Greetings, so today we wanted to start a discussion about the cardiovascular system, and in particular we're going to talk about the heart and the structure of the heart, and how the heart activities are coordinated by an electrical conduction system. So the first thing to think about is that your heart is about the size of your fist, and it sits about here in your chest, but the point of the heart, pointing down towards your feet. What we want to talk about is the conduction system of the heart, which are specialized cardiac miocytes. They're not going to generate any kind of force or tension, but instead they're going to mediate electrical control within the heart. Secondly we want to talk about this pacemaker activity, because, as you all know, the heart has an intrinsic beat, and that's due to these pacemaker cells or this electrical conduction system. And third we want to talk about how this system is regulated, so you know that you can speed up your heart as you run, and you can slow the heart as you sleep. And this is mediated by the autonomic nervous system. And the fourth is we want to relate the activity of a single cardiac myocyte to the entire electrical activity of the heart itself. And how a cardiologist is able to view the electrical activity of the entire heart on what's known as the electrocardiogram. So, we have several things to deal with. The first is what is the structure of the heart? So the structure of the heart, there is actually two pumps in series. We have one which, is on the right side, and this is the side which is going to send blood to the lung for oxygenation, and then we have a second pump which is on the left side. And the receives blood from the lung, and then pumps it out to the circulatory system. So we have in essence a movement, a unidirectional movement of blood through this system from the right side to the left side. In addition, the right and the left sides are divided into two compartments or two chambers. The upper is called the atrium, and the lower is the ventricle. So, we have a right atrium, and a right ventricle, a left atrium, and a left ventricle, and the blood is going to move, then between the atria to the ventricles in a very ordered or unidirectional manner. The thing that we should notice is that the right atria and the left atria are separated by what's called a septum. And the right ventricle and the left ventricle are also divided by what's called the septum. And these septum are made up of cardiac myocytes, so that the electrical activity that's within the two chambers, that is the atria, the right and the left, and the ventricle, the right and the left, can be electrically coupled. The second thing to notice is that the atria and the ventricles are separated. And they are separated at the junction, which is called the base of the heart. And this junction between atria and ventricle does not consist of cardiac myocytes, but instead it's connective tissue. This effectively isolates the electrical activity of what's happening in the upper chambers that is the atria from the electrical activity of what's happening in the lower chambers or in the ventricles. And we'll come back to that thought in a few minutes. Okay so I said to you then that we're going to have an electrical activity, which will depolarize the cells. And as we depolarize the cells then you know that in muscle, after depolarization, is followed by a contraction, and then we will relax. And before relaxation, we have to have a repolarization of the cells. So, the electrical activity will always be before the contractual events. So, what are our electrical activities? They have to go in a unidirectional manner, because we want to have a unidirectional contraction occurring that is in the atria before the ventricles. And this is coordinated by their electrical conduction system, or by these specialized cardiac myocytes, which are called the pacemakers. In the heart, we have several pacemakers. The first is the Sino-Atrial pacemaker, or the SA node, and it is located in the right atrium, towards the upper region of the right atrium. This is a very fast pacemaker, and it beats at about 60 to 100 beats per minute. The second pacemaker resides at the junction between the atria and the ventricle on the right side, and that is shown here. And this is the atria ventricular node or the AV node. At the AV node, we will have a slight pause in the electrical activity that's occurring within the atria, and then the AV node will fire, and it fires at about 40 to 60 beats per minute. What's unusual about this node is that everywhere else across this junction between the atria and the ventricle, the electrical activity cannot move from the upper chambers to the lower chambers. But, at the AV node, the electrical signal now will be allowed to move from the atria then down to the ventricles. So it's the gateway from the upper chamber to the lower chamber, and it brings the electrical activity into the lower chambers. Within the lower chamber