PCIE Me ein sync) ‘Component Function Heart Ata Chambers through which blood flows from veins to ventricles, Atrial contraction adds to Ventricular filling b {snot essential for it. Ventrcles (Chambers whose contractions produce the pressures that drive blood through the pulmonary and systemic vascular systems and back to the hea. Vascular sytem Arteries Low-resistance tubes conducting blood tothe various organs with litle los in pressure. They also act as pressure reservoirs for maintaining blood flow during ventricular relaxation Atterioles ‘Major sites of resistance to flow: responsible for regulating the patern of blood-flow distribution to the variou ‘organs; participate in the regulation of arterial blood pressure. Capillaries Major sites of nutrient, gas, metabolic end product, and fluid exchange between blood and tissues. Venules Capacitance vessels that ae sites of migration of leukocytes from the blood into tissues during inflammation and infection Veins Low-resistance, high-capacitance vessels carrying blood back to the hear. Their capacity for blood is adjust facilitate this flow. Blood Plasma Liquid portion of blood that contains dissolved nutrients, ions, wastes, gases, and other substances. Its composition equilibrates with that of the interstitial fluid atthe capillaries. calls Includes erythrocytes that function mainly in gas transport, leukocytes that function in immune defenses, and platelets (ell fragments) for blood clotting, ‘omponents of the Circulatory System TL The key components of the circulatory system are the heart blood vessels, and blood I, Plasma isthe liquid component of blood: it contains proteins (albumias, globulins, and fibrinogen), nutrients, metabolic end ‘products, hormones, and inorganie electrolytes LL, Plasma proteins, synthesized by the liver, have many functions with the bloodstream, such as exerting osmotic pressure for absorption of incerstialfhuid and participating in the clotting reaction, IV. The blood cells, wich are suspended in plasma, include erythrocytes, leukoeytes, and platelets. V. Erythrocytes, which make up mote than 99% of blood cells, ‘contain hemoglobin, an oxygen-binding protein. Oxygen binds the izon in hemeglobi a. Erythrocytes are produced in the bone marrow and destroyed in the spleen and lives, ». Iron, folic acid, and vitamin B,, are essential fr erythrocyte Torrmation, «. The hormone erythrepoietin, which is produced by the kidney in response to low oxygen supply, timlates erythrocyte differentiation and production by the bone marrow, VI. The leukocytes include neutrophils, eosinophils, basophils, monocytes, and lymphocytes, VIL, Platelets are cell fragments essential for blood clotting, 'VIIL. Blood cells ate descended from stem cells in the bone marrow. Hematopoietic growth factors contol their production. IX. The circulatory system consists of two circuits: the pulmonary irculation—from the right ventziele to the lungs and then to the left atrium—and the systemic circulation—from the left ve te all peripheral organs and tissues and then tothe right ati X. Arteries carry blood away from the heart, and veins earty b toward the heart 4 Inthe systemic circuit, the large artery leaving the left si of the heart is the aorta, and the large veins emptying int ght side ofthe heastaze the superior vena cava aad inte vena cava. The analogous vessels in the pulmonary circu are the pulmonary trunk (leading tothe pulmonary arter and the four pulmonary veins. b. The microcirculation consists of the vessels between art and veins: the arterioles, capillaries, and venules. ressure, Flow, and Resistance 1. Flow between two points in the circulatory system is direct proportional tothe pressure difference between those point inversely proportional to the resistance. IL Resistance is directly proportional tothe viscosity of a fluid to the length of the tube. Itis inversely proportional tothe fe power ofthe tube's radius, which isthe major variable cont changes in resistance and, therefore, blood flow to each org 1. Give average values for total blood volume, erythrocyte votun plasma volume, and hematocrit 2. What are the different classes of plasma proteins, and which the most abundant? 3. Which solute is found in the highest concentration in plasma? Cudiovasula Physiology“Summarize the production, life span, and destruction oF erythrocytes, 5. What are the routes of ion gain, loss, and distribution? How is iron recycled when erythrocytes are destroyed? 6, Describe the contol of erythropoietin secretion anc the effect of, this hormone 7. State the relative proportions of exythrocytes and leukocytes in blood, 8. What is the oxygen status of arterial and venous blood inthe systemic vereus the pulmonary circulation? 9. State the formula relating flow, pressure difference, and resistance. 10. What are the three determinants of resistance? LL. Which determinant of resistance is varied physiologically to alter blood flow? 12, How does variation in hematocrit influence the hemodynamics of blood flow? 13, Trace the path ofa red blood ceil through the entice circulatory system, naming all structures and vessel types it flows throug, beginning and ending in a capillary ofthe left big oe. ECTIC Pomerat ood circulatory system ood vessels heart ardiovascular system vascular system 2.1 Components of the Circulatory System Ibumins ‘bone marrow sorta balk flow series capillaries erioles defensins vin cosinophils asophils erythrocytes ilieubin erythropoiesis ECTION B 42.3 Anatomy [The heart is a muscular organ enclosed in a protective fibrou: ac, the pericardium, and located in the chest (Figure 12.9), fibrous layer is also closely affixed to the heart and is called th epicardium. The extremely narrow space between the pericar+ fdium and the epicardium is filled with a watery fluid that serve a Tubricant as the heart moves within the sac, The wall of the heart, the myocardium, is composed pri marily of cardiac muscle cells, The inner surface of the cardi shambers, as well as the inner wall of all blood vessels i Fined by thin layer of cells known as endothelial cells, or endothelium. ‘ns ted ext, the han be i divided io ight an left halves, each consisting of an atrium and a ventricle. The t ventricles are separated by a muscular wall, the interventricula eptum. Located between the atrium and ventricle in each hal of the heart are the one-way atrioventricular (AV) valves, jwhich permit blood to flow from atrium to ventricle but not