Guyton and Hall Textbook of Medical Physiology PDF

 Guyton and Hall Textbook of Medical Physiology http://avaxho.me/blogs/ChrisRedfield This page intentionally left blank  Twelfth Edition Guyton and Hall Textbook of Medical Physiology John E. Hall, Ph.D....

 Guyton and Hall Textbook of Medical Physiology http://avaxho.me/blogs/ChrisRedfield This page intentionally left blank  Twelfth Edition Guyton and Hall Textbook of Medical Physiology John E. Hall, Ph.D. Arthur C. Guyton Professor and Chair Department of Physiology and Biophysics Associate Vice Chancellor for Research University of Mississippi Medical Center Jackson, Mississippi 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 TEXTBOOK OF MEDICAL PHYSIOLOGY ISBN: 978-1-4160-4574-8  International Edition: 978-0-8089-2400-5 Copyright © 2011, 2006, 2000, 1996, 1991, 1986, 1981, 1976, 1966, 1961, 1956 by Saunders, an imprint of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/permissions. Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment, and drug therapy may become necessary or ­appropriate. Readers are advised to check the most current information provided (i) on procedures ­featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on his or her experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Author assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book. The Publisher Library of Congress Cataloging-in-Publication Data Hall, John E. (John Edward), 1946- Guyton and Hall textbook of medical physiology / John Hall. – 12th ed.    p. ; cm. Rev. ed. of: Textbook of medical physiology. 11th ed. c2006. Includes bibliographical references and index. ISBN 978-1-4160-4574-8 (alk. paper) 1. Human physiology. 2. Physiology, Pathological. I. Guyton, Arthur C. II. Textbook of medical physiology. III. Title. IV. Title: Textbook of medical physiology. [DNLM: 1. Physiological Phenomena. QT 104 H1767g 2011] QP34.5.G9 2011 612–dc22 2009035327 Publishing Director: William Schmitt Developmental Editor: Rebecca Gruliow Editorial Assistant: Laura Stingelin Publishing Services Manager: Linda Van Pelt Project Manager: Frank Morales Design Manager: Steve Stave Illustrator: Michael Schenk Marketing Manager: Marla Lieberman Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1  To My Family For their abundant support, for their patience and understanding, and for their love To Arthur C. Guyton For his imaginative and innovative research For his dedication to education For showing us the excitement and joy of physiology And for serving as an inspirational role model This page intentionally left blank  Preface The first edition of the Textbook of Medical Physiology I have attempted to maintain the same unified orga- was written by Arthur C. Guyton almost 55 years ago. nization of the text that has been useful to students in Unlike most major medical textbooks, which often have the past and to ensure that the book is comprehensive 20 or more authors, the first eight editions of the Textbook enough that students will continue to use it during their of Medical Physiology were written entirely by Dr. Guyton, ­professional careers. with each new edition arriving on schedule for nearly 40 My hope is that this textbook conveys the majesty of years. The Textbook of Medical Physiology, first published the human body and its many functions and that it stim- in 1956, quickly became the best-selling medical physi- ulates students to study physiology throughout their ology textbook in the world. Dr. Guyton had a gift for careers. Physiology is the link between the basic sciences communicating complex ideas in a clear and interesting and medicine. The great beauty of physiology is that it manner that made studying physiology fun. He wrote the integrates the individual functions of all the body’s differ- book to help students learn physiology, not to impress his ent cells, tissues, and organs into a functional whole, the professional colleagues. human body. Indeed, the human body is much more than I worked closely with Dr. Guyton for almost 30 years the sum of its parts, and life relies upon this total function, and had the privilege of writing parts of the 9th and 10th not just on the function of individual body parts in isola- editions. After Dr. Guyton’s tragic death in an automobile tion from the others. accident in 2003, I assumed responsibility for completing This brings us to an important question: How are the the 11th edition. separate organs and systems coordinated to maintain For the 12th edition of the Textbook of Medical proper function of the entire body? Fortunately, our bod- Physiology, I have the same goal as for previous editions— ies are endowed with a vast network of feedback con- to explain, in language easily understood by students, how trols that achieve the necessary balances without which the different cells, tissues, and organs of the human body we would be unable to live. Physiologists call this high work together to maintain life. level of internal bodily control homeostasis. In disease This task has been challenging and fun because our states, functional balances are often seriously disturbed rapidly increasing knowledge of physiology continues to and homeostasis is impaired. When even a single distur- unravel new mysteries of body functions. Advances in bance reaches a limit, the whole body can no longer live. molecular and cellular physiology have made it possi- One of the goals of this text, therefore, is to emphasize the ble to explain many physiology principles in the termi- effectiveness and beauty of the body’s homeostasis mech- nology of molecular and physical sciences rather than anisms as well as to present their abnormal functions in in merely a series of separate and unexplained biological disease. phenomena. Another objective is to be as accurate as possible. The Textbook of Medical Physiology, however, is not Suggestions and critiques from many students, physi- a reference book that attempts to provide a compen- ologists, and clinicians throughout the world have been dium of the most recent advances in physiology. This is sought and then used to check factual accuracy as well as a book that continues the tradition of being written for balance in the text. Even so, because of the likelihood of students. It focuses on the basic principles of physiol- error in sorting through many thousands of bits of infor- ogy needed to begin a career in the health care profes- mation, I wish to issue a further request to all readers to sions, such as medicine, dentistry and nursing, as well send along notations of error or inaccuracy. Physiologists as graduate studies in the biological and health sciences. understand the importance of feedback for proper func- It should also be useful to physicians and health care tion of the human body; so, too, is feedback important for professionals who wish to review the basic ­principles progressive improvement of a textbook of physiology. To needed for understanding the pathophysiology of the many persons who have already helped, I express sin- human disease. cere thanks. vii Preface A brief explanation is needed about several features of needed for immediate discussion but that most students the 12th edition. Although many of the chapters have been will learn in more detail in other courses; second, physi- revised to include new principles of physiology, the text ologic information of special importance to certain fields length has been closely monitored to limit the book size of clinical medicine; and, third, information that will be of so that it can be used effectively in physiology courses for value to those students who may wish to study particular medical students and health care professionals. Many of the physiologic mechanisms more deeply. figures have also been redrawn and are in full color. New ref- I wish to express sincere thanks to many ­persons who erences have been chosen primarily for their ­presentation have helped to prepare this book, including my ­colleagues of physiologic