Welcome. Today we wanted to start a discussion of the, of 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 with the point of the heart. Down pointing down towards your feet. What we want to talk about is the conduction system of the heart, which are specialized cardiac myocytes. And they're going, they are not going to generate any kind of force or tension, but instead, they're going to mediate control, electrical control, within, 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, you run. And it 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 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 hearts, or 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. That is for oxygenation. And then we have a second pump, which is on the left side, and that 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 atria, 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 the between the atria to the ventricles in a, 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 is called and a septum. The right ventricle and the left ventricle are also separated by what’s called the septum. And these septum are made of. Up of cardiac myocytes so that the electrical activity that's, that's within the two chambers. That is the atria the right and the left and the ventricle, the right and the left, are electrically can be electrically coupled. Second thing is to notice is that the atria and the ventricles are separated, and they're separated by at, at, at the junction which is called the base of the heart. And this junction between atria and ventricle is not 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 of, an electrical activity, which will depolarize the cells, and as we depolarize the cells. Then you know that, in muscle, after depolarization, it's followed by a contraction. And then we will relax. So, and before relaxation, we have to have a repolarization of the cells. So the electrical activity will always be before the contractual vents. 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 the specialized cardiac myocites, which are called the pacemakers. In the heart, we have several pacemakers. The first is the sinoatria 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 between, 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, and that is the A, or AV node. At the AV node, we will have a slight pause in the, in the electrical activity that's occurring within the atrium, 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 atrium and the ventricle. The electrical activity cannot move from one chamber, 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, to the ventricles. So it's the gateway from the upper chamber to the lower chamber. And it brings electrical activity into the lower chambers. Within the lower chambers itself, within the septum, the very first, then 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. Se we have a splitting of the Bundle of His into a left. In 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. These all, these 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 40, 400 to 500 milliseconds. So for every beat in your heart, where you hear a" lub-dub, lub-dub," then this, this entire conduction system is going to fire and you will have, consequently. You will have, following upon that, contraction of both, first the atria and then of the ventricles. Now, the pacemaker potential, as you all know, has an unstable resting membrane potential. And that, and so it differs from our fast action fast action potential that we saw in the contractile myocites, which are generating tension. This is, the pacemaker potential's called the Slow Pacemaker Action Potential. And it's duration is 150 milliseconds in, in contrast to what we saw with the contractile myocytes, where their action potential was about 200 to 220 milliseconds. So it's shorter in duration, and it is, it is a pacemaker potential, in that it has an unstable resting membrane potential. The rest, the resting membrane potential starts at about a minus 55 millivolts and then slowly moves towards threshold, and threshold is at minus 35 millivolts. When the resting membrane potential, when the membrane potential reaches minus 35 millivolts then there is a very rapid opening of calcium, voltage gated calcium channels. Which allow calcium to enter the cells and we have a depolarization of the cells. Then, following that, we 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 re-polarization of the cells. And we return to the lower resting membrane potential of a negative 55 millivolts. So, a few things to notice. One is, is that this is slow movement from the, the negative 55 millivolts to a negative 35 millivolts, or threshold. Is called Phase Four, and phase four has the, some odd activities, for channels. One of them is that is a channel called the. Sodium sodium funny channel. This is a voltage gated sodium channel, which physiologists though was very odd because it opened at a very low voltage and then close at a very low voltage. Unlike the voltage gated sodium channel that we see in the, very rapid upstroke or de-polarization. That occurs in the contractile myocytes. So these funny chanles then are opening and closing at a very low voltage. Secondly, the funny channels as they open and close, and the membrane voltage then drifts or moves towards stretch old we also open the calcium voltage channels. So voltage gated calcium. And close during this period. So, phase four then has the opening and closing of the sodium [UNKNOWN] channel and it has also, the opening, closing of a voltage gated calcium channels. Once threshold is met, then phase zero begins. And in phase zero, now, there's 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 three 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. [BLANK_AUDIO] Now as you know as you go through your day the heart rate can change. So, if you are sitting here your heart rate will have a basal rate of about 70 to maybe 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 being pumped to the