HS2 Cardiovascular Physiology Transcript PDF

HS2_CVSPhysiol_L2_LO1 Slide 1 Hello, my name's Tim Murphy, and let's get on with learning outcome 1 of this lesson, which is to identify the key features of the heart and understand the heart's basic function. Slide 2 Before we talk about the role of the heart specifically, let's talk about the rol...

HS2_CVSPhysiol_L2_LO1 Slide 1 Hello, my name's Tim Murphy, and let's get on with learning outcome 1 of this lesson, which is to identify the key features of the heart and understand the heart's basic function. Slide 2 Before we talk about the role of the heart specifically, let's talk about the role of the cardiovascular system in general in homeostasis. And as you're hopefully aware, homeostasis is an important physiological principle that talks about the maintenance of an internal environment necessary for life and ensuring optimal conditions for the maintenance of life. The homeostatic role of the cardiovascular system is to provide a material transport network which assists in maintaining the interstitial fluid, the immediate environment of the cells which make up the tissues and organs of your body. Specifically, the role of the cardiovascular system is to deliver nutrients to the interstitial fluids such as oxygen, glucose, amino acids and fat, and to remove waste products like carbon dioxide, lactic acid and urea. It also has an important role in signalling between tissues and organs by carrying hormones between those tissues and organs, has an important role in controlling body temperature in thermoregulation and also has an important role in the response to infection and maintaining your immune responses in immunity. Now to do all these things, including its primary job of delivering nutrients and removing waste, we need a flow of the plasma in order to constantly deliver the nutrients and constantly remove the waste products from interstitial fluid, and a balanced composition of the plasma to make sure the right amounts of substances are in the blood and the plasma. Now this little picture here is just showing you an example of that. So here's some cells here in your body. They could be any cells in any tissue and they're constantly requiring oxygen, which is the example used in this picture. So we constantly need a supply of oxygen that's coming in, the blood that's flowing around, and that oxygen diffuses at the site of the capillaries in your circulation, out of the plasma and into the interstitial fluid where they can be taken up by the cells. Once the oxygen's been taken up, of course the blood then has to collect more oxygen and so it then flows up to the lungs here. And of course you've got a constant supply of oxygen in the alveolar sacs here coming from the environment that you've breathed in, in the air you've breathed in. And again, the oxygen has to diffuse from the alveolae into the pulmonary capillaries here. And then once the blood's replaced with oxygen, it then flows back to the tissues to deliver that oxygen. Now that that passage of substances between the cells, the interstitial fluid and the plasma is carried out by diffusion, as shown as either end of this picture. And the carriage of the oxygen in this case, or it could be any nutrient, is carried by convection. And convection just means being carried basically. And we need flow. And for flow, for the blood to flow, we need a pump. And of course the heart is the pump. We have the left hand side of your heart that pumps blood from the pulmonary circulation into the systemic circulation here. And the right hand side of your heart takes the blood from systemic circulation and pumps it through the pulmonary circulation. Slide 3 So just to summarise that point, substances move between the interstitial fluid and the plasma by diffusion and substances move between organs by convection, by being carried along in the plasma. Now in order for diffusion to occur you need two things. You need a permeable capillary wall. So the substances in your plasma have to be able to get out, and all the substances in the interstitial fluid here, the waste products of cellular metabolism have to be able to get into the plasma and so you need the wall to be permeable to those substances. And of course for water soluble substances, that means there have to be holes in there and you also need a concentration gradient that's going to force the substance to move. So again, in the case of oxygen, the cell here is constantly using oxygen. So it drains the oxygen from the interstitial fluid and that creates a concentration gradient for the oxygen rich plasma for the oxygen to diffuse out of the plasma into the interstitial fluid and into the cell. Similarly, you require a constantly low concentration of carbon dioxide in the plasma. So as the cell produces carbon dioxide it will diffuse into the interstitial fluid and then into the plasma down its concentration gradient. Now in terms of convection, the sorts of substances that are carried by the plasma can either be dissolved and that's typically small water soluble molecules like glucose or salts. Some other things are suspended in the plasma and these are things like fat globules here, large proteins which are shown in sort of green and blue dots here. Of course we've got cells, so we've got red blood cells here and of course white blood cells or leukocytes which are shown in that sort of pale dot there. So things can be either suspended floating along in the plasma or they can be completely dissolved in the in the water of the plasma. Slide 4 Now what the heart's actually doing is providing a pressure gradient between the heart and the rest of the circulation and blood flow depends on that pressure gradient. And what the pressure gradient is, what the pressure is trying to overcome is resistance to blood flow caused by the conducting vessels or the blood vessels. So blood flow is the pressure gradient divided by the resistance, or to give them their sort of usual physiological symbols, Q, flow is the delta-P, the pressure gradient divided by R, the resistance. Now physiologically speaking, your heart has two sides and it has four chambers, but there are two sides. We have the right heart which receives the de-oxygenated blood from the systemic circulation and pumps it through the pulmonary circulation. And here we have the superior vena cava bringing the oxygenated blood from the upper body and the inferior vena cava bringing the de-oxygenated blood from the lower body into the right atrium. It then contracts and pushes the blood into the right ventricle through a valve. Now a valve is a structure that allows flow in only one direction. And we have atrio-ventricular valves which separate the atria from the ventricles on both sides of the heart. The atrio-ventricular valve in the right side of the heart, on this part of the heart, is called the tricuspid valve. And from there the blood then, when the ventricle contracts, flows out of the heart into the pulmonary arteries through another valve. So again, we don't want the blood going backwards once it's come out of the right ventricle. And the valve separating the right ventricle from the pulmonary arteries is called the pulmonary artery valve. The left side of the heart receives the oxygenated blood from the pulmonary circulation through the pulmonary veins, and the blood flows into the left atrium here. And then when the left atrium pumps, it opens the valve that separates the left atrium from the left ventricle on the left side of the heart. And this atrio-ventricular valve on the left is called the bicuspid valve or mitral valve. And then the contraction of the left ventricle pumps the blood through another valve, in this case the aortic valve, into the aorta. The aorta then carries the blood through, well, through itself and through various branching vessels into the various parts of the body that require the oxygenated blood. Slide 5 Now this mechanical action of the heart or the pumping of the heart actually has two phases. The contractile part is called systole, so you pronounce the ‘e’. And this is when the ventricles or the atria for that matter are contracting and moving the blood around. And then when those chambers are relaxing and filling up with blood, this is called diastole. So contraction of the heart is systole, relaxation of the heart, diastole. And