principles, for the quality of their own refer- in the Department of Physiology and Biophysics at the ences, and for their easy accessibility. The selected biblio­ University of Mississippi Medical Center who provided graphy at the end of the chapters lists papers mainly from valuable suggestions. The members of our faculty and a recently published scientific journals that can be freely brief description of the research and educational activi- accessed from the PubMed internet site at http://www. ties of the department can be found at the web site: http:// ncbi.nlm.nih.gov/sites/entrez/. Use of these references, as physiology.umc.edu/. I am also grateful to Stephanie well as cross-references from them, can give the student Lucas and Courtney Horton Graham for their excellent almost complete coverage of the entire field of physiology. secretarial services, to Michael Schenk and Walter (Kyle) The effort to be as concise as possible has, unfortunately, Cunningham for their expert artwork, and to William necessitated a more simplified and dogmatic presentation Schmitt, Rebecca Gruliow, Frank Morales, and the entire of many physiologic principles than I normally would have Elsevier Saunders team for continued editorial and desired. However, the bibliography can be used to learn ­production excellence. more about the controversies and unanswered questions Finally, I owe an enormous debt to Arthur Guyton that remain in understanding the ­complex functions of the for the great privilege of contributing to the Textbook of human body in health and disease. Medical Physiology, for an exciting career in physiology, Another feature is that the print is set in two sizes. The for his friendship, and for the inspiration that he provided material in large print constitutes the fundamental physi- to all who knew him. ologic information that students will require in virtually all of their medical activities and studies. John E. Hall The material in small print is of several different kinds: first, anatomic, chemical, and other information that is viii  Contents UNIT I Apoptosis—Programmed Cell Death 40 Introduction to Physiology: The Cell and Cancer 40 General Physiology UNIT II CHAPTER 1 Membrane Physiology, Nerve, and Muscle Functional Organization of the Human Body and Control of the “Internal Environment” 3 CHAPTER 4 Cells as the Living Units of the Body 3 Transport of Substances Through Cell Extracellular Fluid—The “Internal Membranes 45 Environment” 3 The Lipid Barrier of the Cell Membrane, “Homeostatic” Mechanisms of the Major and Cell Membrane Transport Proteins 45 Functional Systems 4 Diffusion 46 Control Systems of the Body 6 “Active Transport” of Substances Through Summary—Automaticity of the Body 9 Membranes 52 CHAPTER 2 CHAPTER 5 The Cell and Its Functions 11 Membrane Potentials and Action Potentials 57 Organization of the Cell 11 Basic Physics of Membrane Potentials 57 Physical Structure of the Cell 12 Measuring the Membrane Potential 58 Comparison of the Animal Cell with Resting Membrane Potential of Nerves 59 Precellular Forms of Life 17 Nerve Action Potential 60 Functional Systems of the Cell 18 Roles of Other Ions During the Action Locomotion of Cells 23 Potential 64 Propagation of the Action Potential 64 CHAPTER 3 Re-establishing Sodium and Potassium Genetic Control of Protein Synthesis, Cell Ionic Gradients After Action Potentials Are Function, and Cell Reproduction 27 Completed—Importance of Energy Genes in the Cell Nucleus 27 Metabolism 65 The DNA Code in the Cell Nucleus Is Plateau in Some Action Potentials 66 Transferred to an RNA Code in the Cell Rhythmicity of Some Excitable Tissues— Cytoplasm—The Process of Transcription 30 Repetitive Discharge 66 Synthesis of Other Substances in the Cell 35 Special Characteristics of Signal Transmission Control of Gene Function and Biochemical in Nerve Trunks 67 Activity in Cells 35 Excitation—The Process of Eliciting the The DNA-Genetic System Also Controls Cell Action Potential 68 Reproduction 37 Recording Membrane Potentials and Cell Differentiation 39 Action Potentials 69 ix Contents CHAPTER 6 CHAPTER 11 Contraction of Skeletal Muscle 71 The Normal Electrocardiogram 121 Physiologic Anatomy of Skeletal Muscle 71 Characteristics of the Normal General Mechanism of Muscle Contraction 73 Electrocardiogram 121 Molecular Mechanism of Muscle Contraction 74 Methods for Recording Electrocardiograms 123 Energetics of Muscle Contraction 78 Flow of Current Around the Heart Characteristics of Whole Muscle during the Cardiac Cycle 123 Contraction 79 Electrocardiographic Leads 124 CHAPTER 7 CHAPTER 12 Excitation of Skeletal Muscle: Electrocardiographic Interpretation of Neuromuscular Transmission and Cardiac Muscle and Coronary Blood Flow Excitation-Contraction Coupling 83 Abnormalities: Vectorial Analysis 129 Transmission of Impulses from Nerve Endings Principles of Vectorial Analysis of to Skeletal Muscle Fibers: The Neuromuscular Electrocardiograms 129 Junction 83 Vectorial Analysis of the Normal Molecular Biology of Acetylcholine Formation Electrocardiogram 131 and Release 86 Mean Electrical Axis of the Ventricular Drugs That Enhance or Block Transmission QRS—and Its Significance 134 at the Neuromuscular Junction 86 Conditions That Cause Abnormal Voltages Myasthenia Gravis Causes Muscle Paralysis 86 of the QRS Complex 137 Muscle Action Potential 87 Prolonged and Bizarre Patterns of the QRS Excitation-Contraction Coupling 88 Complex 137 Current of Injury 138 CHAPTER 8 Abnormalities in the T Wave 141 Excitation and Contraction of Smooth Muscle 91 Contraction of Smooth Muscle 91 CHAPTER 13 Nervous and Hormonal Control of Smooth Cardiac Arrhythmias and Their Muscle Contraction 94 Electrocardiographic Interpretation 143 Abnormal Sinus Rhythms 143 UNIT III Abnormal Rhythms That Result from Block The Heart of Heart Signals Within the Intracardiac Conduction Pathways 144 CHAPTER 9 Premature Contractions 146 Cardiac Muscle; The Heart as a Pump and Paroxysmal Tachycardia 148 Function of the Heart Valves 101 Ventricular Fibrillation 149 Physiology of Cardiac Muscle 101 Atrial Fibrillation 151 Cardiac Cycle 104 Atrial Flutter 152 Relationship of the Heart Sounds to Heart Cardiac Arrest 153 Pumping 107 Work Output of the Heart 107 UNIT IV Chemical Energy Required for Cardiac Contraction: The Circulation Oxygen Utilization by the Heart 109 Regulation of Heart Pumping 110 CHAPTER 14 CHAPTER 10 Overview of the Circulation; Biophysics of Rhythmical Excitation of the Heart 115 Pressure, Flow, and Resistance 157 Specialized Excitatory and Conductive System Physical Characteristics of the Circulation 157 of the Heart 115 Basic Principles of Circulatory Function 158 Control of Excitation and Conduction in the Interrelationships of Pressure, Flow, and Heart 118 Resistance 159 x  Contents CHAPTER 15 CHAPTER 20 Vascular Distensibility and Functions of the Cardiac Output, Venous Return, Arterial and Venous Systems 167 and Their Regulation 229 Vascular Distensibility 167 Normal Values for Cardiac Output at Rest Arterial Pressure Pulsations 168 and During Activity 229 Veins and Their Functions 171 Control of Cardiac Output by Venous Return—Role of the Frank-Starling Mechanism CHAPTER 16 of the Heart 229 The Microcirculation and Lymphatic Pathologically High or Low Cardiac Outputs 232 System: Capillary Fluid Exchange, Methods for Measuring Cardiac Interstitial Fluid, and Lymph Flow 177 Output 240 Structure of the Microcirculation and Capillary System 177 CHAPTER 21 Flow of Blood in the Capillaries— Muscle Blood Flow and Cardiac Output Vasomotion 178 During Exercise; the Coronary Circulation and Ischemic Heart Disease 243 Exchange of Water, Nutrients, and Other Substances Between the Blood and Blood Flow Regulation in Skeletal Muscle Interstitial Fluid 179 at Rest and During Exercise 243 Interstitium and Interstitial Fluid 180 Coronary Circulation 246 Fluid Filtration Across Capillaries Is CHAPTER 22 Determined by Hydrostatic and Colloid Osmotic Pressures, as Well as Capillary Cardiac Failure 255 Filtration