Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 concerning different areas of the heart. The shapes and sizes of the P wave, QRS complex, and T wave vary with the electrode locations. To reiterate, the ECG is not a direct record of the changes in membrane potential across individual car- diac muscle cells but is rather a measure of the cur- rents generated in the extracellular fluid by the changes occurring simultaneously in many cardiac cells. To emphasize this point, the bottom of Figure 14–20 shows the simultaneously occurring changes in membrane potential in a single ventricular cell. Because many myocardial defects alter normal im- pulse propagation, and thereby the shapes and timing of the waves, the ECG is a powerful tool for diagnos- ing certain types of heart disease. Figure 14–21 gives one example. It must be emphasized, however, that the ECG provides information concerning only the electri- cal activity of the heart. Thus, if something is wrong with the heart’s mechanical activity, but this defect does not give rise to altered electrical activity, then the ECG will not be of diagnostic value. Excitation-Contraction Coupling As described in Chapter 11, the mechanism that cou- ples excitation—an action potential in the plasma membrane of the muscle cell—and contraction is an increase in the cell’s cytosolic calcium concentration. As is true for skeletal muscle, the increase in cytosolic calcium concentration in cardiac muscle is due mainly to release of calcium from the sarcoplasmic reticulum. This calcium combines with the regulator protein tro- ponin, and cross-bridge formation between actin and myosin is initiated. But there is a difference between skeletal and car- diac muscle in the sequence of events by which the ac- tion potential leads to increased release of calcium from the sarcoplasmic reticulum. In both muscle types, the plasma-membrane action potential spreads into the interior of muscle cells via the T tubules (the lumen of each tubule is continuous with the extracellular fluid). In skeletal muscle, as we saw in Chapter 11, the action potential in the T tubules then causes the direct open- ing of calcium channels in the sarcoplasmic reticulum adjacent to the T tubules. In cardiac muscle (Figure 14–22): (1) The action potential in the T tubule opens voltage-sensitive calcium channels in the T tubule membrane itself; calcium diffuses from the extracellu- lar fluid through these channels into the cells, causing a small increase in cytosolic calcium concentration in 394 PART THREE Coordinated Body Functions 0.3 Time (s) +20 –90 +1 0 P R T Q S ECG Potential (mV)Membrane potential (mV) Ventricular action potential FIGURE 14–20 (Top) Typical electrocardiogram recorded from electrodes connecting the arms. P, atrial depolarization; QRS, ventricular depolarization; T, ventricular repolarization. (Bottom) Ventricular action potential recorded from a single ventricular muscle cell. Note the correspondence of the QRS complex with depolarization and the correspondence of the T wave with repolarization. P T P P T T P T P (b) (a) (c) T P P P P P P P P T T T + QRSQRS QRS QRSQRS T P P QRS QRS QRS QRS QRS FIGURE 14–21 Electrocardiograms from a healthy person and from two persons suffering from atrioventricular block. (a) A normal ECG. (b) Partial block. Damage to the AV node permits only one-half of the atrial impulses to be transmitted to the ventricles. Note that every second P wave is not followed by a QRS and T. (c) Complete block. There is absolutely no synchrony between atrial and ventricular electrical activities, and the ventricles are being driven by a pacemaker in the bundle of His. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 the region of the T tubules and immediately adjacent sarcoplasmic reticulum. (2) This small increase in cal- cium concentration then causes calcium to bind to calcium receptors on the external surface of the sar- coplasmic reticulum membranes. (3) These calcium- sensitive receptors contain intrinsic calcium channels, and activation of the receptors opens the channels, allowing a large net diffusion of calcium from the calcium-rich interior of the sarcoplasmic reticulum into the cytosol (this is termed “calcium-induced calcium release”). (4) It is mainly this calcium that causes the contraction. Thus, even though most of the calcium causing contraction comes from the sarcoplasmic reticulum, the process—unlike that in skeletal muscle—is de- pendent on the movement of extracellular calcium into the muscle, the calcium then acting as the signal for release of the sarcoplasmic-reticulum calcium. Contraction ends when the cytosolic calcium con- centration is restored to its original extremely low value