L3. Cardiac Cycle.pdf

03 Physiology Dr. Asad Zeidan Cardiac Cycle 14th January 2020 Abdelaziz M Tawengi Amira Gamal 1 This document resorted to: 1. “Cardiac Cycle” Lecture Slides, Dr. Asad Zeidan. 2. “Guyton and Hall TB of Medical Physiology 13th Edition” Chapter 9. 3. “Ganong’s Review of Medical Physiology 24th Edition”...

03 Physiology Dr. Asad Zeidan Cardiac Cycle 14th January 2020 Abdelaziz M Tawengi Amira Gamal 1 This document resorted to: 1. “Cardiac Cycle” Lecture Slides, Dr. Asad Zeidan. 2. “Guyton and Hall TB of Medical Physiology 13th Edition” Chapter 9. 3. “Ganong’s Review of Medical Physiology 24th Edition” Chapter 30. Introduction Hello again. Welcome to physiology, will try to explain in detail which may seem long, but with enough ‘recaps’ that we included, you will not have to read everything next time. There is much more to learn and much of the mentioned is simplified, but you can dig deeper! What seems additional now, will be essential later; so understand. Do not memorize without any logic. Good luck! What to Expect We will start with an outline of the phases of cardiac action potential and excitationcontraction coupling. Next, we shall describe the phases of normal cardiac cycle. Of importance, will be the comparison of pressures and volumes during the normal cardiac cycle (pressure volume loop). Then, we will attempt to illustrate the changes in cardiac cycle in common cardiovascular abnormalities. Finally, we will describe the mechanisms of normal heart sounds, define and classify cardiac murmurs. Cardiac Muscle We already know that the heart contains a special type of muscles, which is the cardiac muscle. In fact, it has 3 types of cardiac muscle: ① atrial muscle, ② ventricular muscle, and specialized ③ excitatory and conductive muscle fibers. For simplicity, we can group them into: Types of Cardiac Muscles Contractile Cells - Account for 99% of heart tissue. - Made of Atrial and Ventricular cardiac muscles. - Activated (to contract) by change in the potential. - They contract similar to skeletal muscles, but for a prolonged duration of contraction. - They produce contractions; generting force. Conducting System (pacemaker or excitatory system) - Specialized conductive fibers; nodes and internodal pathways. - They contract weakly, but, they exhibit either automatic rhythmical electrical discharge in the form of action potentials or conduction of the action potentials through the heart. - That is they initiate and distribute electrical activity. Unlike skeletal muscles, if you remove your heart, it would still contract spontaneously. The earlier receives the action potential through the nervous system, whereas, the later has its own pacemaker. While the nervous system regulates the heart rate. - Controls and coordinates the rhythmical beating of the heart. Relevant Anatomy of the Cardiac Muscle Histologically, the cardiac muscle fibers arranged in a latticework (‫ﻜﺔ‬L‫ﺸﺎ‬I‫ ;)ﻣ‬with the fibers dividing, recombining, and then spreading again. Recall that the cardiac and skeletal muscles are striated. Further, actin and myosin filaments lie side by side and slide during contraction in the same manner as occurs in skeletal muscle. The dark areas crossing the cardiac muscle fibers vertically are the intercalated disks; they are cell membranes separating individual cardiac muscle cells (myocytes) yet allowing many individual cells to be connected in series and in parallel with one another forming muscle fibers. At each ID the cell membranes fuse to form permeable “communicating” junctions, gap junctions, that allow rapid diffusion of ions from one cardiac muscle cell to the other. The significance is, when one cell becomes excited, the action potential rapidly spreads throughout all the adjacent cells. 2 On a bigger scale, the conducting system (as we shall see shortly) ensures the depolarization of the atria first and then follow the depolarization the ventricles, each as a single unit. Additionally, the intercalated disks have desmosomes which are intercellular junctions that provide strong adhesion between cells, enabling muscle cells to resist the mechanical stress associated with the stretching and contraction during the cardiac cycle. Cardiac Action Potential The total action potential of a ventricular muscle fiber is ≈ 105 mV. During depolarization, the intracellular potential rises from ≈ −85 mV, between beats (no contraction) to ≈ +20 mV, during each beat. After the initial peak, the membrane remains depolarized for about 0.2 second, exhibiting a plateau, followed by repolarization. The