yackward from ventricle to atrium. The right AV valve is called the tricuspid valve because it has three fibrous flaps, or cusp: (Figure 12.10), The left AV valve has two flaps and is therefor ‘alled the bicuspid valve. Its resemblance to a bishop's headgeat sm Chapter 12 yAATOpOIRT eWFOpITS itn plasma Fibrinogen plasm proteins oli acid platelets :med elements portal system Jobulins pulmonary arteries hematocrit pulmonary cireulation hematopoietic growth factors pulmonazy trunk IGE) pulmonary veins hemoglobin reticulocyte inferior vena cava serum trinsic factor superior vena cava leukocytes systemic cictlation lymphocytes transferrin ymacrophages veins vegakaryocytes ventricle ierocirculation venules nonoeyies vitamin By fnultipotent hematopoietic stem cells 2.2 Pressure, Flow, and Resistance hemodynamics resistance (R) sydrostatic pressure viscosity oiseulle's law Sarena at PETIT 2.1 Components of the Circulatory System emia malaria hemochromatosis pernicious anemia ron deficiency polyeythem on-deficiency anemia sickle-cell disease (a “‘mitre") has earned the left AV valve another commonly use ame, mitral valve. “The opening and closing of the AV valves are passive pro- esses resulting from pressure differences across the valves! hen the blood pressure in an atrium is greater than in the cor esponding ventricle, the valve is pushed open and blood flow: from atrium to ventricle, In contrast, when a contracting ventric pchieves an internal pressure greater than that in its connectet rium, the AV valve between them is forced closed. Therefore, 1ood does not normally move back into the atria but is forced int the pulmonary trunk from the right ventricle and into the aort rom the left ventricle ‘To prevent the AV valves from being pushed up and openit ackward into the atria when the ventricles are contracting (a con- ition called prolapse), the valves are fastened to muscular pro- jections (papillary muscles) of the ventricular walls by fibrous strands (chordae tendineae). The papillary muscles do not open close the valves, They act only to limit the valves’ movement id prevent the backward flow of blood. Injury and disease of these tendons or muscles can lead to valve prolapse. ‘The openings of the right ventricle into the pulmonary trunk fnd_of the left ventricle into the aorta also contain valves. thdRight pulmonary artery Sup Right pulmonary veins Interatial septum ight atrium Right av (neuspia) valve ‘Chordae tendinese Right ventricle (BPI) Figure 12.9 Diagrammatic section ofthe heart, The arrow pulmonary and aortic valves, respectively (see Figures 129 an 2.10). These valves are also referred to asthe semilunar valves, lo the half-moon shape of the cusps. These valves allow blood t nto the arteries during ventricular contraction but prevent blood foi pts ing vet ike the AV valves, they actin a passive manner. Whether they ar spen or closed depends upon the pressure differences across them. Another important point concerning the heart valves is hat, when open, they offer very little resistance to flow. Con- sequently, very small pressure differences across them produc large flows. In disease states, however, a valve may become nar: rowed or not open fully so that it offers a high resistance to flow -ven when open. In such a state, the contracting cardiac chambe fnust produce an unusually high pressure to cause flow acros ne valve ‘There are no valves atthe entrances of the superior and infe or venae cavae (singular, vena cava) into the right atrium, and of he pulmonary veins into the left atrium. However, atrial contract yumps very litle blood back into the veins because atrial contrac ion constrcts their sites of entry into the atria, greatly increasin he resistance to backflow. (Actually, a little blood is ejected ba to the veins, and this accounts for the venous pulse that can ofte ¢ seen in the neck veins when the atria are contracting) Figure 12.11 summarizes the path of blood flow throug the entire circulatory system. [Cardiac Muscle fost of the heart consists of specialized muscle cells with amaz- ing resiliency and stamina. The cardiac muscle cells of the myo- i ed in layers that are tightly bound togeth meer ores and aims Aorta Let pulmonary ane Lett pulmonary Pulmonary trunk Left atrium Let foiuspie AV valve Aortic emitunar vave Let ventricle Papilary muscle Interventieular septum Myocareium Epeareium Pericardial ticispace Pulmonary Pesicarium indicfte the direction of blood flow. completely encircle the blood-filled chambers. When the wa chamber contract, they come together like a fist squee7 uid-filled balloon and exert pressure on the blood they en inlike skeletal muscle cells, which can be rested for prok yeriods and only a fraction of which are activated in a uuscle during most contractions, every heart cell contracts rery beat of the heart. Beating about once every second, c juscle cells may contract almost 3 billion times in an averag ;pan without resting! Remarkably, despite this enormous joad, the human heart has a limited ability to replace its m is, It is thought that only about 1% of heart muscle cel placed per year. In other ways, cardiac muscle is similar to smooth skeletal muscle, It is an electrically excitable tissue that cor emical energy stored in the bonds of ATP into force gener: ction potentials propagate along cell membranes, Ca” the cytosol, and the cycling of force-generating cross-bridj tivated. Some details of the cellular structure and funct ardiac muscle were discussed in Chapter 9 Approximately 1% of cardiac cells do not function in ction but have specialized features that are essential for n heart excitation. These cells constitute a network known : conducting system of the heart and are in electrical contac cardiac muscle cells via gap junctions. The conducting 5 nitiates the heartbeat and helps spread an action potential r ¢broughout the heart, Innervation The heart receives arich supply of sympathet xasympathetic nerve fiers, the latter contained in the vagus n Cudiovasula PhysiologyLe AV oicuspig) valve Right AV (vicuspic) valve Openings to ‘coronary arteries ‘ore seminar valve Pulmonary “seminar valve (BPI Figure 12.10 Superior view of the heart with the atria removed, showing the heatt valves. The left AV valve is often called the mitral valve, Notice that the coronary arteries that perfuse the ‘myocardium exit the heart just outside the aortic valve, ‘entire heart and release norepinephrine, whereas the parasympathetic