Introduction To Physiology PDF

1 Introduction to Physiology The current tendency of physiological thought is clearly toward an increasing emphasis upon the unity of operation of the Human Body. Ernest G. Martin, preface to The Human Body 10th edition, 1917 1.1 Physiology Is an Integrative LO 1.4...

1 Introduction to Physiology The current tendency of physiological thought is clearly toward an increasing emphasis upon the unity of operation of the Human Body. Ernest G. Martin, preface to The Human Body 10th edition, 1917 1.1 Physiology Is an Integrative LO 1.4.3 Explain the law of mass balance LO 1.5.5 Compare negative feedback, positive Science 2 and how it applies to the body’s load of a feedback, and feedforward control. Give an substance. example of each. LO 1.1.1 Define physiology. LO 1.4.4 Define mass flow using math- LO 1.5.6 Explain what happens to setpoints in LO 1.1.2 List the levels of organization from ematical units and explain how it relates to biological rhythms and give some examples. atoms to the biosphere. mass balance. LO 1.1.3 Name the 10 physiological organ LO 1.4.5 Define clearance and give an example. 1.6 The Science of Physiology 18 systems of the body and give their functions. LO 1.6.1 Explain and give examples of the LO 1.4.6 Distinguish between equilibrium and steady state. following components of scientific research: 1.2 Function and Mechanism 4 independent and dependent variables, LO 1.2.1 Distinguish between mechanistic 1.5 Control Systems and experimental control, data, replication, explanations and teleological explanations. variability. Homeostasis 13 LO 1.6.2 Compare and contrast the following 1.3 Themes in Physiology 5 LO 1.5.1 List the three components of a control types of experimental study designs: blind system and give an example. LO 1.3.1 List and give examples of the four study, double-blind study, crossover study, major themes in physiology. LO 1.5.2 Explain the relationship between a prospective and retrospective studies, regulated variable and its setpoint. cross-sectional study, longitudinal study, 1.4 Homeostasis 9 LO 1.5.3 Compare local control, long-distance meta-analysis. LO 1.4.1 Define homeostasis. What happens control, and reflex control. LO 1.6.3 Define placebo and nocebo effects and when homeostasis fails? LO 1.5.4 Explain the relationship between a explain how they may influence the outcome LO 1.4.2 Name and describe the two major response loop and a feedback loop. of experimental studies. compartments of the human body. 2 CHAPTER 1 Introduction to Physiology elcome to the fascinating study of the human body! For most W of recorded history, humans have been interested in how their bodies work. Early Egyptian, Indian, and Chinese writings describe attempts by physicians to treat various diseases and to restore RUNNING PROBLEM What to Believe? Jimmy had just left his first physiology class when he got the text from his mother: Please call. Need to ask you something. His health. Although some ancient remedies, such as camel dung and mother seldom texted, so Jimmy figured it must be important. “Hi, powdered sheep horn, may seem bizarre, we are still using others, Mom! What’s going on?” such as blood-sucking leeches and chemicals derived from medicinal “Oh, Jimmy, I don’t know what to do. I saw the doctor this plants. The way we use these treatments has changed through the morning and he’s telling me that I need to take insulin. But I don’t centuries as we have learned more about the human body. want to! My type of diabetes doesn’t need insulin. I think he’s just There has never been a more exciting time in human physiol- trying to make me see him more by putting me on insulin. Don’t ogy. Physiology is the study of the normal functioning of a living you think I’m right?” organism and its component parts, including all its chemical and Jimmy paused for a moment. “I’m not sure, Mom. He’s prob- physical processes. The term physiology literally means “knowledge ably just trying to do what’s best for you. Didn’t you talk to him of nature.” Aristotle (384–322 bce) used the word in this broad about it?” sense to describe the functioning of all living organisms, not just of “Well, I tried but he didn’t have time to talk. You’re studying these things. Can’t you look it up and see if I really need insulin?” the human body. However, Hippocrates (ca. 460–377 bce), consid- “I guess so. Let me see what I can find out.” Jimmy hung up ered the father of medicine, used the word physiology to mean “the and thought. “Now what?” healing power of nature,” and thereafter the field became closely associated with medicine. By the sixteenth century in Europe, 2 5 9 12 16 19 24 physiology had been formalized as the study of the vital functions of the human body. Currently the term is again used to refer to the study of animals and plants. When the Human Genome Project (www.genome.gov) began Today, we benefit from centuries of work by physiologists who in 1990, scientists thought that by identifying and sequencing all constructed a foundation of knowledge about how the human the genes in human DNA, they would understand how the body body functions. Since the 1970s, rapid advances in the fields of worked. However, as research advanced, scientists had to revise cellular and molecular biology have supplemented this work. A few their original idea that a given segment of DNA contained one decades ago, we thought that we would find the key to the secret of gene that coded for one protein. It became clear that one gene life by sequencing the human genome, which is the collective term may code for many proteins. The Human Genome Project ended for all the genetic information contained in the DNA of a species. in 2003, but before then researchers had moved beyond genomics However, this deconstructionist view of biology has proved to have to proteomics, the study of proteins in living organisms. its limitations, because living organisms are much more than the Now scientists have realized that knowing that a protein is simple sum of their parts. made by a particular cell does not always tell us the significance of that protein to the cell, the tissue, or the functioning organism. The exciting new areas in biological research are called functional 1.1 Physiology Is an Integrative genomics, systems biology, and integrative biology, but fundamen- tally these are all fields of physiology. The integration of func- Science tion across many levels of organization is a special focus of Many complex systems—including those of the human body— physiology. (To integrate means to bring varied elements together to possess emergent properties, which are properties that cannot create a unified whole.) be predicted to exist based only on knowledge of the system’s FIGURE 1.1 illustrates levels of organization ranging from the individual components. An emergent property is not a property molecular level all the way up to populations of different spe- of any single component of the system, and it is greater than the cies living together in ecosystems and in the biosphere. The levels of simple sum of the system’s individual parts. Emergent proper- organization are shown along with the various subdisciplines of ties result from complex, nonlinear interactions of the different chemistry and biology related to the study of each organizational components. level. There is considerable overlap between the different fields of For example, suppose someone broke down a car into its nuts study, and these artificial divisions vary according to who is defin- and bolts and pieces and laid them out on a floor. Could you pre- ing them. Notice, however, that physiology includes multiple levels, dict that, properly assembled, these bits of metal and plastic would from molecular and cellular biology to the ecological physiology become a vehicle capable of converting the energy