Cardiac Physiology Heather Hale SPEP 2009 it is nearly impossible to contemplate the pumping action of the heart without being struck by its simplicity of design, its wide range of activity and functional capacity, and the staggering amount of work it performs relentlessly over the lifetime of an individual Berne and Levy, Principles of Physiology 4th ed., Elsevier Overview The heart as a pump: The heart as a pump: Functional anatomy Functional anatomy Nervous system influence Nervous system influence Effective cardiac pumping Effective cardiac pumping Action potential propagation in the heart Action potential propagation in the heart Pressure-volume relationships Pressure-volume relationships Electrocardiogram readings Electrocardiogram readings What does the heart really do? A lot!!! A lot!!! Main function: serve as a reciprocating pump that develops the necessary pressure gradients to circulate blood throughout the vasculature Main function: serve as a reciprocating pump that develops the necessary pressure gradients to circulate blood throughout the vasculature Cardiac Physiology Cardiac pump cycle How does it work? The heart is composed of two pumps in series The heart is composed of two pumps in series Right heart - Pumps blood through pulmonary circuit Right heart - Pumps blood through pulmonary circuit Left heart - Propels blood through the peripheral (systemic) circulation Left heart - Propels blood through the peripheral (systemic) circulation Both sides are composed of two chambers Both sides are composed of two chambers Atrium - smaller chamber Atrium - smaller chamber Ventricle - large chamber Ventricle - large chamber The right and left sides are not directly connected to each other, but the chambers within each side are connected The right and left sides are not directly connected to each other, but the chambers within each side are connected Blood flow through the heart Systemic blood (tissues/ muscles/organs) uses O 2 De-oxygenated blood returns to right heart Blood is pumped from right heart to lungs Gas exchange occurs Re-oxygenated blood returns to left heart Blood is pumped from left heart back to body Video: Blood flow through the heartions/content/human_heart.html Functional anatomy: right heart Receives systemic (deoxygenated) blood through vena cava Blood flow: Right atrium (tricuspid valve) Right ventricle (pulmonary valve) Pulmonary artery Lungs Functional anatomy: left heart Receives (oxygenated) blood from lungs through pulmonary vein Blood flow: Left atrium (mitral valve) Left ventricle (aortic valve) Aorta Body Functional anatomy: valves Atrioventricular valves (AV valves) Atrioventricular valves (AV valves) Present between each atrium and ventricle Present between each atrium and ventricle Tricuspid + mitral valves Tricuspid + mitral valves Semilunar valves (SL valves; outlet valves) Semilunar valves (SL valves; outlet valves) Present between ventricle and outlet Present between ventricle and outlet Pulmonary + aortic Pulmonary + aortic Open/close passively in response to pressure Open/close passively in response to pressure Valves are critical to maintain unidirectional blood flow Functional anatomy: valve defects Detected as heart murmurs Detected as heart murmurs Abnormal heart sounds (auscultations) Abnormal heart sounds (auscultations) Created by abnormal blood flow patterns Created by abnormal blood flow patterns Types of valve defects Types of valve defects Stenotic = failure to open fully (narrowing) Stenotic = failure to open fully (narrowing) Regurgitant = failure to seal upon closure Regurgitant = failure to seal upon closure These can happen at the same time! These can happen at the same time! Neural influences on heart Some intrinsic rhythmicity exists, but the heart is also influenced by the autonomic nervous system Some intrinsic rhythmicity exists, but the heart is also influenced by the autonomic nervous system Sympathetic influences: Sympathetic influences: Adrenergic receptors (respond to norepinephrine) Adrenergic receptors (respond to norepinephrine) Increases heart rate and pumping Increases heart rate and pumping Parasympathetic influences: Parasympathetic influences: Cholinergic receptors (respond to aceylcholine) Cholinergic receptors (respond to aceylcholine) Decreases heart rate and pumping Decreases heart rate and pumping Cardiac pump cycle Pumping is necessary to cyclically change blood in each chamber Pumping is necessary to cyclically change blood in each chamber Cycle is rhythmic and synchronized Cycle is rhythmic and synchronized Two major