Human Physiology (8th Edition) PDF

Contents in Brief UNIT 1 1 2 3 4 5 6 Introduction to Physiology 1 Molecular Interactions 28 Compartmentation: Cells and Tissues 58 Energy and Cellular Metabolism 92 Membrane Dynamics 121 Communication, Integration, and Homeostasis 164 UNIT 2 7 8 9 10 11 12 13 Integration of Function Cardiovascular P...

Contents in Brief UNIT 1 1 2 3 4 5 6 Introduction to Physiology 1 Molecular Interactions 28 Compartmentation: Cells and Tissues 58 Energy and Cellular Metabolism 92 Membrane Dynamics 121 Communication, Integration, and Homeostasis 164 UNIT 2 7 8 9 10 11 12 13 Integration of Function Cardiovascular Physiology 432 Blood Flow and the Control of Blood Pressure 476 Blood 510 Mechanics of Breathing 532 Gas Exchange and Transport 562 The Kidneys 587 Integrative Physiology II: Fluid and Electrolyte Balance 618 UNIT 4 21 22 23 24 25 26 Homeostasis and Control Introduction to the Endocrine System 194 Neurons: Cellular and Network Properties 223 The Central Nervous System 271 Sensory Physiology 307 Efferent Division: Autonomic and Somatic Motor Control 355 Muscles 374 Integrative Physiology I: Control of Body Movement 414 UNIT 3 14 15 16 17 18 19 20 Basic Cell Processes: Integration and Coordination Metabolism, Growth, and Aging The Digestive System 654 Metabolism and Energy Balance 692 Endocrine Control of Growth and Metabolism 728 The Immune System 754 Integrative Physiology III: Exercise 786 Reproduction and Development 800 Strategies for Success Top Ten Ways to Succeed in Classes that Use Active Learning By Marilla Svinicki, Ph.D., former Director of the University of Texas Center for Teaching Effectiveness Word Roots for Physiology Simplify physiology and medicine by learning Latin and Greek word roots. The list below has some of the most common ones. Using the list, can you figure out what hyperkalemia means?* a- or an- without, absence hypo- beneath or deficient anti- against inter- between -ase signifies an enzyme intra- within auto self -itis inflammation of bi- two kali- potassium brady- slow leuko- white cardio- heart lipo- fat cephalo- head lumen inside of a hollow tube cerebro- brain -lysis split apart or rupture contra- against macro- large -crine a secretion micro- small crypt- hidden mono- one cutan- skin multi- many 5. Engage in active listening to what’s happening in class. -cyte or cyto- cell myo- muscle de- without, lacking oligo- little, few 6. Trust the instructor’s experience in designing class activities and participate willingly if not enthusiastically. di- two para- near, close dys- difficult, faulty -elle small patho-, -pathy related to disease -emia in the blood peri- around endo- inside or within poly- many epi- over post- after erythro- red pre- before exo- outside pro- before extra- outside pseudo- false gastro- stomach re- again -gen, -genie produce retro- backward or behind gluco-, glyco- sugar or sweet semi- half hemi- half sub- below hemo- blood super- above, beyond hepato- liver supra- above, on top of homo- same tachy- rapid hydro- water trans- across, through 1. Make the switch from an authority-based conception of learning to a self-regulated conception of learning. Recognize and accept your own responsibility for learning. 2. Be willing to take risks and go beyond what is presented in class or the text. 3. Be able to tolerate ambiguity and frustration in the interest of understanding. 4. See errors as opportunities to learn rather than failures. Be willing to make mistakes in class or in study groups so that you can learn from them. 7. Be willing to express an opinion or hazard a guess. 8. Accept feedback in the spirit of learning rather than as a reflection of you as a person. 9. Prepare for class physically, mentally, and materially (do the reading, work the problems, etc.). 10. Provide support for your classmate’s attempts to learn. The best way to learn something well is to teach it to someone who doesn’t understand. Dr. Dee’s Eleventh Rule: DON’T PANIC! Pushing yourself beyond the comfort zone is scary, but you have to do it in order to improve. hyper- above or excess * Hyper = excess, kali = potassium, -emia = in the blood, or elevated blood potassium Owner’s Manual Welcome to Human Physiology! As you begin your study of the human body, one of your main tasks will be to construct for yourself a global view of the body, its systems, and the many processes that keep the systems working. This “big picture” is what physiologists call the integration of systems, and it is a key theme in this book. To integrate information, however, you must do more than simply memorize it. You need to truly understand it and be able to use it to solve problems that you have never encountered before. If you are headed for a career in the health professions, you will do this in the clinics. If you plan a career in biology, you will solve problems in the laboratory, field, or classroom. Analyzing, synthesizing, and evaluating information are skills you need to develop while you are in school, and I hope that the features of this book will help you with this goal. One of my aims is to provide you not only with information about how the human body functions but also with tips for studying and problem solving. Many of these study aids have been developed with the input of my students, so I think you may find them particularly helpful. On the following pages, I have put together a brief tour of the special features of the book, especially those that you may not have encountered previously in textbooks. Please take a few minutes to read about them so that you can make optimum use of the book as you study. Each chapter begins with a list of Learning Outcomes to guide you as you read the chapter. Within the chapters look for the Running Problem, Phys in Action, and Try It! activities. Phys in Action are online video clips that I created with the assistance of some of my students. Look for the references to Play Phys in Action @Mastering Anatomy & Physiology Mastering A&P in the figures with associated Phys in Action clips, and watch Kevin and Michael as they demonstrate physiology in action. Pattern recognition is important for all healthcare professionals, so you can begin to develop this skill by learning the key concepts of physiology that repeat over and over as you study different organ systems. Chapter 1 includes two special Focus On features: one on concept mapping, a study strategy that is also used for decision-making in the clinics, and one on constructing and interpreting graphs. The Running Problem in Chapter 1 introduces you to effective ways to find information on the Internet. Be sure to look for the Essentials and Review figures throughout the book. These figures distill the basics about a topic onto one or two pages, much as the Anatomy Summaries do. My students tell me they find them particularly useful for review when there isn’t time to go back and read all the text. We have also retained the four approaches to learning physiology that proved so popular since this book was first published in 1998. 1. Cellular and Molecular Physiology Most physiological research today is being done at the cellular and molecular level, and there have been many exciting developments in molecular medicine and physiology in the 10 years since the first edition. For example, now scientists are paying more attention to primary cilia, the single cilium that FIG. 3.5 Cilia and flagella (a) Cilia on surface of respiratory epithelium occurs on most cells of the body. Primary cilia are thought to play a role in some kidney and other diseases. Look for similar links between molecular and cellular biology, physiology, and mediSEM × 1500 cine throughout the book. This image was taken with a scanning electron 2. Physiology as a Dynamic Field Physiology is a dynamic discipline, with numerous unanswered questions that merit further investigation and research. Many of the “facts” presented in this text are really only our current theories, so you should be prepared to change your mental models as new inforus, mation emerges from scientific research. EMERGING CONCEPTS How to Use this Book 3. An Emphasis on Integration The organ systems of the body do not Respiratory work in isolation, system Nervous although we study system them one at a time. To emphasize the Endocrine system Digestive integrative nature system Circulatory system of physiology, three chapters (Chapters 13, 20, and 25) focus Musculoskeletal system Urinary on how the physisystem ological processes of Reproductive system multiple organ systems coordinate with each other, especially when homeostasis is challenged. The Integration between Systems of the Body Integumentary System 4. A Focus on Problem Solving One of the most valuable life skills students should acquire is the ability to think critically and use information to solve problems. As you study physiology, you should be prepared to practice these skills. You will find a number of features in this book, such as the Concept Check questions and Figure and Graph Questions. These “test yourself” questions are designed to challenge your critical thinking and analysis skills. In each chapter, read the Running Problem as you work through the text and see if you can apply what you’re reading to the clinical scenario described in the problem. Also, be sure to look at the back of the text, where we have combined the index and glossary to save time when you are looking up unfamiliar words. The appendices have the answers to the Concept Check questions, Figure and Graph Questions, and end-of-chapter questions, as well as reviews of physics, logarithms, and basic genetics. The back end papers include a periodic table of the elements, diagrams of anatomical positions of the body, and tables with conversions and normal values of blood components. Take a few minutes to look at all these features so that you can make optimum use of them. It is my hope that by reading this book, you will develop an integrated view of physiology that allows you to enter your chosen profession with respect for the complexity of the human body and a clear vision of the potential of physiological and biomedical research. May you find physiology as fun and exciting I do. Good luck with your studies! Warmest regards, Dr. Dee (as my students call me) [email protected] Phys in Action Video Topics: Try It Activities: pp. 130–131 Fig. 5.4 Osmolarity & Tonicity pp. 154–155 Fig. 5.23 Membrane Potential pp. 458–459 Fig.14.15 Electrocardiogram p. 494 Fig. 15.14 Cardiovascular Control p. 545 Fig. 17.7 The Spirometer p. 549 Fig. 17.10 Respiratory Pressure p. 557 Fig. 17.13 Alveolar Gases p. 573 Fig. 18.7 Hemoglobin-Oxygen Transport p. 610 Fig. 19.13 Renal Clearance p. 793 Fig. 25.8 Blood Pressure & Exercise p. 21 Graphing p. 135 Membrane Models (Lipid bylayer) p. 251 Action Potentials p. 325 Salty-Sweet Taste Experiment p. 468 Frank-Starling Law of the Heart p. 605 Insulin p. 682 Oral Rehydration Therapy EIGHTH EDITION AN INTEGRAT UNIVERSITY OF TEXAS, AUSTIN with contributions by Bruce R. Johnson, Ph.D. and William C. Ober, M.D. ILLUSTRATION COORDINATOR Claire E. Ober, R.N. ILLUSTRATOR Anita lmpaglizzo, ILLUSTRATOR Andrew C. Silverthorn, M.D. CLINICAL CONSULTANT @ Pearson PPROACH Courseware Portfolio Manager: Lauren Harp Content Producer: Deepti Agarwal Managing Producer: Nancy Tabor Courseware Director, Content Development: Barbara Yien Courseware Editorial Assistant: Dapinder Dosanjh Rich Media Content Producer: Nicole Constantine Mastering Content Developer, Science: Lorna Perkins Full-Service Vendor: SPi Global Copyeditor: Alyson Platt Art Project Manager: Stephanie Marquez, Imagineering Art LLC Illustrators: William C. Ober, Anita Impagliazzo, and Cliare E. 