Coefficient 181 Circulatory Dynamics in Cardiac Failure 255 Lymphatic System 186 Unilateral Left Heart Failure 259 Low-Output Cardiac Failure— CHAPTER 17 Cardiogenic Shock 259 Local and Humoral Control of Tissue Edema in Patients with Cardiac Failure 259 Blood Flow 191 Cardiac Reserve 261 Local Control of Blood Flow in Response to Tissue Needs 191 CHAPTER 23 Mechanisms of Blood Flow Control 191 Heart Valves and Heart Sounds; Humoral Control of the Circulation 199 Valvular and Congenital Heart Defects 265 CHAPTER 18 Heart Sounds 265 Nervous Regulation of the Circulation, Abnormal Circulatory Dynamics in Valvular and Rapid Control of Arterial Pressure 201 Heart Disease 268 Nervous Regulation of the Circulation 201 Abnormal Circulatory Dynamics Role of the Nervous System in Rapid in Congenital Heart Defects 269 Control of Arterial Pressure 204 Use of Extracorporeal Circulation During Special Features of Nervous Control Cardiac Surgery 271 of Arterial Pressure 209 Hypertrophy of the Heart in Valvular CHAPTER 19 and Congenital Heart Disease 272 Role of the Kidneys in Long-Term Control of CHAPTER 24 Arterial Pressure and in Hypertension: The Circulatory Shock and Its Treatment 273 Integrated System for Arterial Pressure Regulation 213 Physiologic Causes of Shock 273 Renal–Body Fluid System for Arterial Shock Caused by Hypovolemia— Pressure Control 213 Hemorrhagic Shock 274 The Renin-Angiotensin System: Its Role Neurogenic Shock—Increased Vascular in Arterial Pressure Control 220 Capacity 279 Summary of the Integrated, Multifaceted Anaphylactic Shock and Histamine Shock 280 System for Arterial Pressure Regulation 226 Septic Shock 280 xi Contents Physiology of Treatment in Shock 280 Abnormalities of Micturition 310 Circulatory Arrest 281 Urine Formation Results from Glomerular Filtration, Tubular Reabsorption, and Tubular UNIT V Secretion 310 The Body Fluids and Kidneys Glomerular Filtration—The First Step in Urine Formation 312 CHAPTER 25 Determinants of the GFR 314 The Body Fluid Compartments: Extracellular Renal Blood Flow 316 and Intracellular Fluids; Edema 285 Physiologic Control of Glomerular Filtration Fluid Intake and Output Are Balanced and Renal Blood Flow 317 During Steady-State Conditions 285 Autoregulation of GFR and Renal Blood Flow 319 Body Fluid Compartments 286 CHAPTER 27 Extracellular Fluid Compartment 287 Urine Formation by the Kidneys: II. Tubular Blood Volume 287 Reabsorption and Secretion 323 Constituents of Extracellular and Intracellular Renal Tubular Reabsorption and Secretion 323 Fluids 287 Tubular Reabsorption Includes Passive Measurement of Fluid Volumes in the Different and Active Mechanisms 323 Body Fluid Compartments—the Indicator- Reabsorption and Secretion Along Different Dilution Principle 287 Parts of the Nephron 329 Determination of Volumes of Specific Body Regulation of Tubular Reabsorption 334 Fluid Compartments 289 Use of Clearance Methods to Quantify Kidney Regulation of Fluid Exchange and Osmotic Function 340 Equilibrium Between Intracellular and Extracellular Fluid 290 CHAPTER 28 Basic Principles of Osmosis and Osmotic Urine Concentration and Dilution; Regulation Pressure 290 of Extracellular Fluid Osmolarity and Sodium Osmotic Equilibrium Is Maintained Between Concentration 345 Intracellular and Extracellular Fluids 291 Kidneys Excrete Excess Water by Forming Volume and Osmolality of Extracellular Dilute Urine 345 and Intracellular Fluids in Abnormal States 292 Kidneys Conserve Water by Excreting Glucose and Other Solutions Administered Concentrated Urine 346 for Nutritive Purposes 294 Quantifying Renal Urine Concentration Clinical Abnormalities of Fluid Volume and Dilution: “Free Water” and Osmolar Regulation: Hyponatremia and Hypernatremia 294 Clearances 354 Edema: Excess Fluid in the Tissues 296 Disorders of Urinary Concentrating Ability 354 Fluids in the “Potential Spaces” of the Body 300 Control of Extracellular Fluid Osmolarity and Sodium Concentration 355 Osmoreceptor-ADH Feedback System 355 CHAPTER 26 Importance of Thirst in Controlling Urine Formation by the Kidneys: Extracellular Fluid Osmolarity and Sodium I. Glomerular Filtration, Renal Blood Flow, Concentration 357 and Their Control 303 Salt-Appetite Mechanism for Controlling Multiple Functions of the Kidneys 303 Extracellular Fluid Sodium Concentration and Physiologic Anatomy of the Kidneys 304 Volume 360 Micturition 307 CHAPTER 29 Physiologic Anatomy of the Bladder 307 Renal Regulation of Potassium, Calcium, Transport of Urine from the Kidney Through Phosphate, and Magnesium; Integration the Ureters and into the Bladder 308 of Renal Mechanisms for Control of Blood Filling of the Bladder and Bladder Wall Tone; Volume and Extracellular Fluid Volume 361 the Cystometrogram 309 Regulation of Extracellular Fluid Potassium Micturition Reflex 309 Concentration and Potassium Excretion 361 xii  Contents Control of Renal Calcium Excretion CHAPTER 31 and Extracellular Calcium Ion Concentration 367 Diuretics, Kidney Diseases 397 Control of Renal Magnesium Excretion and Diuretics and Their Mechanisms of Action 397 Extracellular Magnesium Ion Concentration 369 Kidney Diseases 399 Integration of Renal Mechanisms for Control Acute Renal Failure 399 of Extracellular Fluid 370 Chronic Renal Failure: An Irreversible Decrease Importance of Pressure Natriuresis and in the Number of Functional Nephrons 401 Pressure Diuresis in Maintaining Body Sodium and Fluid Balance 371 Specific Tubular Disorders 408 Distribution of Extracellular Fluid Treatment of Renal Failure by Transplantation Between the Interstitial Spaces and or by Dialysis with an Artificial Kidney 409 Vascular System 373 Nervous and Hormonal Factors Increase the UNIT VI Effectiveness of Renal–Body Fluid Feedback Blood Cells, Immunity, and Blood Control 373 Coagulation Integrated Responses to Changes in Sodium Intake 376 CHAPTER 32 Conditions That Cause Large Increases in Red Blood Cells, Anemia, and Polycythemia 413 Blood Volume and Extracellular Fluid Volume 376 Red Blood Cells (Erythrocytes) 413 Conditions That Cause Large Increases in Extracellular Fluid Volume but with Normal Anemias 420 Blood Volume 377 Polycythemia 421 CHAPTER 30 CHAPTER 33 Acid-Base Regulation 379 Resistance of the Body to Infection: H+ Concentration Is Precisely Regulated 379 I. Leukocytes, Granulocytes, the Monocyte- Macrophage System, and Inflammation 423 Acids and Bases—Their Definitions and Meanings 379 Leukocytes (White Blood Cells) 423 Defending Against Changes in H+ Neutrophils and Macrophages Defend Concentration: Buffers, Lungs, and Kidneys 380 Against Infections 425 Buffering of H+ in the Body Fluids 380 Monocyte-Macrophage Cell System (Reticuloendothelial System) 426 Bicarbonate Buffer System 381 Inflammation: Role of Neutrophils Phosphate Buffer System 383 and Macrophages 428 Proteins Are Important Intracellular Buffers 383 Eosinophils 430 Respiratory Regulation of Acid-Base Balance 384 Basophils 431 Renal Control of Acid-Base Balance 385 Leukopenia 431 Secretion of H+ and Reabsorption of HCO3− Leukemias 431 by the Renal Tubules 386 Combination of Excess H+ with Phosphate CHAPTER 34 and Ammonia Buffers in the Tubule Generates Resistance of the Body to Infection: “New” HCO3− 388 II. Immunity and Allergy Innate Immunity 433 Quantifying Renal Acid-Base Excretion 389 Acquired (Adaptive) Immunity 433 Renal Correction of Acidosis—Increased Allergy and Hypersensitivity 443 Excretion of H+ and Addition of HCO3− to the Extracellular Fluid 391 CHAPTER 35 Renal Correction of Alkalosis—Decreased Blood Types; Transfusion; Tissue and Organ Tubular Secretion of H+ and Increased Transplantation 445 Excretion of HCO3− 391 Antigenicity Causes Immune Reactions of Clinical Causes of Acid-Base Disorders 392 Blood 445 Treatment of Acidosis or Alkalosis 393 O-A-B Blood Types 445 Clinical Measurements and Analysis of Rh Blood Types 447 Acid-Base Disorders 393 Transplantation of Tissues and Organs 449 xiii Contents CHAPTER 36 CHAPTER 40 Hemostasis and Blood Coagulation 451 Transport of Oxygen and