body because of the oxygen demands of the skeletal muscles in your legs. And to do that we increase, the heart will increase its rate of firing or its rate of beat. This is done predominantly by changing the vol, the phase four duration. And by changing phase four duration in the, in the action potential, we can more rapidly, move from our basal 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, or increasing the closure time, speeding up the closure of. The potassium channels, the voltage gated potassium channels a phase three and then opening the the time for opening of the voltage gated sodium funny channels and voltage gated calcium channels. So we much more so it takes less time to reach threshold. When you have a heart rate which, a beat, is greater than 100 beats per minute, this is said to be Tachycardia. Now obviously, the, 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 it's not maintained at greater than 100 beats per minute. Now, you also can control the heart rate in that is, that is, we can slow it down. As, as I just indicated. And by slowing down the heart rate to less than 60 beats per minute. This is called Bradycardia. But in a daily life, we have, we have a resting heart rate potential is between 60 to 80 beats per minute. And this is done through the input from the parasympathetic nervous symptom. The parasympathetic nervous system. Acts through the, the muscarinic receptors which are sitting on the heart and it will cause a prolonged opening of the phase three voltage gated potassium channels and by doing that we decrease the. The level of hyper polarization within the cells. So, that we are actually hyper polarizing 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 millibells. In addition to that, it, the, ononotic nervous system slows the opening of the sodium funny channels, and obviously, of the voltage-gated calcium channels. So that the slope for phase four then, is, is reduced. So, it 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 slow heart rate through training. For instance, my son, went in to have his, his, his wisdom teeth taken out. And when he went in to have his wisdom teeth taken out, he sat down in the 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 heart rate of 50. This is someone who is 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 the sympathetic drive to the beta one adrenergic receptors on the heart. [SOUND] But this individual, this fellow actually has a heart rate of only a minus 50. So the surgeon came out and took one look at him and he said, ok what do you play and he said, soccer. Put him under. What was that about? Well, it simply is that athletes with training have a much higher Parasympathetic tone or a Parasympathetic activity on their hearts. So that the heart then at basal level, so it's at resting membrane potential, these hearts the, the heart rate will be much slower. So they have a much slower beat. And in fact Lance Armstrong, who is the famous bicyclist who and was said, said to have a heart rate of about 35 beats per minute at rest. So having a slow heart rate that is a bradycardia can actually be perfectly normal, in a trained individual. But in, in a person who has a pathology in the heart, a bradycardia is an indication that the heart is weak. Or that there is something wrong with the conduction system. And we'll talk about this again in a few minutes. [BLANK_AUDIO] [SOUND] Alright, 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 to we find out what the electrical activity of the entire heart is. And you can do this by placing electrodes on the surfaces of the body and, and what those electrodes will pick up is, is the depolarization of the entire atria or the depolarization of the entire ventricle. So let's see what we, what we mean by this. So we said that we have firing that's going to, to be a uni, unidirectional [SOUND]. Firing, within this car, within this electric conductive system. And first, we will have the SA node will fire, and that the SA nodes fired, it will lead to depolarization of the, of the atrium. And, so the depolarization spreads across all of the atrial cells, and these are the cont, contractal cells of the atria. And it does so by moving through the gap junctions that are located between the cells. [SOUND] 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, and it follows the bundle of [INAUDIBLE] within the septum in both the left and the right branches and then down through the Purkinje fibers and up the walls of the ventricles. So the depolarization of the heart wall occurs also in a very specific manner. And that is that we would have depolarization from the inside of the wall to the outside. So we've depolarized along what's called the endocardium, that's the inner portion of the wall, out to. To the other portion of the wall which is called the epicardium. So we have movement then of the electrical signal through the ventricles and and out through the walls of the ventricles. And as we said, repolarization will occur in the opposite direction, where we move from the outside of the walls towards the inside of the walls, from epicardium to endocardium. And from the apex, which is the tip of the heart, up towards the base, which is here, at the. 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 of the changes across. The car, the contractile cells, that is, the cells of the atrium and the cells of the ventricles. Because they're sufficiently large, when we sum all of that electrical activity together, that we can pick it up on a surface electrode. And this, this trace that we can pick up over time 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 a. 