To heart

Relaxed skeletal muscles Contracted skeletal muscles

Fig. 3. Contractions of the skeletal muscles aid in returning blood to the heart; this is termed the skeletal muscle pump. While standing at rest, the relaxed vein acts as a reservoir for blood; contractions of limb muscles not only decrease this reservoir size (venous diameter), but also actively force the return of more blood to the heart. Note that the resulting increase in blood flow caused by the contractions is only toward the heart because of the valves in the veins.

Relaxed skeletal muscles Contracted skeletal muscles

Fig. 3. Contractions of the skeletal muscles aid in returning blood to the heart; this is termed the skeletal muscle pump. While standing at rest, the relaxed vein acts as a reservoir for blood; contractions of limb muscles not only decrease this reservoir size (venous diameter), but also actively force the return of more blood to the heart. Note that the resulting increase in blood flow caused by the contractions is only toward the heart because of the valves in the veins.

Like capillaries, the walls of the smallest venules are very porous and are the sites from which many phagocytic white blood cells emigrate from the blood into inflamed or infected tissues. Venules and veins are also richly innervated by sympathetic nerves and smooth muscles that constrict when these nerves are activated. Thus, increased sympathetic nerve activity is associated with decreased venous volume, which results in increased cardiac filling and therefore increased cardiac output (via Starling's law of the heart).

Many veins, especially those in the limbs, also feature abundant valves (which are notably also found in the cardiac venous system), thin folds of the intervessel lining that form flaplike cusps. The valves project into the vessel lumen and are directed toward the heart (promoting unidirectional flow of blood). Because blood pressure is normally low in veins, these valves are important in aiding venous return by preventing the backflow of blood (which is especially true in the upright individual). In addition, contractions of skeletal muscles (e.g., in the legs) also play a role in decreasing the size of the venous reservoir and thus the return of blood volume to the heart (Fig. 3).

The pulmonary circulation is composed of a similar circuit. Blood leaves the right ventricle in a single great vessel, the pulmonary artery (trunk), which within a short distance (centimeters) divides into the two main pulmonary arteries, one supplying the right lung and another the left. Once within the lung proper, the arteries continue to branch down to arterioles and then ultimately form capillaries. From there, the blood flows into venules, eventually forming four main pulmonary veins that empty into the left atrium. As blood flows through the lung capillaries, it picks up oxygen supplied to the lungs by breathing air; hemoglobin within the red blood cells becomes loaded with oxygen (oxygenated blood).

2.3. Blood Flow

The task of maintaining an adequate interstitial homeostasis (the nutritional environment surrounding cells) requires that blood flows almost continuously through each of the millions of capillaries in the body. The following is a brief description of the parameters that govern flow through a given vessel. All bloods vessels have certain lengths L and internal radii r through which blood flows when the pressure in the inlet and outlet (Piand Po, respectively) are unequal; in other words, there is a pressure difference (AP) between the vessel ends that supplies the driving force for flow. Because friction develops between moving blood and the stationary vessel walls, this fluid movement has a given resistance (vascular) that is the measure of how difficult it is to create blood flow through a vessel. Then, a relative relationship among vascular flow, the pressure difference, and resistance (i.e., the basic flow equation) can be described:

pressure difference ^ AP

resistance R

where Q is the flow rate (volume/time), AP is the pressure difference (mmHg), and R is the resistance to flow (mmHg X time/volume).

This equation may be applied not only to a single vessel, but also to describe flow through a network of vessels (i.e., the vascular bed of an organ or the entire systemic circulatory system). It is known that the resistance to flow through a cylindrical tube or vessel depends on several factors (described by Poiseuille), including (1) radius, (2) length, (3) viscosity of the fluid (blood), and (4) inherent resistance to flow, as follows:

k r where r is the inside radius of the vessel, L is the vessel length, and ^ is the blood viscosity.

It is important to note that a small change in vessel radius will have a very large influence (fourth power) on its resistance to flow; for instance, decreasing the vessel diameter by 50% will increase its resistance to flow approx 16-fold.

