 60 beats a minute that is lower than the sa notice pacing to begin with and so in those individuals so in the elite athletes which system becomes even more active well it's the parasympathetic nervous system so we say in athletes that you have an increase in vagal tone meaning there's more parasympathetic nervous system that's driving down the heart rate now cardiac output is the same between those two individuals but because the muscle in the ventricles has hypertrophy it's stronger that stroke volume in elite athletes goes up so knowing that those two factors are influencing cardiac output that we know that in elite athletes with low heart rate that their stroke volume is much more and so it's just offsetting okay so they have an increase in vagal tone now with these two systems they will literally drive the heart by kind of it's almost like driving with two feet because they're both active they're both fighting the heart and it's just kind of driven by that control center in the brain stem to which one's having more of an effect at a given time and so when we look at the change in heart rate so if you have something that stimulates an increase in your heart rate so if you get frightened for example what is happening there because this is kind of driving with two feet that we have one on the accelerator one on the brake and normally the brake is a little more active but we need the heart rate to go up and so you are pushing on the accelerator which is the sympathetic nervous system so you get more of a signal there and the parasympathetic nervous system backs off so they're literally fighting with each other for control of the heart now the other factors that we're not going to go into great detail about but i want you to know that at least they're there that we can have chemicals in circulation that can affect heart rate so we can look at just a couple here epinephrine is also called adrenaline and if you remember from the endocrine system that when you stimulate the sympathetic nervous system it's going to have its effect with the neurons just like we were talking about in the previous slide and if you remember the neurotransmitter it's releasing its norepinephrine so that's noradrenaline that's the neurotransmitter that's going to affect directly on the heart so it's little sister molecule is a hormone called epinephrine or adrenaline that's released from the adrenal medulla at the same time so when the sympathetic nervous system is active you're releasing norepinephrine on the sites where the neurons are innervating and you're releasing epinephrine into circulation so epinephrine technically can have enough to have an effect on the heart rate and that will increase it just like the sympathetic nervous system because epinephrine and norepinephrine are very much similar so you have a similar type of effect the other one is is thyroxine or thyroid hormone so you know that in terms of metabolism so if you have more thyroid hormone and circulation we can have an increase in heart rate now we can have an effect on heart rate from ions and circulation and the only thing that i really want you to pay attention to we're not going to go into detail about why this is happening in particular with each one of these ions but what i do want you to recognize is that heart rate is controlled by the autorhythmic cells and we're really talking about action potentials and so if we change the distribution of the ion so if we take potassium for example and pile it on the outside of the cell right if we increase the amount of potassium on the outside of the cell well normally it's higher on the inside and so if you're at rest with high amounts of potassium on the outside now we're affecting the membrane potential because the membrane potential in the autorhythmic cells is about negative 60 so if you put more positive charge on the outside we're going to affect that resting membrane potential and similarly if we do that on a cardiomyocyte we're going to affect the membrane potential and so we can make it either easier to get the threshold and stimulate an action potential or we can make it harder depending on the resting membrane potential and that's all influenced by the distribution of those ions across the membrane okay so all i really want you to remember conceptually is that these ions and different concentrations if we change the distribution across the membrane it can affect the generation of action potentials it's changing the membrane potential okay so other than that when we look at other factors influencing heart rate we have these general changes in physiology with age so heart rate will tend to go down there's even gender differences so it's it's on average faster in females and then we can have other things like exercise are going to influence it and we'll have that increase in vagal tone with athletes there's a lot of factors present there now let's take an example of exercise just to see how all of these factors are working because the difficulty in understanding a lot of these concepts in this whole class in general but when we're looking at the cardiovascular system is that a lot of these things overlap it's not one thing independent of another and so let's take the example of exercise since we're all familiar with that well when we're exercising we're going to need more blood flow to skeletal muscles so we can talk about how the blood vessel is going to react in the next section but here focusing on cardiac output