this little picture here is just showing you the state of the heart in those two phases. So during diastole…we usually focus on the ventricular muscle because that's the most important for the heart's function…during diastole, the ventricular muscle is relaxing. Here the ventricle is distending and the ventricle is filling up with blood coming from the pulmonary circulation. So we have blood flowing in here through the pulmonary veins into the left atrium. The mitral valve at this stage will be open to allow the blood to flow into the ventricle and fill it up. And the aortic valve up here will be closed to stop the blood that's just being ejected in the previous systole systolic event from flowing back into the heart and making sure that blood flows away to the rest of the organs in the body. During systole, the ventricular muscle is contracting as shown here. So it gets much thicker and the whole of the space in the left ventricle gets smaller. The ventricle is contracting and the muscles contracting, the blood is being ejected from the ventricle. So this is the ventricular emptying phase. The aortic valve will be open at this in this situation, so the blood can get out of the ventricle into the aorta and it’s smaller branching vessels and down here into the lower body, and the mitral valve will be closed. We want the blood to go out into the into the arteries here. We don't want the blood to go backwards into the pulmonary circulation again, so the mitral valve is closed to stop that happening and to allow the blood to go down the right path which is the aorta and the arteries. So lastly, muscle relaxing, mitral valve open in the left side of the heart and the tricuspid valve in the right side of the heart, aortic valve or pulmonary artery valve closed and then systole, the ventricular muscle contracting the mitral valve closed and the aortic valve open to allow the blood to flow away into the systemic circulation. HS2_CVSPhysiol_L2_LO2 Slide 1 Now let's address learning outcome 2, which is to know the electrical events of the cardiac cycle, including the pathway of electrical conduction through the heart and the events of a typical electrocardiogram or ECG/EKG, and how this recording is obtained. Slide 2 Cardiac muscle contraction and relaxation is controlled by electrical stimulation represented by the action potential in the membrane of the cardiac muscle cells. When the cardiac muscle cell membrane is depolarised, that causes contraction of the muscle. And when the cardiac muscle cell membrane potential repolarises, that means goes back to its resting level, that causes relaxation of the cardiac muscle cell. And here's a typical cardiac muscle cell here. They're sort of oblong in shape with these jagged bits at the end where the intercalated discs go, and we'll see a bit more about those in a moment. If we depolarize the membrane, that causes an action potential, which is what the little lightning bolt signifies, that causes calcium to enter the cell and the cells to contract. And when all the cardiac muscle cells contract, then the ventricle contracts. When the membrane potential returns to its resting level following the action potential and depolarization, then the calcium levels in the cell go down and the muscle relaxes. And of course all the cardiac muscle cells relax during diastole when the ventricle is relaxing. And that's also indicated here on this little graph. So here's the resting membrane potential when the cell would be relaxed, then it depolarises here as part of the action potential in the red showing the red line here, the membrane potential is increasing and you can see here the muscle starts to contract. It's shown in the middle picture here. And then once the membrane potential starts to return to normal, this repolarization phase here on the right hand side here of the red line, then the muscle starts to relax and go back to (normal) - relaxed. So it's these electrical events which dictate whether the ventricle, or the cardiac muscle, and therefore the ventricle is contracting or relaxing. Slide 3 Now all the cells in your heart, that's including the atrial muscle, the ventricular muscle and the Purkinje fibres, which are the heart's conducting system, which I'm sure Doctor Amaneh has already told you about, all these cells are electrically excitable, that is that their membranes are capable of depolarizing and generating an action potential and causing contraction, or conduction in the case of the Purkinje fibres. The cardiac muscle cells are also electrically coupled to each other, enabling them to all contract together or relax together in a coordinated way, so we can get the whole ventricle to contract or relax at once. And this little diagram here is showing you that. So here's a piece of the heart called the sinoatrial node, which generates the electrical current that's going to make the cells contract and we'll talk a bit more about that in a moment. Here are some cardiac muscle cells here and they're electrically connected to each other by these structures called intercalated discs, which are these little sort of zigzag lines here and you can see them here in close-up. An intercalated disc contains firm mechanical attachments called desmosomes and that allows the cardiac muscle cells to stick together really tightly and pull on each other when they contract to help make the ventricle contract. The intercalated discs also contain low resistance electrical connections called gap junctions. And that's this sort of brown through thing here. It's half a cylinder if you like. And these gap junctions allow the action potentials and the electrical current to spread rapidly between the cells. So the sinoatrial node here is going to generate the initial action potential and depolarize and then the current that's generated by that action potential passes between the cardiac muscle cells through these gap junctions in the intercalated discs. Slide 4 Now as mentioned on the previous slide, the origin of the current that's going to make the cardiac muscle cells depolarize and contract is a part of the heart known as the sinoatrial node or the SA node, as it’s sometimes abbreviated to, or the sinus node, and it's located right up here in the top of the right atrial wall, right where the right atrium meets the superior vena cava. That's the sinoatrial node and it generates spontaneous rhythmic waves of depolarization or rhythmic actual potentials that initiates the electrical signal. And the rate at which it generates these pulses of current sets the basic heart rate. That's why the sinoatrial node is sometimes known as the pacemaker of the heart, as indicated in this number-one labelled structure here. Now the atrial muscle conducts the electrical current rapidly through both atria, and we can see that here. Here's the pulsing of the sinoatrial node generating waves of current that's spread through the heart and the atrial muscle. And some special conducting bundles called inter-nodal pathways conduct that current very rapidly through the right and left atria here. Now after the currents pass through the atria made them contract, there's only one point at which the current can pass from the atria to the ventricles and that's known as the atrio-ventricular node. As this structure here #2 atrio-ventricular node, it's the only point where the electrical current can pass from the atria to the ventricles. So the atria and ventricles are electrically isolated or insulated from one another. The only point the current can get from the atria to the ventricles is through the atrio- ventricular node here and this specialised conducting tissue here called the atrio-ventricular bundle, or if you've got an older textbook, it used to be called the Bundle of His. So once the atrio-ventricular node here is stimulated, the current can then get through from the atria to the ventricles. Now the conduction is quite slow or relatively slow through the AV node. There's a delay of about 0.1 of a second, which in terms of the heart function is quite a long time. That is to allow to the atria to contract after they've been stimulated and pump their contents into the ventricle through the valves here. And you can see in this particular picture, the mitral valve, which is here and the tricuspid valve, which is that white structure over there are both