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 ventricular, the ventricles themselves, are depolarizing. And eventually we have another isoelectric interval which, called the ST interval, which we'll talk about in a second, and, 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 of 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 potentials that you're recording. But along the X-axis, this is time. So this is a sequence, a time sequence of events, and the PR segment is the time between when the SA node fires and the AV nodes, fires. The ST segment is essentially phase two of the fast action potential. This is that iso electric point, or that, where we have calcium that's entering the cells, and potassium leaving the contractal 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 two of the fast action potential. And then R-R is our heart rate. Now if we were ta, to look at the. ECG. So there is an electrocardiogram or an ECG. If we were to look at this tracing for someone who is running, what are the parts, what are the intervals that may change in time? So let's think about that. The first thing is that we have to re-polarize 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 two of the contractile myocyte, that action potential, phase two, must shorten. So ST would be one of the segments, which we would say would shorten. [BLANK_AUDIO] The second phase that might shorten would be obviously R-R. That has to shorten, because we're 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, the de, the 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. So we have the QRS? Turns out that the time it takes for the ventricles to depolarize it, will not change. So, or changes such slight, so slightly, that we really can't pick it up on, on the ECG. So we have three segments then which are changing. The R to R which is heart rate. The ST which is the time between the depolarization and the repolarization. We must shorten that in order to speed up the heart rate. And then we can also see some shortening of the PR segment. And that is the time for the electrical activity to move through the atria. [BLANK_AUDIO] Alright, so lets have a little bit of terminology. 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 will, you will have a QRS complex following it, and then the T wave. Under certain conditions, you can have an ectopic foci, or atopic, or some rogue cells that 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, 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 the electrical activity that we have just described. And when that occurs, you can get arithmeticians, you can get a skipped beat. You can have improper feeling of the, of the chambers. Either of the atria that occurs in the atria or of the ventricle if it occurs in the ventricle. And under these conditions, if they, if they chamber. Is contracting so rapidly because of an arhythmia then you may not be able to fill it and if this occurs in the ventricle this could be lethal. You could have a heart attack. The other thing we have to remember then are the electrical activites of the entire heart Can be observed on the clinical ECG, and that the time intervals as well as whether a specific, a specific wave occurs. Gives information to the cardiologist as to how well the electrical conduction system of the heart is performing. [SOUND] There are some diseases where, for instance, it takes too long for the, for the the ventricles to depolarize, and so you'll have a widening of the QRS. Or you can have a other diseases where you have problems with re-polarization of the heart, and, under those conditions then, it affects the T wave under the ST segment. [BLANK_AUDIO] Alright so let's look at a case. So our case is Mrs. R. She is 80 years old and her resting heart rate is 85 beats per minute. She usually goes to the gym everyday and she works 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. And she felt so badly that she decided to go and see her cardiologist. And when she came in, he took her heart rate and he found that her heart rate was 30 beats per minute. Does she have a, she has bradycardia. And is this from, due to athletic training? No. Her normal resting heart rate was 85 on Thursday, and on Friday it's now 30. So something dramatic has happened to the electrical conduction system within her heart. So he decided to run an electrocardiogram to see what, what changes had occurred within her heart. And their electrocardiogram is what's shown here. So on the X, 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 have a, are, 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 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, are regular. But they are at a much longer interval, which means that they have a different pacemaker. So we somehow have uncoupled the electrical activity that's occurring in the atria. From the electrical activity that's occuring in the ventricle in this particular heart. And what that is is that there's a complete block at the AV node. So, the AV node then is not taking information and listening to the peak, 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 is giving her thirty beats per minute and that new pacemaker would be then [SOUND]. Okay, so what are 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 potentials of the pacemaker and the contractile cells, they're both cardiac miosize but their pacement, their action potentials vary or are very different. Pacemakers the time of the action potentials are 150 milliseconds and we have an unstable resting membrane potential. And in the cardiac myocyte that's contractile, the, the time of the action potential is 220 no 200 to 220 milliseconds and there's a stable resting membrane potential. The pacemaker cells then 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 are trained by the SA node, or in trained by the SA node. Fourth, our heart rate is determined by the autonomic nervous system. The sympathetic nervous system increases heart rate, it speeds up heart rate, and it's acting through the beta one exonergic receptors. The parasympathetic is what slows the heart rate; it's 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, tells the cardiologist something that's 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 this electrical conduction system coordinates the contractal activities of the heart. Okay. So, see you then. [BLANK_AUDIO]
