Frontiers of Biomedical Engineering

BENG 100 - Lecture 15 - Cardiovascular Physiology (cont.)

Chapter 1. The Lipid Membrane and Electric Potential [00:00:00]

Professor Mark Saltzman: So, today we’re going to continue to talk about cardiac physiology. In particular, the electrophysiology of the heart which is quite interesting and important to heart function. One of the–turns out that one of the most important diagnostic measurements that can be made is through a device that was designed by biomedical engineers called an electrocardiograph. We’ll talk about today sort of the origins of electrical activity in the heart, the role that this electrical activity plays in the function of the heart, and then finally how–we’ll talk a little bit about how one can measure that electrical activity which comes from cells in the heart, sort of deep inside your body, but can be measured with electrodes on the surface of your body. You’ll get some more experience with making those measurements in section on Thursday afternoon.

This is–I apologize, a rather complicated diagram, but I wanted to show you a picture that would give you a sense for sort of where the electrical potential that all cells have comes from. You know that cells are bathed in an extracellular fluid and that that extracellular fluid contains molecules, including ions or charged molecules. In fact, the extracellular fluid is very rich in a particular ion, sodium, and has lesser amounts of other ions, potassium and calcium, are the three most important in the electrical activity of membranes; sodium, potassium, and calcium. The extracellular space which is up on the top here is filled with those ions, in particular, has a high concentration of sodium. The intracellular space, or inside the cell, also is a water-rich environment and also has ions. The ion composition inside the cell is different than the composition outside the cell in that the sodium concentration is relatively low. This chart here shows you for a typical cell sodium concentration might be 15 mmol while the extracellular sodium concentration is 145 mmol, so almost ten-fold higher sodium ion concentration outside the cell than inside the cell.

Well, now you know from what you know about the structure of lipid membranes that charged molecules, even though they’re small, charged ions like sodium cannot penetrate through a lipid bilayer, so there’s no way for sodium to get through this lipid bilayer. Even though there’s a very large difference in concentration, these molecules of sodium on the outside can’t diffuse inside because they can’t permeate through the lipid bilayer. Now, potassium, notice, has a very high concentration inside the cell, 120 mmol, and outside the cell the concentration is low, 4.5 mmol, so again a big difference in potassium concentration but going in the opposite direction. If the membrane was permeable, sodium would diffuse in and potassium would diffuse out but it can’t through a plain lipid bilayer.

Well, you also know that cell membranes are not just lipid bilayers. They have proteins inserted in them and we talked about proteins that serve as receptors, for example, the insulin receptor that binds to insulin. We talked about signal transduction through those receptors a few weeks ago. We also talked briefly about the fact that some of these proteins are transport proteins and their role in the cell membrane is to allow molecules that the cell needs to come in or to go out. The glucose transporter is an example of that. The only way that glucose can get inside cells to provide a substrate for a metabolism is because there are specialized proteins in the membrane that allow glucose to cross, in the same way there are specialized proteins that allow ions to cross.

These proteins come in two varieties. Some are active transport proteins like this one which is called the sodium-potassium pump. It’s actually a little machine that sits inside the cell membrane, it’s a protein based machine. Its job is to pump sodium out of the cell and potassium into the cell; sodium goes out potassium goes in. It’s moving those molecules against their concentration gradients and so energy is required for that to happen. It doesn’t happen spontaneously, you can’t move molecules, molecules don’t spontaneously move from regions of low concentration to high concentration. It requires energy and it gets its energy from ATP. This is called the sodium-potassium pump and it’s ubiquitous in cells throughout the body. It’s how cells maintain this low sodium concentration and high potassium concentration inside. It’s because they have these little machines in their membranes that are continually pumping sodium out and potassium in. Does that make sense? It’s the action of this pump that causes these differences in ions to occur.

There are other proteins that serve as channels. You can think of these as very specialized pores in the membrane that allow ions to pass through, and they’re selective. This one is a potassium channel, and so if it is open it allows to potassium to pass through. It only allows passive transport. It’s not a machine like the other one, it’s just a portal or a hole that allows potassium to move down its concentration gradient. If this potassium channel is open, then potassium will naturally move. It will move from high to low concentration, that is, it’ll move from inside the cell to out. If sodium–if there’s a channel for sodium and it happens to be open, and that’s what this is shown here, a channel with the lid off means the channel is open, then sodium can pass from its high concentration to low concentration or from the extracellular space to the intracellular space.