Carbon Dioxide in Events in Hemostasis 451 Blood and Tissue Fluids 495 Vascular Constriction 451 Transport of Oxygen from the Lungs to the Mechanism of Blood Coagulation 453 Body Tissues 495 Conditions That Cause Excessive Bleeding in Transport of Carbon Dioxide in the Blood 502 Humans 457 Respiratory Exchange Ratio 504 Thromboembolic Conditions in the CHAPTER 41 Human Being 459 Regulation of Respiration 505 Anticoagulants for Clinical Use 459 Respiratory Center 505 Blood Coagulation Tests 460 Chemical Control of Respiration 507 Peripheral Chemoreceptor System for Control UNIT VII of Respiratory Activity—Role of Oxygen in Respiration Respiratory Control 508 Regulation of Respiration During Exercise 510 CHAPTER 37 Other Factors That Affect Respiration 512 Pulmonary Ventilation 465 CHAPTER 42 Mechanics of Pulmonary Ventilation 465 Respiratory Insufficiency—Pathophysiology, Pulmonary Volumes and Capacities 469 Diagnosis, Oxygen Therapy 515 Minute Respiratory Volume Equals Respiratory Useful Methods for Studying Respiratory Rate Times Tidal Volume 471 Abnormalities 515 Alveolar Ventilation 471 Pathophysiology of Specific Pulmonary Functions of the Respiratory Passageways 472 Abnormalities 517 Hypoxia and Oxygen Therapy 520 CHAPTER 38 Hypercapnia—Excess Carbon Dioxide in the Pulmonary Circulation, Pulmonary Edema, Body Fluids 522 Pleural Fluid 477 Artificial Respiration 522 Physiologic Anatomy of the Pulmonary Circulatory System 477 UNIT VIII Pressures in the Pulmonary System 477 Aviation, Space, and Deep-Sea Diving Blood Volume of the Lungs 478 Physiology Blood Flow Through the Lungs and Its Distribution 479 CHAPTER 43 Effect of Hydrostatic Pressure Gradients in Aviation, High-Altitude, and the Lungs on Regional Pulmonary Blood Flow 479 Space Physiology 527 Pulmonary Capillary Dynamics 481 Effects of Low Oxygen Pressure on the Body 527 Fluid in the Pleural Cavity 483 Effects of Acceleratory Forces on the Body in Aviation and Space Physiology 531 CHAPTER 39 “Artificial Climate” in the Sealed Spacecraft 533 Physical Principles of Gas Exchange; Weightlessness in Space 533 Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane 485 CHAPTER 44 Physics of Gas Diffusion and Gas Physiology of Deep-Sea Diving and Partial Pressures 485 Other Hyperbaric Conditions 535 Compositions of Alveolar Air and Atmospheric Effect of High Partial Pressures of Individual Air Are Different 487 Gases on the Body 535 Diffusion of Gases Through the Respiratory Scuba (Self-Contained Underwater Breathing Membrane 489 Apparatus) Diving 539 Effect of the Ventilation-Perfusion Ratio on Special Physiologic Problems in Submarines 540 Alveolar Gas Concentration 492 Hyperbaric Oxygen Therapy 540 xiv  Contents UNIT IX Pain Receptors and Their Stimulation 583 The Nervous System: A. General Principles Dual Pathways for Transmission of Pain and Sensory Physiology Signals into the Central Nervous System 584 Pain Suppression (“Analgesia”) System in the CHAPTER 45 Brain and Spinal Cord 586 Organization of the Nervous System, Basic Referred Pain 588 Functions of Synapses, and Visceral Pain 588 Neurotransmitters 543 Some Clinical Abnormalities of Pain General Design of the Nervous System 543 and Other Somatic Sensations 590 Major Levels of Central Nervous System Headache 590 Function 545 Thermal Sensations 592 Comparison of the Nervous System with a Computer 546 UNIT X Central Nervous System Synapses 546 Some Special Characteristics of Synaptic The Nervous System: B. The Special Senses Transmission 557 CHAPTER 49 CHAPTER 46 The Eye: I. Optics of Vision 597 Sensory Receptors, Neuronal Circuits for Physical Principles of Optics 597 Processing Information 559 Optics of the Eye 600 Types of Sensory Receptors and the Stimuli They Detect 559 Ophthalmoscope 605 Transduction of Sensory Fluid System of the Eye—Intraocular Fluid 606 Stimuli into Nerve Impulses 560 CHAPTER 50 Nerve Fibers That Transmit Different Types of The Eye: II. Receptor and Neural Function Signals and Their Physiologic Classification 563 of the Retina 609 Transmission of Signals of Different Intensity Anatomy and Function of the Structural in Nerve Tracts—Spatial and Temporal Elements of the Retina 609 Summation 564 Photochemistry of Vision 611 Transmission and Processing of Signals in Neuronal Pools 564 Color Vision 615 Instability and Stability of Neuronal Circuits 569 Neural Function of the Retina 616 CHAPTER 47 CHAPTER 51 Somatic Sensations: I. General Organization, The Eye: III. Central Neurophysiology the Tactile and Position Senses 571 of Vision 623 Classification of Somatic Senses 571 Visual Pathways 623 Detection and Transmission of Tactile Organization and Function of the Visual Sensations 571 Cortex 624 Sensory Pathways for Transmitting Somatic Neuronal Patterns of Stimulation During Signals into the Central Nervous System 573 Analysis of the Visual Image 626 Transmission in the Dorsal Column–Medial Fields of Vision; Perimetry 627 Lemniscal System 573 Eye Movements and Their Control 627 Transmission of Less Critical Sensory Signals Autonomic Control of Accommodation in the Anterolateral Pathway 580 and Pupillary Aperture 631 Some Special Aspects of Somatosensory Function 581 CHAPTER 52 CHAPTER 48 The Sense of Hearing 633 Tympanic Membrane and the Ossicular System 633 Somatic Sensations: II. Pain, Headache, and Thermal Sensations 583 Cochlea 634 Types of Pain and Their Qualities—Fast Pain Central Auditory Mechanisms 639 and Slow Pain 583 Hearing Abnormalities 642 xv Contents CHAPTER 53 Function of the Brain in Communication— The Chemical Senses—Taste and Smell 645 Language Input and Language Output 703 Sense of Taste 645 Function of the Corpus Callosum and Anterior Commissure to Transfer Thoughts, Memories, Sense of Smell 648 Training, and Other Information Between the Two Cerebral Hemispheres 704 UNIT XI Thoughts, Consciousness, and Memory 705 The Nervous System: C. Motor and CHAPTER 58 Integrative Neurophysiology Behavioral and Motivational Mechanisms of the Brain—The Limbic System and the CHAPTER 54 Hypothalamus 711 Motor Functions of the Spinal Cord; the Cord Activating-Driving Systems Reflexes 655 of the Brain 711 Organization of the Spinal Cord for Motor Limbic System 714 Functions 655 Functional Anatomy of the Limbic System; Key Muscle Sensory Receptors—Muscle Spindles Position of the Hypothalamus 714 and Golgi Tendon Organs—And Their Roles in Muscle Control 657 Hypothalamus, a Major Control Headquarters for the Limbic System 715 Flexor Reflex and the Withdrawal Reflexes 661 Specific Functions of Other Parts of the Limbic Crossed Extensor Reflex 663 System 718 Reciprocal Inhibition and Reciprocal Innervation 663 CHAPTER 59 Reflexes of Posture and Locomotion 663 States of Brain Activity—Sleep, Brain Waves, Scratch Reflex 664 Epilepsy, Psychoses 721 Spinal Cord Reflexes That Cause Muscle Spasm 664 Sleep 721 Autonomic Reflexes in the Spinal Cord 665 Epilepsy 725 Spinal Cord Transection and Spinal Shock 665 Psychotic Behavior and Dementia—Roles CHAPTER 55 of Specific Neurotransmitter Systems 726 Cortical and Brain Stem Control of Motor Schizophrenia—Possible Exaggerated Function 667 Function of Part of the Dopamine System 727 Motor Cortex and Corticospinal Tract 667 CHAPTER 60 Role of the Brain Stem in Controlling Motor The Autonomic Nervous System and the Function 673 Adrenal Medulla 729 Vestibular Sensations and Maintenance of General Organization of the Autonomic Equilibrium 674 Nervous System 729 Functions of Brain Stem Nuclei in Controlling Basic Characteristics of Sympathetic and Subconscious, Stereotyped Movements 678 Parasympathetic Function 731 Autonomic Reflexes 738 CHAPTER 56 Stimulation of Discrete Organs in Some Contributions of the Cerebellum and Basal Instances and Mass Stimulation in Other Ganglia to Overall Motor Control 681 Instances by the Sympathetic and Cerebellum and Its Motor Functions 681 Parasympathetic Systems 738 Basal Ganglia—Their Motor Functions 689 Pharmacology of the Autonomic Nervous Integration of the Many Parts of the Total System 739 Motor