itself, within the septum, the very next pacemaker is called the bundle of His. And this bundle of His will separate into a right and left bundle, it resides within the septum. So we have a splitting of the bundle of His into a left and a right bundle branch. And these will proceed down the septum and up the walls of the ventricles in what's called the Purkinje fibers. All pacemakers do have an intrinsic beat, but this intrinsic beat is slowest of all, and this is between 25 and 45 beats per minute. Repolarization will occur in the opposite direction. The entire event takes about 400 to 500 milliseconds. So for every beat in your heart, where you hear a lub-dub, lub-dub, then this entire conduction system is going to fire, and consequently you will have following upon that, contraction of first the atria, and then of the ventricles. Now the pacemaker potential, as you all know, has an unstable resting membrane potential. And so it differs from our fast action potential that we saw in the contractile myocytes, which are generating tension. The pacemaker potential is called the slow pacemaker action potential, and its duration is 150 milliseconds, in contrast to what we saw with the contractal myocides where their action potential was about 200-220 milliseconds. So it's shorter in duration, and it is a pacemaker potential in that it has unstable resting membrane potential. The resting membrane potential starts at about -55 millivolts, and then slowly moves towards threshold and threshold is -35 millivolts. When the membrane potential reaches minus 35 millivolts, then there is a very rapid opening of voltage gated calcium channels Which allow calcium to enter the cells and we have a depolarization of the cells. Then following that, we'll have an opening of the voltage gated potassium channels. The voltage gated calcium channels close and we have an opening of the voltage gated potassium channels and there is then a repolarization of the cells. And we return to the lower resting membrane potential of a -55 millivolts. So a few things to notice. One is, is that this is slow movement from the -55 millivolts to -35 millivolts or threshold. Is called phase 4, and phase 4 has the odd activities for channels. One of them is that there is a channel called the sodium funny channel. This is a voltage gated sodium channel which physiologists thought was very odd because it opened at very low voltage and then closed at very low voltage. Unlike the voltage gated sodium channel, that we see in the very rapid upstroke or depolarization that occurs in the contractile myocytes. So these funny channels then are opening and closing at a very low voltage. Secondly, the funny channels as they open and close, its membrane voltage then drifts to almost toward threshold. We also open a calcium voltage channels, so voltage gated calcium channels open and close during this period. So phase 4 then has the opening and closing of the sodium funny channels and it has also the opening and closing of the voltage gated calcium channels. Once threshold is net then Phase 0 it begins. And in Phase 0 now, there is a more rapid depolarization and this is due to the opening of the voltage gated calcium channels. The voltage gated calcium channels open calcium enters the cell and we have depolarization. The voltage gated calcium channels close, and we begin Phase 3 with the opening of the voltage gated potassium channels. And as potassium leaves these cells to enter into the extracellular space, then the cells repolarize. Now as you know, as you go through your day, the heart rate can change. So, if you're sitting here, your heart rate will have a basal rate of about 70 to 80 beats per minute, but if you decide that you want to go running, then your heart has to increase its cardiac output. That is you have to increase the amount of blood that's being pumped to the body because of the oxygen demands of the skeletal muscles in your legs. And to do that the heart will increase its rate of firing or urge rate of beats. This is done predominately by changing the phase four duration. And by changing phase four duration in the action potential, we can more rapidly move from our basal of minus 55 resting membrane potential to threshold. This is under the control of the sympathetic nervous system. The sympathetic nervous system speeds up the heart rate then by decreasing or increasing the closure time. Speeding up the closure of the potassium channels, the voltage-gated potassium channels of phase 3. And then the time for opening of the voltage-gated sodium funny channels and of our voltage-gated calcium channels. So it takes a less time to reach threshold. When you have a heart rate which is greater than 100 beats per minute, this is said to be a tachycardia. Now, obviously, that you need to have tachycardia when you're running, but then when you stop and you sit down and relax, then your heart rate will again fall to its resting membrane potential and is not maintained at greater than 100 beats