Medical Physiology PDF - Cardiac Action Potential & ECG

Medical Physiology Dr. Dewan Majid Handouts for: L21: Cardiac action potential and excitation-contraction coupling. L22: Electrical activity of the heart (Electrocardiogram). Learning Objectives: L21: Card...

Medical Physiology Dr. Dewan Majid Handouts for: L21: Cardiac action potential and excitation-contraction coupling. L22: Electrical activity of the heart (Electrocardiogram). Learning Objectives: L21: Cardiac action potential and excitation-contraction coupling. The students should be able to: 1) know the chronology of the electrical events in the heart. 2) sketch a typical action potential in a ventricular muscle and a pacemaker cell, labeling both the voltage and time axes accurately. 3) describe how ionic currents contribute to the five phases of cardiac action potential. 4) explain the ionic mechanism of pacemaker automaticity and rhythmicity. 5) understand the excitation-contraction coupling of myocardial cells.. L22: Electrical activity of the heart (Electrocardiogram). The students should be able to: 1) describe the different components of the electrocardiogram and how they result from the depolarization and repolarization of different regions of the heart. 2) describe the different waves in normal electrocardiogram (ECG). 3) know the standard leads to record ECG. 4) learn how to read the inscription of a normal ECG. 5) how to calculate heart rate from an ECG tracing. Definitions: Automaticity: the ability to spontaneously depolarize and generate an action potential. Conduction: movement of a cardiac action potential from one part of the heart to another. Contractility: the potential to do work, often measured as the ability of muscle tissue to develop tension or shorten. Influenced by heart rate, catecholamines, and other factors. Effective Refractory Period (ERP): the time-period following an action potential upstroke during which a second subsequent action potential cannot be generated by a physiological stimulus. Cardiac Arrhythmia (Dysrhythmia): an abnormality in the rate, rhythmic pattern with which the heart contracts. 1 Medical Physiology Dr. Dewan Majid I. The Heart is a Four Chambered Pump The primary function of the heart is to transfer sufficient blood from the venous system to the arterial side of the circulation under sufficient pressure to maintain the circulatory needs of the body. As illustrated in Figure 1, the heart consists of four chambers which act as two separate pump systems. The right atrium & ventricle (the right heart) pump deoxygenated blood collected from the great veins (superior & inferior vena cava) into the pulmonary circulation, via the pulmonary artery. Blood passing through the pulmonary capillaries is oxygenated by the lungs. The left atrium & ventricle (the left heart) pump oxygenated blood received from the pulmonary system into the systemic circulation. William Harvey (1578- 1657) was the first to prove that the heart circulated blood through the body in animals. Within physiologic limits, the heart pumps exactly the same amount of blood into the arterial circulation as it receives from the venous circulation (conservation of mass). Figure 1. Basic anatomical features of the heart and pattern of blood movement. The atria, which sit dorsal to the ventricles are relatively thin walled, and their primary functions are to serve as a blood reservoir, and to assist in filling the ventricles with blood. In this sense they serve as “primer pumps”. The ventricular chambers have much thicker walls (the left being thicker than the right). They can be thought of as the “power pumps” of the heart since they provide the primary force for pumping blood into the pulmonary and systemic circulations. The path taken by blood in the circulatory system, as well as the proportion of blood flow to various organs in a typical person at rest, can be found in the PowerPoint slides. Note that the kidneys, due to their role as blood filters, receive a disproportionate amount of blood flow (approximately 20% of the total circulated volume at rest). The pattern with which the heart contracts and relaxes is cyclical and is divided into a period of relaxation (diastole), and a period of contraction (systole). Diastole is a passive process in which the heart is filled by blood from the venous system; systole is an active process in which the heart pumps blood into the arteries. 2 Medical Physiology Dr. Dewan Majid The pumping action of the heart is an intrinsic phenomenon; it does not require any outside stimulation from the nervous or endocrine systems in order to occur. However, stimulation from the nervous and endocrine systems can influence heart rate. Propranolol is a drug that blocks sympathetic nervous influence on the heart (causing heart rate to slow), while atropine is a drug that blocks parasympathetic nervous influence (causing heart rate to increase). Two types of events regulate the pumping action of the heart: electrical events, which function at a cellular level, and mechanical events, which function at an organ level. Today’s lecture notes focus on electrical events. II. Generation of action potential in the myocardium An action potential passes over the heart, serving as an impulse that triggers cardiac muscle contraction. The time of appearance of the impulse in different parts of the heart is shown in fractions of a second. The cardiac impulse originates in the sinoatrial node (SAN), and conducts through the right and left atria. The depolarization wavefront then conducts very slowly through the atrioventricular node (AVN). At the distal end of the AVN, the impulse enters the bundle of His (A-V bundle), and then