fibers terminate mainly on special cells found inthe atria and release ‘primarily acetylcholine. The receptors for norepinephrine on cardiac ‘muscle ate mainly beta-adrenergic. Although not discussed in detail in this chapter, there are subtypes of beta-adrenergic receptors on target tissue that vary in their anatomic location and affinity for ‘catecholamines (¢ee Table 6.11), The hormone epinephrine, from the adrenal medulla, binds to the same receptors as norepinephrine and ‘exerts the same actions on the heart, The receptors for acetylcholine are of the muscarinic type, Details about the autonomic nervous system and its receptors were discussed in Chapter 6, Blood Supply The blood being pumped through the heart chambers does not exchange nutrients and metabolic end products ‘with the myocardial cells. They like the cells of all other organs, receive their blood supply via arteries that branch from the aorta. ‘The arteries supplying the myocardium are the coronary arteries, aund the blood flowing through them is the coronary blood flow, ‘The coronary arteries exit from behind the aortic valve cusps in the very first part of the aorta (Gee Figure 12.10) and lead to fa branching network of small arteries, arterioles, capillaries, ‘venules, and vein similar to those in other organs. Most of the cardiac veins drain into a single large vein, the coronary sinus, ‘which empties into the right atrium, 3m Chapter 12 1 Pulmonary arteries Pulmonary arterioles Ccaplanies oflungs Pulmonary venules 1 is } Venae cavae GBPIR) Figure 12.11 Path of blood tow through the entire ciuculatory system, The structures witha the colored box ate located in he heart, PHYSIOLOGICAL INQUIRY 1 How would this diagram be different if it included systemic portal vessel? Answer can be found at end of chapter. Parasympathetic ‘Sympathetic Vagus nerves ‘Thoraeie spinal ies Norepinephrine pinepitine © Bloodstream Figure 12.12 Autonomic innervation of heart. Neurons shown eprescat postganglionic neurons inthe pathways. M = muscarinicype acetylcholine receptor: = beta-adrenergic receptor12.4 Heartbeat Coordination jump blood separately—but simultaneously—into the systemi ind pulmonary vessels. Efficient pumping of blood requires that he atria contract first, followed almost immediately by the ven- icles, Contraction of cardiac muscle, like that of skeletal muscl JJasma membrane. Gap junctions interconnect myocardial cell ind allow action potentials to spread from one cell to another, xcitation ofall cardiac cells. This initial depolarization normally (SA) node, located in the right atrium near the entrant spreads from the SA node throughout the atria and then into an¢ he path of spread of excitation? (2) How does the SA node initia wn action potential? We will deal initially with the first questi snd then return to the second question in the next section, Sequence of Excitation [The SA node is normally the pacemaker for the entire hear. Is lepolarization generates the action potential that leads to depolar: ation of all other cardiac muscle cells. As we will see late, elec ical excitation of the heart is coupled with contraction of cardiac puscle. Therefore, the discharge rate of the SA node determine ne heart rate, the number of times the heart contracts per minute, Dhroughout the myocardium, passing from cell to cell by way of ap junctions, Depolarization first spreads through the muscl left atria contract at essentially the same time, {Phe heart is a dual pump in thatthe left and right sides of the heart ind many smooth muscles, is triggered by depolarization of the {Phe initial excitation of one cardiac cell eventually results in the wises in a small group of conducting-system cells called the the superior vena cava (Figure 12.13). The action potential then, fhroughout the ventricles. This raises two questions: (1) What is The action potential initiated in the SA node spreads ells of the atria, with conduction rapid enough that the right and Superior Atvavertcuer node ieee Bundle ofhis Shoat! nose Internod pathaay Right Right bundle branch Right ventricle Purkinje fibers Inferior. Interventicula Left bundle septum branch (BPI Figure 12.13 Conducting system ofthe heart shown in yellow). The queda the son pot he vein aoe competed sng tn Gee gue 12 igure 1219, which cits of mdied caine els ha font ty bot ce en jr cece sssane, Ti nk ewer at depue Lentil elation saporono! ending Sindh attenuata (AV) nde ett th tse Ft at Te tn ft nce in om eS node tothe AV ade ugh intermodal pt Avia exctation ticular exctation Venta rolaat t Tf if 1 Beains complet eo Complete sAnoce Av node Kalai fection ~ na na) me Time Time Time Time Figure 12.14 Sequence of cardiac excitation, The yellow dot the signal lepram lor denotes areas that are depolarized, The electrocardiogram monitors Cudiovasula PhysiologyFe AV node isan elongated sractare with @ particulary Tapor ‘ant characteristic: The propagation of action potentials through rhe AV node is relatively slow (requiring approximately 0.1 se) This delay allows atrial contraction to be completed before ven cular excitation occurs ‘After the AV node has become excited, the action poten ial propagates down the interventricular septum, This path yay has conducting-system fibers called the bundle of Hi (pronounced “hiss’), ot atrioventricular bundle. The AV nod nd the bundle of His constitute the only electrical connectio tween the atria and the ventricles. Except for this pathway’ he aria are separated from the ventricles by a layer of noncon lucting connective tissue ‘Within the interventricular septum, the bundle of His divide sto right and left bundle branches, which separate at the botton apex) of the heart and enter the walls of both ventricles, Thes athways are composed of Purkinje fibers, which are large fiameter, rapidly conducting cells connected by low-resistanc ap jantions, The branching network of Purkinje fibers conduc ¢ action potential rapidly to myocytes throughout the ventricles. ‘The rapid conduction along the Purkinje fibers and the dif fuse distribution of these fibers cause depolarization of right an ft ventricular cells to occur nearly simultaneously and ensun single coordinated contraction. Actually. though, depolarization ind contraction do begin slightly calir inthe apex ofthe vent es and then spread upward. The result is an efficient contacto hat moves blood toward the ext valves, like squeezing a tube o -othpaste from the bottom up ‘ardiac Action Potentials