presence of the plateau causes ventricular contraction to last 15X longer than that of the skeletal muscle. What Causes the Long Action Potential and the Plateau in Cardiac Muscle? The action potential of a skeletal muscle is caused almost entirely by the sudden opening of large numbers of fast Na+ channels that allow a tremendous number of Na+ to enter the skeletal muscle fiber from the extracellular fluid. These channels remain open for only a few thousandths of a second and close. At the end of this closure, repolarization occurs, and the action potential is over within another thousandth of a second or so. In cardiac muscle, the action potential is caused by opening of two types of channels: ① the same voltage-activated fast Na+ channels and ② L-type Ca2+ channels* (slow Ca2+ channels), which are also called calcium-sodium channels. These are slower to open and remain open for several tenths of a second. During this time, a large quantity of both Ca2+ and Na+ flow into the cardiac muscle fiber maintaining a prolonged period of depolarization (the plateau). Secondly, immediately after the onset of the action potential, the permeability of the cardiac muscle membrane for K+ decreases ≈ fivefold. Consequently, the outflux of positively charged K+ is decreased, delaying the return to resting potential. When the slow L-type Ca2+ channels do close and the influx of calcium and sodium ions stops, the membrane permeability for K+ increases rapidly; returning the membrane potential to its resting potential immediately (as we shall discuss). Phases of Cardiac Muscle Action Potential The aim of this lecture is to understand the basic mechanism of systole and diastole, leaving the heart rate (hence the pacemaker) for subsequent ones. We will look into the action potential of the contractile cells and not of the autorhythmic cells. Phase 0 (depolarization), fast Na+ channels open. When the cardiac cell is stimulated through an action potential and depolarizes, the membrane potential becomes more positive. This happens as voltage-gated sodium channels open and permit rapid Na+ influx. The membrane potential reaches about +20 mV before the Na+ channels close. Phase 1 (initial repolarization), fast Na+ channels close. As Na+ channels close, the cell begins to repolarize, while some K+ leave the cell through open K+ channels. *L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the 3 high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. Phase 2 (plateau), Ca2+ channels open and fast K+ channels close. Following the brief initial repolarization, the action potential then plateaus -as explained earlier- due to: ① increased Ca2+ permeability (positive calcium influxes) as the DHP channels allow Ca2+ influx and ② decreased K+ permeability (positive potassium outflux decreases). To illustrate, the voltage-gated Ca2+ channels were opening slowly during phases 0 and 1, and K+ permeability was decreasing. Phase 3 (rapid repolarization), Ca2+ channels close and slow K+ channels open. The closure of Ca2+ channels and the increased K+ permeability (allowing rapid positive outflux), ends the plateau and returns the cell membrane potential to its resting level. Phase 4 (resting membrane potential) averages about −90 mV. As we mentioned earlier, Ca2+ are essential for muscle contraction. In fact, if you isolate atrial muscle cells and ventricular ones, you would notice that more Ca2+ are needed to induce the ventricular cells to contract. This correlates with the need for stronger contraction to eject the blood from either ventricle. You must have concluded that the plateau of ventricular muscle cells should be longer! You can watch: ‘Cardiac Muscle’ by AK Lectures for a review Now, explain the process on your own, but referring to the permeability of each ion rather than the state of channels. Excitation-Contraction Coupling The term “excitation-contraction coupling” refers to the mechanism by which the action potential causes the myofibrils of muscle to contract. As is true for a skeletal muscle, when an action potential passes over the cardiac muscle cell membrane, the action potential spreads to the interior of the cardiac muscle fiber along the membranes of the transverse (T) tubules. The T tubule action potential in turn, act on the membranes of the longitudinal sarcoplasmic tubules to cause release of calcium ions into the muscle sarcoplasm (cytoplasm) from the sarcoplasmic reticulum (SR). In another few thousandths of a second, these Ca2+ diffuse into the myofibrils and catalyze the chemical reactions that promote sliding of the actin and myosin filaments along one another, which produces the muscle contraction. 