Human Body Foundations II: Cardiac Electrophysiology and Cardiac Function (Physiology) 2024 PDF

Human Body Foundations II: Cardiac Electrophysiology and Cardiac Function (Physiology) 2024 Faculty Charles S Chung PhD Associate Professor of Physiology [email protected] Note: In most cases, if a statement text is in a gray color, it is either an exercise or additional information. Throughout...

Human Body Foundations II: Cardiac Electrophysiology and Cardiac Function (Physiology) 2024 Faculty Charles S Chung PhD Associate Professor of Physiology [email protected] Note: In most cases, if a statement text is in a gray color, it is either an exercise or additional information. Throughout the notes, essential concepts are underlined, but studying all components is important to prepare for additional topics. Lecture 7-ECG Basics Part 1: Cell Physiology to the ECG Learning Objectives Define the major waves, segments, and intervals of an ECG Describe how the waves of an ECG are related to cardiac action potentials (and thus ion channels) 1 Part 1: Cell Physiology to the ECG The electrocardiogram (ECG) or electrokardiogram (EKG) are means of measuring the electrical activity of the heart. EKG comes from a German language source. They mean the same thing! The ECG is typically printed on a normal grid where the following pattern is repeated: https://thephysiologist.org/study-materials/the-normal-ecg/ FIGURE: Standard grid on which an ECG is printed The ECG is normally shown on the repeating grid. Because they were originally printed by chart recorders moving at 25mm/s, the following properties became standard: Small lines on grid are 1 mm apart, bigger lines 5 mm apart Vertical scale is usually 0.1mV/mm (1cm = 10 mm = 1mV) Horizontal scale is usually 0.04s/mm (1cm = 10 mm = 0.4 s) Check for calibration marks (Typically a square-wave printed before the ECG is plotted) 2  Isoelectric Period: No conductance Modified from Boron Baulpaep, Medical Physiology Fig 21-7 Figure: Example features of an electrocardiogram. ECG Terminology An important feature of an ECG is the isoelectric period. The resting voltage of a body won’t be referenced with a 0 as it is on the example figure above. Body movement can also make this drift up and down. Isoelectric Period Reference period The core features are made of waves: P wave SA node depolarizes Atrium depolarizes Q, R, and S waves Ventricle depolarizes T wave Ventricle re-polarizes U wave (not shown) The areas between waves, called intervals if they go peak to peak or segments if they go from between the waves include: R-R interval Heart Rate PR interval Time of electrical signal from SA node to AV node, Bundles of His, Bundle Branches QRS duration Time it takes for the ventricle to depolarizes ST segment QT interval Depolarization to repolarization period 3 The ECG does not measure action potentials. It measures the movement in the direction from a reference to sensing electrode. Boron Baulpaep, Medical Physiology Fig 21-10 FIGURE: Action potentials are potentials (voltages measured inside of the cell. Subtracting two action potentials begins to display what an ECG shows. Guyton and Hall, Textbook of Medical Physiology Fig 5-6,11-2 FIGURE: Left: measure of an action potential. Right: measures of electrical charge (action potential) moving along a cell These images simply highlight that we’re discussing potential differences or movement of depolarization along an axis. 4 ECG waves correspond to conduction of the action potential Boron Baulpaep, Medical Physiology Fig 21-7; Varro et al, Physiol Rev. 2021 Jul 1;101(3):1083-1176. FIGURE: Alignment of some action potentials and a schematic of the ECG. Remember that the ECG is evaluating conduction (or change in action potentials). Physiologically, all of the atrial myocytes do not depolarize at the same time, neither do all of the ventricular myocytes. The depolarization must conduct across the tissues. The P-wave begins as the atrial myocytes near the SA Node depolarize, but as depolarization travels to the left atrium via gap junctions, the charges are moving to the right, giving a positive P-wave. The PQ Interval reflects the delay of the conduction through the AV Node and Bundle of His. Recall that the AV Node has very slow conduction due to decremental conduction. The QRS Complex reflects ventricular depolarization o The Q-wave shows deflection of the Purkinje network and start of depolarization of myocytes down the septum. o The R-wave is a positive wave. o The S-wave occurs when depolarization is complete. The QT interval correlates roughly with the average action potential duration of all of the myocytes The T-wave is the repolarization of the ventricle. Because of the transmural variation in the action potential durations, the repolarization is the reverse of the depolarization. Therefore, the T-wave is positive instead of negative (which is what you would expect if the repolarization would be traveling along the same route as depolarization. 