If the preceding two equations are combined into one expression, which is commonly known as the Poiseuille equation, it can be used to approximate better the factors that influence flow though a cylindrical vessel:

Fig. 4. Pathway of blood flow through the heart and lungs. Note that the pulmonary artery (trunk) branches into left and right pulmonary arteries. There are commonly four main pulmonary veins that return blood from the lungs to the left atrium. (Modified from Tortora and Grabowski, 2000.)

Nevertheless, flow will only occur when a pressure difference exists. Hence, it is not surprising that arterial blood pressure is perhaps the most regulated cardiovascular variable in the human body; this is principally accomplished by regulating the radii of vessels (e.g., arterioles and metarterioles) within a given tissue or organ system. Whereas vessel length and blood viscosity are factors that influence vascular resistance, they are not considered variables that can be easily regulated for the purpose of the moment-to-moment control of blood flow. Regardless, the primary function of the heart is to keep pressure within arteries higher than those in veins, hence creating a pressure gradient to induce flow. Normally, the average pressure in systemic arteries is approx 100 mmHg, and it decreases to nearly 0 mmHg in the great caval veins.

The volume of blood that flows through any tissue in a given period of time (normally expressed in milliliters/minute) is called the local blood flow. The velocity (speed) of blood flow (expressed in centimeters/second) can generally be considered inversely related to the vascular cross-sectional area such that velocity is slowest when the total cross-sectional area is largest.

2.4. Heart

The heart lies in the center of the thoracic cavity and is suspended by its attachment to the great vessels within a fibrous sac known as the pericardium; note that humans have relatively thick-walled pericardia compared to those of the commonly studied large mammalian cardiovascular models (i.e., canine, porcine, or ovine; see also Chapter 7). A small amount of fluid is present within the sac (pericardial fluid); it lubricates the surface of the heart and allows it to move freely during function (contraction and relaxation). The pericardial sac extends upward, enclosing the great vessels (see also Chapters 3 and 4).

The pathway of blood flow through the chambers of the heart is indicated in Fig. 4. Recall that venous blood returns from the systemic organs to the right atrium via the superior and inferior

Fig. 4. Pathway of blood flow through the heart and lungs. Note that the pulmonary artery (trunk) branches into left and right pulmonary arteries. There are commonly four main pulmonary veins that return blood from the lungs to the left atrium. (Modified from Tortora and Grabowski, 2000.)

venae cavae. It next passes through the tricuspid valve into the right ventricles, and from there is pumped through the pulmonary valve into the pulmonary artery. After passing through the pulmonary capillary beds, the oxygenated pulmonary venous blood returns to the left atrium through the pulmonary veins. The flow of blood then passes through the mitral valve into the left ventricle and is pumped through the aortic valve into the aorta.

In general, the gross anatomy of the right heart pump is considerably different from that of the left heart pump; yet, the pumping principles of each are primarily the same. The ventricles are closed chambers surrounded by muscular walls, and the valves are structurally designed to allow flow in only one direction. The cardiac valves passively open and close in response to the direction of the pressure gradient across them.

The myocytes of the ventricles are organized primarily in a circumferential orientation; hence, when they contract, the tension generated within the ventricular walls causes the pressure within the chamber to increase. As soon as the ventricular pressure exceeds the pressure in the pulmonary artery (right) and/or aorta (left), blood is forced out of the given ventricular chamber. This active contractile phase of the cardiac cycle is known as systole. The pressures are higher in the ventricles than the atria during systole; hence, the tricuspid and mitral (atrio-ventricular) valves are closed. When the ventricular myocytes relax, the pressures in the ventricles fall below those in the atria, and the atrioventricular valves open; the ventricles refill, and this phase is known as diastole. The aortic and pulmonary (semilunar or outlet) valves are closed during diastole because the arterial pressures (in the aorta and pulmonary artery) are greater than the intraventricular pressures. For more details on the cardiac cycle, see Chapter 16.

The effective pumping action of the heart requires that there be a precise coordination of the myocardial contractions (millions of cells); this is accomplished via the conduction system of the heart. Contractions of each cell are normally initiated when electrical excitatory impulses (action potentials) propagate along their surface membranes. The myocardium can be viewed as a functional syncytium; action potentials from one cell conduct to the next cell via the gap junctions. In the healthy heart, the normal site for initiation of a heartbeat is within the sinoatrial node, located in the right atrium. For more details on this internal electrical system, refer to Chapter 9.

