Vanders human physiology, the mechanisms of body function 13th ed e widmaier, h raff, k strang (mcgraw hill, 2014)

Brief Contents FROM THE AUTHORS XV ■ GUIDED TOUR THROUGH A CHAPTER XVI ■ UPDATES AND ADDITIONS XX ■ TEACHING AND LEARNING SUPPLEMENTS XXII ■ ACKNOWLEDGMENTS XXIV and Pituitary Gland 33

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VANDER’S HUMAN PHYSIOLOGY: THE MECHANISMS OF BODY FUNCTION,

THIRTEENTH EDITION

Published by McGraw-Hill, a business unit of The McGraw-Hill Companies, Inc., 1221 Avenue of the

this publication may be reproduced or distributed in any form or by any means, or stored in a database or

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Some ancillaries, including electronic and print components, may not be available to customers outside

the United States.

This book is printed on acid-free paper

1 2 3 4 5 6 7 8 9 0 DOW/DOW 1 0 9 8 7 6 5 4 3

ISBN 978–0–07–337830–5

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Van der’s human physiology : the mechanisms of body function – Thirteenth edition / Eric P Widmaier,

Department of Biology, Boston University, Hershel Raff, Medical College of Wisconsin, Aurora

St Luke’s Medical Center, Kevin T Strang, Department of Neuroscience, University of Wisconsin.

pages cm

Includes index.

ISBN 978–0–07–337830–5 — ISBN 0–07–337830–5 (hard copy : alk paper) 1 Human physiology

I Raff, Hershel, 1953- II Strang, Kevin T III Vander, Arthur J., 1933– Human physiology IV Title

V Title: Human physiology

QP34.5.W47 2014

612–dc23

2012041775

The Internet addresses listed in the text were accurate at the time of publication The inclusion of a

website does not indicate an endorsement by the authors or McGraw-Hill, and McGraw-Hill does not

guarantee the accuracy of the information presented at these sites.

www.mhhe.com

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ERIC P WIDMAIER received his Ph.D in 1984 in Endocrinology from the University

of California at San Francisco His postdoctoral training was in endocrinology and physiology at

the Worcester Foundation for Experimental Biology and The Salk Institute in La Jolla, California

His research is focused on the control of body mass and metabolism in mammals, the mechanisms of hormone action, and molecular mechanisms of intestinal and hypothalamic

adaptation to high-fat diets He is currently Professor of Biology at Boston University, where he

teaches Human Physiology and has been recognized with the Gitner Award for Distinguished Teaching by the College of Arts and Sciences, and the Metcalf Prize for Excellence in Teaching by Boston University He is the author of numerous scientific and lay publications, including books about physiology for the general reader He lives outside Boston with his wife Maria and children Caroline and Richard

HERSHEL RAFF received his Ph.D in Environmental Physiology from the Johns

Hopkins University in 1981 and did postdoctoral training in Endocrinology at the University of California at San Francisco He is now a Professor of Medicine (Endocrinology, Metabolism,

and Clinical Nutrition), Surgery, and Physiology at the Medical College of Wisconsin and Director of the Endocrine Research Laboratory at Aurora St Luke’s Medical Center At the Medical College of Wisconsin, he teaches physiology and pharmacology to medical and graduate

students, and is the Endocrinology/Reproduction Unit Director for the new integrated curriculum He was an inaugural inductee into the Society of Teaching Scholars, received the Beckman Basic Science Teaching Award three times, received the Outstanding Teacher Award from the Graduate School, and has been one of the MCW’s Outstanding Medical Student Teachers for each year the award has been given He is also an Adjunct Professor of

Biomedical Sciences at Marquette University He is the former Associate Editor of Advances

in Physiology Education Dr Raff’s basic research focuses on the adaptation to low oxygen

(hypoxia) His clinical interest focuses on pituitary and adrenal diseases, with a special focus

on laboratory tests for the diagnosis of Cushing’s syndrome He resides outside Milwaukee with his wife Judy and son Jonathan

KEVIN T STRANG received his Master’s Degree in Zoology (1988) and his Ph.D

in Physiology (1994) from the University of Wisconsin at Madison His research area is cellular

mechanisms of contractility modulation in cardiac muscle He teaches a large undergraduate

systems physiology course as well as first-year medical physiology in the UW-Madison School

of Medicine and Public Health He was elected to UW-Madison’s Teaching Academy and as

a Fellow of the Wisconsin Initiative for Science Literacy He is a frequent guest speaker

at colleges and high schools on the physiology of alcohol consumption He has twice been awarded the UW Medical Alumni Association’s Distinguished Teaching Award for Basic Sciences, and also received the University of Wisconsin System’s Underkofler/Alliant Energy

Excellence in Teaching Award In 2012 he was featured in The Princeton Review publication, “The Best 300 Professors.” Interested in teaching technology, Dr Strang has produced numerous animations of figures from Vander’s Human Physiology available to instructors and

students He lives in Madison with his wife Sheryl and his children Jake and Amy

Meet the Authors

T O O U R FA M I L I E S : M A R I A , R I C H A R D , A N D C A R O L I N E ; J U D Y A N D J O N A T H A N ;

S H E R Y L , J A K E , A N D A M Y

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Brief Contents

FROM THE AUTHORS XV ■ GUIDED TOUR THROUGH A CHAPTER XVI ■ UPDATES AND ADDITIONS XX ■ TEACHING AND

LEARNING SUPPLEMENTS XXII ■ ACKNOWLEDGMENTS XXIV

and Pituitary Gland 333

Gland 340

Response to Stress 344

Growth 349

of Ca 21 Homeostasis 353

■ 12 Cardiovascular

Physiology 362

the Circulatory System 363

System 387

Cardiovascular Function: Regulation

of Systemic Arterial Pressure 407

■ 14 The Kidneys and

Regulation of Water and Inorganic Ions 490

Total-Body Energy Balance and Temperature 587

Determination, and Sex Differentiation;

General Principles

of Reproductive Endocrinology 603

Palpitations and Heat Intolerance 693

After a Long Airplane Flight 697

Pain, Fever, and Circulatory Failure 699

Nausea, Flushing, and Sweating 703

APPENDIX A A-1 APPENDIX B A-17 GLOSSARY G-1 CREDITS C-1 INDEX I-1

Degradation, and Secretion 58

Proteins and Ligands 68

■ 6 Neuronal Signaling and

the Structure of the

Muscle 286

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Table of Contents

FROM THE AUTHORS XV ■ GUIDED TOUR THROUGH A CHAPTER XVI ■ UPDATES AND ADDITIONS XX ■ TEACHING AND

LEARNING SUPPLEMENTS XXII ■ ACKNOWLEDGMENTS XXIV

1.1 The Scope of Human Physiology 2

1.2 How Is the Body Organized? 2

Muscle Cells and Tissue 3 Neurons and Nervous Tissue 3 Epithelial Cells and Epithelial Tissue 3 Connective-Tissue Cells and Connective Tissue 4 Organs and Organ Systems 4

1.3 Body Fluid Compartments 5

1.4 Homeostasis: A Defining Feature of Physiology 6

1.5 General Characteristics of Homeostatic Control

Systems 7

Feedback Systems 8 Resetting of Set Points 9 Feedforward Regulation 9

1.6 Components of Homeostatic Control Systems 10

Reflexes 10 Local Homeostatic Responses 11

1.7 The Role of Intercellular Chemical Messengers in

Homeostasis 11 1.8 Processes Related to Homeostasis 12

Adaptation and Acclimatization 12 Biological Rhythms 13

Balance of Chemical Substances in the Body 14

1.9 General Principles of Physiology 15

Chapter 1 Clinical Case Study 17

ASSORTED ASSESSMENT QUESTIONS 19

ANSWERS TO PHYSIOLOGICAL INQUIRIES 19

Homeostasis: A Framework for Human Physiology 1

1

2.1 Atoms 21

Components of Atoms 21 Atomic Number 22 Atomic Mass 22 Ions 23 Atomic Composition of the Body 23

the Body 20

S E C T I O N A Cell Structure 46 3.1 Microscopic Observations of Cells 46 3.2 Membranes 48

Membrane Structure 49 Membrane Junctions 51

3.3 Cell Organelles 51

Nucleus 51 Ribosomes 53 Endoplasmic Reticulum 53 Golgi Apparatus 54 Endosomes 54 Mitochondria 54 Lysosomes 55 Peroxisomes 56 Vaults 56 Cytoskeleton 56

3 Cellular Structure, Proteins, and Metabolism 45

2.2 Molecules 23

Covalent Chemical Bonds 23 Ionic Bonds 25

Hydrogen Bonds 25 Molecular Shape 26 Ionic Molecules 26 Free Radicals 26

2.3 Solutions 27

Water 27 Molecular Solubility 28 Concentration 28 Hydrogen Ions and Acidity 29

2.4 Classes of Organic Molecules 30

Carbohydrates 30 Lipids 31 Proteins 34 Nucleic Acids 38 ATP 40

ASSORTED ASSESSMENT QUESTIONS 43 ANSWERS TO PHYSIOLOGICAL INQUIRIES 44

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Transcription: mRNA Synthesis 59

Translation: Polypeptide Synthesis 61

Regulation of Protein Synthesis 63

Determinants of Reaction Rates 73

Reversible and Irreversible Reactions 74

Law of Mass Action 74

S E C T I O N A Neural Tissue 139 6.1 Structure and Maintenance of Neurons 139 6.2 Functional Classes of Neurons 140

6.3 Glial Cells 142 6.4 Neural Growth and Regeneration 143

Structure of the Nervous System 138

5.1 Receptors 121

Receptors and Their Interactions with Ligands 121 Regulation of Receptors 123

5.2 Signal Transduction Pathways 123

Pathways Initiated by Lipid-Soluble Messengers 124 Pathways Initiated by Water-Soluble Messengers 124 Other Messengers 131

Cessation of Activity in Signal Transduction Pathways 133

Messengers 120

4.1 Diffusion 97

Magnitude and Direction of Diffusion 97 Diffusion Rate Versus Distance 98 Diffusion Through Membranes 98

4.2 Mediated-Transport Systems 101

Facilitated Diffusion 102 Active Transport 103

4.3 Osmosis 107

Extracellular Osmolarity and Cell Volume 109

4.4 Endocytosis and Exocytosis 110

Endocytosis 111 Exocytosis 113

4.5 Epithelial Transport 113 Chapter 4 Clinical Case Study 116

Cell Membranes 96

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Table of Contents vii

S E C T I O N A General Principles 192

7.1 Sensory Receptors 192

The Receptor Potential 193

7.2 Primary Sensory Coding 194

Stimulus Type 195 Stimulus Intensity 195 Stimulus Location 195 Central Control of Afferent Information 197

Electroencephalogram 235 The Waking State 236 Sleep 236

Neural Substrates of States of Consciousness 238 Coma and Brain Death 240

8.2 Conscious Experiences 241

Selective Attention 241 Neural Mechanisms of Conscious Experiences 242

8.3 Motivation and Emotion 243

Motivation 243 Emotion 244

and Behavior 234

S E C T I O N B Membrane Potentials 145

6.5 Basic Principles of Electricity 145

6.6 The Resting Membrane Potential 146

6.7 Graded Potentials and Action Potentials 150

Graded Potentials 151 Action Potentials 152

S E C T I O N C Synapses 160

6.8 Functional Anatomy of Synapses 161

6.9 Mechanisms of Neurotransmitter Release 161

6.10 Activation of the Postsynaptic Cell 162

Excitatory Chemical Synapses 162 Inhibitory Chemical Synapses 163

6.11 Synaptic Integration 163

6.12 Synaptic Strength 165

Modification of Synaptic Transmission by Drugs and Disease 166

6.13 Neurotransmitters and Neuromodulators 167

Acetylcholine 168 Biogenic Amines 169 Amino Acid Neurotransmitters 170 Neuropeptides 171

Gases 172 Purines 172

6.14 Neuroeffector Communication 172

S E C T I O N D Structure of the Nervous System 173

6.15 Central Nervous System: Brain 174

Forebrain 175 Cerebellum 177 Brainstem 177

6.16 Central Nervous System: Spinal Cord 177

6.17 Peripheral Nervous System 178

6.18 Autonomic Nervous System 180

6.19 Blood Supply, Blood–Brain Barrier, and

Cerebrospinal Fluid 184 Chapter 6 Clinical Case Study 187

7.3 Ascending Neural Pathways in Sensory Systems 198

Factors That Affect Perception 200

S E C T I O N B Specific Sensory Systems 203 7.5 Somatic Sensation 203

Touch and Pressure 203 Senses of Posture and Movement 203 Temperature 204

Pain 204 Neural Pathways of the Somatosensory System 206

7.6 Vision 207

Light 207 Overview of Eye Anatomy 208 The Optics of Vision 208 Photoreceptor Cells and Phototransduction 211 Neural Pathways of Vision 213

Color Vision 216 Color Blindness 216 Eye Movement 217

7.7 Hearing 217

Sound 217 Sound Transmission in the Ear 218 Hair Cells of the Organ of Corti 221 Neural Pathways in Hearing 222

7.8 Vestibular System 223

The Semicircular Canals 224 The Utricle and Saccule 224 Vestibular Information and Pathways 225