and Excitation if the SA Node [The mechanism by which action potentials are conducted along che membranes of heart cells is similar to that of other excitabl issues like neurons and skeletal muscle cells. As was described i chapters 6 and 9, it involves the controlled exchange of material ons) across cellular membranes, which is one of the general prin- ples of physiology introduced in Chapter 1, However, different yypes of heart cells express unique combinations of ion channel that produce different action potential shapes. In this way, they ar specialized for particular roles in the spread of excitation througl 1 heart. yocardial Cell Action Potentials Figure 12.154 llustrates an idealized ventricular myocardial cell action potential The changes in plasma membrane permeability that underlie ita own in Figure 12.15b. As in skeletal muscle cells and neurons, the resting membrane is much more permeable to K” than to Na’ Therefore, the resting membrane potential is much closer to t equilibrium potential (-90 mV) than to the Na* equilibriun tential (460 mV). Similarly, the depolarizing phase of th ction potential is de mainly o the opening of voltage-gated Na shannels. Sodium ion entry depolarizes the cell and sustains th opening of more Na* channels in positive feedback fashion, ‘Also, asin skeletal muscle cells and neurons, the increase fa permeability is very transient because the Na” channels inae vate quickly, However, unlike other excitable tissues, the reduc son in Na* permeability in cardiac muscle is not accompanie: y immediate repolarization of the membrane to resting level @ Transient kext "Ca? enters and K* exit (Pioteau) at enters 50 (Depolarzaion) (Repolarzston) Membrane potential (nv) Time (see) Figure 12.15 (@ Membrane potential recording from a veotrcula muscle cell. Labels indicate Key ionic movements in each phase. () Simultancously measured permeabilities (P) to K’, Na*, and Ca* during the action potential of (. Several subtypes of K* channels contribute to Px: PHYSIOLOGICAL INQUIRY 1 During the plateau of an action potential, the current due to ‘outward K* movernent is nearly equal tothe current due to inward Ca°* movement. Despite this, the membrane permeability to Ca" is much greater How can the currents be similar despite ‘the permeability difference? Answer can be found at end of chapter Rather, there is a partial repolarization caused by a special class transiently open K* channels, and then the membrane remain jepolarized at a plateau of about 0 mV (see Figure 12.15a) for 4 rolonged period. The reasons for this continued depolarization wre (1) K* permeability declines below the resting value due tq the closure of the K* channels that were open in the resting state hand (2) a large increase in the cell membrane permeability to Ca \ccurs, This second mechanism does not occur in skeletal muscle, ithe explanation for it fll 376 Chapter 12Tnayocardial cells, membrane depolarization causes vollage- sated Ca” channels i the plasma membrane to open, which result 2 a flow of Ca” ions down their electrochemical gradient into the, ll. These channels open much more slowly than do Na* chan ils, and, because they remain open for a prolonged period, the re often referred to as Letype Ca channels (L. = long lasting) These channels are also called dihydropyridine (DH) channels cause they are modified versions of the DHP receptors that func fon as voltage sensors in excitation-contraction coupling of skel- etal muscle (ee Figure 9.12). The flow of positive calcium ions inta ne cell just balances the flow of positive potassium ions out of th ll and keeps the membrane depolarized at the plateau value Ulimately, repolarization does occur due to the eventual inactivation of the L-type Ca”* channels and the opening ot snother subtype of K* channels. These K* channels ate simila Jo the ones described in neurons and skeletal muscle; they open i response to depolarization (but after a delay) and close once the "current has repolarized the membrane to negative values. The action potentials of atrial muscle cells are similar i Shape to those just described for ventricular cells, but the duratio oftheir plateau phase is shorter. Vodal Cell Action Potentials There areimportan difference: ctwen action potentials of cardiac muscle cells and those in nodal lls of the conducting system, Figure 12.16a illustrates the action tential of a cell from the SA node, Note that the SA. node cell foes not have a steady resting potential but, instead, undergoe slow depolarization. This gradual depolarization is known ag pacemaker potential; it brings the membrane potential t reshold, at which point an action potential occurs. ‘Three ion channel mechanisms, which are shown i Figure 12.16b, contribute to the pacemaker potential. The first i progressive reduction in K* permeability. The K* channels that ppened during the repolarization phase of the previous action poten al gradually close due to the membrane’s return to negative poten als. Second, pacemaker cells have a unique set of channels that like most voltage-gated ion channels, open when the membrand tential is at negative values. These nonspecific cation channels onduct mainly an inward, depolarizing, Na* current and, beca pf their unusual gating behavior, have been termed “funy, Fatype channels also known as the hyperpolarization-activated elie nucleotide-gated [HCN] channels). The third pacemaker hhannel isa type of Ca" channel that opens only briefly but com ributes inward Ca" current and an important final depolasizin ost to the pacemaker potential, These channels are called T-ty ‘a? channels (T = transient). Although SA node and AV no. ction potentials are basically similar in shape, the pacemaker cur rents of SA node cells bring them to threshold more rapidly tha WV node cells, which is why SA node cells normally initiate actio tentials and determine the pace of the heart. Once the pacemaker mechanisms have brought a nodal cel Jo threshold, an action potential occurs. The depolarizing phase is used not by Na* but rather by Ca** influx through L-type Ca* wannels. These Ca" currents depolarize the membrane mor lowly than voltage-gated Na” channels, and one results that acto tentials propagate more slowly along nodal-cell membranes thar nother cardiac cells. This explains the slow transmission of car iac excitation through the AV node. As in cardiac muscle cells the long-lasting L-type Ca®* channels prolong the nodal action K? exits Repolariation) hreshole cat enters (Depolarization, Nat enters \ca?