The cell is in dynamic equilibrium, that in its sort of steady state, it’s natural state, there is this active machine that’s pumping sodium out and potassium in. Then, there are these pores that when they exist and when they’re open, are letting these molecules to leak back the other way. The pump always has to be operating because the leak is always happening. Does that make sense? Because you have these differences in ion concentrations across the cell membrane these–and you have the flux of molecules continuously across the membrane. What I’ve shown here are channels that are–they have a lid on them so they’re sometimes open and sometimes closed, they can be both opened and closed. Every cell in your body at a given time is going to have lots of potassium channels that are open and lots of sodium channels that are open. They’re just some that are open all the time. Because of that there’s a continual leakage of potassium out of the cell and a continual leakage of sodium into the cell.

Chapter 2. Creation of Action Potential [00:08:02]

Well, if ions are moving across the cell membrane, ions are charged molecules, and that movement is a current. You usually think of currents as movements of electrons but movements of ions, of positively charged ions, is also current. So, there’s a continual current flow across the membrane. That continual current flow causes a potential difference across the membrane. Now, a membrane that’s at rest, that is in its resting state, is going to have a given number of channels of sodium and potassium that are open. So, there’ll be given current of sodium that’s flowing in and a given current of potassium that’s flowing out. That’s being compensated by the activity of this pump but this current flow creates a membrane potential or voltage.

Just like a battery, because these currents are flowing, if I measure the electrical potential on both sides of this membrane I would get a voltage difference. It turns out that for most cells that voltage difference is negative. The inside of the cell is slightly negative compared to the outside of the cell and it’s in the range of -60 to -90 mV. That’s the backdrop, that’s what you should think of as sort of the resting state of a membrane, it has these channels in it, it exists in this fluid environment where there’s high sodium outside, high potassium inside, current flows, membrane potential generated.

To make it more complicated there are certain of these ion channels that exist in open and closed states. Those open and closed states are regulated by the voltage across the membrane. Here’s one called the voltage dependent sodium channel. The resting state, when the membrane voltage is, let’s say, -90 mV, the channel is closed, and so this channel does not allow for sodium to enter. If it opens, sodium now can enter through new channels. If there are a lot of these voltage-gated channels on the surface. They sense a change in voltage, and they all open, one can have a dramatic change in the currents that flow through the membrane and hence a dramatic change in membrane potential.

Now, that’s exactly what happens when we have an action potential. I show you this diagram that I showed you a few weeks ago when we were talking about the nervous system and how it communicates. I explained it in sort of a superficial way then, but now you can understand it a little better if you think about it in terms of these–of the membrane and the membrane having channels that allow sodium and potassium to flow. Under a resting condition they have a population of channels that’s always allowing sodium and potassium to flow, that creates the potential. Then, they have special channels that open when the voltage is disturbed in some way.

Here, we’re looking at a trace of membrane potential in time. Imagine that you’re very small and you’re sitting on the surface of this membrane but you have special shoes on that measure the voltage or something. You can experience the voltage, the potential drop across the membrane by just standing on this membrane. You’re standing there in the resting state, so you’re watching sodium and potassium go by because of their normal fluxes, and the potential that you measure is, say -75 mV. Now, something happens, there’s some disturbance in the membrane near you, not right where you’re standing but near you there’s a disturbance. That disturbance might be a number of events but what we’ve thought about so far is that there’s a neurotransmitter that binds. Somewhere upstream of you there’s a neurotransmitter that binds to a receptor and it creates a change in membrane potential. A small change in membrane potential, but you feel it. When you feel it at your sight there’s also these voltage sensitive sodium channels that exist in the membrane around you and they go from the closed state to the open state. In response to this small disturbance, some new channels open, these happen to be sodium channels. They open, a lot of them open because there’s a lot of them on your cell because your cell is designed to respond to voltages so it has a lot of these kinds of channels.

