Seeley's Essentials of Anatomy and Physiology (2021) - Heart Functions - PDF

Page 353 CHAPTER 12  Page 354 LEARN TO APPLY IT 12.1 FUNCTIONS OF THE HEART Learning Outcome After reading this section, you should be able to People often refer to the heart as the seat of strong emotions. For example, we may describe a very determined perso...

Page 353 CHAPTER 12  Page 354 LEARN TO APPLY IT 12.1 FUNCTIONS OF THE HEART Learning Outcome After reading this section, you should be able to People often refer to the heart as the seat of strong emotions. For example, we may describe a very determined person as having “a lot of heart” or say that a person who has been disappointed romantically has a “broken heart.” Emotions, however, are a product of brain function, not heart function. The heart is a muscular organ that is essential for life because it pumps blood through the body. Fluids flow through a pipe only if they are forced to do so. The force is commonly produced by a pump, which increases the pressure of the liquid at the pump above the pressure in the pipe. Thus, the liquid flows from the pump through the pipe from an area of higher pressure to an area of lower pressure. If the pressure produced by the pump increases, flow of liquid through the pipe increases. If the pressure produced by the pump decreases, flow of liquid through the pipe decreases. Like a pump that forces water through a pipe, the heart contracts forcefully to pump blood through the blood vessels of the body. Together, the heart, the blood vessels, and the blood make up the cardiovascular system (figure 12.1). The heart of a healthy adult, at rest, pumps approximately 5 liters (L) of blood per minute. For most people, the heart continues to pump at approximately that rate for more than 75 years. During short periods of vigorous exercise, the amount of blood pumped per minute increases several-fold. But if the heart loses its pumping ability for even a few minutes, blood flow through the blood vessels stops, and the person’s life is in danger. Figure 12.1 Cardiov ascular Sy st em Th e h ear t, th e blood v essels, and th e blood ar e th e m ajor com ponents of th e car diov ascu lar sy stem. Although it is a single structure, the heart is actually two pumps in one. The right side of the heart pumps blood to the lungs and back to the left side of the heart through vessels of the pulmonary circulation (figure 12.2). The left side of the heart pumps blood to all other tissues of the body and back to the right side of the heart through vessels of the systemic circulation. Page 355  Figure 12.2 Ov erv iew of t he Circulat ory Sy st em Th e cir cu lator y sy stem consists of th e pu lm onar y and sy stem ic cir cu lations. Th e r igh t side of th e h ear t pu m ps blood th r ou gh v essels to th e lu ngs and back to th e left side of th e h ear t th r ou gh th e pu lm onar y cir cu lation. Th e left side of th e h ear t pu m ps blood th r ou gh v essels to th e body tissu es and back to th e r igh t side of th e h ear t th r ou gh th e sy stem ic cir cu lation. The functions of the heart are 1. Generating blood pressure. Contractions of the heart generate blood pressure, which forces blood through the blood vessels. 2. Routing blood. The heart separates the pulmonary and systemic circulations, which ensures that the blood flowing to tissues has adequate levels of O2. 3. Ensuring one-way blood flow. The valves of the heart ensure a one-way flow of blood through the heart and blood vessels. 4. Regulating blood supply. Changes in the rate and force of heart contraction match blood flow to the changing metabolic needs of the tissues during rest, exercise, and changes in body position. 12.2 SIZE, FORM, AND LOCATION OF THE HEART  Learning Outcomes After reading this section, you should be able to The adult heart is shaped like a blunt cone and is approximately the size of a closed fist. It is larger in physically active adults than in less active but otherwise healthy adults. The heart generally decreases in size after approximately age 65, especially in people who are not physically active. The blunt, rounded point of the heart is the apex and the larger, flat part at the opposite end of the heart is the base. The heart is located in the thoracic cavity between the two pleural cavities that surround the lungs. The heart, trachea, esophagus, and associated structures form a midline partition called the mediastinum (MEE-dee-ah-STIE-num; see figure 1.11). The heart is surrounded by its own cavity, the pericardial cavity (peri, around + cardio, heart) (see chapter 1). It is important for health professionals to know the location and shape of the heart in the thoracic cavity. This knowledge enables them to accurately place a stethoscope to hear the heart sounds, to place chest leads for an electrocardiogram (described later in this chapter), or to administer cardiopulmonary resuscitation (KAR-dee-oh-PUL-moh-nair-ee ree- SUS-ih-TAY-shun; CPR). CPR is an emergency procedure that maintains blood flow in the body if a person’s heart stops. The heart lies obliquely (at an angle) in the mediastinum, with its base directed posteriorly and slightly superiorly and its apex directed anteriorly and slightly inferiorly. The apex is also directed to the left, so that approximately two-thirds of the heart’s mass lies to the left of the midline of the sternum (figure 12.3a). The base of the heart is located just behind the sternum and extends to the space just below the second rib, called the second intercostal space. The apex is just behind the 5th and 6th ribs at the 5th intercostal space and just to the left of the sternum. If you draw an imaginary line straight down from the middle of your left clavicle, it will pass over the apex. This perpendicular line is called the midclavicular line (figure 12.3b). Page 356  Figure 12.3 Locat ion of t he Heart (a) Th e h ear t is in th e th or acic cav ity betw een th e lu ngs, deep and sligh tly to th e left of th e ster nu m. (b) Th e base of th e h ear t, located deep to th e ster nu m , extends su per ior ly to th e second inter costal space, and th e apex of th e h ear t is located deep to th e fifth inter costal space, appr oxim ately 7 –9 cm to th e left of th e ster nu m w h er e th e m idclav icu lar line inter sects w ith th e fifth inter costal space. 12.3 ANATOMY OF THE HEART Learning Outcomes After reading this section, you should be able to The heart lies in the pericardial cavity. The pericardial cavity is formed by the pericardium (per-ih-KAR-dee-um), or pericardial sac, which surrounds the heart and anchors it within the mediastinum (figure 12.4). The pericardium consists of two layers: (1) the fibrous pericardium and (2) the serous pericardium. The fibrous pericardium is the outer layer of the pericardium and is composed of tough, fibrous connective tissue. The serous pericardium is the inner layer and consists of flat epithelial cells with a thin layer of connective tissue. The serous pericardium, like most serous membranes, is composed of two parts: (1) the parietal pericardium and (2) the visceral pericardium. The parietal pericardium lines the fibrous pericardium, whereas the visceral pericardium, or epicardium (EP-ih-KAR-dee-um; upon the heart) covers the heart surface. The parietal and visceral pericardia are continuous with each other where the great vessels enter or leave the heart. The pericardial cavity, located between the visceral and parietal pericardia, is filled with a thin layer of pericardial fluid produced by the serous pericardium. The pericardial fluid helps reduce friction as the heart moves within the pericardium. Figure 12.4 Heart in t he Pericardium Th e per icar diu m consists of an ou ter fibr ou s per icar diu m and an inner ser ou s per icar diu m. Th e ser ou s per icar diu m h as tw o par ts: Th e par ietal per icar diu m lines th e fibr ou s per icar diu m , and th e v iscer al per icar diu m (epicar diu m ) cov er s th e su r face of th e h ear t. Th e per icar dial cav ity , betw een th e par ietal per icar diu m and v iscer al per icar diu m , is filled w ith a sm all am ou nt of per icar dial flu id. Page 357  CLINICAL IMPACT The right and left atria (AY-tree-ah; sing. atrium, entrance chamber) are located at the base of the heart, and the right and left ventricles (VEN- trih-kels; cavities) extend from the base of the heart toward the apex (figure 12.5). A groove called the coronary sulcus (SUL-cuss) extends around the heart, separating the atria from the ventricles. Two additional grooves, or sulci extend inferiorly from the coronary sulcus and indicate the division between the right and left ventricles. The anterior interventricular sulcus is on the anterior surface of the heart, and the posterior interventricular sulcus is on the posterior surface of the heart. Page 358 Page 359  Figure 12.5 Surface of t he Heart (a) In th is anter ior v iew of th e h ear t, th e tw o atr ia (r igh t and left) ar e located su per ior ly at th e base of th e h ear t, and th e tw o v entr icles (r igh t and left) ar e located infer ior ly at th e apex of th e h ear t. Th e su per ior and infer ior v enae cav ae enter th e r igh t atr iu m. Th e pu lm onar y v eins enter th e left atr iu m. Th e pu lm onar y tr u nk exits th e r igh t v entr icle, and th e aor ta exits th e left v entr icle. (b) Ph otogr aph of th e anter ior su r face of th e h ear t. (b) ©R. T. Hu tch ings (c) Poster ior v iew of th e h ear t. Blood first enters the heart at the atria. Veins carry blood to the atria (figure 12.5a, c): The superior vena cava and inferior vena cava carry blood from the body to the right atrium, and four pulmonary veins carry blood from the lungs to the left atrium. Blood exits the heart at the ventricles. Blood flows from the ventricles through large arteries, often called the great vessels or great arteries. The pulmonary trunk, arising from the right ventricle, splits into the right and left pulmonary arteries, which carry blood to the lungs. The aorta (ay-OR-tuh), arising from the left ventricle, carries blood to the rest of the body. The heart is a muscular pump consisting of four chambers: (1) the right atrium, (2) the left atrium, (3) the right ventricle, and (4) the left ventricle (figure 12.6).  