* enters {Pacemaker potential =100 ° 0.18) 030) Time (see) ° Pesttes Relative membrane permea ° O15 030 Time (see) igure 12.16 (a) Membrane potential recording from a car nodal cell Labels indicate key ionic movements in each phase, A gradual reduction in K* permeability also contributes tothe pacemaker potential ce Figure 12.166, and the Na*enteyin th phase is through nonspecific cation channels. (b) Simultancoush ‘measured permeabilities through four different ion chennels dur ‘the action potential shown in (a). Note thatthe letters in parenth (8, T, and L identify the types of ion channels described in the tent. As opposed to the multiple K* channels involved in ventric ‘muscle membrane potential in Figure 12.15b, there is a specific subtype of K* channel that controls Px: in nodal cells, PHYSIOLOGICAL INQUIRY "= Conducting (Purkinje) cells ofthe ventricles contain all of the jon channel types found in both cardiac muscle cells and node cells. Draw a graph of membrane potential versus time (sin Figure 12.153) showing a Purkinje cll action potential. Answer can be found at end of chapter. yotential, but eventually they close and K* channels open ap membrane is repolarized, The return to negative potentials fates the pacemaker mechanisms once again, and the cycle re Thus, the pacemaker potential provides the SA ith_antomaticity, th tyfe . yt Cudiovasula PhysiologyelT-excitation. The slope of the pacemaker potential —that is, Ho yuickly the membrane potential changes per unit time—sietermines yw quickly threshold is reached and the next action potential i cited. The inherent rate of the SA node—the rate exhibited in th sbsence of any neural or hormonal input to the node—is approxi mately 100 depolarizations per minute. (We will discuss later why) che resting heart rate in hurnans is usually slower than that) Because other cells of the conducting system have slow jnherent pacemaker rates, they normally are driven to threshold by, tion potentials from the SA node and do not manifest their ow hythm. However, they can do so under certain circumstances anc re then called ectopic pacemakers. Recall that excitation travel from the SA node to both ventricles only through the AV node; ¢herefore, drug-or disease induced malfunction of the AV node may educe or completely eliminate the transmission of action potential from the atria to the ventricles. This is known as an AV conduction fisorder. If this occurs, autorhythmic cells in the bundle of His and Purkinje network, no longer driven by the SA node, begin to initia citation at their own inherent rate and become the pacemaker for e ventricles, Their rate is quite slow, generally 25 to 40 beats/min, (Therefore, when the AV node is disrupted, the ventricles contract vompletcly out of synchrony with the atria, which continue at th higher rate of the SA node. Under such conditions, the atria are les fective because they are often contracting when the AV valves ‘closed, Fortunately, atrial pumping is relatively unimportant for ardiac function except during strenuous exercise The current treatment for severe AV conduction disorders, well as for many other abnormal rhythms, is permanent surgi al implantation of an artificial pacemaker that electrically stim slates the ventricular cells at @ normal rate [Che Electrocardiogram The electrocardiogram (ECG, also abbreviated EKG—the k is from the German elektrokardiogramm) isa tool for evaluating th Jectrical events within the heart. When action potentials occu imultaneously in many individual (Contractile) myocardial cells, surrents are conducted through the body fluids around the hear ind can be detected by recording electrodes at the surface of the kin, Figure 12.17a illustrates an idealized normal ECG record fs the potential difference between the right and left wrists, (Review Figure 12.14 for an illustration of how this waveform correspond in time With the spread of an action potential through the heart [The first deflection, the P wave, corresponds to current flow dur jing atrial depolarization, The second deflection, the QRS complex, recurring approximately 0.15 sec later, is the result of ventricular lepolarization. It is a complex deflection because the paths taker y the wave of depolarization through the thick ventricular wall Hiffer from instant to instant, and the currents generated in the bods lids change direction accordingly. Regardless of its form (for example, the Q and/or $ portions may be absent), the deflection is til called a QRS complex. The final deflection, the T wave, is th sult of ventricular repolarization, Atrial repolarization is usuall jt evident on the ECG because it occurs at the same time as t IRS complex, ‘A typical ECG makes use of multiple combinations ‘ecording locations on the limbs and chest (called ECG leads) s so obtain as much information as possible concerning different eas of the heart. The shapes and sizes of the P wave, QRS com: ex, and T wave vary with the electrode locations. For referen é e ion potenti: » nen z & 5 5 i = GPIR) Figure 12.17 (@ Weatized electrocandiogram cvorsed from electrodes placed on the wrists. (b) Action potentials ceorded from a single arial muscle cell anda single ventricular muscle cell, synchronized with the ECG trace in panel (@). Note the correspondence of the P wave with tral depolarization, the ‘QRS complex with ventricular depolarization, andthe T wave with ventricular repolarization PHYSIOLOGICAL INQUIRY '= How would the timing of the waves in (a) be changed by a drug, reduces the L-type Ca* current in AV node cells? Answer can be found at end of chapter. see Figure 12.18 and Table 12.4, which describe the placement of leetrodes for the different ECG leads, To reiterate, the ECG is not a direct record of the change: sn membrane potential across individual cardiac muscle cells instead, itis a measure of the currents generated in the extracell- Jar fluid by the changes occurring simultaneously in many cardia‘ lls. To emphasize this point, Figure 12.17b shows the simulta ;cously occurring changes in membrane potential in single atria fund ventricular muscle cells. Because many myocardial defects alter normal action poten- ial propagation and thereby the shapes and timing of the waves, the ECG is a powerful tool for diagnosing certain types of heart lisease. Figure 12.19 gives one example. However, note that th ECG provides information concerning