Background Information

For any animal to carry out its metabolism and survive, it must be able to exchange gases between its cells and the environment. Oxygen gas (O2) must enter the body for the organism to perform cell respiration, and CO2 generated as a waste product during cell respiration must be removed from the body. Gas exchange requires the transport of these molecules. For example, O2 moves from the lungs to body tissues and CO2 moves from body cells to the lungs so that it can be exhaled. The transport of gases and a variety of other molecules necessary for life–for example, nutrients, ions, and hormones–is accomplished by organs and tissues of the cardiovascular system. In addition, the cardiovascular system must transport metabolic waste products to facilitate their removal from the body. In mammals, the cardiovascular system consists of blood as the transport medium, the heart, and blood vessels.

Human blood is a connective tissue that consists of two major components, an aqueous fluid called plasma and the formed elements. Plasma makes up approximately 55% of blood volume. The formed elements consist of red blood cells (erythrocytes), white blood cells (leukocytes), and platelets. Formed elements make up approximately 45% of blood volume. Some molecules dissolve directly in the plasma, many molecules must be attached to transport molecules in the plasma to facilitate their movement through the circulatory system, and others such as oxygen gas are transported within red blood cells. Regardless of how a molecule is transported within an animal’s blood, the organism’s survival requires a pump to move blood through the circulatory system. Of course, the heart is the sophisticated pump that accomplishes this purpose.

The human heart is a four-chambered structure located in the thoracic body cavity. The two upper chambers of the heart are called the atria (singular, atrium), and the two lower chambers are called ventricles. When the heart contracts, both atria contract almost simultaneously, followed by contraction of both ventricles. Before we discuss the events that trigger contraction of the heart, it is important that you understand how blood flows to, through, and away from the heart. Oxygen—poor, carbon dioxide—rich blood enters the right atrium through two large veins, the superior vena cava and the inferior vena cava. The venae cavae collect oxygen—poor blood from virtually all veins in the body. As the heart contracts, blood that has entered the right atrium flows into the right ventricle then from the right ventricle into a large artery called the pulmonary trunk. The pulmonary trunk carries blood away from the heart into one right and one left pulmonary artery. The pulmonary arteries serve to carry oxygen—poor blood to the vessels of the lungs wherein carbon dioxide and oxygen are exchanged. Following oxygenation in the lungs, blood enters the left atrium via four pulmonary veins. During each contraction of the heart, blood flows from the left atrium to the left ventricle. From the left ventricle, blood enters the largest artery in the body, the aorta. The aorta gives rise to major arteries of the body that transport oxygen—rich blood to all body organs. The right side of the heart and the blood vessels that carry blood to and from the lungs form the pulmonary circuit. The left side of the heart, the aorta, and vessels derived from the aorta are part of the systemic circuit because these structures deliver oxygen—rich blood to body organs.

Another important aspect of heart anatomy involves connective tissue valves that function to ensure the one-way flow of blood through the heart. One set of valves, the semilunar valves (aortic and pulmonary), function to prevent the backflow of blood into the ventricles. Two atrioventricular valves, the tricuspid valve and the bicuspid (mitral) valve, prevent the backflow of blood into the right and left atrium, respectively, when the ventricles contract.

Biologists use the term cardiac cycle to describe one complete sequence of events involved in pumping and filling the heart with blood. In one complete beat of the heart, the atria contract nearly simultaneously, followed by contraction of the ventricles. Technically, contraction of the heart chambers is known as systole while relaxation of the heart chambers is called diastole. When the atria are in systole, the ventricles are in diastole; therefore, both ventricles fill with blood. Alternatively, when the ventricles are in systole, the atria are in diastole; this is when the atria fill with blood.

The frequency and duration of the cardiac cycle is determined by the electrical events that govern cardiac muscle contraction. However, unlike skeletal muscle, which will only contract in response to electrical impulses from motor neurons in the brain, cardiac muscle cells contract in response to electrical impulses that are generated within the heart itself. Because these impulses arise from within the heart, the generation and spreading of electrical currents in the heart is known as the intrinsic conduction system. The intrinsic conduction system is so effective that a human heart can continue to beat on its own if removed from the body! Although neurons from the brain are not responsible for causing the heart to beat, neurons that are part of the autonomic nervous system (ANS) are very important for regulating the frequency of heartbeats and contraction strength.