Figure 12.6 Int ernal Anat omy of t he Heart Th e h ear t is cu t in a fr ontal plane to sh ow its inter nal anatom y. Right and Left Atria Blood enters the atria of the heart through blood vessels called veins. The atria function primarily as reservoirs, where blood returning from veins collects before it enters the ventricles. Contraction of the atria forces blood into the ventricles to complete ventricular filling. The right atrium receives blood from three major openings: (1) the superior vena cava, (2) the inferior vena cava, and (3) the coronary sinus. The superior vena cava and the inferior vena cava drain blood from most of the body (figure 12.6), and the smaller coronary sinus drains blood from most of the heart muscle. The left atrium receives blood through the four pulmonary veins, which drain blood from the lungs. The two atria are separated from each other by a partition called the interatrial (between the atria) septum. Right and Left Ventricles The ventricles of the heart are its major pumping chambers. They eject blood into the arteries and force it to flow through the circulatory system. The atria open into the ventricles, and each ventricle has one large outflow route located superiorly near the midline of the heart. The right ventricle pumps blood into the pulmonary trunk, and the left ventricle pumps blood into the aorta. The two ventricles are separated from each other by the muscular interventricular (between the ventricles) septum (figure 12.6). The wall of the left ventricle is thicker than the wall of the right ventricle. As such, the wall of the left ventricle contracts more forcefully and generates a greater blood pressure than the wall of the right ventricle. When the left ventricle contracts, the pressure increases to approximately 120 mm Hg. When the right ventricle contracts, the pressure increases to approximately 24 mm Hg or one-fifth of the pressure in the left ventricle. However, the left and right ventricles pump nearly the same volume of blood. The higher pressure generated by the left ventricle moves blood through the larger systemic circulation, whereas the lower pressure generated by the right ventricle moves blood through the smaller pulmonary circulation (see figure 12.2). The one-way flow of blood through the heart chambers is maintained by the heart valves. There are two types of heart valves: (1) atrioventricular valves and (2) semilunar valves. An atrioventricular (AV) valve is located between each atrium and ventricle. Specifically, the AV valve between the right atrium and the right ventricle is called the tricuspid valve (figure 12.7a), because it is composed of three cusps or flaps of tissue. The AV valve between the left atrium and the left ventricle is called the bicuspid valve, because it is composed of two cusps. The bicuspid valve is also called the mitral (resembling a bishop’s miter, a two-pointed hat) valve (figure 12.7b). These valves allow blood to flow from the atria into the ventricles but prevent it from flowing back into the atria. When the ventricles relax, the higher pressure in the atria forces the AV valves to open, and blood flows from the atria into the ventricles (figure 12.8a). In contrast, when the ventricles contract, blood flows toward the atria and causes the AV valves to close (figure 12.8b). This information may be useful in answering the Learn to Apply It question at the beginning of the chapter. Page 360 Figure 12.7 Heart Valv es (a) A nter ior v iew of th e tr icu spid v alv e, bicu spid v alv e, th e ch or dae tendineae, and th e papillar y m u scles. (b) In su per ior v iew , note th at th e th r ee cu sps of each sem ilu nar v alv e m eet to pr ev ent th e backflow of blood. (a) ©Oktay Or takcioglu /iStock/3 6 0/Getty Im ages RF; (b) ©V ideoSu r ger y /Science Sou r ce; Figure 12.8 Funct ion of t he Heart Valv es (a) A s th e v entr icle r elaxes, th e pr essu r e in th e v entr icle becom es low er th an th e pr essu r e in th e atr iu m. Blood flow ing into th e left atr iu m opens th e bicu spid v alv e, and blood flow s into th e left v entr icle. A t th e sam e tim e, in th e aor ta, blood flow ing back tow ar d th e r elaxed v entr icle cau ses th e aor tic sem ilu nar v alv e to close, and no blood can r eenter th e v entr icle fr om th e aor ta. (b) Wh en th e v entr icle contr acts, blood flow ing tow ar d th e atr iu m cau ses th e bicu spid v alv e to close. Th e incr eased pr essu r e in th e left v entr icle for ces th e aor tic sem ilu nar v alv e open. Page 361  Each ventricle contains cone-shaped, muscular pillars called papillary (PAP-i-lar-ee) muscles. These muscles are attached by thin, strong, connective tissue strings called chordae tendineae (KOR-dee ten-DIN- ee; heart strings) to the free margins of the cusps of the atrioventricular valves. When the ventricles contract, the papillary muscles contract and prevent the valves from opening into the atria by pulling on the chordae tendineae attached to the valve cusps (see figures 12.6 and 12.7a; figure 12.8). Imagine a parachute billowing open, with the parachute cords securing its shape. The parachute fabric is analogous to the cusps of the valves and the parachute cords are analogous to the chordae tendineae. A semilunar valve is located between each ventricle and its associated great artery. The pulmonary semilunar valve is located between the right ventricle and the pulmonary trunk. The aortic semilunar valve is located between the left ventricle and aorta (see figure 12.6). Each valve consists of three pocketlike semilunar (half-moon-shaped) cusps (see figure 12.7b; figure 12.8). When the ventricles relax, the pressures in the aorta and pulmonary trunk are higher than in the ventricles. Blood flows back from the aorta or pulmonary trunk toward the ventricles and enters the pockets of the cusps, causing them to bulge toward and meet in the center of the aorta or pulmonary trunk, thus closing the vessels and blocking blood flow back into the ventricles (figure 12.8a). When the ventricles contract, the increasing pressure within the ventricles forces the semilunar valves to open (figure 12.8b). A plate of connective tissue, sometimes called the cardiac skeleton, or fibrous skeleton, consists mainly of fibrous rings that surround the atrioventricular and semilunar valves and give them solid support (figure 12.9). This connective tissue plate also serves as electrical insulation between the atria and the ventricles and provides a rigid attachment site for cardiac muscle.  Figure 12.9 Cardiac Skelet on Th e car diac skeleton consists of fibr ou s connectiv e tissu e r ings th at su r r ou nd th e h ear t v alv es and separ ate th e atr ia fr om th e v entr icles. Car diac m u scle attach es to th e fibr ou s connectiv e tissu e. Th e m u scle fiber s ar e ar r anged so th at, w h en th e v entr icles contr act, a w r inging m otion is pr odu ced, and th e distance betw een th e apex and th e base of th e h ear t sh or tens. The route of blood flow through the heart is depicted in figure 12.10. Even though blood flow is described for the right and then the left side of the heart, it is important to understand that both atria contract at the same time, and both ventricles contract at the same time. This concept is most important when considering the electrical activity, pressure changes, and heart sounds. ❶ Deoxygenated blood enters the right atrium from the systemic circulation through the superior and inferior venae cavae, and from heart muscle through the coronary sinus. ❷ Most of the blood flowing into the right atrium flows through the tricuspid valve and into the relaxed right ventricle. Before the end of ventricular relaxation, the right atrium contracts, and enough blood is pushed from the right atrium into the right ventricle to complete right ventricular filling. ❸ Following right atrial contraction, the right ventricle begins to contract. This contraction pushes blood against the tricuspid valve, forcing it  closed. After pressure within the right ventricle increases, the pulmonary semilunar valve is forced open, and blood flows into the pulmonary trunk. As the right ventricle relaxes, its pressure falls rapidly, and pressure in the pulmonary trunk becomes greater than in the right ventricle. The backflow of blood forces the pulmonary semilunar valve to close. ❹ The pulmonary trunk branches to form the right and left pulmonary arteries, which carry blood to the lungs, where CO2 is released and O2 is picked up. ❺ Oxygenated blood returning from the lungs enters the left atrium through the four pulmonary veins. ❻ Most of the blood flowing into the left atrium passes through the bicuspid valve and into the relaxed left ventricle. Before the end of ventricular relaxation, the left atrium contracts, and enough blood is pushed from the left atrium into the left ventricle to complete left ventricular filling. ❼ Following left atrial contraction, the left ventricle begins to contract. This contraction pushes blood against the bicuspid valve, forcing it closed. After pressure within the left ventricle increases, the aortic semilunar valve is forced open, and blood flows into the aorta. ❽ Blood flowing through the aorta is distributed to all parts of the body, except to those parts of the lungs supplied by the pulmonary blood vessels. As the left ventricle relaxes, its pressure falls rapidly, and pressure in the aorta becomes greater than in the left ventricle. The backflow of blood forces the aortic semilunar valve to close. Page 362 PROCESS Figure PROCESS Figure 12.10 Blood Flow Through the Heart  Imagine that you are a red blood cell moving through the circulation. After moving into the right atrium, how many heart valves will you pass through before you enter the circulation of the lungs? How many heart valves will you pass through before entering the circulation of the brain? Coronary Arteries The cardiac muscle in the wall of the heart is thick and metabolically very active and therefore requires an ample blood supply. Coronary arteries and cardiac veins provide the pathway for blood through the heart wall. Two coronary arteries supply blood to the wall of the heart (figure 12.11a). The coronary arteries originate from the base of the aorta, just above the aortic semilunar valves. The left coronary artery originates on the left side of the aorta. It has three major branches: (1) the anterior interventricular artery, (2) the circumflex artery, and (3) the left marginal artery. The anterior interventricular artery lies in the anterior interventricular sulcus; the circumflex artery extends around the coronary sulcus on the left to the posterior surface of the heart; and the left marginal artery extends inferiorly along the lateral wall of the left ventricle from the circumflex artery. The branches of the left coronary artery supply much of the anterior wall of the heart and most of the left ventricle. Page 363  Figure 12.11 Blood Supply t o t he Heart Th e v essels of th e anter ior su r face of th e h ear t depicted h er e ar e dar ker in color , w h er eas th e v essels of th e poster ior su r face ar e seen th r ou gh th e h ear t and ar e ligh ter in color. (a) Cor onar y ar ter ies su pply blood to th e w all of th e h ear t. (b) Car diac v eins car r y blood fr om th e w all of th e h ear t back to th e r igh t atr iu m. The right coronary artery originates on the right side of the aorta. It extends around the coronary sulcus on the right to the posterior surface of the heart and gives rise to the posterior interventricular artery, which lies in the posterior interventricular sulcus. The right marginal artery extends inferiorly along the lateral wall of the right ventricle. The right coronary artery and its branches supply most of the wall of the right ventricle. In a resting person, blood flowing through the coronary arteries gives up approximately 70% of its O2. In comparison, blood flowing through arteries to skeletal muscle gives up only about 25% of its O2. The percentage of O2 the blood releases to skeletal muscle increases to 70% or more during exercise, but the percentage of O2 the blood releases to cardiac muscle cannot increase substantially during exercise. Therefore, the rate of blood flow through the coronary arteries must increase above its resting level to provide cardiac muscle with adequate O2 during exercise. When the heart contracts, the blood vessels of the coronary circulation are compressed, reducing blood flow through them. As a consequence, blood flow into the coronary circulation is greatest while the ventricles of the heart are relaxed. This is different compared to blood vessels in other tissues because blood flow into other arteries of the body is highest during contraction of the ventricles. Apply It 1 Describe the effect on the heart if blood flow through the anterior interventricular artery is restricted or completely blocked (Hint: See figure 12.11a). Cardiac Veins The cardiac veins drain blood from the cardiac muscle. Their pathways are nearly parallel to the coronary arteries, and most of them drain blood into the coronary sinus, a large vein located within the coronary sulcus on the posterior aspect of the heart. Blood flows from the coronary sinus into the right atrium (figure 12.11b). Some small cardiac veins drain directly into the right atrium. 