Control System 694 CHAPTER 61 CHAPTER 57 Cerebral Blood Flow, Cerebrospinal Fluid, Cerebral Cortex, Intellectual Functions of the and Brain Metabolism 743 Brain, Learning, and Memory 697 Cerebral Blood Flow 743 Physiologic Anatomy of the Cerebral Cortex 697 Cerebrospinal Fluid System 746 Functions of Specific Cortical Areas 698 Brain Metabolism 749 xvi  Contents UNIT XII Disorders of the Stomach 799 Gastrointestinal Physiology Disorders of the Small Intestine 801 Disorders of the Large Intestine 802 CHAPTER 62 General Disorders of the Gastrointestinal General Principles of Gastrointestinal Tract 803 Function—Motility, Nervous Control, and Blood Circulation 753 UNIT XIII General Principles of Gastrointestinal Motility 753 Metabolism and Temperature Regulation Neural Control of Gastrointestinal Function— Enteric Nervous System 755 CHAPTER 67 Functional Types of Movements in the Metabolism of Carbohydrates, and Formation Gastrointestinal Tract 759 of Adenosine Triphosphate 809 Gastrointestinal Blood Flow—“Splanchnic Central Role of Glucose in Carbohydrate Circulation” 759 Metabolism 810 Transport of Glucose Through the Cell CHAPTER 63 Membrane 810 Propulsion and Mixing of Food in the Glycogen Is Stored in Liver and Muscle 811 Alimentary Tract 763 Release of Energy from Glucose by the Ingestion of Food 763 Glycolytic Pathway 812 Motor Functions of the Stomach 765 Release of Energy from Glucose by the Movements of the Small Intestine 768 Pentose Phosphate Pathway 816 Movements of the Colon 770 Formation of Carbohydrates from Proteins Other Autonomic Reflexes That Affect Bowel and Fats—“Gluconeogenesis” 817 Activity 772 Blood Glucose 817 CHAPTER 64 CHAPTER 68 Secretory Functions of the Alimentary Tract 773 Lipid Metabolism 819 General Principles of Alimentary Tract Transport of Lipids in the Body Fluids 819 Secretion 773 Fat Deposits 821 Secretion of Saliva 775 Use of Triglycerides for Energy: Formation of Esophageal Secretion 776 Adenosine Triphosphate 822 Gastric Secretion 777 Regulation of Energy Release from Pancreatic Secretion 780 Triglycerides 825 Secretion of Bile by the Liver; Functions of the Phospholipids and Cholesterol 826 Biliary Tree 783 Atherosclerosis 827 Secretions of the Small Intestine 786 CHAPTER 69 Secretion of Mucus by the Large Intestine 787 Protein Metabolism 831 CHAPTER 65 Basic Properties 831 Digestion and Absorption in the Transport and Storage of Amino Acids 831 Gastrointestinal Tract 789 Functional Roles of the Plasma Proteins 833 Digestion of the Various Foods by Hydrolysis 789 Hormonal Regulation of Protein Metabolism 835 Basic Principles of Gastrointestinal Absorption 793 CHAPTER 70 Absorption in the Small Intestine 794 The Liver as an Organ 837 Absorption in the Large Intestine: Formation of Feces 797 Physiologic Anatomy of the Liver 837 Hepatic Vascular and Lymph Systems 837 CHAPTER 66 Metabolic Functions of the Liver 839 Physiology of Gastrointestinal Disorders 799 Measurement of Bilirubin in the Bile as a Disorders of Swallowing and of the Esophagus 799 Clinical Diagnostic Tool 840 xvii Contents CHAPTER 71 CHAPTER 75 Dietary Balances; Regulation of Feeding; Pituitary Hormones and Their Control by the Obesity and Starvation; Vitamins and Hypothalamus 895 Minerals 843 Pituitary Gland and Its Relation to the Energy Intake and Output Are Balanced Under Hypothalamus 895 Steady-State Conditions 843 Hypothalamus Controls Pituitary Secretion 897 Dietary Balances 843 Physiological Functions of Growth Hormone 898 Regulation of Food Intake and Energy Posterior Pituitary Gland and Its Relation to Storage 845 the Hypothalamus 904 Obesity 850 CHAPTER 76 Inanition, Anorexia, and Cachexia 851 Thyroid Metabolic Hormones 907 Starvation 852 Synthesis and Secretion of the Thyroid Vitamins 852 Metabolic Hormones 907 Mineral Metabolism 855 Physiological Functions of the Thyroid CHAPTER 72 Hormones 910 Energetics and Metabolic Rate 859 Regulation of Thyroid Hormone Secretion 914 Adenosine Triphosphate (ATP) Functions as Diseases of the Thyroid 916 an “Energy Currency” in Metabolism 859 CHAPTER 77 Control of Energy Release in the Cell 861 Adrenocortical Hormones 921 Metabolic Rate 862 Synthesis and Secretion of Adrenocortical Energy Metabolism—Factors That Influence Hormones 921 Energy Output 863 Functions of the Mineralocorticoids— CHAPTER 73 Aldosterone 924 Body Temperature Regulation, Functions of the Glucocorticoids 928 and Fever 867 Adrenal Androgens 934 Normal Body Temperatures 867 Abnormalities of Adrenocortical Secretion 934 Body Temperature Is Controlled by CHAPTER 78 Balancing Heat Production and Heat Loss 867 Insulin, Glucagon, and Diabetes Mellitus 939 Regulation of Body Temperature— Insulin and Its Metabolic Effects 939 Role of the Hypothalamus 871 Glucagon and Its Functions 947 Abnormalities of Body Temperature Somatostatin Inhibits Glucagon and Insulin Regulation 875 Secretion 949 Summary of Blood Glucose Regulation 949 Diabetes Mellitus 950 UNIT XIV CHAPTER 79 Endocrinology and Reproduction Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, CHAPTER 74 and Teeth 955 Introduction to Endocrinology 881 Overview of Calcium and Coordination of Body Functions by Chemical Phosphate Regulation in the Extracellular Messengers 881 Fluid and Plasma 955 Chemical Structure and Synthesis of Bone and Its Relation to Extracellular Calcium Hormones 881 and Phosphate 957 Hormone Secretion, Transport, and Clearance Vitamin D 960 from the Blood 884 Parathyroid Hormone 962 Mechanisms of Action of Hormones 886 Calcitonin 966 Measurement of Hormone Concentrations Summary of Control of Calcium Ion in the Blood 891 Concentration 966 xviii  Contents Pathophysiology of Parathyroid Hormone, Function of the Placenta 1005 Vitamin D, and Bone Disease 967 Hormonal Factors in Pregnancy 1007 Physiology of the Teeth 969 Response of the Mother’s Body to Pregnancy 1009 CHAPTER 80 Parturition 1011 Reproductive and Hormonal Functions of Lactation 1014 the Male (and Function of the Pineal Gland) 973 CHAPTER 83 Physiologic Anatomy of the Male Sexual Fetal and Neonatal Physiology 1019 Organs 973 Growth and Functional Development of the Spermatogenesis 973 Fetus 1019 Male Sexual Act 978 Development of the Organ Systems 1019 Testosterone and Other Male Sex Hormones 979 Adjustments of the Infant to Extrauterine Life 1021 Abnormalities of Male Sexual Function 984 Special Functional Problems in the Neonate 1023 Erectile Dysfunction in the Male 985 Special Problems of Prematurity 1026 Pineal Gland—Its Function in Controlling Growth and Development of the Child 1027 Seasonal Fertility in Some Animals 986 CHAPTER 81 UNIT XV Female Physiology Before Pregnancy and Sports Physiology Female Hormones 987 Physiologic Anatomy of the Female Sexual CHAPTER 84 Organs 987 Sports Physiology 1031 Female Hormonal System 987 Muscles in Exercise 1031 Monthly Ovarian Cycle; Function of the Respiration in Exercise 1036 Gonadotropic Hormones 988 Cardiovascular System in Exercise 1038 Functions of the Ovarian Hormones— Estradiol and Progesterone 991 Body Heat in Exercise 1039 Regulation of the Female Monthly Body Fluids and Salt in Exercise 1040 Rhythm—Interplay Between the Ovarian Drugs and Athletes 1040 and Hypothalamic-Pituitary Hormones 996 Body Fitness Prolongs Life 1041 Abnormalities of Secretion by the Ovaries 999 Female Sexual Act 1000 Index 1043 Female Fertility 1000 CHAPTER 82 Pregnancy and Lactation 1003 Maturation and Fertilization of the Ovum 1003 Early Nutrition of the Embryo 1005 xix This page intentionally left blank  I Unit Introduction to Physiology: The Cell and General Physiology 1. Functional Organization of the Human Body and Control of the “Internal Environment” 2. The Cell and Its Functions 3. Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction This page intentionally left blank  chapter 1 Unit I Functional Organization of the Human Body and Control of the “Internal Environment” The goal of physiology is reacts with carbohydrate, fat, and protein to release the to explain the physical and energy required for cell function. Further, the general chemical factors that are chemical mechanisms for changing nutrients into energy responsible for the origin, are basically the same in all cells, and all cells deliver end development, and progres- products of their chemical reactions into the surround- sion of life. Each type of life, ing fluids. from the simple virus to Almost all cells also have the ability to reproduce addi- the largest tree or the complicated human being, has its tional cells of their own kind. Fortunately, when cells of own functional characteristics. Therefore, the vast field of a particular type are destroyed, the remaining cells of physiology can be divided into viral physiology, bacterial this type usually generate new cells until the supply is physiology, cellular physiology, plant physiology, human replenished. physiology, and many more subdivisions. Human Physiology. In human physiology, we Extracellular Fluid—The “Internal attempt to explain the specific characteristics and mech- Environment” anisms of the human body that make it a living being. The very fact that we remain alive is the result of com- About 60 percent of the adult human body is fluid, mainly plex control systems, for hunger makes us seek food and a water solution of ions and other substances. Although fear makes us seek refuge. Sensations of cold make us look most of this fluid is inside the cells and is called intracellu- for warmth. Other forces cause us to seek fellowship and lar fluid, about one third is in the spaces outside the cells to reproduce. Thus, the human being is, in many ways, and is called extracellular fluid. This extracellular fluid is like an automaton, and the fact that we are sensing, feel- in constant motion throughout the body. It is transported ing, and knowledgeable beings is part of this automatic rapidly in the circulating blood and then mixed between sequence of life; these special attributes allow us to exist the blood and the tissue fluids by diffusion through the under widely varying conditions. capillary walls. In the extracellular fluid are the ions and nutrients needed by the cells to maintain cell life. Thus, all cells live Cells as the Living Units of the Body in essentially the same environment—the extracellular fluid. For this reason, the extracellular fluid is also called The basic living unit of the body is the cell. Each organ is the internal environment of the body, or the milieu inté- an aggregate of many different cells held together by inter- rieur, a term introduced more than 100 years ago by the cellular supporting structures. great 19th-century French physiologist Claude Bernard. Each type of cell is specially adapted to perform one Cells are capable of living, growing, and performing or a few particular functions. For instance, the red blood their special functions as long as the proper concentra- cells, numbering 25 trillion in each human being, transport tions of oxygen, glucose, different ions, amino acids, fatty oxygen from the lungs to the tissues. Although the red cells substances, and other constituents are available in this are the most abundant of any single type of cell in the body, internal environment. there are about 75 trillion additional cells of other types that perform functions different from those of the red cell. Differences Between Extracellular and Intra­ The entire body, then, contains about 100 trillion cells. cellular Fluids. The extracellular fluid contains large Although the many cells of the body often differ mark- amounts of sodium, chloride, and bicarbonate ions plus edly from one another, all of them have certain basic char- nutrients for the cells, such as oxygen, glucose, fatty acids, acteristics that are alike. For instance, in all cells, oxygen and amino acids. It also contains carbon dioxide that is 3 Unit I Introduction to Physiology: The Cell and General Physiology being transported from the cells to the lungs to be excreted, Lungs plus other cellular waste products that are being trans- ported to the kidneys for excretion. The intracellular fluid differs significantly from the extracellular fluid; for example, it contains large amounts of potassium, magnesium, and phosphate ions instead of the sodium and chloride ions found in the extracellular O2 CO2 fluid. Special mechanisms for transporting ions through the cell membranes maintain the ion concentration dif- Right Left heart heart ferences between the extracellular and intracellular fluids. pump pump These transport processes are discussed in Chapter 4. Gut “Homeostatic” Mechanisms of the Major Functional Systems Homeostasis The term homeostasis is used by physiologists to mean Nutrition and excretion maintenance of nearly constant conditions in the internal environment. Essentially all organs and tissues of the body Kidneys perform functions that help maintain these relatively con- stant conditions. For instance, the lungs provide oxygen to the extracellular fluid to replenish the oxygen used by the cells, the kidneys maintain constant ion concentra- Regulation Excretion tions, and the gastrointestinal system provides nutrients. of A large segment of this text is concerned with the man- electrolytes ner in which each organ or tissue contributes to homeo- stasis. To begin this discussion, the different functional Venous Arterial systems of the body and their contributions to homeosta- end end sis are outlined in this chapter; then we briefly outline the basic theory of the body’s control systems that allow the functional systems to operate in support of one another. Capillaries Extracellular Fluid Transport and Mixing Figure 1-1 General organization of the circulatory system. System—The Blood Circulatory System Extracellular fluid is transported through all parts of the Arteriole body in two stages. The first stage is movement of blood through the body in the blood vessels, and the second is movement of fluid between the blood capillaries and the intercellular spaces between the tissue cells. Figure 1-1 shows the overall circulation of blood. All the blood in the circulation traverses the entire circu- latory circuit an average of once each minute when the body is at rest and as many as six times each minute when a person is extremely active. As blood passes through the blood capillaries, con- Venule tinual exchange of extracellular fluid also occurs between the plasma portion of the blood and the interstitial fluid that fills the intercellular spaces. This process is shown in Figure 1-2. The walls of the capillaries are permeable to most molecules in the plasma of the blood, with the Figure 1-2 Diffusion of fluid and dissolved constituents through exception of plasma protein molecules, which are too the capillary walls and through the interstitial spaces. large to readily pass through the capillaries. Therefore, large amounts of fluid and its dissolved constituents the plasma and the interstitial fluid. That is, the fluid and diffuse back and forth between the blood and the tissue dissolved molecules are continually moving and bounc- spaces, as shown by the arrows. This process of diffu- ing in all directions within the plasma and the fluid in the sion is caused by kinetic motion of the molecules in both intercellular spaces, as well as through the capillary pores. 