Functional Organization of the Human Body PDF

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This document details the functional organization of the human body. It describes various systems, organs, and cells, as well as how they work together in the human body. Concepts like homeostasis, positive and negative feedback, and the roles of systems in maintaining the body's internal environment are discussed.

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CHAPTER 1 Functional Organization of the Human Body...

CHAPTER 1 Functional Organization of the Human Body UNIT I and Control of the “Internal Environment” Physiology is the science that seeks to explain the physi- Each type of cell is specially adapted to perform one cal and chemical mechanisms that are responsible for the or a few particular functions. For example, the red blood origin, development, and progression of life. Each type cells, numbering about 25 trillion in each person, trans- of life, from the simplest virus to the largest tree or the port oxygen from the lungs to the tissues. Although the complicated human being, has its own functional char- red blood cells are the most abundant of any single type of acteristics. Therefore, the vast field of physiology can be cell in the body, there are also trillions of additional cells divided into viral physiology, bacterial physiology, cellular of other types that perform functions different from those physiology, plant physiology, invertebrate physiology, ver- of the red blood cell. The entire body, then, contains about tebrate physiology, mammalian physiology, human physi- 35 to 40 trillion human cells. ology, and many more subdivisions. The many cells of the body often differ markedly from one another but all have certain basic characteristics that Human Physiology. The science of human physiology are alike. For example, oxygen reacts with carbohydrate, traded attempts to explain the specific characteristics and mech- fat, and protein to release the energy required for all cells to anisms of the human body that make it a living being. The fact that we remain alive is the result of complex control to function. Furthermore, the general chemical mecha- nisms for changing nutrients into energy are basically tr systems. Hunger makes us seek food, and fear makes us the same in all cells, and all cells deliver products of their a or seek refuge. Sensations of cold make us look for warmth. chemical reactions into the surrounding fluids. Other forces cause us to seek fellowship and to reproduce. Almost all cells also have the ability to reproduce addi- norbode The fact that we are sensing, feeling, and knowledgeable in beings is part of this automatic sequence of life; these spe- tional cells of their own type. Fortunately, when cells of a particular type are destroyed, the remaining cells of this type moti ons mused. cial attributes allow us to exist under widely varying con- ditions that otherwise would make life impossible. Human physiology links the basic sciences with medicine usually generate new cells until the supply is replenished. Microorganisms Living in the Body Outnumber Hu- naso ano integrates multiple functions of the cells, tissues, and and man Cells. In addition to human cells, trillions of microbes organs into the functions of the living human being. This inte- inhabit the body, living on the skin and in the mouth, gut, know in gration requires communication and coordination by a vast and nose. The gastrointestinal tract, for example, normally array of control systems that operate at every level—from the contains a complex and dynamic population of 400 to 1000 was genes that program synthesis of molecules to the complex species of microorganisms that outnumber our human monge nervous and hormonal systems that coordinate functions of cells. Communities of microorganisms that inhabit the real ·horudwara cells, tissues, and organs throughout the body. Thus, the coor- body, often called microbiota, can cause diseases, but most dinated functions of the human body are much more than the of the time they live in harmony with their human hosts sum of its parts, and life in health, as well as in disease states, and provide vital functions that are essential for survival of relies on this total function. Although the main focus of this their hosts. Although the importance of gut microbiota in book is on normal human physiology, we will also discuss, the digestion of foodstuffs is widely recognized, additional to some extent, pathophysiology, which is the study of disor- roles for the body’s microbes in nutrition, immunity, and dered body function and the basis for clinical medicine.␣ other functions are just beginning to be appreciated and represent an intensive area of biomedical research.