[PHYSIO]-LC11-CARDIOVASCULAR PHYSIOLOGY_ Rhythmical Excitation of the Heart.docx (1).pdf

Atrium and the ventricle contract as a unit (syncytium) to be able to OUTLINE effectively generate the pressure to...

Atrium and the ventricle contract as a unit (syncytium) to be able to OUTLINE effectively generate the pressure to expel blood out of the heart. THE BEATING HEART: I. THE EXCITATORY AND CONDUCTIVE SYSTEM OF THE HEART Electrical Stimulation and Contraction II. THE CONDUCTION SYSTEM III. CARDIAC MUSCLE ACTION POTENTIAL IV. THE REFRACTORY PERIOD V. THE RELATIONSHIP BETWEEN THE ACTION POTENTIAL AND CONTRACTION OF A CARDIAC MYOCYTE VI. THE AUTORHYTHMIC CELL A. Autorhythmic cell: Characteristics B. Autorhythmic cell: Action Potential C. Mechanisms of Autorhythmicity VII. DIFFERENCE BETWEEN PACEMAKER APS AND THE VENTRICULAR MUSCLE APS VIII. THE CONDUCTION SYSTEM OF THE HEART AND THEIR Figure 1. Pathway of the electrical stimulation and contraction of the heart. ACTION POTENTIALS ➔ due to the specialized excitatory and conductive system of the heart IX. EXCITABILITY AND CONDUCTIVITY: IMPULSE GENERATION AND CONDUCTION PROPERTIES OF CARDIAC MUSCLE CELLS X. EXTRINSIC CONTROL OF HEART RATE: ANS 1. Autorhythmicity: (Automaticity) A. Sympathetic Effect on Heart Rate - The ability to initiate an electrical impulse continuously and regularly B. Parasympathetic Effect on Heart Rate without external stimulation. C. Brainbridge (Atrial) Reflex: Atrial stretch reflex, Volume reflex 2. Excitability: XI. THE ECG (ELECTRODIAGRAM) - The ability to respond to an electrical impulse of adequate strength A. Relation of cellular ionic events to surface ECG and duration (i.e. threshold or more) by generating a propagated B. Review of Electrophysiology action potential. C. Action Potential and Electrodiagram (ECG) 3.Conductivity: D. The ECG Leads - The ability to transmit an electrical impulse from one cell to another E. The ECG Paper through the cardiac tissue. F. ECG Terminologies 4.Contractility: G. ECG waves and intervals - The ability to contract in response to stimulation. H. Sequence of Cardiac Excitation Related to ECG I. Relationship of Surface ECG to events of the cardiac cycle SPECIALIZED CARDIAC CELLS THAT CONTROL CARDIAC CONTRACTIONS J. Components of an ECG tracing K. Normal sinus rhythm characteristics L. ECG interpretation: Rate M. ECG interpretation: Rhythm N. Review XII. COMMON ARRYTHMIAS A. Slow Rhythms B. Fast Rhythms C. Arrest Rhythms D. Benign Ectopic Rhythms E. Miscellaneous XIII. DIFFERENTIAL DIAGNOSIS FOR THE HEART RATE (HR) A. Bradycardia B. Tachycardia XIV. TEST YOUR KNOWLEDGE Figure 2. Specialized cells controlling heart contractions. 1. Sinus or Sinoatrial (SA) node - Generates the normal rhythmical impulses of the heart I. THE EXCITATORY AND CONDUCTIVE SYSTEM OF THE HEART (60-100/minute) 2. Atrioventricular (AV) node The human heart has a special system for rhythmic self-excitation (produce its - Impulses from the atria are delayed before passing into the own impulse) and repetitive contraction approximately 100,000 times each day, ventricles (approximately 0.1 second). The physiologic delay or 3 billion times in the average human lifetime. which occurs in the AV node allows the atrium to contract ahead of time before the ventricle. The system FUNCTIONS to: 3. Bundle branches 1. Generate rhythmical electrical impulses to initiate rhythmical contraction of - Carry the impulse toward the apex of the heart (Left and Right the heart muscle Bundle Branches) 2. Conduct these impulses rapidly through the heart 4. Purkinje fibers the atria contract about one sixth of a second ahead of ventricular - Carry the impulse to the heart apex and ventricular walls. contraction Purkinje fiber stimulates the ventricular muscle. allows filling of the ventricles before they pump the blood through the lungs and peripheral circulation allows all portions of the ventricles to contract almost simultaneously (effective pressure generation in the ventricles) Page 1 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Receives innervation from the cardiac plexus fibers II. THE CONDUCTION SYSTEM THE ATRIAL INTERNODAL TRACTS Connect the Sinus Node to the AV Node Structure: tracks of minimally modified myocytes arranged in parallel along the atrial wall Excitatory function: capable of automaticity under extreme conditions Conductive function: conducts action potentials (velocity = 1.7 m/sec) Figure 3. Location of the sinus node. SINUS NODE Otherwise known as sinoatrial (SA) node The Heart’s ‘Natural Pacemaker’ - produces rates at 60-100 BPM at rest Sinus node is located at the junction of the crista terminalis in the upper wall of the right atrium and the opening of the superior vena cava. The SA Node has ‘automaticity’ - its rate is normally faster than all Figure 5. Atrial internodal tracts. other parts of the heart, and therefore, dictates the rate at which Three Major Atrial Circuits: the heart beats. This is known as “Sinus Rate”. That is the normal 1. The anterior internodal tract heart beat. 2. The middle internodal tract 3. The posterior internodal tract The Bachmann’s Bundle This is a narrow band of aligned atrial muscle fibers