4 Thus far, this mechanism of excitation-contraction coupling is the same as that for a skeletal muscle, but there is a second effect that is quite different. In addition to the calcium ions that are released into the sarcoplasm ① from the sarcoplasmic reticulum (≈80%), calcium ions also diffuse into the sarcoplasm ② from the T tubules themselves (≈20%) at the time of the action potential, as the voltage-dependent calcium channels in the membrane of the T tubule open (see figure on right). Calcium ions entering the cell then activate calcium release channels (ryanodine receptor channels), in the sarcoplasmic reticulum membrane, triggering the release of calcium into the sarcoplasm, to interact with troponin to initiate cross-bridge formation and contraction by a similar mechanism to that of the skeletal muscles. The mechanism of the second release of calcium ions through the ryanodine receptor channels is known as calcium-induce calcium release. DHPR Notice that we are concerned with the ‘cardiovascular’ aspect of the whole talk. The details of muscle action and components are of different concern. Ca2+ influx is affected by á epinephrine and â ACh Without the calcium from the T tubules, the strength of cardiac muscle contraction would be reduced considerably as the SR of cardiac muscles does not store enough calcium ions to provide a full contraction. Plus, the T tubules of cardiac muscle has 5X the diameter of the skeletal muscle tubules, meaning 25X the volume. The strength of contraction of cardiac muscle depends to a great extent on the concentration of calcium ions in the extracellular fluids. Remember, a heart placed in a calcium-free solution will quickly stop beating. This is because the T tubules pass directly through the cardiac muscle cell membrane and into the extracellular spaces surrounding the cells, allowing the same extracellular fluid in interstitium to permeate through the T tubules. Consequently, the quantity of Ca2+ in the T tubule system (i.e., the availability of Ca2+ to cause cardiac muscle contraction) depends to a great extent on the extracellular fluid calcium ion concentration. Remember the Ca2+ percentages we mentioned earlier? We need the 20% from the T tubules, to release the remaining 80% from the SR. In contrast, the strength of skeletal muscle contraction is hardly affected by moderate changes in extracellular fluid calcium concentration because skeletal muscle contraction is caused almost entirely by Ca2+ released from the SR (≈100%) inside the skeletal muscle fiber. You would expect the SR to be located closer to the sarcolemma (‘cell membrane’) in this case for an action potential-induced calcium release. Add to your information, the smooth muscle contraction uses 90% Ca2+ from extracellular compartment, while only 10% from the SR. Towards Relaxation At the end of the plateau of a cardiac action potential, the influx of 2+ Ca is suddenly cut off, and Ca2+ in the sarcoplasm are rapidly pumped back out of the muscle fibers into both the SR and the T tubule– extracellular fluid space. Transport of calcium against concentration gradient into the SR is achieved with the help of a calcium–adenosine triphosphatase (ATPase) Na+/K+ ATPase pump can be inhibited by Digitalis & Ouabain; indirectly, â Na+ /Ca2+ exchange Ü á [Ca2+]in This can be used to treat weak heart contractions. 5 pump. If this pump is blocked, then over time Ca2+ concentration will be depleted, until there is not enough in the SR to power the muscle contraction. Calcium ions are also removed from the cell by a Na+/Ca2+ exchanger which is an antiporter (1 Ca2+ out 3 Na+ in). Recall that this is a secondary active transport; without the ion concentration gradient achieved by the Na+/K+ ATPase pump, it will not work. So, the sodium entering the cell during this exchange is then transported out of the cell by the Na+/K+ ATPase pump. Initiation and Conduction of an Impulse Each impulse is initiated by a spontaneous generation of an action potential in the SA node. Notice that the membrane potential generating the impulse within the conducting system is different from that we have discussed. The SA node is located in the superior lateral wall of the right atrium, near the opening of the superior vena cava, and the action potential travels rapidly through both atria via the AV node and then through the AV bundle (bundle of His) into the ventricles. This arrangement of the conducting system allows a delay of more than 0.1 second during