widely open to allow the blood to flow from the atria to the ventricles. So a bit of a conduction delay at the atrio-ventricular node to allow that to happen. And then once the current goes through the AV node, conduction is very rapid through specialised conducting tissue called Purkinje fibres. And there these structures here shown in yellow. Conduction goes very rapidly from the AV node through the Bundle of His, down the septum, which is the wall of muscle that separates the two ventricles to the apex of the heart, which is the bottom here, and then up the walls of the ventricles towards the tips. So the conduction goes down the septum through the Purkinje fibres and then up the walls of the ventricles through more Purkinje fibres that are branching out to smaller and smaller branches, and then finally through the cardiac muscle itself through those gap junctions. Now that conduction from the AV node once it's stimulated to the ventricles is extremely rapid and that allows for coordinated contraction of the ventricular muscle cells, which as we said are also electrically coupled to each other as well as having the Purkinje fibres to make the spread of the current rapid as possible. So just to summarise, the current that makes the heart muscle contract is generated spontaneously in the sinoatrial node or sinus node here, the pacemaker cells. The current then travels rapidly through the two atria. It slows down here at the atrio-ventricular node, which is the only point which the current can pass from the atria to the ventricles. Once the AV node is stimulated, then the current passes rapidly through the Bundle of His, down the intraventricular septum, through the Purkinje fibres and then up the walls of the ventricles again through the Purkinje fibres. And that path of conduction means that the ventricles start contracting from the base first and then contract up towards the top, which helps squeeze the blood from the bottom of the heart up through the aortic valve, which is that structure shown there, and the pulmonary valve, which you can't actually see in this picture. Slide 5 Now these electrical events can be measured using a technique called, or producing a recording called, an electrocardiogram or ECG as it's abbreviated. And you'll quite often hear the term EKG, in fact, that's probably used more often by medics and clinicians, probably reflecting its European origins. This technique was invented in the early 1900s and this is an example here of a British physiologist called Augustus Waller from Saint Mary's Hospital in London demonstrating the technique on his dog to the Royal Society in 1909. Now in in modern times, we use metal electrodes to record the currents, but he's using salty water here as a conductive substance to measure the currents on his dog. And people in parliament got very upset. They thought the dog was being hurt or tortured or something, (not understanding) that the electrodes are being used to record electrical current, electrical currents, not to deliver them. Slide 6 Now the physiological basis of the ECG is the fact that the currents that are passing through the heart when it's being depolarized from the SA node through the atria, through the AV node, the Bundle of His, the septum, and so on, form or create electrical potentials which can be measured because they spread to the surrounding tissue including the skin. So if we put electrodes on the skin on opposite sides of the heart, we can record electrical potentials generated by these currents and recording of those electrical potentials is the electrocardiogram. Now what we're going to be talking about in this lecture is the simplest form of ECG, which is called a three-lead ECG. And to give it its full name, it's a 3 bipolar limb-lead ECG. And to get this sort of ECG, you put the recording electrodes rather placed on both arms and the left leg. And the standard or classical way to do it is to put them on the wrists, the two arm electrodes, and on the left ankle for the left leg, one with the earth lead (electrode) on the right ankle. Now probably the sort of ECGs that a lot of you might do, you'll require the subject to be moving and if they're doing exercise, they'll be on an exercise bike or a treadmill or something like that. So for convenience, what you can do is put the electrodes on the shoulders here instead of the ankles. They’re what are called the arm electrodes and the leg electrodes you can put on the lower abdomen here. So you can see this one's on this guy's lower left abdomen instead of his left ankle, and the earth electrodes on the lower right abdomen here for the right ankle. And that's OK, you get a very similar recording rather than putting the electrodes on the wrists and ankles. Now, it's important to understand that a ‘lead’ in this context is a recording from a pair of electrodes on opposite sides of the heart and the electrical circuit they form using the subject's skin and the recording device. So a ‘lead’ is not the bit of wire here that's stuck on the electrode. Actually, a lead is the electrical circuit formed by the two electrodes, the recording device that are connected to it by the wires and the subject's skin. So a lead is a recording from a pair of electrodes, not just from one bit of wire. Now you can see we've got 3 in this arrangement, excluding the earth, of course, we've got three possible leads. Next bit (italics) is wrong: So we've got Lead 1 is where the right arm or right side is positive and the left side is negative here. Lead II is where the right upper electrode is positive and the lower (left leg) electrode is negative. Sorry, I've got them back-to-front there. Correct here: (For Lead II) the right arm is negative and the lower left is positive and Lead III is where the left arm or left side is negative and the left leg is positive. So Lead I records right arm, left arm or right side, left side. Lead II records right arm-left leg and Lead III records left arm-left leg. And you can see those 3 recording vectors as they're known or directions forms a triangle, an equilateral triangle around the heart. And that's known as Einthoven's triangle after the guy that's sort of credited with inventing this recording technique. Slide 7 Now, why do we need these three different recording angles? If you like, you know, you might be thinking, well, why can't, why can't we just have two electrodes and, and, and one lead? (I sound like Morty Smith). Well, these leads can really only see things in one dimension. So the different leads allow for different views of the heart. And an analogy is made with looking at this car here, for example. So if I asked you what sort of condition this car was in, you'd say well, and what it looked like, you'd say well it's got 4 headlights and it's sort of red and the bonnet, the hoods looks good and it seems in fairly good condition. But if I asked you, well, you know, what are the wheels like and do the tail-lights work and so on, you wouldn’t really be able to tell me because you simply couldn't see them. But if you moved around a bit, you could say, oh, it's got white walled tyres and it's a convertible and it's, the tail-lights are all working and in good shape and, and the doors are, are sort of, they're not damaged or anything. So by moving around, you can get a, a full three-dimensional view of the car. And it's the same with the leads in the heart. If you position the leads, the electrodes, so you've got different leads on different sides of the heart, you can examine the electrical activity in different parts of the heart using those leads. And indeed, as I said, a 12-lead ECG is probably more commonly used to diagnose pathology. And you see a lot more detail with the 12-lead ECG than you do with the three-lead ECG. Slide 8 So let's look now at a typical ECG recording. And this is a typical Lead II trace. And again, Lead I and Lead III will have slightly different shapes. The waves will have slightly different shapes, same events, but different shapes. We'll be looking at the Lead II recording here. So you can see the 1st event that happens is called the P wave. And the P wave here is signalling or indicating atrial depolarization. So when the current passing through the atria prior to it contracting, it's the P wave. Next we have what's called the QRS complex. And the QRS complex indicates