by active transport of calcium back into the sarcoplasmic reticulum. Also, an amount of calcium equal to the small amount that had entered the cell from the extracellular fluid during excitation is trans- ported out of the cell, so that the total cellular calcium content remains constant. (The transport mechanisms involved in these movements offer an excellent review of key aspects of calcium transport described in Chap- ter 6. The transport into the sarcoplasmic reticulum is by primary active Ca-ATPase pumps; the transport across the plasma membrane is also by Ca-ATPase pumps plus Ca/Na exchangers.) As we shall see, how much cytosolic calcium con- centration increases during excitation is a major de- terminant of the strength of cardiac-muscle contrac- tion. In this regard, cardiac muscle differs importantly from skeletal muscle, in which the increase in cyto- solic calcium occurring during membrane excitation is always adequate to produce maximal “turning-on” of cross bridges by calcium binding to all troponin sites. In cardiac muscle, the amount of calcium released from the sarcoplasmic reticulum is not usually sufficient to saturate all troponin sites. Therefore, the number of ac- tive cross bridges and thus the strength of contraction can be increased still further if more calcium is released from the sarcoplasmic reticulum. Refractory Period of the Heart Ventricular muscle, unlike skeletal muscle, is incapable of any significant degree of summation of contractions, and this is a very good thing. Imagine that cardiac muscle were able to undergo a prolonged tetanic con- traction. During this period, no ventricular filling could occur since filling can occur only when the ven- tricular muscle is relaxed, and the heart would there- fore cease to function as a pump. The inability of the heart to generate tetanic con- tractions is the result of the long absolute refractory period of cardiac muscle, defined as the period dur- ing and following an action potential when an ex- citable membrane cannot be re-excited. As described in Chapter 11, the absolute refractory periods of skele- tal muscle are much shorter (1 to 2 ms) than the du- ration of contraction (20 to 100 ms), and a second con- traction can therefore be elicited before the first is over (summation of contractions). In contrast, because of the long plateau in the cardiac-muscle action potential, the absolute refractory period of cardiac muscle lasts almost as long as the contraction (250 ms), and the muscle cannot be re-excited in time to produce sum- mation (Figure 14–23). In this and previous sections, we have presented various similarities and differences between cardiac and skeletal muscle. These were summarized in Table 11–6. 395 Circulation CHAPTER FOURTEEN “Excitation” (Depolarization of plasma membrane) Opening of voltage-sensitive plasma membrane Ca 2+ channels in T tubules Flow of Ca 2+ into cytosol Flow of Ca 2+ into cytosol Ca 2+ binds to Ca 2+ receptors on the external surface of the sarcoplasmic reticulum Contraction Cytosolic Ca 2+ concentration Multiple steps Opening of Ca 2+ channels intrinsic to these receptors FIGURE 14–22 Excitation-contraction coupling in cardiac muscle. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 Mechanical Events of the Cardiac Cycle The orderly process of depolarization described in the previous sections triggers a recurring cardiac cycle of atrial and ventricular contractions and relaxations (Fig- ure 14–24). For orientation, we shall first merely name the parts of this cycle and their key events. Then we shall go through the cycle again, this time describing the pressure and volume changes that cause the events. The cycle is divided into two major phases, both named for events in the ventricles: the period of ven- tricular contraction and blood ejection, systole, fol- lowed by the period of ventricular relaxation and blood filling, diastole. At an average heart rate of 72 beats/min, each cardiac cycle lasts approximately 0.8 s, with 0.3 s in systole and 0.5 s in diastole. As illustrated in Figure 14–24, both systole and di- astole can be subdivided into two discrete periods. During the first part of systole, the ventricles are con- tracting but all valves in the heart are closed, and so no blood can be ejected. This period is termed isovol- umetric ventricular contraction because the ventricu- lar volume is constant. The ventricular walls are de- veloping tension and squeezing on the blood they enclose, raising the ventricular blood pressure, but be- cause the volume of blood in the ventricles is constant and because blood, like water, is essentially incom- pressible, the ventricular muscle fibers cannot shorten. Thus, isovolumetric