␣ CELLS ARE THE LIVING UNITS OF THE BODY EXTRACELLULAR FLUID—THE “INTERNAL ENVIRONMENT” The basic living unit of the body is the cell. Each tissue or organ is an aggregate of many different cells held together About 50% to 70% of the adult human body is fluid, mainly by intercellular supporting structures. a water solution of ions and other substances. Although 3 UNIT I Introduction to Physiology: The Cell and General Physiology ⑧ most of this fluid is inside the cells and is called intracellu- regulated, normally varying only a few millimoles per liter, lar fluid, about one-third is in the spaces outside the cells even with large changes in sodium intake, but these varia- and is called extracellular fluid. This 0extracellular fluid is tions of sodium concentration are at least 1 million times in constant motion throughout the body. It is transported greater than for hydrogen ions. rapidly in the circulating blood and then mixed between Powerful control systems exist for maintaining concen- the blood and tissue fluids by diffusion through the capil- trations of sodium and hydrogen ions, as well as for most lary walls. of the other ions, nutrients, and substances in the body at In the extracellular fluid are the ions and nutrients levels that permit the cells, tissues, and organs to perform needed by the cells to maintain life. Thus, all cells live in their normal functions, despite wide environmental varia- & essentially the same environment—the extracellular fluid. - > tions and challenges from injury and diseases. For this reason, the extracellular fluid is also called the Much of this text is concerned witho how each organ or internal environment of the body, or the milieu intérieur, a tissue contributes to homeostasis. Normal body functions term introduced by the great 19th-century French physi- require integrated actions of cells, tissues, organs, and ologist Claude Bernard (1813–1878). multiple nervous, hormonal, and local control systems Cells are capable of living and performing their spe- that together contribute to homeostasis and good health. cial functions as long as the proper concentrations of oxygen, glucose, different ions, amino acids, fatty sub- Homeostatic Compensations in Diseases. Disease is - > stances, and other constituents are available in this inter- often considered to be a state of disrupted homeostasis. nal environment. However, even in the presence of disease, homeostatic mechanisms continue to operate and maintain vital func- Differences in Extracellular and Intracellular Fluids. tions through multiple compensations. In some cases, different The extracellular fluid contains large amounts of sodium, these compensations may lead to major deviations of the body’s functions from the normal range,= fom - - > chloride, and bicarbonate ions plus nutrients for the cells, making it diffi- such as oxygen, glucose, fatty acids, and amino acids. It cult to distinguish the primary cause of the disease from also contains carbon dioxide that is being transported the compensatory responses. For example, diseases that from the cells to the lungs to be excreted, plus other cel- impair the kidneys’ ability to excrete salt and water may lular waste products that are being transported to the kid- lead to high blood pressure, which initially helps return neys for excretion. excretion to normal so that a balance between intake and The intracellular fluid contains ·large amounts of potas- renal excretion can be maintained. This balance is needed sium, magnesium, and phosphate ions instead of the to maintain life, but, over long periods of time, the high kiMgiPOy sodium and chloride ions found in the extracellular fluid. Special mechanisms for transporting ions through the cell blood pressure can damage various organs, including the kidneys, causing even greater increases in blood pressure membranes maintain the ion concentration differences and more renal damage. Thus, homeostatic compensa- between the extracellular and intracellular fluids. These tions that ensue after injury, disease, or major environ- transport processes are discussed in Chapter 4.␣ mental challenges to the body may represent trade-offs that are necessary to maintain vital body functions but, in the long term, contribute to additional abnormalities HOMEOSTASIS—MAINTENANCE OF of body function. The discipline of pathophysiology seeks A NEARLY CONSTANT INTERNAL to explain how the various physiological processes are al- ENVIRONMENT tered in diseases or injury. In 1929, the American physiologist Walter Cannon This chapter outlines the different functional systems e (1871–1945) coined the term homeostasis to describe the of the body and their contributions to homeostasis. We S maintenance of nearly constant conditions in the internal then briefly discuss the basic theory of the body’s control equimbi environment. Essentially,o all organs and tissues of the body perform functions that help maintain these relatively con- - > systems that allow the functional systems to operate in support of one another.