which stretches from the right auricle to the base of the left auricular appendage “The inter-auricular band". Figure 6. Location of the AV node. ATRIOVENTRICULAR (AV) NODE AV node is located between the atrium and the ventricle Receives impulse from SA Node Delivers impulse to the His-Purkinje System Produces rates at 40-60 BPM if SA Node fails to deliver an impulse Conduction through the AV Node is slow, allowing appropriate fill time for the ventricles prior to ventricular contraction Figure 4. Different cardiac cells. The A-V Node Excitatory function: dominant pacemaker, influenced by autonomic Main communication of action potential from the atria to the tone ventricles; “physiologic delay” Characteristics: Small, flattened, ellipsoid strip of specialized cardiac Little (5-10mm) (don’t contain contractile tissues) fusiform bundle of muscle cells, found somewhere within the Triangle of Koch at the base of the Size: About 3 mm wide, 15 mm long, 1 mm thick right atrium Location: superior posterolateral wall of the right atrium (crista AV nodal cells: short and fusiform, arranged without any clear terminalis) below the opening of the superior vena cava orientation Cells: no contractile muscle filaments, only 3-5 um in Responsible for introducing a delay between atrial and ventricular diameters systole (between atria and ventricles) Connect directly with the atrial muscle fibers Page 2 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Figure 9. Location of the Bundle of His. BUNDLE OF HIS Begins conduction to ventricles Figure 7. Cadaveric section of the heart showing the different leaflets and AV Junctional Tissue: produces rates at 40-60bpm (like the AV valves. node) The AV node is functionally divided into three regions: The eponymous bundle, discovered by Wilhelm His in 1983, is 1. AN region basically a continuation of the lowermost NH part of the AV - transitions from atria to node node. The bundle is short (maybe 10mm). - transitional zone: transitions from atria to AV node 2. N region (the central AV node) (mid portion) - where the delay mainly happens: conduction slows down to the most sluggish rate of all (about 0.05m/sec) - this is where the delay would happen because action potential is slowest at this point 3. NH region - merges into the Bundle of His; where “junctional rhythm” originates - Node to His—NH: node connect with Bundle of His Figure 10. Locations of the Bundle Branches and Purkinje Fibers. PURKINJE NETWORK Bundle Branches Purkinje Fibers Moves the impulse through the ventricles for contraction Provides “Escape Rhythm”: produces rates of 20-40 BPM provide effective conduction within the ventricles Effective conduction system within the ventricles Figure 11. Histological section and morphology of Purkinje Fibers. Purkinje cells are large, wide cells with a clearer cytoplasm and a diameter usually at least double that of surrounding myocytes. Histologically, the Purkinje cells are larger than regular contractile Figure 8. Different regions of the AV node (top) and the appearance of their myocytes. Their main function is conduction which explains how graphs (bottom). they don’t have much contractile tissues. Structure: parallel-aligned large heavily modified myocytes, spreading out from the central Bundle of His, along two bundle branches, and into hundreds of terminal ramifications. Excitatory function: minimal normally, but capable of automaticity with a slow rate - slow automaticity: 20-40 BPM Page 3 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Conductive function: responsible for the distributed delivery of the - The specialized conducting fibers (Purkinje fibers) cardiac action potential to the myocardium at high velocity (up to Divided into 5 phases: 4m/s) No contractile function III. CARDIAC MUSCLE ACTION POTENTIAL What produces the ACTION POTENTIALS? BRIEF changes in cell membrane permeability - Alter the rate of movement of ions across the membrane (alteration would disturb permeability) - change the membrane voltage Accomplished by the opening and closing of ion channels Mainly by Na+, K+, Ca++ ions (changes in the electronegativity of the cell membrane produces action potential) Figure 14. Action potential of a Fast response. 2. The SLOW response - named as such because the upstroke or the rate of rise or your phase 0, depolarization occurs slowly, not as fast; slope Occurs in: a. Sinoatrial (SA) node (natural pacemaker) b. Atrioventricular (AV) node (conducts the cardiac impulse form the atria to the ventricles) Lacks the early repolarization phase (phase 1) FIgure 12. Difference in the membrane potential during depolarization. Figure 15. Action potential of a Slow response. Skeletal vs. Cardiac Muscle: Table 1. Action Potentials and Refractory Periods Figure 13. Concentrations of ions with respect to their locations. At rest, the main extracellular ion is Na+, and the main intracellular ion is K+ - which actually determines the equilibrium of resting membrane potential which is -94mV Any disturbance from the action potential would now produce the different phases of your action potential. Two Main Types of Action Potential: - different from action potentials of nerves