7.9 Chemical Senses 225

Taste 226 Smell 227

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viii Table of Contents

10.1 Motor Control Hierarchy 301

Voluntary and Involuntary Actions 302

10.2 Local Control of Motor Neurons 303

Interneurons 303 Local Afferent Input 304

Pathways They Control 308

Cerebral Cortex 308 Subcortical and Brainstem Nuclei 310 Cerebellum 310

Descending Pathways 311

10.4 Muscle Tone 312

Abnormal Muscle Tone 312

10.5 Maintenance of Upright Posture and Balance 313

10.6 Walking 313 Chapter 10 Clinical Case Study 316

11.5 Mechanisms of Hormone Action 328

Hormone Receptors 328 Events Elicited by Hormone–Receptor Binding 328 Pharmacological Effects of Hormones 329

Control by Plasma Concentrations of Mineral Ions

or Organic Nutrients 330 Control by Neurons 330 Control by Other Hormones 330

Control of Muscle Tension 278

Control of Shortening Velocity 279

Muscle Adaptation to Exercise 279

Lever Action of Muscles and Bones 281

9.7 Skeletal Muscle Disorders 282

Muscle Cramps 282

Hypocalcemic Tetany 282

Muscular Dystrophy 283

Myasthenia Gravis 283

S E C T I O N B Smooth and Cardiac Muscle 286

9.8 Structure of Smooth Muscle 286

9.9 Smooth Muscle Contraction and Its

Cellular Structure of Cardiac Muscle 292

Excitation–Contraction Coupling in Cardiac Muscle 292

8.4 Altered States of Consciousness 245

Schizophrenia 246

The Mood Disorders: Depressions and Bipolar Disorders 246

Psychoactive Substances, Dependence, and Tolerance 247

8.5 Learning and Memory 249

Memory 249

The Neural Basis of Learning and Memory 249

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Table of Contents ix

S E C T I O N A Overview of the Circulatory System 363 12.1 Components of the Circulatory System 363 12.2 Pressure, Flow, and Resistance 364

S E C T I O N B The Heart 368 12.3 Anatomy 368

Cardiac Muscle 369

12.4 Heartbeat Coordination 370

Sequence of Excitation 371 Cardiac Action Potentials and Excitation of the SA Node 372 The Electrocardiogram 374

Excitation–Contraction Coupling 376 Refractory Period of the Heart 376

12.5 Mechanical Events of the Cardiac Cycle 377

Mid-Diastole to Late Diastole 378 Systole 378

Early Diastole 380 Pulmonary Circulation Pressures 380 Heart Sounds 381

12.6 The Cardiac Output 381

Control of Heart Rate 381 Control of Stroke Volume 382

12.7 Measurement of Cardiac Function 385

S E C T I O N C The Vascular System 387 12.8 Arteries 387

Arterial Blood Pressure 387 Measurement of Systemic Arterial Pressure 390

12.9 Arterioles 391

Local Controls 392 Extrinsic Controls 394 Endothelial Cells and Vascular Smooth Muscle 395 Arteriolar Control in Specific Organs 395

12.10 Capillaries 395

Anatomy of the Capillary Network 397 Velocity of Capillary Blood Flow 398 Diffusion Across the Capillary Wall: Exchanges of Nutrients and Metabolic End Products 398

Bulk Flow Across the Capillary Wall: Distribution of the Extracellular Fluid 399

12.11 Veins 402

Determinants of Venous Pressure 402

12.12 The Lymphatic System 404

Mechanism of Lymph Flow 404

Physiology 362

11.7 Types of Endocrine Disorders 331

Hyposecretion 331 Hypersecretion 331 Hyporesponsiveness and Hyperresponsiveness 331

S E C T I O N B The Hypothalamus and Pituitary Gland 333

11.8 Control Systems Involving the Hypothalamus

and Pituitary Gland 333

Posterior Pituitary Hormones 333 Anterior Pituitary Gland Hormones and the Hypothalamus 335

S E C T I O N C The Thyroid Gland 340

11.9 Synthesis of Thyroid Hormone 340

11.10 Control of Thyroid Function 341

11.11 Actions of Thyroid Hormone 342

Metabolic Actions 342 Permissive Actions 342 Growth and Development 342

S E C T I O N D The Endocrine Response to Stress 344

11.13 Physiological Functions of Cortisol 345

11.14 Functions of Cortisol in Stress 345

11.15 Adrenal Insufficiency and Cushing’s

Syndrome 346

S E C T I O N E Endocrine Control of Growth 349

11.17 Bone Growth 349

Growth Hormone and Insulin-Like Growth Factors 350 Thyroid Hormone 352

Insulin 352 Sex Steroids 352 Cortisol 352

S E C T I O N F Endocrine Control of Ca 21 Homeostasis 353

11.20 Effector Sites for Ca 21 Homeostasis 353

Bone 353 Kidneys 354 Gastrointestinal Tract 354

11.21 Hormonal Controls 354

Parathyroid Hormone 354 1,25-Dihydroxyvitamin D 355 Calcitonin 356

11.22 Metabolic Bone Diseases 356

Hypercalcemia 356 Hypocalcemia 357

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x Table of Contents

S E C T I O N A Basic Principles of Renal Physiology 491 14.1 Renal Functions 491

14.3 Basic Renal Processes 494

Glomerular Filtration 497 Tubular Reabsorption 500 Tubular Secretion 501 Metabolism by the Tubules 502 Regulation of Membrane Channels and Transporters 502

“Division of Labor” in the Tubules 502

14.4 The Concept of Renal Clearance 502 14.5 Micturition 503

Incontinence 504

of Water and Inorganic Ions 490

13.1 Organization of the Respiratory System 447

The Airways and Blood Vessels 447

Site of Gas Exchange: The Alveoli 448

Relation of the Lungs to the Thoracic (Chest) Wall 450

13.2 Ventilation and Lung Mechanics 450

How Is a Stable Balance Achieved Between Breaths? 452

Inspiration 454

S E C T I O N D Integration of Cardiovascular Function:

Regulation of Systemic Arterial Pressure 407

12.13 Baroreceptor Reflexes 410

Arterial Baroreceptors 410

The Medullary Cardiovascular Center 411

Operation of the Arterial Baroreceptor Reflex 411

Other Baroreceptors 412

Arterial Pressure 413

S E C T I O N E Cardiovascular Patterns in Health and

S E C T I O N F Blood and Hemostasis 428

Regulation of Blood Cell Production 432

Formation of a Platelet Plug 433

Blood Coagulation: Clot Formation 434

Anticlotting Systems 437

Anticlotting Drugs 438

Expiration 454 Lung Compliance 455 Airway Resistance 458 Lung Volumes and Capacities 459 Alveolar Ventilation 459

13.3 Exchange of Gases in Alveoli and Tissues 461

Partial Pressures of Gases 462 Alveolar Gas Pressures 464 Gas Exchange Between Alveoli and Blood 465 Matching of Ventilation and Blood Flow in Alveoli 466 Gas Exchange Between Tissues and Blood 467

13.4 Transport of Oxygen in Blood 467

What Is the Effect of P O2 on Hemoglobin Saturation? 468 Effects of CO 2 and Other Factors in the Blood and Different Isoforms on Hemoglobin Saturation 470

and Lungs 472 13.7 Control of Respiration 473

Neural Generation of Rhythmic Breathing 473 Control of Ventilation by P O2 , P CO2 , and H1

Concentration 474 Control of Ventilation During Exercise 478

Other Ventilatory Responses 479

13.8 Hypoxia 480

Why Do Ventilation–Perfusion Abnormalities Affect O 2 More Than CO 2 ? 481

Emphysema 481 Acclimatization to High Altitude 482

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16.2 Endocrine and Neural Control of the Absorptive and Postabsorptive States 578

Insulin 578 Glucagon 582 Epinephrine and Sympathetic Nerves to Liver and Adipose Tissue 583

Cortisol 583 Growth Hormone 584 Hypoglycemia 584

S E C T I O N B Regulation of Total-Body Energy Balance and Temperature 587

Metabolic Rate 587

Control of Food Intake 589 Overweight and Obesity 590 Eating Disorders: Anorexia Nervosa and Bulimia Nervosa 591 What Should We Eat? 591

16.6 Regulation of Body Temperature 592

Mechanisms of Heat Loss or Gain 592 Temperature-Regulating Reflexes 593 Temperature Acclimatization 595

16.7 Fever and Hyperthermia 595 Chapter 16 Clinical Case Study 598

16 Regulation of Organic Metabolism and Energy

Balance 572

15.1 Overview of the Digestive System 534

15.2 Structure of the Gastrointestinal Tract Wall 535

15.3 General Functions of the Gastrointestinal and

Accessory Organs 538 15.4 Digestion and Absorption 540

Carbohydrate 541 Protein 541 Fat 542 Vitamins 544 Water and Minerals 545

15.5 How Are Gastrointestinal Processes

Regulated? 545

Basic Principles 546 Mouth, Pharynx, and Esophagus 548 Stomach 550

Absorption of Food 533

S E C T I O N B Regulation of Ion and Water Balance 506

14.6 Total-Body Balance of Sodium and Water 506

14.7 Basic Renal Processes for Sodium and Water 506

Primary Active Na1

Reabsorption 506 Coupling of Water Reabsorption to Na1

Reabsorption 507 Urine Concentration: The Countercurrent Multiplier System 509

14.8 Renal Sodium Regulation 513

Control of GFR 513 Control of Na1

Reabsorption 514

14.9 Renal Water Regulation 516

Osmoreceptor Control of Vasopressin Secretion 516 Baroreceptor Control of Vasopressin Secretion 517

14.11 Thirst and Salt Appetite 518

S E C T I O N C Hydrogen Ion Regulation 524

14.16 Sources of Hydrogen Ion Gain or Loss 524

14.19 Renal Mechanisms 525

HCO 32 Handling 525 Addition of New HCO 32 to the Plasma 526

14.20 Classification of Acidosis and Alkalosis 527

Hemodialysis, Peritoneal Dialysis, and Transplantation 529

Pancreatic Secretions 555 Bile Secretion 557 Small Intestine 559 Large Intestine 560

15.6 Pathophysiology of the Gastrointestinal Tract 562

Ulcers 562 Vomiting 562 Gallstones 564 Lactose Intolerance 564 Constipation and Diarrhea 565

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xii Table of Contents

18.1 Cells and Secretions Mediating Immune Defenses 653

Immune Cells 653 Cytokines 654

18.2 Innate Immune Responses 654

Defenses at Body Surfaces 656 Inflammation 656

Interferons 660 Toll-Like Receptors 661

18.3 Adaptive Immune Responses 662

Overview 662 Lymphoid Organs and Lymphocyte Origins 662 Functions of B Cells and T Cells 664

Lymphocyte Receptors 666 Antigen Presentation to T Cells 668

NK Cells 670 Development of Immune Tolerance 670 Antibody-Mediated Immune Responses: Defenses Against Bacteria, Extracellular Viruses, and Toxins 671

Defenses Against Virus-Infected Cells and Cancer Cells 674

18.4 Systemic Manifestations of Infection 676 18.5 Factors That Alter the Resistance to Infection 678

Acquired Immune Deficiency Syndrome (AIDS) 679 Antibiotics 679

18.6 Harmful Immune Responses 680

Graft Rejection 680 Transfusion Reactions 680 Allergy (Hypersensitivity) 681 Autoimmune Disease 683 Excessive Inflammatory Responses 683

17.19 Pregnancy 633

Egg Transport 633 Intercourse, Sperm Transport, and Capacitation 634 Fertilization 634

Early Development, Implantation, and Placentation 635 Hormonal and Other Changes During Pregnancy 638 Parturition 639

Lactation 643 Contraception 645 Infertility 646

17.20 Menopause 646 Chapter 17 Clinical Case Study 649

S E C T I O N A Gametogenesis, Sex Determination, and

Sex Differentiation; General Principles of Reproductive

Endocrinology 603

17.1 Gametogenesis 603

17.2 Sex Determination 605

17.3 Sex Differentiation 605

Differentiation of the Gonads 606

Differentiation of Internal and External Genitalia 606

Sexual Differentiation of the Brain 606

17.4 General Principles of Reproductive

Formation of the Corpus Luteum 625

Sites of Synthesis of Ovarian Hormones 626

17.14 Control of Ovarian Function 626

Follicle Development and Estrogen Synthesis During the Early and

Middle Follicular Phases 626

LH Surge and Ovulation 629

The Luteal Phase 629

17.15 Uterine Changes in the Menstrual Cycle 630

17.16 Additional Effects of Gonadal Steroids 632

17.17 Puberty 633

17.18 Female Sexual Response 633

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Table of Contents xiii

C A S E A Woman with Palpitations and Heat

Intolerance 693

19.A1 Case Presentation 693

19.A2 Physical Examination 693

19.A3 Laboratory Tests 694

C A S E D College Student with Nausea, Flushing, and Sweating 703

19.D1 Case Presentation 703 19.D2 Physical Examination 703 19.D3 Laboratory Tests 704 19.D4 Diagnosis 704 19.D5 Physiological Integration 704 19.D6 Therapy 706

APPENDIX A: Answers to Test Questions and General Principles

Assessments A-1 APPENDIX B: Index of Clinical Terms A-17

GLOSSARY G-1 CREDITS C-1 INDEX I-1

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Index of Exercise Physiology