12.4 HISTOLOGY OF THE HEART Learning Outcomes After reading this section, you should be able to The heart wall is composed of three layers of tissue: (1) the epicardium, (2) the myocardium, and (3) the endocardium (figure 12.12). The epicardium (EP-ih-KAR-dee-um), also called the visceral pericardium, is a thin, serous membrane forming the smooth outer surface of the heart. It consists of simple squamous epithelium overlying a layer of loose connective tissue and adipose tissue. The myocardium (MY-oh-KAR-dee-um) is the thick, middle layer of the heart, composed of cardiac muscle cells. The myocardium is responsible for contraction of the heart chambers. The endocardium (EN-doh-KAR-dee-um) is the smooth inner surface of the heart, which consists of simple squamous epithelium over a layer of connective tissue. The endocardium allows blood to move easily through the heart. The heart valves are formed by folds of endocardium that include a thick layer of connective tissue.  Figure 12.12 Heart Wall Th is enlar ged section of th e h ear t w all illu str ates th e epicar diu m (v iscer al per icar diu m ), th e m y ocar diu m , and th e endocar diu m. The surfaces of the interior walls of the ventricles are modified by ridges and columns of cardiac muscle called trabeculae carneae. Smaller muscular ridges are also present in portions of the atria. Page 364 CLINICAL IMPACT Cardiac muscle cells are elongated, branching cells that contain one, or occasionally two, centrally located nuclei (figure 12.13). Cardiac muscle cells contain actin and myosin myofilaments organized to form sarcomeres, which are joined end-to-end to form myofibrils (see chapter 7). The actin and myosin myofilaments are responsible for muscle contraction, and their organization gives cardiac muscle a striated (banded) appearance much like that of skeletal muscle. However, the striations are less regularly arranged and less numerous than in skeletal muscle. Page 365  Figure 12.13 Cardiac Muscle Cells (a) Car diac m u scle cells ar e br anch ing cells w ith centr ally located nu clei. Th e cells ar e joined to one anoth er by inter calated disks, w h ich allow action potentials to pass fr om one car diac m u scle cell to th e next. (b) In a ligh t m icr ogr aph of car diac m u scle tissu e, th e m u scle fiber s appear str iated becau se of th e ar r angem ent of th e indiv idu al m y ofilam ents. (c) A s in skeletal m u scle, sar com er es join end-to-end to for m m y ofibr ils, and m itoch ondr ia pr ov ide A TP for contr action. Sar coplasm ic r eticu lu m and T tu bu les ar e v isible bu t ar e not as nu m er ou s as th ey ar e in skeletal m u scle. (b) ©Ed Resch ke Like skeletal muscle, cardiac muscle relies on Ca2 + and ATP for contraction. Calcium ions enter cardiac muscle cells in response to action potentials and activate the process of contraction much as they do in skeletal muscle. ATP production occurs primarily in mitochondria and depends on O2 availability. Cardiac muscle cells have many mitochondria, which produce ATP at a rate rapid enough to sustain the normal energy requirements of cardiac muscle. An extensive capillary network provides adequate O2 to the cardiac muscle cells. Unlike skeletal muscle, cardiac muscle cannot develop a significant oxygen deficit. Development of a large oxygen deficit could result in muscular fatigue and cessation of cardiac muscle contraction. Cardiac muscle cells are organized into spiral bundles or sheets (see figure 12.9). When cardiac muscle fibers contract, not only do the muscle fibers shorten but the spiral bundles twist to compress the contents of the heart chambers. Cardiac muscle cells are bound end-to-end and laterally to adjacent cells by specialized cell-to-cell contacts called intercalated (in- TER-kah-lay-ted) disks (figure 12.13). The membranes of the intercalated disks are highly folded, and the adjacent cells fit together, greatly increasing contact between them and preventing cells from pulling apart. Specialized cell membrane structures in the intercalated disks called gap junctions (see chapter 4) allow cytoplasm to flow freely between cells. This enables action potentials to pass quickly and easily from one cell to the next. The cardiac muscle cells of the atria or ventricles, therefore, contract at nearly the same time. The heart’s highly coordinated pumping action depends on this characteristic. 12.5 STIMULATION OF THE HEART Learning Outcomes After reading this section, you should be able to Muscle contractions do not occur unless the muscle has been stimulated. In chapter 7 we discussed the relationship between the stimulation of skeletal muscle fibers and the sequence of events that leads to contraction of those same muscle fibers. Similarly, cardiac muscle cells must be stimulated before they contract. Recall from section 12.3 that blood flows from the atria into the ventricles and then out of the heart through the great arteries. The movement of blood through the heart is determined by a coordinated sequence of cardiac muscle contractions, with atrial contraction first, followed by ventricular contraction. Figure 12.14 illustrates the coordination of the stimulation and contraction of the areas of the heart. ❶ The heart is at rest and all chambers are relaxed. ❷ Cardiac muscle cells in the atrial wall are stimulated as action potentials spread across the atrial wall and towards the ventricles. ❸ Cardiac muscle cells in the atrial wall contract, pushing blood into the ventricles. ❹ Cardiac muscle cells in the ventricular wall are stimulated as action potentials spread across the ventricular wall from the apex of the heart towards its base. ❺ Cardiac muscle cells in the ventricular wall contract, pushing blood into the great arteries. Page 366 PROCESS Figure PROCESS Figure 12.14 Coordination of Cardiac Muscle Stimulation and Contraction. During which step of this process is blood flowing through the atrioventricular valves? the semilunar valves? Like action potentials in skeletal muscle and neurons, those in cardiac muscle exhibit depolarization followed by repolarization. In cardiac muscle, however, a period of slow repolarization greatly prolongs the action potential (figure 12.15). In contrast to action potentials in skeletal muscle, which take less than 2 milliseconds (ms) to complete, action potentials in cardiac muscle take approximately 200 to 500 ms to complete. In addition, unlike in skeletal muscle, in which an action potential is initiated at each cell by a motor neuron (see chapter 7), action potentials in cardiac muscle can spread from one cell to adjacent cells through gap junctions at intercalated disks. Figure 12.15 Comparison of Act ion Pot ent ials in Skelet al and Cardiac Muscle (a) A n action potential in skeletal m u scle consists of depolar ization and r epolar ization ph ases. Th e r efr actor y per iod is indicated by th e purple sh aded ar ea. (b) A n action potential in car diac m u scle consists of depolar ization, plateau , and r epolar ization ph ases. Car diac m u scle does not r epolar ize as  r apidly as skeletal m u scle (indicated by the break in the curve) becau se of th e plateau ph ase. Du e to th e pr olonged action potential and r efr actor y per iod (indicated by th e purple sh aded ar ea), car diac m u scle contr acts and r elaxes alm ost com pletely befor e anoth er action potential can be pr odu ced. In cardiac muscle, each action potential consists of a depolarization phase followed by a period of slow repolarization called the plateau phase. At the end of the plateau phase, a rapid repolarization phase takes place. During the final repolarization phase, the membrane potential achieves its maximum degree of repolarization (figure 12.15b) and returns to the resting membrane potential. The opening and closing of membrane channels are responsible for the changes in the permeability of the cell membrane that produce action potentials (see chapter 8). The initial, rapid depolarization phase of the action potential results from the opening of voltage-gated Na+ channels, which increases the permeability of the cell membrane to Na+. Sodium ions then diffuse into the cell, causing depolarization. The depolarization of cardiac muscle fibers by Na+ is critical for the next steps in producing contractions of cardiac muscle. Sodium entry triggers opening of voltage-gated Ca2 + channels, and Ca2 + begins diffusing into the cell, contributing to the overall depolarization. At the peak of depolarization, the Na+ channels close, and a small number of K+ channels open. However, the Ca2 + channels remain open. Thus, the exit of K+ from the cell is counteracted by the continued movement of Ca2 + into the cell. Consequently, the plateau phase is primarily the result of the opening of voltage-regulated Ca2 + channels. The slow diffusion of Ca2 + into the cell is the reason the cardiac muscle fiber action potential lasts longer than the action potentials in skeletal muscle fibers. The plateau phase ends, and the repolarization phase begins as the Ca2 + channels close and many K+ channels open, allowing K+ to move out of the cell. Page 367 Action potentials in cardiac muscle exhibit a refractory period, like that of action potentials in skeletal muscle and in neurons. The refractory period lasts about as long as the plateau phase of the action potential in cardiac muscle. The prolonged action potential and refractory period allow cardiac muscle to contract and relax almost completely before another action potential can be produced. Also, the long refractory period in cardiac muscle prevents tetanic, sustained contractions from occurring, thus ensuring a rhythm of contraction and relaxation for cardiac muscle. Therefore, action potentials in cardiac muscle are different from those in skeletal muscle because the plateau phase makes the action potential and its refractory period last longer. Apply It 2 Why is it important