4  Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” Few cells are located more than 50 micrometers from a These substances include different end products of cel- capillary, which ensures diffusion of almost any substance lular metabolism, such as urea and uric acid; they also from the capillary to the cell within a few seconds. Thus, include excesses of ions and water from the food that the extracellular fluid everywhere in the body—both that might have accumulated in the extracellular fluid. of the plasma and that of the interstitial fluid—is continu- The kidneys perform their function by first filtering ally being mixed, thereby maintaining homogeneity of the large quantities of plasma through the glomeruli into the Unit I extracellular fluid throughout the body. tubules and then reabsorbing into the blood those sub- stances needed by the body, such as glucose, amino acids, Origin of Nutrients in the Extracellular Fluid appropriate amounts of water, and many of the ions. Most Respiratory System. Figure 1-1 shows that each time of the other substances that are not needed by the body, the blood passes through the body, it also flows through especially the metabolic end products such as urea, are the lungs. The blood picks up oxygen in the alveoli, thus reabsorbed poorly and pass through the renal tubules into acquiring the oxygen needed by the cells. The membrane the urine. between the alveoli and the lumen of the pulmonary capillaries, the alveolar membrane, is only 0.4 to 2.0 Gastrointestinal Tract. Undigested material that micrometers thick, and oxygen rapidly diffuses by molec- enters the gastrointestinal tract and some waste products ular motion through this membrane into the blood. of metabolism are eliminated in the feces. Gastrointestinal Tract. A large portion of the blood Liver. Among the functions of the liver is the detoxi- pumped by the heart also passes through the walls of the fication or removal of many drugs and chemicals that are gastrointestinal tract. Here different dissolved nutrients, ingested. The liver secretes many of these wastes into the including carbohydrates, fatty acids, and amino acids, are bile to be eventually eliminated in the feces. absorbed from the ingested food into the extracellular fluid of the blood. Regulation of Body Functions Nervous System. The nervous system is composed Liver and Other Organs That Perform Primarily of three major parts: the sensory input portion, the central Metabolic Functions. Not all substances absorbed from nervous system (or integrative portion), and the motor out- the gastrointestinal tract can be used in their absorbed put portion. Sensory receptors detect the state of the body form by the cells. The liver changes the chemical compo- or the state of the surroundings. For instance, receptors in sitions of many of these substances to more usable forms, the skin apprise one whenever an object touches the skin and other tissues of the body—fat cells, gastrointestinal at any point. The eyes are sensory organs that give one a mucosa, kidneys, and endocrine glands—help modify the visual image of the surrounding area. The ears are also absorbed substances or store them until they are needed. sensory organs. The central nervous system is composed The liver also eliminates certain waste products produced of the brain and spinal cord. The brain can store informa- in the body and toxic substances that are ingested. tion, generate thoughts, create ambition, and determine reactions that the body performs in response to the sen- Musculoskeletal System. How does the musculo­ sations. Appropriate signals are then transmitted through skeletal system contribute to homeostasis? The answer is the motor output portion of the nervous system to carry obvious and simple: Were it not for the muscles, the body out one’s desires. could not move to the appropriate place at the appropri- An important segment of the nervous system is called ate time to obtain the foods required for nutrition. The the autonomic system. It operates at a subconscious level musculoskeletal system also provides motility for pro- and controls many functions of the internal organs, includ- tection against adverse surroundings, without which ing the level of pumping activity by the heart, movements the entire body, along with its homeostatic mechanisms, of the gastrointestinal tract, and secretion by many of the could be destroyed instantaneously. body’s glands. Hormone Systems. Located in the body are eight Removal of Metabolic End Products major endocrine glands that secrete chemical substances Removal of Carbon Dioxide by the Lungs. At the called hormones. Hormones are transported in the extra- same time that blood picks up oxygen in the lungs, carbon cellular fluid to all parts of the body to help regulate cel- dioxide is released from the blood into the lung alveoli; the lular function. For instance, thyroid hormone increases respiratory movement of air into and out of the lungs car- the rates of most chemical reactions in all cells, thus help- ries the carbon dioxide to the atmosphere. Carbon dioxide is ing to set the tempo of bodily activity. Insulin controls the most abundant of all the end products of metabolism. glucose metabolism; adrenocortical hormones control sodium ion, potassium ion, and protein metabolism; and Kidneys. Passage of the blood through the kidneys parathyroid hormone controls bone calcium and phos- removes from the plasma most of the other substances phate. Thus, the hormones provide a system for regula- besides carbon dioxide that are not needed by the cells. tion that complements the nervous system. The nervous 5 Unit I Introduction to Physiology: The Cell and General Physiology system regulates many muscular and secretory activi- Examples of Control Mechanisms ties of the body, whereas the hormonal system regulates Regulation of Oxygen and Carbon Dioxide many metabolic functions. Concentrations in the Extracellular Fluid. Because oxygen is one of the major substances required for chemical reactions in the cells, the body has a spe- Protection of the Body cial control mechanism to maintain an almost exact Immune System. The immune system consists of the and constant oxygen concentration in the extracellu- white blood cells, tissue cells derived from white blood lar fluid. This mechanism depends principally on the cells, the thymus, lymph nodes, and lymph vessels that chemical characteristics of hemoglobin, which is pres- protect the body from pathogens such as bacteria, viruses, ent in all red blood cells. Hemoglobin combines with parasites, and fungi. The immune system provides a mech- oxygen as the blood passes through the lungs. Then, as anism for the body to (1) distinguish its own cells from the blood passes through the tissue capillaries, hemo- foreign cells and substances and (2) destroy the invader globin, because of its own strong chemical affinity for by phagocytosis or by producing sensitized lymphocytes or oxygen, does not release oxygen into the tissue fluid specialized proteins (e.g., antibodies) that either destroy if too much oxygen is already there. But if the oxygen or neutralize the invader. concentration in the tissue fluid is too low, sufficient oxygen is released to re-establish an adequate concen- Integumentary System. The skin and its various tration. Thus, regulation of oxygen concentration in the appendages, including the hair, nails, glands, and other tissues is vested principally in the chemical character- structures, cover, cushion, and protect the deeper tissues istics of hemoglobin itself. This regulation is called the and organs of the body and generally provide a bound- oxygen-buffering function of hemoglobin. ary between the body’s internal environment and the out- Carbon dioxide concentration in the extracellular fluid side world. The integumentary system is also important is regulated in a much different way. Carbon dioxide is for temperature regulation and excretion of wastes and a major end product of the oxidative reactions in cells. it provides a sensory interface between the body and the If all the carbon dioxide formed in the cells continued to external environment. The skin generally comprises about accumulate in the tissue fluids, all energy-giving reactions 12 to 15 percent of body weight. of the cells would cease. Fortunately, a higher than nor- mal carbon dioxide concentration in the blood excites the respiratory center, causing a person to breathe rapidly and Reproduction deeply. This increases expiration of carbon dioxide and, Sometimes reproduction is not considered a homeo- therefore, removes excess carbon dioxide from the blood static function. It does, however, help maintain homeo- and tissue fluids. This process continues