The intrinsic conduction system consists of groups of specialized muscle cells called conduction fibers. Some cells of this system simply conduct electrical impulses to other regions of the heart while others, known as pacemaker cells, spontaneously produce electrical impulses (also called action potentials) that determine heart rate. The intrinsic conduction sequence of electrical events is initiated by a small cluster (node) of cells located in the right atrium called the sinoatrial (SA) node. The SA node is considered the true "pacemaker" of the heart because it produces impulses at a rate of approximately 75 impulses/minute. This node of cells determines the overall rate of contraction by all other cells in the heart. As electrical impulses from the SA node spread to cardiac muscle cells in the atria, those cells are stimulated to contract (atrial systole). The impulse moves from cells of the atria to a node of cells, called the atrioventricular (AV) node, located between the two ventricles. The impulse is delayed momentarily by the AV node. This delay allows the ventricles to fill with blood while the atria are in systole. After this delay, electrical impulses travel through a series of cells called the atrioventricular bundle (bundle of His) to cells called Purkinje fibers. The Purkinje fibers are located in the walls of the ventricles; therefore, once electrical impulses have reached the Purkinje fibers, the ventricles contract (systole). This entire sequence takes approximately 0.2 seconds. The aforementioned electrical events are measured and recorded using an electrocardiograph, which produces a tracing of these events called an electrocardiogram (ECG or EKG).

Neurons of the ANS can regulate heart rate by influencing the pacemaker cells, particularly cells of the SA node. Sympathetic nervous system neurons release the neurotransmitter norepinephrine, which triggers SA node cells to produce electrical impulses with greater frequency, thus increasing heart rate. Epinephrine released by the adrenal gland also increases heart rate. Exercise and stress–for example, going on a blind date or being anxious about a biology exam–can cause an increase in heart rate by stimulating sympathetic nervous system neurons. This increase in heart rate is designed to provide the additional oxygen and nutrients that body organs require to increase their metabolism and respond to the stress. This response is commonly referred to as the fight-or-flight response. Conversely, neurons of the parasympathetic nervous system oppose the actions of the sympathetic nervous system. Parasympathetic neurons release acetylcholine, a neurotransmitter that decreases the frequency of impulse generation by cells of the SA node. These parasympathetic effects are responsible for returning heart rate to normal after a stressful event. The parasympathetic nervous system also slows heart rate during times when body organs have a reduced requirement for oxygen, such as when you are sleeping. Thus, the ANS is critical for the fine-tuned control of heart rate necessary to ensure the proper transport of nutrients to body organs. Other details about how the ANS regulates heart rate and blood vessel diameter are discussed later in this section.

Although the heart is a pump in the simplest sense, the factors that control heart rate are multidimensional and complex. Physiologists use the term hemodynamics to describe the study of blood flow, blood pressure, and the regulation of those processes necessary for blood pressure homeostasis. One very important concept in hemodynamics is cardiac output (CO). Cardiac output is the amount of blood pumped by one ventricle in one minute (ml blood/minute), and is determined by the following relationship:

CO = SV (stroke volume) x HR (heart rate)

Stroke volume (SV) is the amount of blood (in milliliters) pumped by one ventricle during one beat. In a healthy human heart, SV is approximately 70 ml. Stroke volume is a measure of the difference between end diastolic volume and end systolic volume in each ventricle. End diastolic volume is the amount of blood that fills each ventricle at the end of ventricular diastole, approximately 120 ml/ventricle. End systolic volume is the amount of blood that remains in each ventricle at the end of ventricular systole. Although the heart is a fairly efficient pump, it is impossible to expel all blood from a ventricle when it contracts. End systolic volume is approximately 50 ml of blood per ventricle. Thus, each contraction, or "stroke," of a ventricle expels approximately 70 ml of blood. At rest, normal heart rate (HR) rate is approximately 75 beats/minute. Using these values, CO at rest is approximately 5250 ml of blood per ventricle per minute. During exercise, stress, or in response to a number of stimuli, CO can increase dramatically to accommodate an increased need to supply body tissues with oxygenated blood. In fact, in well-conditioned athletes, CO can increase by more than four times the normal value of 5250 ml/minute!