to prevent tetanic contractions in cardiac muscle but not in skeletal muscle? Unlike skeletal muscle that requires neural stimulation to contract, cardiac muscle can contract without neural stimulations. Contraction of the atria and ventricles is coordinated by specialized cardiac muscle cells in the heart wall that form the conduction system of the heart (figure 12.16). PROCESS Figure PROCESS Figure 12.16 Conduction System of the Heart  Why is it important for stimulation of the ventricles to begin at the apex and spread toward the base? All the cells of the conduction system can produce spontaneous action potentials. The conduction system of the heart includes (1) the sinoatrial node, (2) atrioventricular node, (3) atrioventricular bundle, (4) the bundle branches, and (5) Purkinje fibers. The sinoatrial (SA) node, which functions as the heart’s pacemaker, is located in the superior wall of the right atrium and initiates the contraction of the heart. The SA node produces action potentials at a faster rate than other areas of the heart and has a larger number of Ca2 + channels than other cells in the heart. In addition, the Na+ and Ca2 + channels in the SA node spontaneously open and close at a rhythmic rate. The heart rate can be affected by certain drugs. Calcium channel blocking agents, for example, are drugs that slow the heart by decreasing the rate of action potential production in the SA node. Calcium channel blockers decrease the rate at which Ca2 + moves through Ca2 + channels. As a result, it takes longer for depolarization to reach threshold, and the interval between action potentials increases. Figure 12.16 illustrates the pathways action potentials would follow through the conduction system of the heart. ❶ Action potentials originate in the SA node and spread through the myocardium of the right and left atrium, causing atrial contraction. ❷ Action potentials reach the atrioventricular (AV) (AY-tree-oh-ven- TRIK-you-lar) node, located in the lower portion of the right atrium. When action potentials reach the AV node, they spread slowly through it and then into the atrioventricular (AV) bundle, a group of specialized cardiac muscle cells in the interventricular septum. The slow rate of action potential conduction in the AV node allows the atria to complete their contraction before action potentials are delivered to the ventricles. ❸ The AV bundle then divides into two branches of conducting tissue, called the left and right bundle branches. Action potentials pass down the bundle branches toward the apex of the heart. ❹ At the tips of the left and right bundle branches, the conducting tissue forms many small bundles of Purkinje (per-KIN-jee) fibers. The  Purkinje fibers pass to the apex of the heart and then extend to the cardiac muscle of the ventricle walls. The AV bundle, the bundle branches, and the Purkinje fibers are composed of specialized cardiac muscle fibers that conduct action potentials more rapidly than do other cardiac muscle fibers. Consequently, action potentials are rapidly delivered to all the cardiac muscle of the ventricles. The coordinated contraction of the ventricles depends on the conduction of action potentials by the conduction system. The organization of the conduction system of the heart, particularly the Purkinje fibers, ensures that ventricular contractions begin at the apex and then spread up the ventricular walls. This pattern of movement pushes the blood up toward the great vessels (see figure 12.10). Page 368 Apply It 3 If blood supply is reduced in a small area of the heart through which the left bundle branch passes, how will this affect ventricular contraction? Following their contraction, the ventricles begin to relax. After the ventricles have completely relaxed, another action potential originates in the SA node to begin the next cycle of contractions. The SA node is the pacemaker of the heart, but other cells of the conduction system are also capable of producing action potentials spontaneously. For example, if the SA node is unable to function, another area, such as the AV node, becomes the pacemaker. The resulting heart rate is much slower than normal. When action potentials originate in an area of the heart other than the SA node, the result is called an ectopic (ek-TOP- ik) beat. Ectopic beats may cause very small portions of the heart to contract rapidly and independently of all other areas. This condition, called fibrillation (fih-brih-LAY-shun), reduces the output of the heart to only a few milliliters of blood per minute when it occurs in the ventricles. Unless ventricular fibrillation is stopped, the person dies in just a few minutes. To stop the process of fibrillation, health professionals use a technique called defibrillation, in which they apply a strong electrical shock to the chest region. The shock causes simultaneous depolarization of all cardiac muscle fibers. Following depolarization, the SA node can recover and produce action potentials before any other area of the heart. Consequently, the normal pattern of action potential generation and the normal rhythm of contraction are reestablished. Action potentials conducted through the heart during the cardiac cycle produce electrical currents that can be measured at the surface of the body. Electrodes placed on the body surface and attached to a recording device can detect the small electrical changes resulting from the action potentials in all of the cardiac muscle cells. The record of these electrical events is an electrocardiogram (ee-LEK-troh-KAR-dee-oh-gram; ECG or EKG) (figure 12.17). Figure 12.17 Elect rocardiogram Th e m ajor w av es and inter v als of an electr ocar diogr am ar e labeled. Each th in h or izontal line on th e ECG r ecor ding r epr esents 1 m illiv olt (m V ), and each th in v er tical line r epr esents 0.04 second. The normal ECG consists of a (1) P wave, (2) a QRS complex, and (3) a T wave. The P wave results from depolarization of the atrial myocardium, and the beginning of the P wave precedes the onset of atrial contraction. The QRS complex consists of three individual waves: the Q, R, and S waves. The QRS complex results from depolarization of the ventricles, and the beginning of the QRS complex precedes ventricular contraction. The T wave represents repolarization of the ventricles, and the beginning of the T wave precedes ventricular relaxation. A wave representing repolarization of the atria cannot be seen because it occurs during the QRS complex. The time between the beginning of the P wave and the beginning of the QRS complex is the PQ interval, commonly called the PR interval because the Q wave is very small. During the PQ interval, the atria contract and begin to relax. At the end of the PQ interval, the ventricles begin to depolarize. The QT interval extends from the beginning of the QRS complex to the end of the T wave and represents the length of time required for ventricular depolarization and repolarization. Page 369 MICROBES IN YOUR BODY  Apply It 4 Given that Streptococcus pneumoniae microlesions interrupt the electrical activity that flows between cardiac muscle cells, the heart can experience severe stress and may malfunction or stop contracting altogether. Using what you learned about skeletal muscle contraction, would microlesions in skeletal muscle cause the same type of reaction as in cardiac muscle? Page 370 It is important to note that the ECG is a record of electrical events of the heart and is not a direct measurement of mechanical events. This means that neither the force of contraction nor the blood pressure can be determined from an ECG. However, each deflection in the ECG record indicates an electrical event within the heart and correlates with a subsequent mechanical event. Consequently, the ECG is an extremely valuable tool for diagnosing a number of cardiac abnormalities, particularly because it is painless, easy to record, and nonsurgical. Analysis of an ECG can reveal abnormal heart rates or rhythms; problems in conduction pathways, such as blockages; hypertrophy or atrophy of portions of the heart; and the approximate location of damaged cardiac muscle. Table 12.1 describes several conditions associated with abnormal heart rhythms. Heart rate in excess of 100 beats per Elevated body temperature, minute (bpm) excessive sympathetic stimulation, toxic conditions Heart rate less than 60 bpm Increased stroke volume in athletes, excessive vagus nerve stimulation, nonfunctional SA node, carotid sinus syndrome Heart rate varies as much as 5% during Cause not always known; respiratory cycle and up to 30% occasionally caused by during deep respiration ischemia, inflammation, or cardiac failure  Sudden increase in heart rate to 150–250 Excessive sympathetic bpm for a few seconds or even for stimulation, abnormally several hours; P waves precede every elevated permeability of QRS complex; P wave is inverted and cardiac muscle to Ca2 + superimposed on T wave As many as 300 P waves/min and 125 QRS complexes/min; resulting in two or three P waves (atrial contractions) for every QRS complex (ventricular contraction) No P waves, normal QRS and T waves, irregular timing; ventricles are constantly stimulated by atria; reduced ventricle filling; increased chance of fibrillation Often associated with damage to AV node or ventricular muscle Apply It 5 Explain how the ECGs would appear for a person who has a damaged left bundle branch (see Apply It 3) and for a person who has many ectopic beats originating from her atria. 