EFFECTS ON CARDIOVASCULAR

SYSTEM, 381–85

Atrial pumping (atrial fibrillation), 380

Cardiac output (increases), 381–85, 386, 410

Distribution during exercise, 418–21, 420t, 427

Control mechanisms, 382–83

Coronary blood flow (increases), 370

Gastrointestinal blood flow (decreases), 416

Heart attacks (protective against), 426

Heart rate (increases), 381, 382

Lymph flow (increases), 404–5

Maximal oxygen consumption (increases), 420–21

Mean arterial pressure (increases), 389–90

Renal blood flow (decreases), 416

Skeletal muscle blood flow (increases), 417, 418

Skin blood flow (increases), 418

Stroke volume (increases), 382–85

Summary, 385–86

Venous return (increases), 383

Role of respiratory pump, 403, 419

Role of skeletal muscle pump, 403, 419

EFFECTS ON ORGANIC METABOLISM, 584–85

Cortisol secretion (increases), 583

Diabetes mellitus (protects against), 581–82

Epinephrine secretion (increases), 583

Fuel homeostasis, 584–85

Fuel source, 85, 86, 275, 584–85

Glucagon secretion (increases), 582

Glucose mobilization from liver (increases), 584–85

Glucose uptake by muscle (increases), 585

Growth hormone secretion (increases), 584

Insulin secretion (decreases), 582

Metabolic rate (increases), 587–88

Plasma glucose changes, 582

Plasma lactic acid (increases), 276, 477–78

Sympathetic nervous system activity (increases), 584, 585

Respiratory rate (increases), 275, 474–78Role of Hering-Breuer reflex, 474

EFFECTS ON SKELETAL MUSCLE, 279–80

Adaptation to exercise, 279–81Arterioles (dilate), 408

Changes with aging, 280Fatigue, 275–76

Glucose uptake and utilization (increase), 275Hypertrophy, 259, 280, 341

Local blood flow (increases), 392, 407, 416–17Local metabolic rate (increases), 74

Local temperature (increases), 74Nutrient utilization, 584–85Oxygen extraction from blood (increases), 275Recruitment of motor units, 279

OTHER EFFECTS

Aging, 280, 418–20Body temperature (increases), 593Central command fatigue, 276Gastrointestinal blood flow (decreases), 416Immune function, 678

Menstrual function, 585, 635Metabolic acidosis, 477Metabolic rate (increases), 587–88Muscle fatigue, 275–76

Osteoporosis (protects against), 347, 356, 648Stress, 584–85, 586

Weight loss, 589, 591

TYPES OF EXERCISE

Aerobic, 280Endurance exercise, 280, 420–21Long-distance running, 276, 280Moderate exercise, 280–81Swimming, 420, 479Weightlifting, 276, 280–81, 420

Trang 18

detailed Table of Contents), and special attention to the clinical relevance of much of the basic science (see the Index of Clini-cal Terms in Appendix B) This index is organized according

to disease; infectious or causative agents; and the treatments, diagnostics, and therapeutic drugs used to treat disease This

is a very useful resource for instructors and students interested

in the extensive medical applications of human physiology that are covered in this book

As textbooks become more integrated with digital

con-tent, we are pleased that McGraw-Hill has provided Vander’s

continues to expand and develop Students will again find a Connect Plus site associated with the text The assessments have been updated and are now authored by one of the author team, Kevin Strang For the first time we also have Learn-

diagnos-tic tool that constantly assesses student knowledge of course material

We are always grateful to receive e-mail messages from instructors and students worldwide who are using the book and wish to offer suggestions regarding content Finally, no textbook such as this could be written without the expert and critical eyes of our many reviewers; we are thankful to those colleagues who took time from their busy schedules to read all

or a portion of a chapter (or more) and provide us with their insights and suggestions for improvements

It is with great pleasure that we present the thirteenth edition

of Vander’s Human Physiology The cover of this edition reflects

some of the major themes of the textbook: homeostasis,

exer-cise, pathophysiology, and cellular and molecular mechanisms

of body function These themes and others have now been

introduced in Chapter 1, called “General Principles of

Physi-ology.” These principles have been integrated throughout the

remaining chapters in order to continually reinforce their

importance Each chapter opens with a preview of those

prin-ciples that are particularly relevant for the material covered in

that chapter The principles are then reinforced when specific

examples arise within a chapter Finally, assessments are

pro-vided at the end of each chapter to provide immediate

feed-back for students to gauge their understanding of the chapter

material and its relationship to physiological principles These

assessments tend to require analytical and critical thinking;

answers are provided in an appendix

Users of the book will also benefit from expanded ments of the traditional type, such as multiple choice and

assess-thought questions, as well as additional Physiological Inquiries

associated with various key figures In total, approximately 70

new assessment questions have been added to the textbook; this

is in addition to the several hundred test questions available on

the McGraw-Hill Connect site associated with the book

As in earlier editions, there is extensive coverage of cise physiology (see the special exercise index that follows the

From the Authors

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11

S E C T I O N C

The Thyroid Gland

11.9 Synthesis of Thyroid Hormone 11.10 Control of Thyroid Function 11.11 Actions of Thyroid Hormone

Metabolic Actions Permissive Actions Growth and Development

11.12 Hypothyroidism and Hyperthyroidism

S E C T I O N D

The Endocrine Response to Stress

11.13 Physiological Functions

of Cortisol 11.14 Functions of Cortisol in Stress 11.15 Adrenal Insufficiency and Cushing’s Syndrome 11.16 Other Hormones Released During Stress

S E C T I O N E

Endocrine Control of Growth

11.17 Bone Growth 11.18 Environmental Factors Influencing Growth 11.19 Hormonal Influences on Growth

Growth Hormone and Insulin-Like Growth Factors Thyroid Hormone Insulin Sex Steroids Cortisol

S E C T I O N F

Endocrine Control of Ca 2 1 Homeostasis

11.20 Effector Sites for Ca 2 1 Homeostasis

Bone Kidneys Gastrointestinal Tract

11.21 Hormonal Controls

Parathyroid Hormone 1,25-Dihydroxyvitamin D Calcitonin

11.22 Metabolic Bone Diseases

Hypercalcemia Hypocalcemia

Chapter 11 Clinical Case Study

The Endocrine System

MRI of a human brain showing the connection between the

hypothalamus (orange) and the pituitary gland (red)

Control by Plasma Concentrations

of Mineral Ions or Organic Nutrients Control by Neurons Control by Other Hormones

11.7 Types of Endocrine Disorders

Hyposecretion Hypersecretion Hyporesponsiveness and Hyperresponsiveness

Posterior Pituitary Hormones Anterior Pituitary Gland Hormones and the Hypothalamus

See Chapter 19 for complete, integrative case studies.

growth hormone and IGF-1 result in the thickening of many bones in the body, most noticeably in the hands, feet, and head The jaw, particularly, enlarges to give the characteristic facial appearance called prognathism

(from the Greek pro, “forward,” and gnathos, “jaw”) that is associated

with acromegaly This was likely the cause of our patient's chronic mouth pain The enlarged sinuses that resulted from the thickening of his skull many internal organs—such as the heart—also become enlarged interfere with their ability to function normally In some acromegalics, the tissues comprising the larynx enlarge, resulting in a deepening of the voice as in our subject The enlarged and deformed tongue was likely this is called obstructive sleep apnea because the tongue base weakens

13 for a discussion of sleep apnea) Finally, roughly half of all people with acromegaly have elevated blood pressure (hypertension) The cause of requires treatment with antihypertensive drugs

As described earlier, adults continue to make and secrete growth hormone even after growth ceases That is because growth hormone

(continued)

actions of growth hormone in metabolism are to increase the concentrations of glucose and fatty acids in the blood and decrease the sensitivity of skeletal muscle and adipose tissue to insulin Not surprisingly, therefore, one of the stimuli that increases growth hormone concentrations in the healthy adult is a decrease in blood these metabolic crises, however, is transient; once glucose or fatty acid concentrations are restored to normal, growth hormone concentrations decrease to baseline In acromegaly, however, growth hormone concentrations are almost always increased

Consequently, acromegaly is often associated with increased plasma concentrations of glucose and fatty acids, in some cases

As in Cushing's syndrome (Section D), therefore, the presence of chronically increased concentrations of growth hormone may result in diabetes-like symptoms This explains why our patient had

a high fasting plasma glucose concentration

Our subject was fortunate to have had a quick diagnosis This case study illustrates one of the confounding features of endocrine disorders The rarity of some endocrine diseases (e.g., acromegaly that the symptoms of a given endocrine disease can be varied and insidious in their onset, often results in a delayed diagnosis This means that in many cases, a patient is subjected to numerous tests for more common disorders before a diagnosis of endocrine disease is made

Treatment of gigantism and acromegaly usually requires surgical removal of the pituitary tumor The residual normal pituitary tissue is

If this treatment is impossible or not successful, treatment with acting analogs of somatostatin is sometimes necessary (Recall that somatostatin is the hypothalamic hormone that inhibits GH secretion.) Our patient elected to have surgery This resulted in a reduction in his plasma growth hormone and IGF-1 concentrations With time, several of his symptoms were reduced, including the increased plasma glucose concentrations However, within 2 years, his growth hormone range for his age and a follow-up MRI revealed that the tumor had radiation therapy focused on the pituitary tumor, followed by regular but did not completely normalize his hormone concentrations His antihypertensive drugs (see Chapter 12)

long-Clinical terms: acromegaly, gigantism, prognathism

Figure 11.33 Appearance of an individual with gigantism and acromegaly

358 Chapter 11

A 35-year-old man visited his dentist with

a complaint of chronic mouth pain and the dentist concluded that there was no appeared enlarged and his tongue was thickened and large The dentist referred noted enlargement of the jaw and tongue, very deep voice The patient acknowledged that his voice seemed to have

ring because it was too tight The patient's height and weight were within

normal ranges His blood pressure was significantly elevated, as was his

his wife could no longer sleep in the same room as he because of his

physician referred the patient to an endocrinologist, who ordered a series

of tests to better elucidate the cause of the diverse symptoms

The enlarged bones and facial features suggested the possibility

of acromegaly (from the Greek akros, “extreme” or “extremities,” and

megalos, “large”), a disease characterized by excess growth hormone

test that revealed greatly elevated concentrations of both hormones

tumor of the anterior pituitary gland A 1.5 cm mass was discovered in

the sella turcica, consistent with the possibility of a growth hormone–

secreting tumor Because the patient was of normal height, it was linear growth ceased because of closure of the epiphyseal plates

been well above normal height because of the growth-promoting

as pituitary giants and have a condition called gigantism In many

cases, the affected person develops both gigantism and later acromegaly, as occurred in the individual shown in Figure 11.33 Acromegaly and gigantism arise when chronic, excess amounts of growth hormone are secreted into the blood In almost all cases, acromegaly and gigantism are caused by benign growth hormone at very high rates, which in turn results in are abnormal tissue, they are not suppressed adequately by normal negative feedback inhibitors like IGF-1, so the growth hormone concentrations remain elevated These tumors are typically very slow growing, and, if they arise after puberty, it may be many years before a person realizes that there is something wrong In our patient, the changes in his appearance were gradual enough that

he attributed them simply to “aging,” despite his relative youth

Even when linear growth is no longer possible (after the growth plates have fused), very high plasma concentrations of

of the Hands in a 35-Year-Old Man

(continued)

wid78305_ch11_319-361.indd 358 30/01/13 6:38 PM

xvi

Clinical Case Studies

The authors have drawn from their teaching and research

experiences and the clinical experiences of colleagues to

provide students with real-life applications through clinical

case studies in each chapter

General Principles of Physiology—NEW!

General Principles of Physiology have been integrated throughout each chapter in order to continually reinforce their importance Each chapter opens with a preview of those principles that are particularly relevant for the material covered

in that chapter The principles are then reinforced when specific examples arise within a chapter

Guided Tour Through a Chapter

I n Chapters 6–8 and 10, you learned that the nervous system is one of the two major control systems of the body, and now we turn our attention to the other—

the endocrine system The endocrine system consists

of all those glands, called endocrine glands , that secrete hormones, as well as hormone-secreting cells located in various organs such as the heart, kidneys, liver, and stomach

which carries them from their site of secretion to the cells upon which they act The cells a particular hormone influences are known as the target cells for that hormone

The aim of this chapter is to first present a detailed overview

of endocrinology—that is, a structural and functional analysis

of general features of hormones—followed by a more detailed analysis of several important hormonal systems Before continuing, you should review the principles of ligand- receptor interactions and cell signaling that were described

in Chapter 3 (Section C) and Chapter 5, because they pertain

to the mechanisms by which hormones exert their actions

Hormones functionally link various organ systems together As such, several of the general principles of physiology first introduced in Chapter 1 apply to the study

of the endocrine system, including the principle that the functions of organ systems are coordinated with each other

This coordination is key to the maintenance of homeostasis, another important general principle of physiology that will be covered in Sections C, D, and F In many cases, the actions of one hormone can be potentiated, inhibited, or counterbalanced by the actions of another This illustrates the general principle of physiology that most physiological functions are controlled by multiple regulatory systems, often working in opposition It will be especially relevant

in the sections on the endocrine control of metabolism and the control of pituitary gland function Finally, this chapter exemplifies the general principle of physiology that information f low between cells, tissues, and organs is an essential feature of homeostasis and allows for integration of physiological processes

wid78305_ch11_319-361.indd 320 09/01/13 9:54 PM

Trang 20

TABLE 11.6 Major Hormones Influencing

Growth

Hormone Principal Actions

Growth hormone

Major stimulus of postnatal growth: Induces precursor cells to differentiate and secrete insulin-like growth factor 1 (IGF-1), which stimulates cell division

Stimulates liver to secrete IGF-1 Stimulates protein synthesis Insulin Stimulates fetal growth

Stimulates postnatal growth by stimulating secretion of IGF-1

Stimulates protein synthesis Thyroid

Testosterone Stimulates growth at puberty, in large part by

stimulating the secretion of growth hormone Causes eventual epiphyseal closure Stimulates protein synthesis in male Estrogen Stimulates the secretion of growth hormone

at puberty Causes eventual epiphyseal closure Cortisol Inhibits growth

Stimulates protein catabolism

Figure 11.20 (a) Location of the bilobed thyroid gland

(b) A cross section through several adjoining follicles filled with colloid (b): © Biophoto Associates/Photo Researchers

Artery

Larynx

Thyroid gland

Common carotid artery

Trachea

(a)

Thyroid follicle (contains colloid)

Follicular cells Section of one follicle

(b)

Figure 11.9 The ability of thyroid hormone to “permit”

epinephrine-induced release of fatty acids from adipose tissue

cells Thyroid hormone exerts this effect by causing an increased

number of beta-adrenergic receptors on the cell Thyroid hormone

by itself stimulates only a small amount of fatty acid release

P H Y S I O L O G I C A L I N Q U I R Y

■ A patient is observed to have symptoms that are consistent with

elevated concentrations of epinephrine in the blood, including a

rapid heart rate, anxiety, and elevated fatty acid concentrations

and found to be in the normal range What might explain this?