ventricular depolarization. So you can see that goes the Q wave is this little downward deflection here. The R wave is this big upward deflection. And then the S wave is this downward deflection here at the end. So it's called the QRS complex and that's caused by the different directions, of course, the current is passing in, travelling through in the ventricle. So remember that the current goes down the septum to start with, as we mentioned, from the AV node. Then it goes up the walls of the ventricles on the outside. So down the septum is a big upward deflection. And then the current of course reverses and goes in the opposite direction to travel up the outside wall of the ventricle, which is why the current reverses and goes downward like that. The Q wave is caused by the fact that the left-hand side of the septum depolarizes slightly before the right-hand side. And you can't see the Q wave clearly, clearly on all traces. On some of them it's very prominent, on others it's quite small. It's usually fairly small on a Lead II recording. And the S wave here is caused by, at the very tops of the ventricles, the current sort of goes around in a bit of a circular direction rather than sort of up and down, but basically the shape of that QRS complex is caused by the direction in which the current is travelling in the ventricles and the fact that it reverses, after it's gone down the septum to go up the walls of the ventricles. We then have a bit of a flat spot here called the ST segment before we have the T wave and that is ventricular repolarisation. So you remember I said at the start of this little section that the ventricles had to repolarise in order for them to relax. The T wave there reflects the repolarizing current that's returning the cardiac muscle cells to their normal (resting) membrane potential that's associated with ventricular relaxation. So P wave atrial depolarization, QRS complex, ventricular depolarization, T wave ventricular repolarization, and there's a couple of other factors here that that are worth mentioning. Firstly is the PR interval here and that's the start of the P wave to the start of the QRS complex. It's called the PR interval because as I said, it's often very difficult to see the Q wave. And so on some traces you can only see the R-S complex. And what that time-period (PR interval) represents is the time for the conduction of the action potential from the SA node through the atria and through the AV node to the ventricles. So it takes the time for the current to get from the SA node, through the atria, through the AV node. And when the ventricles start to depolarise, that's when the current is hitting those Purkinje fibres and muscle at the top of the ventricular septum. Now that time should be between 0.12 and 0.2 seconds, because you remember we said there was a conduction delay of about 0.1 second at the AV node. Now if it's longer than that, in other words, if it's 0.2 to 0.35 seconds, you've got something called first-degree heart block. Now that's usually asymptomatic. It means you doesn't sort of associate it with any sort of heart problem. It depends on how long that PR interval is. If it's longer than 0.35 (seconds) then you might have a problem, but it may indicate some underlying or developing condition affecting conduction of the current from the SA node to the ventricles. Usually it means there's some damage or ischemia with the AV node that's stopping the current from getting through. Then we have the ST segment, and this is a period where the ventricles are fully depolarized, so the entire heart is isoelectric. That means there's no current flowing in the heart at this point. The muscle cells are all fully depolarized and there's a little period where they're contracting, so there's no current flowing through and it's before the T wave when they repolarize and start to relax. So there should be no current during this ST interval, this flat spot here, or as it’s shown over here rather, it's better this spot, here, the ST segment, which is why it's on the zero line. If it's raised up higher or lower, so it's position relative to the rest of the ECG has changed, that can indicate some sort of damage to the heart, either ischemia, which means it's not got enough oxygen, or infarction, which means it's slightly worse, it means (a part of) the heart has no blood flow at all. So if the heart's not getting enough oxygen or we have infarction, which is the no blood flow at all to a part of the heart, that can change the position of that ST segment. And finally, we have the QT interval shown here. That's the start of the QRS complex to the end of the T wave and that is the total time for which the ventricles are depolarized. So they start depolarizing here, and they finish repolarizing at the end of the T segment. Now that QT time varies a bit. It varies with your heart rate, your age, and your gender. So generally women are allowed a slightly longer QT interval than men. But if you've got a normal heart rate of say 70 beats per minute, it should be about 0.4 seconds. If it's longer than that and you have something called prolonged QT syndrome, that's a problem because it means your heart is depolarized for a longer than normal time. And that can lead to a condition called a ventricular arrhythmia, where parts of the ventricle don't contract in sequence and it affects the ability of your heart to pump blood out, or (ventricular) fibrillation, which is where your cardiac muscle cells are completely uncoordinated from other muscle cells and you get different parts of the heart contracting at different times and no coordinated contraction. Now, if you have an electrolyte imbalance, particularly if you have abnormal levels of potassium or calcium in your blood, it can affect the QT interval. And there's also a number of drugs which unfortunately can prolong the QT interval. Slide 9 Just a little bit more on this ST segment and its relation to heart function. And as I said, if it changes its position relative to the rest of the ECG, that can indicate problems with the heart. If the ST segment is depressed, that causes (suggests) ischemia, and if it's elevated, that indicates a myocardial infarct. And the way to remember that is that depressed and ischemia both have an ‘s’ in and elevated and infarct both have the letter ‘t’ in, sort of a way of remembering that. Now this picture here explains why that is. I don't expect you to really know what that is, but it does give some examples down the bottom here. So on the left is an ischemic heart. That's a heart that might have less than normal blood flow, so it's not getting enough oxygen. And you can see in this ECG trace down here, the ST segment is depressed. You can see it's below the isoelectric or the zero-millivolt line, so a depressed ST segment indicates ischemia. That means some cardiac muscle cells that are not getting enough oxygen to carry out their normal function. Over here is an example of an elevated ST segment where you might have a myocardial infarct. So an infarct is a bit more serious than ischemia. It means that some blood vessels supplying parts of the heart are completely blocked, meaning those cells are getting no oxygen or blood flow at all. It means they're not getting any glucose or anything from the blood. And in infarction you get an elevated ST segment as shown in this ECG trace, so you can see here basically the ST segment's joined in with the T wave. So depressed ST segment ischemia, elevated ST segment is infarction. And I won't go into the, I won't go into detail about the reasons for that. Basically means that the membrane potential of those cells that are affected is different to the rest of the heart that has normal blood flow because (those cells are) not getting enough oxygen. And that sets up a localised current between those normal cells and the damaged cells, there shouldn't be any current during this period, but now there is because the membrane potential of those damaged cells is different to the normal ones. It's what causes these changes in the ST segment. HS2_CVSPhysiol_L2_LO3 Slide 1 Learning outcome 3 of this first lecture is to understand the mechanical events of the cardiac cycle, their relationship to the ECG and heart sounds. Slide 2 Now, we've already just described the electrical events of the cardiac cycle, but in this lecture