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Acknowledgements of third party content appear on page C-1, which constitutes an extension of this copyright page. PEARSON, ALWAYS LEARNING, Mastering™ A&P, BioFlix, and A&P Flix are exclusive trademarks in the U.S. and/or other countries owned by Pearson Education, Inc. or its affiliates. Unless otherwise indicated herein, any third-party trademarks that may appear in this work are the property of their respective owners and any references to third-party trademarks, logos or other trade dress are for demonstrative or descriptive purposes only. Such references are not intended to imply any sponsorship, endorsement, authorization, or promotion of Pearson’s products by the owners of such marks, or any relationship between the owner and Pearson Education, Inc. or its affiliates, authors, licensees or distributors. Library of Congress Cataloging-in-Publication Data Catalogue in Publication Data is on file with the Library of Congress 1 18 ISBN 10: 0-13-460519-5; ISBN 13: 978-0-13-460519-7 (Student edition) ISBN 10: 0-13-470434-7; ISBN 13: 978-0-13-470443-0 (Instructor’s Review Copy) www.pearson.com ABOUT THE AUTHOR DEE UNGLAUB SILVERTHORN Teaching Award, the 2009 Outstanding Undergraduate Science studied biology as an undergraduate Teacher Award from the Society at Newcomb College of Tulane Unifor College Science Teachers, the versity, where she did research on American Physiological Society’s cockroaches. For graduate school, Claude Bernard Distinguished Lecshe switched to studying crabs and turer and Arthur C. Guyton Physireceived a Ph.D. in marine science ology Educator of the Year, and from the Belle W. Baruch Institute multiple awards from UT–Austin, for Marine and Coastal Sciences at including the Burnt Orange Apple the University of South Carolina. Award. The first edition of her Her research interest is epithelial textbook won the 1998 Robert W. transport, and most recently work Hamilton Author Award for best in her laboratory has focused on textbook published in 1997–1998 transport properties of the chick Michael Chirillo, Dee Silverthorn, and Kevin Christmas by a University of Texas faculty allantoic membrane. Her teaching member. Dee was the president of the Human Anatomy and career started in the Physiology Department at the Medical UniPhysiology Society in 2012–2013, has served as editor-in-chief of versity of South Carolina but over the years she has taught a wide Advances in Physiology Education, and is currently chair of the range of students, from medical and college students to those still American Physiological Society Book Committee. She works with preparing for higher education. At the University of Texas–Ausmembers of the International Union of Physiological Sciences to tin, she teaches physiology in both lecture and laboratory settings, improve physiology education in developing countries, and this and instructs graduate students on developing teaching skills in the book has been translated into seven languages. Her free time is life sciences. In 2015 she joined the faculty of the new UT-Austin spent creating multimedia fiber art and enjoying the Texas hill Dell Medical School. She has received numerous teaching awards country with her husband, Andy, and their dogs. and honors, including a 2011 UT System Regents’ Outstanding About the Illustrators William C. Ober, M.D. (art coordinator and illustrator) received his undergraduate degree from Washington and Lee University and his M.D. from the University of Virginia. He also studied in the Department of Art as Applied to Medicine at Johns Hopkins University. After graduation, Dr. Ober completed a residency in Family Practice and later was on the faculty at the University of Virginia in the Department of Family Medicine and in the Department of Sports Medicine. He also served as Chief of Medicine of Martha Jefferson Hospital in Charlottesville, VA. He is currently a visiting Professor of Biology at Washington & Lee University, where he has taught several courses and led student trips to the Galapagos Islands. He was part of the Core Faculty at Shoals Marine Laboratory, where he taught Biological Illustration for 22 years. The textbooks illustrated by Medical & Scientific Illustration have won numerous design and illustration awards. Claire E. Ober, R.N. (illustrator) practiced pediatric and obstetric nursing before turning to medical illustration as a full-time career. She returned to school at Mary Baldwin College where she received her degree with distinction in studio art. Following a five-year apprenticeship, she has worked as Dr. Ober’s partner in Medical and Scientific Illustration since 1986. She was also on the Core Faculty at Shoals Marine Laboratory and co-taught Biological Illustration at both Shoals Marine Lab and at Washington and Lee University. iii iv ABOUT THE AUTHORS About the Clinical Consultant Andrew C. Silverthorn, M.D. is a graduate of the United States Military Academy (West Point). He served in the infantry in Vietnam, and upon his return entered medical school at the Medical University of South Carolina in Charleston. He was chief resident in family medicine at the University of Texas Medical Branch, Galveston, and is currently a family physician in solo practice in Austin, Texas. When Andrew is not busy seeing patients, he may be found on the golf course or playing with his two rescue dogs, Molly and Callie. About the Contributor Bruce Johnson, Ph.D. is a Senior Research Associate in the Department of Neurobiology and Behavior at Cornell University. He earned biology degrees at Florida State University (B.A.), Florida Atlantic University (M.S.), and at the Marine Biological Laboratory in Woods Hole (Ph.D.) through the Boston University Marine Program. For three decades, he has led Cornell’s highly-praised Principles of Neurophysiology course, in which students receive hands-on instruction in principles and methods in neurophysiology. He is a coauthor of Crawdad: a CDROM Lab Manual for Neurophysiology and the Laboratory Manual for Physiology. Bruce has directed and taught in neuroscience faculty workshops sponsored by NSF (Crawdad), ADInstruments (Crawdad and CrawFly), the Grass Foundation and the Faculty for Undergraduate Neuroscience (FUN). He has also lead workshops and neuroscience courses at the Universities of Copenhagen (Denmark), Cologne (Germany), Ibadan (Nigeria), and the Marine Biological Laboratory. Bruce has been named a Most Influential Faculty Member by the graduating senior class at Cornell and awarded the John M. and Emily B. Clark Award for Distinguished Teaching at Cornell. His other teaching awards include the FUN Educator of the Year Award, FUN Career Service Award, and co-recipient of the 2016 Award for Education in Neuroscience, sponsored by the Society for Neuroscience. He is currently the Editor-in-Chief of the Journal of Undergraduate Neuroscience Education. Bruce’s research addresses the cellular and synaptic mechanisms of motor network plasticity. DEDICATION The 8th edition is dedicated to my colleagues who read every word of the first edition manuscript and provided valuable feedback that helped shape the book. Park City, Utah, June 1995 (Standing, L to R): Judy Sullivan, Patricia Munn, Dee Silverthorn, Mary Ann Rokitka, Richard Walker, Pat Berger, Norman Scott (Seated) Shana Ederer, Prentice Hall development editor v This page intentionally left blank NEW TO THIS EDITION The Eighth Edition of Human Physiology: An Integrated Approach builds upon the thorough coverage of integrative and molecular physiology topics that have always been the foundation of this book. The biggest change is a completely revised Chapter 24 on immunology. This field has expanded dramatically since the First Edition published in 1997, and it was time to step back and re-think the presentation of this complicated and complex subject. Neurophysiology is also changing rapidly, requiring multiple updates in Chapters 8 through 11. In nearly every chapter the latest developments in research and medicine meant changes to the presentation of information. Continuing the revision of the art introduced in the Seventh Edition, we created additional Review and Essentials figures that students can use for quick review as well as new Anatomy Summaries and concept maps. Figures from previous editions that were significantly modified or eliminated are still available to instructors on the Instructor’s DVD and in the Instructor Resources area of Mastering A&P. In addition to the online Phys in Action videos that are referenced in related figures, we have new Try It! activities throughout the book. These activities present data, usually from classic experiments, and ask the students to interpret the results. Topics include Benjamin Franklin’s little-known experiment that helped development of the phospholipid bilayer model of the membrane, and the experiments that resulted in oral rehydration therapy for treating cholera. HIGHLIGHTS OF CONTENT UPDATES Chapter 1 Introduction to Physiology New Focus on Graphing with a new Try It! activity Added information on the connectome and microbiome Updated information on literature searches and citations Chapter 6 Communication, Integration, and Homeostasis Chapter 7 Introduction to the Endocrine System Four new element names in the periodic table, inside the back cover of the text Added ribbon diagram/Richardson diagram of proteins Chapter 3 Compartmentation: Cells and Tissues Explanations of light and electron microscopy New Emerging Concepts box on induced pluripotent stem cells (iPSs) Chapter 5 Membrane Dynamics New Try It! activity on lipid bilayers Three Phys in Action video references in Figures 5.4, 5.6, and 5.23 Updated information on calcitonin gene-related peptide Updated information on melatonin and melatonin-related drugs Chapter 8 Neurons: Cellular and Network Properties Update on mechanisms of axonal transport and associated diseases: dynein, kinesin, fragile X, Alzheimer’s, microcephaly Try It! activity on action potentials New link to online calculator for Nernst and GHK equations Added discussion of resistance of extracellular fluid to discussion of resistance to current flow Added space constant discussion Chapter 9 The Central Nervous System Added lateral sulcus, insula, cerebral aqueduct Re-classification of stages of sleep Pericytes in blood-brain barrier formation Dopaminergic pathways and addiction Chapter 10 Sensory Physiology Chapter 2 Molecular Interactions Juxtacrine signaling Updated information on NIH Common Fund’s Building Blocks, Biological Pathways, and Networks Program Updated the discussion on cytokine families Re-classified receptor-enzymes as catalytic receptors GPCR for eicosanoids New Try It! activity on sweet and salty taste Additional information on non-neural sensors and Merkel cells Chapter 11 Efferent Division: Autonomic and Somatic Motor Control Expanded table on properties of autonomic neurotransmitter receptors Added NN and NM nicotinic subtypes Added discussion of sarin nerve gas Updated anti-nicotine vaccine Etiology of diabetic neuropathy Chapter 12 Muscles Expanded discussion of myosin light chains in striated muscle New table with autonomic effects on smooth muscles vii viii FM/BM TITLE Chapter 13 Integrative Physiology I: Control of Body Movement Addition information on reflexes and muscle tone Updated Parkinson’s treatments Expanded tetanus Running Problem Chapter 14 Cardiovascular Physiology New Running problem on atypical presentation of myocardial infarction in a woman New section and new figure on coronary circulation New Try It! activity on Starling’s law of the heart Added discussion of echocardiography Expanded ejection fraction discussion New discussion of ion channel subtypes Chapter 15 Blood Flow and the Control of Blood Pressure Updated information on pericytes and their functions New discussion of blood-retinal barrier Updated discussion of angiogenesis including angiopoietin and angiopoietin/Tie signaling pathway. New Review quantitative question on Bernoulli’s principle of fluid flow New sections on coronary blood flow and cerebral blood flow Updated statistics on CV diseases Added neurogenic shock Chapter 16 Blood Revised art, includes Figures 16.2, 16.4, 16.6, and 16.7 Updated information on treatment for sickle cell disease Chapter 17 Mechanics of Breathing Forced vital capacity test FEV1 /FVC ratio New figure and Figure Question for forced vital capacity test Antenatal corticosteroids to prevent NRDS Chapter 18 Gas Exchange and Transport Updated information on action of carbonic anhydrase Updated information on hemoglobin-based blood substitutes Carotid body plasticity in