per minute. Now you also can control the heart rate and that is we can slow it down, as I just indicated. And by slowing down the heart rate, to less than 60 beats per minute, this is called bradycardia. But, in the daily life we have a resting heart rate potential is between about 60 to 80 beats per minute. And this is done through the input from the parasympathetic nervous system. The parasympathetic nervous system acts through the muscurenic receptors which are sitting on the heart. And it will cause a prolonged opening of the phase 3 voltage gated potassium channels and by doing that we decrease the level of hyperpolarization within the cells, so that we are actually hyperpolarizing the cells. More potassium is leaving these cells than under normal circumstances. So instead of starting at a minus 55 millivolts, we may be starting at a minus 65 millivolts. In addition to that, the autonomic nervous system slows the opening of the sodium funny channels and, obviously, of the voltage gated calcium channels, so that the slope for phase 4 then is reduced. So, takes longer for the cells to reach threshold. And by doing so then, it slows heart rate. So, when do we have a slowed heart rate? So, we have a slowed heart rate when we're sleeping but you can also have a slowed heart rate through training. For instance, my son went in to have his wisdom teeth taken out and when he went in to have his wisdom tooth taken out, he sat down in the office of the oral surgeon and the nurse came out and she took his heart rate. And then, she went back to the oral surgeon and said, he has a rate rate of 50. This is someone who's about to go in for surgery to have his wisdom teeth removed and he has a heart rate of 50. If it was I who was sitting in the chair, I would probably have a heart rate of 150, because I would be nervous. And so my heart rate would increase due to sympathetic drive to the beta-1 adrenergic receptors on the heart. But, this individual, this fellow actually has heart rate of only a minus 50. So, the surgeon came on and take one look at him and he said, okay, what do you play? He said, soccer, put them under, what was that about? Simply is that athletes with training, have a much higher parasympathetic tone, or parasympathetic activity on their hearts. So that their heart then at basal level, so there is that resting membrane potential of this hearts. The heart rate would be much slower, so they have a much slower beat. And in fact, Lance Armstrong who is the famous bicyclist, and was said to have a heart rate of about 35 beats per minutes at rest. So having a slow heart rate that is a Bradycardia can actually be perfectly normal in a trained individual. But in a person who has the pathology in the heart, a Bradycardia is an indication that the heart is weak or that there's something wrong with the conduction system. And we'll talk about this again in a few minutes. All right, so, now let's start thinking a bit about the electrical activity of the entire heart. So, we've been talking about the electrical activity of the nodes in particular and now we want to talk about how do we find out what the electrical activity if the entire heart is. And you can do this by placing electrodes on the surfaces of the body. And what these electrons will pick up is the depolarization of the entire atria or the depolarization of the entire ventricle. So let's see what we mean by this. So we said that we have firing that's going to be a unidirectional firing within this electrical conductive system. At first we will have the SA node will fire. And that the SA node fires, it will lead to depolarization of the atria. So the depolarization spreads across all of the atrial cells, and these are the contractile cells of the atria. And it does so by moving through the SCAP junctions that are located between the cells. When the depolarization reaches the AV node, there's a slight pause, and then the AV node will fire. And when the AV node fires, then the electrical signal is sent across the AV boundary, that is across our cardiac skeleton into the septum. And it follows the Bundle of his within the septum in both the left and the right branches and then down through the Purkinje fibres and up the walls of the ventricles. So the depolarization of the heart wall occurs also in a very specific manner, and that is is that we will have depolarization from the inside of the wall to the outside. So we depolarize along what's called the endocardium, that's the inner portion of the wall, out to the outer portion of the wall, which is called the epicardium. So we have movement then of the electrical signal through the ventricles and out though the walls of the ventricles. And as we said, repolarization will occur in the opposite direction, we move from the outside of the walls towards the inside of the walls for epicardium to endocardium and from the apex which is the tip of the heart up towards the base which is here at the top of the ventricles. Now, this electrical activity can