in gasoline into of populations. movement? Who could predict that the right combination of ele- At all levels, physiology is closely tied to anatomy. The struc- ments into molecules and assemblages of molecules would result in ture of a cell, tissue, or organ must provide an efficient physical a living organism? Among the most complex emergent properties base for its function. For this reason, it is nearly impossible to study in humans are emotion, intelligence, and other aspects of brain the physiology of the body without understanding the underlying function. None of these properties can be predicted from knowing anatomy. Because of the interrelationship of anatomy and physi- the individual properties of nerve cells. ology, you will find Anatomy Summaries throughout the book.  1.1 Physiology Is an Integrative Science 3 EMERGING CONCEPTS unit of structure capable of carrying out all life processes. A lipid and protein barrier called the cell membrane (also called the CHAPTER The Changing World of Omics plasma membrane) separates cells from their external environment. If you read the scientific literature, it appears that contem- Simple organisms are composed of only one cell, but complex porary research has exploded into an era of “omes” and organisms have many cells with different structural and functional “omics.” What is an “ome”? The term apparently derives specializations. 1 from the Latin word for a mass or tumor, and it is now used Collections of cells that carry out related functions are called to refer to a collection of items that make up a whole, such tissues {texere, to weave}. Tissues form structural and functional as a genome. One of the earliest uses of the “ome” suffix in units known as organs {organon, tool}, and groups of organs inte- biology is the term biome, meaning all organisms living in grate their functions to create organ systems. Chapter 3 reviews a major ecological region, such as the marine biome or the the anatomy of cells, tissues, and organs. desert biome. A genome, for example, is a collection of all The 10 physiological organ systems in the human body are the genetic material of an organism. Its physiome describes illustrated in FIGURE 1.2. Several of the systems have alternate the organism’s coordinated molecular, cellular, and physi- names, given in parentheses, that are based on the organs of the ological functioning. system rather than the function of the system. The integumen- The related adjective “omics” describes the research tary system {integumentum, covering}, composed of the skin, related to studying an “ome.” Adding “omics” to a root word forms a protective boundary that separates the body’s internal has become the cutting-edge way to describe a research environment from the external environment (the outside world). field. For example, pharmacogenomics (the influence of The musculoskeletal system provides support and body genetics on the body’s response to drugs) is now as impor- movement. tant as genomics, the sequencing of DNA (the genome). Four systems exchange materials between the internal and There is even a journal named OMICS! New “omes” emerge every year. The human con- external environments. The respiratory (pulmonary) sys- nectome project (www.neuroscienceblueprint.nih.gov/ tem exchanges gases; the digestive (gastrointestinal) system connectome/) sponsored by the American National Insti- takes up nutrients and water and eliminates wastes; the urinary tutes of Health is a collaborative effort by multiple institu- (renal) system removes excess water and waste material; and the tions to map all the neural connections of the human brain. reproductive system produces eggs or sperm. NIH also sponsors the human microbiome project (https:// The remaining four systems extend throughout the body. The commonfund.nih.gov/hmp/overview), whose goal is to circulatory (cardiovascular) system distributes materials by study the effects of microbes that normally live on or in the pumping blood through vessels. The nervous and endocrine human body. Ignored as unimportant for many years, these systems coordinate body functions. Note that the figure shows microbes are now being shown to have an influence on them as a continuum rather than as two distinct systems. Why? both health and disease. Because the lines between these two systems have blurred as we have learned more about the integrative nature of physiological function. The one system not illustrated in Figure 1.2 is the diffuse These special review features illustrate the anatomy of the physi- immune system, which includes but is not limited to the ana- ological systems at different levels of organization. tomical structures known as the lymphatic system. The specialized At the most basic level of organization shown in Figure cells of the immune system are scattered throughout the body. 1.1, atoms of elements link together to form molecules. Collec- They protect the internal environment from foreign substances by tions of molecules in living organisms form cells, the smallest intercepting material that enters through the intestines and lungs FIG. 1.1 Levels of organization and the related fields of study PHYSIOLOGY ECOLOGY CELL MOLECULAR BIOLOGY BIOLOGY CHEMISTRY Organ Populations of Ecosystem of Atoms Molecules Cells Tissues Organs Organisms Biosphere systems one species different species 4 CHAPTER 1 Introduction to Physiology FIG. 1.2 Organ systems of the human body and their integration FIG. 1.2 Organ Systems of the Human Body and their Integration System Name Includes Representative Functions The Integration between Systems of the Body Circulatory Heart, blood Transport of materials between all Integumentary System vessels, blood cells of the body Respiratory Digestive Stomach, Conversion of food into particles system intestine, liver, that can be transported into the pancreas body; elimination of some wastes Nervous system Endocrine Thyroid gland, Coordination of body function adrenal gland through synthesis and release of regulatory molecules Immune Thymus, spleen, Defense against foreign Endocrine lymph nodes invaders Digestive system system Integumentary Skin Protection from external Circulatory environment system Musculoskeletal Skeletal mus- Support and movement cles, bone Nervous Brain, spinal Coordination of body function cord through electrical signals and Musculoskeletal release of regulatory molecules system Urinary Reproductive Ovaries and Perpetuation of the species system uterus, testes Reproductive Respiratory Lungs, airways Exchange of oxygen and carbon system dioxide between the internal and external environments This schematic figure indicates relationships between Urinary Kidneys, bladder Maintenance of water and systems of the human body. The interiors of some solutes in the internal hollow organs (shown in white) are part of the environment; waste removal external environment. or through a break in the skin. In addition, immune tissues are These process maps are also called flow charts, and they are frequently closely associated with the circulatory system. used in health care. You will be able to practice mapping with spe- Traditionally, physiology courses and books are organized by cial end-of-chapter questions throughout the book. organ system. Students study cardiovascular physiology and regu- lation of blood pressure in one chapter, and then study the kidneys and control of body fluid volume in a different chapter. In the functioning human, however, the cardiovascular and renal systems 1.2 Function and Mechanism communicate with each other, so that a change in one is likely to We define physiology as the normal functioning of the body, but cause a reaction in the other. For example, body fluid volume influ- physiologists are careful to distinguish between function and mecha- ences blood pressure, while changes in blood pressure