␣ - stant conditions. For example, the lungs provide oxygen to the extracellular fluid to replenish the oxygen used by EXTRACELLULAR FLUID TRANSPORT the cells, the kidneys maintain constant ion concentra- AND MIXING SYSTEM—THE BLOOD tions, and the gastrointestinal system provides nutrients CIRCULATORY SYSTEM while eliminating waste from the body. The various ions, nutrients, waste products, and other Extracellular fluid is transported through the body in two constituents of the body are normally regulated within a stages. The first stage is movement of blood through the ① range of values, rather than at fixed values. For some of the body in the blood vessels. The second is movement of ② body’s constituents, this range is extremely small. Varia- fluid between the blood capillaries and the intercellular tions in the blood hydrogen ion concentration, for exam- spaces between the tissue cells. ple, are normally less than 5 nanomoles/L (0.000000005 Figure 1-1 shows the overall circulation of blood. All the moles/L). The blood sodium concentration is also tightly blood in the circulation traverses the entire circuit an average 4 Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” Lungs Arteriole UNIT I CO2 O2 Right Left heart heart pump pump Venule Gut Figure 1-2. Diffusion of fluid and dissolved constituents through the capillary walls and interstitial spaces. Nutrition That is, the fluid and dissolved molecules are continually and moving and bouncing in all directions in the plasma and excretion fluid in the intercellular spaces, as well as through capil- lary pores. Few cells are located more than 50 microm- eters from a capillary, which ensures diffusion of almost any substance from the capillary to the cell within a few Kidneys seconds. Thus, the extracellular fluid everywhere in the body—both that of the plasma and that of the interstitial fluid—is continually being mixed, thereby maintaining homogeneity of extracellular fluid throughout the body.␣ Regulation ORIGIN OF NUTRIENTS IN THE of Excretion electrolytes EXTRACELLULAR FLUID I Respiratory System. Figure 1-1 shows that each time blood passes through the body, it also flows through the Venous end Arterial end lungs. The blood picks up oxygen in alveoli, thus acquiring - the oxygen needed by cells. The membrane between the - - alveoli and the lumen of the pulmonary capillaries, the ~ - alveolar membrane, is only 0.4 to 2.0 micrometers thick, and oxygen rapidly diffuses by molecular motion through - Capillaries this membrane into the blood.␣ - Figure 1-1. General organization of the circulatory system. Gastrointestinal Tract. A large portion of the blood pumped by the heart also passes through the· walls of the gastrointes- of once each minute when the body is ⑧ at rest and as many tinal tract. Here different dissolved nutrients, including car- as six times each minute when a person is extremely active. - > bohydrates, fatty acids, and amino acids, are absorbed from TCFA As blood passes through blood capillaries, continual ingested food into the extracellular fluid of the blood.␣ - > exchange of extracellular fluid occurs between the plasma portion of the blood and the interstitial fluid that · fills the Liver and Other Organs That Perform Primarily Meta- intercellular spaces. This process is shown in Figure 1-2. bolic Functions.②Not all substances absorbed from the The capillary walls are permeable to most molecules in gastrointestinal tract can be used in their absorbed form the blood plasma, with the exception of plasma proteins, - by the cells. The liver changes the chemical compositions which are too large to pass through capillaries readily. - - of many of these substances to more usable forms, and Therefore, large amounts of fluid and its dissolved con- other tissues of the body—fat cells, gastrointestinal mu- stituents diffuse back and forth between the blood and the cosa, kidneys, and endocrine glands—help⑧ modify the FGKE tissue spaces, as shown by the arrows in Figure 1-2. absorbed substances oro store them until they are needed. This process of diffusion is caused by kinetic motion The liver also eliminates certain waste products produced of the molecules in the plasma and the interstitial fluid. in the body and toxic substances that are ingested.␣ 5 UNIT I Introduction to Physiology: The Cell and General Physiology Musculoskeletal System. How does the musculoskeletal performs in response to the sensations. Appropriate sig- system contribute to homeostasis? The answer is obvious nals are then transmitted through the motor output por- and simple. Were it not for the muscles, the body could tion of the nervous system to carry out one’s desires. not move to obtain the foods required for nutrition. The An important segment of the nervous system is called musculoskeletal system also provides motility for protec- the autonomic system. It operates at a subconscious level tion against adverse surroundings, without which the en- and controls many functions of internal organs, including the > Nervous System. The nervous system is composed of side world. The integumentary system is also important - > three major parts—the sensory input portion, the central for temperature regulation and excretion of wastes, and sCM nervous system (or integrative portion), and the motor out- it provides a sensory interface between the body and the - - put portion. Sensory receptors detect the state of the body external environment. The skin generally comprises about and its surroundings. For example, receptors in the skin alert us whenever an object touches the skin. The eyes 12% to 15% of body weight.␣ ↳ percuve onmental are sensory organs that give us a visual image of the sur- REPRODUCTION stimuli rounding area. The ears are also sensory organs. The cen- tral nervous system is composed of the brain and spinal Although reproduction is sometimes not considered a cord. The brain stores information, generates thoughts, homeostatic function, it helps maintain homeostasis by creates ambition, and determines reactions that the body generating new beings to take the place of those that are 6 Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” dying. This may sound like a permissive usage of the term Reference homeostasis, but it illustrates that in the final analysis, set point essentially all body structures are organized to help main- Error signal Effectors tain the automaticity and continuity of life.