12.6 CARDIAC CYCLE Learning Outcome After reading this section, you should be able to The right and left halves of the heart can be viewed as two separate pumps. Each pump consists of a primer pump—the atrium—and a power pump— the ventricle. The atria act as primer pumps because they complete the filling of the ventricles with blood, and the ventricles act as power pumps because they produce the major force that causes blood to flow through the pulmonary and systemic circulations. The term cardiac cycle refers to the repetitive pumping process that begins with the onset of cardiac muscle contraction and ends with the beginning of the next contraction (figure 12.18). Pressure changes produced within the heart chambers as a result of cardiac muscle contraction move blood from areas of higher pressure to areas of lower pressure. Page 371 PROCESS Figure PROCESS Figure 12.18 Cardiac Cycle  Often, ventricular systole is divided into two phases: the isovolumetric (same-volume) phase and the ventricular ejection phase. What are some differences between these two phases? Atrial systole (SIS-toh-lee; a contracting) refers to contraction of the two atria. Ventricular systole refers to contraction of the two ventricles. Atrial diastole (die-AS-toh-lee; dilation) refers to relaxation of the two atria, and ventricular diastole refers to relaxation of the two ventricles. When the terms systole and diastole are used alone, they refer to ventricular contraction or relaxation. The ventricles contain more cardiac muscle than the atria and produce far greater pressures, which force blood to circulate throughout the vessels of the body. Page 372 During the cardiac cycle, changes in chamber pressure and the opening and closing of the heart valves determine the direction of blood movement. As the cardiac cycle is described, it is important to focus on these pressure changes and heart valve movements. Before we start, it is also important to have a clear image of the state of the heart. At the beginning of the cardiac cycle, the atria and ventricles are relaxed, the AV valves are open, and the semilunar valves are closed. Figure 12.18 illustrates the major events of the cardiac cycle. ❶ Blood returning to the heart first enters the atria. Since the AV valves are open, blood flows into the ventricles, filling them to approximately 70% of their volume. ❷ Atrial systole—The atria contract, forcing additional blood to flow into the ventricles to complete their filling. The semilunar valves remain closed. ❸ Ventricular systole—At the beginning of ventricular systole, contraction of the ventricles pushes blood toward the atria, causing the AV valves to close as the pressure in the ventricles begins to increase. ❹ As ventricular systole continues, the increasing pressure in the ventricles exceeds the pressure in the pulmonary trunk and aorta, the semilunar  valves are forced open, and blood is ejected into the pulmonary trunk and aorta. ❺ Ventricular diastole—At the beginning of ventricular diastole, the pressure in the ventricles decreases below the pressure in the aorta and pulmonary trunk. The semilunar valves close and prevent blood from flowing back into the ventricles. As diastole continues, the pressure continues to decline in the ventricles until atrial pressures are greater than ventricular pressures. Then the AV valves open, and blood flows directly from the atria into the relaxed ventricles. During the previous ventricular systole, the atria were relaxed and blood collected in them. When the ventricles relax and the AV valves open, blood flows into the ventricles (see figure 12.18, step 1) and they begin to fill again. Figure 12.19 displays the main events of the cardiac cycle and should be examined from top to bottom for each period. 1. The ECG indicates the electrical events that cause the atria and ventricles to contract and relax. 2. The pressure graph shows the pressure changes within the left atrium (blue dashed line), left ventricle (black line), and aorta (red dashed line) resulting from atrial and ventricular contraction and relaxation. The pressure changes in the right side of the heart are not shown here, but they are similar to those in the left side, only lower. 3. The volume graph presents the changes in left ventricular volume as blood flows into and out of the left ventricle as a result of the pressure changes. 4. The sound graph records the closing of valves caused by blood flow. Page 373 Figure 12.19 Ev ent s of t he Cardiac Cy cle (Top) Th e car diac cy cle is div ided into fiv e per iods. From top to bottom, th ese gr aph s sh ow an electr ocar diogr am ; pr essu r e ch anges for th e left atr iu m (blue dashed line), th e left v entr icle (black  line), and th e aor ta (red dotted line); left v entr icu lar v olu m e cu r v e; and th e sequ ence of th e h ear t sou nds. By reviewing the events of each period, you can see that as the atria are stimulated (P wave in Panel 1), we can see an increase in left atrial pressure (blue dashed line in Panel 2). See figure 12.18 for illustrations of the valves and blood flow. Apply It 6 Describe the effect of a leaky (incompetent) aortic semilunar valve on the volume of blood in the left ventricle just before ventricular contraction. Describe the effect of a severely narrowed opening through the aortic semilunar valves on the amount of work the heart must do to pump the normal volume of blood into the aorta during each beat of the heart. Page 374 12.7 HEART SOUNDS Learning Outcome After reading this section, you should be able to The stethoscope (STETH-oh-skope; stetho, the chest) was originally developed to listen to the sounds of the lungs and heart and is now used to listen to other sounds of the body as well. Figure 12.20 shows the sites on the thorax where the heart sounds can best be heard with a stethoscope. There are two main heart sounds. The first heart sound can be represented by the syllable lubb, and the second heart sound can be represented by dupp. The first heart sound has a lower pitch than the second. The first heart sound occurs at the beginning of ventricular systole and results from closure of the AV valves (see figure 12.18, step 3, and figure 12.19). The second heart sound occurs at the beginning of ventricular diastole and results from closure of the semilunar valves (see figure 12.18, step 5, and figure 12.19). The valves usually do not make sounds when they open.  Figure 12.20 Locat ion of t he Heart Valv es in t he Thorax Su r face m ar kings of th e h ear t in an adu lt m ale. Th e positions of th e fou r h ear t v alv es ar e indicated by blue ellipses, and th e sites w h er e th e sou nds of th e v alv es ar e best h ear d w ith a steth oscope ar e indicated by pink circles. ©Ju ice Im ages/A lam y RF Clinically, ventricular systole occurs between the first and second heart sounds. Ventricular diastole occurs between the second heart sound and the first heart sound of the next beat. Because ventricular diastole lasts longer than ventricular systole, there is less time between the first and second heart sounds than between the second heart sound and the first heart sound of the next beat. Apply It 7 Compare the rate of blood flow out of the ventricles between the first and second heart sounds of the same beat to the rate of blood flow out of the ventricles between the second heart sound of one beat and the first heart sound of the next beat. In some individuals, a heart valve does not close completely and thus is called an incompetent valve. Such valves leak when they are supposed to be closed and allow blood to flow in the reverse direction. For example, an incompetent bicuspid valve allows blood to flow from the left ventricle to the left atrium during ventricular systole. This reduces the amount of blood pumped into the aorta. It also dramatically increases the blood pressure in the left atrium and in the pulmonary veins during ventricular systole. During diastole, the excess blood pumped into the atrium once again flows into the ventricle, along with the blood that normally flows from the lungs to the left atrium. Therefore, the volume of blood entering the left ventricle is greater than normal. The increased filling of the left ventricle gradually causes it to hypertrophy and can lead to heart failure. The increased pressure in the pulmonary veins can cause edema in the lungs. This information may be useful in answering the Learn to Apply It question at the beginning of the chapter. Abnormal heart sounds called murmurs are usually a result of faulty valves. For example, an incompetent valve fails to close tightly, so blood leaks through the valve when it is closed, making a swishing sound immediately after the valve closes. For example, an incompetent AV valve produces a swishing sound immediately after the first heart sound. When the opening of a valve is narrowed, or stenosed (STEN-ohzd; a narrowing), a swishing sound precedes closure of the stenosed valve. For example, when the bicuspid valve is stenosed, a swishing sound precedes the first heart sound. Apply It 8 If normal heart sounds are represented by lubb-dupp, lubb- dupp, what does a heart sound represented by lubb-duppshhh, lubb-duppshhh represent? What does lubb-shhhdupp, lubb- shhhdupp represent (assuming that shhh represents a swishing sound)? 12.8 REGULATION OF HEART FUNCTION Learning Outcomes After reading this section, you should be able to Various measurements can be taken to assess the heart’s function. Cardiac output (CO) is the volume of blood pumped by either ventricle of the heart each minute. Stroke volume (SV) is the volume of blood pumped per ventricle each time the heart contracts, and the heart rate (HR) is the number of times the heart contracts each minute. Cardiac output can be calculated by multiplying the stroke volume times the heart rate: Under resting conditions, the heart rate is approximately 72 beats/min, and the stroke volume is approximately 70 mL/beat. Consequently, the cardiac output is slightly more than 5 L/min: The heart rate and the stroke volume vary considerably among people. Athletes tend to have a higher stroke volume and lower heart rate at rest because exercise has increased the size of their hearts. Nonathletes are more likely to have a higher heart rate and lower stroke volume. During exercise, the heart rate in a nonathlete can increase to 190 bpm, and the stroke volume can increase to 115 mL/beat. Therefore, the cardiac output increases to approximately 22 L/min: This cardiac output is several times greater than the cardiac output under resting conditions. Athletes can increase their cardiac output to a greater degree than nonathletes. The control mechanisms that modify the stroke volume and the heart rate are classified as intrinsic and extrinsic. Intrinsic regulation results from the heart’s normal functional characteristics and does not depend on either neural or hormonal regulation. It is functional whether the heart is in place in the body or is removed and maintained outside the body under proper conditions. Extrinsic regulation involves neural and hormonal control. Neural regulation of the heart results from sympathetic and parasympathetic reflexes, and the major hormonal regulation comes from epinephrine and norepinephrine secreted by the adrenal medulla. Intrinsic regulation refers to mechanisms contained within the heart itself. An example involves the affect cardiac muscle length has on force of contraction. The force of contraction produced by cardiac muscle is related to the degree of stretch of cardiac muscle fibers. And the degree of stretch of cardiac muscle in the ventricles at the end of ventricular diastole is determined by the amount of blood in the ventricles. You can relate this to filling a balloon with water. As more water (greater volume) is added to the balloon, the wall of the balloon stretches more. Preload is the degree to which the ventricular walls are stretched at the end of diastole, and venous return is the amount of blood that returns to the heart. If venous return increases, the heart fills to a greater volume and stretches the cardiac muscle fibers, producing a greater preload. In response, cardiac muscle fibers contract with more force. The stronger force of contraction causes an increased volume of blood to be ejected from the heart, resulting in a greater stroke volume. As venous return increases, resulting in a greater preload, cardiac output increases. Conversely, if venous return decreases, resulting in a lower preload, the cardiac output decreases. The relationship between preload and stroke volume is called Starling’s law of the heart. Because venous return is influenced by many conditions, Starling’s law of the heart has a major influence on cardiac output. For example, muscular activity during exercise causes increased