passage of the cardiac impulse from the atria into the ventricles, which allows the atria to contract ahead of the ventricles, thereby pumping blood into the ventricles before the strong ventricular contraction begins. Thus, the atria act as primer pumps for the ventricles, and the ventricles in turn provide the major source of power for moving blood through the body’s vascular system. Cardiac Cycle Let us get more scientific than just saying a ‘heartbeat’. The cardiac cycle refers to all or any of the cardiac events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. Diastole and Systole. The cardiac cycle consists of a phase of relaxation called diastole, during which the heart fills with blood, followed by a phase of contraction called systole. The total duration of the cardiac cycle, including systole and diastole, is the reciprocal (‫ )ﻣﻘﻠﻮب اﻟﻌﺪد‬of the heart rate. For example, if heart rate is 72 beats/min, the duration of the cardiac cycle is $ %&' , which is, 0.833 second per beat. () *+,Before explaining the cardiac cycle, we have to consider two events to set the scene: Atrial Systole. The Atria Act as Primer Pumps for the Ventricles Atrial systole refers to the contraction of the heart muscle of the left and right atria. Blood normally flows continually from the great veins into the atria; about 80% of the blood flows directly (passively, mainly under the pressure gradient*) through the atria into the ventricles even before the atria contract as the AV valves are open. Then normally the atria contract at the same time, causing an additional 20% filling of the ventricles. However, the heart can continue to operate without this extra 20% because it normally has the capability of pumping 300 to 400% more blood than is required. Therefore, when the atria fail to function, the difference is may be noticed only upon exercising as acute signs of heart failure, especially shortness of breath. *We did not mention gravity as a main player; as our heart still beat efficiently when we 6 are upside down Ventricular Systole The ventricles were filling with blood during ventricular diastole preceded by the atrial systole to fill the ventricle. Next is ventricular systole, during which large amounts of blood start to accumulate in the right and left atria because of the closed AV valves. Therefore, as soon as systole is over and the ventricular pressures fall again, the moderately increased pressures that have developed in the atria during ventricular systole (atrial diastole) immediately push the AV valves open and allow blood to flow rapidly into the ventricles. This period of ventricular diastole is called the period of rapid filling of the ventricles, lasting for about the first third of diastole. During the middle third of diastole, only a small amount of blood normally flows into the ventricles through the atria directly after returning through veins. During the last third of diastole, the atria contract and give an additional thrust to the inflow of blood into the ventricles. From now on: - Systole and diastole refer to the left ventricle unless said otherwise. - The phases of the cycle are identical in both halves of the heart. - The cardiac cycle is a ‘cycle’ where atria and ventricles are in a particular phase; atria are in systole then ventricles are in diastole and so on. Let us consider the cardiac cycle Ventricular Systole 1. Isovolumetric Ventricular Contraction Say the ventricles are filled with blood and are about to start contraction (systole). Immediately after ventricular contraction begins, the ventricular pressure rises abruptly causing the AV valves to close. At that point in time, AV valves and semilunar (aortic and pulmonary) valves are closed and the ventricles are closed chambers. The ventricle starts to build up pressure while the volume remains the same. Therefore, during this period, contraction is occurring in the ventricles, but no emptying occurs. This period is called the period of isovolumic or isometric contraction, meaning that cardiac muscle tension is increasing but little or no shortening of the muscle fibers is occurring. 2. Ejection Phase Once the ventricular pressure is high enough (slightly above 80 mmHg in LV and slightly above 8 mmHg in RV), it pushes the semilunar valves open against the pressures in the aorta and pulmonary artery. Immediately, blood begins to pour out of the ventricles. Approximately 60% of the blood in the ventricle at the end of diastole is ejected during systole; about 70% of this portion flows out during the first third of the ejection period, with the remaining 30% emptying during the next two thirds. Therefore, the first third is called the period of rapid ejection, and the last two thirds are called the period of slow ejection. 