only the electrical activity f the heart. If something is wrong with the heart's mechanical «tivity and the defect does not give rise to altered electrical activ ty, the ECG will be of limited diagnostic value. Excitation—Contraction Coupling IThe mechanisms linking cardiac muscle cell action potential 10 contraction were described in detail in the chapter on muscl haysiology (Chapter 9; review Figure 9.40), The small amount ST Chapter 12Lesa Lead i ° Figure 12.18 Placement of electrodes in clectrocardiography. Bach cording (postive pole) electrodes, thus providing different angles for “ 1,11, and II} form a tangle between electrodes on the writs and lft he triangle by combining two electrodes as reference. (For example, fr resting a reference point slong the line bevween them, penting toward cording electrodes placed on the chest as shown, with the limb leads. SUS g ec the I lead ne ree pmbin leads uses a different combination of reference (negative pole) an Ue electrical activity of the heart (a) The standard limb leads rihmiatrpnns azo eure L, the right wrist and foot are combined as the negative pole, thus fing electrode onthe left wrist) (b) The precordial leads (V1-Vé into a reference point a the center of the heart Standard Limb Leads Reference -) Electrode Lead Right arm, Lead Right arm Lead I Left arm “Augmented Limb Leads WR Left arm and left leg VL. Right acm and left eg VE Right arm and left arm Precordial (Chest) Leads vi ‘Combined limb leads I > oO vs po 9 va 2 2 9 vs 2 2 @ vo a a o Recording (+) Electrode Left arm Leftleg Leltleg ‘Right arm, Left arm Leltleg 4th intercostal space, righ of sternum. 4th intercostal space, left of steraum Sth intercostal space, left of sternum. Sth intercostal space, centered on clavicle Sth intercostal space, left of V4 Sth intercostal space, under left arm. Cudiovasula PhysiologyRs ors ors pes phe eli Cy Rs ors p PLA? poe 0 Figure 12.19 Blectrocardiograms from a healthy person and from two people suffering from atrioventricular block. (a) A normal ECG, (b Partial block. Damage to the AV node permits only every ‘ther arial impulse to be transmitted to the ventricles. Note that every second P wave is not followed by a QRS anc T. @) Complete block. There is no synchrony between atria] and ventricular electri activites, and the ventricles are being driven by avery slow pacemaker cel in the bundle of His PHYSIOLOGICAL INQUIRY 1 Some people have a potentially lethal defect of ventricular ‘muscle, in which the current through voltage-gated K* channels responsible for repolarization is delayed and reduced. How could this defect be detected on their ECG recordings? Answer can be found at end of chapter tracellular Ca™* entering through L-type Ca”* channels durin plateau of the action potential triggers the release of a large uantity of Ca’* from the ryanodine receptors in the sarcoplasmic] ticulum membrane. Ca activation of thin filaments and cross. ridge cycling then lead to generation of force, just asin skeletal iscle (review Figures 9.15 and 9.11). Contraction ends when "a is returned to the sarcoplasmic reticulum and extracellul uid by Ca*t-ATPase pumps and Na’/Ca** countertransporters, The amount that cytosolic Ca” concentration increase: flaring excitation is a major determinant of the strength of car liac muscle contraction. You may recall that in skeletal muscle, kingle action potential releases sufficient Ca” to fully saturate fren is sar asia carson, By contra he ot: "a released from the sarcoplasmic reticulum in cardiac mus. juring a resting heartbeat is not usually sufficient to saturate all foponin sites. Therefore, the number of active eross-bridges—| ind thus the strength of contraction—can be increased if m "a is released from the sarcoplasmic reticulum (as would occur, for example, during exercise). The mechanisms that vary eytosol "2?" concentration will be discussed later. ‘efractory Period of the Heart ‘ardiac muscle is incapable of undergoing summation of contrac ions like that occurring in skeletal muscle (review Figure 9.19), and is is a very good thing. If a prolonged, tetanic contraction wer ‘occur in the heart, it would cease to function as a pump becaus the ventricles can only adequately fill with blood while they at Jaxed The inability of the heart t te tet tract Tension ceveloped z i -Retractory_.\ period Time (msee) igure 12.20 Relationship between membrane potential changes rd contraction in a ventricular muscle cll. The refractory period lasts Jost as long asthe contraction, Tension scale not shown, 3s the result of the long absolute refractory period of cardia nuscle, defined as the period dusing and following an action poten. ial when an excitable membrane cannot be re-excited. AS in the ase of neurons and skeletal muscle fibers the main mechanism is the inactivation of Na” channels. The absolute refractory period of eletal muscle is much shorter (2 to 4 msed) than the duration of contraction 20 to 100 msec), so a second action potential can be icited while the contraction resulting fom the first action poten: al is still under way (See Figure 910). In contrast, because of the longed, depolarized plateau inthe cardiac muscle action poten al, the absolute refractory period of eardiac muscle lasts almost ag jong as the contraction (approximately 250 msec), and the muscl annot be re-excited multiple times during an ongoing contacto [Figure 12.20; also review Figure 94D. 112.5 Mechanical Events of the Cardiac Cycle [The orderly process of depolarization described in the previous sions triggers a recurring cardiac eycle of atrial and ventricu- jar contractions and relaxations (Figure 12.21). First, we will pre- ent an overview of the cycle, naming the phases and key events |\ closer look at the eyele will follow, with a discussion of the pres sure and volume changes that cause the events. ‘The cycle is divided into two major phases, both named for vents in the ventricles: the period of ventricular contraction an ood ejection called systole, and the alternating period of ven- ricular relaxation and blood filling, diastole. For a typical heart ate of 72 beats/min, each cardiac cycle lasts approximately 0. 