until the concen- stasis by generating new beings to take the place of those tration returns to normal. that are dying. This may sound like a permissive usage of the term homeostasis, but it illustrates that, in the final Regulation of Arterial Blood Pressure. Several sys- analysis, essentially all body structures are organized tems contribute to the regulation of arterial blood pres- such that they help maintain the automaticity and con- sure. One of these, the baroreceptor system, is a simple tinuity of life. and excellent example of a rapidly acting control mecha- nism. In the walls of the bifurcation region of the carotid arteries in the neck, and also in the arch of the aorta in the thorax, are many nerve receptors called barorecep- Control Systems of the Body tors, which are stimulated by stretch of the arterial wall. When the arterial pressure rises too high, the barore- The human body has thousands of control systems. The ceptors send barrages of nerve impulses to the medulla most intricate of these are the genetic control systems of the brain. Here these impulses inhibit the vasomotor that operate in all cells to help control intracellular func- center, which in turn decreases the number of impulses tion and extracellular functions. This subject is discussed transmitted from the vasomotor center through the sym- in Chapter 3. pathetic nervous system to the heart and blood vessels. Many other control systems operate within the organs Lack of these impulses causes diminished pumping activ- to control functions of the individual parts of the organs; ity by the heart and also dilation of the peripheral blood others operate throughout the entire body to control the vessels, allowing increased blood flow through the ves- interrelations between the organs. For instance, the respi- sels. Both of these effects decrease the arterial pressure ratory system, operating in association with the nervous back toward normal. system, regulates the concentration of carbon dioxide in Conversely, a decrease in arterial pressure below nor- the extracellular fluid. The liver and pancreas regulate mal relaxes the stretch receptors, allowing the vasomotor the concentration of glucose in the extracellular fluid, center to become more active than usual, thereby caus- and the kidneys regulate concentrations of hydrogen, ing vasoconstriction and increased heart pumping. The sodium, potassium, phosphate, and other ions in the decrease in arterial pressure also raises arterial pressure extracellular fluid. back toward normal. 6  Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment” Normal Ranges and Physical Characteristics Negative Feedback Nature of Most Control Systems of Important Extracellular Fluid Constituents Most control systems of the body act by negative feed- Table 1-1 lists some of the important constituents and back, which can best be explained by reviewing some of physical characteristics of extracellular fluid, along with the homeostatic control systems mentioned previously. their normal values, normal ranges, and maximum limits In the regulation of carbon dioxide concentration, a high Unit I without causing death. Note the narrowness of the nor- concentration of carbon dioxide in the extracellular fluid mal range for each one. Values outside these ranges are increases pulmonary ventilation. This, in turn, decreases usually caused by illness. the extracellular fluid carbon dioxide concentration Most important are the limits beyond which abnormal- because the lungs expire greater amounts of carbon diox- ities can cause death. For example, an increase in the body ide from the body. In other words, the high concentra- temperature of only 11°F (7°C) above normal can lead to a tion of carbon dioxide initiates events that decrease the vicious cycle of increasing cellular metabolism that destroys concentration toward normal, which is negative to the the cells. Note also the narrow range for acid-base balance initiating stimulus. Conversely, if the carbon dioxide con- in the body, with a normal pH value of 7.4 and lethal values centration falls too low, this causes feedback to increase only about 0.5 on either side of normal. Another impor- the concentration. This response is also negative to the tant factor is the potassium ion concentration because initiating stimulus. whenever it decreases to less than one-third normal, a In the arterial pressure-regulating mechanisms, a person is likely to be paralyzed as a result of the nerves’ high pressure causes a series of reactions that promote inability to carry signals. Alternatively, if the potassium ion a lowered pressure, or a low pressure causes a series of concentration increases to two or more times normal, the reactions that promote an elevated pressure. In both heart muscle is likely to be severely depressed. Also, when instances, these effects are negative with respect to the the calcium ion concentration falls below about one-half initiating stimulus. normal, a person is likely to experience tetanic contraction Therefore, in general, if some factor becomes exces- of muscles throughout the body because of the spontane- sive or deficient, a control system initiates negative feed- ous generation of excess nerve impulses in the peripheral back, which consists of a series of changes that return nerves. When the glucose concentration falls below one- the factor toward a certain mean value, thus maintaining half normal, a person frequently develops extreme mental homeostasis. irritability and sometimes even convulsions. “Gain” of a Control System. The degree of effective- These examples should give one an appreciation for ness with which a control system maintains constant con- the extreme value and even the necessity of the vast num- ditions is determined by the gain of the negative feedback. bers of control systems that keep the body operating in For instance, let us assume that a large volume of blood health; in the absence of any one of these controls, serious is transfused into a person whose baroreceptor pressure body malfunction or death can result. control system is not functioning, and the arterial pres- sure rises from the normal level of 100 mm Hg up to Characteristics of Control Systems 175 mm Hg. Then, let us assume that the same volume of The aforementioned examples of homeostatic control blood is injected into the same person when the barore- mechanisms are only a few of the many thousands in the ceptor system is functioning, and this time the pressure body, all of which have certain characteristics in common increases only 25 mm Hg. Thus, the feedback control sys- as explained in this section. tem has caused a “correction” of −50 mm Hg—that is, from Table 1-1 Important Constituents and Physical Characteristics of Extracellular Fluid Normal Value Normal Range Approximate Short-Term Unit Nonlethal Limit Oxygen 40 35-45 10-1000 mm Hg Carbon dioxide 40 35-45 5-80 mm Hg Sodium ion 142 138-146 115-175 mmol/L Potassium ion 4.2 3.8-5.0 1.5-9.0 mmol/L Calcium ion 1.2 1.0-1.4 0.5-2.0 mmol/L Chloride ion 108 103-112 70-130 mmol/L Bicarbonate ion 28 24-32 8-45 mmol/L Glucose 85 75-95 20-1500 mg/dl Body temperature 98.4 (37.0) 98-98.8 (37.0) 65-110 (18.3-43.3) °F (°C) Acid-base 7.4 7.3-7.5 6.9-8.0 pH 7 Unit I Introduction to Physiology: The Cell and General Physiology 175 mm Hg to 125 mm Hg. There remains an increase in not enough blood is available for the heart to pump effec- pressure of +25 mm Hg, called the “error,” which means tively. As a result, the arterial pressure falls and the flow that the control system is not 100 percent effective in pre- of blood to the heart muscle through the coronary vessels venting change. The gain of the system is then calculated diminishes. This results in weakening of the heart, fur- by the following formula: ther diminished pumping, a further decrease in coronary blood flow, and still more weakness of the heart; the cycle Correction repeats itself again and again until death occurs. Note that Gain = Error each cycle in the