disease states Chapter 19 The Kidneys New map for factors influencing GFR Updated model of organic anion transport, including OAT family transporters New figure and table on renal handling of some common substances New Try It! activity on glucosuria and the discovery of insulin PAH clearance and calculation of renal plasma f low discussion New term: renal handling New Figure Question Updated glomerular filtration barrier to include glomerular capillary glycocalyx, slit diaphragm Chapter 20 Integrative Physiology II: Fluid and Electrolyte Balance New section on role of kidney in hypertension New Concept Check question Expanded discussion of K+ handling Added zona gomerulosa, paraventricular and supraoptic nuclei New section on endocrine pathologies in fluid balance New Level 3 Review question on Liddle’s syndrome Chapter 21 The Digestive System New Try It! activity on role of the SGLT in treating diarrhea New information on cholera vaccine Updated discussion on microfold cells Added guanylate cyclase-C (GC-C), uroguanylin and guanylin, plecanatide Chapter 22 Metabolism and Energy Balance Updated model for appetite Updated pharmacological trials for anorexia Latent autoimmune diabetes; also called type 1.5; gestational diabetes (GDM); MODY, maturity-onset diabetes of the young. Added mechanism of action of metformin Added cardiovascular risk calculator link Chapter 23 Endocrine Control of Growth and Metabolism Expanded discussion of melanocortins and their receptors in the control of food intake. Agouti-related protein (AGRP), MC4R receptors Added explanation of the role of ghrelin in growth hormone release New figure for feedback control of growth hormone release Updated discussion on off-label use of growth hormone in adults Primary cilia in chrondrocytes and osteocytes act as mechnotransducers Role of calcium-sensing receptor and NALCN channel in neuronal excitability New figure and discussion of intestinal and renal Ca2 + transport Skeletal deformaties in ciliopathies New figure and discussion of bone remodeling, including RANK, RANKL, osteoprotegerin, osteoid New Review question on osteopetrosis Chapter 24 The Immune System 6 NEW figures. Most art significantly revised. Added concepts include long-lived plasma cells, mucosaassociated lymphoid tissue (MALT), self-antigens, negative selection, hygiene hypothesis, Zika virus, DAMPS – dangerassociated molecular patterns, B cell receptors, regulatory T cells (Tregs) Updated information on IgD, contact-dependent signaling Chapter 26 Reproduction and Development Kisspeptin control of GNRH and role in puberty Origin of the acrosome Flibanserin for low libido in women ACKNOWLEDGMENTS Writing, editing, and publishing a textbook is a group project that requires the talent and expertise of many people. No one scientist has the detailed background needed in all areas to write a book of this scope, and I am indebted to all my colleagues who so generously share their expertise in each edition. I particularly want to acknowledge Bruce Johnson, Cornell University, Department of Neurobiology and Behavior, a superb neurobiologist and educator, who once again ensured that the chapters on neurobiology are accurate and reflect the latest developments in that rapidly changing field. I would also like to thank Michael Chirillo, a former graduate teaching assistant of mine, for his work developing the Try It! features in between interviewing for and starting a medical residency program. Peter English, a colleague and former student, has also joined the team helping with this revision. A huge thank you goes to immunologists Natalie Steinel, from UT-Austin Dell Medical School, and Tynan A. Becker, from University of Alaska, for their assistance and critical review of the Chapter 24 revision. Brian Sumner, a 3rd year medical student at the George Washington University School of Medicine, graciously volunteered time out of his busy clinical rotations to read the revised chapter and ensure that it was student-friendly. The art team of Bill Ober, M.D. and Claire Ober, R.N. has worked with me since the first edition, and I am always grateful for their scientifically astute suggestions and revisions. They were joined in the last edition by Anita Impagliazzo, who brought a fresh eye and new figure ideas. Instructors and students often contact me directly about the book, and for this edition I would particularly like to thank Allison Brekke, James Mayer, and Dean A. Wiseman for comments and suggestions. Thanks also to my students who keep me informed of the typos that creep in no matter how many people look at the manuscript and pages. Many other people devoted their time and energy to making this book a reality, and I would like to thank them all, collectively and individually. I apologize in advance to anyone whose name I have omitted. Reviewers I am particularly grateful to the instructors who reviewed one or more chapters of the last edition. There were many suggestions in their thoughtful reviews that I was unable to include in the text, but I appreciate the time and thought that went into their comments. The reviewers for this edition include: Jake Brashears, San Diego City College Trevor Cardinal, California Polytechnic State University Michael S. Finkler, Indiana University Kokomo Victor Fomin, University of Delaware Jill Gifford, Youngstown State University David Kurjiaka, Grand Valley State University Mary Jane Niles, University of San Francisco Rudy M. Ortiz, University of California, Merced Jennifer Rogers, University of Iowa Jia Sun, Imperial Valley College Alan Sved, University of Pittsburgh Many other instructors and students took time to write or e-mail queries or suggestions for clarification, for which I thank them. I am always delighted to have input, and I apologize that I do not have room to acknowledge them all individually. Specialty Reviews No one can be an expert in every area of physiology, and I am deeply thankful for my friends and colleagues who reviewed entire chapters or answered specific questions. Even with their help, there may be errors, for which I take full responsibility. The specialty reviewers for this edition were: Natalie Steinel, UT-Austin Dell Medical School Tynan A. Becker, University of Alaska Photographs I would like to thank Kristen Harris, University of Texas who generously provided micrographs from her research. Supplements Damian Hill once again worked with me to revise and improve the Instructor Resource Manual that accompanies the book. I believe that supplements should reflect the style and approach of the text, so I am grateful that Damian has continued to be my alter-ego for so many editions. Peter English is helping with Mastering activities this revision. I would also like to thank my colleagues who helped with the test bank and media supplements for this edition: Heidi Bustamante, University of Colorado, Boulder Chad M. Wayne, University of Houston Margaret Flemming, Austin Community College Cheryl Neudauer, Minneapolis Community & Technical College The Development and Production Team Writing a manuscript is only a first step in the long and complicated process that results in a bound book with all its ancillaries. The team that works with me on book development deserves a lot of credit for the finished product. Gary Hespenheide designed a bright and cheerful cover that continues our tradition of images that show science as art. Anne A. Reid, my long-time developmental ix x ACKNOWLEDGMENTS editor, is always wonderful to work with, and provides thoughtful suggestions that improve what I wrote. The team at Pearson Education worked tirelessly to see this edition move from manuscript to bound book. My acquisitions editor, Kelsey Volker Churchman, was joined by Lauren Harp, Senior Acquisitions Editor for the second part of this revision. Ashley Williams and Kate Abderholden, assistant editors, kept track of everyone and everything for us. Chriscelle Palaganas, Program Manager, provided excellent guidance and support throughout the whole production process. The task of coordinating production fell to Pearson Content Producer Deepti Agarwal. Nathaniel Jones handled composition and project management, and Project Manager Stephanie Marquez at the art house, Imagineering, managed the team that prepared the art for production. Katrina Mohn was the photo researcher who found the wonderful new photos that appear in this edition. Nicole Constantine was the assistant media producer who kept my supplements authors on task and on schedule. Wendy Mears is the product marketing manager who works with the excellent sales teams at Pearson Education and Pearson International, and Derek Perrigo is the Field Marketing Manager for the anatomy and physiology list. Justin Trombold, Ph.D. Kurt Venator, Ph.D. Kira Wenstrom, Ph.D. Finally, special thanks to my colleagues in the American Physiological Society, the Human Anatomy & Physiology Society, and the International Union of Physiological Sciences whose experiences in the classroom have enriched my own understanding of how to teach physiology. I would also like to recognize a special group of friends for their continuing support: Penelope Hansen (Memorial University, St. John’s), Mary Anne Rokitka (SUNY Buffalo), Rob Carroll (East Carolina University School of Medicine), Cindy Gill (Hampshire College), and Joel Michael (Rush Medical College), as well as Ruth Buskirk, Jeanne Lagowski, Jan M. Machart and Marilla Svinicki (University of Texas). As always, I thank my family and friends for their patience, understanding, and support during the chaos that seems inevitable with book revisions. The biggest thank you goes to my husband Andy, whose love, support, and willingness to forgo home-cooked meals on occasion help me meet my deadlines. A Work in Progress Special Thanks As always, I would like to thank my students and colleagues who looked for errors and areas that needed improvement. I’ve learned that awarding one point of extra credit for being the first student to report a typo works really well. My graduate teaching assistants over the years have all played a huge role in my teaching, and their input has helped shape how I teach. Many of them are now faculty members themselves. They include: Ari Berman, Ph.D. Lawrence Brewer, Ph.D. Kevin Christmas, Ph.D. Michael Chirillo, M.D., Ph.D. Lynn Cialdella Kam, M.S., M.B.A., Ph.D. Sarah Davies Kanke, Ph.D. Peter English, Ph.D. Carol C. Linder, Ph.D. Karina Loyo-Garcia, Ph.D. Jan M. Machart, Ph.D. Tonya Thompson, M.D. Patti Thorn, Ph.D. One of the most rewarding aspects of writing a textbook is the opportunity it has given me to meet or communicate with other instructors and students. In the 20 years since the first edition was published, I have heard from people around the world and have had the pleasure of hearing how the book has been incorporated into their teaching and learning. Because science textbooks are revised every 3 or 4 years, they are always works in progress. I invite you to contact me or my publisher with any suggestions, corrections, or comments about this edition. I am most reachable through e-mail at silverthorn@ utexas.edu. You can reach my editor at the following address: Applied Sciences Pearson Education 1301 Sansome Street San Francisco, CA 94111 Dee U. Silverthorn [email protected] University of Texas Austin, Texas CONTENTS UNIT 1 Basic Cell Processes: Integration and Coordination CHAPTER 1 CHAPTER 2 Introduction to Physiology 1 Molecular Interactions 28 Physiology Is an Integrative Science 2 RUNNING PROBLEM What to Believe? 2 RUNNING PROBLEM Chromium Supplements 29 EMERGING CONCEPTS The Changing World of Omics 3 Function and Mechanism 4 Themes in Physiology 5 FOCUS ON... Mapping 6 Theme 1: Structure and Function Are Closely Related 8 Theme 2: Living Organisms Need Energy 8 Theme 3: Information Flow Coordinates Body Functions 9 Theme 4: Homeostasis Maintains Internal Stability 9 Homeostasis 9 Molecules and Bonds 29 Most Biomolecules Contain Carbon, Hydrogen, and Oxygen 29 Electrons Have Four Important Biological Roles 33 Covalent Bonds between Atoms Create Molecules 33 Noncovalent Bonds Facilitate Reversible Interactions 39 Noncovalent Interactions 40 Hydrophilic Interactions Create Biological Solutions 40 Molecular Shape Is Related to Molecular Function 40 Hydrogen Ions in Solution Can Alter Molecular Shape 41 Protein Interactions 46 Proteins Are Selective about the Molecules They Bind 46 Protein-Binding Reactions Are Reversible 47 What Is the Body’s Internal Environment? 