and skeletal muscles 1. The FAST response - named as such because phase 0 or the phase of depolarization is very fast, horizontal The action potential of the atrial and ventricular myocytes and the Purkinje fibers. Occurs in: - Normal atrial and ventricular MYOCYTES (contractile tissues) Page 4 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Figure 16. Skeletal muscle action potential Skeletal muscle potential: rapid upstroke and rapid downstroke. Figure 19. Movement of ions during cardiac muscle action potential. PHASES & Ion Permeability: Phase 4 - Resting membranepotential near the K+ equilibrium potential - K+ efflux reaching the resting membrane potential which Figure 17. Cardiac muscle action potential. is -90 mv Phase 0 Cardiac muscle action potential: rapid upstroke but there is a delay in - Depolarizing impulse opens fast Na+ channels and depolarization, there is a plateau, which differentiates them from the inactivates K+ channels other action potentials. - rapid depolarization due to the inward Na+ current. Phase 1 Phases of Cardiac Muscle Action Potential - Transient opening of K+ channels and Na+ channels begin to close - initial repolarization due to closure of your Na+ channels they become on coming more negative Phase 2 - Ca2+ channels are open (key difference between nerve AP) - Calcium gets in so it delays your repolarization. Phase 3 - Repolarization, Ca2+ inactivate and K+ channels open Refractory period: Na+ channels are inactive until membrane is repolarized. THE CARDIAC MYOCYTE ACTION POTENTIAL Figure 18. Phases of cardiac muscle action potential Repolarization is delayed because of the presence of a plateau due to inward of Ca2+ current. So instead of becoming more negative again because of the potassium efflux, there is an extension because of being more positive of Calcium influx. Phase 4: Potassium equilibrium Figure 20. Cardiac myocyte action potential. Page 5 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo PHASES: Phase 0: rapid depolarization When action potential comes into the cell it will now trigger your - due to the fast opening of Na+ channel, you infuse depolarization which is phase 0. more Na+ in the inner portion of the cell thus The membrane potential changes from -90 mV to +50 mV. becoming more positive. K+ activated temporarily. Triggered by the arrival of AP from adjacent cell Phase 1: Early repolarization This happens very quickly: the rate of change is about 250 V/sec, i.e - transient opening of your K current (Ito). the change occurs over about 0.5 msec. - Ito current is responsible for this. Bring down your Ends in an “overshoot” AP (around +20 to +50 mV) Action Potential to a more negative level because Due to the opening of fast voltage-gated sodium channels of the efflux of K and closure of Na channel. The After opening, the sodium channels close and become inactive opening of your K and closing your Na produce (absolute refractory ) more negative level. Phase 2: Plateau Ionic events during Phase 0 are: - calcium channel open leading to becoming more positive 1. Closure of Kir potassium channels - Key difference in Neuronal AP they don’t have the phase 2 2. Opening of fast voltage-gated sodium channels Phase 3: Repolarization - due to opening again of K+ channel until they reach III. PHASE 1 OF THE CARDIAC ACTION POTENTIAL your resting membrane potential INITIAL REPOLARISATION: The “NOTCH” Phase 4: Resting potential PHASE 4 OF THE CARDIAC ACTION POTENTIAL RESTING MEMBRANE POTENTIAL: -90mV Figure 23. Phase 1. The AP is said to approach zero (bottoms out at +30 mV) The exact duration of this phase is not clear Mediated by opening of potassium channels, which permit the “transient outward” potassium current (Ito) responsible for a transition to a more positive to a more negative. - exists only for a brief period following Figure 21. Phase 4. depolarization, and which allows potassium ions to leave the cell A quiescent period during which the cardiac myocyte waits for a Opening of the Na+/Ca2+ exchanger (INCX) = which is a current depolarizing signal in a state of silent readiness. pumping calcium into the cells, in exchange for sodium During this period, the potential difference across the membrane - mediated by an antiporter protein which normally sits at approximately −90 mV runs in the opposite direction. Mediated by Ik1 inward rectifying potassium current by the Kir - net effect is a loss of intracellular sodium and a inward rectifying potassium channel, more negative intracellular membrane potential. - allow potassium ions to pass out of the cell at very low voltages (around -90 mV), but are basically impermeable Ionic events during this phase are: to potassium at more positive voltages. 