be picked up by the electrodes that we placed on the surface of the body. We do not see the deflections that would be due just simply to the activity of the nodes. But we can see the summation of all the changes across the contractile cells, that is the cells of the atrium and the cells of the ventricle. Because they're sufficiently large, when we sum all of that electrical activity together then we can pick it up on a surface electrode. This trace that we can pick up overtime is called the electrocardiogram. So let's see what that looks like. So the electrocardiogram is what's diagrammed here and the first thing that we notice is that we have a positive deflection and this is called the P wave and the P wave is our atrial depolarization. So this is the sum of all of the contractile cells which are within the atria that are now depolarizing. There's then an isoelectric interval and then we start with a QRS complex. And the QRS complex is the ventricular depolarization. So the AV node fires, and then we have the ventricles themselves are depolarizing. And eventually we have another isoelectric interval which called the ST interval which we'll talk about in second. And then another wave, a positive wave, which is called the T wave. And the T wave is the ventricular repolarization. So this is where all of the cells now are repolarizing within the ventricle. So a couple things to notice. So we said that we have this PR interval, and that these intervals are timed, like the entire sequence is timed. So if you look at this electrocardiogram on the x axis, this is the millivolts. This is the actual, the potentials that you're recording. But along the x axis this is time. So this is a timed sequence of events. And the PR segment is the time between when the SA node fires and the AV node fires. The ST segment is essentially phase 2 of the fast action potential. This is that isoelectric point or where we had calcium is entering the cells and potassium is leaving the contractile cells. And we have no change really because of the positive charges entering and the positive charges which are leaving the cells. And so that's an isoelectric event and it's phase 2 of the fast action potential. And then R-R is our heart rate. Now if we were to look at the ECG, so this is an electrocardiogram or an ECG. If we were to look at this tracing for someone who is running, what are the intervals that may change in time? So, let's think about that. The first thing is is that we have to repolarize the heart faster so that we can have the next beat. So the very first thing that must change would be that that ST segment has to shorten, because phase 2 of the contractual myocyte, that action potential phase 2 must shorten. So, ST would be one of the segments which we would say, would shorten. The second phase that might shorten would be, obviously, R-R. That has to shorten because we are increasing heart rate, so, R-R will shorten And then what's the third phase that's going to shorten? So let's think about that. The third phase that shortens is the movement of depolarization through the atria. So it's how quickly the atria depolarizes. And the atria will depolarize slightly faster so that we will have a slightly shorter PR segment. So the PR segment also shortens. What about the QRS? Turns out that the time it takes for the ventricles to depolarize will not change. So our change is so slightly that we really can't pick it up on the ECG. So we have three segments then which are changing the R-R, which is heart rate, the ST which is the time between the depolarization and repolarization. We must shorten that in order to speed up the heart rate. And then we also can see some shortening of the PR segment. And that is the time for the electrical activity to move through the atrium. Right,so let's have a little bit of terminology. So the rhythm if it's initiated by the SA node, no matter what its rate, whether it's tachycardia, bradycardia or normal rate, this is called a sinus rhythm. And for every P wave that you will have a QRS complex following it, and then a T wave. Under certain conditions, you can have an ectopic foci or you can have some rogue cells which all of a sudden start firing. And they're no longer listening to the beat of the fastest node. And the fastest node is the SA node, and it usually sets the heart rate for the entire heart. Under these conditions the second set of cells which is firing is called an ectopic foci. And they can interfere with the sequential movement of electrical activity that we have just described. And when that occurs, you can get arrythmias, you can get a skipped beat, you can have improper filling of the Of the chambers either of the atria, if it occurs in the atria or of the ventricle, if it occurs in the ventricle. And under these conditions, if the chamber is contracting so rapidly because of an arrhythmia, then you may not be able to fill it. And if this occurs in the ventricle, this could be lethal. You can have a heart attack. And