10 Binding Reactions Obey the Law of Mass Action 47 Homeostasis Depends on Mass Balance 10 The Dissociation Constant Indicates Affinity 48 Excretion Clears Substances from the Body 12 Multiple Factors Alter Protein Binding 48 Homeostasis Does Not Mean Equilibrium 13 The Body Regulates the Amount of Protein in Cells 51 Control Systems and Homeostasis 13 Local Control Is Restricted to a Tissue 13 Reaction Rate Can Reach a Maximum 51 CHAPTER SUMMARY 55 | REVIEW QUESTIONS 56 Reflex Control Uses Long-Distance Signaling 14 Response Loops Begin with a Stimulus 14 Feedback Loops Modulate the Response Loop 15 CHAPTER 3 Negative Feedback Loops Are Homeostatic 15 Compartmentation: Cells and Tissues 58 Positive Feedback Loops Are Not Homeostatic 16 Functional Compartments of the Body 59 RUNNING PROBLEM Pap Tests Save Lives 59 Feedforward Control Allows the Body to Anticipate Change 17 Biological Rhythms Result from Changes in a Setpoint 17 The Science of Physiology 18 The Lumens of Some Organs Are Outside the Body 59 Functionally, the Body Has Three Fluid Compartments 61 Biological Membranes 61 Good Scientific Experiments Must Be Carefully Designed 18 FOCUS ON... Graphing 20 The Cell Membrane Separates Cell from Environment 61 The Results of Human Experiments Can Be Difficult to Interpret 22 Membrane Proteins May Be Loosely or Tightly Bound to the Membrane 62 CHAPTER SUMMARY 25 | REVIEW QUESTIONS 26 Membranes Are Mostly Lipid and Protein 61 Membrane Lipids Create a Hydrophobic Barrier 62 Membrane Carbohydrates Attach to Both Lipids and Proteins 64 xi xii CONTENTS Intracellular Compartments 64 Enzymes 98 Cells Are Divided into Compartments 65 Enzymes Are Proteins 99 The Cytoplasm Includes Cytosol, Inclusions, Fibers, and Organelles 65 Reaction Rates Are Variable 99 Inclusions Are in Direct Contact with the Cytosol 65 Enzymes May Be Activated, Inactivated, or Modulated 99 Microtubules Form Centrioles, Cilia, and Flagella 68 Enzymes Lower Activation Energy of Reactions 100 EMERGING CONCEPTS Single Cilia Are Sensors 68 Enzymatic Reactions Can Be Categorized 101 Cytoplasmic Protein Fibers Come in Three Sizes 68 The Cytoskeleton Is a Changeable Scaffold 68 Motor Proteins Create Movement 69 Organelles Create Compartments for Specialized Functions 70 The Nucleus Is the Cell’s Control Center 71 Tissues of the Body 73 Metabolism 102 Cells Regulate Their Metabolic Pathways 102 Catabolic Pathways Produce ATP 104 One Glucose Molecule Can Yield 30–32 ATP 109 Anaerobic Metabolism Makes Two ATP 109 Extracellular Matrix Has Many Functions 73 Proteins Are the Key to Cell Function 110 Cell Junctions Hold Cells Together to Form Tissues 73 DNA Guides the Synthesis of RNA 113 Epithelia Provide Protection and Regulate Exchange 75 Alternative Splicing Creates Multiple Proteins from One DNA Sequence 114 Connective Tissues Provide Support and Barriers 80 Muscle and Neural Tissues Are Excitable 82 Tissue Remodeling 84 Apoptosis Is a Tidy Form of Cell Death 84 Stem Cells Can Create New Specialized Cells 85 EMERGING CONCEPTS Induced Pluripotent Stems Cells 85 FOCUS ON... The Skin 86 Organs 87 mRNA Translation Links Amino Acids 114 EMERGING CONCEPTS Purple Petunias and RNAi 114 Protein Sorting Directs Proteins to Their Destination 115 Proteins Undergo Posttranslational Modification 115 CHAPTER SUMMARY 118 | REVIEW QUESTIONS 119 CHAPTER SUMMARY 88 | REVIEW QUESTIONS 90 CHAPTER 5 CHAPTER 4 Energy and Cellular Metabolism 92 RUNNING PROBLEM Tay-Sachs Disease: A Deadly Inheritance 93 Membrane Dynamics 121 RUNNING PROBLEM Cystic Fibrosis 122 Homeostasis Does Not Mean Equilibrium 122 Osmosis and Tonicity 124 Energy in Biological Systems 93 The Body Is Mostly Water 124 Energy Is Used to Perform Work 94 The Body Is in Osmotic Equilibrium 124 Energy Comes in Two Forms: Kinetic and Potential 94 Energy Can Be Converted from One Form to Another 95 Thermodynamics Is the Study of Energy Use 95 Chemical Reactions 96 Energy Is Transferred between Molecules during Reactions 96 Activation Energy Gets Reactions Started 96 Energy Is Trapped or Released during Reactions 96 Net Free Energy Change Determines Reaction Reversibility 98 Osmolarity Describes the Number of Particles in Solution 125 Tonicity Describes the Volume Change of a Cell 126 Transport Processes 131 Cell Membranes Are Selectively Permeable 131 Diffusion 132 Lipophilic Molecules Cross Membranes by Simple Diffusion 134 Protein-Mediated Transport 136 Membrane Proteins Have Four Major Functions 136 CONTENTS Channel Proteins Form Open, Water-Filled Passageways 138 Long-Distance Communication May Be Electrical or Chemical 167 Carrier Proteins Change Conformation to Move Molecules 139 Cytokines May Act as Both Local and Long-Distance Signals 167 Facilitated Diffusion Uses Carrier Proteins 141 Signal Pathways 168 Active Transport Moves Substances against Their Concentration Gradients 142 Receptor Proteins Are Located Inside the Cell or on the Cell Membrane 168 Carrier-Mediated Transport Exhibits Specificity, Competition, and Saturation 144 Membrane Proteins Facilitate Signal Transduction 170 Vesicular Transport 146 Phagocytosis Creates Vesicles Using the Cytoskeleton 146 Endocytosis Creates Smaller Vesicles 147 The Most Rapid Signal Pathways Change Ion Flow through Channels 171 Most Signal Transduction Uses G Proteins 173 CLINICAL FOCUS LDL: The Lethal Lipoprotein 147 Many Lipophobic Hormones Use GPCR-cAMP Pathways 173 Exocytosis Releases Molecules Too Large for Transport Proteins 147 G Protein-Coupled Receptors Also Use Lipid-Derived Second Messengers 173 Epithelial Transport 149 Catalytic Receptors Have Enzyme Activity 175 Epithelial Transport May Be Paracellular or Transcellular 149 Integrin Receptors Transfer Information from the Extracellular Matrix 175 Transcellular Transport of Glucose Uses Membrane Proteins 150 Transcytosis Uses Vesicles to Cross an Epithelium 151 The Resting Membrane Potential 152 Novel Signal Molecules 175 Calcium Is an Important Intracellular Signal 176 Gases Are Ephemeral Signal Molecules 177 BIOTECHNOLOGY Calcium Signals Glow in the Electricity Review 152 Dark 177 The Cell Membrane Enables Separation of Electrical Charge in the Body 152 CLINICAL FOCUS From Dynamite to All Living Cells Have a Membrane Potential 153 Some Lipids Are Important Paracrine Signals 178 The Resting Membrane Potential Is Due Mostly to Potassium 156 Changes in Ion Permeability Change the Membrane Potential 157 Medicine 178 Modulation of Signal Pathways 179 Receptors Exhibit Saturation, Specificity, and Competition 179 Integrated Membrane Processes: Insulin Secretion 158 One Ligand May Have Multiple Receptors 179 CHAPTER SUMMARY 160 | REVIEW QUESTIONS 161 Cells Must Be Able to Terminate Signal Pathways 181 CHAPTER 6 Communication, Integration, and Homeostasis 164 Up and Down-Regulation Enable Cells to Modulate Responses 180 Many Diseases and Drugs Target the Proteins of Signal Transduction 181 Homeostatic Reflex Pathways 181 Cannon’s Postulates Describe Regulated Variables and Control Systems 182 RUNNING PROBLEM Diabetes Mellitus: A Growing Epidemic 165 Long-Distance Pathways Maintain Homeostasis 182 Cell-to-Cell Communication 165 Gap Junctions Create Cytoplasmic Bridges 165 Control Systems Vary in Their Speed and Specificity 186 Contact-Dependent Signals Require Cell-to-Cell Contact 165 Complex Reflex Control Pathways Have Several Integrating Centers 188 Local Communication Uses Paracrine and Autocrine Signals 167 CHAPTER SUMMARY 191 | REVIEW QUESTIONS 192 xiii xiv CONTENTS UNIT 2 Homeostasis and Control CHAPTER 7 Introduction to the Endocrine System 194 Hormones 195 RUNNING PROBLEM Graves’ Disease 195 Hormones Have Been Known Since Ancient Times 195 CLINICAL FOCUS Diabetes: The Discovery of Receptor or Second Messenger Problems Cause Abnormal Tissue Responsiveness 215 Diagnosis of Endocrine Pathologies Depends on the Complexity of the Reflex 215 Hormone Evolution 217 FOCUS ON... The Pineal Gland 218 CHAPTER SUMMARY 220 | REVIEW QUESTIONS 221 Insulin 196 What Makes a Chemical a Hormone? 196 Hormones Act by Binding to Receptors 197 CHAPTER 8 Hormone Action Must Be Terminated 197 Neurons: Cellular and Network Properties 223 The Classification of Hormones 199 Most Hormones Are Peptides or Proteins 199 Steroid Hormones Are Derived from Cholesterol 200 Some Hormones Are Derived from Single Amino Acids 202 Control of Hormone Release 205 The Endocrine Cell Is the Sensor in Simple Endocrine Reflexes 205 RUNNING PROBLEM Mysterious Paralysis 224 Organization of the Nervous System 224 Cells of the Nervous System 226 Neurons Carry Electrical Signals 226 Establishing Synapses Depends on Chemical Signals 229 Glial Cells Provide Support for Neurons 231 Can Stem Cells Repair Damaged Neurons? 233 Electrical Signals in Neurons 234 Many Endocrine Reflexes Involve the Nervous System 205 The Nernst Equation Predicts Membrane Potential for a Single Ion 234 Neurohormones Are Secreted into the Blood by Neurons 205 The GHK Equation Predicts Membrane Potential Using Multiple Ions 234 The Pituitary Gland Is Actually Two Fused Glands 205 Ion Movement Creates Electrical Signals 235 The Posterior Pituitary Stores and Releases Two Neurohormones 207 Gated Channels Control the Ion Permeability of the Neuron 235 The Anterior Pituitary Secretes Six Hormones 207 CLINICAL FOCUS Mutant Channels 236 A Portal System Connects the Hypothalamus and Anterior Pituitary 209 Current Flow Obeys Ohm’s Law 236 Anterior Pituitary Hormones Control Growth, Metabolism, and Reproduction 209 Action Potentials Travel Long Distances 239 Feedback Loops Are Different in the Hypothalamic-Pituitary Pathway 211 Hormone Interactions 212 In Synergism, the Effect of Interacting Hormones Is More than Additive 213 Graded Potentials Reflect Stimulus Strength 237 Na+ and K+ Move across the Membrane during Action Potentials 240 One Action Potential Does Not Alter Ion Concentration Gradients 242 Axonal Na + Channels Have Two Gates 242 A Permissive Hormone Allows Another Hormone to Exert Its Full Effect 213 Action Potentials Will Not Fire during the Absolute Refractory Period 243 Antagonistic Hormones Have Opposing Effects 213 Action Potentials Are Conducted 245 Endocrine Pathologies 214 Larger Neurons Conduct Action Potentials Faster 245 Hypersecretion Exaggerates a Hormone’s Effects 214 Conduction Is Faster in Myelinated Axons 247 Hyposecretion Diminishes or Eliminates a Hormone’s Effects 215 Chemical Factors Alter Electrical Activity 249 BIOTECHNOLOGY The Body’s Wiring 249 CONTENTS Cell-To-Cell Communication in the Nervous System 249 The Behavioral State System Modulates Motor Output 292 Neurons Communicate at Synapses 249 Why Do We Sleep? 