Normal CO is required to deliver the amount of blood necessary to maintain normal body functions. One benefit of exercise is that most forms of exercise–particularly high-impact aerobic exercise–can lead to an increase in the elasticity of the heart, which means that the ventricles are capable of filling with more blood. This increase in elasticity produces an increase in stroke volume. Because stroke volume increases in a well-conditioned athlete, resting heart rate can decrease and an athlete can still continue to maintain CO–this is just one beneficial aspect of exercise. Conversely, individuals who do not exercise their heart on a regular basis can show less elasticity in the wall of the ventricles and thus a lower stroke volume. Therefore, to maintain normal cardiac output, heart rate must compensate by increasing–thus putting more strain on the heart. When one considers that this individual may compound a lack of exercise with other conditions such as a diet rich in saturated fats and cholesterol–both of which can accumulate in the chambers of the heart–it is easy to understand why a lack of exercise and poor diet are considered risk factors for cardiovascular disease.

Normal cardiac output is necessary for maintaining proper blood pressure– technically defined as arterial pressure–the amount of pressure blood exerts on the wall of an artery. The normal blood pressure value of 120/80 recorded when you visit your physician is a measure, in millimeters of mercury (mm Hg), of systolic blood pressure created by contraction of the left ventricle compared with diastolic pressure during ventricular diastole.

Blood pressure will rise with ventricular systole and fall with ventricular diastole. This rise and fall can be measured as a "pulse" on the wall of an artery as elastic tissue in the arterial wall stretches during ventricular systole and recoils during ventricular diastole. It is particularly important that pressure within the cardiovascular system be sufficient to keep blood moving through the system properly. Mean arterial pressure (MAP) is the average blood pressure within systemic arteries. This pressure represents the average pressure due to ventricular systole and is considered the "driving force" that delivers blood to body organs.

Another important measure of hemodynamics is blood flow. Blood flow refers to the volume of blood moving through an area over a given time. Typically, flow is expressed in milliliters of blood per minute. Blood flow is affected by two major factors: blood pressure and total peripheral resistance. The relationship of these factors is shown below.

Blood Flow (F) =
Blood Pressure (BP)

Total Peripheral Resistance (TPR)

Blood flow is directly proportional to blood pressure and inversely proportional to resistance. In this relationship, blood pressure actually refers to the difference in pressure between two points–for example the two ends of a blood vessel. Resistance refers to any factor that interferes with or opposes blood flow. Total peripheral resistance is a measure of all resistance factors that blood encounters as it travels through the cardiovascular system. It is important that you be familiar with the many factors that contribute to resistance. Blood vessel diameter, blood vessel radius, and blood thickness (viscosity) are particularly important factors. There is an inverse relationship between blood vessel diameter and blood resistance. A large—diameter blood vessel has less resistance than a small—diameter blood vessel because in a larger blood vessel, there is less friction between blood cells themselves and the walls of the vessel. A good example of this is the difference between drinking from a drinking straw and drinking from a thin-diameter straw used to stir coffee. The thin-diameter straw has a much higher resistance. This is also the reason firefighters use large— diameter fire hoses instead of small—diameter garden hoses.

Technically, resistance is inversely proportional to vessel radius to the fourth power. Therefore, water traveling in a hose with a 1-inch radius experiences 16 times more resistance than blood traveling through a hose with a 2-inch radius. This same principle also applies to blood vessels. As a result, very small changes in vessel diameter can produce large changes in peripheral resistance, blood flow, and blood pressure. Resistance is also directly proportional to vessel length. The longer the path that blood must travel, the greater the friction between blood and the vessel wall. Therefore, blood traveling in shorter blood vessels encounters less resistance than blood traveling through longer vessels. Although both vessel diameter and length influence blood pressure and flow, vessel diameter exerts a much greater influence over hemodynamics than vessel length. This is because vessels in humans rarely change in length; however, vessel diameter can and does change a lot in response to conditions such as exercise, stress, and temperature changes. An increase in blood vessel diameter is called vasodilation, while a decrease in vessel diameter is known as vasoconstriction.