␣ Brain medulla Sympathetic Blood vessels Vasomotor nervous system Heart centers CONTROL SYSTEMS OF THE BODY UNIT I The human body has thousands of control systems. Some Feedback signal of the most intricate of these systems are genetic control systems that operate in all cells to help regulate intracel- Baroreceptors Arterial lular and extracellular functions. This subject is discussed pressure in Chapter 3. oppoteare a Sensor Controlled variable Many other control systems operate within the organs Figure 1-3. Negative feedback control of arterial pressure by the ar- to regulate functions of the individual parts of the organs; terial baroreceptors. Signals from the sensor (baroreceptors) are sent others operate throughout the entire body to control the to the medulla of the brain, where they are compared with a refer- interrelationships between the organs. For example, the ence set point. When arterial pressure increases above normal, this abnormal pressure increases nerve impulses from the baroreceptors respiratory system, operating in association with the to the medulla of the brain, where the input signals are compared nervous system, regulates the concentration of carbon with the set point, generating an error signal that leads to decreased dioxide in the extracellular fluid. The liver and pancreas sympathetic nervous system activity. Decreased sympathetic activity control glucose concentration in the extracellular fluid, causes dilation of blood vessels and reduced pumping activity of the and the kidneys regulate concentrations of hydrogen, heart, which return arterial pressure toward normal. sodium, potassium, phosphate, and other ions in the extracellular fluid. Regulation of Arterial Blood Pressure. Several systems contribute to arterial blood pressure regulation. One of these, the baroreceptor system, is an excellent example of EXAMPLES OF CONTROL MECHANISMS ~ a rapidly acting control mechanism (Figure 1-3). In the division two Regulation of Oxygen and Carbon Dioxide Concen- walls of the bifurcation region of the carotid arteries in into trations in the Extracellular Fluid. Because oxygen is - - the neck, and also in the arch of the aorta in the thorax, one of the major substances required for chemical reac- are many nerve receptors called baroreceptors that are tions in cells, the body has a special control mechanism to stimulated by stretch of the arterial wall. When arterial maintain an almost exact and constant oxygen concentra- pressure rises too high, the baroreceptors send & barrages 44quantity tion in the extracellular fluid. This mechanism depends of nerve impulses to the medulla of the brain. Here, these principally on the chemical characteristics of hemoglobin, impulses inhibit the vasomotor center, which in turn de- which is present in red blood cells. Hemoglobin com- creases the number of impulses transmitted from the bines with oxygen as the blood passes through the lungs. vasomotor center through the sympathetic nervous sys- Then, as the blood passes through the tissue capillaries, tem to the heart and blood vessels. Lack of these impulses hemoglobin, because of its own strong chemical affinity causes diminished pumping activity by the heart and dila- for oxygen, does not release oxygen into the tissue fluid tion of peripheral blood vessels, allowing increased blood if too much oxygen is already there. However, if oxygen flow through the vessels. Both these effects decrease the concentration in the tissue fluid is too low, sufficient oxy- arterial pressure, moving it back toward normal. gen is released to re-establish an adequate concentration. Conversely, a decrease in arterial pressure below nor- Thus, regulation of oxygen concentration in the tissues mal relaxes the stretch receptors, allowing the vasomotor relies to a great extent on the chemical characteristics of center to become more active than usual, thereby causing hemoglobin. This regulation is called the oxygen-buffering vasoconstriction and increased heart pumping. The initial function of hemoglobin. decrease in arterial pressure thus initiates negative feed- - Carbon dioxide concentration in the extracellular fluid - > back mechanisms that raise arterial pressure back toward is regulated in a much different way. Carbon dioxide is a normal.␣ major end product of oxidative reactions in cells. If all the carbon dioxide formed in the cells continued to accumu- Normal Ranges and Physical late in the tissue fluids, all energy-giving reactions of the Characteristics of Important Extracellular cells would cease. Fortunately, a higher than normal car- Fluid Constituents bon dioxide concentration in the blood excites the respira- Table 1-1 lists some important constituents and physical tory center, causing a person to breathe rapidly and deeply. characteristics of extracellular fluid, along with their nor- This deep rapid breathing increases expiration of carbon mal values, normal ranges, and maximum limits without dioxide and, therefore, removes excess carbon dioxide causing death. Note the narrowness of the normal range from the blood and tissue fluids. This process continues for each one. Values outside these ranges are often caused until the concentration returns to normal.