ventricular contraction is analo- gous to an isometric skeletal-muscle contraction: the muscle develops tension, but does not shorten. Once the rising pressure in the ventricles exceeds that in the aorta and pulmonary trunk, the aortic and pulmonary valves open, and the ventricular ejection period of systole occurs. Blood is forced into the aorta and pulmonary trunk as the contracting ventricular muscle fibers shorten. The volume of blood ejected from each ventricle during systole is termed the stroke volume (SV). During the first part of diastole, the ventricles be- gin to relax, and the aortic and pulmonary valves close. (Physiologists and clinical cardiologists do not all agree on the dividing line between systole and diastole; as presented here, the dividing line is the point at which ventricular contraction stops and the pulmonary and aortic valves close.) At this time the AV valves are also closed. Accordingly, no blood is entering or leaving the ventricles since once again all the valves are closed. Ac- cordingly, ventricular volume is not changing, and this period is termed isovolumetric ventricular relaxation. Note then, that the only times during the cardiac cy- cle that all valves are closed are the periods of isovol- umetric ventricular contraction and relaxation. The AV valves then open, and ventricular filling occurs as blood flows in from the atria. Atrial contraction occurs at the end of diastole, after most of the ventricular fill- ing has taken place. This is an important point: The ventricle receives blood throughout most of diastole, not just when the atrium contracts. Indeed, in a per- son at rest, approximately 80 percent of ventricular fill- ing occurs before atrial contraction. This completes the basic orientation. We can now analyze, using Figure 14–25, the pressure and volume changes that occur in the left atria, left ventricle, and aorta during the cardiac cycle. Events on the right side of the heart are described later. Electrical events (ECG) and heart sounds, the latter described in a subsequent section, are at the top of the figure so that their timing can be correlated with phases of the cycle. Mid-Diastole to Late Diastole Our analysis of events in the left atrium and ventricle, and the aorta begins at the far left of Figure 14–25 with the events of mid-diastole to late diastole. The left atrium and ventricle are both relaxed, but atrial pres- sure is very slightly higher than ventricular pressure. Because of this pressure difference, the AV valve is open, and blood entering the atrium from the pul- monary veins continues on into the ventricle. To reem- phasize a point made earlier: All the valves of the heart offer very little resistance when they are open, and so only very small pressure differences across them are required to produce relatively large flows. Note that at this time—indeed, throughout all of diastole—the aor- tic valve is closed because the aortic pressure is higher than the ventricular pressure. 396 PART THREE Coordinated Body Functions +20 0 –80 Membrane potential (mV) 0 150 300 Time (ms) Refractory period Tension developed Plateau Action potential FIGURE 14–23 Relationship between membrane potential changes and contraction in a ventricular muscle cell. The refractory period lasts almost as long as the contraction. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 397 Circulation CHAPTER FOURTEEN Systole(a) (b) Blood flows out of ventricle Atrium relaxed Ventricle contracts Ventricle contractsAtrium relaxed Closed Closed Closed Open Diastole Blood flows into ventricle Atrial contraction Atrium contracts Ventricle relaxed Open ClosedClosed Closed Closed Open Ventricle relaxed Atrium relaxed Ventricle relaxed Atrium relaxed Aortic and pulmonary valves: AV valve: Aortic and pulmonary valves: AV valve: Isovolumetric ventricular contraction Isovolumetric ventricular relaxation Ventricular ejection Ventricular filling FIGURE 14–24 Divisions of the cardiac cycle: (a) systole; (b) diastole. For simplicity, only one atrium and ventricle are shown. The phases of the cycle are identical in both halves of the heart. The direction in which the pressure difference favors flow is denoted by an arrow; note, however, that flow, although favored by a pressure difference, will not actually occur if a valve prevents it. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 Throughout diastole, the aortic pressure is slowly falling because blood is moving out of the arteries and through the vascular system. In contrast, ventricular pressure is rising slightly because blood is entering the relaxed ventricle from the atrium, thereby expanding the ventricular volume. Near the end of diastole the SA node discharges, the atrium depolarizes (as signified by the P wave of the ECG) and contracts (note the rise in atrial pressure), and a small volume of blood is added to the ventricle (note the small rise in ventricular pressure and blood volume). The amount of blood in the ventricle at the end of diastole is called the end-diastolic volume (EDV). Systole From the AV node, the wave of depolarization passes into and through the ventricle (as signified by the QRS complex of the ECG), and this triggers ventricular con- traction. Remember that just before the contraction, the aortic valve was closed and the AV valve was open. As the ventricle contracts, ventricular pressure rises very rapidly, and almost immediately this pressure ex- ceeds the atrial pressure, closing the AV valve and thus preventing backflow of blood into the atrium. Since the aortic pressure still exceeds the ventricular pressure, the aortic valve remains closed, and the ventricle can- not empty despite its contraction. 398 PART THREE Coordinated Body Functions DiastoleDiastole Systole QRS P T ECG Heart sounds Aortic pressure Left ventricular pressure Left ventricular volume Position of AV Valves Phase of cardiac cycle Position of aortic and pulmonary valves Open Open 14321 Open 1 = Ventricular filling 2 = Isovolumetric ventricular contraction 3 = Ventricular ejection 4 = Isovolumetric ventricular relaxation End- systolic volume End-diastolic volume 130 65 0 50 110 1st 2d Pressure (mmHg)Left ventricular volume (ml) Left atrial pressure FIGURE 14–25 Summary of events in the left atrium, left ventricle, and aorta during the cardiac cycle. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 This brief phase of isovolumetric ventricular con- traction ends when the rapidly rising ventricular pres- sure exceeds aortic pressure. The aortic valve opens, and ventricular ejection occurs. The ventricular vol- ume curve shows that ejection is rapid at first and then tapers off. Note that the ventricle does not empty com- pletely. The amount of blood remaining after ejection is called the end-systolic volume (ESV). Thus: Stroke volume ϭ End-diastolic volume Ϫ End-systolic volume SV EDV ESV As shown in Figure 14–25, normal values for an adult at rest are stroke volume ϭ 70 ml, end-diastolic vol- ume ϭ 135 ml, and end-systolic volume ϭ 65 ml. As blood flows into the aorta, the aortic pressure rises along with the ventricular pressure. Throughout ejection, only very small pressure differences exist be- tween the ventricle and aorta because the aortic valve opening offers little resistance to flow. Note that peak ventricular and aortic pressures are reached before the end of ventricular ejection; that is, these pressures start to fall during the last part of sys- tole despite continued ventricular contraction. This is because the strength of ventricular contraction and rate of blood ejection diminish during the last part of sys- tole as shown by the ventricular volume curve. There- fore the ejection rate becomes less than the rate at which blood is leaving the aorta. Accordingly, the vol- ume and therefore the pressure in the aorta begin to decrease. Early Diastole Diastole begins as ventricular contraction and ejection stop and the ventricular muscle begins to relax (recall that the T wave of the ECG corresponds to the end of the plateau phase of ventricular action potentials— that is, to the onset of ventricular repolarization). Im- mediately, the ventricular pressure falls significantly below aortic pressure, and the aortic valve closes. However, at this time, ventricular pressure still exceeds atrial pressure, so that the AV valve also remains closed. This early diastolic phase of isovolumetric ven- tricular relaxation ends as the rapidly decreasing ven- tricular pressure falls below atrial pressure, the AV valve opens, and rapid ventricular filling begins. The ventricle’s previous contraction compressed the elastic elements of this chamber in such a way that the ventricle actually tends to recoil outward once sys- tole is over. This expansion, in turn, lowers ventricu- lar pressure more rapidly than would otherwise occur and may even create a negative (subatmospheric) pres- sure in the ventricle, which enhances filling. Thus, some energy is stored within the myocardium during contraction, and its release during the subsequent re- laxation aids filling. The fact that ventricular filling is almost complete during early diastole is of the greatest importance. It ensures that filling is not seriously impaired during pe- riods when the heart is beating very rapidly, and the duration of diastole and therefore total filling time are reduced. However, when rates of approximately 200 beats/min or more are reached, filling