1. Closure of the fast voltage-gated sodium channels 2. Opening of potassium channels, the Kv channels, PHASE 0 OF THE CARDIAC ACTION POTENTIAL (Ito current) RAPID DEPOLARIZATION 3. Opening of the Na+/Ca2+ exchanger (INCX) PHASE 2 OF THE CARDIAC ACTION POTENTIAL The PLATEAU Figure 22. Phase 0. Page 6 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Three potassium currents are responsible for this process: 1. Ikr, via the Kv11.1 potassium channel 2. Iks, via the Kv7.1 potassium channel 3. Ik1, via the Kir2.X potassium channel SUMMARY: Figure 24. Phase 2. The membrane potential remains relatively stable (near to 0 mV) The main feature which distinguishes the cardiac AP from the neuronal AP This triggers the release of calcium from the SR, and initiates muscle contraction The most important ionic event which takes place this period is the inward flow of calcium through L-type and T-type calcium channels: a. L-type voltage-gated calcium channels - have large single channel conductance and long‐lasting Figure 26. Principal Ionic Currents and Channels That Generate the Various currents. Phases of the Action Potential in a Cardiac Cell b. T-type voltage-gated calcium channels - have tiny single channel conductance and transient current T type is for tiny and transient and L type is for larger and long IV. THE REFRACTORY PERIOD lasting. Basically the inward flow of Calcium is your L type because it has a longer duration. Once Ca channels are close then K channels DEFINITION open and now transmit again to K out of the cell so the cell will "The property of reduced responsiveness to stimuli during become more electronegative. This repolarization stops once it particular phases of the excitatory processes“ reaches Resting Membrane Potential. The myocyte which has just depolarized will not be inclined to These types of voltage-gated channels open at -50 mV (T-type) and depolarize until a certain period of time has passed. at -30 mV (L-type) Due to inactivation of the fast voltage-gated sodium The L-type channels open slowly channels, which undergo a conformational change after activating which takes some time (and a negative membrane potential) to reverse PHASE 3 OF THE CARDIAC ACTION POTENTIAL SLOW REPOLARIZATION SUBDIVISIONS OF THE REFRACTORY PERIOD A. Absolute refractory period: where the threshold for depolarization is infinite no stimulus, no matter how great, will be able to make this myocyte depolarize again maintained by the obstinate refusal of voltage-gated sodium channels - They will simply not reopen for anything until the membrane potential has dropped to below -40mV. B. Relative refractory period: where stimuli of normal magnitude do not produce any depolarization but unnaturally large stimuli can still produce a depolarization Figure 25. Phase 3. of a lower magnitude Occurs when the calcium channels close, and potassium channels there are fewer sodium channels available (some will still be in open their refractory state) Slowly returns the cell to the resting membrane potential (-90 mV) The Potassium channels - all remain closed at very negative (resting) membrane potentials and at very positive (early depolarized) membrane potentials - they can really only remain open from the end of Phase 2 to the end of Phase 3. The repolarizing potassium currents stop flowing once the membrane potential is in the territory of the Kir inward rectifying channel - maintains Phase 4 at the resting membrane potential by remaining open Figure 27. Refractory periods Page 7 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo 3. No organized sarcomere structure The pink line is the absolute refractory period while the green line is the relative refractory period. Very strong stimuli happens during this time of Relative Refractory period it can produce action potential but in a lower magnitude compared to normal one. V. THE RELATIONSHIP BETWEEN THE ACTION POTENTIAL AND CONTRACTION OF A CARDIAC MYOCYTE Rapid depolarization (phase 0) precedes cell shortening (contraction) Completion of repolarization occurs just before peak shortening Relaxation of the muscle takes place mainly during phase 4 of the action potential The duration of contraction usually parallels the duration of the action potential. Figure 29. Morphological characteristics of SA node cells and AV node cells (top). Bottom Left: example of a cardiac muscle which is made up of striations and myofibrils; Bottom Right: example of conduction myofibers, an example is Purkinje fiber which is larger with clearer cytoplasm. B. AUTORHYTHMIC CELL: ACTION POTENTIAL The autorhythmic cell has a different form of action potential known as slow response action potential found in the SA node and AV node. B1. PHASES OF ACTION POTENTIAL (SINO-ATRIAL NODE) Figure 28. Action potential and contraction of a cardiac myocyte The duration of contraction (violet line) usually parallels the duration of the action potential (blue line). Unlike in skeletal muscles, the contraction happens later than the action potential. VI. THE AUTORHYTHMIC CELL The first type of myocyte is the contractile cell which makes up 99% of our cells. Second type is the autorhythmic cell which makes up the other 1% Figure 30. Different phases of action potential in the SA node of the cardiac muscle. Forms 1% of the cardiac muscle fibers Phase 4: Slow depolarization due to Na+ and Ca2+ leak until threshold. Table 2. Two important functions - This phase 4 is not resting membrane potential Act as a pacemaker - Set the rhythm of because of the early/slow depolarization that is electrical excitation already happening in this phase. - It is not resting at all, instead it is going