phases: Two major phases: Diastole Diastole Systole Systole Both are defined by action of the ventricle! Both are defined by action of the ventricle! Cardiac pump cycle: diastole Filling stage Filling stage Ventricular relaxation Ventricular relaxation Blood flows down pressure gradient from atria to ventricle Blood flows down pressure gradient from atria to ventricle AV valves open AV valves open Outlet valves closed Outlet valves closed Blood volume in ventricle at end of diastole = end diastolic volume (EDV) Cardiac pump cycle: systole Emptying/ejection stage Emptying/ejection stage Ventricular contraction Ventricular contraction Blood pumped from ventricles to arteries Blood pumped from ventricles to arteries AV valves closed AV valves closed Outlet valves open Outlet valves open Blood volume in ventricle at end of systole = end systolic volume (ESV) Cardiac pump cycle: stroke volume The volume of blood ejected from the heart in one pump cycle is called the stroke volume Cardiac physiology Heart rate = number of diastolic/systolic phases occurring per unit time Heart rate = number of diastolic/systolic phases occurring per unit time Cardiac output = bulk flow of blood generated by pumping action of heart Cardiac output = bulk flow of blood generated by pumping action of heart CO (mL/min) = HR (beats/min) x SV (mL/beat) Cardiac physiology Venous return (VR) = variable flow of blood entering the heart Venous return (VR) = variable flow of blood entering the heart Variable to compensate for physiological state Variable to compensate for physiological state i.e. VR during exercise i.e. VR during exercise Autoregulation: VR = CO Autoregulation: VR = CO (The stroke volume will be altered such that the heart pumps out the same volume of blood it receives during diastole) (The stroke volume will be altered such that the heart pumps out the same volume of blood it receives during diastole) Functional anatomy: conduction The heart is excited by the coordinated contraction of cardiac muscle cells The heart is excited by the coordinated contraction of cardiac muscle cells Cells act as syncitium due to gap junctions Cells act as syncitium due to gap junctions Impulse initiating concuction = action potential Impulse initiating concuction = action potential Important cardiac features: Important cardiac features: Sinoatrial node (SA node) Sinoatrial node (SA node) Atrioventricular node (AV node) Atrioventricular node (AV node) Bundle of His Bundle of His Purkinje fibers Purkinje fibers Conduction: SA node Node at junction of superior vena cava and R atrium Node at junction of superior vena cava and R atrium Function = spontaneously generates APs Function = spontaneously generates APs Intrinsic cardiac pacemaker Intrinsic cardiac pacemaker Conduction: AV node Located behind tricuspid valve Located behind tricuspid valve Function: conduction delay (critical for cardiac pumping) Function: conduction delay (critical for cardiac pumping) AP propagation: AP propagation: Slow (delay between atria + ventricles) Slow (delay between atria + ventricles) Few gap junctions Few gap junctions Less negative RMP Less negative RMP Only forward conduction! Conduction: bundle of His Muscle fibers within interventricular septum - splits into 2 branches Muscle fibers within interventricular septum - splits into 2 branches Function: conduct AP impulse throughout the R + L ventricles Function: conduct AP impulse throughout the R + L ventricles Rapid conduction occurs within msec of receiving the impulse Rapid conduction occurs within msec of receiving the impulse Conduction: purkinje fibers Fibers spread throughout endocardial surface of ventricular muscle Fibers spread throughout endocardial surface of ventricular muscle Function: to conduct AP impulse to the actual ventricular muscle mass Function: to conduct AP impulse to the actual ventricular muscle mass Very rapid conduction transmission Very rapid conduction transmission Cardiac conduction summary Cardiac conduction velocities Cardiac action potentials Cardiac muscle functions as a syncitium, with fibers separated by intercalated disks Cardiac muscle functions as a syncitium, with fibers separated by intercalated disks Depolarization spreads over entire heart Depolarization spreads over entire heart Followed by contraction of entire myocardium Followed by contraction of entire myocardium So the heart functionally behaves as one cell! Finally, the recruitment of cells to actively participate in contraction is not a regulatory event that occurs in the heart Finally, the recruitment of cells