portion, we're going to talk about mechanical events. So the cardiac cycle is the sequence of events occurring in the heart during a single heartbeat and covers the cycles of cardiac contraction and relaxation. And we've already talked in general about systole and diastole, but we're going to go a little bit deeper here and now talk about the changes in pressure and volume in the various cardiac chambers during the cycle and their association with what are known as the heart sounds made by the valves closing or the so called ‘lub-dub’ sounds of the heartbeat. And just to remind you, diastole represents the period of time when the ventricles are relaxed and filling with blood and systole represents the time during which the left and right ventricles contract and eject blood. But we can go a little bit deeper than that. There are actually four phases of the cardiac cycle in terms of mechanical events, diastolic filling, isovolumetric contraction, ejection of blood from the ventricle and isovolumetric relaxation. And we're going to talk a little bit more detail about these events over the next couple of slides. And here's just some diagrams to remind you of the events during diastole. So blood is flowing into the left, the ventricles, they're filling up with blood. The atrioventricular valves are open. That's the tricuspid valve on the right side of the heart and the mitral valve on the left side of the heart. And what are called the semilunar valves, that's the aortic valve and the pulmonary artery valves are closed. During systole, when the heart is contracting and ejecting blood, the opposite is true. So the atrioventricular valves are closed and the semilunar valves, the aortic and pulmonary artery valves are open to make sure the blood goes into the pulmonary artery here or the aorta and doesn't go backwards into the atria. Slide 3 So first of all, let's look at what's called Phase One, which is sort of mid-diastole and, and sort of the middle of ventricular filling, or diastolic filling. And these pictures are the next few slides are going to have the same basic format. So there's a picture of the state of the heart here. And you can see, as we just said, during diastole, you're filling, the atrioventricular valves are open, the blood flows in passively. That means it just flows straight from the pulmonary veins or the vena cavae through the atrium straight into the ventricles. The AV valves are open as we just said and the semilunar valves here from the aorta and the pulmonary artery are closed. There shouldn't be any noise in the heart during this point and similarly there's no electrical events happening. And you might say if the heart's relaxing, what about the T wave? Well, we're coming to that, so don't worry about that. The T wave's already happened at this point. Now this graph here is showing you the pressure in the key parts pertaining to the left ventricle, because again, the left ventricle pumps to the entire body except for the lung. So we tend to be more focused on that. So this is the pressure in the aorta and the blood, the blood pressure in the aorta is usually reasonably high, but during diastole it's falling. So you can see here it's sort of dropping from 90 down to about 80 millimetres of mercury, which is as low as it gets. The yellow line here is the pressure in the left atrium and you can see it's very low. It's only about 10 millimetres of mercury and the pressure in the left ventricle is even lower. At this stage, it's probably only about two or three millimetres of mercury. It's important of course, that the pressure in the ventricle is lower than it is in the atrium, otherwise the blood won't flow from the atrium to the ventricle. So very low pressure, but still a pressure gradient, as we talked about in our introductory lecture, is important for flow to occur. The bottom panel here is showing you the volume of blood in the left ventricle, and you can see that's slowly climbing here as blood flows into the ventricle from the atrium and it's pushing or stretching the wall of the heart on both sides as the ventricles fill up with blood. Slide 4 Late in Phase One, we have the first contractile event and it's included as part of a ventricular diastole because it's atrial contraction, which technically doesn't involve the ventricles. Again, this event is in late diastole is still in Phase One, doesn't make any noise. We've got the P wave here, which you remember from the ECG is the atria depolarising and then the atrium contracts as well. And you can see that in the picture here that the left and right atria are contracting, and that squirts a little bit more of blood, little bit of blood into the ventricles here through the open AV valves. You can see there's a little increase in pressure there in the left atrium, shown by the yellow line as they contract. And there's a little bit of an increase in pressure in the ventricle too, with some blood pumped into it. And you can see there's a little surge in ventricular volume there as some blood’s pumped in. Now, point worth noting here is that most of the filling of the ventricles during diastole is passive. That means the blood just flows straight in from the in the left side of the heart from the pulmonary veins or in the right side of the heart from the vena cavae, straight through the open valves into the ventricle. You don't need the atrium to contract to fill the ventricles up. It really adds a little bit of blood at the end. Now that's what happens in the resting heart when you're just sitting down, not doing any exercise. If you are doing exercise, then atrial contraction is important for filling, which is why if you've got problems with the atria, you often don't notice it unless you're trying to do some form of exercise. Slide 5 Phase 2 is called isovolumetric contraction, and this is a brief period occurring during early ventricular systole. So here's the heart here we've had, we've had the P wave and atrial contractions already happened. Now we've got the QRS complex, which you remember is the ventricle depolarizing, the ventricular muscle depolarizing, and just after it depolarizes, it starts to contract, which is what these arrows are indicating here. Now as soon as the ventricles start to contract, the pressure inside them goes up. You can see the blue line here is starting to go up as soon as the pressure in the ventricle is higher than the pressure in the atrium. So as soon as the pressure in here is higher than the pressure up here, it's going to push the mitral valve shut and this is depicted on the left side of the heart, but the same thing is happening on the right side of the heart. The tricuspid valve will close, and the closing of those valves makes the first heart sound up here. S1 is the first heart sound. So it's the closure of the atrioventricular valves and in the left heart, left side of the heart, that's the mitral valve, that makes the first heart sound. Now the blood can't flow anywhere yet because it has to, in the left side of the heart, it has to go out into the aorta. In order for that semilunar valve or aortic valve to open, the pressure in the ventricle has to be higher than the pressure in the aorta. And you can see when the ventricle starts to contract in the blue line here, its pressure is very low. It's only about 10 millimetres of mercury. The pressure in the aorta is about 80 millimetres of mercury, much higher because it's full of blood from the previous contraction. So there's a period there where the ventricles contracting, but all the valves are closed because we're waiting for the pressure in the ventricle to be high enough to force open the aortic valve in the left side of the heart. And the same thing's happening in the right side of the heart, except at lower pressures. So that is called isovolumetric contraction or isovolumetric ventricular contraction, because the ventricle is contracting, but the blood can't escape because the pressure isn't high enough yet to open the aortic valve. And you can see here the volume of blood in the ventricle isn't changing during this period. Slide 6 Then we move to Phase 3 and ventricular ejection. So once the pressure in the ventricle is higher than it is in the aorta, once it gets above 80 millimetres of mercury, and I should say this isn't a fixed number, it depends on what your diastolic blood