292 Neurons Secrete Chemical Signals 250 EMERGING CONCEPTS Brain Glymphatics 294 Neurotransmitters Are Highly Varied 251 Physiological Functions Exhibit Circadian Rhythms 295 CLINICAL FOCUS Myasthenia Gravis 253 Emotion and Motivation Involve Complex Neural Pathways 296 BIOTECHNOLOGY Of Snakes, Snails, Spiders, and Sushi 254 Neurotransmitters Are Released from Vesicles 254 Moods Are Long-Lasting Emotional States 297 Stronger Stimuli Release More Neurotransmitter 257 Learning and Memory Change Synaptic Connections in the Brain 297 Integration of Neural Information Transfer 258 Postsynaptic Responses May Be Slow or Fast 258 Pathways Integrate Information from Multiple Neurons 261 Synaptic Activity Can Be Modified 261 Long-Term Potentiation Alters Synapses 264 Disorders of Synaptic Transmission Are Responsible for Many Diseases 264 xv Learning Is the Acquisition of Knowledge 298 Memory Is the Ability to Retain and Recall Information 298 Language Is the Most Elaborate Cognitive Behavior 300 Personality Is a Combination of Experience and Inheritance 301 CHAPTER SUMMARY 303 | REVIEW QUESTIONS 305 CHAPTER SUMMARY 266 | REVIEW QUESTIONS 268 CHAPTER 10 CHAPTER 9 The Central Nervous System 271 Emergent Properties of Neural Networks 272 RUNNING PROBLEM Infantile Spasms 272 Evolution of Nervous Systems 272 Anatomy of the Central Nervous System 274 Sensory Physiology 307 RUNNING PROBLEM Ménière’s Disease 308 General Properties of Sensory Systems 308 Receptors Are Sensitive to Particular Forms of Energy 309 Sensory Transduction Converts Stimuli into Graded Potentials 310 A Sensory Neuron Has a Receptive Field 310 The CNS Develops from a Hollow Tube 274 The CNS Integrates Sensory Information 310 The CNS Is Divided into Gray Matter and White Matter 274 Coding and Processing Distinguish Stimulus Properties 312 Bone and Connective Tissue Support the CNS 277 The Brain Floats in Cerebrospinal Fluid 277 Somatic Senses 315 The Blood-Brain Barrier Protects the Brain 279 Pathways for Somatic Perception Project to the Cortex and Cerebellum 315 Neural Tissue Has Special Metabolic Requirements 280 Touch Receptors Respond to Many Different Stimuli 317 CLINICAL FOCUS Diabetes: Hypoglycemia and the Brain 281 Skin Temperature Receptors Are Free Nerve Endings 318 The Spinal Cord 281 The Brain 282 The Brain Stem Is the Oldest Part of the Brain 283 Nociceptors Initiate Protective Responses 318 CLINICAL FOCUS Natural Painkillers 320 Chemoreception: Smell and Taste 322 The Cerebellum Coordinates Movement 285 Olfaction Is One of the Oldest Senses 322 The Diencephalon Contains the Centers for Homeostasis 285 Taste Is a Combination of Five Basic Sensations 324 The Cerebrum Is the Site of Higher Brain Functions 287 Taste Transduction Uses Receptors and Channels 325 Brain Function 288 The Ear: Hearing 328 The Cerebral Cortex Is Organized into Functional Areas 289 Hearing Is Our Perception of Sound 329 The Spinal Cord and Brain Integrate Sensory Information 290 Sound Transduction Is a Multistep Process 329 Sensory Information Is Processed into Perception 291 Sounds Are Processed First in the Cochlea 333 The Motor System Governs Output from the CNS 291 Auditory Pathways Project to the Auditory Cortex 333 The Cochlea Is Filled with Fluid 330 xvi CONTENTS Hearing Loss May Result from Mechanical or Neural Damage 334 The Ear: Equilibrium 335 The Vestibular Apparatus Provides Information about Movement and Position 335 The Semicircular Canals Sense Rotational Acceleration 335 The Otolith Organs Sense Linear Acceleration and Head Position 337 Summary of Sympathetic and Parasympathetic Branches 367 The Somatic Motor Division 368 A Somatic Motor Pathway Consists of One Neuron 368 The Neuromuscular Junction Contains Nicotinic Receptors 370 CHAPTER SUMMARY 371 | REVIEW QUESTIONS 372 Equilibrium Pathways Project Primarily to the Cerebellum 337 The Eye and Vision 338 CHAPTER 12 The Skull Protects the Eye 338 Muscles 374 Light Enters the Eye through the Cornea 339 RUNNING PROBLEM Periodic Paralysis 375 The Lens Focuses Light on the Retina 341 Skeletal Muscle 376 Phototransduction Occurs at the Retina 343 Skeletal Muscles Are Composed of Muscle Fibers 376 EMERGING CONCEPTS Melanopsin 344 Myofibrils Are Muscle Fiber Contractile Structures 377 Photoreceptors Transduce Light into Electrical Signals 344 Muscle Contraction Creates Force 380 Signal Processing Begins in the Retina 347 Actin and Myosin Slide Past Each Other during Contraction 382 CHAPTER SUMMARY 352 | REVIEW QUESTIONS 353 Myosin Crossbridges Move Actin Filaments 383 Calcium Signals Initiate Contraction 383 Myosin Heads Step along Actin Filaments 384 CHAPTER 11 Acetylcholine Initiates Excitation-Contraction Coupling 385 Efferent Division: Autonomic and Somatic Motor Control 355 BIOTECHNOLOGY Watching Myosin Work 385 RUNNING PROBLEM A Powerful Addiction 356 The Autonomic Division 356 Skeletal Muscle Contraction Requires a Steady Supply of ATP 388 Fatigue Has Multiple Causes 389 Autonomic Reflexes Are Important for Homeostasis 357 Skeletal Muscle Is Classified by Speed and Fatigue Resistance 390 Antagonistic Control Is a Hallmark of the Autonomic Division 358 Resting Fiber Length Affects Tension 392 Autonomic Pathways Have Two Efferent Neurons in Series 358 Sympathetic and Parasympathetic Branches Originate in Different Regions 359 The Autonomic Nervous System Uses a Variety of Chemical Signals 359 Autonomic Pathways Control Smooth and Cardiac Muscle and Glands 359 Autonomic Neurotransmitters Are Synthesized in the Axon 362 Autonomic Receptors Have Multiple Subtypes 363 The Adrenal Medulla Secretes Catecholamines 364 Force of Contraction Increases with Summation 393 A Motor Unit Is One Motor Neuron and Its Muscle Fibers 393 Contraction Force Depends on the Types and Numbers of Motor Units 394 Mechanics Of Body Movement 395 Isotonic Contractions Move Loads; Isometric Contractions Create Force without Movement 395 Bones and Muscles around Joints Form Levers and Fulcrums 397 Muscle Disorders Have Multiple Causes 399 Smooth Muscle 400 Autonomic Agonists and Antagonists Are Important Tools in Research and Medicine 364 Smooth Muscle Is More Variable Than Skeletal Muscle 401 Primary Disorders of the Autonomic Nervous System Are Relatively Uncommon 366 Myosin Phosphorylation Controls Contraction 403 CLINICAL FOCUS Diabetes: Autonomic Neuropathy 366 Calcium Initiates Smooth Muscle Contraction 405 Smooth Muscle Lacks Sarcomeres 402 MLCP Controls Ca2+ Sensitivity 405 CONTENTS Some Smooth Muscles Have Unstable Membrane Potentials 406 Chemical Signals Influence Smooth Muscle Activity 407 Cardiac Muscle 409 CHAPTER SUMMARY 410 | REVIEW QUESTIONS 411 xvii Autonomic Reflexes 417 Skeletal Muscle Reflexes 417 Golgi Tendon Organs Respond to Muscle Tension 418 Muscle Spindles Respond to Muscle Stretch 418 Stretch Reflexes and Reciprocal Inhibition Control Movement around a Joint 420 Flexion Reflexes Pull Limbs Away from Painful Stimuli 421 CHAPTER 13 Integrative Physiology I: Control of Body Movement 414 Neural Reflexes 415 Neural Reflex Pathways Can Be Classified in Different Ways 415 RUNNING PROBLEM Tetanus 415 The Integrated Control of Body Movement 422 Movement Can Be Classified as Reflex, Voluntary, or Rhythmic 423 The CNS Integrates Movement 425 Control of Movement in Visceral Muscles 428 EMERGING CONCEPTS Visualization Techniques in Sports 428 CHAPTER SUMMARY 429 | REVIEW QUESTIONS 430 UNIT 3 Integration of Function CHAPTER 14 CLINICAL FOCUS Fibrillation 455 Cardiovascular Physiology 432 The Electrocardiogram Reflects Electrical Activity 455 RUNNING PROBLEM Myocardial Infarction 433 Overview of the Cardiovascular System 433 The Cardiovascular System Transports Materials throughout the Body 433 The Cardiovascular System Consists of the Heart, Blood Vessels, and Blood 434 Pressure, Volume, Flow, And Resistance 436 The Heart Contracts and Relaxes during a Cardiac Cycle 459 CLINICAL FOCUS Gallops, Clicks, and Murmurs 462 Pressure-Volume Curves Represent One Cardiac Cycle 462 Stroke Volume Is the Volume of Blood Pumped per Contraction 464 Cardiac Output Is a Measure of Cardiac Performance 464 The Autonomic Division Modulates Heart Rate 464 The Pressure of Fluid in Motion Decreases over Distance 436 Multiple Factors Influence Stroke Volume 466 Pressure Changes in Liquids without a Change in Volume 436 Contractility Is Controlled by the Nervous and Endocrine Systems 467 Blood Flows from Higher Pressure to Lower Pressure 438 Resistance Opposes Flow 438 Velocity Depends on the Flow Rate and the Cross-Sectional Area 439 EMERGING CONCEPTS Stem Cells for Heart Disease 470 EDV and Arterial Blood Pressure Determine Afterload 470 CHAPTER SUMMARY 472 | REVIEW QUESTIONS 474 Cardiac Muscle And The Heart 440 The Heart Has Four Chambers 440 Heart Valves Ensure One-Way Flow in the Heart 443 CHAPTER 15 Cardiac Muscle Cells Contract without Innervation 446 Blood Flow and the Control of Blood Pressure 476 Calcium Entry Is a Feature of Cardiac EC Coupling 447 RUNNING PROBLEM Essential Hypertension 477 Cardiac Muscle Contraction Can Be Graded 447 The Blood Vessels 478 The Coronary Circulation Supplies Blood to the Heart 445 Myocardial Action Potentials Vary 448 The Heart as a Pump 452 Blood Vessels Contain Vascular Smooth Muscle 478 Arteries and Arterioles Carry Blood Away from the Heart 478 Electrical Signals Coordinate Contraction 452 Exchange Takes Place in the Capillaries 479 Pacemakers Set the Heart Rate 453 Blood Flow Converges in the Venules and Veins 480 xviii CONTENTS Angiogenesis Creates New Blood Vessels 480 Blood Pressure 481 Blood Cell Production 513 Blood Cells Are Produced in the Bone Marrow 513 Blood Pressure Is Highest in Arteries and Lowest in Veins 481 Hematopoiesis Is Controlled by Cytokines 514 Arterial Blood Pressure Reflects the Driving Pressure for Blood Flow 482 Colony-Stimulating Factors Regulate Leukopoiesis 515 Blood Pressure Is Estimated by Sphygmomanometry 483 Erythropoietin Regulates RBC Production 515 Cardiac Output and Peripheral Resistance Determine Mean Arterial Pressure 484 Changes in Blood Volume Affect Blood Pressure 484 CLINICAL FOCUS SHOCK 485 Resistance in the Arterioles 486 Myogenic Autoregulation Adjusts Blood Flow 486 Paracrine Signals Influence Vascular Smooth Muscle 488 The Sympathetic Branch Controls Most Vascular Smooth Muscle 489 Distribution of Blood to the Tissues 489 Cerebral Blood Flow Stays Nearly Constant 491 Coronary Blood Flow Parallels the Work of the Heart 491 Regulation of Cardiovascular Function 492 The Baroreceptor Reflex Controls Blood Pressure 492 Orthostatic Hypotension Triggers the Baroreceptor Reflex 494 Other Systems Influence Cardiovascular Function 495 Thrombopoietin Regulates Platelet Production 515 Red Blood Cells 517 Mature RBCs Lack a Nucleus 517 Hemoglobin Synthesis Requires Iron 517 RBCs Live about Four Months 517 FOCUS ON... Bone Marrow 518 RBC Disorders Decrease Oxygen Transport 519 CLINICAL FOCUS Diabetes: Hemoglobin and Hyperglycemia 522 Platelets 522 Hemostasis and Coagulation 523 Hemostasis Prevents Blood Loss from Damaged Vessels 523 Platelet Activation Begins the Clotting Process 523 Coagulation Converts a Platelet Plug into a Clot 525 Anticoagulants Prevent Coagulation 527 CHAPTER SUMMARY 529 | REVIEW QUESTIONS 530 Exchange at the Capillaries 495 Velocity of Blood Flow Is Lowest in the Capillaries 496 Most Capillary Exchange Takes Place by Diffusion and Transcytosis 496 Capillary Filtration and Absorption Take Place by Bulk Flow 497 The Lymphatic System 499 Edema Results from Alterations in Capillary Exchange 500 Cardiovascular Disease 501 Risk Factors for CVD Include Smoking and Obesity 501 CLINICAL FOCUS Diabetes and Cardiovascular Disease 502 Atherosclerosis Is an Inflammatory Process 502 Hypertension Represents a Failure of Homeostasis 502 EMERGING CONCEPTS Inflammatory Markers for Cardiovascular Disease 504 CHAPTER SUMMARY 505 | REVIEW QUESTIONS 507 CHAPTER 17 Mechanics of Breathing 532 RUNNING PROBLEM Emphysema 533 The Respiratory System 533 Bones and Muscles of the Thorax Surround the Lungs 534 Pleural Sacs Enclose the Lungs 534 Airways Connect Lungs to the External Environment 537 The Airways Warm, Humidify, and Filter Inspired Air 538 CLINICAL FOCUS Congestive Heart Failure 538 Alveoli Are the Site of Gas Exchange 538 Pulmonary Circulation Is High-Flow, Low-Pressure 539 Gas Laws 540 Air Is a Mixture of Gases 540 Gases Move Down Pressure Gradients 540 CHAPTER 16 Blood 510 Boyle’s Law Describes Pressure-Volume Relationships 540 Ventilation 542 Lung Volumes Change during Ventilation 542 RUNNING PROBLEM Blood Doping in Athletes 511 During Ventilation, Air Flows because of Pressure Gradients 544 Plasma and the Cellular Elements of Blood 511 Inspiration Occurs When Alveolar Pressure Decreases 544 Plasma Is Extracellular Matrix 511 Expiration Occurs When Alveolar Pressure Increases 546 Cellular Elements Include RBCs, WBCs, and Platelets 513 Intrapleural Pressure Changes during Ventilation 547 CONTENTS Lung Compliance and Elastance May Change in Disease States 548 Surfactant Decreases the Work of Breathing 549 Airway Diameter Determines Airway Resistance 550 Overview of Kidney Function 592 Kidneys Filter, Reabsorb, and Secrete 592 The Nephron Modifies Fluid Volume and Osmolarity 592 Filtration 594 Rate and Depth of Breathing Determine the Efficiency of Breathing 551 The Renal Corpuscle Contains Filtration Barriers 595 Alveolar Gas Composition Varies Little during Normal Breathing 553 Capillary Pressure Causes Filtration 596 Ventilation and