to actively participate in contraction is not a regulatory event that occurs in the heart Cardiac action potentials Two functional syncitiums: Atrial & Ventricular Two functional syncitiums: Atrial & Ventricular APs are conducted between these two (from atrial ventricular syncitium) via the AV bundle APs are conducted between these two (from atrial ventricular syncitium) via the AV bundle Spread of AP between each cardiac cell: Spread of AP between each cardiac cell: Occurs within intercalated disks Occurs within intercalated disks High in gap junctions (high electrical conductance) High in gap junctions (high electrical conductance) Cardiac ion channels Resting K + channels Fast Na channels Outward K + channels Slow Ca 2+ channels Delayed K + channels Cardiac action potentials Frequent spontaneous depolarizations occur in the SA node SA node cells control the heart rate by emitting new APs before the AV node or purkinje fibers Depolarization spreads through heart, developing unique APs at each site Ventricular action potentials Phase 0: depolarization Phase 0: depolarization Phase 1: early repolarization Phase 1: early repolarization Phase 2: Plateau Phase 2: Plateau Phase 3: terminal repolarization Phase 3: terminal repolarization Phase 4: RMP Phase 4: RMP Ventricular action potentials Phase 0: depolarization Phase 0: depolarization Spontaneous depolarization Spontaneous depolarization Threshold potential reached Threshold potential reached Fast voltage-gated Na + channels open Fast voltage-gated Na + channels open Na + channels inactivate and dont contribute to phases 1-4 Na + channels inactivate and dont contribute to phases Ventricular action potentials Phase 1: early repolarization Phase 1: early repolarization Due to transient K + channels Due to transient K + channels Open rapidly for K + efflux Open rapidly for K + efflux These actually inactivate very soon after they are activated These actually inactivate very soon after they are activated Ventricular action potentials Phase 2: plateau Phase 2: plateau Delayed K + channels open Delayed K + channels open K + efflux will repolarize K + efflux will repolarize At the same time, Ca 2+ channels are activated At the same time, Ca 2+ channels are activated Ca 2+ entry will depolarize Ca 2+ entry will depolarize K + /Ca 2+ movement works against each other to create plateau K + /Ca 2+ movement works against each other to create plateau Ventricular action potentials Phase 3: terminal reploarization Phase 3: terminal reploarization Ca 2+ channels inactivate Ca 2+ channels inactivate K + channels still open! K + channels still open! Delayed K + channels open fully and are at peak activity Delayed K + channels open fully and are at peak activity Massive K + efflux with no counteraction by Ca 2+ Massive K + efflux with no counteraction by Ca Ventricular action potentials Phase 4: resting potential Phase 4: resting potential Delayed K + channels close Delayed K + channels close Potential now generated by resting K + channels Potential now generated by resting K + channels Sets cardiac cells back to resting membrane potential to prepare for another AP Sets cardiac cells back to resting membrane potential to prepare for another AP Nodal action potentials Action potentials in the SA node Automaticity (pacemaker cells) Primarily phase 0 Phases are absent! Slow voltage-gated Ca + channels Action potentials in the AV node Action potentials in the AV node Similar to SA node Similar to SA node Conduction is slow! Conduction is slow! Significance of cardiac APs Normal rhythmic contractions of heart occur due to spontaneous SA activity Normal rhythmic contractions of heart occur due to spontaneous SA activity The heart rate (interval between beats) is determined by how long it takes cells to reach threshold level and fire an AP The heart rate (interval between beats) is determined by how long it takes cells to reach threshold level and fire an AP Neural influences from autonomic nervous system affect the rate of depolarization Neural influences from autonomic nervous system affect the rate of depolarization Cardiac Physiology Pressure-volume relationships Terms Pre-load Pre-load load on the muscle prior to contraction load on the muscle prior to contraction Muscle length determined by EDV Muscle length determined by EDV Afterload = Load muscle sees during contraction Afterload = Load muscle sees during contraction Total load = pre-load + afterload Total load = pre-load + afterload Contractility Contractility vigor of contraction forcefullness vigor of contraction forcefullness