progresses down the right and left bundle branches, and into the terminal portions of the Purkinje fiber system which delivers the depolarization wavefront to the entire endocardial surface of the left and right ventricles at almost the same instance in time. A flow chart that traces the progress of the cardiac impulse can be found in the PowerPoint slides. SAnode right left atria AVnode ofHis bundle right leftbundlebranch Figure 2. The pattern of transmission of the cardiac impulse through the heart during normal sinus rhythm III. Phases of the Cardiac Action Potential By convention the cardiac action potential is subdivided into 5 distinct phases (0 through 4) (see Figure 3). The action potential seen in the heart is not the same as that seen in the nervous system, consisting of a near-instantaneous depolarization (phase 0) and a brief overshoot (phase 1), a depolarized plateau (phase 2), and then a quick repolarization (phase 3) and return to resting state (phase 4). This helps to ensure that the heart does not receive further stimulus during a period when it is already contracting, thus preventing tetanus in the heart muscle. The different phases of the action potential are influenced by ion flux, in particular the flux of sodium (resting potential, +60mV) and potassium (resting potential, -100mV). The rapid depolarization of phase 0 is triggered by the rapid opening of Na+ channels in the heart cells. The prolonged plateau of phase 2 comes from the slow opening of Ca2+ channels and the closure of K+ channels. The repolarization in phase 3 comes from the opening of K+ channels. Natchannelsopenrapiddepolaritation slowlastopening plateauofphaser opening ofItchannels repolarization 3  Medical Physiology Dr. Dewan Majid Slowcattopen Kt lose Atchannels open Figure 3. The pattern of transmission of the cardiac impulse through the heart during normal sinus rhythm IV. Multiple Ionic Currents Underlie the 5 Phases of the Cardiac Action Potential The phases are designated as: Na Phase 0 (upstroke) - Na+ conductance dominance, no K+ conductance Phase 1 (notch or rapid repolarization phase) - Na+ conductance is inactivated quickly, K+ NAOKO conductance appears and closed quickly. quilrrepolarization Phase 2 (plateau phase) - L-type Ca2+ conductance, no Na+ nor K+ conductance Phase 3 (period of rapid repolarization) - reduced Ca2+ conductance and increased K+ conductance Phase 4: (resting or diastolic period) - K+ conductance dominance Pacemakercell CAAnode duringrepol funnysodiumchannelsslowlyopen typecaltchannelstbneflyopengallreach.es acemaner threshold 0 itypecaltchannelopenearge.catinflux open rtypeclose repolarization Atchannels Nonpacemakercell atriadventricles briefly Fastnatchannelscausefastdepolarication Channelsopen A pace fastnatChannelsclosetransient plateau typecastchannelsopenmoreslowly thebdlangotkeffluxhcaltinfluxcreat.es platala 0 ltypeialtchannelsc.ae repolarization RMP 0 delayedchannels opento movebackto O O Figure 4. Ionic conductance at different phases of cardiac action potential. 4  Medical Physiology Dr. Dewan Majid Ventricular SA node, AV node Purkinje fiber strengthandamplitudeofAPbtwn atria ventriclearethesameBUT thedurationdependsonthecardiaccelltype Atrial plateau Figure is in phase longer ventricles 5: Schematic representation of the action potentials recorded from different regions of the heart. A, Ventricular myocardium; B, SA, AV nodes and Purkinje fiber; C. Atrial myocardium. SA node, AV node, and Purkinje fibers display automaticity (phase 4 depolarization). Action potentials in the SA and AV node have a slow upstroke velocity that is produced by the L-type Ca current. The upstroke in cells outside the nodes is produced by the Na current. The duration of the atrial action potential is less than half that of the ventricular action potential. Such differences result from regional differences in ion channel expression. to atriaserve pumpbloodintotheventricles lowpressure left ventriclepumpsbloodinto contraction entire systemic circulation IV. Electrophysiological Basis they needalonger for Normal moresustained Automaticity (Impulse Formation) longerAp Automaticity is defined as the ability of heart cells to spontaneously depolarize and generate an action potential, known as a pacemaker potential. In a normal healthy heart, only cells in the regions of the SA node, AV node, and His-Purkinje conduction system have the property of automaticity. The SA node is the heart’s normal pacemaker. This ability stems from the presence of “leaky” sodium F-type (funny; If) channels, which allow Na+ to enter the cells, and calcium in T-channels (Ica) that allow Ca2+ ions to enter the cell. initiatoAp PACEMAKERLEUS Normally, cells in the SA node have the greatest automaticity (firing rate) and therefore function as the normal pacemaker for the heart. If automaticity of the SA node becomes depressed or automaticity of cells outside the SA node becomes enhanced and results in the generation of an action potential at a site outside the SA node, this region is referred to as an ectopic pacemaker. group cellsgeneratingelectricalimpulsesoutside of ofnormalpacemakerregions theycantakeoverwhenSAnodeis5 asy functional  Medical Physiology out hyperpolarize acetylcholine Dr. Dewan Majid Nathan_depolance noepi Cells that can reach threshold in the shortest amount of time have the greatest automaticity since they can produce action potentials at a more rapid rate than other cells. It is known that the diastolic depolarization that underlies automaticity results from an imbalance between the net inward flux of positive ions (Na or Ca) that act to depolarize the cell vs. the outward flux of positive K ions, which