Alveolar Blood Flow Are Matched 553 GFR Is Relatively Constant 598 Auscultation and Spirometry Assess Pulmonary Function 556 GFR Is Subject to Autoregulation 598 CHAPTER SUMMARY 558 | REVIEW QUESTIONS 559 CHAPTER 18 Gas Exchange and Transport 562 RUNNING PROBLEM High Altitude 563 Gas Exchange in the Lungs and Tissues 563 Lower Alveolar Po2 Decreases Oxygen Uptake 564 Diffusion Problems Cause Hypoxia 565 EMERGING CONCEPTS Diabetes: Diabetic Nephropathy 595 Hormones and Autonomic Neurons Also Influence GFR 600 Reabsorption 600 Reabsorption May Be Active or Passive 600 Renal Transport Can Reach Saturation 602 BIOTECHNOLOGY Artificial Kidneys 603 Peritubular Capillary Pressures Favor Reabsorption 604 Secretion 605 Competition Decreases Penicillin Secretion 606 Excretion 607 BIOTECHNOLOGY The Pulse Oximeter 567 Clearance Is a Noninvasive Way to Measure GFR 607 Gas Solubility Affects Diffusion 567 Clearance Helps Us Determine Renal Handling 609 Gas Transport In The Blood 569 Hemoglobin Binds to Oxygen 569 Oxygen Binding Obeys the Law of Mass Action 570 xix Micturition 612 CHAPTER SUMMARY 614 | REVIEW QUESTIONS 615 Hemoglobin Transports Most Oxygen to the Tissues 571 PO2 Determines Oxygen-Hb Binding 571 CHAPTER 20 EMERGING CONCEPTS Blood Substitutes 572 Integrative Physiology II: Fluid and Electrolyte Balance 616 Oxygen Binding Is Expressed as a Percentage 572 Several Factors Affect O2-Hb Binding 573 Carbon Dioxide Is Transported in Three Ways 575 Regulation of Ventilation 578 Neurons in the Medulla Control Breathing 579 CO2, Oxygen, and pH Influence Ventilation 580 Protective Reflexes Guard the Lungs 582 Higher Brain Centers Affect Patterns of Ventilation 582 CHAPTER SUMMARY 584 | REVIEW QUESTIONS 585 Fluid and Electrolyte Homeostasis 617 ECF Osmolarity Affects Cell Volume 617 Multiple Systems Integrate Fluid and Electrolyte Balance 617 RUNNING PROBLEM Hyponatremia 617 Water Balance 620 Daily Water Intake and Excretion Are Balanced 620 The Kidneys Conserve Water 621 The Renal Medulla Creates Concentrated Urine 621 CLINICAL FOCUS Diabetes: Osmotic Diuresis 623 CHAPTER 19 Vasopressin Controls Water Reabsorption 623 The Kidneys 587 Blood Volume and Osmolarity Activate Osmoreceptors 625 Functions of the Kidneys 588 The Loop of Henle Is a Countercurrent Multiplier 625 RUNNING PROBLEM Gout 588 Anatomy of the Urinary System 589 Sodium Balance and ECF Volume 629 Aldosterone Controls Sodium Balance 630 The Urinary System Consists of Kidneys, Ureters, Bladder, and Urethra 589 Low Blood Pressure Stimulates Aldosterone Secretion 630 The Nephron Is the Functional Unit of the Kidney 589 Natriuretic Peptides Promote Na+ and Water Excretion 632 ANG II Has Many Effects 632 xx CONTENTS Potassium Balance 635 Behavioral Mechanisms in Salt and Water Balance 636 Drinking Replaces Fluid Loss 636 Low Na+ Stimulates Salt Appetite 636 Acids and Bases in the Body Come from Many Sources 642 pH Homeostasis Depends on Buffers, Lungs, and Kidneys 642 Avoidance Behaviors Help Prevent Dehydration 636 Buffer Systems Include Proteins, Phosphate Ions, and HCO3¯ 643 Integrated Control of Volume, Osmolarity, and Blood Pressure 636 Ventilation Can Compensate for pH Disturbances 644 Osmolarity and Volume Can Change Independently 637 Dehydration Triggers Homeostatic Responses 638 Kidneys Assist in Blood Pressure Homeostasis 641 Endocrine Problems Disrupt Fluid Balance 641 Acid-Base Balance 641 pH Changes Can Denature Proteins 641 Kidneys Use Ammonia and Phosphate Buffers 645 The Proximal Tubule Secretes H+ and Reabsorbs HCO3¯ 645 The Distal Nephron Controls Acid Excretion 646 Acid-Base Disturbances May Be Respiratory or Metabolic 647 CHAPTER SUMMARY 651 | REVIEW QUESTIONS 652 UNIT 4 Metabolism, Growth, and Aging CHAPTER 21 The Liver Secretes Bile 676 The Digestive System 654 Most Digestion Occurs in the Small Intestine 676 RUNNING PROBLEM Cholera in India 655 Anatomy of the Digestive System 655 The Digestive System Is a Tube 655 The GI Tract Wall Has Four Layers 658 Digestive Function and Processes 659 We Secrete More Fluid than We Ingest 660 FOCUS ON... The Liver 677 Bile Salts Facilitate Fat Digestion 678 Carbohydrates Are Absorbed as Monosaccharides 678 Proteins Are Digested into Small Peptides and Amino Acids 680 Some Larger Peptides Can Be Absorbed Intact 681 Digestion and Absorption Make Food Usable 661 Nucleic Acids Are Digested into Bases and Monosaccharides 683 Motility: GI Smooth Muscle Contracts Spontaneously 661 The Intestine Absorbs Vitamins and Minerals 683 GI Smooth Muscle Exhibits Different Patterns of Contraction 663 The Intestine Absorbs Ions and Water 683 CLINICAL FOCUS Diabetes: Delayed Gastric Emptying 663 The Large Intestine Concentrates Waste 684 Regulation of GI Function 664 The Enteric Nervous System Can Act Independently 664 GI Peptides Include Hormones, Neuropeptides, and Cytokines 665 Integrated Function: The Cephalic Phase 667 Chemical and Mechanical Digestion Begins in the Mouth 668 Saliva Is an Exocrine Secretion 668 Regulation of the Intestinal Phase 683 Diarrhea Can Cause Dehydration 686 EMERGING CONCEPTS The Human Microbiome Project 687 Immune Functions of the GI Tract 687 M Cells Sample Gut Contents 687 Vomiting Is a Protective Reflex 687 CHAPTER SUMMARY 689 | REVIEW QUESTIONS 690 Swallowing Moves Food from Mouth to Stomach 668 Integrated Function: The Gastric Phase 669 The Stomach Stores Food 669 CHAPTER 22 Gastric Secretions Protect and Digest 670 Metabolism and Energy Balance 692 The Stomach Balances Digestion and Defense 673 Integrated Function: The Intestinal Phase 673 Appetite and Satiety 693 RUNNING PROBLEM Eating Disorders 693 Intestinal Secretions Promote Digestion 674 BIOTECHNOLOGY Discovering Peptides: Research in The Pancreas Secretes Enzymes and Bicarbonate 674 Reverse 694 CONTENTS Energy Balance 694 Energy Input Equals Energy Output 695 Oxygen Consumption Reflects Energy Use 695 CLINICAL FOCUS Estimating Fat–The Body Mass CHAPTER 23 Endocrine Control of Growth and Metabolism 728 Index 696 Review Of Endocrine Principles 729 Many Factors Influence Metabolic Rate 697 RUNNING PROBLEM Hyperparathyroidism 729 Energy Is Stored in Fat and Glycogen 697 Adrenal Glucocorticoids 729 Metabolism 698 Ingested Energy May Be Used or Stored 698 Enzymes Control the Direction of Metabolism 698 Fed-State Metabolism 700 Carbohydrates Make ATP 700 Amino Acids Make Proteins 700 Fats Store Energy 700 CLINICAL FOCUS Antioxidants Protect the Body 703 Plasma Cholesterol Predicts Heart Disease 703 Fasted-State Metabolism 704 Glycogen Converts to Glucose 704 Proteins Can Be Used to Make ATP 705 Lipids Store More Energy than Glucose or Protein 706 Homeostatic Control of Metabolism 707 The Pancreas Secretes Insulin and Glucagon 707 The Insulin-to-Glucagon Ratio Regulates Metabolism 707 Insulin Is the Dominant Hormone of the Fed State 708 Insulin Promotes Anabolism 708 The Adrenal Cortex Secretes Steroid Hormones 729 Cortisol Secretion Is Controlled by ACTH 731 Cortisol Is Essential for Life 731 Cortisol Is a Useful Therapeutic Drug 733 Cortisol Pathologies Result from Too Much or Too Little Hormone 733 CRH and ACTH Have Additional Physiological Functions 734 Thyroid Hormones 734 Thyroid Hormones Contain Iodine 736 TSH Controls the Thyroid Gland 736 Thyroid Pathologies Affect Quality of Life 737 Growth Hormone 739 Growth Hormone Is Anabolic 739 Growth Hormone Is Essential for Normal Growth 741 Genetically Engineered hGH Raises Ethical Questions 741 Tissue and Bone Growth 741 Tissue Growth Requires Hormones and Paracrine Factors 741 Bone Growth Requires Adequate Dietary Calcium 742 CLINICAL FOCUS New Growth Charts 742 Calcium Balance 743 Glucagon Is Dominant in the Fasted State 711 Plasma Calcium Is Closely Regulated 744 Diabetes Mellitus Is a Family of Diseases 712 Three Hormones Control Calcium Balance 746 Type 1 Diabetics Are Prone to Ketoacidosis 715 Multiple Factors Control Bone Remodeling 747 Type 2 Diabetics Often Have Elevated Insulin Levels 717 Calcium and Phosphate Homeostasis Are Linked 748 Metabolic Syndrome Links Diabetes and Cardiovascular Disease 718 Osteoporosis Is a Disease of Bone Loss 750 CHAPTER SUMMARY 751 | REVIEW QUESTIONS 752 Multiple Hormones Influence Metabolism 719 Regulation of Body Temperature 719 Body Temperature Balances Heat Production, Gain, and Loss 719 CHAPTER 24 The Immune System 754 Body Temperature Is Homeostatically Regulated 720 Overview 755 Movement and Metabolism Produce Heat 722 RUNNING PROBLEM HPV: To Vaccinate or Not? 755 The Body’s Thermostat Can Be Reset 723 Anatomy of the Immune System 757 Lymphoid Tissues Are Everywhere 757 CHAPTER SUMMARY 725 | REVIEW QUESTIONS 726 Leukocytes Are the Immune Cells 757 xxi xxii CONTENTS Development of Immune Cells 760 FOCUS ON... The Thymus Gland 661 Ventilatory Responses to Exercise 790 Cardiovascular Responses to Exercise 791 Lymphocytes Mediate the Adaptive Immune Response 761 Cardiac Output Increases during Exercise 791 The Immune System Must Recognize “Self” 761 Muscle Blood Flow Increases during Exercise 791 Early Pathogen Exposure Strengthens Immunity 762 Blood Pressure Rises Slightly during Exercise 792 Molecules of the Innate Immune Response 762 Many Molecules of the Innate Immune Response Are Always Present 762 Antigen Presentation and Recognition Molecules 763 The Baroreceptor Reflex Adjusts to Exercise 792 Feedforward Responses to Exercise 793 Temperature Regulation During Exercise 794 Exercise and Health 794 Antigen-Recognition Molecules 764 Exercise Lowers the Risk of Cardiovascular Disease 795 B Lymphocytes Produce Antibodies 764 Type 2 Diabetes Mellitus May Improve with Exercise 795 Pathogens of the Human Body 765 Bacteria and Viruses Require Different Defense Mechanisms 765 Viruses Can Only Replicate inside Host Cells 766 Stress and the Immune System May Be Influenced by Exercise 796 CHAPTER SUMMARY 797 | REVIEW QUESTIONS 798 The Immune Response 766 Barriers Are the Body’s First Line of Defense 766 CHAPTER 26 Innate Immunity Provides Nonspecific Responses 766 Reproduction and Development 800 Antigen-Presenting Cells Bridge Innate and Adaptive Responses 768 RUNNING PROBLEM Infertility 801 Adaptive Immunity Creates Antigen-Specific Responses 768 Sex Determination 801 Antibody Functions 769 Integrated Immune Responses 773 Bacterial Invasion Causes Inflammation 773 Viral Infections Require Intracellular Defense 773 Specific Antigens Trigger Allergic Responses 776 MHC Proteins Allow Recognition of Foreign Tissue 777 Immune System Pathologies 778 Autoimmune Disease Results from Antibodies against Self-Antigen 779 Immune Surveillance Removes Abnormal Cells 779 Neuro-Endocrine-Immune Interactions 780 Stress Alters Immune System Function 780 Modern Medicine Includes Mind-Body Therapeutics 781 CHAPTER SUMMARY 782 | REVIEW QUESTIONS 784 Sex Chromosomes Determine Genetic Sex 802 Sexual Differentiation Occurs Early in Development 802 CLINICAL FOCUS X-Linked Inherited Disorders 805 Basic Patterns of Reproduction 806 CLINICAL FOCUS Determining Sex 806 Gametogenesis Begins in Utero 806 The Brain Directs Reproduction 807 Environmental Factors Influence Reproduction 810 Male Reproduction 810 Testes Produce Sperm and Hormones 811 Spermatogenesis Requires Gonadotropins and Testosterone 814 Male Accessory Glands Contribute Secretions to Semen 815 Androgens Influence Secondary Sex Characteristics 815 Female Reproduction 815 CHAPTER 25 Integrative Physiology III: Exercise 786 RUNNING PROBLEM Malignant Hyperthermia 787 Metabolism and Exercise 787 Hormones Regulate Metabolism during Exercise 788 The Ovary Produces Eggs and Hormones 818 A Menstrual Cycle Lasts about One Month 818 Hormonal Control of the Menstrual Cycle Is Complex 819 Hormones Influence Female Secondary Sex Characteristics 823 Procreation 823 Oxygen Consumption Is Related to Exercise Intensity 789 The Human Sexual Response Has Four Phases 823 Several Factors Limit Exercise 790 The Male Sex Act Includes Erection and Ejaculation 824 CONTENTS Sexual Dysfunction Affects Males and Females 824 Contraceptives Are Designed to Prevent Pregnancy 825 Growth and Aging 833 Puberty Marks the Beginning of the Reproductive Years 833 Menopause and Andropause Are a Consequence of Aging 833 Infertility Is the Inability to Conceive 826 Pregnancy and