Depends on degree of Ca 2+ activation in cardiac muscle Depends on degree of Ca 2+ activation in cardiac muscle Isolated versus intact cardiac muscle Changing muscle load Increasing pre-load Increasing pre-load Increases the degree of shortening cardiac muscle is capable of Increases the degree of shortening cardiac muscle is capable of Increases the SV! Increases the SV! Increasing afterload Increasing afterload Negatively affects cardiac muscle shortening Negatively affects cardiac muscle shortening Decreases the SV! Decreases the SV! Afterload increases during pathophysiologic states such as hypertension or valve obstruction Afterload increases during pathophysiologic states such as hypertension or valve obstruction SV = EDV ESV Law of LaPlace Defines the pressure-volume relationship of the working heart Defines the pressure-volume relationship of the working heart Cardiac muscle fibers surround the ventricular wall such that changes in the fiber length is proportional to changes in the ventricular radius Cardiac muscle fibers surround the ventricular wall such that changes in the fiber length is proportional to changes in the ventricular radius Ventricular wall tension (T) depends on the intraventricular pressure (P) and radius (r) Ventricular wall tension (T) depends on the intraventricular pressure (P) and radius (r) T = P r Law of La Place Situation A: Beginning of diastole Beginning of diastole Prior to filling Prior to filling T = P r T = P r Situation B: End of diastole (EDP) End of diastole (EDP) Pre-load (after filling) Pre-load (after filling) 2T = P 2r 2T = P 2r Enlarged radius = greater tension! Enlarged radius = greater tension! Law of La Place Situation C: Beginning of contraction Beginning of contraction Prior to ejection Prior to ejection 50T = 25P 2r 50T = 25P 2r pressure from filling pressure from filling Situation D: End of systole (ESP) End of systole (ESP) 50T = 50P r 50T = 50P r radius but still lots of pressure radius but still lots of pressure Pressure-volume loops Pressure volume loops After diastolic filling = EDV develops a small pressure (EDP), which is the pre-load After filling ceases, P left ventricle > P left atrium Mitral valve closes Pressure volume loops Mitral valve closes, but blood remains in ventricle so ventricular pressure keeps rising During isovolumetric contraction, P ventricle > P aorta Pressure volume loops When P ventricle < P aorta the aortic valve closes Relaxation begins and pressure within the ventricle drops The cycle starts over with filling when P ventricle < P atrium Altered P-V loops pre-load = SV afterload = SV Altered P-V loops contractility = SV Venous Return VR = volume of blood brought back to heart VR = volume of blood brought back to heart Through autoregulation, the heart adapts to any influences on blood volume such that Through autoregulation, the heart adapts to any influences on blood volume such that VR = CO The Frank-Starling law of the heart Output values for R + L ventricles are maintained in balance Output values for R + L ventricles are maintained in balance Venous pools Peripheral venous pool - 60% circulating blood is in veins of systemic organs Peripheral venous pool - 60% circulating blood is in veins of systemic organs Central venous pool - blood in the great veins of the thorax and right atrium Central venous pool - blood in the great veins of the thorax and right atrium Frank Starling mechanism: Frank Starling mechanism: Peripheral veins constrict Peripheral veins constrict Blood into central pool Blood into central pool central venous pressure central venous pressure cardiac filling cardiac filling Blood flow through venous pools Blood flow rate (Q) between central and venous pools determined by driving pressure (dP) and resistance (R) within the veins:Q = dP/R Blood flow rate (Q) between central and venous pools determined by driving pressure (dP) and resistance (R) within the veins:Q = dP/R P PV = peripheral venous pool pressure P PV = peripheral venous pool pressure P CV = central venous pool pressure P CV = central venous pool pressure Venous return curves Pressure between peripheral & central Pressure between peripheral & central Curve represents venous return at varying P PV Curve represents venous return at varying P PV When pressures are balanced and P CV = P PV (7mmHg) then VR = 0 When pressures are balanced and P CV = P PV (7mmHg) then VR = 0 Shows how P CV affects VR when other variables are constant! Venous return curves If P CV while P PV stays the same, then increase driving force for blood flow and