a. The circulatory system's main role is to move materials from a source compartment to a sink compartment.

b. An exchange is a two-way transfer of materials from one compartment to another.

c. Unicellular and small aquatic animals can exchange materials directly with the water by diffusion alone (Figure 45.1).

d. Organs in a complex animal body must rely on a circulatory system to accomplish the exchange of materials.

e. The transport of the respiratory gases oxygen and carbon dioxide throughout the body is called gas exchange or respiration, and should not be confused with cellular respiration.

f. External exchange occurs when blood exchanges O2 and CO2 with the atmosphere in the lungs, gills, and skin.

g. Internal exchange occurs when the blood gases are exchanged through the tissues.

a. Vertebrates and many other animals (Figure 45.3) have a closed circulatory system confined to a series of vessels, whose extracellular compartment consists of blood plasma and interstitial fluid.

b. The majority of animal species have an open circulatory system and a single acellular fluid called hemolymph (Figure 45.2).

c. In a closed system, blood is confined to vessels that eventually become only one cell thick, at which point they are called capillaries.

d. Capillaries form a capillary bed in which each tissue cell is close enough to be served by diffusion alone.

a. Vertebrate blood vessels that lead away from the heart are called arteries and those leading to the heart are called veins (Figure 45.4).

b. Both arteries and veins have walls made of smooth muscle that aid in blood circulation by contracting; artery walls are much thicker than vein walls and can withstand the higher blood pressures created by the heart.

c. Blood leaves the heart through the aorta, which divides into smaller arteries and arterioles.

d. Venules converge into larger veins, which finally end in the inferior and superior vena cavae.

e. Most veins have one-way valves to prevent the backflow of blood (Figure 45.5).

f. The mammalian circulatory system is a double-circulation system composed of pulmonary circulation through the lungs and systemic circulation through the rest of the body.

g. The right side of the heart collects blood into the right atrium, passes it into the right ventricle, to the lungs through the pulmonary artery, then from the lungs through the pulmonary vein, to the left atrium, the left ventricle, and out to the body via the aorta (Figure 45.6).

h. Vertebrate hearts have evolved through stages that still exist in extant animals (Figure 45.7).

i. A fish heart forces blood through the gills for oxygenation and then to the rest of the body in a single-circulation system (Figure 45.8).

a. The heart maintains a cardiac cycle rhythm of contraction (systole) and relaxation (diastole).

b. Passages from the atria to the ventricles are closed by atrioventricular (AV) valves: a tricuspid on the right side and a bicuspid on the left side (Figure 45.9).

c. The valves are connected to the heart wall by connective tissue called chordae tendineae ("heart strings") and papillary muscles.

d. Semilunar valves at the origins of the aorta and pulmonary artery operate passively, opening under pressure from the contracting ventricles and then closing during diastole.

e. Vertebrate heart tissue is a unique striated muscle made of cells connected together with many gap junctions; the entire interconnected tissue is called a myocardium.

f. An isolated heart can continue to beat if it is supplied with blood; it has its own pacemaker, which stimulates contraction.

g. The pace of an intact mammalian heart is set by the sinoatrial (SA) node, a block of specialized muscle tissue located in the right atrium (Figure 45.10).

h. An action potential generated by the SA cells is conducted to the atrial myocardium and spreads rapidly through the entire atrial muscle, contracting the atria in unison.

i. This contraction quickly reaches the atrioventricular (AV) node, a second control center located just above the right ventricle.

j. The AV node fires and sends an action potential through the atrioventricular bundle, in the septum between the ventricles.

k. This bundle divides into two bundles that are continuous with the Purkinje fibers connected directly to the ventricular myocardium, and the AV node action potential is thus conducted to the entire mass of ventricular tissue.

a. Blood pressure rises sharply (systolic pressure) as blood is forced out of the heart, then falls again (diastolic pressure) as the heart relaxes.

b. Sidebar 45.1 covers blood pressure and its measurement.

c. Blood flows through vessels that vary in size from an internal diameter of about a centimeter to only a few micrometers.