up, Found in the: depolarizing slowly until it reaches the threshold - Sinoatrial Node which will fire an action potential, activating the - Atrioventricular Node Phase 0. - Purkinje Fibers - In phase 4, the slow depolarizing action potential is Form the conductive system (conduct - Network of specialized due to entry of Na+ and Ca2+. Once it reaches the action potential) cardiac muscle fibers that threshold the Ca2+ channels will open which is provide a path for each now the Phase 0. cycle of cardiac excitation Phase 0: At threshold, rapid depolarization, Ca2+ channels to progress through the open. heart - Unlike in the rapid action potential wherein the Phase 0 is due to Na+ influx, the Phase 0 of this AP is A. AUTORHYTHMIC CELL: CHARACTERISTICS due to Ca2+ influx. Initiate action potentials Phase 3: Repolarization, K+ efflux (channels open) - Do not contribute to the contractile force of the heart - After phase 0, it has no phase 1 and 2. It proceeds to 1. Smaller than contractile cells phase 3 that is repolarization due to K+ efflux 2. Do not contain many myofibrils (similar with fast AP). Page 8 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Officially NO phase 1 or phase 2 1. Autorhythmic cells do not have stable resting membrane Have unstable resting potentials called “pacemaker potentials” potential (RMP) - Phase 4 which is not resting/slowly rising is also called the - Instead of a flat line (refer to Figure 32), the pacemaker potential. RMP keeps on moving up. The RMP, also called Use calcium influx (rather than sodium) for rising phase of the the Pacemaker potential, is the reason why the action potential cells can produce autorhythmicity. 2. Natural leakiness to Na & Ca → spontaneous and gradual depolarization B2. THE CARDIAC ACTION POTENTIAL (AP) - This keeps the slow depolarization wherein Other differences include the following: Na+ and Ca2+ are leaking into the cells making ○ The resting membrane potential (phase 4) of the it more positive. fast-response cells is considerably more negative (-90 3. Unstable resting membrane potential (pacemaker mV) than that of the slow-response cells (-60 mV). potential) ○ The slope of the upstroke (phase 0), the amplitude of 4. Gradual depolarization reaches threshold (-40 mv) → the action potential, and the overshoot (membrane spontaneous AP generation voltage positive to 0 mV) are greater in the fast-response cells than in the slow- response cells. Causes of autorhythmicity/unstable resting membrane potential: ○ In slow-response cardiac tissue, the action potential is propagated more slowly, and conduction is more likely to be blocked by Beta- blockers than in fast-response cardiac tissue Figure 33. Different causes of autorhythmicity. 1. Slow leakage of K+ out & faster leakage of Na+ in Causes slow depolarization ○ Na+ is moving in faster than K+ going out Occurs through If channels (f=funny) that open at negative membrane potentials and start closing as membrane approaches threshold potential ○ Historically, they cannot identify what causes the influx of Na+ (please refer to the graph above). They just say, “there’s a funny current that is happening”. However, studies found out that there are actually specialized Na+ Figure 31. Difference in the action potential of fast-response (top) and channels that would leak the Na+ into the cell. slow-response (bottom) cells. 2. Ca2+ channels opening as membrane approaches threshold At threshold additional Ca2+ ion channels open causing C. MECHANISMS OF AUTORHYTHMICITY more rapid depolarization The heart can automatically produce its own potential due to the ○ Ca2+ channels open further once they reach following: the threshold. These deactivate shortly after 3. Slow K+ channels open as membrane depolarizes causing an efflux of K+ and a repolarization of membrane Repolarization is due to K+ channels being open (the same with the other action potentials) VII. DIFFERENCE BETWEEN PACEMAKER APS AND THE VENTRICULAR MUSCLES APS The pacemaker cell slowly depolarizes in Phase 4 ○ no resting membrane potential - there is a constant drift towards more positive values, mediated by the "funny current" The depolarization threshold is less negative (-50 mV) Figure 32. Difference in the action potential of a sinus nodal fiber The Phase 0 depolarization is more gradual than the depolarization and a ventricular muscle fiber. of a ventricular myocyte ○ lack functional voltage-gated sodium channels Page 9 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo ○ Mediated by L-type calcium channels - open and close The rising phase of action potential is due to Ca2+ entry much more slowly. (Autorhythmic myocardium) There is no Phase 1 The repolarization is due to K+ efflux There is no Phase 2 Hyperpolarization is not possible for contractile muscle, but it is There is a steep rapid Phase 3 possible for pacemaker cell. ○ The final membrane potential at the end of Phase 3 is ○ Pacemaker cell can be hyperpolarize which means that something like -60-65 mV, slightly less negative they can go beyond their baseline by the effects of ACh (acetylcholine) ○ Parasympathetic stimulation (of pacemaker cell) will cause hyperpolarization of the