increase VR If P CV while P PV stays the same, then increase driving force for blood flow and increase VR When lower P CV below 0 mmHg, veins in thorax collapse and restricts any further increase in VR When lower P CV below 0 mmHg, veins in thorax collapse and restricts any further increase in VR Venous return curves Slope of curve determined by resistance of vessels Slope of curve determined by resistance of vessels If lower resistance, then raise VR curve (steeper) because get more VR for given pressure difference If lower resistance, then raise VR curve (steeper) because get more VR for given pressure difference Increasing vascular resistance will lessen the steepness of the VR curve Increasing vascular resistance will lessen the steepness of the VR curve Effects of P PV on VR curve When P PV (increased blood volume or sympathetic stimulation) then shift upward + right When P PV (increased blood volume or sympathetic stimulation) then shift upward + right If P PV (extreme blood loss or decreased sympathetic tone) then shift downward + left If P PV (extreme blood loss or decreased sympathetic tone) then shift downward + left Effects of P CV on CO & VR If P CV = 2 mmHg, then CO = VR = 5L/min If P CV = 2 mmHg, then CO = VR = 5L/min Effects of P CV on CO & VR If P CV to 0, then CO to ~2 L/min and VR to 7 L/min Large increase in VR would increase the central venous pool volume When V CV then P CV to 2 mmHg Effects of P CV on CO & VR If P CV to 4, then CO to ~7 L/min and VR to 3 L/min Large decrease in VR would decrease the central venous pool volume When V CV then P CV to 2 mmHg Effects of P CV on CO & VR P CV is always driven to equilibrium in order to maintain the Starling mechanism of CO=VR Cardiac Physiology Integrated cardiac cycle Integrated cycle: diastole Begins with closure of aortic valve and opening of AV valves Begins with closure of aortic valve and opening of AV valves Blood enters ventricle, but some is also still filling the atrium through the vena cava so the pressures in both chambers rise in unison = diastasis Blood enters ventricle, but some is also still filling the atrium through the vena cava so the pressures in both chambers rise in unison = diastasis Integrated cycle: systole Follows ventricular filling Follows ventricular filling Correlates to ECG P-wave Correlates to ECG P-wave As pressure, more volume forced into ventricle As pressure, more volume forced into ventricle This is important when HR because there is less time for passive ventricle filling, and need to receive as much blood as possible! This is important when HR because there is less time for passive ventricle filling, and need to receive as much blood as possible! Integrated cycle: atrial contraction Begins as mitral valves close and left ventriclar pressure exceeds aortic pressure Begins as mitral valves close and left ventriclar pressure exceeds aortic pressure Correlates to ECG R-wave Correlates to ECG R-wave This is the first heart sound (as mitral valve snaps shut) This is the first heart sound (as mitral valve snaps shut) Rapid ejection of blood from ventricles as aortic valve opens Rapid ejection of blood from ventricles as aortic valve opens Integrated cycle: relaxation As blood leaves ventricle, the pressure drops to below the aortic pressure and aortic valve closes As blood leaves ventricle, the pressure drops to below the aortic pressure and aortic valve closes Correlates to ECG R-wave Correlates to ECG R-wave Second heart sound (as aortic valve snaps shut) Second heart sound (as aortic valve snaps shut) Relaxation of ventricle walls as cycle begins again Relaxation of ventricle walls as cycle begins again Integrated cycle: pressures Diastolic pressure (P D ) = lowest pressure in aorta after diastolic filling Diastolic pressure (P D ) = lowest pressure in aorta after diastolic filling Systolic pressure (P S ) = peak pressure achieved during systolic ejection Systolic pressure (P S ) = peak pressure achieved during systolic ejection Pulse pressure (P P ) = pressure difference during phases Pulse pressure (P P ) = pressure difference during phases P P = P S P D Integrated cycle: heart sounds First heart sound = start of systole as AV valves close First heart sound = start of systole as AV valves close Second heart sound = during ventricular relaxation as semilunar valves close Second heart sound = during ventricular relaxation as semilunar valves close Failure of valves to open/ close fully causes abnormal heart sounds - can clinically detect valve defects! Failure of valves to open/ close fully causes abnormal heart