Answer can be found at end of chapter

Little or no fatty acids released Small amount

of fatty acids released

Large amount

of fatty acids released

Epinephrine + thyroid hormone Epinephrine Thyroid hormone Time

Thyroid hormone Epinephrine

Epinephrine + thyroid hormone

of the textbook They are designed to help students become more engaged in learning

a concept or process depicted in the art These questions challenge a student to analyze the content of the figure, and occasionally to recall information from previous chapters

Many of the questions also require quantitative skills Many instructors find that these Physiological Inquiries make great exam questions

Summary Tables

Summary tables are used to bring together large amounts of information that

may be scattered throughout the book or to summarize small or moderate

amounts of information The tables complement the accompanying figures to

provide a rapid means of reviewing the most important material in the chapter

Anatomy and Physiology Revealed (APR)

Icon—NEW!

APR icons are found in figure legends These icons indicate

that there is a direct link to APR available

in the eBook provided with Connect Plus

for this title!

Descriptive Art Style

A realistic three-dimensional perspective is included in

many of the figures for greater clarity and understanding

of concepts presented

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Figure 11.22 TRH-TSH-thyroid hormone sequence T 3 and T 4 inhibit secretion of TSH and TRH by negative feedback, indicated by the E symbol

Target cells for thyroid hormone

T4 converted to T3Respond to increased T3 Plasma thyroid hormone

Hypothalamus

Neural inputs Begin

Figure 11.16 Hormone secretion by the anterior pituitary gland is controlled by hypophysiotropic hormones released by hypothalamic neurons and reaching the anterior pituitary gland by way of the hypothalamo–hypophyseal portal vessels

Hypothalamo–

hypophyseal portal vessels

Arterial inflow from heart Blood flow

Capillaries

in median

Anterior pituitary gland capillaries

Anterior gland cells

Hypothalamic neuron

Hypophysiotropic hormones

Anterior gland capillary

b Pseudohypoparathyroidism is caused by target-organ resistance to the action of PTH

c Secondary hyperparathyroidism is caused by vitamin

D deficiency due to inadequate intake, absorption, or activation in the kidney (e.g., in kidney disease)

SEC TI O N F R EV I EW QU E S T IONS

1 Describe bone remodeling

2 Describe the handling of Ca 2 1 by the kidneys and gastrointestinal tract

3 What controls the secretion of parathyroid hormone, and what are the major effects of this hormone?

4 Describe the formation and action of 1,25-(OH) 2 D How does parathyroid hormone influence the production of this hormone?

SEC TI O N F K EY T E R M S

calcitonin 356 1,25-(OH) 2 D 355 hydroxyapatite 354 hypercalcemia 356 hypocalcemia 357 mineralization 354 osteoclast 354 osteocyte 354

osteoid 353 parathyroid gland 355 parathyroid hormone (PTH) 354 vitamin D 355 vitamin D 2 (ergocalciferol) 355 vitamin D 3 (cholecalciferol) 355

SEC TI O N F CL I N IC A L T E R M S

bisphosphonate 356 humoral hypercalcemia of malignancy 357 hypocalcemic tetany 357 osteomalacia 356 osteoporosis 356 primary hyperparathyroidism 356 primary

hypoparathyroidism 357

pseudohypoparathyroidism 357 PTH-related peptide (PTHrp) 357 rickets 356 secondary hyperparathyroidism 357 selective estrogen receptor modulator (SERM) 356

SEC TI O N F SU M M A RY

I The effector sites for the regulation of plasma Ca 2 1 concentration are bone, the gastrointestinal tract, and the kidneys

II Approximately 99% of total-body Ca 2 1 is contained in bone as minerals on a collagen matrix Bone is constantly remodeled

as a result of the interaction of osteoblasts and osteoclasts, a process that determines bone mass and provides a means for raising or lowering plasma Ca 2 1 concentration

III Ca 2 1 is actively absorbed by the gastrointestinal tract, and this process is under hormonal control

xviii

Flow Diagrams

Long a hallmark of this book, extensive use of flow diagrams is continued

in this edition They have been updated to assist in learning

Key to Flow Diagrams

End of Section

At the end of sections throughout the book, you will find a summary, review questions, key terms, and clinical terms

Uniform Color-Coded Illustrations

Color-coding is effectively used to promote learning For example, there are specific colors for extracellular fluid, the intracellular fluid, muscle filaments, and transporter molecules

Multilevel Perspective

Illustrations depicting complex structures or processes combine macroscopic and microscopic views to help students see the relationships between increasingly detailed drawings

Guided Tour Through a Chapter

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C H A P T E R 11 GENERAL PRINCIPLES ASSESSMENT Answers found in Appendix A

1 Referring back to Tables 11.3 , 11.4 , and 11.5 , explain how

certain of the actions of epinephrine, cortisol, and growth hormone illustrate in part the general principle of physiology

that most physiological functions are controlled by multiple regulatory

systems, often working in opposition

2 Another general principle of physiology is that structure is a

determinant of—and has coevolved with—function The structure

of the thyroid gland is very unlike other endocrine glands How

is the structure of this gland related to its function?

3 Homeostasis is essential for health and survival How do

parathyroid hormone, ADH, and thyroid hormone contribute

to homeostasis? What might be the consequence of having too little of each of those hormones?

Figure 11.3 By storing large amounts of hormone in an

endocrine cell, the plasma concentration of the hormone can

be increased within seconds when the cell is stimulated Such rapid responses may be critical for an appropriate response to a challenge to homeostasis Packaging peptides in this way also prevents intracellular degradation

Figure 11.5 Because steroid hormones are derived from

cholesterol, they are lipophilic Consequently, they can freely diffuse through lipid bilayers, including those that constitute secretory vesicles Therefore, once a steroid hormone is synthesized, it diffuses out of the cell

Figure 11.9 One explanation for this patient's symptoms may

be that his or her circulating concentration of thyroid hormone was elevated This might occur if the person's thyroid was overstimulated due, for example, to thyroid disease The

C H A P T E R 11 ANSWERS TO PHYSIOLOGICAL INQUIRIES

is possible The colloid permits a long-term store of iodinated thyroglobulin that can be used during times when dietary iodine intake is reduced or absent

Figure 11.24 Plasma cortisol concentrations would increase

This would result in decreased ACTH concentrations in the systemic blood, and CRH concentrations in the portal vein blood, due to increased negative feedback at the pituitary gland shrink in size (atrophy) as a consequence of the decreased ACTH concentrations (decreased “trophic” stimulation of the adrenal cortex)

Figure 11.28 Note from the figure that a decrease in plasma

glucose concentrations results in an increase in growth hormone concentrations This makes sense, because one of the metabolic actions of growth hormone is to increase the

control of the anterior pituitary gland by a very small number

of discrete neurons within the hypothalamus

Figure 11.21 Iodine is not widely found in foods; in the absence

of iodized salt, an acute or chronic deficiency in dietary iodine

p q y p p y concentrations will decrease This is a form of secondary hypoparathyroidism

Visit this book’s website at www.mhhe.com/widmaier13 for chapter quizzes, interactive learning exercises, and other study tools.

human physiology

wid78305_ch11_319-361.indd 361 09/01/13 9:54 PM

C H A P T E R 11 TEST QUESTIONS Answers found in Appendix A

1–5: Match the hormone with the function or feature (choices a–e)

a tropic for the adrenal cortex

b is controlled by an amine-derived hormone of the hypothalamus

c antidiuresis

d stimulation of testosterone production

e stimulation of uterine contractions during labor

6 In the following figure, which hormone (A or B) binds to receptor X with higher affinity?

B

Concentration of free hormone

A

7 Which is not a symptom of Cushing's disease?

a high blood pressure

b bone loss

c suppressed immune function

d goiter

e hyperglycemia (increased blood glucose)

8 Tremors, nervousness, and increased heart rate can all be symptoms of

a increased activation of the sympathetic nervous system

b excessive secretion of epinephrine from the adrenal medulla

c hyperthyroidism

d hypothyroidism

e answers a, b, and c (all are correct)

9 Which of the following could theoretically result in short stature?

a pituitary tumor making excess thyroid-stimulating hormone

b mutations that result in inactive IGF-1 receptors

c delayed onset of puberty

d decreased hypothalamic concentrations of somatostatin

e normal plasma GH but decreased feedback of GH on GHRH

10 Choose the correct statement

a During times of stress, cortisol acts as an anabolic hormone

in muscle and adipose tissue

b A deficiency of thyroid hormone would result in increased cellular concentrations of Na 1 /K 1 -ATPase pumps in target tissues

c The posterior pituitary is connected to the hypothalamus by long portal vessels

d Adrenal insufficiency often results in increased blood pressure and increased plasma glucose concentrations

e A lack of iodide in the diet will have no significant effect on the concentration of circulating thyroid hormone for at least several weeks

11 A lower-than-normal concentration of plasma Ca 2 1 causes

a a PTH-mediated increase in 25-OH D

b a decrease in renal 1-hydroxylase activity

c a decrease in the urinary excretion of Ca 2 1

d a decrease in bone resorption

e an increase in vitamin D release from the skin

12 Which of the following is not consistent with primary

hyperparathyroidism?

a hypercalcemia

b elevated plasma 1,25-(OH) 2 D

c increased urinary excretion of phosphate ions

d a decrease in Ca 2 1 resorption from bone

e an increase in Ca 2 1 reabsorption in the kidney

CHAPTER 11 QUANTITATIVE AND THOUGHT QUESTIONS Answers found at www.mhhe.com/widmaier13

1 In an experimental animal, the sympathetic preganglionic fibers

to the adrenal medulla are cut What happens to the plasma concentration of epinephrine at rest and during stress?

2 During pregnancy, there is an increase in the liver’s production and, consequently, the plasma concentration of the major plasma binding protein for thyroid hormone This causes

a sequence of events involving feedback that results in an increase in the plasma concentrations of T 3 but no evidence of hyperthyroidism Describe the sequence of events

3 A child shows the following symptoms: deficient growth, failure to show sexual development, decreased ability to respond to stress What is the most likely cause of all these symptoms?

4 If all the neural connections between the hypothalamus and pituitary gland below the median eminence were severed, the secretion of which pituitary gland hormones would be affected?

Which pituitary gland hormones would not be affected?

5 Typically, an antibody to a peptide combines with the peptide and renders it nonfunctional If an animal were given an antibody to somatostatin, the secretion of which anterior pituitary gland hormone would change and in what direction?