The heart normally functions in a very efficient fashion; the following properties are needed to maintain this effectiveness: (1) the contractions of the individual myocytes must occur at regular intervals and be synchronized (not arrhythmic); (2) the valves must fully open (not be stenotic); (3) the valves must not leak (not be insufficient or regurgitant); (4) the ventricular contractions must be forceful (not failing or lost because of an ischemic event); and (5) the ventricles must fill adequately during diastole (no arrhythmias or delayed relaxation). The subsequent chapters in this book cover normal and abnormal performance of the heart and various clinical treatments to enhance function.

2.5. Regulation of Cardiovascular Function

Cardiac output in a normal individual at rest ranges between 4 and 6 L/min, but during severe exercise the heart may be required to pump four to seven times this amount. There are two primary modes by which the blood volume pumped by the heart at any given moment is regulated: (1) intrinsic cardiac regulation in response to changes in the volume of blood flowing into the heart and (2) control of heart rate and cardiac contractility by the autonomic nervous system. The intrinsic ability of the heart to adapt to changing volumes of inflowing blood is known as the Frank-Starling mechanism (law) of the heart, named after the two great pioneering physiologists of a century ago.

In general, the Frank-Starling response can be described simply: The more the heart is stretched (increased blood volume), the greater will be the subsequent force of ventricular contraction and thus the amount of blood ejected through the semilunar valves (aortic and pulmonary). In other words, within its physiological limits, the heart will pump out all the blood that enters it without allowing excessive damming of blood in veins. The underlying basis for this phenomenon is related to the optimization of the lengths of sarcomeres (the functional subunits of striate muscle); there is optimization in the potential for the contractile proteins (actin and myosin) to form crossbridges. It should also be noted that "stretch" of the right atrial wall (e.g., because of increased venous return) can directly increase the rate of the sinoatrial node by 10-20%; this also aids in the amount of blood that will ultimately be pumped per minute by the heart. For more details on the contractile function of heart, refer to Chapter 8.

The pumping effectiveness of the heart is also effectively controlled by both the sympathetic and parasympathetic components of the autonomic nervous system. There is extensive innervation of the myocardium by such nerves (for more details of this innervation, see Chapter 10). To get a feel for how effective the modulation of the heart by this innervation is, it has been reported that the cardiac output often can be increased by more than 100% by sympathetic stimulation; in contrast, output can be nearly terminated by parasympathetic (vagal) stimulation.

Cardiovascular function is also modulated through reflex mechanisms that involve baroreceptors, the chemical composition of the blood, and/or via the release of various hormones. More specifically, baroreceptors, which are located in the walls of some arteries and veins, exist to monitor their relative blood pressure. Those specifically located in the carotid sinus help to maintain normal blood pressure reflexively in the brain, whereas those located in the area of the ascending arch of the aorta help to govern general systemic blood pressure (for more details, see Chapter 10).

Chemoreceptors that monitor the chemical composition of blood are located close to the baroreceptors of the carotid sinus and arch of the aorta in small structures known as the carotid and aortic bodies. The chemoreceptors within these bodies detect changes in blood levels of O2, CO2, and H+. Hypoxia (a low availability of O2), acidosis (increased blood concentrations of H+), and/or hypercapnia (high concentrations of CO2) stimulate the chemoreceptors to increase their action potential firing frequencies to the brain cardiovascular control centers. In response to this increased signaling, the central nervous system control centers (hypothalamus) in turn cause an increased sympathetic stimulation to arterioles and veins, producing vasoconstriction and a subsequent increase in blood pressure. In addition, the chemoreceptors simultaneously send neural input to the respiratory control centers in the brain to induce the appropriate control of respiratory function (e.g., increased O2 supply and reduced CO2 levels). It is beyond the scope of this book to discuss the details of the hormonal regulatory system, which include: (1) the renin-angiotensin-aldosterone system, (2) the release of epinephrine and norepinephrine, (3) antidiuretic hormones, and (4) atrial natriuretic peptides (released from the atrial heart cells).