alter kidney nism. The function of a physiological system or event is the “why” function because the kidneys regulate fluid volume. In this book, of the system or event: Why does a certain response help an animal you will find several integrative physiology chapters that highlight survive in a particular situation? In other words, what is the adaptive the coordination of function across multiple organ systems. significance of this event for this animal? Understanding how different organ systems work together is For example, humans are large, mobile, terrestrial animals, just as important as memorizing facts, but the complexity of inter- and our bodies maintain relatively constant water content despite actions can be challenging. One way physiologists simplify and living in a dry, highly variable external environment. Dehydration integrate information is by using visual representations of physi- is a constant threat to our well-being. What processes have evolved ological processes called maps. The Focus on Mapping feature in in our anatomy and physiology that allow us to survive in this hos- this chapter will help you learn how to make maps. The first type tile environment? One is the production of highly concentrated of map, shown in FIGURE 1.3a, is a schematic representation of urine by the kidney, which allows the body to conserve water. This structure or function. The second type of map, shown in Figure statement tells us why we produce concentrated urine but does not 1.3b, diagrams a physiological process as it proceeds through time. tell us how the kidney accomplishes that task.  1.3 Themes in Physiology 5 Thinking about a physiological event in terms of its adap- tive significance is the teleological approach to science. For RUNNING PROBLEM CHAPTER example, the teleological answer to the question of why red blood When Jimmy got back to his room, he sat down at his computer cells transport oxygen is “because cells need oxygen and red blood and went to the Internet. He typed diabetes in his search box— cells bring it to them.” This answer explains why red blood cells and came up with 267 million results. “That’s not going to work. transport oxygen—their function—but says nothing about how the What about insulin?” Nearly 48 million results. “How in the world 1 cells transport oxygen. am I going to get any answers?” He clicked on the first sponsored In contrast, most physiologists study physiological processes, ad that advertised “Information for type 2 diabetes.” That might be or mechanisms—the “how” of a system. The mechanistic good. His mother had type 2 diabetes. But it was for a pharma- approach to physiology examines process. The mechanistic ceutical company trying to sell him a drug. “Maybe my physiology answer to the question “How do red blood cells transport oxygen?” prof can help me with this search. I’ll ask tomorrow.” is “Oxygen binds to hemoglobin molecules in the red blood cells.” Q1: What search terms could Jimmy have used to get fewer This very concrete answer explains exactly how oxygen transport results? occurs but says nothing about the significance of oxygen transport 2 5 9 12 16 19 24 to the animal. Students often confuse these two approaches to thinking about physiology. Studies have shown that even medical students tend to answer questions with teleological explanations when the more At the systems level, we know about most of the mechan- appropriate response would be a mechanistic explanation.1 Often ics of body function from centuries of research. The unanswered they do so because instructors ask why a physiological event occurs questions today mostly involve integration and control of these when they really want to know how it occurs. Staying aware of the mechanisms, particularly at the cellular and molecular levels. Nev- two approaches will help prevent confusion. ertheless, explaining what happens in test tubes or isolated cells can Although function and mechanism seem to be two sides of the only partially answer questions about function. For this reason, same coin, it is possible to study mechanisms, particularly at the animal and human trials are essential steps in the process of apply- cellular and subcellular level, without understanding their func- ing basic research to treating or curing diseases. tion in the life of the organism. As biological knowledge becomes more complex, scientists sometimes become so involved in studying complex processes that they fail to step back and look at the sig- 1.3 Themes in Physiology nificance of those processes to cells, organ systems, or the animal. “Physiology is not a science or a profession but a point of view.”3 Conversely, it is possible to use teleological thinking incorrectly by Physiologists pride themselves on relating the mechanisms they saying, “Oh, in this situation the body needs to do this.” This may study to the functioning of the organism as a whole. For students, be a good solution, but if a mechanism for doing this doesn’t exist, being able to think about how multiple body systems integrate their the situation cannot be corrected. function is one of the more difficult aspects of learning physiology. Applying the concept of integrated functions and mechanisms To develop expertise in physiology, you must do more than simply is the underlying principle in translational research, an memorize facts and learn new terminology. Researchers have approach sometimes described as “bench to bedside.” Transla- found that the ability to solve problems requires a conceptual tional research uses the insights and results gained from basic bio- framework, or “big picture,” of the field. medical research on mechanisms to develop treatments and This book will help you build a conceptual framework for strategies for preventing human diseases. For example, researchers physiology by explicitly emphasizing the basic biological concepts, working on rats found that a chemical from the pancreas named or themes, that are common to all living organisms. These con- amylin reduced the rats’ food intake. These findings led directly to cepts form patterns that repeat over and over, and you will begin a translational research study in which human volunteers injected to recognize them when you encounter them in specific contexts. a synthetic form of amylin and recorded their subsequent food Pattern recognition is an important skill in healthcare professions, intake, but without intentionally modifying their lifestyle.2 The and it will also simplify learning physiology. drug suppressed food intake in humans, and was later approved by In the past few years, three different organizations issued the Food and Drug Administration for treatment of diabetes reports to encourage the teaching of biology using these fun- mellitus. damental concepts. Although the descriptions vary in the three reports, five major themes emerge: 1. structure and function across all levels of organization 1 2. energy transfer, storage, and use D. R. Richardson. A survey of students’ notions of body function as teleo- logic or mechanistic. Advan Physiol Educ 258: 8–10, Jun 1990. Access free at 3. information flow, storage, and use within single organisms and http://advan.physiology.org. within a species of organism 2 S. R. Smith et al. Pramlintide treatment reduces 24-h caloric intake and 3 meal sizes and improves control of eating in obese subjects: a 6-wk transla- R. W. Gerard. Mirror to Physiology: A Self-Survey of Physiological Science. tional research study. Am J Physiol Endocrinol Metab 293: E620–E627, 2007. Washington, DC: American Physiology Society, 1958. FIG. 1.3 Focus on... Mapping Why use maps to study physiology? The answer is Mapping is not just a study technique. Scientists map out simple: maps will help you organize information you are learning the steps in their experiments. Healthcare professionals in a way that