time does be- come inadequate, and the volume of blood pumped during each beat is decreased. The significance of this will be described in Section F. Early ventricular filling also explains why the con- duction defects that eliminate the atria as effective pumps do not seriously impair ventricular filling, at least in otherwise normal individuals at rest. This is true, for example, of atrial fibrillation, a state in which the cells of the atria contract in a completely uncoor- dinated manner and so fail to serve as effective pumps. Thus, the atrium may be conveniently viewed as merely a continuation of the large veins. Pulmonary Circulation Pressures The pressure changes in the right ventricle and pul- monary arteries (Figure 14–26) are qualitatively simi- lar to those just described for the left ventricle and aorta. There are striking quantitative differences, how- ever; typical pulmonary artery systolic and diastolic pressures are 24 and 8 mmHg, respectively, compared to systemic arterial pressures of 120 and 70 mmHg. Thus, the pulmonary circulation is a low-pressure sys- tem, for reasons to be described in a later section. This difference is clearly reflected in the ventricular archi- tecture, the right ventricular wall being much thinner 399 Circulation CHAPTER FOURTEEN 1 = Ventricular filling 2 = Isovolumetric ventricular contraction 3 = Ventricular ejection 4 = Isovolumetric ventricular relaxation 50 0 Pressure (mmHg) Time Right ventricular pressure 4312 1 Pulmonary artery pressure FIGURE 14–26 Pressures in the right ventricle and pulmonary artery during the cardiac cycle. This figure is done on the same scale as Figure 14–25 to facilitate comparison. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 than the left. Despite its lower pressure during con- traction, however, the right ventricle ejects the same amount of blood as the left over a given period of time. In other words, the stroke volumes of the two ventri- cles are identical. Heart Sounds Two sounds, termed heart sounds, stemming from car- diac contraction are normally heard through a stetho- scope placed on the chest wall. The first sound, a soft low-pitched lub, is associated with closure of the AV valves at the onset of systole and isovolumetric ven- tricular contraction (see Figure 14–24); the second sound, a louder dup, is associated with closure of the pulmonary and aortic valves at the onset of diastole and isovolumetric ventricular relaxation (see Figure 14–24). These sounds, which result from vibrations caused by the closing valves, are perfectly normal, but other sounds, known as heart murmurs, are frequently a sign of heart disease. Murmurs can be produced by blood flowing rap- idly in the usual direction through an abnormally nar- rowed valve (stenosis), by blood flowing backward through a damaged, leaky valve (insufficiency), or by blood flowing between the two atria or two ventricles via a small hole in the wall separating them. The exact timing and location of the murmur pro- vide the physician with a powerful diagnostic clue. For example, a murmur heard throughout systole sug- gests a stenotic pulmonary or aortic valve, an insuffi- cient AV valve, or a hole in the interventricular sep- tum. In contrast, a murmur heard during diastole suggests a stenotic AV valve or an insufficient pul- monary or aortic valve. The Cardiac Output The volume of blood pumped by each ventricle per minute is called the cardiac output (CO), usually ex- pressed in liters per minute. It is also the volume of blood flowing through either the systemic or the pul- monary circuit per minute. The cardiac output is determined by multiplying the heart rate (HR)—the number of beats per minute— and the stroke volume (SV)—the blood volume ejected by each ventricle with each beat: CO ϭ HR ϫ SV Thus, if each ventricle has a rate of 72 beats/min and ejects 70 ml of blood with each beat, the cardiac out- put is: CO ϭ 72 beats/min ϫ 0.07 L/beat ϭ 5.0 L/min These values are within the normal range for a resting average-sized adult. Since, by coincidence, total blood volume is also approximately 5 L, this means that es- sentially all the blood is pumped around the circuit once each minute. During periods of strenuous exer- cise in well-trained athletes, the cardiac output may reach 35 L/min; that is, the entire blood volume is pumped around the circuit seven times a minute. Even sedentary, untrained individuals can reach cardiac out- puts of 20–25 L/min during exercise. The following description of the factors that alter the two determinants of cardiac output—heart rate and stroke volume—applies in all respects to both the right and left heart since stroke volume and heart rate are the same for both under