7 Ventricular Diastole 3. Isovolumetric Relaxation At the end of systole, ventricular relaxation begins suddenly allowing both the right and left intraventricular pressures to decrease rapidly. The elevated pressures in the distended large arteries that have just been filled with blood from the contracted ventricles immediately push blood back toward the ventricles, which snaps the semilunar valves closed. The ventricular muscle continues to relax, even though the ventricular volume does not change, giving rise to the period of isovolumic or isometric relaxation. During this period, the intraventricular pressures rapidly decrease back to their low diastolic levels. 4. Ventricular Filling: Early Diastole Once the intraventricular pressure drops below that of the atria, the AV valves open and initiate the ventricular filling. As we mentioned blood start to flow passively into the ventricles even before the atria contract. 5. Ventricular Filling: Atrial Systole As we mentioned, the atria start to contract, causing the additional 20% filling of the ventricles. ‘The Cardiac Cycle - McGraw Hill’ End-Diastolic Volume, End-Systolic Volume, and Stroke Volume During diastole, normal filling of the ventricles increases the volume of each ventricle to about 110-120 mL, which is called the end diastolic volume. Then, as the ventricles empty during systole, the volume decreases about 70 mL, which is called the stroke volume. The remaining volume in each ventricle, about 40-50 mL, is the end-systolic volume. The fraction of the end-diastolic volume that is ejected is called the ejection fraction— usually equal to about 0.6 (or 60%). ESV + SV = EDV 50mL + 70mL = 120mL When the heart contracts strongly, the end-systolic volume may decrease to as little as 10 to 20 mL (‫ﺔ أ„†… ﺗﺨˆج‬p‫ﻤ‬n ƒ ‚ ‫ﺔ أﻗﻞ ﻣﻦ اﻟﺪم ﺗ|~} ﻌ‬p‫ﻤ‬n). Conversely, when large amounts of blood flow into the ventricles during diastole, the end-diastolic volumes can increase up to 180 mL in the healthy heart (‫ﺔ أ„†… ﺗﺨˆج‬p‫ﻤ‬n ƒ ‚ ‫ﺔ أ„†… ﻣﻦ اﻟﺪم ﺗﺪﺧﻞ ﻌ‬p‫ﻤ‬n). By both increasing the end-diastolic volume and decreasing the end-systolic volume, the stroke volume can be increased to more than double that which is normal. Preload and Afterload ① Preload: The degree of tension (stretch) on the muscle when it begins to contract (at the end of ventricular filling during diastole, maximum filling). As the relaxed ventricle fills during diastole, the walls are stretched and the sarcomeres elongated. Sarcomere length is estimated by the volume of the ventricle as each shape has a conserved surface-area-tovolume ratio. This is because we cannot measure it directly without dissection. Preload is 8 estimated from end-diastolic pressure once the ventricle has become filled (mmHg). However, for simplicity think of preload as the volume of blood. More ventricular filling = More preload Preload increases in: hypervolemia (e.g., over transfusion, polycythemia), regurgitation (leaking) of cardiac valves (e.g., leaking [or regurgitant] aortic valve would allow some back flow to left ventricle during diastole) and heart failure. ② Afterload: The load (pressure) against which the muscle exerts its contractile force. The afterload of the left ventricle is the pressure in the aorta leading from the ventricle (sometimes it is loosely considered to be the resistance in the circulation rather than the pressure.) As aortic pressure increases, the afterload increases on the left ventricle. á Afterload = á Cardiac workload Afterload increases in: hypertension and vasoconstriction. Curves & More Curves Events of the cardiac cycle for the left side of the heart. The top three curves in order show the pressure changes in the aorta, left ventricle, and left atrium. The fourth curve depicts the changes in left ventricular volume, the fifth depicts the electrocardiogram, and the sixth depicts a phonocardiogram, which is a recording of the sounds produced by the heart—mainly by the heart valves—as it pumps. As it is extremely important to understand the events behind each curve, we will try to discuss them as we explained most of the mechanisms already. The graph is explained twice every curve alone, then all together. First Curve: Aortic Pressure Curve As the aortic valve is forced open after the isovolumetric contraction, blood immediately flows out of the ventricle into the aorta and then into the systemic distribution