makes sense to you and they will make that informa- create maps to guide them while diagnosing and treating tion easier to recall on a test. Creating a map requires higher-level patients. You can use mapping for almost every subject thinking about the relationships among items on the map. you study. What is a map? Mapping is a nonlinear way of organizing material. A map can take a variety of forms but usually consists of terms (words or short phrases) linked by arrows to indicate associations. You can label the connecting arrows to describe the type of linkage between the terms results in Studying Better grades (structure/function, cause/effect) or with explanatory phrases. Here are two typical maps used in physiology. Structure/function maps focus on the relationships Process maps or flow charts between anatomical structures and their functions. follow normal homeostatic control pathways or the body’s responses to abnormal (pathophysiological) SANDWICHES events as they unfold over time. Person working outside on a hot, dry day Outside components Fillings Loses body water by evaporation Dressings Breads Tortillas Wraps Vegetables Cheeses Meats and sauces Body fluids become more concentrated Practice making maps. Many maps appear in this textbook, and they can serve as the starting point for your own maps. However, the real benefit of Internal receptors mapping comes from preparing maps yourself rather than memorizing someone sense change in else’s maps. Your instructor can help you get started. internal concentration The next page walks you through the process of creating a structure-function map. Thirst pathways stimulated HINTS To help you get started, the end-of-chapter questions in this book include at Person seeks out least one list of terms to map for each chapter. and drinks water Write your terms on individual slips of paper or small sticky notes so that you can rearrange the map more easily. Water added Some terms may seem to belong to more than one group. Do not duplicate to body fluids the item but make a note of it, as this term will probably have several arrows decreases their pointing to it or leading away from it. concentration If arrows crisscross, try rearranging the terms on the map. Use color to indicate similar items. Add pictures and graphs that are associated with specific terms in your map. Electronic mapping. Some people do not like the messiness of hand-drawn maps. There are several electronic ways of making maps, including PowerPoint or free and commercial software programs. Free concept mapping software is available from IHMC CmapTools at http://cmap.ihmc.us. Or search for the term free concept map to find other resources on the Web. A popular commercial program for mapping is Inspiration (www.inspiration.com).  STEP 1: Write out the terms to map. Cell membrane Nucleolus If you need help generating ideas for topics to Ribosomes Endoplasmic map, the end-of-chapter mapping questions in reticulum each chapter have lists of terms to help you get Nucleus The Cell started. Golgi Mitochondria Cytoplasm STEP 2: Organize the terms. The Cell Put your key term on the top. Then put your terms in groups that are similar. Cytoplasm Mitochondria Endoplasmic Nucleus Nucleolus reticulum Cell membrane Ribosomes Golgi These are the 3 main These are all found inside the cell. Parts in parts of a cell. the left column do not have membranes. Parts in the right column have membranes. STEP 3: Link the terms. The Cell consists of Cell membrane Cytoplasm Nucleus contains contains Protein fibers Membranous organelles Inclusions Nucleolus You may think of additional terms to add as you work. Cytoskeleton Golgi Endoplasmic reticulum Mitochondria Ribosomes can be found in Smooth ER Rough ER Labeling arrows Makes proteins such as can help explain linkages. Once you have created your map, sit back and think Science is a collaborative field. A useful way to study with a about it. Are all the items in the right place? You may map is to trade maps with a classmate and try to under- want to move them around once you see the big stand each other’s maps. Your maps will almost certainly picture. Add new concepts or correct wrong links. not look the same! It’s OK if they are different. Remember Review by recalling the main concept and then moving that your map reflects the way you think about the subject, to the more specific details. Ask yourself questions like, which may be different from the way someone else thinks What is the cause and what is the effect? What parts about it. Did one of you put in something the other forgot? are involved? What are the main characteristics? Did one of you have an incorrect link between two items? 7 8 CHAPTER 1 Introduction to Physiology 4. homeostasis and the control systems that maintain it converts normal hemoglobin to the form associated with sickle 5. evolution cell disease. Many physiologically significant molecular interactions that In addition, all three reports emphasize the importance of under- you will learn about in this book involve the class of biological mol- standing how science is done and of the quantitative nature of ecules called proteins. Functional groups of proteins include enzymes biology. TABLE 1.1 lists the core concepts in biology from the three that speed up chemical reactions, signal molecules and the receptor pro- reports. teins that bind signal molecules, and specialized proteins that func- In this book, we focus on the four themes most related to tion as biological pumps, filters, motors, or transporters. Chapter 2 physiology: structure-function relationships, biological energy use, describes molecular interactions involving proteins in more detail. information flow within an organism, and homeostasis and the Interactions between proteins, water, and other molecules control systems that maintain it. The first six chapters introduce influence cell structure and the mechanical properties of cells and the fundamentals of these themes, which you may already be tissues. Mechanical properties you will encounter in your study of familiar with from earlier biology or chemistry classes. The themes physiology include compliance (ability to stretch), elastance (stiffness or and their associated concepts, with variations, then re-appear over the ability to return to the unstretched state), strength, flexibility, and over in subsequent chapters of this book. Look for them in the and fluidity (viscosity). summary material at the end of the chapters and in the end-of- chapter questions as well. Compartmentation Compartmentation is the division of space into separate compartments. Compartments allow a cell, a tissue, Theme 1: Structure and Function or an organ to specialize and isolate functions. Each level of orga- Are Closely Related nization is associated with different types of compartments. At the macroscopic level, the tissues and organs of the body form discrete The integration of structure and function extends across all levels functional compartments, such as body cavities or the insides of of organization, from the molecular level to the intact body. This hollow organs. At the microscopic level, cell membranes separate theme subdivides into two major ideas: molecular interactions and cells from the fluid surrounding them and also create tiny compart- compartmentation. ments within the cell called organelles. Compartmentation is the Molecular Interactions The ability of individual molecules to theme of Chapter 3. bind to or react with other molecules is essential for biologi- cal function. A molecule’s function depends on its structure Theme 2: Living Organisms Need Energy and shape, and even a small change to the structure or shape may have significant effects on the function. The classic exam- Growth, reproduction, movement, homeostasis—these and all ple of this phenomenon is the change in one amino acid