Now, what happens when all these new sodium channels open? There’s a rush of sodium from outside the cell to inside the cell. Sodium’s positively charged, you get a rush of current going by you, and that rush of current depolarizes the membrane. Remember I said the membrane had a negative potential, it’s more negative on the inside than outside, but all of a sudden you’ve opened all these sodium channels and a rush of sodium goes in, a rush of positively charged molecules go into the cell, make the inside of the cell less negative because you’re adding a lot more positive charge to it. That event is called depolarization. If you were standing on the cell with your magic boots that were electrically active somehow you would experience this dramatic change in membrane potential. The membrane becoming a lot less negatively charged, even positively charged. That’s due totally to this rush of sodium through these new channels that have opened.

Well, there’s a second set of channels called potassium, voltage-gated potassium channels that also open but they’re slower than the sodium channels. When they open they allow a lot more potassium to rush the other way because, you remember, potassium is high inside and low outside. First you get a rush of current going in one direction, then you get a rush of current going in the other. What causes in terms of membrane potential is a rapid depolarization, and then a rapid repolarization and these channels eventually close again and the membrane returns to its resting state. If you don’t understand all the details of that, that’s fine, it’s described in the book and also described in other membrane physiology books that you could go to.

It’s not important that you understand all the details but that you have a sense for what’s happening, is that within this small region of the cell membrane we focused on there was some kind of a small disturbance, it opened all these voltage-gated channels, caused rushes of current which changed the membrane potential. That is, in this case what I’ve described to you, is an action potential. A small change here causes a large change at my local site, and then I pass that on this way, because I’m now standing at the site where there’s a huge disturbance in membrane potential and that’s going to cause some current to flow, a little bit to flow downstream. That little bit that flows downstream is going to cause the voltage-gated channels here to open, and an action potential to be generated at this site. If you follow that line of thinking, then an initial disturbance over here creates a massive membrane potential here, which moves to here, which moves to here, which moves to here, and that’s an action potential being transmitted down a neuron. Make sense?

Chapter 3. Electrophysiological Differences between Nervous System and Heart [00:15:50]

That’s what we talked about when we were talking about the nervous system. We were talking about information flowing from dendrites, dendrites that have receptors for neurotransmitters, those receptors for neurotransmitters causing a small membrane disturbance which then gets converted into an action potential. That action potential moves down the axon, say in this direction to that direction. Why doesn’t it move back? Why does it only move in one direction? Well, it turns out that it’s very interesting physiology that when these membrane–when these voltage-gated membrane channels get opened they become incapable of being reactivated for some period of time.

The voltage-gated sodium channels open, they close, and then they can’t be opened again for some period of time. Just a few milliseconds but long enough for the action potential to pass out of their region so that you don’t get currents that flow like–or action potentials that flow like this. They only flow in one direction because these channels need to recover. You understand now a little bit more about why action potentials flow down axons and when they reach these termini, the axon termini, what do they do? This sudden change in membrane potential activates a new process, and that new process is release of neurotransmitter from the synapse. That neurotransmitter then activates another cell, generating an action potential, sending it down its axon, and so on.

In the nervous system messages pass from neurotransmitter to action potential, neurotransmitter, action potential, neurotransmitter, action potential. Because there might be many, many neurons impinging on one particular neuron that I’m interested in and some are sending positive messages, some are sending negative messages, sending these little disturbances. Whether this axon generates an action potential or not depends on the sum total of the small disturbances that it’s receiving at any one time, Neurons can integrate information. That information is acquired from all the neurotransmitters that are impinging on the dendrites that cause small disturbances that may or may not add up to the large disturbance which becomes an action potential. You go on to study neuroscience or just physiology, you’ll learn more about this but I think you can probably understand the basic concept. In the action potential and a neuron we were thinking about a cell that had a receiving end, that receives neurotransmitter inputs, that causes membrane potentials to change, that somehow decides to initiate an action potential. That action potential flows very rapidly down this specialized process called an axon, reaching the axon termini, and then neurotransmitters are released to the next cell.

Heart cells are the same in that they contain these special voltage-gated membrane channels, these voltage-gated ion channels that allow for an action potential to form. They’re capable of doing an action potential because they have these voltage-gated sodium and potassium channels. Because of that, heart muscle cells fall into the same category as nervous–of neurons in that they’re in the general category called excitable cells. They’re excitable cells, means they’re capable of making an action potential. To have an action potential they need to have these specialized voltage-gated ion channels in their membranes. Cardiac myocytes have that, they also have actin and myosin. They’re muscle cells and they’re capable of contracting, meaning that this myocyte here can shorten itself. It can make itself shorter by contracting just like a muscle, a whole muscle contracts.