venous return, resulting in increased preload, stroke volume, and cardiac output. This is beneficial because increased cardiac output is needed during exercise to supply O2 to exercising skeletal muscles. Afterload refers to the pressure against which the ventricles must pump blood. People suffering from hypertension have an increased afterload because their aortic pressure is elevated during contraction of the ventricles. Recall that left-ventricular pressure must increase above aortic pressure to force open the aortic semilunar valve. The heart must do more work to pump blood from the left ventricle into the aorta, which increases the workload on the heart and can eventually lead to heart failure. A reduced afterload decreases the work the heart must do. People who have lower blood pressure have a reduced afterload and develop heart failure less often than people who have hypertension. However, the afterload influences cardiac output less than preload influences it. The afterload must increase substantially before it decreases the volume of blood pumped by a healthy heart. Page 375 CLINICAL IMPACT Extrinsic regulation includes nervous regulation and chemical regulation. Nervous Regulation: Baroreceptor Reflex The autonomic nervous system influences the pumping action of the heart and thereby affects cardiac output by altering both heart rate and stroke volume. Sympathetic and parasympathetic nerve fibers innervate the heart and have a major effect on the SA node. Stimulation by sympathetic nerve fibers causes the heart rate and the stroke volume to increase, whereas stimulation by parasympathetic nerve fibers causes the heart rate to decrease. The baroreceptor (bar-oh-ree-SEP-ter; baro, pressure) reflex is a mechanism of the nervous system that plays an important role in regulating heart function. Baroreceptors are stretch receptors that monitor blood pressure in the aorta and in the wall of the internal carotid arteries, which carry blood to the brain. Changes in blood pressure result in changes in the stretch of the walls of these blood vessels—and changes in the frequency of action potentials produced by the baroreceptors. The action potentials are transmitted along nerve fibers from the stretch receptors to the medulla oblongata of the brain. Within the medulla oblongata is a cardioregulatory center, which receives and integrates action potentials from the baroreceptors. The cardioregulatory center controls the action potential frequency in sympathetic and parasympathetic nerve fibers that extend from the brain and spinal cord to the heart. The cardioregulatory center also influences sympathetic stimulation of the adrenal gland. Epinephrine and norepinephrine, released from the adrenal gland, increase the stroke volume and heart rate. Figure 12.21 shows how the baroreceptor reflex keeps the heart rate and stroke volume within normal ranges. When the blood pressure increases, the baroreceptors are stimulated. Action potentials are sent along the nerve fibers to the medulla oblongata at increased frequency. This prompts the cardioregulatory center to increase parasympathetic stimulation and decrease sympathetic stimulation of the heart. As a result, the heart rate and stroke volume decrease, causing blood pressure to decline. Page 376 Homeostasis Figure 12.21 Barorecept or Reflex Th e bar or eceptor r eflex m aintains h om eostasis in r esponse to ch anges in blood pr essu r e. (1 ) Blood pr essu r e is w ith in its nor m al r ange. (2 ) Blood pr essu r e incr eases ou tside th e nor m al r ange, w h ich cau ses h om eostasis to be distu r bed. (3 ) Bar or eceptor s in th e car otid ar ter ies and aor ta detect th e incr ease in blood pr essu r e and th e car dior egu lator y center in th e br ain alter s au tonom ic stim u lation  of th e h ear t. (4 ) Hear t r ate and str oke v olu m e decr ease. (5) Th ese ch anges cau se blood pr essu r e to decr ease. (6 ) Blood pr essu r e r etu r ns to its nor m al r ange, and h om eostasis is r estor ed. When the blood pressure decreases, less stimulation of the baroreceptors occurs. A lower frequency of action potentials is sent to the medulla oblongata of the brain, and this triggers a response in the cardioregulatory center. The cardioregulatory center responds by increasing sympathetic stimulation of the heart and decreasing parasympathetic stimulation. Consequently, the heart rate and stroke volume increase, causing blood pressure to increase. If the decrease in blood pressure is large, sympathetic stimulation of the adrenal medulla also increases. The epinephrine and norepinephrine secreted by the adrenal medulla also increase the heart rate and stroke volume, also causing the blood pressure to increase toward its normal value (figure 12.21). Apply It 9 In response to a severe hemorrhage, blood pressure lowers, the heart rate increases dramatically, and the stroke volume lowers. If low blood pressure activates a reflex that increases sympathetic stimulation of the heart, why is the stroke volume low? Chemical Regulation: Chemoreceptor Reflex Epinephrine and small amounts of norepinephrine released from the adrenal medulla in response to exercise, emotional excitement, or stress also influence the heart’s function. Epinephrine and norepinephrine bind to receptor proteins on cardiac muscle and cause increased heart rate and stroke volume. Excitement, anxiety, or anger can affect the cardioregulatory center, resulting in increased sympathetic stimulation of the heart and increased cardiac output. Depression, on the other hand, can increase parasympathetic stimulation of the heart, causing a slight reduction in cardiac output. The medulla oblongata of the brain also contains chemoreceptors that are sensitive to changes in pH and CO2 levels. A decrease in pH, often caused by an increase in CO2, results in sympathetic stimulation of the heart (figure 12.22). Page 377 Homeostasis Figure 12.22 Chemorecept or Reflex—pH Th e ch em or eceptor r eflex m aintains h om eostasis in r esponse to ch anges in blood concentr ations of CO2 and H + (or pH). (1 ) Blood pH is w ith in its nor m al r ange. (2 ) Blood pH incr eases ou tside th e nor m al r ange. (3 ) Ch em or eceptor s in th e m edu lla oblongata detect incr eased blood pH. Contr ol center s in th e br ain decr ease sy m path etic stim u lation of th e h ear t and adr enal m edu lla. (4 ) Hear t r ate and str oke v olu m e decr ease, r edu cing blood flow to lu ngs. (5) Th ese ch anges cau se blood pH to decr ease (as a r esu lt of incr ease in blood CO2). (6 ) Blood pH r etu r ns to its nor m al r ange, and h om eostasis is r estor ed.  Changes in the extracellular concentration of K+ , Ca2 + , and Na+ , which influence other electrically excitable tissues, also affect cardiac muscle function. An excess of extracellular K+ causes the heart rate and stroke volume to decrease. If the extracellular K+ concentration increases further, normal conduction of action potentials through cardiac muscle is blocked, and death can result. An excess of extracellular Ca2 + causes the heart to contract arrhythmically. Reduced extracellular Ca2 + causes both the heart rate and stroke volume to decrease. Figure 12.23 summarizes how nervous and chemical factors interact to regulate the heart rate and stroke volume. PROCESS Figure PROCESS Figure 12.23 Summary of Extrinsic Regulation  Cardiac muscle is described as being under involuntary control. Why is it that some individuals can seemingly “control” their heart rate through meditation? ❶ Sensory neurons carry action potentials from baroreceptors to the cardioregulatory center. Chemoreceptors in the medulla oblongata influence the cardioregulatory center. ❷ The cardioregulatory center controls the frequency of action potentials in the parasympathetic neurons extending to the heart. The parasympathetic neurons decrease the heart rate. ❸ The cardioregulatory center controls the frequency of action potentials in the sympathetic neurons extending to the heart. The sympathetic neurons increase the heart rate and the stroke volume. ❹ The cardioregulatory center influences the frequency of action potentials in the sympathetic neurons extending to the adrenal medulla. The sympathetic neurons increase the secretion of epinephrine and some norepinephrine into the general circulation. Epinephrine and norepinephrine increase the heart rate and stroke volume. Page 378 SYSTEMS PATHOLOGY  Page 379 Figure 12.24 Apply It 10 Severe ischemia in the wall of a ventricle can cause the death of cardiac muscle cells. Inflammation develops around the necrotic (dead) tissue, and macrophages invade and phagocytize dead cells. At the same time, blood vessels and connective tissue grow into the necrotic area and begin to deposit connective tissue to replace the necrotic tissue. While Paul was still recovering in the hospital, another patient was admitted with a similar condition. After about a week, that person’s blood pressure suddenly decreased to very low levels, and he died within a short time. An autopsy revealed a large amount of blood in the pericardial sac and a rupture in the wall of the left ventricle. Explain these effects. Figure 12.25 Page 380 Page 381  Body temperature affects the metabolism in the heart just as it affects other tissues. Elevated body temperature increases the heart rate, and reduced body temperature slows the heart rate. For example, the heart rate is usually elevated when a person has a fever. During heart surgery, the body temperature is sometimes intentionally lowered to slow the heart rate and metabolism. E F F E C T S O F A G I N G O N T H E H E A R T SUMMA RY  1. The heart generates blood pressure. 2. The heart routes blood through the systemic and pulmonary circulations. 3. The heart’s pumping action and its valves ensure a one-way flow of blood through the heart and blood vessels. 4. The heart helps regulate blood supply to tissues. The heart is approximately the size of a closed fist and is located in the pericardial cavity. Pericardium 1. The pericardium is a sac consisting of fibrous and serous pericardia. The fibrous pericardium is lined by the parietal pericardium. 2. The outer surface of the heart is lined by the visceral pericardium (epicardium). 3. Between the visceral and parietal pericardia is the pericardial cavity, which is filled with pericardial fluid. External Anatomy 1. The atria are separated externally from the ventricles by the coronary sulcus. The right and left ventricles are separated externally by the interventricular sulci. 2. The inferior and superior venae cavae enter the right atrium. The four pulmonary veins enter the left atrium. 3. The pulmonary trunk exits the right ventricle, and the aorta exits the left ventricle. Heart Chambers and Internal Anatomy 1. There are four chambers in the heart. The left and right atria receive blood from veins and function mainly as reservoirs. Contraction of the atria completes ventricular filling. 2. The atria are separated internally from each other by the interatrial septum.  3. The ventricles are the main pumping chambers of the heart. The right ventricle pumps blood into the pulmonary trunk, and the left ventricle, which has a thicker wall, pumps blood into the aorta. 