well to meet the demand of the skeletal muscles we need to increase cardiac output so we can deliver oxygen and nutrients so we know things have to change and so we can first take this influence of the autonomic nervous system right so we look at the autonomics nervous system and follow us along well what's going to happen well we need an increase in sympathetic nervous system activity because that's going to increase heart rate and contractility so remember it's driving with two breaks and so we can't just say the sympathetic's going up that we have both the sympathetic nervous system activity increasing and parasympathetic nervous system activity decreasing so the overall effect there because both of them goes to the nodes is that we're going to get a decrease or sorry an increase in heart rate now because the sympathetic nervous system not only goes to the nodes but also to the cardiomyocytes that sympathetic nervous system is going to increase contractility now let's bring in the hormones for a second because remember i said that when the sympathetic nervous system activity goes up you're going to release norepinephrine from the neurons but you're also going to release epinephrine so epinephrine is going to be in circulation so you're going to have these hormones in circulation that are also going to contribute just a little bit to contractility because it's going to mimic the same thing as a sympathetic nervous system so contractility goes up so when contractility goes up that means if we have the same end diastolic volume coming in that we're going to increase the strength of the contraction we're going to eject more blood so stroke volume is going to go up so that means when we're looking at those volumes in the ventricle that if we push more blood out that means less blood is going to remain and so the end systolic volume goes down because we've pushed out more so if that end systolic volume is going down that means that the stroke volume has increased we've injected more now if we take in consideration what's going on in the heart well we're going to have more venous return because we're going to have skeletal muscles we'll look at the specific details when we get especially to the veins that when we're increasing the contraction of the muscles that we're actually squeezing more blood back to the heart and when we're having a change in the heart rate that affects how much blood's coming back and so those together we're going to see an increase in venous return okay so when more blood is entering the heart that means the end diastolic volume is going up and we know that that is increasing preload so what does preload do to a normal heart independent of all the rest of the stuff we're talking about we increase preload what happens well that's going to stretch out the sarcomeres this is the frank starling law of the heart we stretch the sarcomeres out to a more optimal position and it's going to contract harder and so we're going to get an increase in stroke volume so now we have an increase in both of these factors that influence cardiac output an increase in heart rate increases cardiac output and then the increase in contractility and increase in preload is also going to affect stroke volume and that's going to influence cardiac output so this is a challenge with understanding a lot of these physiological concepts is seeing how all of these work independently so we can understand them but then we have to see the bigger picture because they are all occurring at the same time okay so exercise can increase cardiac output to meet the demand in the body the last thing we're going to discuss is some of the clinical conditions associated with the heart and given the nature of the course where we are learning and understanding the physiology primarily it's often that we don't have a lot of time to go through the clinical conditions when the wheels fall off and when the physiology goes wrong so especially in this section what i what i want to drive home is that if you understand the physiology learning the pathologies or the clinical conditions with these systems becomes a lot easier that if you are able to think about it and think conceptually about how things can go wrong you're going to have an easier time learning the specifics about the cases when they do so i'm a concept guy well you need to understand the concepts before you can understand the pathologies and so it becomes really easy you can learn the details but if you don't have a solid foundation in the physiology it's really hard to learn the pathologies so all i want to do here is think about the system and where things can go wrong now i will show you a slide coming up that will list out some of these conditions i'm not providing this in the notes because i don't want you to remember those yet all i want you to do is see that if we could go through a discussion about the physiology and where things could go wrong that there are clinical conditions that are specific to those concepts so let's think about the heart well what could go wrong what do we learn about the physiology where things could go wrong let's take a few let's examples about blood delivery so we talked about coronary circulation what if there's a problem there because we have we have heart muscle that needs to contract on average 72 times in a minute 2.5 billion times in a row this requires adequate blood delivery if you don't deliver the blood you're not going to deliver the oxygen and