That’s different than neurons so they have this capacity to transmit action potentials; they have this capacity to contract. Now, in muscle cells, as we’ll see in a few minutes, those things are linked. When a muscle cell experiences an action potential it doesn’t do what a nerve cells does, which is pass that information along to another cell via neurotransmitters, instead it contracts. It also passes along the action potential but it doesn’t do that through a chemical synapse like in neurons, it does it through an electrical synapse in that these cells are very tightly welded together. Remember we talked about in the nervous system, the two cells don’t physically touch, there’s a space in between that’s called the synapse and it’s over this synapse that neurotransmitters act. They’re released from the pre-synaptic cell and they create a change in the post-synaptic cell. Cardiac myocytes are basically welded together. In fact, there are special junctions called gap junctions in between them that allow the easy flow of current.

If an action potential flows through this myocyte, from this end to the other, it doesn’t have to–it basically flows straight into the next cell because they’re directly electrically coupled. If an action potential arises and comes from this direction, it flows very quickly down this membrane, it causes this cell to contract, it flows right into the next cell causing this cell to contract, flows right into the next cell causing it to contract. So, in cardiac muscle wherever the action potential starts it contracts first, then the action potential flows into the neighboring cells, they contract. You can think about the cardiac myocardium, the sheet that I showed you last time, the muscular walls of the heart, as being sort of a sheet of these cells that are all connected to each other. If I start an action potential in one space, it’s going to flow over the surface. As it flows over the surface cells will be contracting right behind it; so electrical flow followed immediately by contraction locally. Does that make sense?

Chapter 4. The Cardiac Conduction System [00:22:44]

You could imagine that this now–because they’re directly electrically coupled, signals can pass very quickly over the surface of the heart. They can pass very quickly from one to another, so I just need to start an action potential in one place, it’ll be propagated everywhere. I might like to control that because I’d like to have the heartbeat function in this controlled fashion we were talking about last time. So how does the heart solve this problem of control of how this wave of action potential moves over the surface of the heart? Well, it does that through a specialized group of pathways that are collectively called the cardiac conduction system.

This is a terrible diagram. I’m going to show you the next one, I’ll show you a little bit better on the next one, and so you’ll see, it but imagine–just look at the surface here. This is the heart, the left ventricle, the left atrium, the right ventricle, the right atrium, and there’s this pathway. The heart has something like a nervous system in that this black region here is a pathway that’s called the cardiac conduction system. It consists of several important points. The first is called the sinoatrial node or SA node and it’s in the right atrium. The next point is the atrial ventricular node which sits on a fibrous substance called the septum which separates the atria from the ventricles. The heart is kind of tilted to one side, it’s not straight up and down, so the atria are up here and the ventricles are down here, there’s a septum in between and that’s where this AV node sits.

It turns out that this septum is electrically insulating and so if a action potential–a wave of action potential gets generated up in the atrium, it stops when it hits the septum, it doesn’t move directly to the ventricles. The muscles of the atrium and the muscles of the ventricle are electrically isolated. The only point of connection between them is this specialized fiber pathway called the AV node. That AV node leads into a series of branching fibers that are called the Purkinje system, Purkinje fibers down here. These are fibers that very rapidly conduct action potentials or electrical signals. What I want you to see in this slide is to notice that while all of these cells are excitable, they have the property of generating and sustaining an action potential, they’re excitable, an action potential can be generated–the shape of the action potential varies in different cells.

That’s all this diagram shows you. You don’t need to know the details but notice that some things are different. For example, in the SA node it’s a very slow rise of potential followed by a slow fall and then a much slower rise again compared to ventricular muscle, for example, that has a very rapid uptake, a sustained depolarization phase and then a rapid repolarization back to baseline. There are differences in the ways that these things undergo action potentials. What do you think that’s based on? What’s different about these cells? Well, if the action potential is the result of these voltage-gated channels that must mean that ventricular muscle cells have a different set of voltage-gated channels than SA node cells. They might have totally different molecules that are doing the transport or they might just have different numbers of these molecules in their membranes, but that’s the difference in physiology.