of other processes that take place in an organism require the continu- the hemoglobin protein. (Hemoglobin is the oxygen-carrying ous input of energy. Where does this energy come from, and how pigment of the blood.) This one small change in the protein is it stored? We will answer those questions and describe some of TABLE 1.1 Biology Concepts Scientific Foundations for Future The 2010 Advanced Placement Biology Physicians (HHMI and AAMC)1 Vision and Change (NSF and AAAS)2 Curriculum (College Board)3 Structure/function from molecules to Structure and function (anatomy and Relationship of structure to function organisms physiology) Physical principles applied to living systems Pathways and transformations of energy Energy transfer Chemical principles applied to living and matter systems Biomolecules and their functions Information flow, exchange, and storage Continuity and change Organisms sense and control their inter- Systems Regulation (“a state of dynamic balance”) nal environment and respond to external change Evolution as an organizing principle Evolution Evolution 1 Scientific Foundations for Future Physicians. Howard Hughes Medical Institute (HHMI) and the Association of American Medical Colleges (AAMC), 2009. www.aamc.org/ scientificfoundations 2 Vision and Change: A Call to Action. National Science Foundation (NSF) and American Association for the Advancement of Science (AAAS). 2011. http://visionandchange.org/finalreport. The report mentioned the integration of science and society as well. 3 College Board AP Biology Course Description, The College Board, 2010. http://apcentral.collegeboard.com/apc/public/repository/ap-biology-course-description.pdf. The AP report also included “Interdependence in Nature” and “Science, Technology and Society” as two of their eight themes.  1.4 Homeostasis 9 the ways that energy in the body is used for building and breaking down molecules in Chapter 4. In subsequent chapters, you will RUNNING PROBLEM CHAPTER learn how energy is used to transport molecules across cell mem- After his second physiology class, Jimmy introduced himself to branes and to create movement. his professor and explained his problem. The professor’s first suggestion was simple: try to narrow the search. “One of the best Theme 3: Information Flow Coordinates ways to search is to combine terms using the connector AND. 1 If you remember set theory from your math class, the connec- Body Functions tor AND will give you the intersection of the sets. In other words, Information flow in living systems ranges from the transfer of infor- you’ll get only the results that occur in both sets.” mation stored in DNA from generation to generation (genetics) to Seemed simple enough. Jimmy went back to the Internet and the flow of information within the body of a single organism. At tried diabetes and insulin. That search still had 46 million results the organismal level, information flow includes translation of DNA’s but on the first page was a link to the American Diabetes Asso- genetic code into proteins responsible for cell structure and function. ciation, diabetes.org. Now he was getting somewhere. In the human body, information flow between cells coordinates Q2: What kinds of websites should Jimmy be looking for in his function. Cell-to-cell communication uses chemical signals, electrical results list, and how can he recognize them? signals, or a combination of both. Information may go from one cell to its neighbors (local communication) or from one part of 2 5 9 12 16 19 24 the body to another (long-distance communication). Chapter 6 discusses chemical communication in the body. When chemical signals reach their target cells, they must get In 1929, an American physiologist named Walter B. Cannon their information into the cell. Some molecules are able to pass wrote a review for the American Physiological Society.5 Using through the barrier of the cell membrane, but signal molecules observations made by numerous physiologists and physicians dur- that cannot enter the cell must pass their message across the cell ing the nineteenth and early twentieth centuries, Cannon proposed membrane. How molecules cross biological membranes is the topic a list of variables that are under homeostatic control. We now of Chapter 5. know that his list was both accurate and complete. Cannon divided his variables into what he described as environmental factors that Theme 4: Homeostasis Maintains Internal Stability affect cells (osmolarity, temperature, and pH) and “materials for cell needs” (nutrients, water, sodium, calcium, other inorganic ions, Organisms that survive in challenging habitats cope with external oxygen, as well as “internal secretions having general and continu- variability by keeping their internal environment relatively sta- ous effects”). Cannon’s “internal secretions” are the hormones and ble, an ability known as homeostasis {homeo-, similar + @stasis, other chemicals that our cells use to communicate with one condition}. Homeostasis and regulation of the internal environ- another. ment are key principles of physiology and underlying themes in In his essay, Cannon created the word homeostasis to describe each chapter of this book. The next section looks in detail at the regulation of the body’s internal environment. He explained the key elements that he selected the prefix homeo- (meaning like or similar) rather Play BioFlix Animation of this important than the prefix homo- (meaning same) because the internal environ- @Mastering Anatomy & Physiology theme. ment is maintained within a range of values rather than at an exact fixed value. He also pointed out that the suffix -stasis in this instance means a condition, not a state that is static and unchang- 1.4 Homeostasis ing. Cannon’s homeostasis, therefore, is a state of maintaining “a The concept of a relatively stable internal environment is attrib- similar condition,” similar to Claude Bernard’s relatively constant uted to the French physician Claude Bernard in the mid-1800s. internal environment. During his studies of experimental medicine, Bernard noted the Some physiologists contend that a literal interpretation of stability of various physiological functions, such as body tempera- stasis {a state of standing} in the word homeostasis implies a static, ture, heart rate, and blood pressure. As the chair of physiology at unchanging state. They argue that we should use the word homeody- the University of Paris, he wrote “La fixité du milieu intérieur est namics instead, to reflect the small changes constantly taking place la condition de la vie libre, indépendante.” (The constancy of the in our internal environment {dynamikos, force or power}. Whether internal environment is the condition for a free and independent the process is called homeostasis or homeodynamics, the important life.)4 This idea was applied to many of the experimental observa- concept to remember is that the body monitors its internal state tions of his day, and it became the subject of discussion among and takes action to correct disruptions that threaten its normal physiologists and physicians. function. 4 C. Bernard. Leçons sur les phénomènes de la vie communs aux animaux et aux végé- 5 taux (Vol. 1, p. 113), Paris: J.-B. Baillière, 1885. (http://obvil.paris-sorbonne.fr/ W. B. Cannon. Organization for physiological homeostasis. Physiol Rev 9: corpus/critique/bernard_lecons-phenomenes-vie-I/body-2) 399–443, 1929. 