d. To best understand blood flow through a series of tubes, one must first understand the factors of flow and resistance within a tube (Figure 45.11).

e. Contraction of blood vessels is called vasoconstriction and relaxation is called vasodilation.

f. Arterial blood pressure depends on the cardiac output, the volume of blood expelled by the heart each minute.

g. Resistance to blood flow is almost all peripheral resistance from small blood vessels such as the arterioles, since they are narrow vessels whose total cross-sectional area is small (Figure 45.12).

h. Blood pressure is kept to a narrow range, as it is proportional to the product of the cardiac output and the peripheral resistance.

i. Figure 45.13 summarizes the control mechanisms intrinsic to the heart and also including extrinsic control circuits.

j. Baroreceptor reflexes regulate this system extrinsically.

k. Cardiac control centers can change the heartbeat.

l. Vasomotor control centers adjust the peripheral resistance through vasodilation and vasoconstriction.

m. Sidebar 45.2 explains the circulatory changes that occur during shock.

n. The contraction strength of the ventricles is regulated intrinsically via the Frank-Starling mechanism (Figure 45.14).

o. Superimposed on these processes, the end-diastolic volume is affected by the venous return–the volume of blood delivered by the vena cava to the right atrium.

p. About 20 percent of Americans have hypertension–high blood pressure–for various reasons.

a. Blood is a tissue made of cells dispersed in a fluid matrix, the plasma.

b. The hematocrit is the fraction of blood that the cells occupy, and can be measured after centrifugation.

c. Most blood cells are red blood cells, or erythrocytes (Figure 45.15), which are filled with hemoglobin.

d. White blood cells, or leucocytes, make up a much smaller proportion of the cells, though their function in the immune system is extremely important.

e. The plasma carries small fragments called platelets, which participate in blood clotting.

f. In adults, new red and white blood cells are constantly produced in the bone marrow.

g. About 180 billion blood cells per day are destroyed, and created, in the human body.

h. Mammalian blood plasma contains a number of ions and other solutes; plasma proteins have many functions.

a. Each tissue is served by a capillary bed (Figure 45.16).

b. Thoroughfare channels connect the arterioles leading into a capillary bed with the venules leading out of the bed (Figure 45.17).

c. Precapillary sphincters, rings of smooth muscle surrounding each capillary, can contract and regulate blood flow into the capillary.

d. Nutrients, O2, and other materials carried into each capillary bed move from the capillaries into the interstitial fluid and then into the cells of the tissue, while wastes from the tissue move back into the blood.

e. Hydrostatic pressure, from the fluid itself, and osmotic pressure, from the diffusion of water, are both responsible for the movement of materials across the capillary walls (Figure 45.18).

f. Capillary beds provide ultrafiltration in restricting the movement of proteins but allowing protein-free liquid to move back and forth.

a. Some of the plasma that leaves the capillaries, lymph, is picked up by the lymphatic system, which is made of auxiliary vessels leading back to the main circulation (Figure 45.19).

b. Lymph runs through lymphatic capillaries running throughout intercellular "cul de sac" spaces in almost all tissues.

c. Lymphatic flow is driven primarily by pressure from the organs through which the lymphatics pass, supplemented by some contraction of smooth muscle around the larger lymphatic vessels.

d. Edema is the swelling of tissues with fluid, and can be caused by excess interstitial fluid not returning to the circulation.

e. Elephantiasis (Figure 45.20) is caused by edema that results from blockage of the lymphatics by nematode parasites.

a. Both infectious diseases (such as rheumatic fever) and functional diseases (such as atherosclerosis) can damage the heart and may even cause death.

b. The principal risk factors in cardiovascular disease are a sedentary lifestyle, a diet rich in fats, overeating, smoking, obesity, excessive use of alcohol, diabetes, stress, and a family history of heart disease.

c. Atherosclerosis is caused by deposits of fatty plaques, or atheromas, in the walls of arteries (Figure 45.21).

d. Even a slight narrowing, or stenosis, of a blood vessel can have a profound effect on circulation.