Parturition 826 Fertilization Requires Capacitation 826 The Developing Embryo Implants in the Endometrium 827 The Placenta Secretes Hormones During Pregnancy 827 Pregnancy Ends with Labor and Delivery 830 The Mammary Glands Secrete Milk During Lactation 830 xxiii CHAPTER SUMMARY 834 | REVIEW QUESTIONS 836 Appendices Appendix A Answers A-1 Appendix B Physics and Math A-36 Appendix C Genetics A-39 Photo Credits C-1 Glossary/Index GI-1 This page intentionally left blank Move Beyond Memorization: Prepare for Tomorrow’s Challenges The goals for the Eighth Edition of Human Physiology: An Integrated Approach are to provide an integrated and up-to-date introduction to core concepts in physiology and to equip you with skills for solving real-world problems. Challenge Yourself: Apply What You Learn Learning physiology requires that you use information rather than simply memorizing what you think will be on the test. The Eighth Edition text and Mastering™ A&P program provide multiple opportunities for you to practice answering the more challenging types of questions that you are likely to see on a test or exam. Running Problems explore a real-world disease or disorder that unfolds in short segments throughout the chapter. You can check your understanding by comparing your answers with those in Problem Conclusion at the end of each chapter. Related Coaching Activities can be assigned in Mastering A&P. see pp. 84–85 FIG. 7.15 Hypocortisolism (a) Hyposecretion from Damage to the Pituitary Additional Practice Questions include Concept Check Questions, which are placed at intervals throughout the chapter, and Review Questions, which are provided at the end of the chapter and organized into four levels of difficulty. An answer key is in Appendix A. (b) Hyposecretion from Atrophy of the Adrenal Cortex Hypothalamus CRH Hypothalamus CRH Anterior pituitary ACTH Anterior pituitary ACTH Adrenal cortex Cortisol Adrenal cortex Cortisol Symptoms of deficiency Symptoms of deficiency FIGURE QUESTION Figure Questions challenge you to apply visual literacy skills as you read an illustration or photo. Answers to these questions appear at the end of the text, in Appendix A. For each condition, use arrows to indicate whether levels of the three hormones in the pathway will be increased, decreased, or unchanged. Draw in negative feedback loops where functional. See p. 217 Practice Solving Real-World Problems NEW! Additional questions for each “Try it” activity are available in Mastering A&P. Topics include NEW! “Try it” boxes present a real-world research problem or classic experiment and guide you through the process of analyzing the data and thinking like a scientist. Graphing (Chapter 1), Cell Membranes (Chapter 5), Action Potentials (Chapter 8), Salty-Sweet Taste Experiment (Chapter 10), Frank-Starling Law of the Heart (Chapter 14), Insulin (Chapter 19) and Oral Rehydration Therapy (Chapter 21). See p. 251 Graph Questions encourage you to interpret real data presented in graphs. Answers to these questions appear at the end of the text, in Appendix A. Study More Efficiently Using the Figures Eye-tracking research has shown that learning and comprehension levels are higher for students who study both the figures and the text together than for students who only read the text. This book offers dozens of illustrations designed to help you learn physiology more efficiently, and make the best use of your study time. Essentials Figures distill the basics of a topic into one or two pages, helping you to see the big picture of human physiology. Instructors can assign related Mastering A&P coaching activities that explore these topics in greater depth. FIG. 5.23 Play Phys in Action ESSENTIALS Membrane Potential The electrical disequilibrium that exists between the extracellular fluid (ECF) and intracellular fluid (ICF) of living cells is called the membrane potential difference (Vm), or membrane potential for short. The membrane potential results from the uneven distribution of electrical charge (i.e., ions) between the ECF and ICF. What creates the membrane potential? 1. Ion concentration gradients between the ECF and ICF 2. The selectively permeable cell membrane @Mastering Anatomy & Physiology (a) In illustrations, this uneven distribution of charge is often shown by the charge symbols clustered on each side of the cell membrane. + + + – – – – + – – + Cell + – – – (ICF) + – – + – + – – – + + + + + ECF + The ICF has a slight excess of anions (–). The ECF has a slight excess of cations (+). Creation of a Membrane Potential in an Artificial System To show how a membrane potential difference can arise from ion concentration gradients and a selectively permeable membrane, we will use an artificial cell system where we can control the membrane’s permeability to ions and the composition of the ECF and ICF. (b) When we begin, the cell has no membrane potential: The ECF (composed of Na+ and Cl– ions) and the ICF (K+ and large anions, A– ) are electrically neutral. The system is in chemical disequilibrium, with concentration gradients for all four ions. The cell membrane acts as an insulator to prevent free movement of ions between the ICF and ECF. + – + – – – + – – + – + KEY + + + + – – – + + + Sodium ion – Chloride ion + Potassium ion – Large anion – + (c) Now we insert a leak channel for K+ into the membrane, making the cell freely permeable to K+. The transfer of just one K+ from the cell to the ECF creates an electrical disequilibrium: the ECF has a net positive charge (+1) while the ICF has a net negative charge (–1). The cell now has a membrane potential difference, with the inside of the cell negative relative to the outside. – + – + – + + + – – + – + – + + – + (d) As additional K+ ions leave the cell, going down their concentration gradient, the inside of the cell becomes more negative and the outside becomes more positive. If K+ was uncharged, like glucose, it would diffuse out of the cell until the concentration outside [K]out equaled the concentration inside [K]in. But K+ is an ion, so we must consider its electrical gradient. Remember the rule for movement along electrical gradients: Opposite charges attract, like charges repel. 154 See p. 154 + – – + – + – The A– cannot follow K+ out of the cell because the cell is not permeable to A–. 4 Additional K+ leaves the cell. 5 Now the negative charge inside the cell begins to attract ECF K+ back into the cell: an electrical gradient in the opposite direction from the concentration gradient. + – + – + 3 + – – K+ starts to move out of the cell down its concentration gradient. – + + + 2 – + – – How much K+ will leave the cell? + – – + We insert a leak channel for K+. – – – 1 + – – + + + – Selected figures from the text are explored in accompanying Phys in Action video tutors and in coaching activities in Mastering A&P. Anatomy Summary Figures provide succinct visual overviews of a physiological system from a macro to micro perspective. Whether you are learning the anatomy for the first time or refreshing your memory, these summaries show you the essential features of each system in a single figure. FIG.9.3 ANATOMY SUMMARY... The Central Nervous System (a) Posterior View of the CNS (b) Sectional View of the Meninges The meninges and extracellular fluid cushion the delicate brain tissue. Venous sinus Cranium Cranium Cerebral hemispheres Dura mater Subdural space Arachnoid membrane Cerebellum Pia mater Brain Cervical spinal nerves Subarachnoid space FIGURE QUESTION Moving from the cranium in, name the meninges that form the boundaries of the venous sinus and the subdural and subarachnoid spaces. Thoracic spinal nerves (c) Posterior View of Spinal Cord and Vertebra Central canal Gray matter Sectioned vertebrae Lumbar spinal nerves White matter Spinal nerve Spinal cord Pia mater Arachnoid membrane Meninges Dura mater Sacral spinal nerves Body of vertebra Autonomic ganglion Spinal nerve Coccygeal nerve See p. 276 276 Review Figures visually present foundational concepts that you may already be familiar with. You may find it helpful to check out these figures before learning new physiology concepts. Selected figures from the text can be assigned as Art-Labeling Activities in Mastering A&P. See p. 44 Get Online Coaching Through Mastering A&P Mastering A&P provides tutorials and review questions that you can access before, during, and after class. Phys in Action! Video Tutors and Coaching Activities help you visualize and master challenging physiological concepts by demonstrating laboratory procedures and realworld applications. Demonstrations include pulmonary function test, tilt table, exercise testing, and more. EXPANDED! Interactive Physiology 2.0 Coaching Activities teach complex physiological processes using exceptionally clear animations, interactive tutorials, games, and quizzes. IP2 features new graphics, quicker navigation, and a mobilefriendly design. New topics include Generation of an Action Potential and Cardiac Cycle. IP2 and IP animations can be assigned from the Mastering A&P Item Library or accessed through the Mastering A&P Study Area. Mastering A&P offers thousands of tutorials, activities, and questions that can be used to test yourself, or assigned for homework and practice. Additional highlights include: Nurses Need Physiology Case Studies guide you through the steps of diagnosing and treating patients in real-world clinical scenarios. Dynamic Study Modules are manageable, mobilefriendly sets of questions with extensive feedback for you to test, learn, and retest yourself on basic concepts. A&P Flix Animations use 3-D, movie-quality graphics to help you visualize complex physiology processes. PhysioEx Laboratory Simulations offer a supplement or substitute for wet labs due to cost, time, or safety concerns. Access the Complete Textbook Online or Offline with Pearson eText You can read your textbook without having to add weight to your bookbag. The Pearson eText mobile app offers offline access and can be downloaded for most iOS and Android phones and tablets from the Apple App or Google Play stores. Powerful interactive and customization functions in the eText platform include instructor and student notetaking, highlighting, bookmarking, search, and links to glossary terms. Additional Support for Students & Instructors NEW! Ready-to-Go Teaching Modules help instructors efficiently make use of the best teaching tools before, during, and after class. Accessed through the Instructor Resources area of Mastering A&P, and curated by author Dee Silverthorn, modules include skill development applications for Human Physiology including Concept Mapping and Graphing. Learning Catalytics allows students to use their smartphone, tablet, or laptop to respond to questions in class. Visit learningcatalytics.com to learn more. The Mastering A&P Instructor Resources Area includes the following downloadable tools for instructors who adopt the Eighth Edition for their classes: Customizable PowerPoint® lecture outlines include customizable images and provide a springboard for lecture prep. All of the figures, photos, and tables from the text are available in JPEG and PowerPoint® formats, in labelled and unlabelled versions, and with customizable labels and leader lines. Test bank provides thousands of customizable questions across Bloom’s taxonomy levels. Each question is tagged to chapter learning outcomes that can also be tracked within Mastering Anatomy & Physiology assessments. Available in Microsoft® Word and TestGen® formats. Animations and videos bring human physiology concepts to life. A comprehensive Instructor Resource Manual, co-authored by Dee Silverthorn and Damian Hill, includes a detailed teaching outline for each chapter, along with a wealth of activities, examples, and analogies that have been thoroughly class-tested with thousands of students. Customizable Study Questions, co-authored by Dee Silverthorn and Damian Hill, help students focus their reading on the most important points in each chapters and are organized by chapter section headers for easy editing to reflect the material covered in class. 