␣ by illness, injury, or major environmental challenges. 7 UNIT I Introduction to Physiology: The Cell and General Physiology Table 1-1 Important Constituents and Physical Characteristics of Extracellular Fluid Constituent Normal Value Normal Range Approximate Short-Term Nonlethal Limit Unit Oxygen (venous) 40 25–40 10–1000 mm Hg Carbon dioxide (venous) 45 41–51 5–80 mm Hg Sodium ion 142 135–145 115–175 mmol/L Potassium ion 4.2 3.5–5.3 1.5–9.0 mmol/L Calcium ion 1.2 1.0–1.4 0.5–2.0 mmol/L Chloride ion 106 98–108 70–130 mmol/L Bicarbonate ion 24 22–29 8–45 mmol/L Glucose 90 70–115 20–1500 mg/dl Body temperature 98.4 (37.0) 98–98.8 (37.0) 65–110 (18.3–43.3) °F (°C) Acid–base (venous) 7.4 7.3–7.5 6.9–8.0 pH Most important are the limits beyond which abnor- the extracellular fluid carbon dioxide concentration malities can cause death. For example, an increase in the because the lungs expire greater amounts of carbon diox- body temperature of only 11°F (7°C) above normal can ide from the body. Thus, the high concentration of carbon lead to a vicious cycle of increasing cellular metabolism dioxide initiates events that decrease the concentration that destroys the cells. Note also the narrow range for toward normal, which is negative to the initiating stimu- acid–base balance in the body, with a normal pH value lus. Conversely, a carbon dioxide concentration that falls of 7.4 and lethal values only about 0.5 on either side of too low results in feedback to increase the concentration. normal. Whenever the potassium ion concentration This response is also negative to the initiating stimulus. decreases to less than one-third normal, o paralysis may In the arterial pressure–regulating mechanisms, a high result from the inability of the nerves to carry signals. pressure causes a series of reactions that promote reduced Alternatively, if potassium ion concentration increases pressure, or a low pressure causes a series of reactions that to two or more times normal, the heart muscle is likely promote increased pressure. In both cases, these effects to be② severely depressed. Also, when the calcium ion are negative with respect to the initiating stimulus. concentration falls below about one-half normal, a per- Therefore, in general, if some factor becomes exces- son is likely to experience&tetanic contraction of muscles sive or deficient, a control system initiates negative feed- throughout the body because of the spontaneous genera- back, which consists of a series of changes that return tion of excess nerve impulses in peripheral nerves. When the factor toward a certain mean value, thus maintaining the glucose concentration falls below one-half normal, a homeostasis. person frequently exhibits extreme mental irritability and sometimes even has convulsions. Gain of a Control System. The degree of effectiveness These examples should give one an appreciation for with which a control system maintains constant condi- the necessity of the vast numbers of control systems that tions is determined by the gain of negative feedback. keep the body operating in health. In the absence of any For example, let us assume that a large volume of blood one of these controls, serious body malfunction or death is transfused into a person whose baroreceptor pressure can result.␣ control system is ⑧not functioning, and the arterial pres- sure rises from the normal level of 100 mm Hg up to 175 mm Hg. Then, let us assume that the same volume of CHARACTERISTICS OF CONTROL SYSTEMS blood is injected into the same person when the barore- The aforementioned examples of homeostatic control ceptor system is functioning, and this time the pressure mechanisms are only a few of the many thousands in the increases by only 25 mm Hg. Thus, the feedback control body, all of which have some common characteristics, as system has caused a “correction” of −50 mm Hg, from explained in this section. 175 mm Hg to 125 mm Hg. There remains an increase in pressure of +25 mm Hg, called the “error,” which means Negative Feedback Nature of Most that the control system is not 100% effective in preventing Control Systems change. The gain of the system is then calculated by using Most control systems of the body act by negative feed- the following formula: back, which can be explained by reviewing some of the Correction Gain = homeostatic control systems mentioned previously. In Error the regulation of carbon dioxide concentration, a high Thus, in the baroreceptor system example, the correc- concentration of carbon dioxide in the extracellular fluid tion is −50 mm Hg, and the error persisting is +25 mm Hg. increases pulmonary ventilation. This, in turn, decreases Therefore, the gain of the person’s baroreceptor system 8 Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” 5 overcome by the negative feedback control mechanisms of the body, and the vicious cycle then fails to develop. Pumping effectiveness of heart Return to For example, if the person in the aforementioned example (Liters pumped per minute) 4 normal bleeds only 1 liter instead of 2 liters, the normal negative Bled 1 liter feedback mechanisms for controlling cardiac output and 3 arterial pressure can counterbalance the positive feedback UNIT I and the person can recover, as shown by the dashed curve Bled 2 liters of Figure 1-4. 