Chapter 5. The Heartbeat and EKG [00:26:47]

What we’re going to get to the by the end here is I’m going to try to convince you that this–these changes that are occurring in individual myocytes, this rush of current that underlies the action potential generation is what we measure when we measure an EKG. That what you’re measuring is sort of the sum of all of these electrical potentials that are occurring as your heartbeat changes in electrical–because your heart cells are all experiencing changes in electrical potential and because your body is basically a salt solution which conducts electricity, that you can measure those changes in electrical potential happening in cells in the heart by having electrodes just on the surface of your skin. The EKG arises from all of these action potentials that are happening within all of the thousands of cells within your heart. This diagram is a little easier to understand. It had more words than I liked so I blocked some of them out. The other one are things that we’ve already talked about before, the SA node is now familiar to you, the sinoatrial node, the AV node, this specialized bundle of His which carries potential–action potentials very quickly from the AV node down to the Purkinje system, and the Purkinje system which branches throughout the ventricular wall.

How does–is a heartbeat regulated? It turns out that some of these cells are capable of generating their own action potentials. They don’t need to be stimulated by some outside disturbance; they generate an action potential on their own. The most famous of these is the SA node up here. The SA node, if you look at it, here’s the action potential in the SA node, depolarization, repolarization, now look what happens here. The cell, when most membranes we’ve talked about are at resting state, resting state such that their membrane potential stays constant until its disturbed by something from outside, this cell actually is slowly changing its membrane potential on its own. It does that with a very consistent frequency, such that at some point this slow rise of action potential is going–this slow rise of membrane potential is going to go high enough that it causes its own disturbance and causes its own action potential.

This is called a self-propagating action potential. Cells like cells of the SA node that are capable of doing this have special properties of their ion channels. The end result is that the SA node is just making action potentials on a very regular basis. If you measured, if you put an electrode, or if you shrunk yourself and you had your magic boots and you could stand on the SA node, you would measure an action potential about 60 times a minute. Once a second, the SA node is just creating an action potential. Now, when it creates that action potential what happens? It disturbs the cells that are around it. When the SA node creates an action potential it causes a voltage disturbance in the cells around it and they start making action potentials. Starting from this source in the SA node, a wave of action potentials starts to move over the atrium, over the atria. First the right and then the left, and what happens as this wave of action potentials spreads over the atria? What happens–what else do muscle cells do? They contract, and so a self-propagating action potential in the SA node induces an action potential wave that spreads over the atria, the atria contract. They contract–if you watch them they contract from the region of the SA node out to the right slightly before the left, but it passes pretty fast over these relatively small surface areas.

Now, remember that there’s a septum in between the atrium and the ventricle so this action potential wave would stop and not go down to the ventricle except for the AV node. When the action potential comes down these pathways, these specialized pathways from the SA node, it reaches the AV node. The AV node has another special property in that when it’s stimulated to make an action potential, it hesitates. It hesitates for a fraction of a second and then it starts its own action potential. So, it receives the disturbance, it waits and then it makes its own action potential. What happens? Start to put the picture together now, SA node action potential, wave of action potential of the atria, contraction of the atria, AV node gets the signal, waits, generates an action potential and that action potential quickly propagates down through the bundle of His in the Purkinje system. What do they do? They carry this action potential down into the ventricles. They start action potentials in the ventricle, which then passes a wave over the ventricular muscle, and after that wave of action potentials comes contraction and ventricular contraction.

Now, why does the AV node wait? It waits in order to control the heartbeat in the way that we described last time, so that you want the atria to contract and deliver their blood to the ventricles before the ventricle starts to contract. You want the ventricle to wait until it’s filled up with blood from the atrial contraction and then start to contract. So, the AV node provides that separation in time of the atrial contractions and the ventricle contractions. Now, how would you like the ventricular–now remember when the ventricle contracts it’s a big contraction and wants to force blood in what direction? Up out of the top, that’s where the pulmonary artery and the aorta are; remember from the model they’re up at the top of the heart. So, you would like for this muscle to very effectively eject blood out of the ventricular chambers and into these two large vessels.