arteries. The entry of blood into the arteries during systole causes the walls of these arteries to stretch and the pressure to increase to about 120 mmHg. Next, at the end of systole, after the left ventricle stops ejecting blood and the aortic valve closes, the elastic walls of the arteries maintain a high pressure in the arteries, even during diastole. An incisura (little increase) occurs in the aortic pressure curve when the aortic valve closes. This is caused by a short period of backward flow of blood immediately before closure of the valve, followed by sudden cessation of the backflow. After the aortic valve has closed, the pressure in the aorta decreases slowly throughout diastole because the blood stored in the distended elastic arteries flows continually through the peripheral vessels back to the veins. 9 Second Curve: Atrial pressure Curve We will isolate this curve to inspect it more clearly. If we consider the atrial pressure alone during the cardiac cycle, then three minor pressure elevations, called the a, c, and v atrial pressure waves. The a wave is caused by atrial contraction. Ordinarily, the right atrial pressure increases 4-6 mmHg during atrial contraction, and the left atrial pressure increases about 7-8 mmHg. Next, the c wave occurs when the ventricles begin to contract, partly due to slight backflow of blood into the atria at the onset of ventricular contraction but mainly due to bulging of the AV valves backward toward the atria. As the ventricle contracts for ejection, the atria continue its diastole as seen in x wave as a further reduction in pressure. The v wave occurs toward the end of ventricular contraction as the atria slowly and passively fill with blood from the veins while the AV valves are closed. Then, when ventricular contraction is over, the AV valves open, allowing this stored atrial blood to flow rapidly into the ventricles and causing the y wave. Third curve: Ventricular Pressure Curve When the LV contracts during the isovolumetric contraction, the ventricular pressure increases rapidly until the aortic valve opens. That happens once the ventricular pressure surpasses the aortic pressure to allow ejection. Notice that with the opening of the aortic valve, the aorta and the left ventricle maintained almost the same pressure as they are a ‘unified’ chamber by then. 70% of the ejected blood leaves within the first third of the systole and the pressure starts to drop. Once it drops below the aortic pressure, the aortic valve closes for isovolumetric relaxation by the backflow of blood on the semilunar valves. As it drops below the atrial pressure, the AV valves open and ventricular filling start again. Upon atrial systole, an initial increase in the pressure occurs as due to the forced release of blood from the atria. For the Fourth curve: Ventricular Volume Curve, it would be easy to follow as we have already considered the cardiac cycle and the other curve. Just follow the order of events! Notice, during the isovolumetric phase of systole and diastole the volume is constant! The Fifth Curve: Electrocardiogram, will be taken in subsequent lectures and the Sixth curve: Phonocardiogram* will elaborated upon when we consider heart sounds. *A phonocardiogram (PCG) is a plot of recording of the sounds and murmurs made by the heart with 10 the help of the machine called the phonocardiograph ▸ ▸ ▸ ▸ ▸ ▸ ▸ ▸ ▸ Atrial Systole To start an impulse, the SA node reaches threshold and fires. Impulse spreads throughout the atria (P wave on the ECG). The atrial contraction starts; á in atrial pressure curve (a wave). More blood is squeezed into the ventricle; á in ventricular pressure curve. Throughout atrial contraction, atrial pressure slightly exceeds ventricular pressure, so the AV valve remains open. The blood fills the ventricle until the EDV (110-120 mL). Isovolumetric Ventricular Contraction The impulse passes through the AV node, and the conduction system to excite the ventricles. Ventricular contraction; ventricular pressure immediately exceeds atrial pressure; AV valves close. Ventricular pressure continues to increase, before it exceeds aortic pressure to open the aortic valve. As no blood enters or leaves the ventricle, the ventricular chamber remains at constant volume, and the muscle fibers remain at constant length. Ventricular Ejection ▸ When ventricular pressure exceeds aortic pressure; the aortic valve is forced open; ejection of blood begins. ▸ Blood is forced into the aorta faster than blood is draining off into the smaller vessels at the other end (out of the aorta); rise