10 CHAPTER 1 Introduction to Physiology If the body fails to maintain homeostasis of the critical vari- the chapters of this book. The influence of this one disorder on ables listed by Walter Cannon, then normal function is disrupted many systems of the body makes it an excellent example of the and a disease state, or pathological condition {pathos, suffering}, integrative nature of physiology. may result. Diseases fall into two general groups according to their origin: those in which the problem arises from internal failure of What Is the Body’s Internal Environment? some normal physiological process, and those that originate from some outside source. Internal causes of disease include the abnor- Claude Bernard wrote of the “constancy of the internal environ- mal growth of cells, which may cause cancer or benign tumors; the ment,” but why is constancy so essential? As it turns out, most production of antibodies by the body against its own tissues (auto- cells in our bodies are not very tolerant of changes in their sur- immune diseases); and the premature death of cells or the failure roundings. In this way they are similar to early organisms that of cell processes. Inherited disorders are also considered to have lived in tropical seas, a stable environment where salinity, oxygen internal causes. External causes of disease include toxic chemicals, content, and pH vary little and where light and temperature cycle physical trauma, and foreign invaders such as viruses and bacteria. in predictable ways. The internal composition of these ancient In both internally and externally caused diseases, when creatures was almost identical to that of seawater. If environmen- homeostasis is disturbed, the body attempts to compensate tal conditions changed, conditions inside the primitive organisms (FIG. 1.4). If the compensation is successful, homeostasis is restored. changed as well. Even today, marine invertebrates cannot tolerate If compensation fails, illness or disease may result. The study of significant changes in salinity and pH, as you know if you have ever body functions in a disease state is known as pathophysiology. maintained a saltwater aquarium. You will encounter many examples of pathophysiology as we study In both ancient and modern times, many marine organisms the various systems of the body. relied on the constancy of their external environment to keep their One very common pathological condition in the United internal environment in balance. In contrast, as organisms evolved States is diabetes mellitus, a metabolic disorder characterized and migrated from the ancient seas into estuaries, then into fresh- by abnormally high blood glucose concentrations. Although we water environments and onto the land, they encountered highly speak of diabetes as if it were a single disease, it is actually a whole variable external environments. Rains dilute the salty water of family of diseases with various causes and manifestations. You will estuaries, and organisms that live there must cope with the influx learn more about diabetes in the focus boxes scattered throughout of water into their body fluids. Terrestrial organisms, including humans, face the challenge of dehydration—constantly losing internal water to the dry air around them. Keeping the internal FIG. 1.4 Homeostasis environment stable means balancing water loss with appropriate water intake. Organism in But what exactly is the internal environment of the body? homeostasis For multicellular animals, it is the watery internal environment that surrounds the cells, a “sea within” the body called the extra- External change cellular fluid (ECF) {extra-, outside of} (FIG. 1.5). Extracellular fluid serves as the transition between an organism’s external envi- Internal ronment and the intracellular fluid (ICF) inside cells {intra-, change within}. Because extracellular fluid is a buffer zone between cells and the outside world, elaborate physiological processes have evolved to keep its composition relatively stable. Internal change When the extracellular fluid composition varies outside its results in loss of homeostasis normal range of values, compensatory mechanisms activate and try to return the fluid to the normal state. For example, when you drink a large volume of water, the dilution of your extracellu- lar fluid triggers a mechanism that causes your kidneys to remove Organism attempts excess water and protect your cells from swelling. Most cells of mul- to compensate ticellular animals do not tolerate much change. They depend on the constancy of extracellular fluid to maintain normal function. Homeostasis Depends on Mass Balance Compensation fails Compensation succeeds In the 1960s, a group of conspiracy theorists obtained a lock of Napoleon Bonaparte’s hair and sent it for chemical analysis in an attempt to show that he died from arsenic poisoning. Today, Illness or disease Wellness a group of students sharing a pizza joke about the garlic odor on their breath. At first glance these two scenarios appear to have little  1.4 Homeostasis 11 FIG. 1.5 The body’s internal and external environments CHAPTER (a) Extracellular fluid is a buffer between cells and the (b) A box diagram represents the ECF, ICF, and external outside world. environment as three separate compartments. Cells contain 1 intracellular fluid (ICF). External Extracellular Intracellular External environment fluid (ECF) fluid (ICF) Cells are surrounded Cells ECF by the extracellular environment fluid (ECF). The cell membrane separates cells from FIGURE QUESTION the ECF. Put a * on the cell membrane of the box diagram. in common, but in fact Napoleon’s hair and “garlic breath” both external environment plus metabolic water production (input). The demonstrate how the human body works to maintain the balance concentrations of other substances, such as oxygen and carbon that we call homeostasis. dioxide, salts, and hydrogen ions (pH), are also maintained through The human body is an open system that exchanges heat and mass balance. The following equation summarizes the law of mass materials with the outside environment. To maintain homeosta- balance: sis, the body must maintain mass balance. The law of mass balance says that if the amount of a substance in the body Total amount of = intake + production - is to remain constant, any gain must be offset by an equal loss substance x in the body excretion - metabolism (FIG. 1.6a). The amount of a substance in the body is also called the body’s load, as in “sodium load.” Most substances enter the body from the outside environment, For example, water loss to the external environment (output) but some (such as carbon dioxide) are produced internally through in sweat and urine must be balanced by water intake from the metabolism (Fig. 1.6b). In general, water and nutrients enter the FIG. 1.6 Mass balance (a) Mass balance in an open system (b) Mass balance in the body requires input equal to output. Input Input Output Intake through Excretion by intestine, lungs, kidneys, liver, skin BODY BODY lungs, skin To maintain constant level, output must equal input. LOAD LOAD Metabolic Metabolism production to a new substance Law of Mass Balance Output Intake or Excretion or Mass balance = Existing + metabolic – metabolic body load production removal 12 CHAPTER 1 Introduction to Physiology body as food and drink absorbed through the intestine. Oxygen and other gases and volatile molecules enter through the lungs. A RUNNING PROBLEM few lipid-soluble chemicals make their way to the internal environ- Jimmy called his mother with the news that he had found some ment by penetrating the barrier of the skin. good information on the American Diabetes Association website To maintain mass balance, the body has two options for out- (www.diabetes.org). According to that organization, someone put. The simplest option is simply to excrete the material. Excre- with type 2 diabetes might begin to require insulin as the disease tion is defined as the elimination of material from the body, progresses. But Jimmy’s mother was still not convinced that she usually through the urine, feces, lungs, or skin. For example, car- needed to start insulin injections. bon dioxide (CO2) produced during metabolism is excreted by the “My friend Ahn read that some