6 A drug that blocks the action of norepinephrine is injected directly into the hypothalamus of an experimental animal, and the secretion rates of several anterior pituitary gland hormones are observed to change How is this possible, given the fact that norepinephrine is not a hypophysiotropic hormone?

xix

End of Chapter

At the end of the chapters, you will find

comprehension of key concepts

questions that test the student’s ability to relate the material covered in a given chapter to one

or more of the General Principles of Physiology described in Chapter 1 This provides a

powerful unifying theme to understanding all

of physiology, and is also an excellent gauge of

a student’s progress from the beginning to the end of a semester

challenge the student to go beyond the memorization of facts, to solve problems and

to encourage thinking about the meaning or broader significance of what has just been read

chapter

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Chapter 1 Homeostasis: A Framework for Human

Physiology

New section introducing and describing the important

General Principles of Physiology, providing an

instructional framework that unifies all the chapters

Chapter 2 Chemical Composition of the Body

Increased emphasis on the physiological relevance of

chemical principles; expanded discussion of the use of

isotopes in physiology with a new PET scan figure; ionic

bonds treated in a new section

Chapter 3 Cellular Structure, Proteins, and

Metabolism

Importance of cholesterol in determining membrane

fluidity is now discussed and illustrated

Chapter 4 Movement of Molecules Across Cell

Membranes

Compensatory endocytosis now discussed

Chapter 5 Control of Cells by Chemical

Messengers

Illustrations of receptor conformations with and without

bound ligand are now depicted to emphasize

binding-induced shape changes linked to receptor activation; IP 3

receptor/ion channel now depicted in illustration of cell

Chapter 7 Sensory Physiology

A new table has been added summarizing the general principles of sensory stimulus processing; discussion

of Müller cells added to section on retinal function;

expanded discussion and illustration of the mechanism

by which retinal dissociates from its opsin and is enzymatically reassociated

Chapter 8 Consciousness, the Brain, and Behavior

A comparison between PET, MRI, and EEG as effective tools for assessing tumors, clots, or hemorrhages in the brain has been added; new discussion of high-frequency gamma-wave patterns; updated the NREM designations to the new Phase N1–N3 nomenclature;

discussion of hypnic jerk movements added; new section added describing the neural basis of the conscious state, including the role of RAS monoamine, orexins/

hypocretins, and the “sleep center” of the brain;

discussion of narcolepsy; new discussion regarding the role of the right cerebral hemisphere in the emotional context of language; new figure illustrating brain regions

Updates and Additions

In addition to updating material throughout the text to reflect cutting-edge changes in physiology and medicine, the authors have

introduced the following:

These are outlined in Chapter 1 in a new section called General Principles of Physiology, and include such things as

homeostasis, structure/function relationships, information flow, and several others Beginning with Chapter 2, the

introduction to each chapter provides a preview for the student of the general principles that will be covered in that

chapter Within the chapter, the principles are reinforced where appropriate At the end of each chapter, one or more

assessments are provided that enable the student to relate the material in that chapter to an understanding of unifying

physiological themes

complement the many test questions available free of charge to students on the McGraw-Hill website that accompanies

the textbook

indicated that this learning tool is extremely valuable, and thus we have added additional inquiries associated with key

figures

In addition to new assessments, and the usual editing to make sure the text remains even more reader-friendly, up-to-date,

and accurate, approximately 25 new pieces of art have been added, and another 25 existing pieces of art have been considerably

modified to provide updated information A sampling of substantive changes to each chapter follows

Trang 24

involved in consciousness; a new figure showing a model

of the regulation of sleep/wake transitions; new figure

of a CT scan of the brain of a person with an epidural hemorrhage

Chapter 9 Muscle

A new figure illustrating cardiac muscle excitation–

contraction coupling; reorganization of the first two sections of the chapter such that events are described in the order in which they occur: excitation, E–C coupling, sliding filament mechanism; updated discussion about muscle fatigue; new discussion about myostatin and its role in muscle mass; new discussion about caldesmon’s role

in smooth muscle function

Chapter 10 Control of Body Movement

Interconnections of structures participating in the motor control hierarchy have been updated; new example demonstrating the importance of association areas in motor control

Chapter 11 The Endocrine System

Role of pendrin in thyroid hormone synthesis now introduced and illustrated; steroid synthetic pathway simplified to illustrate major events; improved illustration

of anatomical relationship between hypothalamus and anterior pituitary gland; addition of numerous specific examples to highlight general principles, such as hyporesponsiveness; new figure showing production of insulin from proinsulin

Chapter 12 Cardiovascular Physiology

Numerous figures have been updated or improved for clarity, or modified to include additional important information; discussion added about internodal pathways between the SA and AV nodes; new description about transient outward K 1 channels in myocytes; new table added comparing hemodynamics of systemic and pulmonary circuits; new discussion about VEGF antibodies and angiogenesis; section on hypertension has been updated to include the latest information about the effects of a high-salt diet, the findings of the DASH diet study, and other environmental causes or links to hypertension

Chapter 13 Respiratory Physiology

New information about the cystic fibrosis channel mutation and treatment of cystic fibrosis; new figure showing the muscles of respiration; new improved illustration of respiratory cycle; enhanced illustration of the factors that change the shape of the O 2 dissociation

curve including a panel on fetal hemoglobin; new figure on brainstem respiratory control centers and simplification of the description of respiratory control

Chapter 14 The Kidneys and Regulation of Water and Inorganic Ions

New figure showing major anatomical structures of the kidney; new figure and text describing the effects

of vasopressin on the volume and osmolarity of the filtrate along the length of the nephron; revised and expanded discussion of the local and central control

reorganization of portions of the text to improve the flow of the chapter

Chapter 16 Regulation of Organic Metabolism and Energy Balance

New figure on energy expenditure during common activities; streamlined text with greater emphasis on general principles of physiology

Chapter 17 Reproduction

Reorganization of first two sections into a single new section entitled Gametogenesis, Sex Determination, and Sex Differentiation; General Principles of Reproductive Endocrinology; several new figures illustrating the events of gametogenesis, embryonic development of the male and female reproductive tracts, development of external genitalia in males and females, and synthesis of gonadal steroids; new section on anabolic steroid use

Chapter 18 The Immune System

Additional artwork and photographs including a new micrograph of a human blood smear, a new micrograph of a leukocyte undergoing diapedesis, and

a computer model of an immunoglobulin

Chapter 19 Medical Physiology: Integration Using Clinical Cases

This chapter reinforces the General Physiological Principles introduced in Chapter 1 by demonstrating how these principles relate to human disease

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text website Chapters offer a series of interactive activities

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Steven Magill, Medical College of Wisconsin David L Mattson, Medical College of Wisconsin Donald W Michielli , Brooklyn College of the City University of

New York

Kevin Middleton , California State University Paul Nealen , Indiana University of PA Lisa Parks , North Carolina State University Mark Paternostro , West Virginia University Timothy Plagge , San Diego Mesa College Jocelyn Parks Ramos , Ivy Tech Community College Laurel B Roberts , University of Pittsburgh Angela M Seliga , Boston University Virginia K Shea , University of North Carolina Mark Smith , Santiago Canyon College

Andrea Sobieraj , Brown University Nadja Spitzer , Marshall University Ruy Tchao , University of the Sciences Dana K Vaughan , University of Wisconsin–Oshkosh Gordon M Wahler , Midwestern University

R Douglas Watson , University of Alabama at Birmingham Eliot Williams, University of Wisconsin–Madison SMPH Loren E Wold , The Research Institute at Nationwide Children’s

Hospital/The Ohio State University

Yuri Zagvazdin , Nova Southeastern University

The authors are indebted to the many individuals who assisted with the numerous digital and ancillary products associated with these text Thank you to Beth Altschafl, Patti Atkins, Janet Casagrand, Patricia Clark, Mike Griffin, David Johnson, Tami Mau, Carla Reinstadtl, Laurel Bridges Roberts, Rebecca Sheller, Andrea Jeanne Sobieraj, Nadja Spitzer, and Melanie Waite-Wright

The authors are also indebted to the editors and staff at McGraw-Hill Higher Education who contributed to the devel-opment and publication of this text, particularly Developmen-tal Editor Fran Simon, Brand Manager Marija Magner, Project Manager Sherry Kane, Production Supervisor Sandy Ludovissy, Designer Tara McDermott, and Photo Researcher John Leland

We also thank freelance copy editor C Jeanne Patterson and freelance proofreader Beatrice Sussman As always, we are grate-ful to the many students and faculty who have provided us with critiques and suggestions for improvement

Eric P Widmaier Hershel Raff Kevin T Strang

The authors are deeply indebted to the following individuals for

their contributions to the thirteenth edition of Vander’s Human

Physiology Their feedback on the twelfth edition or their critique

of the revised text provided invaluable assistance and greatly

improved the final product Any errors that may remain are

solely the responsibility of the authors

Allan Albig, Indiana State University

Lisa Carney Anderson, University of Minnesota

Heather Wilson-Ashworth, Utah Valley University

Kim Barrett, University of California, San Diego

Daniel Bergman, Grand Valley State University

Nicole Berthelemy , Weber State University

Robert W Blair , University of Oklahoma Health Sciences Center

Eric Blough , Marshall University

Carol A Britson , University of Mississippi

George A Brooks, University of California–Berkeley

Martin G Burg , Grand Valley State University

Patricia Cai , Brooklyn College of CUNY

Edwin R Chapman , University of Wisconsin–Madison

Pat Clark , IUPUI

Maria Elena de Bellard , CSUN

Lee D Faucher, University of Wisconsin–Madison SMPH

James S Ferraro , Southern Illinois University–School

of Medicine

Margaret Flanigan Skinner , University of Wyoming

Kennon M Garrett , University of Oklahoma Health

Sciences Center

Nicholas Geist , Sonoma State University

Brian Geraghty , CUNY @ Brooklyn College & Kingsborough

Community College

Chaya Gopalan , St Louis College of Pharmacy

Marion Greaser, University of Wisconsin–Madison

Eric Green , Salt Lake Community College

Chi-Ming Hai , Brown University

Janet L Haynes , Long Island University

Steve Henderson , California State University

David W Johnson , University of New England

Kelly Johnson , Kansas University

Tim Juergens, University of Wisconsin–Madison SMPH

Kenneth Kaloustian , Quinnipiac University

David King , Nova Southeastern University

Brian H Kipp , Grand Valley State University

Sumana Koduri, Medical College of Wisconsin

Dean V Lauritzen , City College of San Francisco

Mingyu Liang, Medical College of Wisconsin

Christian Lytle, University of California, Riverside

Acknowledgments

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1

T he purpose of this chapter is to provide an orientation to the

subject of human physiology and the central role of homeostasis

in the study of this science An understanding of the functions

of the body also requires knowledge of the structures and relationships of

the body parts For this reason, this chapter also introduces the way the

body is organized into cells, tissues, organs, and organ systems Lastly,

several “General Principles of Physiology” are introduced These serve as

unifying themes throughout the textbook, and the student is encouraged

to return to them often to see how they apply to the material covered in

subsequent chapters

Muscle Cells and Tissue Neurons and Nervous Tissue Epithelial Cells and Epithelial Tissue Connective-Tissue Cells and Connective Tissue Organs and Organ Systems

Control Systems

Reflexes Local Homeostatic Responses

Chemical Messengers in Homeostasis

Chapter 1 Clinical Case Study

Homeostasis:

A FR AME WORK FOR HUMAN PHYSIOLOGY

Maintenance of body temperature

is an example of homeostasis.

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2 Chapter 1

1.1 The Scope of Human Physiology

Physiology is the study of how living organisms function

As applied to human beings, its scope is extremely broad At

one end of the spectrum, it includes the study of individual

molecules—for example, how a particular protein’s shape

and electrical properties allow it to function as a channel for

ions to move into or out of a cell At the other end, it is

con-cerned with complex processes that depend on the integrated

functions of many organs in the body—for example, how the

heart, kidneys, and several glands all work together to cause

the excretion of more sodium ions in the urine when a person

has eaten salty food

Physiologists are interested in function and integration—

how parts of the body work together at various levels of

organi-zation and, most importantly, in the entire organism Even when

physiologists study parts of organisms, all the way down to

indi-vidual molecules, the intention is ultimately to apply the

infor-mation they gain to understanding the function of the whole

body As the nineteenth-century physiologist Claude Bernard

put it, “After carrying out an analysis of phenomena, we must

. . always reconstruct our physiological synthesis, so as to see

the joint action of all the parts we have isolated. . . .”

In this regard, a very important point must be made

about the present and future status of physiology It is

easy for a student to gain the impression from a textbook

that almost everything is known about the subject, but

nothing could be farther from the truth for physiology

Many areas of function are still only poorly understood,

such as how the workings of the brain produce conscious

thought and memory

Finally, in many areas of this text, we will relate

physiology to medicine Some disease states can be viewed

as physiology “gone wrong,” or pathophysiology , which

makes an understanding of physiology essential for the

study and practice of medicine Indeed, many

physiolo-gists are actively engaged in research on the physiological

bases of a wide range of diseases In this text, we will give

many examples of pathophysiology to illustrate the basic

physiology that underlies the disease A handy index of all

the diseases and medical conditions discussed in this text

appears in Appendix B We begin our study of

physiol-ogy by describing the organization of the structures of the

human body

1.2 How Is the Body Organized?

Before exploring how the human body works, it is

neces-sary to understand the components of the body and their

anatomical relationships to each other The simplest

struc-tural units into which a complex multicellular organism

can be divided and still retain the functions

begins as a single cell, a fertilized egg, which divides to

create two cells, each of which divides in turn to result in

four cells, and so on If cell multiplication were the only

event occurring, the end result would be a spherical mass

of identical cells During development, however, each cell

becomes specialized for the performance of a particular function, such as producing force and movement or gen-erating electrical signals The process of transforming an

unspecialized cell into a specialized cell is known as cell

Fertilized egg

Cell division and growth

Cell differentiation

Specialized cell types

Tissues

Functional unit (nephron)

Organ (kidney)

Organ system (Urinary system)

Epithelial cell

tissue cell

Connective-Neuron Muscle

cell

Epithelial tissue

Connective tissue

Nervous tissue

Muscle tissue

Ureter

Bladder Urethra Kidney

Figure 1.1 Levels of cellular organization The nephron is not drawn to scale

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structure and function of each of the three types of muscle cells in Chapter 9

Neurons and Nervous Tissue

A neuron is a cell of the nervous system that is specialized

to initiate, integrate, and conduct electrical signals to other cells, sometimes over long distances A signal may initiate new electrical signals in other neurons, or it may stimulate a gland cell to secrete substances or a muscle cell to contract Thus, neurons provide a major means of controlling the activities of other cells The incredible complexity of connections between neurons underlies such phenomena as consciousness and per-ception A collection of neurons forms nervous tissue, such

as that of the brain or spinal cord In some parts of the body, cellular extensions from many neurons are packaged together along with connective tissue (described shortly); these neuron extensions form a nerve, which carries the signals from many neurons between the nervous system and other parts of the body Neurons, nervous tissue, and the nervous system will be covered in Chapter 6