nutrients that are going to allow the contractions to take place so if blood delivery gets impaired cardiac function can be impaired so these are the types of things like atherosclerotic plaques that build up in coronary circulation that limit blood flow and you may be familiar that if plaques build up in coronary circulation you could end up having heart attack because you have ischemic events in the heart which is a lack of oxygen and nutrients and those cells are going to die and they're a mitotic they don't come back it's replaced with scar tissue and you are left with a scar instead of contractile tissue so this can affect function so blood delivery is extremely important that's one place where things go wrong it's not just a plaque any condition that's going to decrease oxygen and nutrients delivered to the heart could have a drastic effect on the heart but we learned that all of the cardiac function is driven initially by the electrical events so if there's a problem with an electrical event remember we just gave this area this concept of abnormal electrical events they're called arrhythmias right that's the name so arrhythmias can decrease cardiac output because the electrical events should be coordinated for a proper contraction through all four chambers so it should start in the sa node if we have an ectopic focus that starts somewhere else if we have a origin of a beat that starts somewhere other than the snow this is an arrhythmia because it's not going to be coordinated properly so we know that the ions are spread from cell to cell through gap junctions and this is how it's all coordinated so it could be that the site of the origin of the beat can be away from the sa node we could have a problem with how the signal is being sent through the cell so maybe the pathways of the electrical events are impaired somehow maybe there's destruction of the av node and we get some heart block maybe there's a heart attack that occurred and you have scar tissue and that doesn't have gap junctions and so that's going to create a potential for an arrhythmia but the basic concept again is that the heart is coordinated very specifically of how the electrical events occur because they are leading to the contractions so we can disrupt that and have clinical conditions that occur in the heart well generally speaking just changes in cardiac output how much blood is ejected now this might be because blood delivery has gone down and the heart's not contracted properly the electrical events are impaired and so we have an arrhythmia and the arrhythmia can either decrease the heart rate or can change the heart rate or influence contractility so how much blood is being pushed out are we is the heart stretched out as it has the muscle weakened well we're going to decrease stroke volume so there's a lot of things there but just the amount of blood that's ejected eventually could be impaired by lots of different things but that's a important concept to remember because that's the measurement of cardiac efficiency we could have chemical imbalances i touched upon this just briefly just talking about ion changes across the membrane right we could have a case of hyperkalemia where we have high amounts of potassium in the blood and that can affect cardiac function in fact when we look at it that they used to put i'm not sure if they do it anymore but in in lethal injections that they would put in potassium chloride in there to raise up potassium levels around the heart and the heart will stop so that's just the chemical imbalances just the ion imbalance across the membrane changes the membrane potential and then we're going to affect action potentials and if action potentials are affected that can change the electrical events and it can change contractility so the source of a clinical condition might be chemical imbalances and the last thing is developmental abnormalities we call these congenital heart defects what if you're in terms of development just creating an abnormal structure to the heart sometimes the aorta isn't placed in the right place it kind of overlaps into the right ventricle sometimes you have a hole in your atria sometimes you have a hole in the septum of the ventricles you're exchanging blood between the two sides the valves could develop improperly and these will lead to problems these will lead to clinical conditions where you're not properly ejecting the blood you're not sending it into the right circuit you're not sending proper amounts of oxygen and nutrients out to be delivered so if you just take a look at this list we talked about the problems on the left side here this is just understanding the physiology now we can learn about specific conditions right this is just memorization later if you fully understand the physiology so blood delivery can create angina can create heart attacks electrical events or arrhythmias we talk about fibrillation cardiac output can happen with congestive heart failure not pumping properly chemical imbalances with ions developmental abnormalities these i don't want to remember the conditions unless we talked about them specifically in the lectures but i just want you to take a look at this list and realize that if you understand the left column and you fully understand the physiology then all it is on the right is learning about specifics and memorizing the names and the details associated with it and then you can learn how to treat it but it starts with a solid foundation in physiology