5 The U-wave Not seen on most ECGs Hard to see at fast rates Could be Purkinje repolarization Often pathologic Electrolyte imbalance? https://www.nottingham.ac.uk/nursing/practice/resources/cardiology/function/u_wave.php FIGURE: an ECG trace with a visible U-wave (arrows). Definition of R-wave and a note on the QRS Complexes R-wave is always positive If there are two positive deflections, there is an R’ Features of the QRS complex can be missing https://www.cvphysiology.com/Arrhythmias/A009 FIGURE: examples of QRS complexes with or without a Q, R, or S wave or with a 2nd R wave, called R’. 6 Changing Action Potentials Example of how Different Action Potentials cause Different ECGs: a Species Comparison Differences in currents in a mouse compared to a human: Ito (Phase 1), IKs (Phase 2/3) are lower mice IKur (Phase 1,2) is much higher in mice Conn's Handbook of Models for Human Aging (Second Edition) 2018, Pages 271-285 FIGURE: Schematic of ECG (top) and associated transmural action potentials (bottom) in human (left) and mouse (right hearts). In mice, the 2nd peak may be referred to as J, but we’ll refer to them as R’. 7 Integration/Pathophysiology Thought experiments to think about how ion currents and action potentials relate to ECGs. Why is long-QT syndrome related to ion channels and/or action potentials? A pathologically long QT interval can be due to changes in the calcium or potassium currents A pathologically long QT may be associated with a prolonged Phase 2 action potential Since the QRS complex is from depolarization (Phase 0 of the action potential), what happens to the QRS complex if sodium channels are inhibited? Rectifier Potassium currents (IKr, IKs) impact repolarization. If you inhibit or enhance the rectifier currents, what happens to the T-wave? Most of the above exercises modify channels themselves. However, you can change the ECG by changing the extracellular ion concentration. Here are some examples: https://twitter.com/Innov_Medicine/status/1570920105936326661 https://twitter.com/innov_medicine/status/1625516795003019265 Can you think of WHY extracellular ion concentrations would change the action potential? (Hint: What happens to Nernst/Goldman equation outputs?) 8 Part 2: Rate, Rhythm, and Axis There are three essential outputs of an ECG: Rate, Rhythm, and Axis. Rate is the easiest to quantify. We’ll introduce Rhythm here, but many rhythms are pathologic so we won’t detail them in this course. The Axis is likely the most new and hardest to quantify. This will take up the most content Rate The R-R Interval, as shown above, is the time between two R-wave peaks. Because this is the period of the beating and the frequency or rate is 60/period. Therefore, the Heart Rate can be calculated as HR=60/RR. However, the heart rate can be estimated quickly and simply because of the standard grid of the ECG. Since one box is 0.2 seconds wide, we can use the big boxes to calculate the rate. If the R-R Interval were one box apart, the rate would be 60 seconds per minute divided by 0.2s = 300 beats/min. Two boxes would be 60/.04s=150 beats/min (BPM) https://en.ecgpedia.org/wiki/Rate FIGURE: example of how to estimate the heart rate using the simple rules. For the ECG shown, the R-R Interval is more than 4 boxes apart, but less than 5. Therefore the heart rate must be between 60 and 75 BPM. To utilize this quick method, you can memorize the sequence: Box 0 Start of the R-wave Box 1 300 BPM Box 2 150 BPM Box 3 100 BPM Box 4 75 BPM Box 5 60 BPM Box 6 50 BPM Where those numbers are the BPM if the R-R interval were within the big boxes 2 Rhythm The rhythm provides information about the source and speed of the major pacing events (typically the feature reflecting ventricular depolarization and repolarization). When discussing Rhythm, generally can state: Source + Speed (or