In addition to regulating heart rate directly, the ANS is also involved in controlling vasoconstriction and vasodilation. For example, during prolonged exercise the ANS will trigger vasodilation of blood vessels in skin and muscles to improve blood flow to muscles. This process also functions to cool body temperature by radiating heat away from the skin. Conversely, vasoconstriction can occur during conditions of stress as a way to increase blood pressure.

The ANS cannot control heart rate or blood vessel diameter without the involvement of sensory neurons that signal the ANS to produce necessary changes. An important set of sensory neurons called baroreceptors are located in the wall of the aorta and the internal carotid arteries. These neurons respond to changes in blood pressure and relay impulses to the medulla oblongata of the brain. In the medulla, impulses are relayed to clusters of neurons that form important cardiovascular control centers. One group of neurons, called the cardioacceleratory center, consists of sympathetic nervous system neurons that, when stimulated, send electrical impulses to the SA and AV nodes to increase heart rate. Related neurons also send impulses to smooth muscle cells in the walls of blood vessels to stimulate vasoconstriction. Therefore, if blood pressure were to decrease for any reason, baroreceptors would send impulses to the brain that stimulate sympathetic nervous system neurons to increase heart rate and trigger vasoconstriction in an effort to raise blood pressure. Conversely, when blood pressure increases, baroreceptors send impulses to the medulla to inhibit neurons of the cardioacceleratory center. In this situation, the baroreceptors also stimulate a group of neurons in the medulla called the cardioinhibitory center. These neurons are part of the parasympathetic division of the ANS, and when stimulated they send impulses to the SA and AV nodes to decrease heart rate. Most blood vessels do not receive impulses from parasympathetic neurons; hence, vasodilation is brought about by the inhibition of sympathetic neurons. This neural control is essential for blood pressure homeostasis.

Another important factor that influences blood pressure is blood viscosity. Blood viscosity will change in conditions such as anemia, where a lack of blood cells decreases blood thickness. When viscosity decreases, blood flows with less resistance, thus decreasing blood pressure. Similarly, decreases in blood volume due to excessive bleeding (hemorrhaging) will also reduce blood pressure. Conversely, blood viscosity can increase when an individual is producing an excess number of red blood cells (a condition called polycythemia) and when an individual is experiencing excessive dehydration. "Thicker blood" produces an increase in peripheral resistance.

Clearly, blood pressure homeostasis involves many aspects of cardiovascular physiology. Familiarity with the relationships between blood pressure, blood flow, resistance, and cardiac output is essential for understanding and appreciating the complexities of hemodynamics. It is possible to study basic aspects of hemodynamics in human patients by following changes in cardiovascular functions during exercise, stress, and other conditions. However, it is obviously impossible to perform invasive experimental manipulations on human patients for the benefit of helping you learn about the human cardiovascular system and blood pressure homeostasis. CardioLab will provide you with an outstanding opportunity to learn about important parameters that influence blood pressure and blood flow. You will be manipulating parameters such as heart rate, blood vessel radius, blood viscosity, ventricular volume, venous capacity, and blood volume to simulate the effects of changes in these parameters on hemodynamics. Through these experiments you will learn how organs of the cardiovascular system maintain blood pressure homeostasis in response to different stimuli. You will also use CardioLab to simulate real—life conditions that affect blood pressure such as exercise, hemorrhaging, shock, and cardiovascular disorders.

References

  1. Marieb, E. N. Human Anatomy and Physiology, 6th ed. San Francisco, CA: Benjamin Cummings, 2004.

  2. Silverthorn, D. U. Human Physiology: An Integrated Approach, 3rd ed. San Francisco, CA: Benjamin Cummings, 2004.