AP bringing it to a more negative level which makes it harder to reach for the next threshold Duration of the autorhythmic myocardium is slightly shorter than the contractile muscle There is no refractory period for Pacemaker cell AP so they can have rapid stimulation which might be one of the factors for arrhythmia FIgure 34. The ventricular muscle action potential (blue) and the pacemaker action potential (red) Figure 35. Pacemaker action potential. The pacemaker cell slowly depolarizes. The threshold is less negative. Phase 0 is more gradual There is no phase 1 and 2 Figure 36. Action potential of a Ventricular Myocyte (top); Action potential of a Phase 3 is steep Pacemaker cell (bottom). Table 3. Comparison of Action Potentials in Ventricular Muscle and in Pacemaker Cell VIII. THE CONDUCTION SYSTEM OF THE HEART AND THEIR ACTION POTENTIALS Figure 37. Different action potentials of the conduction system of the heart. The slow response is manifested by your SA node and AV node The membrane potential of Autorhythmic myocardium is unstable Purkinje fiber fast response but may have slow response also which starts at -60 mV The events leading to action potential is the net entry of Na+ through the If channels, reinforced by Ca2+ entry until it reaches the threshold (Autorhythmic myocardium) Page 10 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo IX. EXCITABILITY AND CONDUCTIVITY: IMPULSE GENERATION AND CONDUCTION Figure 38. Electrical Pathway of the Heart: 1. Sinus node, 2. Right atrium, 3. Left atrium, 4. AV node, 5. Impulses spread through the ventricle, 6. Right ventricle, 7. Left ventricle Figure 39. Control of the autonomic nervous system showing parasympathetic fibers innervating the AV node and SA node (blue line) and sympathetic fibers Excitability – the ability of the muscles to conduct stimulus to innervating the AV node, SA node, and ventricular muscles (green line). different parts of the heart Sinoatrial (SA) node generates impulses about 75 (60- 100) A. SYMPATHETIC EFFECT ON HEART RATE times/minute Norepinephrine and Epinephrine increase If channel activity - origin of stimulation ○ Binds to ß1 adrenergic receptors which activate cAMP and - activates right atrium and left atrium and then the impulse increase If channel open time would go to the AV node Increase If channel = more sodium gets into the - right atrium contracts and stimulated earlier than the left atrium cell Atrioventricular (AV) node delays the impulse approximately 0.1 ○ Causes more rapid pacemaker potential and faster rate of second action potentials. Impulse passes from atria to ventricular via the atrioventricular more sodium gets in = faster rate of action bundle (bundle of His) potential - AV bundle splits into two pathways in the interventricular septum (bundle branches) which bifurcates to left and right bundles - Right ventricles is stimulated ahead of time then the left ventricle 1. Bundle Branches - carry the impulse toward the apex of the heart (Left and Right bundle branches) 2. Purkinje fibers - carry the impulse to the heart apex and ventricular walls. X. EXTRINSIC CONTROL OF HEART RATE: AUTONOMIC NERVOUS SYSTEM A cardiac control center in the medulla oblongata speeds up or slows down in the heart rate by the way of the autonomic nervous system branches: ○ Parasympathetic system (slows heart rate) from Vagus Figure 40. Comparison in the action potentials of normal stimulation and nerve sympathetic stimulation. ○ Sympathetic system (increases heart rate) from Sympathetic ganglia Hormones epinephrine and norepinephrine from the adrenal B. PARASYMPATHETIC EFFECT ON HEART RATE medulla also stimulate faster heart rate. Acetylcholine binds to muscarinic receptors ○ Ach: neurotransmitter for parasympathetic system ○ Increases K+ permeability and decreases Ca2+ permeability = hyperpolarizing the membrane (membrane more negative) Longer time to threshold = slower rate of action potentials Page 11 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo XI. THE ECG (ELECTROCARDIOGRAM) EKG Invented by Willem Einthoven in 1901 Prix nobel prize in 1924 Electrodes used were pails of salt solutions The patients’ extremities would be immersed to dissolve the solutions, which is now replaced by simpler electrodes Figure 41. Comparison in the action potentials of normal stimulation and parasympathetic stimulation. Table 4. Summary of the Sympathetic and Parasympathetic Activities on Heart Rate SYMPATHETIC ACTIVITY PARASYMPATHETIC ACTIVITY Increased chronotropic effects: Decreased chronotropic effects: ↑ heart rate ↓ heart rate Figure 44. Previous set-up of ECG Increased dromotropic effects: Decreased dromotropic effects: most frequently performed tests in clinical medicine ↑ conduction of APs ↓ conduction of APs a graphic recording of the electrical potentials produced by the Increased inotropic effects: Decreased inotropic effects: cardiac tissue ↑ contractility ↓ contractility recorded by applying electrodes to various locations on the body surface and connecting them to a recording apparatus Clinical Values - why do we request for an ECG? Mainly to look for: C. BAINBRIDGE (ATRIAL REFLEX): ATRIAL STRETCH, VOLUME REFLEX ○ Arrhythmia