regularity) Source Normal P-wave and PQ interval? “Sinus Rhythm” Speeds Bradycardic HR60 BPM, 100 BPM Tachycardia Bradycardia 3 big boxes or less More than 5 big boxes apart A more detailed discussion of rhythms requires a discussion of pathophysiology. However, here is a list of a few rhythms: Atrial Flutter Ventricular Tachycardia Atrial Fibrillation, Ventricular Fibrillation Ventricular Premature Contraction (escape!) Bundle-Branch Blocks However, you can understand many pathophysiologic rhythms if you understand the core concepts of: Automaticity Re-entry One final concept you might run into is a heart rate correction for the R-R interval. Its known as Bazzett’s formula: QTc=QT / square root of RR 3 Cardiac Axis Review again: ECG provides a direction of change of action potentials ECG derived from 2 electrodes If depolarization conducts from negative electrode to positive electrode, positive deflection (top) If depolarization conducts from positive electrode to negative electrode, negative deflection (bottom) If depolarization moves perpendicular to the electrodes, no signal will be detected Boron Baulpaep, Medical Physiology Fig 21-10 FIGURE: Reminder that the ECG reflects the conduction of action potentials along the axis of the electrodes. 4 12-lead ECG Chest Limb Ground/Reference https://clinicalview.gehealthcare.com/poster/diagnostic-ecg-lead-placement 1 2 Chest 3 4 5 6 7 Limb 8 9 10 https://clinicalview.gehealthcare.com/poster/diagnostic-ecg-lead-placement Ground/Reference https://clinicalview.gehealthcare.com/poster/diagnostic-ecg-lead-placement FIGURE: Lead placement for a traditional (top) and modified (bottom) 12-lead ECG. The 12-lead ECG actually has only 10 markers stuck on the body. Only 9 are actually used to read signals (the 10th is a reference for the chest leads. The layout was modified (bottom) so that the limb leads that were at the wrist and ankle are now at the shoulder and hips. 5 Mean Electrical Axis The Mean Electrial Axis or MEA provides information of what direction the depolarization conducts around the chest. i.e. it provides the major direction of conduction of the action potentials within the body along the frontal or coronal plane. Frontal: The potentials are described using Einthoven’s Triangle. It uses three of the electrodes to create 6 vectors (leads). Ganong’s Review of Medical Physiology FIGURE: The 3 limb leads used to create Einthoven’s Triangle. Standard Limb Leads Einthoven’s Triangle uses the Right Arm (RA), Left arm (LA) and Left Leg (LL) electrodes as the three corners of the triangle. As noted, one side must be defined as positive. For Lead I, the positive lead is the LA, the negative lead is the RA, meaning it is a vector that points horizontal (right to left) across the chest (0º) For Lead II, the positive lead is the LL, the negative lead is the RA, meaning it is a vector that points from the right arm to the left leg 60º below the horizontal For Lead III, the positive lead is the LL, the negative lead is the LA, meaning it is a vector that points from the left arm to the leg, 120º away from the Lead I axis (vector) 6 Augmented Chest Leads: Three additional leads known as the Augmented Chest Leads are obtained using the 3 limb leads. Instead of using one lead as the negative, the ECG takes two leads at a time and makes them negative. Boron Baulpaep, Medical Physiology Fig 21-8 FIGURE: The direction (arrow pointing positive) that the ECG lead is measuring. The Augmented leads point to the right arm (aVR) at -150º away from Lead I, the left arm (aVL) at -30º away from Lead I, and down the front axis of the body (aVF) at 90º away from Lead I. (Angles measured clockwise). If the conduction of depolarization is moving along the axis of the lead, it will create a positive deflection of the wave. If the conduction of repolarization is moving along the axis of the lead, it will produce a negative deflection of the wave. Therefore, one can predict the shape of the ECG. 7 Walk through this via the following alignment. Imagine the heart is oriented as drawn for the same torso on the right. (Head) Right Arm Left Arm If we look along Lead I (right arm to left arm): When the SA Node depolarizes, the conduction will generally move right to left, which means there will be a positive P-wave indicating atrial depolarization. When the ventricle depolarizes, the conduction will move from the endocardium to the epicardium and first down the septum before coming back to the base along the other ventricular walls. So there will be a strong deflection positive (R-wave) along the lead at first, which will reverse as it comes completes depolarization. The ventricular re-polarization will follow a reverse path. Thus, the T-wave is positive because it is a repolarization but in the opposite direction as the depolarization (QRS). If there is a pathology, like the signal goes down one side of the heart before going down the other (bundle branch block), then you might have two positive deflections. 