doctors say that if you eat a lungs. Many foreign substances that enter the body, such as drugs high-fiber diet, you won’t need any other treatment for diabetes.” or artificial food additives, are excreted by the liver and kidneys. “Mom, that doesn’t sound right to me.” (Any foreign substance in the body is called a xenobiotic, from the “But it must be,” Jimmy’s mother replied. “It says so in The Greek word xenos, a stranger.) Doctors’ Medical Library.” A second output option for maintaining mass balance is to Q3: Go to The Doctors’ Medical Library at www.medical-library. convert the substance to a different substance through metabo- net and search for the article called “Fiber” by typing the word lism. Nutrients that enter the body become the starting point for into the Search box or by using the alphabetical listing of Library metabolic pathways that convert the original nutrient to a different Articles. What does Dr. Kennedy, the author of the article, say molecule. However, converting the original nutrient to something about high-fiber diet and diabetes? different then creates a new mass balance disturbance by adding Q4: Should Jimmy’s mother believe what it says on this web- more of the new substance, or metabolite, to the body. (Metabolite is site? How can Jimmy find out more about who created the site the general term for any product created in a metabolic pathway.) and what their credentials are? Scientists use mass flow to follow material throughout the body. Mass flow describes the rate of transport of a substance x 2 5 9 12 16 19 24 as it moves through body fluids or into and out of the body. The equation for mass flow is reason, clearance is only an indirect measure of how substance Mass flow = concentration of x * volume flow x is handled by the body. For example, urea is a normal metabo- (amount x/min) = (amount x/vol) * (vol/min) lite produced from protein metabolism. A typical value for urea clearance is 70 mL plasma cleared of urea per minute, written as where volume flow describes the flow of blood, air, urine, and the 70 mL plasma/min. Knowing the rate at which urea disappears like. does not tell us anything about where urea is going. (It is being For example, suppose a person is given an intravenous (IV) excreted by the kidneys.) infusion of glucose solution that has a concentration of 50 grams The kidney and the liver are the two primary organs that of glucose per liter of solution. If the infusion is given at a rate of clear solutes from the body. Hepatocytes {hepaticus, pertaining to the 2 milliliters per minute, the mass flow of glucose into the body is: liver + cyte, cell}, or liver cells, metabolize many different types of molecules, especially xenobiotics such as drugs. The resulting 50 g glucose * 2 mL solution/min = 0.1 g glucose/min metabolites may be secreted into the intestine for excretion in the 1000 mL solution feces or released into the blood for removal by the kidneys. Phar- The rate of glucose input into the body is 0.1 g glucose/min. maceutical companies testing chemicals for their potential use as Mass flow applies not only to the entry, production, and therapeutic drugs must know the clearance of the chemical before removal of substances but also to the movement of substances they can develop the proper dosing schedule. from one compartment in the body to another. When materials Clearance also takes place in tissues other than the liver and enter the body, they first become part of the extracellular fluid. kidneys. Saliva, sweat, breast milk, and hair all contain substances Where a substance goes after that depends on whether or not it can that have been cleared from the body. Salivary secretion of the cross the barrier of the cell membrane and enter the cells. hormone cortisol provides a simple noninvasive source of hormone for monitoring chronic stress. An everyday example of clearance is “garlic breath,” which Excretion Clears Substances from the Body occurs when volatile lipid-soluble garlic compounds in the blood It is relatively easy to monitor how much of a substance enters pass into the airways and are exhaled. The lungs also clear ethanol the body from the outside world, but it is more difficult to track in the blood: exhaled alcohol is the basis of the “breathalyzer” molecules inside the body to monitor their excretion or metab- test used by law enforcement agencies. Drugs and alcohol secreted olism. Instead of directly measuring the substance, we can fol- into breast milk are potentially dangerous because a breastfeeding low the rate at which the substance disappears from the blood, infant will ingest these substances. a concept called clearance. Clearance is usually expressed as a The 1960s analysis of Napoleon Bonaparte’s hair tested it volume of blood cleared of substance x per unit of time. For this for arsenic because hair follicles help clear some compounds from  1.5 Control Systems and Homeostasis 13 the body. The test results showed significant concentrations of the Steady state is not the same as equilibrium {aequus, poison in his hair, but the question remains whether Napoleon was equal + libra, balance}, however. Equilibrium implies that the CHAPTER murdered, poisoned accidentally, or died from stomach cancer. composition of the body compartments is identical. If we examine the composition of the ECF and ICF, we find that the concentra- tions of many substances are different in the two compartments (FIG. 1.7). For example, sodium (Na+) and chloride (Cl-) are far 1 Concept Check more concentrated in the ECF than in the ICF, while potassium 1. If a person eats 12 milligrams (mg) of salt in a day and excretes (K+) is most concentrated in the ICF. Because of these concentra- 11 mg of it in the urine, what happened to the remaining 1 mg? tion differences, the two fluid compartments are not at equilib- 2. Glucose is metabolized to CO2 and water. Explain the effect of rium. Instead the ECF and ICF exist in a state of relatively stable glucose metabolism on mass balance in the body. disequilibrium {dis- is a negative prefix indicating the opposite of the base noun}. For living organisms, the goal of homeostasis is to maintain the dynamic steady states of the body’s compartments, not to make the compartments the same. Homeostasis Does Not Mean Equilibrium When physiologists talk about homeostasis, they are speaking of the stability of the body’s internal environment—in other words, the 1.5 Control Systems and Homeostasis stability of the extracellular fluid compartment (ECF). One reason To maintain homeostasis, the human body monitors certain key for focusing on extracellular fluid homeostasis is that it is relatively functions, such as blood pressure and blood glucose concentration, easy to monitor by taking a blood sample. When you centrifuge that must stay within a particular operating range if the body is to blood, it separates into two parts: plasma, the fluid component, remain healthy. These important regulated variables are kept plus the heavier blood cells. Plasma is part of the extracellular within their acceptable (normal) range by physiological control fluid compartment, and its composition can be easily analyzed. It mechanisms that kick in if the variable ever strays too far from is much more difficult to follow what is taking place in the intracel- its setpoint, or optimum value. There are two basic patterns lular fluid compartment (ICF), although cells do maintain cellular of control mechanisms: local control and long-distance reflex homeostasis. control. In a state of homeostasis, the composition of both body com- In their simplest form, all control systems have three partments is relatively stable. This condition is a dynamic steady components (FIG. 1.8): (1) an input signal; (2) a controller, or state. The modifier dynamic indicates that materials are con- integrating center {integrare, to