steady-state conditions. It must also be emphasized that heart rate and stroke vol- ume do not always change in the same direction. For example, as we shall see, stroke volume decreases fol- lowing blood loss while heart rate increases. These changes produce opposing effects on cardiac output. Control of Heart Rate Rhythmical beating of the heart at a rate of approxi- mately 100 beats/min will occur in the complete ab- sence of any nervous or hormonal influences on the SA node. This is, as we have seen, the inherent au- tonomous discharge rate of the SA node. The heart rate may be much lower or higher than this, however, since the SA node is normally under the constant influence of nerves and hormones. As mentioned earlier, a large number of parasym- pathetic and sympathetic postganglionic fibers end on the SA node. Activity in the parasympathetic (vagus) nerves causes the heart rate to decrease, whereas ac- tivity in the sympathetic nerves increases the heart rate. In the resting state, there is considerably more parasym- pathetic activity to the heart than sympathetic, and so the normal resting heart rate of about 70 beats/min is well below the inherent rate of 100 beats/min. Figure 14–27 illustrates how sympathetic and parasympathetic activity influences SA-node function. Sympathetic stimulation increases the slope of the pacemaker potential, causing the SA-node cells to reach threshold more rapidly and the heart rate to in- crease. Stimulation of the parasympathetics has the opposite effect—the slope of the pacemaker potential decreases, threshold is reached more slowly, and heart rate decreases. Parasympathetic stimulation also hy- perpolarizes the plasma membrane of the SA-node cells so that the pacemaker potential starts from a more negative value. How do the neurotransmitters released by the au- tonomic neurons change the slope of the potential? They mainly influence the special set of ion channels through which sodium ions move into the cell to cause the diastolic depolarization. Norepinephrine, the sym- pathetic neurotransmitter, enhances this current by 400 PART THREE Coordinated Body Functions Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 opening more of these channels, whereas acetyl- choline, the parasympathetic neurotransmitter, closes them. [This last fact is surprising since, as described earlier for synapses (Chapter 8) and motor endplates (Chapter 11), the usual effect of acetylcholine is to open, not close, channels that allow ion movement; this should reinforce the generalization that a messenger’s effect on its target cells is determined by the signal transduction pathways triggered by binding of that messenger to its receptors, pathways that can differ from target to target.] Factors other than the cardiac nerves can also alter heart rate. Epinephrine, the main hormone lib- erated from the adrenal medulla, speeds the heart by acting on the same beta-adrenergic receptors in the SA node as norepinephrine released from neurons. The heart rate is also sensitive to changes in body temperature, plasma electrolyte concentrations, hor- mones other than epinephrine, and a metabolite— adenosine—produced by myocardial cells. These factors are normally of lesser importance, however, than the cardiac nerves. Figure 14–28 summarizes the major determinants of heart rate. As stated in the previous section on innervation, sympathetic and parasympathetic neurons innervate not only the SA node but other parts of the conduct- ing system as well. Sympathetic stimulation also in- creases conduction velocity through the AV node, whereas parasympathetic stimulation decreases the rate of spread of excitation through the AV node and other portions of the conducting system. Control of Stroke Volume The second variable that determines cardiac output is stroke volume, the volume of blood ejected by each ventricle during each contraction. As stated earlier, the ventricles do not completely empty themselves of blood during contraction. Therefore, a more forceful contraction can produce an increase in stroke volume by causing greater emptying. Changes in the force of contraction can be produced by a variety of factors, but three are dominant under most physiological and pathophysiological conditions: (1) changes in the end- diastolic volume (that is, the volume of blood in the 401 Circulation CHAPTER FOURTEEN 60 0 –40 –60 Time Membrane potential (mV) a, b and c are pacemaker potentials: a = control b = during sympathetic stimulation c = during parasympathetic stimulation Threshold potential ba c FIGURE 14–27 Effects of sympathetic and parasympathetic nerve stimulation on the slope of the pacemaker potential of an SA-nodal cell. Note that parasympathetic stimulation not only reduces the slope of the pacemaker potential but also causes the membrane potential to be more negative before the pacemaker potential begins. Adapted from Hoffman and Cranefield. SA node Activity of parasympathetic nerves to heart Plasma epinephrine Activity of sympathetic nerves to heart Heart rate FIGURE 14–28 Major factors that influence heart rate. All effects are exerted upon the SA node. The figure shows how heart rate is increased; reversal of all the arrows in the boxes would illustrate how heart rate is decreased. Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill Companies, 2001 ventricles just before contraction); (2) changes in the magnitude of sympathetic nervous system input to the ventricles; and (3) afterload (that is, the arterial pres- sures against which the ventricles pump). Relationship between Ventricular End-Diastolic Vol- ume and Stroke Volume: The Frank-Starling Mech- anism The mechanical properties of cardiac muscle are the basis for an inherent mechanism for altering stroke volume: The ventricle contracts more forcefully during systole when it has been filled to a greater de- gree during diastole. In other words, all other factors being equal, the stroke volume increases as the end- diastolic volume increases, as illustrated in Figure 14–29, termed a ventricular function curve. This rela- tionship between stroke volume and end-diastolic vol- ume is known as the Frank-Starling mechanism (also called Starling’s law of the heart) in recognition of the two physiologists who identified it. What accounts for the Frank-Starling mechanism? Basically it is simply a length-tension relationship, as described for skeletal muscle in Chapter 11, in that end- diastolic volume is a major determinant of how stretched the ventricular sarcomeres are just before contraction. Thus, the greater the end-diastolic vol- ume, the greater the stretch, and the more forceful the contraction. However, a comparison of Figure 14–29 with Figure 11–25 reveals an important difference be- tween the length-tension relationship in skeletal and cardiac muscle. The normal point for cardiac muscle in a resting individual is not at its optimal length for contraction, as it is for most resting skeletal muscles, but is on the rising phase of the curve; for this reason, additional stretching of the cardiac-muscle fibers by greater filling causes increased force of contraction. The significance of the Frank-Starling mechanism is as follows: At any given heart rate, an increase in the venous return—the flow of blood from the veins into the heart—automatically forces an increase in car- diac output by increasing end-diastolic volume and hence stroke volume. One important function of this relationship is maintaining the equality of right and left cardiac outputs. Should the right heart, for exam- ple, suddenly begin to pump more blood than the left, the increased blood flow to the left ventricle would au- tomatically produce an increase in left ventricular out- put. This ensures that blood will not accumulate in the lungs. The Sympathetic Nerves Sympathetic nerves are distributed not only to the conducting system, as de- scribed earlier, but to the entire myocardium. The effect of the sympathetic mediator norepinephrine acting on beta-adrenergic receptors is to increase ventricular contractility, defined as the strength of contraction at any given end-diastolic volume. Plasma epinephrine acting on these receptors also increases myocardial contractility. Thus, the increased force of con- traction and stroke volume resulting from sympathetic- nerve stimulation or epinephrine is independent of a change in end-diastolic ventricular volume. Note that a change in contraction force due to in- creased end-diastolic volume (the Frank-Starling mechanism) does not reflect increased contractility. In- creased contractility is specifically defined as an in- creased contraction force at any given end-diastolic volume. The relationship between the Frank-Starling mech- anism and the cardiac sympathetic nerves is illustrated in Figure 14–30. The orange ventricular function curve 402 PART THREE Coordinated Body Functions 4003002001000 Ventricular end-diastolic volume (ml) Normal resting value 100 200 Stroke volume (ml) FIGURE 14–29 A ventricular function curve, which expresses the relationship between ventricular end-diastolic volume and stroke volume (the Frank-Starling mechanism). The horizontal axis could have been labeled “sarcomere length,” and the vertical “contractile force.” In other words, this is a length-tension curve, analogous to that for skeletal muscle (“see” Figure 11–25). 