4. The ventricles are separated internally by the interventricular septum. Heart Valves 1. The heart valves ensure one-way flow of blood. 2. The tricuspid valve (three cusps) separates the right atrium and the right ventricle, and the bicuspid valve (two cusps) separates the left atrium and the left ventricle. 3. The papillary muscles attach by the chordae tendineae to the cusps of the tricuspid and bicuspid valves and adjust tension on the valves. 4. The aorta and pulmonary trunk are separated from the ventricles by the semilunar valves. 5. The skeleton of the heart is a plate of fibrous connective tissue that separates the atria from the ventricles, acts as an electrical barrier between the atria and ventricles, and supports the heart valves. Route of Blood Flow Through the Heart 1. The left and right sides of the heart can be considered separate pumps. 2. Blood flows from the systemic vessels to the right atrium and from the right atrium to the right ventricle. From the right ventricle, blood flows to the pulmonary trunk and from the pulmonary trunk to the lungs. From the lungs, blood flows through the pulmonary veins to the left atrium, and from the left atrium, blood flows to the left ventricle. From the left ventricle, blood flows into the aorta and then through the systemic vessels. Blood Supply to the Heart 1. The left and right coronary arteries originate from the base of the aorta and supply the heart. 2. The left coronary artery has three major branches: the anterior interventricular, the circumflex, and the left marginal arteries. 3. The right coronary artery has two major branches: the posterior interventricular and the right marginal arteries.  4. Blood returns from heart tissue through cardiac veins to the coronary sinus and into the right atrium. Small cardiac veins also return blood directly to the right atrium. Heart Wall The heart wall consists of the outer epicardium, the middle myocardium, and the inner endocardium. Cardiac Muscle 1. Cardiac muscle is striated; it depends on ATP for energy and on aerobic metabolism. 2. Cardiac muscle cells are joined by intercalated disks that allow action potentials to be propagated throughout the heart. The movement of blood through the heart is determined by a coordinated sequence of cardiac muscle contractions: atria contract first, followed by ventricular contraction. Action Potentials in Cardiac Muscle 1. Action potentials in cardiac muscle are prolonged compared to those in skeletal muscle and have a depolarization phase, a plateau phase, and a repolarization phase. 2. The depolarization is due mainly to opening of the voltage-gated Na+ channels, and the plateau phase is due to opened voltage-gated Ca2+ channels. Repolarization at the end of the plateau phase is due to the opening of K+ channels for a brief period. 3. The prolonged action potential in cardiac muscle ensures that contraction and relaxation occur and prevents tetany. 4. The SA node located in the upper wall of the right atrium is the normal pacemaker of the heart, and cells of the SA node have more voltage-gated Ca2+ channels than do other areas of the heart. Conduction System of the Heart  1. The conduction system of the heart is made up of specialized cardiac muscle cells. 2. The SA node produces action potentials that are propagated over the atria to the AV node. 3. The AV node and the atrioventricular bundle conduct action potentials to the ventricles. 4. The right and left bundle branches conduct action potentials from the atrioventricular bundle through Purkinje fibers to the ventricular muscle. 5. An ectopic beat results from an action potential that originates in an area of the heart other than the SA node. Page 382 Electrocardiogram 1. An ECG is a record of electrical events within the heart. 2. An ECG can be used to detect abnormal heart rates or rhythms, abnormal conduction pathways, hypertrophy or atrophy of the heart, and the approximate location of damaged cardiac muscle. 3. A normal ECG consists of a P wave (atrial depolarization), a QRS complex (ventricular depolarization), and a T wave (ventricular repolarization). 4. Atrial contraction occurs during the PQ interval, and the ventricles contract and relax during the QT interval. 1. Atrial systole is contraction of the atria, and ventricular systole is contraction of the ventricles. Atrial diastole is relaxation of the atria, and ventricular diastole is relaxation of the ventricles. 2. During atrial systole, the atria contract and complete filling of the ventricles. 3. During ventricular systole, the AV valves close, pressure increases in the ventricles, the semilunar valves are forced open, and blood flows into the aorta and pulmonary trunk.  4. At the beginning of ventricular diastole, pressure in the ventricles decreases. The semilunar valves close to prevent backflow of blood from the aorta and pulmonary trunk into the ventricles. 5. When the pressure in the ventricles is low enough, the AV valves open, and blood flows from the atria into the ventricles. 1. The first heart sound results from closure of the AV valves. The second heart sound results from closure of the semilunar valves. 2. Abnormal heart sounds, called murmurs, can result from incompetent (leaky) valves or stenosed (narrowed) valves. Cardiac output (volume of blood pumped per ventricle per minute) is equal to the stroke volume (volume of blood ejected per beat) times the heart rate (beats per minute). Intrinsic Regulation of the Heart 1. Intrinsic regulation refers to regulation mechanisms contained within the heart. 2. As venous return to the heart increases, the heart wall is stretched, and the increased stretch of the ventricular walls is called preload. 3. A greater preload causes the cardiac output to increase because stroke volume increases (Starling’s law of the heart). 4. Afterload is the pressure against which the ventricles must pump blood. Extrinsic Regulation of the Heart 1. Extrinsic regulation refers to nervous and chemical mechanisms. 2. Sympathetic stimulation increases stroke volume and heart rate; parasympathetic stimulation decreases heart rate. 3. The baroreceptor reflex detects changes in blood pressure. If blood pressure increases suddenly, the reflex causes a decrease in heart rate and stroke volume; if blood pressure decreases suddenly, the reflex causes an increase in heart rate and stroke volume.  4. Emotions influence heart function by increasing sympathetic stimulation of the heart in response to exercise, excitement, anxiety, or anger and by increasing parasympathetic stimulation in response to depression. 5. Alterations in body fluid levels of CO2, pH, and ion concentrations, as well as changes in body temperature, influence heart function. REMEM BERING AND UNDERS TANDIN G 1. Describe the size and location of the heart, including its base and apex. 2. Describe the structure and function of the pericardium. 3. What chambers make up the left and right sides of the heart? What are their functions? 4. Describe the structure and location of the tricuspid, bicuspid, and semilunar valves. What is the function of these valves? 5. What are the functions of the atria and ventricles? 6. Starting in the right atrium, describe the flow of blood through the heart. 7. Describe the vessels that supply blood to the cardiac muscle. 8. Define heart attack and infarct. How does atherosclerotic plaque affect the heart? 9. Describe the three layers of the heart. Which of the three layers is most important in causing contractions of the heart? 10. Describe the structure of cardiac muscle cells, including the structure and function of intercalated disks. 11. Describe the events that result in an action potential in cardiac muscle. 12. Explain how cardiac muscle cells in the SA node produce action potentials spontaneously and why the SA node is the heart’s pacemaker. 13. What is the function of the conduction system of the heart? Starting with the SA node, describe the route of an action potential as it goes through the conduction system of the heart. 14. Explain the electrical events that generate each portion of the electrocardiogram. How do they relate to contraction events? 15. What contraction and relaxation events occur during the PQ interval and the QT interval of the electrocardiogram? 16. Define cardiac cycle, systole, and diastole. 17. Describe blood flow and the opening and closing of heart valves during the cardiac cycle. 18. Describe the pressure changes that occur in the left atrium, left ventricle, and aorta during ventricular systole and diastole (see figure 12.19). 19. What events cause the first and second heart sounds? 20. Define murmur. Describe how either an incompetent or a stenosed valve can cause a murmur. 21. Define cardiac output, stroke volume, and heart rate. 22. What is Starling’s law of the heart? What effect does an increase or a decrease in venous return have on cardiac output? 23. Describe the effect of parasympathetic and sympathetic stimulation on heart rate and stroke volume. Page 383 24. How does the nervous system detect and respond to the following? a. a decrease in blood pressure b. an increase in blood pressure 25. What is the effect of epinephrine on the heart rate and stroke volume? 26. Explain how emotions affect heart function. 27. What effects do the following have on cardiac output? a. a decrease in blood pH b. an increase in blood CO2 28. How do changes in body temperature influence the heart rate?  CRITICA L THINKIN G 1. A friend tells you that an ECG revealed that her son has a slight heart murmur. Should you be convinced that he has a heart murmur? Explain. 2. Explain the effect on Starling’s law of the heart if the parasympathetic (vagus) nerves to the heart are cut. 3. Describe the effect on heart rate if the sensory nerve fibers from the baroreceptors are cut. 4. An experiment is performed on a dog in which the arterial blood pressure in the aorta is monitored before and after the common carotid arteries are clamped. Explain the change in arterial blood pressure that would occur. (Hint: Baroreceptors are located in the internal carotid arteries, which are superior to the site of clamping of the common carotid arteries.) 5. What would be the effects on the heart if a person took a large dose of a drug that blocks calcium channels? 6. What happens to cardiac output following the ingestion of a large amount of fluid? 7. At rest, the cardiac output of athletes and nonathletes can be equal, but the heart rate of athletes is lower than that of nonathletes. At maximum exertion, the maximum heart rate of athletes and nonathletes can be equal, but the cardiac output of athletes is greater than that of nonathletes. Explain these differences. 8. Explain why it is useful that the walls of the ventricles are thicker than those of the atria. 