2 Positive Feedback Can Sometimes Be Useful. The body 1 sometimes uses positive feedback to its advantage. Blood clotting is an example of a valuable use of positive feed- Death back. When a blood vessel is ruptured, and a clot begins to 0 form, multiple enzymes called clotting factors are activated 1 2 3 within the clot. Some of these enzymes act on other inac- Hours tivated enzymes of the immediately adjacent blood, thus Figure 1-4. Recovery of heart pumping caused by negative feedback causing more blood clotting. This process continues until after 1 liter of blood is removed from the circulation. Death is caused by positive feedback when 2 liters or more blood is removed. the hole in the vessel is plugged and bleeding no longer occurs. On occasion, this mechanism can get out of hand for control of arterial pressure is −50 divided by +25, or and cause formation of unwanted clots. In fact, this is what −2. That is, a disturbance that increases or decreases the initiates most acute heart attacks, which can be caused by - arterial pressure does so only one-third as much as would a clot beginning on the inside surface of an atherosclerotic occur if this control system were not present. plaque in a coronary artery and then growing until the ar- The gains of some other physiological control systems tery is blocked. are much greater than that of the baroreceptor system. Childbirth is another situation in which positive feed- For example, the gain of the system controlling internal back is valuable. When uterine contractions become body temperature when a person is exposed to moder- strong enough for the baby’s head to begin pushing ately cold weather is about −33. Therefore, one can see through the cervix, stretching of the cervix sends signals that the temperature control system is much more effec- through the uterine muscle back to the body of the uterus, tive than the baroreceptor pressure control system.␣ causing even more powerful contractions. Thus, the uter- ine contractions stretch the cervix, and cervical stretch Positive Feedback May Cause Vicious causes stronger contractions. When this process becomes Cycles and Death powerful enough, the baby is born. If they are not pow- Why do most control systems of the body operate by erful enough, the contractions usually die out, and a few negative feedback rather than by positive feedback? If days pass before they begin again. one considers the nature of positive feedback, it is obvi- Another important use of positive feedback is for the ous that positive feedback leads to instability rather than generation of nerve signals. Stimulation of the mem- stability and, in some cases, can cause death. brane of a nerve fiber causes slight leakage of sodium ions Figure 1-4 shows an example in which death can ensue through sodium channels in the nerve membrane to the from positive feedback. This figure depicts the pumping fiber’s interior. The sodium ions entering the fiber then effectiveness of the heart, showing the heart of a healthy change the membrane potential, which, in turn, causes human pumping about 5 liters of blood per minute. If the more opening of channels, more change of potential, still person suddenly bleeds a total of 2 liters, the amount of more opening of channels, and so forth. Thus, a slight leak blood in the body is decreased to such a low level that becomes an explosion of sodium entering the interior of not enough blood is available for the heart to pump effec- the nerve fiber, which creates the nerve action potential. tively. As a result, the arterial pressure falls, and the flow This action potential, in turn, causes electrical current to of blood to the heart muscle through the coronary ves- flow along the outside and inside of the fiber and initiates sels diminishes. This scenario results in weakening of the additional action potentials. This process continues until heart, further diminished pumping, a further decrease the nerve signal goes all the way to the end of the fiber. in coronary blood flow, and still more weakness of the In each case in which positive feedback is useful, the heart; the cycle repeats itself again and again until death positive feedback is part of an overall negative feedback occurs. Note that each cycle in the feedback results in process. For example, in the case of blood clotting, the further weakening of the heart. In other words, the initi- positive feedback clotting process is a negative feedback ating stimulus causes more of the same, which is positive process for the maintenance of normal blood volume. feedback. Also, the positive feedback that causes nerve signals Positive feedback is sometimes known as a “vicious allows the nerves to participate in thousands of negative cycle,” but a mild degree of positive feedback can be feedback nervous control systems.