of aortic pressure curve. ▸ Ventricular volume decreases substantially as blood is rapidly pumped out. ▸ The ESV (about 50 mL) and the SV (around 70 mL). Isovolumetric Ventricular Relaxation ▸ When the aortic valve closes due to aortic backflow, but the AV valve is not yet open, because ventricular pressure still exceeds atrial pressure. ▸ All valves are once again closed for a brief period of time and no blood can enter or leave the ventricle. ▸ As the ventricle continues to relax; the pressure steadily falls. Rapid Ventricular Filling (Early Diastole) ▸ When the ventricular pressure falls below the atrial pressure, the AV valves open, and ventricular filling occurs once again. ▸ It occurs rapidly at first because of the increased atrial pressure due to venous return. ▸ The atrial pressure starts to fall. ▸ During late ventricular diastole, when ventricular filling is proceeding very slowly, the SA node fires again, and the cardiac cycle stars over. 11 The Volume-Pressure Diagram On the right, this loop is called the ‘VolumePressure Diagram’ or the ‘Pressure-Volume Loop’ of the cardiac cycle for normal function of the left ventricle. Notice that on the X-axis is the ventricular volume (mL), and on the Y-axis is the left interventricular pressure (mmHg). It is divided into 4 phases: III IV II Phase I: Period of filling. It begins at a ventricular volume of I about 50 mL (ESV left from last heartbeat) and a diastolic pressure of 2-3 mmHg. As venous blood flows into the ventricle from the left atrium, the ventricular volume normally increases to about 120 mL (EDV). Therefore, the volume-pressure diagram during phase I extends along the line from point A to point B with the volume increasing to 120 mL and the diastolic pressure rising to about 5-7 mmHg. Phase II: Period of isovolumetric contraction. We said, the volume of the ventricle does not change because all valves are closed. However, the pressure inside the ventricle increases to equal the pressure in the aorta, at a pressure value of about 80 mmHg. Phase III: Period of ejection. During ejection, the systolic pressure rises even higher because of still more contraction of the ventricle. At the same time, the volume of the ventricle decreases because the aortic valve has now opened and blood flows out of the ventricle into the aorta. The decrease in blood is equal to that of the ejected blood; stroke volume. Phase IV: Period of isovolumic relaxation. At the end of the period of ejection (point D), the aortic valve closes as the ventricular pressure falls back to the diastolic pressure level, without any change in volume. Thus, the ventricle returns to its starting point, with about 50 mL of blood left in the ventricle and at an atrial pressure of 2-3 mmHg. Heart Sounds Sixth curve: Phonocardiogram (see below) Using a stethoscope, one cannot hear the opening of the valves because this is a relatively slow and makes no noise. When the valves close, the veins of the valves and the surrounding fluids vibrate under the influence of sudden pressure changes, giving off sound that travels in all directions through the chest. So, the heart sounds are made by: 1. The closure of the heart valves. 2. The acceleration and deceleration or vibration the adjacent walls of the heart and major vessels around the heart due to the blood flow. There are 4 heart sounds, of which the first two are normally heard during each cardiac cycle. While one may hear the 3rd or 4th heart sounds in certain conditions. 12 ▸ S1: 1st Sound (Lub) Closure of the AV valves. The vibration pitch is low, sound is louder and relatively longer-lasting. Indicates the beginning of ventricular systole. ▸ S2: 2nd Sound (Dup) Closure of semilunar valves Short, sharp snap because these valves close rapidly, and the surroundings vibrate for a short period. Indicates the end of ventricular systole. Now, you must have noticed on the graph above that systole occurs after the first sound, while the second heart sound indicates the beginning of diastole. Also, it is clear that systole (30%) is shorter in duration compared to diastole (70%) for a given normal cardiac cycle. For the curious ones, the third and fourth heart sound are both heard during diastole. The 3rd sound is heard at the beginning of the middle diastole. It is benign in youth, some athletes, and sometimes in pregnancy. However, if it re-emerges later in life it may signal cardiac problems. For simplicity, it is caused by the rushing of blood back and forth between the walls of the ventricles as being released from the atria. The 4th sound is