200 100 1000 200 300 400 Ventricular end-diastolic volume (ml) Control Sympathetic stimulation Normal resting value Stroke volume (ml) FIGURE 14–30 Effects on stroke volume of stimulating the sympathetic nerves to the heart. Stroke volume is increased at any given end-diastolic volume; that is, the sympathetic stimulation has increased ventricular contractility. [...]... any other part of the vascular system because of the huge cross-sectional area of the capillaries Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III Coordinated Body Functions © The McGraw−Hill Companies, 2001 14 Circulation Circulation CHAPTER FOURTEEN III Capillary blood flow is determined by the resistance of the arterioles supplying the capillaries and by the number... sets of tubes, the velocity of flow decreases as the sum of the cross-sectional areas of the tubes increases This is precisely the case in the cardiovascular system (Figure 14–45) The blood velocity is very great in the aorta, slows progressively in the arteries and arterioles, and then slows markedly as the blood passes through the huge cross-sectional area of the capillaries The velocity of flow then... facilitate venous return These mechanisms are the skeletal-muscle pump and the respiratory pump During skeletal-muscle contraction, the veins running through the muscle are partially compressed, which reduces their diameter and forces more blood back to the heart Now we can describe a major function of the peripheral-vein valves: When 423 Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth... cross-sectional area and flow velocity The total cross-sectional area of the small tubes is three times greater than that of the large tube Accordingly, velocity of flow is one-third as great in the small tubes Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III Coordinated Body Functions 14 Circulation © The McGraw−Hill Companies, 2001 Mean linear Total velocity cross-sectional... 14–35 Movement of blood into and out of the arteries during the cardiac cycle The lengths of the arrows denote relative quantities flowing into and out of the arteries and remaining in the arteries Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III Coordinated Body Functions 14 Circulation © The McGraw−Hill Companies, 2001 Circulation CHAPTER FOURTEEN MAP) in the cycle... progressively increases in the venules and veins because the cross-sectional area decreases To reemphasize, flow velocity is not dependent on proximity to the heart but rather on total cross-sectional area of the vessel type The huge cross-sectional area of the capillaries accounts for another important feature of capillaries: 417 Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition... only by carrier-mediated transport through the blood-brain barrier (Chapter 8) At the other end of the spectrum are liver capillaries, which have large intercellular clefts as well as large holes in the plasma membranes of the endothelial cells so that even protein molecules can readily pass across them This is very important because two of the major functions of the liver are the synthesis of plasma proteins... cleft Endothelial cell 2 Capillary lumen FIGURE 14–42 Capillary cross section There are two endothelial cells in the figure, but the nucleus of only one is seen because the other is out of the plane of section The fused-vesicle channel is part of endothelial cell 2 Adapted from Lentz clefts The endothelial cells generally contain large numbers of endocytotic and exocytotic vesicles, and sometimes these... lymphatic-vessel smooth muscle is responsive to stretch, so when there is no accumulation of interstitial fluid, and hence no entry of lymph into the lymphatics, the smooth muscle is inactive As lymph 425 Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition 4 26 III Coordinated Body Functions © The McGraw−Hill Companies, 2001 14 Circulation PART THREE Coordinated Body Functions... after ejection is the end-systolic volume, and the volume ejected is the stroke volume 405 Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition 4 06 III Coordinated Body Functions © The McGraw−Hill Companies, 2001 14 Circulation PART THREE Coordinated Body Functions III Pressure changes in the systemic and pulmonary circulations have similar patterns, but the pulmonary pressures . QUESTIONS 4 06 PART THREE Coordinated Body Functions Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill. Norepinephrine, the sym- pathetic neurotransmitter, enhances this current by 400 PART THREE Coordinated Body Functions Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth. (minor) TABLE 14 6 Effects of Autonomic Nerves on the Heart Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition III. Coordinated Body Functions 14. Circulation © The McGraw−Hill