9. Describe the effect of an incompetent aortic semilunar valve on ventricular and aortic pressure during ventricular systole and diastole. Answers to this chapter’s odd-numbered critical thinking questions appear in Appendix D Design Elements: (Microbes in Your Body): Janice Haney Carr/CDC; (Clinical Impact): Comstock/Alamy Stock Photo  Page 384 CHAPTER 13  Page 385 LEARN TO APPLY IT 13.1 FUNCTIONS OF THE CIRCULATORY SYSTEM Learning Outcome After reading this section, you should be able to The blood vessels of the body form a network more complex than an interstate highway system. The blood vessels carry blood to within two or three cell diameters of nearly all the trillions of cells that make up the body. Blood flow through them is regulated, so that cells receive adequate nutrients and so that waste products are removed. Blood vessels remain functional, in most cases, in excess of 70 years. And like many other structures of the body, when blood vessels are damaged, they repair themselves. Blood vessels outside the heart are divided into two classes: (1) the pulmonary vessels, which transport blood from the right ventricle of the heart through the lungs and back to the left atrium, and (2) the systemic vessels, which transport blood from the left ventricle of the heart through all parts of the body and back to the right atrium (see chapter 12 and figure 12.2). Together, the pulmonary vessels and the systemic vessels constitute the circulatory system. Blood flow through the circulatory system is ensured by the pumping action of the heart. On its own, the circulatory system has five functions:  1. Carries blood. Blood vessels carry blood from the heart to all the tissues of the body and back to the heart. 2. Exchanges nutrients, waste products, and gases with tissues. Nutrients and O2 diffuse from blood vessels to cells in essentially all areas of the body. Waste products and CO2 diffuse from the cells, where they are produced, to blood vessels. 3. Transports substances. Blood transports hormones, components of the immune system, molecules required for coagulation, enzymes, nutrients, gases, waste products, and other substances to and from all areas of the body. 4. Helps regulate blood pressure. The circulatory system and the heart work together to regulate blood pressure within a normal range. 5. Directs blood flow to the tissues. The circulatory system directs blood to tissues when increased blood flow is required to maintain homeostasis. 13.2 GENERAL FEATURES OF BLOOD VESSEL STRUCTURE Learning Outcome After reading this section, you should be able to The three main types of blood vessels are (1) arteries, (2) capillaries, and (3) veins. Arteries (AR-ter-ees) carry blood away from the heart; usually, the blood is oxygenated (oxygen-rich). Blood is pumped from the ventricles of the heart into large, elastic arteries, which branch repeatedly to form progressively smaller arteries. As they become smaller, the artery walls undergo a gradual transition from having more elastic tissue than smooth muscle to having more smooth muscle than elastic tissue (figure 13.1a–c). The arteries are normally classified in one of three categories: (1) elastic arteries, (2) muscular arteries, or (3) arterioles. The various arteries form a continuum from the largest elastic arteries to the smallest arterioles. Page 386  Figure 13.1 Blood Vessel St ruct ure With th e exception of capillar ies and v enu les, blood v essel w alls consist of th r ee lay er s, or tu nics: th e ou ter tu nica adv entitia, th e m iddle tu nica m edia, and th e inner tu nica intim a. Blood flows from arterioles into capillaries (KAP-i-lair-ees). It is at the capillaries where exchange of substances such as O2, nutrients, CO2, and other waste products occurs between the blood and the tissue fluid. Capillaries have thinner walls than do arteries (figure 13.1d). Blood flows through capillaries more slowly, and there are far more of them than of any other blood vessel type. From the capillaries, blood flows into veins. Veins (VANES) carry blood toward the heart; usually, the blood is deoxygenated (oxygen-poor). Compared to arteries, the walls of veins are thinner and contain less elastic tissue and fewer smooth muscle cells (figure 13.1e–g). Starting at capillaries and proceeding toward the heart, small-diameter veins come together to form larger-diameter veins, which are fewer in number. Veins increase in diameter and decrease in number as they progress toward the heart, and their walls increase in thickness. Veins may be classified, from smallest to largest, as (1) venules, (2) small veins, (3) medium-sized veins, or (4) large veins. Page 387 Except in capillaries and venules, blood vessel walls consist of three layers, or tunics (TOO-niks). From the inner to the outer wall, the tunics are (1) the tunica intima, (2) the tunica media, and (3) the tunica adventitia, or tunica externa (figure 13.2; see figure 13.1). Figure 13.2 Phot omicrograph of an Art ery and a Vein Th e ty pical str u ctu r e of a m ediu m -sized ar ter y (A ) and v ein (V ). Note th at th e ar ter y h as a th icker w all th an th e v ein. Th e pr edom inant lay er in th e w all of th e ar ter y is th e tu nica m edia w ith its cir cu lar lay er s  of sm ooth m u scle. Th e pr edom inant lay er in th e w all of th e v ein is th e tu nica adv entitia, and th e tu nica m edia is th inner. Ed Resch ke/Ph otolibr ar y /Getty Im ages The tunica intima (TOO-ni-kah IN-ti-mah), or innermost layer, consists of an endothelium (en-doh-THEE-lee-um), composed of simple squamous epithelial cells, a basement membrane, and a small amount of connective tissue. In muscular arteries, the tunica intima also contains a layer of thin elastic connective tissue. The tunica media, or middle layer, consists of smooth muscle cells arranged circularly around the blood vessel. It also contains variable amounts of elastic and collagen fibers, depending on the size and type of the vessel. In muscular arteries, a layer of elastic connective tissue forms the outer margin of the tunica media. The tunica adventitia (TOO-ni-kah ad-ven-TISH-ah) is composed of dense connective tissue adjacent to the tunica media; the tissue becomes loose connective tissue toward the outer portion of the blood vessel wall. Elastic arteries are the largest-diameter arteries and have the thickest walls (see figure 13.1a). Compared to other arteries, a greater proportion of their walls is composed of elastic tissue, and a smaller proportion is smooth muscle. The aorta and pulmonary trunk are examples of elastic arteries. Elastic arteries stretch when the ventricles of the heart pump blood into them. The elastic recoil of these arteries prevents blood pressure from falling rapidly and maintains blood flow while the ventricles are relaxed. The muscular arteries include medium-sized and small arteries. The walls of medium-sized arteries are relatively thick compared to their diameter. Most of the wall’s thickness is from smooth muscle cells of the tunica media (see figure 13.1b). Medium-sized arteries are frequently called distributing arteries because the smooth muscle tissue enables these vessels to control blood flow to different body regions. Contraction of the smooth muscle in blood vessels, called vasoconstriction (VAY-soh-con- STRIK-shun), decreases blood vessel diameter and blood flow. Relaxation of the smooth muscle in blood vessels, called vasodilation (VAY-soh-die-LAY- shun), increases blood vessel diameter and blood flow. Medium-sized arteries supply blood to small arteries. Small arteries have about the same structure as the medium-sized arteries, except for a smaller diameter and thinner walls. The smallest of the small arteries have only three or four layers of smooth muscle in their walls. Arterioles (ar-TEER-ee-oles) transport blood from small arteries to capillaries. Arterioles (see figure 13.1c) are the smallest arteries in which the three tunics can be identified. The tunica media of arterioles consists of only one or two layers of circular smooth muscle cells. Small arteries and arterioles are adapted for vasodilation and vasoconstriction. Blood flows from arterioles into capillaries. Capillaries branch to form networks (figure 13.3; see figure 13.1d). Blood flow through capillary networks is regulated by smooth muscle cells called precapillary sphincters. These precapillary sphincters are located at the origin of the branches of the capillaries and, by contracting and relaxing, regulate the amount of blood flow through the various sections of the network. Figure 13.3 Capillary Net work A capillar y netw or k stem s fr om an ar ter iole. Th e netw or k for m s nu m er ou s br anch es. Blood flow s th r ou gh capillar ies into v enu les. Sm ooth m u scle cells, called pr ecapillar y sph incter s, r egu late blood flow th r ou gh th e capillar ies. Blood flow decr eases w h en th e pr ecapillar y sph incter s constr ict and incr eases w h en th ey dilate. Page 388 Capillary walls are very thin and consist only of endothelium. The thin walls of capillaries facilitate diffusion between the capillaries and surrounding cells. Each capillary is 0.5–1 millimeter (mm) long. Capillaries branch without changing their diameter, which is approximately the same as the diameter of a red blood cell (7.5 μm).  Red blood cells flow through most capillaries in single file and are frequently folded as they pass through the smaller-diameter capillaries. As blood flows through capillaries, blood gives up O2 and nutrients to the tissue spaces and takes up CO2 and other by-products of metabolism. Capillary networks are more numerous and more extensive in the lungs and in highly metabolic tissues, such as the liver, kidneys, skeletal muscle, and cardiac muscle, than in other tissue types. Blood flows from capillaries into venules and from venules into small veins. Venules (VEN-yools) have a diameter slightly larger than that of capillaries and are composed of endothelium resting on a delicate connective tissue layer (see figure 13.1e). The structure of venules, except for their diameter, is very similar to that of capillaries. Small veins are slightly larger in diameter than venules. All three tunics are present in small veins. The tunica media contains a continuous layer of smooth muscle cells, and the connective tissue of the tunica adventitia surrounds the tunica media (see figure 13.1f). Medium-sized veins collect blood from small veins and deliver it to large veins. The three thin but distinctive tunics make up the wall of the medium- sized and large veins. The tunica media contains some circular smooth muscle and sparsely scattered elastic fibers. The predominant layer in veins is the outer tunica adventitia, which consists primarily of dense collagen fibers (see figures 13.1g and 13.2). Consequently, veins are more distensible than arteries. The connective tissue of the tunica adventitia determines the degree to which they can distend. Veins that have diameters greater than 2 mm contain valves, which ensure that blood flows toward the heart but not in the opposite direction (figure 13.4). Each valve consists of folds in the tunica intima that form two flaps. These valves are similar in shape and function to the semilunar valves of the heart. There are many valves in medium-sized veins and more valves in veins of the lower limbs than in veins of the upper limbs. This prevents blood from flowing toward the feet in response to the pull of gravity.