A sympathetic reflex initiated by increased blood in the atria ○ Myocardial ischemia and infarction Increase in Atrial pressure or Volume increases the HEART RATE ○ Atrial and ventricular hypertrophy Prevents damming of blood in veins, atria, and pulmonary circulation ○ Pericarditis to prevent acute pulmonary congestion ○ Determination of the effect of cardiac drugs Stretch of atria sends signals to VMC via vagal afferents (CN IX, X) to ○ Disturbances in electrolyte balance (K, Ca) increase HR and contractility ○ Evaluation of function of cardiac pacemakers Significance: We don’t want the blood to accumulate in the heart, hence the heart rate should be increased to remove the excess blood that enters the heart LIMITATIONS OF THE ECG The ECG reveals the heart rate and rhythm only during the time that the ECG is taken ○ If intermittent cardiac rhythm abnormalities are present, the ECG is likely to miss them ○ Ambulatory monitoring is needed to record transient Figure 42. Effect of Atrial Stretch on Heart Rate arrhythmias The ECG can often be normal or nearly normal in patients with undiagnosed coronary artery disease or other forms of heart disease (false negative results) Many “abnormalities” that appear on the ECG turn out to have no medical significance after a thorough evaluation is done (false positive results). A. RELATION OF CELLULAR IONIC EVENTS TO SURFACE ECG How does action potential (AP) relate to ECG? ○ AP determines electronegativity or charges measuring it from inside out (negative in, positive out), the reverse is true for ECG (negative out, positive in) ○ Extracellular charge of resting myocyte membrane is positive ○ Depolarization makes it negative ○ This difference in charge along the myocardium produces an electric field Figure 43. Effect of Vagal tone on Heart Rate. ○ The difference between two surface measurements of electric field strength is the potential difference (voltage) measured by the ECG leads. ○ Each pair of electrodes is a “lead” Page 12 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Figure 46. Different nodes, branches, and fibers of the heart. Impulses form in the SA node then transmitted to the conduction system to produce the depolarization and repolarization of the muscle cells SA node stimulates the atrial muscles AV node stimulates the ventricular muscles Figure 47. Action potentials. C. ACTION POTENTIAL AND ELECTROCARDIOGRAM (ECG) Atrial depolarization/atrial action potential activates the depolarization of the atria and will be recorded as P-wave P-wave represents atrial depolarization QRS complexes are produced by ventricular action potential T- wave represents ventricular repolarization Basic parts of ECG: 1. P-wave Figure 45. Recording the depolarization wave (A and B) and the repolarization 2. QRS complex wave (C and D) from a cardiac muscle fiber. 3. T-wave B. REVIEW OF ELECTROPHYSIOLOGY Four (4) Electrophysiologic Events Involved in the Genesis of the ECG ○ Impulse formation (SA node) – source of impulse ○ Transmission of the impulse (conduction fibers) ○ Depolarization ○ Repolarization Figure 48. Parts of the ECG. Page 13 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo Table 5. Limb leads (Placement and Vectors) Electrode Electrode placement label (color-coded) RA On the right arm, avoiding thick muscle. LA In the same location where RA was placed, but on the left arm. RL On the right leg, lateral calf muscle. LL In the same location where RL was placed, but on the left leg. Figure 49. The ECG machine with LEADS or electrodes (top) and the position of the patient during ECG recording (bottom) How to record an ECG? 1. Position the patient in supine. 2. Attach the electrodes in the chest and lower extremities. 3. Start the machine. (The result will be recorded in the recording apparatus) D. THE ECG LEADS The standard ECG/EKG has 12 leads: ○ 3 Standard limb leads – Bipolar: I,II,III leads that are attached on the extremities ○ 3 Augmented limb leads – Unipolar: aVR, aVL, aVF ○ 6 Precordial (or Chest) leads: V1,V2,V3,V4,V5,V6 leads that are attached on the chest V1 and V2 represents the septal wall V3 and V4 represents the anterior wall V5 and V6 represents the lateral wall Figure 52. Positions of the limb leads on the body. Figure 50. The Standard Limb Leads Figure 53. Representation of the limb leads. Lead I summates the difference of action potentials from right to left. It represents the left side or the lateral wall of the heart (the arrow pointing towards the left) Lead II and III represent the inferior wall of the heart aVR represents the right side Figure 51. Precordial Chest Leads. aVL represents the left side/ lateral wall of the heart Page 14 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo aVF inferior wall of the heart It has a measure of time and voltage. One small box = 0.04 sec a. Bipolar leads One big box = 0.2 sec Two electrodes placed at two different sites. How many BIG boxes make up one second? 5 boxes Register the difference in potential between these two How many BIG boxes make up 6 seconds? 