Epithelial Cells and Epithelial Tissue

Epithelial cells are specialized for the selective secretion and

absorption of ions and organic molecules, and for protection These cells are characterized and named according to their unique shapes, including cuboidal (cube-shaped), columnar (elongated), squamous (flattened), and ciliated Epithelial tissue (known as an epithelium) may form from any type of epithelial cell Epithelia may be arranged in single-cell-thick tissue, called a simple epithelium, or a thicker tissue consist-ing of numerous layers of cells, called a stratified epithelium The type of epithelium that forms in a given region of the body reflects the function of that particular epithelium For example, the epithelium that lines the inner surface of the main airway, the trachea, consists of ciliated epithelial cells (see Chapter 13) The beating of these cilia helps propel mucus

up the trachea and into the mouth, which aids in preventing airborne particles and pollutants from reaching the sensitive lung tissue

Epithelia are located at the surfaces that cover the body

or individual organs, and they line the inner surfaces of the tubular and hollow structures within the body, such as the tra-chea just mentioned Epithelial cells rest on an extracellular

protein layer called the basement membrane , which (among

the cell anchored to the basement membrane is called the lateral side; the opposite side, which typically faces the interior (called the lumen) of a structure such as the trachea or the tubules of the kidney (see Figure 1.1 ), is called the apical side

baso-A defining feature of many epithelia is that the two sides of all the epithelial cells in the tissue may perform different physio-logical functions In addition, the cells are held together along their lateral surfaces by extracellular barriers called tight junctions (look ahead to Figure 3.9, b and c, for a depiction

of tight junctions) Tight junctions enable epithelia to form boundaries between body compartments and to function as selective barriers regulating the exchange of molecules For

differentiation , the study of which is one of the most

exciting areas in biology today About 200 distinct kinds

of cells can be identified in the body in terms of

differ-ences in structure and function When cells are classified

according to the broad types of function they perform,

however, four major categories emerge: (1) muscle cells,

(2) neurons, (3) epithelial cells, and (4) connective-tissue

cells In each of these functional categories, several cell

types perform variations of the specialized function For

example, there are three types of muscle cells— skeletal,

cardiac, and smooth These cells differ from each other

in shape, in the mechanisms controlling their contractile

activity, and in their location in the various organs of the

body, but each of them is a muscle cell

In addition to differentiating, cells migrate to new tions during development and form selective adhesions with

loca-other cells to produce multicellular structures In this manner,

the cells of the body arrange themselves in various

combina-tions to form a hierarchy of organized structures

Differenti-ated cells with similar properties aggregate to form tissues

Corresponding to the four general categories of differentiated

cells, there are four general types of tissues: (1) muscle tissue ,

(2) nervous tissue , (3) epithelial tissue , and (4) connective

tissue The term tissue is used in different ways It is formally

defined as an aggregate of a single type of specialized cell

However, it is also commonly used to denote the general

cel-lular fabric of any organ or structure—for example, kidney

tissue or lung tissue, each of which in fact usually contains all

four types of tissue

One type of tissue combines with other types of tissues

to form organs , such as the heart, lungs, and kidneys Organs,

in turn, work together as organ systems , such as the urinary

system ( see Figure 1.1 ) We turn now to a brief discussion of

each of the four general types of cells and tissues that make up

the organs of the human body

Muscle Cells and Tissue

As noted earlier, there are three types of muscle cells These

cells form skeletal, cardiac, or smooth muscle tissue All

muscle cells are specialized to generate mechanical force

Skeletal muscle cells are attached through other structures

to bones and produce movements of the limbs or trunk

They are also attached to skin, such as the muscles

produc-ing facial expressions Contraction of skeletal muscle is under

voluntary control, which simply means that you can choose

to contract a skeletal muscle whenever you wish Cardiac

muscle cells are found only in the heart When cardiac

mus-cle cells generate force, the heart contracts and consequently

pumps blood into the circulation Smooth muscle cells

sur-round many of the tubes in the body—blood vessels, for

example, or the tubes of the gastrointestinal tract—and their

contraction decreases the diameter or shortens the length of

these tubes For example, contraction of smooth muscle cells

along the esophagus—the tube leading from the pharynx to

the stomach—helps “squeeze” swallowed food down to the

stomach Cardiac and smooth muscle tissues are said to be

“involuntary” muscle, because you cannot consciously alter

the activity of these types of muscle You will learn about the

Trang 31

4 Chapter 1

of a mixture of proteins; polysaccharides (chains of sugar molecules); and, in some cases, minerals, specific for any given tissue The matrix serves two general functions: (1) it provides a scaffold for cellular attachments; and (2) it trans-mits information in the form of chemical messengers to the cells to help regulate their activity, migration, growth, and differentiation

The proteins of the extracellular matrix consist of

proteins called fibers —ropelike collagen fibers and

proteins that contain carbohydrate In some ways, the cellular matrix is analogous to reinforced concrete The fibers of the matrix, particularly collagen, which consti-tutes as much as one-third of all bodily proteins, are like the reinforcing iron mesh or rods in the concrete The carbo-hydrate-containing protein molecules are analogous to the surrounding cement However, these latter molecules are not merely inert packing material, as in concrete, but function as adhesion or recognition molecules between cells Thus, they are links in the communication between extracellular mes-senger molecules and cells

Organs and Organ Systems

Organs are composed of two or more of the four kinds of tissues arranged in various proportions and patterns, such

as sheets, tubes, layers, bundles, and strips For example, the kidneys consist of (1) a series of small tubes, each composed

of a simple epithelium; (2) blood vessels, whose walls contain varying quantities of smooth muscle and connective tissue;

(3) extensions from neurons that end near the muscle and epithelial cells; (4) a loose network of connective-tissue elements that are interspersed throughout the kidneys and include the protective capsule that surrounds the organ

Many organs are organized into small, similar subunits

often referred to as functional units , each performing the

function of the organ For example, the functional unit of the kidney, the nephron, contains the small tubes mentioned in the previous paragraph The total production of urine by the kidneys is the sum of the amounts produced by the 2 million

or so individual nephrons

Finally, we have the organ system, a collection of organs that together perform an overall function For example, the kidneys; the urinary bladder; the ureters, the tubes leading from the kidneys to the bladder; and the urethra, the tube leading from the bladder to the exterior, constitute the urinary

organ systems in the body

To sum up, the human body can be viewed as a complex society of differentiated cells that combine structurally and functionally to carry out the functions essential to the sur-vival of the entire organism The individual cells constitute the basic units of this society, and almost all of these cells individually exhibit the fundamental activities common to all forms of life, such as metabolism and replication Key

to the survival of all body cells is the internal environment of

the body; this refers to the fluids that surround cells and exist

in the blood These fluid compartments and one other—that which exists inside cells—are described next

example, the epithelial cells at the surface of the skin form a

barrier that prevents most substances in the external

environ-ment from entering the body through the skin In the kidney

tubules, the apical membranes transport useful solutes such

as the sugar glucose from the tubule lumen into the epithelial

cell; the basolateral sides of the cells transport glucose out of

the cell and into the surrounding fluid where it can reach the

bloodstream The tight junctions prevent glucose from

leak-ing “backward.”

Connective-Tissue Cells

and Connective Tissue

anchor, and support the structures of the body Some

connective-tissue cells are found in the loose meshwork of

cells and fibers underlying most epithelial layers; this is called

loose connective tissue Another type called dense connective

tissue includes the tough, rigid tissue that makes up tendons

and ligaments Other types of connective tissue include bone,

cartilage, and adipose (fat-storing) tissue Finally, blood is a

type of fluid connective tissue This is because the cells in the

blood have the same embryonic origin as other connective

tis-sue, and because the blood connects the various organs and

tissues of the body through the delivery of nutrients, removal

of wastes, and transport of chemical signals from one part of

the body to another

An important function of some connective tissue is to

form the extracellular matrix (ECM) around cells The

immediate environment that surrounds each individual

cell in the body is the extracellular f luid Actually, this

fluid is interspersed within a complex ECM consisting

Basolateral membranes Blood vessel

Tubular lumen

Tight junction

Apical membrane

Basement membrane

Glucose molecule Epithelial cell

Figure 1.2 Epithelial tissue lining the inside of a structure such as a

kidney tubule The basolateral side of the cell is attached to a basement

membrane Each side of the cell can perform different functions, as

in this example in which glucose is moved across the epithelium, first

directed into the cell, and then directed out of the cell

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stomach, small and large intestines, anus, pancreas, liver, gallbladder

Digestion and absorption of nutrients and water;

elimination of wastes

testes, ovaries, hypothalamus, kidneys, pituitary, thyroid, parathyroids, adrenals, stomach, small intestine, liver, adipose tissue, heart, and pineal gland; and endocrine cells in other organs

Regulation and coordination of many activities in the body, including growth, metabolism, reproduction, blood pressure, water and electrolyte balance, and others

pathogens; regulation of body temperature

participation in immune defenses; absorption of fats from digestive system

Regulation and coordination of many activities in the body;

detection of and response to changes in the internal and external environments; states of consciousness; learning;

memory; emotion; others

glands Female: Ovaries, fallopian tubes, uterus, vagina, mammary glands

Male: Production of sperm; transfer of sperm to female Female: Production of eggs; provision of a nutritive environment for the developing embryo and fetus; nutrition

of the infant

hydrogen ion concentration in the body fluids

excretion of salts, water, and organic wastes

1.3 Body Fluid Compartments

Water is present within and around the cells of the body, and

within all the blood vessels When we refer to “body fluids,”

we are referring to a watery solution of dissolved substances

such as oxygen, nutrients, and wastes Body fluids exist in

two major compartments, intracellular fluid and extracellular

fluid Intracellular fluid is the fluid contained within all the

cells of the body and accounts for about 67% of all the fluid

in the body Collectively, the fluid present in the blood and

in the spaces surrounding cells is called extracellular fluid ,

that is, all the fluid that is outside of cells Of this, only about

20%–25% is in the fluid portion of blood, which is called the

plasma , in which the various blood cells are suspended The

remaining 75%–80% of the extracellular fluid, which lies

around and between cells, is known as the interstitial fluid

The space containing interstitial fluid is called the tium Therefore, the total volume of extracellular fluid is

summarizes the relative volumes of water in the different fluid compartments of the body Water accounts for about 55%–60%

of body weight in an adult

As the blood flows through the smallest of blood sels in all parts of the body, the plasma exchanges oxygen, nutrients, wastes, and other substances with the interstitial fluid Because of these exchanges, concentrations of dissolved substances are virtually identical in the plasma and intersti-tial fluid, except for protein concentration (which, as you will learn in Chapter 12, remains higher in plasma than in inter-stitial fluid) With this major exception, the entire extracel-lular fluid may be considered to have a homogeneous solute composition In contrast, the composition of the extracellular

Trang 33

ves-6 Chapter 1

life-sustaining forces (“humours”) in the body It would take millennia, however, for scientists to determine what it was that was being balanced and how this balance was achieved

The advent of modern tools of science, including the nary microscope, led to the discovery that the human body is composed of trillions of cells, each of which can permit move-ment of certain substances—but not others—across the cell membrane Over the course of the nineteenth and twentieth centuries, it became clear that most cells are in contact with the interstitial fluid The interstitial fluid, in turn, was found

ordi-to be in a state of flux, with water and solutes such as ions and gases moving back and forth through it between the cell inte-riors and the blood in nearby capillaries (see Figure 1.3 )

It was further determined by careful observation that most of the common physiological variables found in healthy organisms such as humans—blood pressure; body tempera-ture; and blood-borne factors such as oxygen, glucose, and sodium ions, for example—are maintained within a predictable range This is true despite external environmental conditions that may be far from constant Thus was born the idea, first put forth by Claude Bernard, of a constant internal environment that is a prerequisite for good health, a concept later refined

by the American physiologist Walter Cannon, who coined the

term homeostasis

Originally, homeostasis was defined as a state of

rea-sonably stable balance between physiological variables such as those just described However, this simple definition cannot give one a complete appreciation of what homeostasis entails

There probably is no such thing as a physiological variable that

is constant over long periods of time In fact, some variables undergo fairly dramatic swings around an average value dur-ing the course of a day, yet are still considered to be in balance

That is because homeostasis is a dynamic, not a static, process

fluid is very different from that of the intracellular fluid

Maintaining differences in fluid composition across the cell

membrane is an important way in which cells regulate their

own activity For example, intracellular fluid contains many

different proteins that are important in regulating cellular

events such as growth and metabolism These proteins must

be retained within the intracellular fluid and are not required

in the extracellular fluid

Compartmentalization is an important feature of

physi-ology and is achieved by barriers between the compartments

The properties of the barriers determine which substances

can move between compartments These movements, in turn,

account for the differences in composition of the different

com-partments In the case of the body fluid compartments, plasma

membranes that surround each cell separate the intracellular

fluid from the extracellular fluid Chapters 3 and 4 describe the

properties of plasma membranes and how they account for the

profound differences between intracellular and extracellular

fluid In contrast, the two components of extracellular fluid—

the interstitial fluid and the plasma—are separated by the wall

of the blood vessels Chapter 12 discusses how this barrier

nor-mally keeps 75%–80% of the extracellular fluid in the

intersti-tial compartment and restricts proteins mainly to the plasma

With this understanding of the structural

organiza-tion of the body, we turn to a descriporganiza-tion of how balance is

achieved in the internal environment of the body

1.4 Homeostasis: A Defining Feature

of Physiology

From the earliest days of physiology—at least as early as the

time of Aristotle—physicians recognized that good health

was somehow associated with a balance among the multiple

Red blood cell

70 60 50 40 30 20

10 (7%)

(26%)

(67%)

Figure 1.3 Fluid compartments of the body Volumes are for an average 70-kilogram (kg) (154-pound [lb]) person (a) The bidirectional

arrows indicate that fluid can move between any two adjacent compartments Total-body water is about 42 liters (L), which makes up about

55%–60% of body weight (b) The approximate percentage of total-body water normally found in each compartment

person’s body weight is due to extracellular body water?