8 Hexaxial Reference System aVR -150º aVL -30º I 0º III 120º II 60º aVF 90º FIGURE: Hexaxial Reference System. The hexaxial reference system provides a means of quantifying the direction of the MEA. The six black axes reflect the direction of the vector created from Einthoven’s Triangle. The key is to take magnitude of the QRS complex and plot it appropriately. Note that positive will be drawn along the black part of the axis. A negative deflection will be plotted on the negative (gray) part of the axis. Once you plot the QRS magnitude along an axis, this becomes a vector. It is important that your scales (ticks) match. 9 Example vector addition: aVR -150º aVL -30º I 0º III 120º II 60º aVF 90º Figure: Example ECG and vector addition. In the example above, the aVR is measured. The vector addition gives a value, but the peak is negative (a Q-wave!). So instead of plotting a vector along the black part of the aVR axis, we plot it along the gray axis. If we follow up with the aVF, we can measure the scale, but since it is positive, we’ll plot it along the black axis. Then we perform vector addition and create a summed vector that plots near the 60º axis. QUICK Method for estimating the Mean Electrical Axis The exact angle is often not needed clinically. Therefore, we can estimate the MEA. It takes just two steps: 1. Find the largest deviation (QRS magnitude). This wave is most Parallel to MEA. 2. Find the most isoelectric RS segment. This is the most Perpendicular to MEA. The MEA must be within 30-60º of the axis with the largest QRS vector. (see the blue in the later figure) The MEA is 90º away from the axis that is most isoelectric, so you can imagine that it is 60-120º away from the axis in either direction. (see the red in the later figure) 10 Figure: Sample six frontal leads of an ECG. Note that Lead II (blue box covering the calibration mark) has the largest QRS complex magnitude. Lead III has the most isoelectric amplitude (the S-wave goes down about the same amount the R-wave goes up). aVR -150º aVL -30º I 0º III 120º II 60º aVF 90º Figure: Using the quick method, we first see that Lead II has the highest magnitude QRS, so the vector is probably within the blue wedge. We also see that Lead III has the most isoelectric trace, so the vector should be roughly perpendicular to that, which is drawn within the red wedge. The two wedges overlap in the same region we drew our vector using vector addition! 11 Characterizing the MEA (Head) Right Arm Left Arm aVR -150º aVL -30º I 0º III 120º II 60º aVF 90º Figure: The MEA can be characterized using the following limits The axis is characterized in the four components. Normal QRS axis -30º to 90º Left Axis Deviation -30º to -90º Right Axis Deviation 90º to 180º Extreme Axis Deviation -90º to -180º So the previous exercise produced a Normal MEA. Practice Exercise from Lecture (and Link to additional samples). https://thoracickey.com/electrical-axis-and-axis-deviation/ 12 Chest Leads Chest leads (V1-V6) provide information in an orientation perpendicular to the frontal plane. Changing MEA The MEA can move. In the most deviated axes, it is most likely you’ll see a pathological axis. Examples include: Abnormal orientation Congenital: situs inversus Body shape Pathologic: right lung pneumothorax … Hypertrophy Exercise: What happens to MEA if RV hypertrophies? Additional resources The following links contain additional ECG waves or explanations about the ECG, especially the axes. Cardiac Axis trainer: https://david-shrk.github.io/ecgaxistrainer/ Highly recommended if you want to practice the simple rules or get used to axis https://ecgwaves.com/topic/ecg-normal-p-wave-qrs-complex-st-segment-t-wave-j-point/ Alternate axis interpretation methods: https://litfl.com/ecg-axis-interpretation/ https://thoracickey.com/electrical-axis-and-axis-deviation/ 13