You all have roommates, true; I don’t know if you all share toothpaste with your roommates, but if you do then some fraction of you, probably about half, are irritated with your roommates because they grab the toothpaste tube at the top. You might have brothers and sisters who do this, they grab it near the top and they squeeze it because they only care about getting their little toothpaste out and so you get this–that’s not an effective way to get toothpaste out, squeezing it from the top because some of the energy goes down into the bottom and forces this toothpaste down here and the thing gets all out of the shape. What if you wanted to get all of the toothpaste out of the tube on one squeeze, how would you do it? You’d go from the bottom up, you’d starting squeezing from the bottom and you’d squeeze it up. If you were good at this, and you could practice this at home, you get toothpaste and you could see how much of the–what fraction you can get out with a single squeeze. I think you’d find your best is to start from the bottom and squeeze sort of systematically going up, and that’s what the heart does. That’s why this Purkinje system is here; too rapidly conduct signals from the SA node down to the base of the ventricle and really start the contraction down here. The contraction starts at the bottom and squeezes up and the blood is propelled out. One of the roles of the Purkinje system is to carry this potential into the ventricles in a way that provides maximum benefit from the contraction of the cells that result.

Now, a couple of other things that are interesting to know here. One is that the SA node is not the only collection of cells in the heart that are capable of generating their own action potentials. Actually the AV node is also capable of generating the action potential and so are the cells in the Purkinje system. They all can generate action potentials, but it turns out that the SA node does it the fastest. It does it about 60 beats per minute. The AV node does it at maybe 40 beats per minute and the Purkinje fibers do it at even a lower rate than that. What does that mean? It means that the SA node is functioning properly, the AV node doesn’t matter what it’s doing in terms of automatic generation of potentials, because that potential that was first generated by the SA node arrives at the AV node before it generates its own potential. Who determines the heart rate? The fastest beating automatic cell and those are generally in the SA node.

What happens if you have a disease in your SA node and it stops functioning? Then the AV node will take over because it’s no longer being stimulated by the SA nodes action potential and the wave that results, it will start beating but the heart will beat slower, it will beat at 40 beats per minute let’s say. If you had some disease there and that didn’t work anymore than the Purkinje system–so the heart has sort of a failsafe system built in such that if this automatic beat generator fails there are inferior, not such good quality, but still capable beat generators further down the line. Often those–the AV node itself, you’re not going to be able to function in the same way because you’re not going to get the same cardiac output because you’re heart isn’t beating fast enough.

There are ways to treat that now, and the most common way of treating that is by putting a pacemaker into the heart. The pacemaker is a device designed by biomedical engineers, about the size of a hockey puck, but now even smaller than that, that sits in your chest and it basically does what the SA node is supposed to do, generates a potential with a very regular period. There’s a wire that goes from this artificial device into your heart, into the atrial muscle, and sits there and stimulates the tissue around the SA node to replace its function, so that’s how a pacemaker works. This technology has evolved to the point where there’s sort of wireless–you can send signals in, you could change the rate, you can reprogram the pacemaker without having to take it out and actually physically reprogram it, so these are quite sophisticated engineering devices now.

I said something about action potentials and ion currents. I’m not going to say anything more about that now. I will say that in neurons what is important in a propagation of an action potential is sodium and potassium, but in muscle cells calcium is also a much more important player. The reason that calcium is a much more important player is, as you will learn if you study more physiology, calcium is the most important ion in terms of initiating contraction. So, movement of calcium around muscle cells is very important. This just shows an action potential in, for example, a ventricular cell. It has this rapid upstroke, this plateau in depolarization and this recovery. So, this might be an action potential you’d record from a ventricular muscle cell, and if at the same time you were recording this action potential and you were also measuring contraction. Think of this measurement as how much contraction the cell has done, at this point in its resting state and in this point it’s in its most contracted state, then the contraction follows the action potential by about 100 milliseconds. As the contraction happens–as the action potential happens the contraction happens about 100-150 milliseconds after that, the maximum response; but these things are coupled but they’re not simultaneous.