1.1 Physiology Is an Integrative Science 2 LO 1.1.1 Define physiology. LO 1.1.2 List the levels of organization from atoms to the biosphere. LO 1.1.3 Name the 10 physiological organ systems of the body and give their functions. LO 1.4.3 and ho substa LO 1.4.4 emati of a sing mathin how it relates to ce and give an example. ish between equilibrium and 1.2 Function and Mechanism 4 LO 1.2.1 Distinguish between mechanistic explanations and teleological explanations. 1.3 Themes in Physiology 5 LO 1.3.1 List and give examples of the four major themes in physiology. 1.4 Homeostasis g LO 1.4.1 Define homeostasis. What happens when homeostasis fails? LO 1.4.2 Name and describe the two major compartments of the human body..5 Control Systems and Homeostasis 13 LO 1.5.1 List the three components of a control system and give an example. LO 1.5.2 Explain the relationship between a regulated variable and its setpoint. LO 1.5.3 Compare local control, long-distance control, and reflex control. LO 1.5.4 Explain the relationship between a response loop and a feedback loop. LO 1.5.5 Compare negative feedback, positive feedback, and feedforward control. Give an example of each. LO 1.5.6 Explain what happens to setpoints in biological rhythms and give some examples. 1. 6 The Science of Physiology 18 LO 1.6.1 Explain and give examples of the following components of scientific research: independent and dependent variables, experimental control, data, replication, variability. LO 1.6.2 Compare and contrast the following types of experimental study designs: blind study, double-blind study, crossover study, prospective and retrospective studies, cross-sectional study, longitudinal study, meta-analysis. LO 1.6.3 Define placebo and nocebo effects and explain how they may influence the outcome of experimental studies. 2 CHAPTER 1 Introduction to Physiology elcome to the fascinating study of the human body! For most 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 health. Although some ancient remedies, such as camel dung and powdered sheep horn, may seem bizarre, we are still using others, such as blood-sucking leeches and chemicals derived from medicinal plants. The way we use these treatments has changed through the centuries as we have learned more about the human body. There has never been a more exciting time in human physiology. Physiology is the study of the normal functioning of a living organism and its component parts, including all its chemical and physical processes. The term physiology literally means “knowledge of nature.” Aristotle (384–322 bce) used the word in this broad sense to describe the functioning of all living organisms, not just of the human body. However, Hippocrates (ca. 460–377 bce), considered the father of medicine, used the word physiology to mean “the healing power of nature,” and thereafter the field became closely associated with medicine. By the sixteenth century in Europe, 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. Today, we benefit from centuries of work by physiologists who constructed a foundation of knowledge about how the human body functions. Since the 1970s, rapid advances in the fields of cellular and molecular biology have supplemented this work. A few decades ago, we thought that we would find the key to the secret of life by sequencing the human genome, which is the collective term for all the genetic information contained in the DNA of a species. However, this deconstructionist view of biology has proved to have its limitations, because living organisms are much more than the simple sum of their parts. W 1.1 Physiology Is an Integrative Science Many complex systems—including those of the human body— possess emergent properties, which are properties that cannot be predicted to exist based only on knowledge of the system’s individual components. An emergent property is not a property of any single component of the system, and it is greater than the simple sum of the system’s individual parts. Emergent properties result from complex, nonlinear interactions of the different components. For example, suppose someone broke down a car into its nuts and bolts and pieces and laid them out on a floor. Could you predict that, properly assembled, these bits of metal and plastic would become a vehicle capable of converting the energy in gasoline into movement? Who could predict that the right combination of elements into molecules and assemblages of molecules would result in a living organism? Among the most complex emergent properties in humans are emotion, intelligence, and other aspects of brain function. None of these properties can be predicted from knowing the individual properties of nerve cells. 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 mother seldom texted, so Jimmy figured it must be important. “Hi, Mom! What’s going on?” “Oh, Jimmy, I don’t know what to do. I saw the doctor this morning and he’s telling me that I need to take insulin. But I don’t want to! My type of diabetes doesn’t need insulin. I think he’s just trying to make me see him more by putting me on insulin. Don’t you think I’m right?” Jimmy paused for a moment. “I’m not sure, Mom. He’s probably just trying to do what’s best for you. Didn’t you talk to him about it?” “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?” “I guess so. Let me see what I can find out.” Jimmy hung up and thought. “Now what?” 2 5 9 12 16 19 24 When the Human Genome Project (www.genome.gov) began in 1990, scientists thought that by identifying and sequencing all the genes in human DNA, they would understand how the body worked. However, as research advanced, scientists had to revise their original idea that a given segment of DNA contained one gene that coded for one protein. It became clear that one gene may code for many proteins. The Human Genome Project ended in 2003, but before then researchers had moved beyond genomics to proteomics, the study of proteins in living organisms. Now scientists have realized that knowing that a protein is 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 genomics, systems biology, and integrative biology, but fundamentally these are all fields of physiology. The integration of function across many levels of organization is a special focus of physiology. (To integrate means to bring varied elements together to create a unified whole.) FIGURE 1.1 illustrates levels of organization ranging from the molecular level all the way up to populations of different species living together in ecosystems and in the biosphere. The levels of organization are shown along with the various subdisciplines of chemistry and biology related to the study of each organizational level. There is considerable overlap between the different fields of study, and these artificial divisions vary according to who is defining them. Notice, however, that physiology includes multiple levels, from molecular and cellular biology to the ecological physiology of populations. At all levels, physiology is closely tied to anatomy. The structure of a cell, tissue, or organ must provide an efficient physical base for its function. For this reason, it is nearly impossible to study the physiology of the body without understanding the underlying anatomy. Because of the interrelationship of anatomy and physiology, you will find Anatomy Summaries throughout the book. 1.1 Physiology Is an Integrative Science unit of structure capable of carrying out all life processes. A lipid and protein barrier called the cell membrane (also called the plasma membrane) separates cells from their external environment. Simple organisms are composed of only one cell, but complex organisms have many cells with different structural and functional specializations. Collections of cells that carry out related functions are called tissues {texere, to weave}. Tissues form structural and functional units known as organs {organon, tool}, and groups of organs integrate their functions to create organ systems. Chapter 3 reviews the anatomy of cells, tissues, and organs. The 10 physiological organ systems in the human body are illustrated in FIGURE 1.2. Several of the systems have alternate names, given in parentheses, that are based on the organs of the system rather than the function of the system. The integumentary system {integumentum, covering}, composed of the skin, forms a protective boundary that separates the body’s internal environment from the external environment (the outside world). The musculoskeletal system provides support and body movement. Four systems exchange materials between the internal and external environments. The respiratory (pulmonary) system exchanges gases; the digestive (gastrointestinal) system takes up nutrients and water and eliminates wastes; the urinary (renal) system removes excess water and waste material; and the reproductive system produces eggs or sperm. The remaining four systems extend throughout the body. The circulatory (cardiovascular) system distributes materials by pumping blood through vessels. The nervous and endocrine systems coordinate body functions. Note that the figure shows them as a continuum rather than as two distinct systems. Why? 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 immune system, which includes but is not limited to the anatomical structures known as the lymphatic system. The specialized cells of the immune system are scattered throughout the body. They protect the internal environment from foreign substances by intercepting material that enters through the intestines and lungs The Changing World of Omics If you read the scientific literature, it appears that contemporary research has exploded into an era of “omes” and “omics.” What is an “ome”? The term apparently derives from the Latin word for a mass or tumor, and it is now used to refer to a collection of items that make up a whole, such as a genome. One of the earliest uses of the “ome” suffix in biology is the term biome, meaning all organisms living in a major ecological region, such as the marine biome or the desert biome. A genome, for example, is a collection of all the genetic material of an organism. Its physiome describes the organism’s coordinated molecular, cellular, and physiological functioning. The related adjective “omics” describes the research related to studying an “ome.” Adding “omics” to a root word has become the cutting-edge way to describe a research field. For example, pharmacogenomics (the influence of genetics on the body’s response to drugs) is now as important as genomics, the sequencing of DNA (the genome). There is even a journal named OMICS! New “omes” emerge every year. The human connectome project (www.neuroscienceblueprint.nih.gov/ connectome/) sponsored by the American National Institutes of Health is a collaborative effort by multiple institutions to map all the neural connections of the human brain. NIH also sponsors the human microbiome project (https:// commonfund.nih.gov/hmp/overview), whose goal is to study the effects of microbes that normally live on or in the human body. Ignored as unimportant for many years, these microbes are now being shown to have an influence on both health and disease. These special review features illustrate the anatomy of the physiological systems at different levels of organization. At the most basic level of organization shown in Figure 1.1, atoms of elements link together to form molecules. Collections of molecules in living organisms form cells, the smallest FIG. 1.1 Levels of organization and the related fields of study ECOLOGY PHYSIOLOGY MOLECULAR BIOLOGY CELL BIOLOGY CHEMISTRY Atoms Molecules Cells Tissues Organs Organ systems Organisms Populations of one species Ecosystem of different species Biosphere CHAPTER EMERGING CONCEPTS 3 1 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 Circulatory Heart, blood vessels, blood Transport of materials between all cells of the body Digestive Stomach, intestine, liver, pancreas Conversion of food into particles that can be transported into the body; elimination of some wastes Endocrine Thyroid gland, adrenal gland Coordination of body function through synthesis and release of regulatory molecules Immune Thymus, spleen, lymph nodes Defense against foreign invaders Integumentary Skin Protection from external environment Musculoskeletal Skeletal muscles,