6, with 0.3 sec in systole and 0.5 sec in diastole. ‘As Figure 1221 illustrates, both systole and diastole can 1 subdivided into two discrete periods, During the first part o systole, the Ventticles are contracting but all valves in the hear hue closed and so no blood can be ejected. This period is terme: jsovolumetrie ventricular contraction because the ventricular vol sme is constant (iso means “equal” or in this context “unchanging”, [The ventricular walls are developing tension and squeezing on th lood they enclose, increasing the Ventricular blood pressure. How: because the volume of blood in the ventric tant 380 Chapter 12ay Syst0le SETTER TERT] Atria ‘elased Ventiles contact AV vanes: closed Aortic and pulmonary valves: closed (©) Diastole lovolumetrie ventrieula relaxation Atria are Feloxed ‘relaxed Ventrices relaxes AV valves: otic and pulmonary valves: rivieuar ejeetion Blood flows out of ventile Ventites contract Venteeula fing Blood tows ito ventretes Atal contraction Sorina VO Ventrices relaxes [BPI Figure 12.21 Divisions ofthe cardiac cycle: systole; () jection in Which the pressure difference favors flow is denoted by an ecause blood, like water, is essentially incompressible, the ventric lar muscle fibers cannot shorten. Thus, isovolumetric ventricula Contraction is analogous to an isometric skeletal muscle contrac: ion; the muscle develops tension, but it does not shorten. Once the increasing pressure in the ventricles exceeds tha 0 the aorta and pulmonary trunk, the aortic and pulmonary valv ;pen and the ventricular ejection period of systole occurs. Blo forced into the aorta and pulmonary trunk as the contacting ven tricular muscle fibers shorten. The volume of blood ejected from ach ventricle during systole is called the stroke volume (SV). During the fist part of diastole, the ventricles begin to rela rnd the aortic and pulmonary valves close. (Physiologists and car ogists do notall the dividing line bet tal diastole. The phases ofthe cycle are identical in both halves ofthe heart. row; te, however, that flow will not actually occur if a valve prevents al; reseted bere, th viding ine ithe pitt ous conocton sp and he pliant Tse) Ath tes the A vate ae a se. hee od etinge ving te vee, Veni tl pecungng ntse clelntme n Slnation Ne, te, tt the oy tes ng the tn all le re cede eps of ol via coast lmao Nene AV ves pe ant vnc filing 0 bod sn om te aie Au contac ver asl afer mosof te venir lingas te ae ene ess ot thonghout mt of ist nt Cudiovasula PhysiologyAortic pressure Pressure (mmHg) Lef atrial pressure Let ventricular pressure Ene-ciastalc Left ventreular volume 5 3 6s 5 vohme 3 cons 5 . z res § “ ana ter sounts Diatole [ sya Distole Fi E = A a Fi Phase of cardiac cycle nicl filing sovolumetrie venrculr contagion ivieular ejection volumetric ventricular relaxalon [PIF Figure 12.22 summary of events in the lef atrium, left vehtrcleand arta during the cardiac cycle (sometimes called the “Wiggers” iageam), Sce text fr a description of the numbered steps 382 Chapter 12[o® he airium contracts. Indeed, ina person at rest, approximate 0% of ventricular filling occurs before atrial contraction. This completes the basic orientation. Using Figure 12.22, fe can now analyze the pressure and volume changes that occu the left atrium, left ventricle, and aorta ducing the cardiac cycle. Events on the right side of the heart are very similar except for the solute pressures, iid-Diastole to Late Diastole ur analysis of events in the left atrium and ventricle and the aort egins at the far left of Figure 12.22 with the events of mid- t ate diastole, The numbers that follow correspond to the numbere -vents shown in that figure. ‘The left atrium and ventricle are both relaxed, but atrial pressure is slightly higher than ventricular pressure because {the atrium is filling with blood that is entering from the veins ‘The AV valve is held open by this pressure difference, and blood entering the atrium from the pulmonary veins continues on into the ventricle. To reemphasize a point made earlier, all the valves ofthe heart offe ery litte resistance when they are open, so very small pressure dif rences actoss them are requited to produce relatively large flows. Note that at this time and throughout all of diastole, the aortic valve is closed because the aortic pressure is higher than the ventricular pressure. ‘Throughout diastole, the aortic pressure is slowly decreasing because blood is moving out of the arteries and through the vascular system, In contrast, ventricular pressure is increasing 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 and the atria depolaize, as signified by the P wave of the ECG. Contraction of the atrium causes an increase in atrial pressure ‘The increased atrial pressure forces 2 small additional volume of blood into the ventricle, sometimes referred to as| the “atrial kick.” ‘This brings us to the end of ventricular diastole, so the amount of blood in the ventricle at this time is called the end-diastolic volume (EDV), bystole [Thus far, the ventricle has been relaxed as it fills with blood, But immediately following the atrial contraction, the ventricles begit 10 contract From the AV node, the wave of depolarization passes into and throughout the ventricular tisste—as signified by the ‘QRS complex of the ECG—and this triggers ventricular contraction. As the ventricle contracts, ventricular pressure increases rapidly; almost immediately this pressure exceeds the atrial pressure, This change in pressure gradient forces the AV valve to close; this prevents the backflow of blood into the atrium. Because the aortic pressure still exceeds the ventricular this time. the aortic val Josed and The ventricle cannot empty despite i contraction, For brief time, then, all valves are closed during this phase isovolumetric ventricular contraction, Backward bulgi the closed AV valves causes a small upward deflection the atrial pressure wave. ‘This brief phase ends when the rapidly increasing ventricular pressure exceeds aortic pressure The pressure gradient now forces the aortic valve to of and ventricular ejection begins. ‘The ventricular volume curve shows that ejection i ra first and then slows down, ‘The amount of blood remaining in the ventricle after ejection is called the end-systolic volume (ESV). Note that the ventricle does not empty completely. The amo llood that does exit during each cycle is the difference bet shat it contained at the end of diastole and what remains : end of systole. Therefore, stroke volume = End-diastolic volume ~ End-systolie volu sv ‘EDV sv As Figure 12.22 shows, typical values for an adult at rest ar liiastolic volume = 135 mL, end-systolic volume = 65 mL. stroke volume = 70 mL. {® _Astiood flows into the arta, the artic pressure