Answer can be found at end of chapter

Trang 34

time This has led to the concept that homeostasis is a state

of dynamic constancy In such a state, a given variable like

blood glucose may vary in the short term but is stable and dictable when averaged over the long term

It is also important to realize that a person may be homeostatic for one variable but not homeostatic for another Homeostasis must be described differently, therefore, for each variable For example, as long as the concentration of sodium ions in the blood remains within a few percentage points of its normal range, sodium homeostasis exists How-ever, a person whose sodium ion concentrations are homeo-static may suffer from other disturbances, such as abnormally high carbon dioxide levels in the blood resulting from lung disease, a condition that could be fatal Just one nonhomeo-static variable, among the many that can be described, can have life-threatening consequences Often, when one variable becomes dramatically out of balance, other variables in the body become nonhomeostatic as a consequence For example, when you exercise strenuously and begin to get warm, you perspire to help maintain body temperature homeostasis This is important, because many cells (notably neurons) mal-function at elevated temperatures However, the water that

is lost in perspiration creates a situation in which total-body water is no longer in balance In general, if all the major organ systems are operating in a homeostatic manner, a person is in good health Certain kinds of disease, in fact, can be defined

as the loss of homeostasis in one or more systems in the body

To elaborate on our earlier definition of physiology, therefore,

when homeostasis is maintained, we refer to physiology; when

it is not, we refer to pathophysiology (from the Greek pathos,

meaning “suffering” or “disease”)

1.5 General Characteristics

of Homeostatic Control Systems

The activities of cells, tissues, and organs must be regulated and integrated with each other so that any change in the extracellular fluid initiates a reaction to correct the change The compensating mechanisms that mediate such responses

are performed by homeostatic control systems

Consider again an example of the regulation of body temperature This time, our subject is a resting, lightly clad man in a room having a temperature of 20 8 C and moderate humidity His internal body temperature is 37 8 C, and he is losing heat to the external environment because it is at a lower temperature However, the chemical reactions occurring within the cells of his body are producing heat at a rate equal to the rate of heat loss Under these conditions, the body under-

goes no net gain or loss of heat, and the body temperature

remains constant The system is in a steady state , defined

as a system in which a particular variable— temperature, in this case—is not changing but in which energy—in this case, heat—must be added continuously to maintain a constant

condition (Steady state differs from equilibrium , in which

a particular variable is not changing but no input of energy

is required to maintain the constancy.) The steady-state

tem-perature in our example is known as the set point of the

ther-moregulatory system

Consider swings in the concentration of glucose in the blood

carbohydrates in food are broken down in the intestines into

glucose molecules, which are then absorbed across the

intesti-nal epithelium and released into the blood As a consequence,

blood glucose concentrations increase considerably within

a short time after eating Clearly, such a large change in the

blood concentration of glucose is not consistent with the idea

of a stable or static internal environment What is important is

that once the concentration of glucose in the blood increases,

compensatory mechanisms restore it toward the

concentra-tion it was before the meal These homeostatic compensatory

mechanisms do not, however, overshoot to any significant

degree in the opposite direction That is, the blood glucose

usually does not decrease below the premeal concentration,

or does so only slightly In the case of glucose, the endocrine

system is primarily responsible for this adjustment, but a wide

variety of control systems may be initiated to regulate other

processes In later chapters, we will see how every organ and

tissue of the human body contributes to homeostasis,

some-times in multiple ways, and usually in concert with each other

Homeostasis, therefore, does not imply that a given physiological function or variable is rigidly constant with

respect to time but that it fluctuates within a predictable and

often narrow range When disturbed above or below the

nor-mal range, it is restored to nornor-mal

What do we mean when we say that something varies within a normal range? This depends on just what we are

monitoring If the oxygen level in the blood of a healthy

per-son breathing air at sea level is measured, it barely changes

over the course of time, even if the person exercises Such a

system is said to be tightly controlled and to demonstrate very

little variability or scatter around an average value Blood

glu-cose concentrations, as we have seen, may vary considerably

over the course of a day Yet, if the daily average glucose

centration was determined in the same person on many

con-secutive days, it would be much more predictable over days

or even years than random, individual measurements of

glu-cose over the course of a single day In other words, there may

be considerable variation in glucose values over short time

periods, but less when they are averaged over long periods of

100 120

140

Lunch Dinner

Figure 1.4 Changes in blood glucose concentrations during

a typical 24 h period Note that glucose concentration increases

after each meal, more so after larger meals, and then returns to the

premeal concentration in a short while The profile shown here is

that of a person who is homeostatic for blood glucose, even though

concentrations of this sugar vary considerably throughout the day.

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8 Chapter 1

from the skin Like the person shown in the chapter opening photo, our subject hunches his shoulders and folds his arms in order to reduce the surface area of the skin available for heat loss This helps somewhat, but excessive heat loss still con-tinues, and body temperature keeps decreasing, although at a slower rate Clearly, then, if excessive heat loss (output) cannot

be prevented, the only way of restoring the balance between heat input and output is to increase input, and this is precisely what occurs Our subject begins to shiver, and the chemical reactions responsible for the skeletal muscle contractions that constitute shivering produce large quantities of heat

Feedback Systems

The thermoregulatory system just described is an example of a

negative feedback system, in which an increase or decrease in

the variable being regulated brings about responses that tend

to move the variable in the direction opposite (“negative” to) the direction of the original change Thus, in our example,

a decrease in body temperature led to responses that tended

to increase the body temperature—that is, move it toward its original value

Without negative feedback, oscillations like some of those described in this chapter would be much greater and, there-fore, the variability in a given system would increase Negative feedback also prevents the compensatory responses to a loss of homeostasis from continuing unabated Details of the mecha-nisms and characteristics of negative feedback in different sys-tems will be addressed in later chapters For now, it is important

to recognize that negative feedback plays a vital part in the checks and balances on most physiological variables

Negative feedback may occur at the organ, cellular, or molecular level For instance, negative feedback regulates many enzymatic processes, as shown in schematic form in

reactions.) In this example, the product formed from a strate by an enzyme negatively feeds back to inhibit further action of the enzyme This may occur by several processes, such as chemical modification of the enzyme by the product

sub-of the reaction The production sub-of adenosine triphosphate (ATP) within cells is a good example of a chemical process regulated by feedback Normally, glucose molecules are enzymatically broken down inside cells to release some of the chemical energy that was contained in the bonds of the molecule This energy is then stored in the bonds of ATP

The energy from ATP can later be tapped by cells to power such functions as muscle contraction, cellular secretions, and transport of molecules across cell membranes As ATP accumulates in the cell, however, it inhibits the activity of some of the enzymes involved in the breakdown of glucose

Therefore, as ATP concentrations increase within a cell, further production of ATP slows down due to negative feed-back Conversely, if ATP concentrations decrease within a cell, negative feedback is removed and more glucose is bro-ken down so that more ATP can be produced

Not all forms of feedback are negative In some cases,

positive feedback accelerates a process, leading to an

“explo-sive” system This is counter to the principle of homeostasis, because positive feedback has no obvious means of stopping

Not surprisingly, therefore, positive feedback is much less

This example illustrates a crucial generalization about

homeostasis Stability of an internal environmental variable is

achieved by the balancing of inputs and outputs In the

pre-vious example, the variable (body temperature) remains

con-stant because metabolic heat production (input) equals heat

loss from the body (output)

Now imagine that we rapidly reduce the temperature of the

room, say to 5 8 C, and keep it there This immediately increases

the loss of heat from our subject’s warm skin, upsetting the

bal-ance between heat gain and loss The body temperature therefore

starts to decrease Very rapidly, however, a variety of homeostatic

these responses The reader is urged to study Figure 1.5 and its

leg-end carefully because the figure is typical of those used throughout the

remainder of the book to illustrate homeostatic systems, and the legend

emphasizes several conventions common to such figures

The first homeostatic response is that blood vessels to the

skin become constricted (narrowed), reducing the amount of

blood flowing through the skin This reduces heat loss from

the blood to the environment and helps maintain body

tem-perature At a room temperature of 5 8 C, however, blood

ves-sel constriction cannot completely eliminate the extra heat loss

Return of body temperature toward original value Heat loss from body Heat production

Constriction of skin

blood vessels Curling up Shivering

(Body’s responses) Body temperature

Heat loss from body

Room temperature Begin

Figure 1.5 A homeostatic control system maintains body

temperature when room temperature decreases This flow

diagram is typical of those used throughout this book to illustrate

homeostatic systems, and several conventions should be noted

The “Begin” sign indicates where to start The arrows next to each

term within the boxes denote increases or decreases The arrows

connecting any two boxes in the figure denote cause and effect;

that is, an arrow can be read as “causes” or “leads to.” (For example,

decreased room temperature “leads to” increased heat loss from the

body.) In general, you should add the words “tends to” in thinking

about these cause-and-effect relationships For example, decreased

room temperature tends to cause an increase in heat loss from the

body, and curling up tends to cause a decrease in heat loss from the

body Qualifying the relationship in this way is necessary because

variables like heat production and heat loss are under the influence

of many factors, some of which oppose each other.

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as the presence of pathogens, but this is not the case Indeed, the set points for many regulated variables change on a rhyth-mic basis every day For example, the set point for body tem-perature is higher during the day than at night

Although the resetting of a set point is adaptive in some cases, in others it simply reflects the clashing demands of dif-ferent regulatory systems This brings us to one more gener-alization It is not possible for everything to be held constant

by homeostatic control systems In our earlier example, body temperature was maintained despite large swings in ambient temperature, but only because the homeostatic control system brought about large changes in skin blood flow and skeletal muscle contraction Moreover, because so many properties of the internal environment are closely interrelated, it is often possible to keep one property relatively stable only by moving others away from their usual set point This is what we mean

by “clashing demands,” which explains the phenomenon tioned earlier about the interplay between body temperature and water balance during exercise

The generalizations we have given about homeostatic

is that, as is illustrated by the regulation of body temperature, multiple systems usually control a single parameter The adap-tive value of such redundancy is that it provides much greater fine-tuning and also permits regulation to occur even when one

of the systems is not functioning properly because of disease

Feedforward Regulation

Another type of regulatory process often used in conjunction with

feedback systems is feedforward Let us give an example of

feedfor-ward and then define it The temperature-sensitive neurons that trigger negative feedback regulation of body temperature when

common in nature than negative feedback Nonetheless, there

are examples in physiology in which positive feedback is very

important One well-described example, which you will learn

about in Chapter 17, is the process of parturition (birth) As the

uterine muscles contract and a baby’s head is pressed against

the mother’s cervix during labor, signals are relayed via nerves

from the cervix to the mother’s brain The brain initiates the

secretion into the blood of a molecule called oxytocin from the

mother’s pituitary gland Oxytocin is a potent stimulator of

fur-ther uterine contractions As the uterus contracts even harder in

response to oxytocin, the baby’s head is pushed harder against

the cervix, causing it to stretch more; this stimulates yet more

nerve signals to the mother’s brain, resulting in yet more

oxy-tocin secretion This self-perpetuating cycle continues until

finally the baby pushes through the stretched cervix and is born

Resetting of Set Points

As we have seen, changes in the external environment can

dis-place a variable from its set point In addition, the set points for

many regulated variables can be physiologically reset to a new

value A common example is fever, the increase in body

temper-ature that occurs in response to infection and that is somewhat

analogous to raising the setting of a thermostat in a room The

homeostatic control systems regulating body temperature are

still functioning during a fever, but they maintain the

tempera-ture at an increased value This regulated increase in body

tem-perature is adaptive for fighting the infection, because elevated

temperature inhibits proliferation of some pathogens In fact,

this is why a fever is often preceded by chills and shivering The

set point for body temperature has been reset to a higher value,

and the body responds by shivering to generate heat

The example of fever may have left the impression that set points are reset only in response to external stimuli, such

Figure 1.6 Hypothetical example of negative feedback (as

denoted by the circled minus sign and dashed feedback line) occurring

within a set of sequential chemical reactions By inhibiting the activity

of the first enzyme involved in the formation of a product, the product

can regulate the rate of its own formation.

was removed?

Answer can be found at end of chapter.

Stability of an internal environmental variable is achieved by balancing inputs and outputs It is not the absolute magnitudes of the inputs and outputs that matter but the balance between them.

In negative feedback, a change in the variable being regulated brings about responses that tend to move the variable in the direction opposite the original change—that is, back toward the initial value (set point).

Homeostatic control systems cannot maintain complete constancy of any given feature of the internal environment

Therefore, any regulated variable will have a more or less narrow range of normal values depending on the external environmental conditions.

The set point of some variables regulated by homeostatic control systems can be reset—that is, physiologically raised or lowered.

It is not always possible for homeostatic control systems to maintain every variable within a narrow normal range in response to an environmental challenge There is a hierarchy of importance, so that certain variables may be altered markedly

to maintain others within their normal range.