sounds - can clinically detect valve defects! Right heart cycles Same excitation system as left heart (SA node) with similar mechanical events Same excitation system as left heart (SA node) with similar mechanical events Systole + diastole synchronized with left heart Systole + diastole synchronized with left heart Valves open + close in unison Valves open + close in unison Pump same amount of blood per unit time Pump same amount of blood per unit time Major difference is the pressure levels - the R heart has much lower pressures since pulmonary resistance is very low! Cardiac Physiology Electrocardiogram (ECG) ECG basics Cardiac cells generate a current due to the electrical potential and ion flow Cardiac cells generate a current due to the electrical potential and ion flow Currents are detected by electrodes that are connected at two extremities: Currents are detected by electrodes that are connected at two extremities: Electrodes are paired - positive + negative Electrodes are paired - positive + negative These are called leads These are called leads Direction of current flow gives the lead axis Direction of current flow gives the lead axis ECG: Lead axes Current directionDeflection on ECG (-) to (+) upward (+) to (-) downward oblique angle smaller peak oblique angle smaller peak perpendicular none perpendicular none ECG: Lead axes ECG: leads A pair of leads detects current flow Different leads are applied to detect current in 12 different directions Leads are groups as bipolar or augmented or chest ECG: bipolar leads Standard leads I, II, and III Standard leads I, II, and III Lead I: (+) left arm(-) right arm Lead I: (+) left arm(-) right arm Lead II: (+) left leg(-) right arm Lead II: (+) left leg(-) right arm Lead III:(+) left leg(-) left arm Lead III:(+) left leg(-) left arm ECG: augmented limb leads Negative pole is midpoint of two leads Negative pole is midpoint of two leads aVR: (+) right arm(-) left arm/foot aVR: (+) right arm(-) left arm/foot aVL: (+) left arm(-) right arm/foot aVL: (+) left arm(-) right arm/foot aVF:(+) left foot(-) right/left arms aVF:(+) left foot(-) right/left arms ECG: chest (precordial) leads Leads on horizontal plane (not frontal plane) Leads on horizontal plane (not frontal plane) (-) lead has common ground connecting alle three limbs (-) lead has common ground connecting alle three limbs (+) lead is on chest and is represented as V1-V6 (+) lead is on chest and is represented as V1-V6 ECG sequence: P wave Depolarization starts at SA node within the superior right side of the heart Depolarization starts at SA node within the superior right side of the heart Atria are activated and current moves downward and to the left Atria are activated and current moves downward and to the left Small deflection is seen on the ECG Small deflection is seen on the ECG The P wave deflection is small because the atria have thin walls (small muscle mass) and thus conduct very little electrical activity ECG sequence: P wave ECG sequence: Q wave First part of ventricle begins to depolarize First part of ventricle begins to depolarize Current flows from left to right and slightly downward Current flows from left to right and slightly downward Lead I generates small negative deflection (Q wave) Lead I generates small negative deflection (Q wave) There is also a small positive deflection due to the aVF lead (start of R wave) There is also a small positive deflection due to the aVF lead (start of R wave) ECG sequence: Q wave ECG sequence: R/S waves Current flows down ventricle to apex of heart Current flows down ventricle to apex of heart The net electrical field is downward The net electrical field is downward Both leads generate a positive upward deflection (R wave) Both leads generate a positive upward deflection (R wave) At the purkinje fibers, the aVF lead generates the S wave (a small downward deflection) At the purkinje fibers, the aVF lead generates the S wave (a small downward deflection) There is a lot of electrical potential in the ventricle, so the readout on the ECG is a large peak! ECG sequence: R/S wave Information obtained from ECG Heart rate / rhythm Heart rate / rhythm Normal is 60-80bpm Normal is 60-80bpm Tachycardia results in > 100bpm Tachycardia results in > 100bpm Bradycardia results in less than < 60bpm Bradycardia results in less than < 60bpm Disorders of conduction system Disorders of conduction system Myocardial or percardial disorders Myocardial or percardial disorders Ischemia Ischemia Infarction Infarction Integrated cardiac cycle graphs Pressure volume loop summary