30 boxes leads. It is important to know this because in measuring the heart rate b. Unipolar leads one will be utilizing these boxes. Measure the absolute electrical potential at one site Requires a reference site F. ECG TERMINOLOGIES Reference site formed by the limb leads Wave c. Precordial Leads: Placement and Vectors ○ movement away from the baseline in either a positive or V1: 4th intercostal space to the right of the sternum. Only a negative direction lead that is placed at the right. ○ P and T wave V2: 4th intercostal space to the left of the sternum. Segment V3: halfway between V2 and V4. ○ a line between wave forms V4: the left midclavicular line in the 5th intercostal space. ○ S-T segment Landmark: below the nipple Interval V5: the left anterior axillary line at the same horizontal ○ a waveform and a segment level as V4. ○ P-R interval V6: the left midaxillary line at the same horizontal level as Complex V4 and V5. ○ consists of several wave forms ○ QRS complex (made up of: Q, R, and S wave) Figure 54. Placement of Precordial Leads Figure 57. Appearance of the different waves present on the ECG recording. In most ECGs, R and S waves are present while Q wave is not, but regardless we name it as QRS complex. Q wave is a pathologic finding of an old myocardial infarction. Figure 55. Flow of current of the different Precordial Leads G. ECG WAVES AND INTERVALS What do they represent in ECG? When current flows toward red arrowheads, upward deflection ○ P wave: atrial systole occurs in ECG. ○ PR interval: physiologic delay in the AV node When current flows away from red arrowheads, downward ○ QRS complex: ventricular systole deflection occurs in ECG. ○ T wave: ventricular repolarization When current flows perpendicular to red arrows, no deflection or biphasic deflection occurs. E. THE ECG PAPER Figure 58. Representation of the different waves of intervals Figure 56. Measurement equivalence of the boxes. Page 15 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo One by one representation: 5. Conduction Through Purkinje Fibers 1. Impulse Formation in SA Node Figure 59. Initiation of the cardiac cycle normally begins with initiation of the Figure 63. Conduction time through the Purkinje system is represented by a impulse at the SA (sinoatrial) node small portion of the last part of the PR interval. 2. Atrial Depolarization = P-wave 6. Ventricular Depolarization = QRS Complex Figure 60. After the SA node fires, the resulting depolarization wave passes through the right and left atria, which produces Figure 64. The QRS complex on the EKG represents the depolarization of the the P-wave on the surface EKG and stimulates atrial contraction ventricular muscle mass. 3. Impulse Delay at the A-V Node = PR-interval 7. Plateau Phase of Repolarization = ST Segment Figure 61. The AV node slows impulse conduction, which allows time for blood to be pumped from the atria to the ventricles. Figure 65. The Plateau Phase lasts up to several hundred milliseconds, Conduction time through the AV node accounts for most of the duration of the represented by the ST segment PR interval. 8. Final Rapid (Phase 3) Repolarization = T-wave 4. Conduction Through Bundle Branches Figure 66. Repolarization of the ventricles generates a current in the body fluids Figure 62. A small portion of the last part of the PR interval is represented by and produces a T-wave. This takes place slowly, and generates a wide wave. the conduction time through the bundle branches Page 16 of 20 [PHYSIOLOGY] 1.11 CARDIOVASCULAR PHYSIOLOGY: Rhythmic Excitation of the Heart - Dr. M. Butardo H. SEQUENCE OF CARDIAC EXCITATION RELATED TO ECG The R wave (positive wave) is generated by ventricular depolarization, and its peak corresponds to the beginning of systole (yellow part) (specifically, of isovolumetric contraction). The T-wave represents ventricular repolarization, corresponds to the phase of decreased contraction (slow ejection). The peak of the T-wave correlates reasonably well with the onset of diastole, i.e. the closure of the aortic valve. This now represents the closure of the av valve and then diastole will happen (violet part) J. COMPONENTS OF AN ECG TRACING Normal values and duration Figure 67. Sequence of excitations with ECG reading How to summarize cardiac excitation in relation to ECG? ○ Atrial excitation happens before ventricular excitation so that enough blood would be filling up the ventricles. ○ Atrial excitation begins with the SA node activation. (it is not yet represented in the ECG). Then it would stimulate the atria (P-wave production). ○ Atrial depolarization corresponds to your P wave. And then once it has depolarized the atrium, it will go to the AV node. This will be represented by your PR interval. There's a delay that happens in the AV node, and then the ventricles depolarize. They are ready to contract now, this will now represent our QRS complex. And then when repolarization happens or relaxation happens that Figure 69. Normal ECG presentation. represents the T wave, which is ventricular repolarization while PR interval represents the conduction delay in the Table 6. Normal duration of wave intervals. AV node. Ventricular depolarization represented by your Wave Interval Duration (sec) QRS complex and ventricular repolarization represented P-wave < 0.12 by T wave. (