pressure is, which is something we'll talk about in the next lecture. But once the pressure in the ventricle exceeds aortic pressure, it open forces open the semilunar valve here and the blood flows out into the aorta. And you can see the volume of blood here in the ventricle is going down and the pressure in the ventricle continues to rise because the ventricle is still contracting here. And you can see that indicated by these arrows. And the space in here getting smaller and the walls of the ventricle getting thicker. Now the pressure in the aorta goes up as well because some blood is being pumped into it and that higher volume of blood in the aorta makes the pressure go up in it as well. So the ventricle keeps contracting, pressure keeps rising, pressure in the aorta goes up until the contraction peaks here. And after contractions peak, you can see now we're getting the T wave on the ECG, which precedes the ventricle relaxing. And you can see we're just starting to get the pressure drop here in the ventricle and the aorta as that contraction peaks and sort of stops for a second before it starts to relax. And here you can see the volume of blood coming out of the left ventricle. Slide 7 So once your contractile event is over, we enter diastole again. And the first part of diastole is called isovolumetric relaxation (Phase 4). And that really occurs just after the T wave is finished here. So the muscle starts to relax, there's a brief period here where the pressure in the aorta exceeds ventricular pressure because there's a large volume of blood here, our ventricles finish contracting, finished ejecting blood. So when the pressure in the aorta is higher in than the pressure in the left ventricle, it pushes the aortic valve closed. And again the same thing's happening in the right side of the heart. As soon as the pressure in the pulmonary artery is higher than it is in the right ventricle, it pushes the pulmonary artery valve closed. And the closure of those semilunar valves makes the second heart sound. So the second heart sound is closure of the semilunar valves, first heart sounds, closure of the atrioventricular valves, second heart sound, closure of the semilunar valves. Now in order for the heart to start filling up with, or the ventricle rather, to start filling up with blood, the pressure in the ventricle has to be lower than atrial pressure up here. And you can see at that point where the semilunar valves close, the pressure in the left ventricle is about 100 millimetres of mercury. And the pressure in the left atrium shown by the yellow line down here is only about, it's about 15 millimetres of mercury. So we need the pressure in the ventricle to get low enough such that it's below atrial pressure and the mitral valve will open again and allow blood to refill the ventricle down here. While we're waiting for the pressure in the relaxing ventricle to fall below atrial pressure is called isovolumetric relaxation. And it's again, the volume of blood in the ventricle isn't changing here because we need the mitral valve to open for the blood to fill up the ventricle again. Slide 8 And then we're back to Phase One, in this case, diastolic filling, in this case early- to mid-diastole. So as soon as the pressure in the ventricle, the relaxing ventricle here is below atrial pressure, the mitral valve will open on the left side of the heart, the same thing that our tricuspid valve will open on the right side of the heart. And you get a rapid inflow of blood here, which very rapidly fills the ventricle. Again, the filling is passive so we don't, we're not relying on atrial contraction. The blood just very rapidly flows in straight from the pulmonary veins through the left atrium into the left ventricle. And that very rapid inflow of blood at the start of diastolic filling sometimes can create what's called a third heart sound. Now, you don't always hear this, and in fact it's fairly rare in young people. It's thought to be the walls of the ventricle vibrating a little bit as the blood rushes in, and that's what makes that sound. But it's quite hard to hear. If you're an older person and you have a third heart sound. It could be, I mean, you could have a bit of an issue with the valve, but normally there's only the two heart sounds. Slide 9 Now what I've just shown you is my rendering of what's called a Wiggers diagram. And a Wiggers diagram basically depicts the relationship of all the events that occur in the left ventricle during the cardiac cycle. So here's all the slightly more professional version of what I just showed you. Here we've got, as I showed you, late Phase One here is late diastole. Sorry, mid to late diastole, the heart's filling up with blood. We get the P wave here associated with atrial contraction that squirts a little bit more blood into the heart. Then with this solid line here, we've got the onset of isovolumetric contraction. So he's a QRS complex here preceding the contraction. As soon as the pressure in the ventricle exceeds atrial pressure, we get the first heart sound shown there in what's called a phonocardiogram, which is the sounds of the heart. Then isovolumetric contraction, the pressure in the ventricle is rising, but the semilunar valve, the aortic valve won't open until the pressure in the ventricle exceeds aortic pressure. So there's a period there where the volume of blood in the ventricle isn't changing. Then we get ventricular ejection once the pressure in the ventricle exceeds aortic pressure and the heart reaches its peak pressure of 120 millimetres of mercury here. Then once the pressure, the contractile event is over, we get the T wave here which is repolarization of the cardiac muscle preceding relaxation. Once the pressure in the ventricle is below aortic pressure, we get the closure of the aortic valve and the pulmonary artery valve on the other side of the heart, which makes the second heart sound, closure of the semilunar valves. We then have isovolumetric contraction (relaxation, it should be) because we need the pressure in the ventricle here, which is blue, to be below atrial pressure down here for the mitral valve to open. So there's a period where the ventricle's relaxing, but there's no change in the volume of blood in it during this because all the valves are closed. And then once the pressure in the ventricle is below atrial pressure, the mitral valve opens and we get very rapid filling here of the ventricle. Slide 10 Now you've been putting up with my sort of drawings or various drawings of the heart and so on and illustrations. But I thought we might just towards the end of this lecture, or this lecture chunklet, to finish off with an actual heart in in action. So what we're going to see here is an echocardiogram, which is an ultrasound image of the heart while it's pumping. And we can see in this particular one, not only the ventricles contracting and relaxing, but it's also the mitral valve and the aortic valve opening and closing. So what you're seeing here, as you can see hopefully is this little window here is showing you the section through the heart that we're seeing. And this little window lines up with the window here from the top of the slide as the sort of angle that the echocardiogram is taking. And you can see here the left ventricle here – sorry I haven't got my laser pointer - I can't have it on for this particular slide, but there's a left ventricle there labelled as LV, the left atrium LA, the aorta AO, and the right ventricle at the top of the image there, RV. I'll just play the image there. So this is a real human heart beating at sort of real time speed. And you can see here the mitral valve, it's closed when the left ventricle is contracting, and it's open when the left ventricle is relaxed. And you can see when the left atrium is contracting, it pushes the mitral valve open there. Well, it's already open there before it contracts. It should be, of course. And here you can see the aorta. And here you can see the aortic valve here. So it's opening there when the left ventricle is contracting, and it's closed when the left ventricle is relaxing. Some other things here you can see of course the left ventricle and right ventricle are contracting at the same time, which is what we want of course. Now it says note the left wall thickness compared with the right ventricle. Well, it's