I think I’ve covered what’s shown in this slide here. This is just a simpler version of what we’ve talked about, generation of the signal in the SA node, movement to the AV node, hesitation. Then, movement of this signal down the septum in between the left and the right ventricle, through the Purkinje system, and the heartbeat being generated in this regular anatomical pattern. That happens because these specialized tissues are able to conduct signals very rapidly, and you can see here in this slide, this is how fast a signal the velocity of an action potential being propagated through different tissues goes very rapidly through pathways like through the atrium, through the bundle of His, and very rapidly through the Purkinje system. That’s why the signal gets transmitted so rapidly from the AV node down to the base of the heart. These diagrams are in the Power Points which are posted. I just encourage you to look at them, together with reading the chapter and hopefully that will help you to understand this process.

Chapter 6. Conclusion [00:40:36]

Which brings us back to thinking, at the end, about what I’ve talked about several times during the lecture; that is, that you can measure something about the physiology of the heart by measuring all of this electrical activity. One way to measure it would be to put electrodes directly into the heart and physically put them right near the site of action and measure exactly what’s happening. That could be–you could get a very detailed picture of what’s happening in the heart that way. That can be done but that’s an invasive process. There are cardiologists that do that, they do this everyday on people. They put a catheter into your heart, a catheter that goes through one of the vessels, an artery in your leg. It’s pushed up into the heart and then there are recording electrodes on the end and they can measure electrical activity directly in the heart at different locations. That’s called cardiac catheterization and cardiac electrophysiology, and it’s widely used to diagnose disease in the heart.

That’s usually not the first thing you do because that’s an invasive procedure. What is important about EKG is that it’s not invasive. You can do it without entering the body, by just measuring something that’s happening on the surface. You can do it very simply by placing electrodes at different positions on the body. You’ve all seen a diagram like this that shows a typical trace of an EKG, it’s measured in milivolt here, it’s a relatively small potential because there’s some distance–the potentials that were actually generated in the heart are tens of milivolts, but you’re measuring at a distance away and so that signal’s been attenuated, you’re only measuring fractions of a milivolt at the surface. What you see is a little bump, followed by a delay, followed by a very big wave, followed by a delay, followed by one and sometimes two smaller waves. This is the signal that you see–that you’ve seen on screens by patients beds in countless movies and television shows.

What do these represent? Well, they’re called by letters of the alphabet. This one’s called the P wave that represents the activity caused during atrial contraction, so all of those currents that are generated during atrial contraction show up as a P wave. The QRS complex, this very big signal here, is contraction of the ventricle. What does this represent here, the distance between the P wave and the QRS wave? This represents the delay in signal transmitting through the AV node. If your AV node was not functioning you’d expect that to shorten, that lag would shorten. You’d also expect that your cardiac performance would not be so good, because you don’t have this delay then the ventricle is contracting before it’s fully filled by the atrial contractions.

You can diagnose that problem, somebody comes in, they’re short of breath, they’re having trouble, they don’t know what it is, you measure their EKG, you see that this is shortened and you know that there’s a problem with their cardiac conduction system, in particular, with the AV node. That’s how physicians use these tools. The T wave is re-polarization of the ventricles. This is the return of all of this current back into the cell after this massive depolarization. The U wave, which is only very rarely seen, represents relaxation of the muscles, the papillary muscles inside, which control some of the valve function. We’ll talk about this more in section.

If you’ve had a full electrocardiogram you’ll know that they put many electrodes on your body. They put–a full electrocardiograph would take 12 electrodes and some of them are placed on your limbs and some of them are placed around your chest, sort of wrapped around your chest in a fashion. The reason for doing that is that you can–if you put several electrodes then you could look at the potential difference that’s generated by looking at any two of those electrodes. If I have one up here and one up here and I look at the voltage difference here, it might not be the same as the voltage difference measured between here and here. Why is that? Because your heart is oriented in space, it’s a three dimensional object. All of these cells are at particular three-dimensional positions inside this three dimensional object. As these currents happen they happen in a very spatially oriented way. So, the potential difference I measure at a distance, here and here for example, is different.

It’s sort of like looking at the heart from different vantage points, looking at the electrical activity of the heart from different vantage points. One of the things that cardiologists have learned how to do is how to look at potentials that are generated from different spatial locations, and correlate that with things that are happening over the complex geography of the heart. Why do you have more than one electrode? It’s so you can look at the heart from sort of different angles. Questions? Good, see you on Thursday.

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