The overall functional arrangement of the blood circulatory system is shown in Fig. 5. The role of the heart needs to be considered in three different ways: as the right pump, as the left pump, and as the heart muscle tissue with its own metabolic and flow requirements. As described here, the pulmonary (right heart) and systemic (left heart) circulations are arranged in a series. Thus, cardiac output increases in each at the same rate; hence, an increased systemic need for a greater cardiac output will automatically lead to a greater flow of blood through the lungs (inducing a greater potential for O2 delivery).

In contrast, the systemic organs are functionally in a parallel arrangement; hence, (1) nearly all systemic organs receive blood with an identical composition (arterial blood), and (2) the flow through each organ can be and is controlled independently. For example, during exercise the circulatory response is an increase in blood flow through some organs (e.g., heart, skeletal muscle, and brain), but not others (e.g., kidney and gastrointestinal system). The brain, heart, and skeletal muscles typify organs in which blood flows solely to supply the metabolic needs of the tissue; they do not recondition the blood.

The blood flow to the heart and brain is normally only slightly greater than that required for their metabolism; hence, small

Fig. 5. A functional representation of the blood circulatory system at a given moment in time. The percentages indicate the approximate relative percentages of the cardiac output that is delivered to the major organ systems within the body of a healthy subject at rest.

interruptions in flow are not well tolerated. For example, if coronary flow to the heart is interrupted, electrical and/or functional (pumping ability) activities will be altered noticeably within a few beats. Likewise, stoppage of flow to the brain will lead to unconsciousness within a few seconds, and permanent brain damage can occur in as little as 4 min without flow. The flow to skeletal muscles can dramatically change (flow can increase from 20-70% of total cardiac output) depending on use, and thus their metabolic demand.

Many organs in the body perform the task of continually reconditioning the circulating blood. Primary organs performing such tasks include (1) the lungs (O2 and CO2 exchange); (2) the kidneys (blood volume and electrolyte composition, Na+, K+, Ca2+, Cl" and phosphate ions); and (3) the skin (tempera ture). Blood-conditioning organs can often withstand, for short periods of time, significant reductions of blood flow without subsequent compromise.

2.6. Coronary Circulation

To sustain viability, it is not possible for nutrients to diffuse from the chambers of the heart through all the layers of cells that make up the heart tissue. Thus, the coronary circulation is responsible for delivering blood to the heart tissue itself (the myocardium). The normal heart functions almost exclusively as an aerobic organ with little capacity for anaerobic metabolism to produce energy. Even during resting conditions, 7080% of the oxygen available in the blood circulating through the coronary vessels is extracted by the myocardium.

Lymph iioik-

Lymph iioik-

Fig. 6. Schematic diagram showing the relationship between the lymphatic system and the cardiopulmonary system. The lymphatic system is unidirectional, with fluid flowing from interstitial space back to the general circulatory system. The sequence of flow is from blood capillaries (systemic and pulmonary) to the interstitial space, to the lymphatic capillaries (lymph), to the lymphatic vessels, to the thoracic duct, into the subclavian veins (back to the right atrium). (Modified from Tortora and Grabowski, 2000.)

Fig. 6. Schematic diagram showing the relationship between the lymphatic system and the cardiopulmonary system. The lymphatic system is unidirectional, with fluid flowing from interstitial space back to the general circulatory system. The sequence of flow is from blood capillaries (systemic and pulmonary) to the interstitial space, to the lymphatic capillaries (lymph), to the lymphatic vessels, to the thoracic duct, into the subclavian veins (back to the right atrium). (Modified from Tortora and Grabowski, 2000.)

It then follows that, because of the limited ability of the heart to increase oxygen availability by further increasing oxygen extraction, increases in myocardial demand for oxygen (e.g., during exercise or stress) must be met by equivalent increases in coronary blood flow. Myocardial ischemia results when the arterial blood supply fails to meet the needs of the heart muscle for oxygen and/or metabolic substrates. Even mild cardiac ischemia can result in anginal pain, electrical changes (detected on an electrocardiogram), and the cessation of regional cardiac contractile function. Sustained ischemia within a given myo-cardial region will most likely result in an infarction.

As noted, as in any microcirculatory bed, the greatest resistance to coronary blood flow occurs in the arterioles. Blood flow through such vessels varies approximately with the fourth power of the radii of these vessels; hence, the key regulated variable for the control of coronary blood flow is the degree of constriction or dilatation of coronary arteriolar vascular smooth muscle. As with all systemic vascular beds, the degree of coronary arteriolar smooth muscle tone is normally controlled by multiple independent negative-feedback loops. These mechanisms include various neural, hormonal, and local nonmetabolic and local metabolic regulators.