not really that obvious here, but you can see the left ventricular wall gets quite thick when it's contracting. Again, that's to do with the high resistance to flow in the systemic circulation as composed to as compared to the pulmonary circulation. The mitral valve we just pointed out here opening and closing and the aortic valve here opening and closing during the events. And of course, there's an ECG at the bottom of the trace there. Slide 11 So just a couple of things before we finish up this lecture section. Do the ventricles completely empty of blood each contraction or ejection? And the answer hopefully you've picked up so far is that that's not true. The ventricles eject about 2/3 or, if you want to put it in in decimal sort of language, 67% of their contents each systole and that amount's sort of variable. It depends on whether you're resting or whether you're exercising or how intense your exercise is or what sort of exercise you're doing. But generally the heart pumps out somewhere between 55 and 75% of its contents, depending on what you're doing. It doesn’t completely empty of blood each time. The volume of blood in the heart at the end of filling, at the end of diastole is called the end diastolic volume. And that sort of makes sense, it's the volume of blood in the ventricles at the end of diastole. The volume of blood ejected by ventricular contraction each time during that ejection phase is called the stroke volume or SV as it's usually abbreviated. And that ratio of stroke volume to end diastolic volume is called the ejection fraction or EF. So when we said the heart ejects 2/3 or 67% of its contents, that's what we're talking about, we're talking about the ejection fraction. And in our examples, if we want to be strictly correct, it's because we're talking about the left ventricular ejection fraction or LVEF, and it's a fair chance we'll ask you to calculate one of these. We'll give you some values of various parameters here and we'll probably ask you to calculate something like this in an exam setting. So there's some practise questions coming up to help you with that. HS2_CVPhysiol_L2_LO4 Slide 1 Now we're on to the 4th and final learning outcome of this lecture on cardiac physiology. That's to understand the concept of cardiac output, the factors determining cardiac output, and physiological control of these factors. Slide 2 Now, cardiac output is defined as the amount of blood that your heart pumps out per minute. It's the product of the heart rate, that's the number of cardiac cycles per minute, and it's a little bit variable, but an average person, your resting heart rate is about 70 beats per minute or BPM. And the stroke volume, or SV, which we've just talked about in the previous learning outcome section, is the volume of blood ejected by the ventricle in each cycle, which is about 70 millilitres roughly. So the cardiac output is the product, CO is the product of heart rate and stroke volume, HR and SV. If we take those two values there, 70 beats per minute and 70 millilitres, we get about 4900 millilitres of blood per minute or we round it up usually to five litres per minute. Now again, that's quite variable. So if you're a smaller person, you've probably got a lower cardiac output. If you're a larger person, you've probably got a higher cardiac output, but for an average sized person with an average heart rate, it's about 5 litres per minute. It's important to understand that both sides of the heart pump out five litres per minute. The right- hand side of the heart pumps out five litres per minute. The left-hand side of the heart pumps out five litres per minute. Now you might be wondering why isn't cardiac output then 10 litres per minute? Well, the argument is that no single organ in your body receives 10 litres of blood per minute at resting heart rate, at resting sort of values. So the entire cardiac output goes to the lungs, which is five litres per minute and all the output to the left side of the heart goes to the rest of the body here. And they (all organs apart from the lungs) also see 5 litres per minute. So no single organ gets 10 litres per minute of blood at least at this resting value. So cardiac output is defined as 5 litres per minute whenever you're talking about it. Now cardiac output has to match your metabolic demands of your body and so if you start exercising, and your muscle here is described as lower limbs and upper limbs here (in the diagram). But your muscle starts using up a lot more oxygen. Of course, the blood has to circulate more quickly to deliver the oxygen more rapidly. So your cardiac output has to go up, then. And if you're doing maximum aerobic capacity exercise, your cardiac output can get up to 25 litres per minute, or even much higher than that if you're a trained athlete. So it's the job of your heart to be able to modulate its output to satisfy the metabolic demands of your body. So for the rest of this little next few slides, we're going to talk about the control of cardiac output. Slide 3 So how are these two variables controlled, heart rate and stroke volume? Well, heart rate is primarily under the control of what's called the autonomic nervous system and also a key hormone, adrenaline. Stroke volume is controlled by three key factors. The contractile force developed by the ventricular muscle and the heart muscle, like any other muscle in your body, contract with varying degrees of force and that's called myocardial contractility. The volume of blood in the heart at the end of diastole, that can also affect stroke volume and that's called the extent of ventricular filling or preload. And finally the work the heart has to do to eject the blood and that's referred to in physiological terms as after load. So if we look at our little table down the bottom here, here's our cardiac output, here's our two factors that determine our heart rate and our stroke volume. Stroke volume is primarily controlled by three things, that contractile force of the ventricular muscle or myocardial contractility, the extent of filling of the heart during diastole or that end diastolic volume which is called preload and the work the heart has to do to eject the blood which is called afterload. Changes in all of those three things can affect stroke volume. Heart rate is also under the control of the autonomic nervous system and adrenaline, a hormone release from the adrenal gland. And it's also important to note that these two things can also affect myocardial contractility. So there's a bit of an overlap between the mechanisms controlling rate and stroke volume in terms of their effects of myocardial contractility. Slide 4 So let's talk in a bit more detail about how these factors are controlled. And we'll start off with heart rate. And as I just said, heart rate is under the control of the autonomic nervous system primarily, and also adrenaline that we'll talk a little bit more about in a minute. So the autonomic nervous system, as I hope you're aware, controls involuntary actions in our body, the activity of our visceral organs, that's separate from the motor nerves that control the contraction of skeletal muscle and so on. And it has two divisions called the parasympathetic and sympathetic divisions, and they usually produce opposite effects on the organs and tissues that they innervate. And the heart's no different. So the parasympathetic nerves in in the heart innervate the atria only. They're shown in blue in this picture here. The parasympathetic nerves come down and they really, if you want to be very specific, only really innervate the SA node and the AV node. So parasympathetic nerves innervate the atria only. Their stimulation decreases the rate or frequency of action potentials generated by the SA node. And by decreasing the frequency with which the SA node depolarises, they decrease heart rate and a decrease in heart rate is called bradycardia. So parasympathetic nerves, as it says here, slows the heart rate. Sympathetic nerves, which are shown in red here, they innervate both the atria and the ventricular muscle as well. So parasympathetic nerves, atria only; sympathetic nerves, atria and the ventricles, and their stimulation increases the frequency of action potentials generated by the SA node. And thus sympathetic nerves increase heart rate when they stimulate the heart and that's called