the other thing that we have to remember then are the electrical activities of the entire heart can be observed on the clinical ECG. That the time intervals, as well as whether a specific wave occurs gives information to the cardiologist as to how well the electrical conduction system of the heart is performing. There are some diseases where for instance, it takes too long for the ventricles to depolarize and so you will have a widening of the QRS. Or you can have other diseases where you have problems with repolarization of the heart and under those conditions then it affects the T wave and the ST segment. All right, so let's look at a case. So our case is Mrs. R, she's 80 years old, and her normal resting heart rate is 85 beats per minute. She usually goes to the gym every day and she works out on an electrical stepper. And on Friday, she was unable to do her morning exercises. She got up in the morning and didn't feel very well, and by the time she got to the gym, she tried to get onto the electrical stepper, but she just couldn't get enough energy and was unable to do her exercises. She felt so badly that she decided to go and see her cardiologist. When she came in, he took her heart rate and he found that her heart rate was 30 beats per minute. She has bradycardia and is this from due to athletic training? No. Her normal resting heart rate was 85 on Thursday and on Friday is now 30. So, something dramatic has happened to the electrical conduction system within her heart. So he decided to run electrocardiogram to see what changes had occurred within her heart, and the electrocardiogram is what showing here. So on the Y-axis we have millivolts and on the X-axis we have time. And as you can see, there are P waves which are present, and that the P waves have a very set time interval. So the P waves are occurring, so that means that the SA node is firing. The SA node is firing and it's firing on a regular basis, so she has a normal SA node. But then if you look at the R in the QRS complex, there's a P wave followed by a QRS here, but then we have a P, which is not followed by the QRS. And then we have another P which again, is not followed by the PRS and that the R to R intervals are actually longer than the P to P intervals. So, the R to R intervals are more R regular but they are at in much longer interval. Which means that they have a different pacemaker. So, we've somehow have uncoupled the electrical activity that's occurring the atria from the electrical activity that's occurring in the ventricle in this particular heart. And what that is, is that there is a complete block at the AV node. So the AV node then, is not taking the information and listening to the pace which is being set by the SA node. But instead, the atria are then contracting at one pace, but the ventricles at a much slower pace. So the new pacemaker, is a pacemaker that's giver her a 30 bpm. And that new pacemaker then would be the, HIS bundle or the Prekinjes. Okay, so one of our key concepts. So the first is, each heartbeat or one cardiac cycle involves electrical activation of the atria and the ventricles in the right and the left chambers. Secondly, that the action potential of the pacemaker and the contractile cells, they're both cardiac myocytes, but their pacement, their action potentials vary or are very different. The pacemakers, the time of the action potential is 150 milliseconds. And we have an unstable resting membrane potential, and in the cardiac myocyte that’s contractile. The time of the action potential is 200 to 220 milliseconds and there's a stable resting membrane potential. The pacemaker cells and have these unstable resting membrane potential. The SA node is the fastest pacemaker in the heart and in the normal heart it sets the beat. So all of the other pacemakers are trained by the SA node, are entrained by the SA node. Fourth, our heart rate is determined by the autonomic nervous system. The sympathetic nervous system increases heart rate, speeds up heart rate and its acting through the beta-1 adrenergic receptors. The parasympathetic is what slows the heart rate, is the break for the system and it's acting through the vagus innervation or the vagal innervation. And it is through the muscarinic receptors which are present on the heart. Five, the electrocardiogram is the sum of the electrical activity of the entire heart. So the P waves depict the atrial depolarization, the QRS complex depicts the ventricular depolarization. And the T wave is the ventricular repolarization. And six, disease of the electrical conduction system can be manifested by changes in the electrocardiogram itself. So both the timing, and whether or not a specific wave is occurring tells the cardiologist something of what may be part of the disease process that's occurring within the electrical conduction system. Okay, so the next time we come in, we're going to talk about how electrical conduction system coordinates the contractile activities of the heart. Okay, so see you then