␣ 9 UNIT I Introduction to Physiology: The Cell and General Physiology More Complex Types of Control for understanding normal physiology as well as for treat- Systems—Feed-Forward and Adaptive ment of diseases. Control Age-related and ethnic or racial differences in physiol- Later in this text, when we study the nervous system, we ogy also have important influences on body composition, shall see that this system contains great numbers of inter- physiological control systems, and pathophysiology of connected control mechanisms. Some are simple feedback diseases. For example, in a lean young male the total body systems similar to those already discussed. Many are not. water is about 60% of body weight. As a person grows and For example, some movements of the body occur so rap- ages, this percentage gradually decreases, partly because idly that there is not enough time for nerve signals to travel ⑧ aging is usually associated with declining skeletal muscle from the peripheral parts of the body all the way to the mass and increasing fat mass. Aging may also cause a brain and then back to the periphery again to control the decline in the function and effectiveness of some organs movement. Therefore, the brain uses a mechanism called and physiological control systems. feed-forward control to cause required muscle contrac- These sources of physiological variability—sex differ- tions. Sensory nerve signals from the moving parts apprise ences, aging, ethnic, and racial—are complex but impor- the brain about whether the movement is performed cor- tant considerations when discussing normal physiology rectly. If not, the brain corrects the feed-forward signals and the pathophysiology of diseases.␣ that it sends to the muscles the next time the movement is required. Then, if still further correction is necessary, SUMMARY—AUTOMATICITY OF THE this process will be performed again for subsequent move- BODY ments. This process is called adaptive control. Adaptive control, in a sense, is delayed negative feedback. The main purpose of this chapter has been to discuss Thus, one can see how complex the feedback control briefly the overall organization of the body and the means systems of the body can be. A person’s life depends on all whereby the different parts of the body operate in har- of them. Therefore, much of this text is devoted to dis- mony. To summarize, the body is actually a social order of cussing these life-giving mechanisms.␣ about 35 to 40 trillion cells organized into different func- tional structures, some of which are called organs. Each functional structure contributes its share to the mainte- PHYSIOLOGICAL VARIABILITY nance of homeostasis in the extracellular fluid, which is Although some physiological variables, such as plasma called the internal environment. As long as normal con- concentrations of potassium, calcium, and hydrogen ditions are maintained in this internal environment, the ions, are tightly regulated, others, such as body weight cells of the body continue to live and function properly. and adiposity, show wide variation among different indi- Each cell benefits from homeostasis and, in turn, each viduals and even in the same individual at different stages cell contributes its share toward the maintenance of of life. Blood pressure, cardiac pumping, metabolic rate, homeostasis. This reciprocal interplay provides continu- nervous system activity, hormones, and other physi- ous automaticity of the body until one or more functional ological variables change throughout the day as we move systems lose their ability to contribute their share of func- about and engage in normal daily activities. Therefore, tion. When this happens, all the cells of the body suffer. when we discuss “normal” values, it is with the under- Extreme dysfunction leads to death; moderate dysfunc- standing that many of the body’s control systems are con- tion leads to sickness. stantly reacting to perturbations, and that variability may uneasy exist among different individuals, depending on body weight and height, diet, age, sex, environment, genetics, Bibliography and other factors. Adolph EF: Physiological adaptations: hypertrophies and superfunc- For simplicity, discussion of physiological functions tions. Am Sci 60:608, 1972. often focuses on the “average” 70-kg young, lean male. 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Am J Physiol Regul Integr Comp Physiol many other physiological functions and normal values 289:R633, 2005. are often discussed in terms of male physiology. However, Dickinson MH, Farley CT, Full RJ, et al: How animals move: an integra- there are clearly differences in male and female physiology tive view. Science 288:100, 2000. Eckel-Mahan K, Sassone-Corsi P: Metabolism and the circadian clock beyond the obvious differences that relate to reproduc- converge. Physiol Rev 93:107, 2013. tion. These differences can have important consequences 10 Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” Guyton AC: Arterial Pressure and Hypertension. Philadelphia: WB Nishida AH, Ochman H: A great-ape view of the gut microbiome. Nat Saunders, 1980. Rev Genet 20:185, 2019. Herman MA, Kahn BB: Glucose transport and sensing in the mainte- Orgel LE: The origin of life on the earth. Sci Am 271:76,1994. nance of glucose homeostasis and metabolic harmony. 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