tachycardia, an increase in heart rate. So as it says here, sympathetic nerves increase the heart rate. Now, because the sympathetic nerves also innovate the ventricular muscle, they increase the force with which the ventricular muscle contracts and that's increased contractility. Now specifically that relates to a, a factor controlling stroke volume, but I thought I'd mention it now because it's we've got the picture here. So parasympathetic nerves slow the heart down; sympathetic nerves increase heart rate and they do that by changing the frequency with which the SA node generates its action potentials. Now a hormone called adrenaline, you'll see it in some textbooks, particularly American textbooks, called epinephrine, is a hormone released from the medulla of the adrenal gland. Its effects on the heart are similar to those of sympathetic nerve stimulation. In other words, it increases the heart rate and increases the force with which the ventricular muscle contracts. And this is important because adrenaline is typically something that's released during exercise. Again, what you'll find, we're mentioning exercise a lot as an example of the cardiovascular control here and adrenaline is typically released during exercise and it helps increase our heart rate and the force of ventricular muscle contraction to increase our cardiac output when we're undertaking exercise. Slide 5 Now let's talk about control of stroke volume and we as we said, there's three factors that control stroke volume and we'll talk about them in order. So the first one is the contractile force developed by the ventricular muscle. And like all muscles in your body, the heart muscle too can be made to contract with varying degrees of force and we call this myocardial contractility. Now if we increase the contractile force developed by the cardiac muscle, that will increase the peak systolic pressure developed by the ventricle. And we said, if you hopefully remember from the previous section, that's normally about 120 millimetres of mercury. But if we increase the contractile force, there'll be a higher systolic pressure developed than that. And the result of that is that more blood will be ejected. In other words, you'll have a higher stroke volume. So increased contractile force means increased peak systolic pressure developed by the ventricular muscle and the ventricle, and more blood will be ejected, You'll have a higher stroke volume. The opposite's true as well. So if we have decreased contractile force, there'll be a lower than normal systolic pressure developed and less blood will be ejected. We have a lower stroke volume. Now, typically your body is trying to increase myocardial contractility and again, exercise is the classic example. So sympathetic nerves can increase the contractility of the ventricular muscle, as can adrenaline release during exercise and some drugs that are used to treat heart failure or inadequate myocardial contractility. Your body's not usually interested in decreasing myocardial contractility. So there's no real physiological mechanism for decreasing contractility. And usually what happens is, is that you just have an absence of the thing stimulating increase contractility. But usually, if you do have decreased myocardial contractility, it's a result of some pathology of the heart. So some damage to the heart muscle and this might mean some form of heart disease such as angina or you might have an infective disease of the heart like endocarditis or some congenital problem like cardiomyopathy. We've got heart failure that over time you've had a myocardial infarct or something else that has damaged the cardiac muscle such that it can no longer contract properly. So increased myocardial contractility means the contracting ventricle develops, it contracts more quickly, really develops greater pressure and you get more blood ejected. Decreased myocardial contractility usually is not useful for you and it results from some sort of heart disease. The next factor that affects stroke volume is the volume of blood in the ventricle at the end of diastole or the end diastolic volume. And this is the key determinate of what's known as preload, which is essentially the degree of stretch on the ventricular wall before it contracts. So if you have for some reason more blood filling up the ventricle during diastole, and the amount of blood that flows back to the heart is called venous return. It's sort of the opposite of cardiac output. More blood flowing into the ventricle means an increased end diastolic volume and more stretch on the wall of the heart, particularly the ventricle as shown by the dotted line here. And that increased volume of blood in the heart is called preload and it exerts more stretch on the wall. And the heart when it’s stretched, responds to that when with increased contractile force when it's made to contract and a higher ventricular pressure, which again resulted in increased stroke volume. So increased preload means increased blood volume of blood flowing into the ventricle during diastole, during filling that stretches the heart wall. Stretching the heart wall makes it respond with greater contractile force and the ventricle develops greater pressure and that results in an increased stroke volume, here shown by the thickened black arrow. Slide 6 This relationship between end diastolic volume and stroke volume is called Starling's Law of the Heart. And basically changes in the end diastolic volume alter the degree of stretch on the ventricular myocardium causing the ventricular contraction with greater force or lesser force if of course, if there's less blood flowing into the heart, so a lower end diastolic volume. And the result of this is that stroke volume or output matches the venous return, which is the input, the blood flowing in. Or put it even more simply, the blood in is proportional to blood out. And that's reflected by something called the Starling curve, which is shown in this picture here. And it shows the relationship between ventricular filling, which is the end diastolic volume, and emptying, which is the stroke volume. And you can see here that as we increase the end diastolic volume, an increase in diastolic volume causes an increase in stroke volume because the heart contracts with greater force if there's more blood in it to start with. And these little pictures up here are just showing you the, the, the physiological mechanism for that. It's increasing the potential overlap between the thick and thin filaments in the muscle. But I don't, you don't have to understand the mechanism. Just know that increased end diastolic volume means greater stroke volume. And the opposite’s true, too. Of course a decreased end diastolic volume means a lesser stroke volume. The third factor is the work the heart has to do to eject the blood and this is called the afterload. So the preload is the degree of stretch on the heart wall before it contracts and the afterload is the work the heart has to do to pump the blood out after it starts contracting. Now the main determinant of afterload is something called peripheral resistance, that is the resistance to blood flow provided by the blood vessels, the arteries. So when the heart contracts, the reason it has to develop pressure is to push the blood through the arteries, which are resisting flow, and the resistance of those arteries can change. And that changes what's called the afterload on the heart. And increasing afterload decreases the stroke volume. So the more work the heart has to do to pump the blood out, generally the less it's able to pump out, and the opposite's true too. So if you have a decreased afterload, you get an increase in stroke volume. And this is the key difference between preload and afterload. Increased preload means an increased stroke volume, increased afterload means a decreased stroke volume. So it's important to remember those that difference. And how do you know what the peripheral resistance is? Well, it's indicated really by arterial blood pressure and that's something we're going to cover in the next lesson. Slide 7 And there's a little summary there. I won't read this out. So this is summarising all four learning outcomes of this talk. I haven't got the cardiac output there, it's on the next slide, but I'll put them into separate slides in the lesson anyway.