e. Stenosis of an artery results in ischemia (see Sidebar 45.2), or decreased blood flow to a region of tissue and starvation for oxygen.

f. Ischemia is obvious in an experimental procedure where a cardiac artery is tied off (Figure 45.22), causing a myocardial infarction, or death of the cardiac tissue and heart attack.

g. A serious heart attack is characterized by extreme pain, called angina pectoris, radiating into the left shoulder and arm, and difficulty breathing.

h. Plaques also stimulate blood clots, or thrombi (singular, thrombus).

i. A coronary thrombosis is a thrombus in a cardiac artery.

j. A thrombus may break loose, becoming an embolus, and travel to some other point, such as the brain, where it can produce a stroke.

a. Most animals larger than a millimeter or two in thickness require organs of external gas exchange, such as lungs, gills, skin, or the tracheal system of arthropods (Figure 45.23), all of which provide the large surface/volume ratios needed for efficiency in the exchange.

b. As a general rule, terrestrial animals draw air into tubes and pockets, and aquatic animals circulate water around and through protruding gills.

c. Gas-exchange structures linked to a circulatory system all depend on fluids moving past the exchange surface.

d. On the inside, they are perfused by moving blood through the lungs, gills, or skin, and on the outside, they are ventilated by moving the external air or water over the surface.

e. Fish gills can remove as much as 80 percent of the oxygen in the water flowing through them by using countercurrent exchange, described in Concepts 45.1 (Figure 45.24).

f. Insects use a system of tracheae, tubules open to the atmosphere via openings called spiracles.

g. In vertebrates, air is drawn into the lungs through a large trachea, which is covered with the epiglottis to prevent food from entering it.

h. The trachea branches into two smaller bronchi (singular, bronchus), which then branch into a series of bronchioles of decreasing size that end in small pockets called alveoli (Figure 45.25).

i. In mammals the muscular diaphragm forms the floor of the thoracic cavity and inflates the lungs by contracting and changing the size of the cavity.

j. During inhalation, or inspiration, the diaphragm contracts (Figure 45.26); exhalation, or expiration occurs passively as the muscles relax.

k. Alveoli are covered by a thin film of water and would be in danger of collapsing under surface tension, except for the action of a surfactant produced in the alveolar walls.

l. Respiratory distress syndrome occurs in premature newborn babies, since the surfactant produces by the alveoli is not made until late in fetal development.

a. Though a small amount of oxygen is dissolved in blood plasma or hemolymph, an animal's oxygen balance depends most heavily on oxygen-carrying blood proteins.

b. Hemoglobin is the most common of these proteins.

c. Hemoglobin and myoglobin both bind oxygen, and hemoglobin is the more efficient of the two.

d. The Bohr effect is an adaptation of hemoglobin that shifts its oxygen-binding capacity in the presence of hydrogen ions and carbon dioxide (Figure 45.27).

a. Removal of carbon dioxide is a critical function of the circulatory system.

b. Most CO2 is disposed of through the action of carbonic anhydrase and the anion exchange protein in the erythrocyte membrane, which conducts a chloride shift by exchanging the bicarbonate for chloride ion.

c. Hemoglobin also plays a role in removal of CO2, as it binds about a quarter of the CO2 in the blood to its N-terminal amino group.

a. The circuit of neurons that control breathing in mammals is illustrated in Figure 45.28.

b. The inspiratory and expiratory neurons that control breathing operate reciprocally through inhibitory neurons.

c. Stretch receptors in the lungs superimpose a second regulatory system, sending signals to inhibit the inspiratory neurons when the lungs are stretched by expansion.

a. Breathing normally keeps the concentrations of respiratory gases in the blood within certain limits.

b. The ventilation rate is regulated by signals from sensory cells in contact with the blood that monitors its O2 and CO2 levels and its pH.

c. In mammals, the chemosensors for this regulation are located in the medulla oblongata, and on the carotid bodies and aortic bodies on major arteries (Figure 45.29).

d. Breathing is more sensitive to the CO2 level of the blood than to the O2 level (Figure 45.30), and ventilation becomes much more rapid as CO2 levels in the blood increase.