acts to hyperpolarize the cell. The influx of positively charged Ca and Na ions carried through either the ICa or If in the SA node or Purkinje system is greater than the efflux of K ions carried through K channels in these cells. This results in a gradual build-up of positive charges within the cell, and depolarization of the membrane to threshold. Factors that increase K+ efflux (acetylcholine acting on M2 receptor) will act to hyperpolarize a cell towards EK (-90 mV), and thus reduce spontaneous depolarization. Factors that increase Ca2+ and/or Na+ influx during diastole (such as norepinephrine) by activating ICa and If will depolarize the membrane potential towards ENa or ECa, and thus enhance automaticity. Regulation of automaticity- Neurotransmitters such as acetylcholine and norepinephrine alter automaticity primarily by altering the steepness of the slope of diastolic depolarization. Sympathetic stimulation (β1-adrenergic agonists) increase the magnitude of both the Ca current, and If. A greater influx of Ca and/or Na ions results in a steeper slope of phase 4 depolarization. This is the mechanism by which sympathetic stimulation causes an increase in heart rate. Vagal stimulation (m2-muscarinic agonists) increase the magnitude of K current. A greater efflux of K ions results in a shallower slope of phase 4 depolarization. This is the mechanism by which vagal stimulation causes a slowing in heart rate. Very intense vagal stimulation may also reduce automaticity by hyperpolarizing the maximum diastolic potential (making it more negative). Bladrenergic Malta depolarize Mamascarinionat hyperplane V. Excitation-contraction coupling: Excitation-contraction coupling is what allows the heart to contract when exposed to electric potential. Once the membrane potential of a cardiac cell reaches a certain level, voltage-sensitive calcium channels allow Ca2+ ions from the extracellular space to flood into the cytosol, triggering ryanodine receptors on the sarcoplasmic reticulum (SR), which releases more calcium and increases the cytosolic Ca2+ concentration further. This causes the cardiac muscle to contract in much the same way as skeletal muscle. cells pacemakercellgeneratesanapandspreaasit.to nonadjacentpacemaker through junctions gapElectrocardiogram VI. The Surface utypechannelsopeninthesarcolemma the – This diagrams the difference in the electric voltages seen at the left and right sides of the heart, caused by the cardiac impulse. P wave: The initial spread of depolarization across the right and left atria produces a voltage deflection called the P wave.atrialdepolarization atriacontraction ventriculardepolarization QRS complex: The depolarization of the ventricular myocardium is detected as the QRS complex, with the initial downward deflection (Q wave) reflecting depolarization of the septum. Depolarization spreads from the endocardium (where the Purkinje fibers terminate) outward to whathappensduringRmp pacemakercellsarenot noelectrialactivitybloodfromthebody lungs depolariving enterstheheart inferiorvenacavarightatria pulmonaryveinleftatium as uneatriumrelaxtheypassivelyfill pressureincreases avualuesopenand bloodpassivelyflowstoventricles THEN AParetired 6 andatriacontract Medical Physiology Dr. Dewan Majid the epicardium. The voltage deflection caused by the repolarization of the atria is obscured by this complex. The T wave reflects ventricular repolarization, and the QT interval reflects the time for complete ventricular repolarization. affenticle file ref atriadepot Figure 6: Normal electrocardiogram (ECG) There are a number of different ways to record an EKG, including Einthoven’s triangle, which involves a triangle of electrodes placed on the collarbones and the abdomen, surrounding the heart; the standard EKG leads, which have electrodes attached to the left arm, right arm, and left leg; and variants of the standard EKG leads, such as placing electrodes on both legs and one arm or something similar. No single one of these methods can provide a complete EKG picture, but combining them can provide a better view of heart activity. Standard EKG leads: Bipolar Limb Leads: Lead I – RA to LA Lead II – RA to LL Lead III – LA to LL Unipolar Limb Leads: aVR – RA aVL – LA aVF – LL Chest Leads: V1 V2 V3 V4 V5 V6 7 Medical Physiology Dr. Dewan Majid Figure 7: ECGs are normally printed on a grid. The horizontal axis represents time and the vertical axis represents voltage. The standard values on this grid are shown in the adjacent image: A small box is 1 mm x 1 mm big and represents 0.1 mV x 0.04 seconds. A large box is 5 mm x 5mm big and represents 0.5 mV x 0.2 seconds wide. The "large" box is represented by a heavier line weight than the small boxes. Éᵈ ONOf initialdepolarication septumwall btwnv4 Rventicles moving away from t electrode negative Figure 8: Inscription of a normal electrocardiogram (ECG). Sinoatrial nodal depolarization is not visible on the surface ECG; the P wave corresponds to atrial muscle depolarization. The PR interval denotes conduction through the atrial muscle, atrioventricular node, and His- Purkinje system. The QRS complex reflects ventricular muscle depolarization. The ST segment, T wave, and U wave (if present) represent ventricular repolarization. The J point lies at the junction of the end of the QRS complex and beginning of the ST segment. The QT interval is measured from the onset of the QRS to the end of the T wave. Note the gridlines. On the horizontal axis, each 1-mm line (“small” box) denotes 0.04 second (40 msec); a “big” box denotes. 0.2 second (200 msec). On the vertical axis, 1 mm (small box) corresponds to 0.1 mV; 10 mm (two big boxes) therefore denotes 1 mV. 8