restore}, that integrates in- stantly moving back and forth between the two compartments. In coming information and initiates an appropriate response; and a steady state, there is no net movement of materials between the (3) an output signal that creates a response. Long-distance reflex compartments. control systems are more complex than this simple model, however, as they may include input from multiple sources and have output that acts on multiple targets. FIG. 1.7 Steady-state disequilibrium Local Control Is Restricted to a Tissue The body compartments are in a dynamic steady state but are not at equilibrium. Ion concentrations are very different in the The simplest form of control is local control, which is re- extracellular fluid compartment (ECF) and the intracellular fluid stricted to the tissue or cell involved (FIG. 1.9). In local control, compartment (ICF). a relatively isolated change occurs in a tissue. A nearby cell or group of cells senses the change in their immediate vicinity ECF ICF and responds, usually by releasing a chemical. The response is 140 restricted to the region where the change took place—hence the 120 term local control. One example of local control can be observed when oxygen Concentration (mmol/L) 100 concentration in a tissue decreases. Cells lining the small blood 80 60 FIG. 1.8 A simple control system 40 20 Input Integrating Output Response signal center signal Na+ Cl- K+ Na+ Cl- K+ 14 CHAPTER 1 Introduction to Physiology FIG. 1.9 A comparison of local control and reflex control expanded into the following sequence of seven steps to form a pattern that is found with slight variations in all (a) Local control: In (b) Reflex control: In reflex control, cells at a reflex pathways: local control, cells in distant site control the response. the vicinity of the Stimulus S sensor S input signal S change initiate the integrating center S response. Brain evaluates the output signal S target S response change and initiates a response. The input side of the response loop starts with a Brain stimulus—the change that occurs when the regulated vari- able moves out of its desirable range. A specialized sen- sor monitors the variable. If the sensor is activated by Systemic change in blood the stimulus, it sends an input signal to the integrating pressure sensed center. The integrating center evaluates the information here. coming from the sensor and initiates an output signal. The output signal directs a target to carry out a response. LOCAL CHANGE If successful, the response brings the regulated variable back into the desired range. Blood vessels In mammals, integrating centers are usually part of the nervous system or endocrine system. Output signals REFLEX LOCAL RESPONSE may be chemical signals, electrical signals, or a combina- RESPONSE tion of both. The targets activated by output signals can is initiated by cells at a distant site. be any cell of the body. Response Loops Begin with a Stimulus KEY To illustrate response loops, let’s apply the concept to a Stimulus simple nonbiological example. Think about an aquarium Integrating center whose heater is programmed to maintain the water tem- perature (the regulated variable) at 30 °C (Fig. 1.10). The Response room temperature is 25 °C. The desired water tempera- ture (30 °C) is the setpoint for the regulated variable. Assume that initially the aquarium water is at room vessels that bring blood to the area sense the lower oxygen con- temperature, 25 °C. When you turn the control box on, you set centration and respond by secreting a chemical signal. The signal the response loop in motion. The thermometer (sensor) registers molecule diffuses to nearby muscles in the blood vessel wall, bring- a temperature of 25 °C. It sends this information through a wire ing them a message to relax. Relaxation of the muscles widens (input signal) to the control box (integrating center). The control (dilates) the blood vessel, which increases blood flow into the tissue box is programmed to evaluate the incoming temperature signal, and brings more oxygen to the area. compare it with the setpoint for the system (30 °C), and “decide” whether a response is needed to bring the water temperature up to the setpoint. The control box sends a signal through another Reflex Control Uses Long-Distance Signaling wire (output signal) to the heater (the target), which turns on and Changes that are widespread throughout the body, or systemic in starts heating the water (response). This sequence—from stimulus nature, require more complex control systems to maintain homeo- to response—is the response loop. stasis. For example, maintaining blood pressure to drive blood flow This aquarium example involves a variable (temperature) con- throughout the body is a systemic issue rather than a local one. trolled by a single control system (the heater). We can also describe Because blood pressure is body-wide, maintaining it requires long- a system that is under dual control. For example, think of a house distance communication and coordination. We will use the term that has both heating and air conditioning. The owner would like reflex control to mean any long-distance pathway that uses the ner- the house to remain at 70 °F (about 21 °C). On chilly autumn vous system, endocrine system, or both. mornings, when the temperature in the house falls, the heater turns A physiological reflex can be broken down into two parts: a on to warm the house. Then, as the day warms up, the heater is no response loop and a feedback loop (FIG. 1.10). As with the simple longer needed and turns off. When the sun heats the house above control system just described, a response loop has three pri- the setpoint, the air conditioner turns on to cool the house back to mary components: an input signal, an integrating center to integrate 70 °F. The heater and air conditioner have antagonistic control over the signal, and an output signal. These three components can be house temperature because they work in opposition to each other.  1.5 Control Systems and Homeostasis 15 FIG. 1.10 The steps in a reflex pathway CHAPTER Reflex Steps In the aquarium example shown, 1 Water temperature is the control box is set to maintain below the setpoint. STIMULUS a water temperature of 30 ± 1 °C. 1 Water temperature Feedback loop 2 Thermometer senses 1 is 25 °C. SENSOR temperature decrease. 3 Signal passes from sensor to control INPUT box through the wire. SIGNAL 2 Thermometer 4 Control box is Feedback programmed loop to respond to INTEGRATING Water temperature below CENTER 7 temperature 29 degrees. 3 Wire increases. 5 Signal passes through OUTPUT wire to heater. SIGNAL 4 Control box 5 6 6 Heater turns on. TARGET Wire to heater Heater 7 Water temperature increases. RESPONSE Similar situations occur in the human body when two branches the water. The sensor continuously monitors the temperature and of the nervous system or two different hormones have opposing sends that information to the control box. When the temperature effects on a single target. warms up to the maximum acceptable value, the control box shuts off the heater, thus ending the reflex response. Concept Check Negative Feedback Loops Are Homeostatic 3. What is the drawback of having only a single control system (a For most reflexes, feedback loops are homeostatic—that is, designed heater) for maintaining aquarium water temperature in some desired range? to keep the system at or near a setpoint so that the regulated variable is relatively stable. How well an integrating center succeeds in main- taining stability depends on the sensitivity of the system. In the case of our aquarium, the control box is programmed to have a sensitivity Feedback Loops Modulate the Response Loop of { 1 °C. If the water temperature drops from 30 °C to 29.5 °C, The response loop is only the first part of a reflex. For example, in