increase along withthe venvicular pressure. Throughout ejection, small pressure differences exist betwen the ventricle and bone the open artic valve offers little resistance to flo (@ _ Nowe that peak ventricular and aortic pressures are rea before the end of ventricular ejection; that is, these pressures start to decrease during the last part of syst despite continued ventricular contraction, This is beca the strength of ventricular contraction diminishes dr the lst part of systole. (® This force reduction is demonstrated by the reduced 1 blood ejection during the last part of systole. (@ The volume and pressure in the aorta decrease asthe 1 blood ejection from the ventricles becomes slower than rate al which blood drains out ofthe arteries int the tis Early Diastole [This phase of diastole begins as the ventricular muscle relaxe section comes to an end. @ Recall thatthe T wave of the ECG corresponds to ventricular repolarization, @ As the ventricles relax, the ventricular pressure deeres below aortic pressure, which remains significantly increased duc tothe volume of blood tht just entered change in the pressure gradient forces the aortic valve close, The combination of elastic recoil ofthe aorta an blood rebounding against the valve eauses a rebound 0 aortic pressure called the dirotic notch, [@ The AV valve also remains closed because the ventric pressure i still higher than atrial pressure, For a brict time, then, all valves are again closed during this phas ixovolumetric ventricular relaxation @ This phase ends asthe rapidly decreasing ventricular pressure decreases below atrial pressure Cudiovasula Physiology(@ This change in pressure gradient results in the opening of the AV valve @ _ Venous blood that had accumulated in te atrium since the AV valve closed flows rapidly into the ventricles. @ _Theratc of blood flow is enhanced during this inital filling phase by a rapid decrease in ventricular pressure. This occurs because the ventrcl's previous contraction compressed the elastic elements ofthe chamber in such a ‘way thatthe ventricle actually tens to recoil outward once systole i over, This expansion, in turn lowers ventricular pressure more rapidly than would otherwise occur and may even create a negative (subatmospheric) pressure. Thus, some nergy is stored within the myocardium during contraction, ands release during the subsequent relaxation ads filling ‘The fact that most ventricular filling is completed during arly diastole is of great importance. It ensures that filling is not criously impaired when the heart is beating very rapidly, and the juration of diastole and, therefore, total filling time are reduced, However, when heart rates of approximately 200 beats/min or mot reached, filling time becomes inadequate and the volume o! jlood pumped during each beat decreases. The clinical signiti. cance of this will be described in Section E, Early ventricular filling also explains why the conductior lefects that eliminate the atria as effective pumps do not seriously impair ventricular filling, at least in otherwise healthy individuals rest, This is true, for example, during atrial fibrillation, a sta jn which the cells of the atria contract in a completely uncoordi- hhated manner and so the atria fail t work as effective pumps. Pulmonary Circulation Pressures The pressure changes in the right ventricle and pulmonary series (Figure 12.23) are qualitatively similar to those just lescribed for the left ventricle and aorta, There are striking yuantitative differences, however. Typical pulmonary arte- ial systolic and diastolic pressures are 25 and 10 mmHg, spectively, compared to systemic arterial pressures of 120 ind 80 mmHg. Therefore, the pulmonary cixculation is a low-pressure system, for reasons to be described later. This lifference is clearly reflected in the ventricular anatomy— he right ventricular wall is much thinner than the left Despite the difference in pressure during contraction, how- fer, the stroke volumes of the two ventricles are the same. Heart Sounds [Iwo heart sounds resulting from cardiac contraction are nor nally heard through a stethoscope placed on the chest wall, The first sound, a soft, low-pitched lub, is associated with closut the AV valves; the second sound, a louder dup, is associated with Josure of the pulmonary and aortic valves. Note in Figure 12. at the lub marks the onset of systole and the dup occurs at nnsetof diastole. These sounds, which result from vibrations caused y the closing valves, are normal, but other sounds, known as heart murmurs, can be a sign of heart disease ‘Murmurs can be produced by heart defects that cause blood ow to be turbulent. Normally, blood flow through valves and ves ls is laminar flow—that is, it flows in smooth concentric layer (Figure 12.24), Turbulent flow can be caused by blood flowin, fs) aa ane lve (tenosisy, by blood Towing backward through a damaged, jcaky valve (insufficiency); or by blood flowing between the tw tria or two ventricles through a small hole in the wall separating them (called a septal defect) 1 = Ventricular fing 2= lrovalumetic ventricular contraction 3 Ventricular ejection 4 frovolumetiec ventricular relaxation Pulmonary artery venticulr pressure Time (PIR) Figure 12.23 Pressures inthe right ventricle and pulmonary artery during the cardiac cyele, Note that the pressures a lower than in the left ventricle an aorta PHYSIOLOGICAL INQUIRY 1 Ifa person had a ole inthe interventricular septum, would the blood ejected into the aorta have lower than normal oxygen levels? Answer can be found at end of chapter Stenotie vave Normal open valve Narrowed vate urbulent flow Laminar flow = cuiet Insufficient vave V6 iS Normal closed valve Leaky valve Turbulent backaw = murmur No fow = quit cs Figure 12.24 teat valve defects causing turbulent blood flow and murmurs. @) Normal valves allow smoot, laminar flow of blood inthe forward direction when open and prevent backward flow of blood when| closed, No sound is heard in either state (b) Stenoic valves cause rapid turbulent forward flow of blood, making a high-pitched, whistling ‘murmur, Valve insuficency results in turbulent backward flow when the vale should be closed, eausing low-ptched gurgling marmur PHYSIOLOGICAL INQUIRY 1 What valve defect() would be indicated by the following sequence of heart sounds: lub-whisale-dup-gurgle? Answer can be found at end of chapter. idly in the usual direction through an abnormall 384 Chapter 12