It should be noted that the local metabolic regulators of arteriolar tone are usually the most important for coronary flow regulation; these feedback systems involve oxygen demands of the local cardiac myocytes. In general, at any point in time, coronary blood flow is determined by integrating all the different controlling feedback loops into a single response (i.e., inducing either arteriolar smooth muscle constriction or dilation). It is also common to consider that some of these feedback loops are in opposition. Interestingly, coronary arteriolar vasodilation from a resting state to one of intense exercise can result in an increase of mean coronary blood flow of approx 0.5-4.0 mL/min/g.

As with all systemic circulatory vascular beds, the aortic or arterial pressure (perfusion pressure) is vital for driving blood through the coronaries and thus needs to be considered another important determinant of coronary flow. More specifically, coronary blood flow varies directly with the pressure across the coronary microcirculation, which can be considered essentially as the aortic pressure because coronary venous pressure is typically near zero. However, because the coronary circulation perfuses the heart, some very unique determinants for flow through these capillary beds may also occur; e.g., during systole, myocardial extravascular compression causes coronary flow to be near zero, yet it is relatively high during diastole (note that this is the opposite of all other vascular beds in the body).

2.7. Lymphatic System

The lymphatic system represents an accessory pathway by which large molecules (e.g., proteins and long-chain fatty acids) can reenter the general circulation and thus not accumulate in the interstitial space. If such particles accumulate in the interstitial space, then filtration forces exceed reabsorptive forces, and edema occurs. Almost all tissues in the body have lymph channels that drain excessive fluids from the interstitial space (exceptions include portions of skin, the central nervous system, the endomysium of muscles, and bones with prelymphatic channels).

The lymphatic system begins in various tissues with blindend specialized lymphatic capillaries that are roughly the size of regular circulatory capillaries, but they are less numerous (Fig. 6). However, the lymphatic capillaries are very porous and thus can easily collect the large particles within the interstitial fluid known as lymph. This fluid moves through the converging lymphatic vessels and is filtered through lymph nodes, in which bacteria and particulate matter are removed. Foreign particles that are trapped in the lymph nodes are destroyed (phagocytized) by tissue macrophages lining an inner meshwork of sinuses. Lymph nodes also contain T and B lymphocytes, which can destroy foreign substances by a variety of immune responses. There are approx 600 lymph nodes located along the lymphatic vessels; they are 1-25 mm long (bean shaped) and covered by a capsule of dense connective tissue. Lymph flow is unidirectional through the nodes (Fig. 6).

The lymphatic system is also one of the major routes for absorption of nutrients from the gastrointestinal tract (particularly for the absorption of fat and lipid-soluble vitamins A, D, E, and K). For example, after a fatty meal, lymph in the thoracic duct may contain as much as 1-2% fat.

The majority of lymph then reenters the circulatory system in the thoracic duct, which empties into the venous system at the juncture of the internal jugular and subclavian veins (which then enters into the right atrium; see Chapters 3 and 4). The flow of lymph from tissues toward the entry point into the circulatory system is induced by two main factors: (1) higher tissue inter stitial pressures and (2) the activity of the lymphatic pumps (contractions within the lymphatic vessels themselves, contractions of surrounding muscles, movement of parts of the body, and/or pulsations of adjacent arteries). In the largest lymphatic vessels (e.g., thoracic duct), the pumping action can generate pressures as high as 50-100 mm Hg. Valves located in the lymphatic vessel, like in veins, aid in the prevention of the backflow of lymph.

Approximately 2.5 L of lymphatic fluid enter the general blood circulation (cardiopulmonary system) each day. In the steady state, this indicates a total body net transcapillary fluid filtration rate of 2.5 L per day. When compared with the total amount of blood that circulates each day (approx 7000 L per day), this seems almost insignificant; however, blockage of such flow will quickly cause serious edema. Therefore, the lymphatic circulation plays a critical role in keeping the interstitial protein concentration low and in removing excess capillary filtrate from tissues throughout the body.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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