generally abnormal in young adults and children. It can almost never be heard using the stethoscope, but still can be recorded using the phonocardiogram. The sound occurs when the atria contracts causing an inrush of blood into the ventricles, which initiates vibrations similar of S3. It is pathological in some cases, usually in a case of a failing or hypertrophic left ventricle like in systemic hypertension, where the sound is caused by the turbulence as blood is forced into a stiff ventricle, immediately before S1 in late diastole. (Physiological) Splitting of Second Heart Sound We said that the 2nd heart sound is caused by the closure of the aortic valve (name this part of the sound as A2) and the closure of the pulmonary valve (P2, again, meaning this is the ‘pulmonary valve’ component of S2). During inspiration, the chest wall expands causing the intrathoracic pressure to drop (more -ve, acts like a vacuum), which allows the lungs to fill with air and expand. At the same time, this induces an increase in the venous return from the body into the right atrium via the superior and inferior venae cavae, then into the right ventricle by increasing the pressure gradient (‘vacuum’ pulls the blood from the body into the right side of the heart). Simultaneously, there is a reduction in blood volume returning from the lungs into the left atrium (the blood wants to stay in the lungs because of the vacuum surrounding the lungs, and pulmonary vascular resistance is lower because the lungs are expanded). Since there is an increase in blood volume in the right ventricle during inspiration, the pulmonary valve (P2) stays open longer during ventricular systole due to an increase in ventricular emptying time, whereas the aortic valve (A2) closes slightly earlier due to a reduction in left ventricular volume and ventricular emptying time. Thus, the P2 component is delayed relative to that of the A2 component. 13 During expiration, the chest wall collapses and increases the intrathoracic pressure (less -ve). Therefore, there is no longer an increase in blood return to the right ventricle versus the left ventricle and the right ventricle volume is no longer increased. This allows the pulmonary valve to close earlier such that it overlaps the closing of the aortic valve, and the split is no longer heard. In precise, the pulmonic valve usually closes slightly after the aortic valve for S2 splitting to happen. Notice on the figure to the right that S2 is unified during expiration, yet it is split into two components (A2 and P2) during inspiration. Two mechanisms of splitting are involved: 1. Inspiration-induced decrease in intrathoracic pressure and increased filling of the right side of the heart. This extra volume will require little extra time for ejection. 2. Inspiration-induced decrease in pulmonary vascular resistance, which transiently reduces pulmonary artery pressure, contributing to increased ejection time. Cardiac Cycle: Association With Heart Sounds ▸ Normally, only S1 and S2 are heard with a stethoscope. S3 and S4 are detectable by phonocardiogram and rarely S4 is heard in normal individuals. ▸ S3 occurs during transition between rapid filling and slow filling of ventricle. ▸ S4 is caused by oscillations of the ventricles during atrial contraction. Murmurs Abnormal heart sounds produced with excessive degree of turbulence of blood flow in the heart chambers. They occur when there is an abnormality of the cardiac valves (e.g., stenosis which is an abnormal narrowing). Murmurs could be functional (physiologic murmur) and is considered as benign (innocent murmur), or pathologic resulting from various problems (e.g., narrowing or leaking of valves, or presence of abnormal shunts). Heart murmurs are most frequently categorized by timing (there are 6 more classification criteria), into systolic heart murmurs, diastolic heart murmurs and continuous murmurs. ▸ Systolic murmurs: Majority of murmurs are systolic, usually early in systole and disturb the end of S1. Physicians focus on the end of S1 for soft systolic murmurs. 1. Murmurs of aortic stenosis 2. Murmurs of mitral insufficiency (regurgitation, ‘leaky’ valves) ▸ Diastolic murmurs: Very rare, low frequency, low intensity and best identified with the bell of the stethoscope. 1. Murmurs of aortic insufficiency (regurgitation) 2. Murmurs of mitral stenosis ▸ Continuous murmurs: Common, but less than systolic, typically associated with a Patent ductus arteriosus (PDA). Don’t hesitate to contact Abdelaziz M Tawengi/ Amira Gamal regarding any clarification, 14 concern or suggestion!