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10 Chapter 1

environment, such as a change in temperature, plasma

the environmental change A stimulus acts upon a receptor to

produce a signal that is relayed to an integrating center The

signal travels between the receptor and the integrating center

along the afferent pathway (the general term afferent means

“to carry to,” in this case, to the integrating center)

An integrating center often receives signals from many receptors, some of which may respond to quite different types

of stimuli Thus, the output of an integrating center reflects the net effect of the total afferent input; that is, it represents an integration of numerous bits of information

The output of an integrating center is sent to the last component of the system, whose change in activity consti-tutes the overall response of the system This component is

known as an effector The information going from an

inte-grating center to an effector is like a command directing the effector to alter its activity This information travels along the

efferent pathway (the general term efferent means “to carry

away from,” in this case, away from the integrating center)

Thus far, we have described the reflex arc as the sequence of events linking a stimulus to a response If the response produced by the effector causes a decrease in the magnitude of the stimulus that triggered the sequence of events, then the reflex leads to negative feedback and we have

a typical homeostatic control system Not all reflexes are associated with such feedback For example, the smell of food stimulates the stomach to secrete molecules that are impor-tant for digestion, but these molecules do not eliminate the smell of food (the stimulus)

feedback homeostatic reflex arc in the process of tion The temperature receptors are the endings of certain neu-rons in various parts of the body They generate electrical signals

thermoregula-in the neurons at a rate determthermoregula-ined by the temperature These electrical signals are conducted by nerves containing processes from the neurons—the afferent pathway—to the brain, where the integrating center for temperature regulation is located The

it begins to decrease are located inside the body In addition,

there are temperature-sensitive neurons in the skin; these cells, in

effect, monitor outside temperature When outside temperature

decreases, as in our example, these neurons immediately detect

the change and relay this information to the brain The brain

then sends out signals to the blood vessels and muscles,

result-ing in heat conservation and increased heat production In this

manner, compensatory thermoregulatory responses are activated

before the colder outside temperature can cause the internal body

temperature to decrease In another familiar example, the smell of

food triggers nerve responses from odor receptors in the nose to

the cells of the digestive system The effect is to prepare the

diges-tive system for the arrival of food before we even consume it, for

example by inducing saliva to be secreted in the mouth and

caus-ing the stomach to churn and produce acid Thus, feedforward

regulation anticipates changes in regulated variables such as

inter-nal body temperature or energy availability, improves the speed

of the body’s homeostatic responses, and minimizes fluctuations

in the level of the variable being regulated—that is, it reduces the

amount of deviation from the set point

In our examples, feedforward regulation utilizes a set of

external or internal environmental detectors It is likely, however,

that many examples of feedforward regulation are the result of

a different phenomenon—learning The first times they occur,

early in life, perturbations in the external environment

prob-ably cause relatively large changes in regulated internal

environ-mental factors, and in responding to these changes the central

nervous system learns to anticipate them and resist them more

effectively A familiar form of this is the increased heart rate that

occurs in an athlete just before a competition begins

1.6 Components of Homeostatic

Control Systems

Reflexes

The thermoregulatory system we used as an example in the

pre-vious section and many of the other homeostatic control systems

belong to the general category of stimulus–response sequences

known as reflexes Although in some reflexes we are aware of

the stimulus and/or the response, many reflexes regulating the

internal environment occur without our conscious awareness

In the narrowest sense of the word, a reflex is a

spe-cific, involuntary, unpremeditated, “built-in” response to a

particular stimulus Examples of such reflexes include

pull-ing your hand away from a hot object or shuttpull-ing your eyes

as an object rapidly approaches your face Many responses,

however, appear automatic and stereotyped but are actually

the result of learning and practice For example, an

experi-enced driver performs many complicated acts in operating

a car To the driver, these motions are, in large part,

auto-matic, stereotyped, and unpremeditated, but they occur only

because a great deal of conscious effort was spent learning

them We term such reflexes learned or acquired reflexes

In general, most reflexes, no matter how simple they may

appear to be, are subject to alteration by learning

The pathway mediating a reflex is known as the reflex

arc , and its components are shown in Figure 1.7 A stimulus

is defined as a detectable change in the internal or external

Response

Afferent pathway

Negative feedback

Integrating center

(Compare to set point)

Efferent pathway

Effector Receptor

Stimulus Begin

Figure 1.7 General components of a reflex arc that functions

as a negative feedback control system The response of the system has the effect of counteracting or eliminating the stimulus This phenomenon of negative feedback is emphasized by the minus sign

in the dashed feedback loop.

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Local Homeostatic Responses

In addition to reflexes, another group of biological responses,

called local homeostatic responses , is of great importance for

homeostasis These responses are initiated by a change in the external or internal environment (that is, a stimulus), and they induce an alteration of cell activity with the net effect of counter-acting the stimulus Like a reflex, therefore, a local response is the result of a sequence of events proceeding from a stimulus Unlike a reflex, however, the entire sequence occurs only in the area of the stimulus For example, when cells of a tissue become very meta-bolically active, they secrete substances into the interstitial fluid that dilate (widen) local blood vessels The resulting increased blood flow increases the rate at which nutrients and oxygen are delivered to that area, and the rate at which wastes are removed The significance of local responses is that they provide individual areas of the body with mechanisms for local self-regulation

1.7 The Role of Intercellular Chemical Messengers

in Homeostasis

Essential to reflexes and local homeostatic responses—and therefore to homeostasis—is the ability of cells to communicate with one another In this way, cells in the brain, for example, can

be made aware of the status of activities of structures outside the brain, such as the heart, and help regulate those activities to meet new homeostatic challenges In the majority of cases, intercellular

integrating center, in turn, sends signals out along neurons that

cause skeletal muscles and the muscles in skin blood vessels to

contract The neurons to the muscles are the efferent pathway,

and the muscles are the effectors The dashed arrow and the

negative sign indicate the negative feedback nature of the reflex

Almost all body cells can act as effectors in homeostatic reflexes Muscles and glands, however, are the major effectors

of biological control systems In the case of glands, for

exam-ple, the effector may be a hormone secreted into the blood A

hormone is a type of chemical messenger secreted into the

blood by cells of the endocrine system (see Table 1.1 )

Hor-mones may act on many different cells simultaneously because

they circulate throughout the body

Traditionally, the term reflex was restricted to situations

in which the receptors, afferent pathway, integrating center,

and efferent pathway were all parts of the nervous system, as

in the thermoregulatory reflex However, the principles are

essentially the same when a blood-borne chemical messenger,

rather than a nerve, serves as the efferent pathway, or when

a hormone-secreting gland serves as the integrating center

In our use of the term reflex, therefore, we include

hor-mones as reflex components Moreover, depending on the

specific nature of the reflex, the integrating center may reside

either in the nervous system or in a gland In addition, a gland

may act as both receptor and integrating center in a reflex

For example, the gland cells that secrete the hormone

insu-lin, which decreases plasma glucose concentration, also detect

increases in the plasma glucose concentration

Figure 1.8 Reflex for minimizing the decrease in body temperature that occurs on exposure to a reduced external environmental

temperature This figure provides the internal components for the reflex shown in Figure 1.5 The dashed arrow and the E indicate the

negative feedback nature of the reflex, denoting that the reflex responses cause the decreased body temperature to return toward normal

An additional flow-diagram convention is shown in this figure: blue boxes always denote events that are occurring in anatomical structures

(labeled in blue italic type in the upper portion of the box).

Answer can be found at end of chapter.

Heat loss

INTEGRATING CENTER

Heat production STIMULUS

Smooth muscle in skin blood vessels

Contraction (Shivering)

Skeletal muscle

Begin

Temperature-sensitive neurons

Signaling rate

Decreased body temperature

Specific neurons in brain

Compare to set point; alter rates of firing

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12 Chapter 1

There is one category of local chemical messengers that

are not inter cellular messengers—that is, they do not nicate between cells Rather, the chemical is secreted by a cell

commu-into the extracellular fluid and then acts upon the very cell that

secreted it Such messengers are called autocrine substances (or

agents) (see Figure 1.9 ) Frequently, a messenger may serve both paracrine and autocrine functions simultaneously—that is, mol-ecules of the messenger released by a cell may act locally on adja-cent cells as well as on the same cell that released the messenger

A point of great importance must be emphasized here

to avoid later confusion A neuron, endocrine gland cell, and other cell type may all secrete the same chemical messenger

In some cases, a particular messenger may sometimes tion as a neurotransmitter, a hormone, or a paracrine or auto-crine substance Norepinephrine, for example, is not only a neurotransmitter in the brain; it is also produced as a hormone

func-by cells of the adrenal glands

All types of intercellular communication described thus far in this section involve secretion of a chemical messenger into the extracellular fluid However, there are two important types of chemical communication between cells that do not require such secretion In the first type, which occurs via gap junctions (physical linkages connecting the cytosol between two cells; see Chapter 3), molecules move from one cell to an adja-cent cell without entering the extracellular fluid In the second type, the chemical messenger is not actually released from the cell producing it but rather is located in the plasma membrane

of that cell When the cell encounters another cell type ble of responding to the message, the two cells link up via the membrane-bound messenger This type of signaling, sometimes

capa-termed juxtacrine, is of particular importance in the growth and

differentiation of tissues as well as in the functioning of cells that protect the body against pathogens (Chapter 18)

1.8 Processes Related to Homeostasis

Adaptation and Acclimatization

The term adaptation denotes a characteristic that favors

survival in specific environments Homeostatic control systems are inherited biological adaptations The ability to

communication is performed by chemical messengers There are

three categories of such messengers: hormones,

As noted earlier, a hormone functions as a chemical

messenger that enables the hormone-secreting cell to

com-municate with cells acted upon by the hormone—its target

cells —with the blood acting as the delivery system

Hor-mones are produced in and secreted from endocrine glands

or in scattered cells that are distributed throughout another

organ They play key roles in essentially all physiological

pro-cesses, including growth, reproduction, metabolism, mineral

balance, and blood pressure, and are often produced whenever

homeostasis is threatened

In contrast to hormones, neurotransmitters are

chemi-cal messengers that are released from the endings of neurons

onto other neurons, muscle cells, or gland cells A

neurotrans-mitter diffuses through the extracellular fluid separating the

neuron and its target cell; it is not released into the blood like

a hormone Neurotransmitters and their roles in neuronal

sig-naling and brain function will be covered in Chapter 6 In the

context of homeostasis, they form the signaling basis of some

reflexes, as well as playing a vital role in the compensatory

responses to a wide variety of challenges, such as the

require-ment for increased heart and lung function during exercise

Chemical messengers participate not only in reflexes

but also in local responses Chemical messengers involved in

local communication between cells are known as paracrine

substances (or agents) Paracrine substances are synthesized

by cells and released, once given the appropriate stimulus,

into the extracellular fluid They then diffuse to

neighbor-ing cells, some of which are their target cells Given this

broad definition, neurotransmitters could be classified as

a subgroup of paracrine substances, but by convention they

are not Once they have performed their functions,

para-crine substances are generally inactivated by locally existing

enzymes and therefore they do not enter the bloodstream in

large quantities Paracrine substances are produced

through-out the body; an example of their key role in homeostasis that

you will learn about in Chapter 15 is their ability to

fine-tune the amount of acid produced by cells of the stomach in

Blood

vessel

Local cell Local cell

Target cells in close proximity to site of release of paracrine substance

Neuron or effector cell in close proximity

to site of transmitter release

neuro-Autocrine substance acts on same cell that secreted the substance

Figure 1.9 Categories of chemical messengers With the exception of autocrine messengers, all messengers act between

cells—that is, intercellularly.

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sleep, metabolism is slower than during the active hours, and therefore body temperature decreases at that time A crucial point concerning most body rhythms is that they are inter-nally driven Environmental factors do not drive the rhythm

but rather provide the timing cues important for ment , or setting of the actual hours of the rhythm A classic

entrain-experiment will clarify this distinction

Subjects were put in experimental chambers that pletely isolated them from their usual external environment, including knowledge of the time of day For the first few days, they were exposed to a 24 h rest–activity cycle in which the room lights were turned on and off at the same times each day Under these conditions, their sleep–wake cycles were

com-24 h long Then, all environmental time cues were eliminated, and the subjects were allowed to control the lights themselves Immediately, their sleep–wake patterns began to change On average, bedtime began about 30 min later each day, and so did wake-up time Thus, a sleep–wake cycle persisted in the com-plete absence of environmental cues Such a rhythm is called

a free-running rhythm In this case, it was approximately

24.5 h rather than 24 This indicates that cues are required to entrain or set a circadian rhythm to 24 h

The light–dark cycle is the most important mental time cue in our lives—but not the only one Others include external environmental temperature, meal timing, and many social cues Thus, if several people were undergoing the experiment just described in isolation from each other, their free-running rhythms would be somewhat different, but if they were all in the same room, social cues would entrain all of them to the same rhythm

Environmental time cues also function to phase-shift

rhythms—in other words, to reset the internal clock Thus, if you fly west or east to a different time zone, your sleep–wake cycle and other circadian rhythms slowly shift to the new light–dark cycle These shifts take time, however, and the dis-parity between external time and internal time is one of the causes of the symptoms of jet lag—a disruption of homeo-stasis that leads to gastrointestinal disturbances, decreased vigilance and attention span, sleep problems, and a general feeling of malaise

Similar symptoms occur in workers on permanent or rotating night shifts These people generally do not adapt

respond to a particular environmental stress is not fixed,

however, but can be enhanced by prolonged exposure to

that stress This type of adaptation—the improved

func-tioning of an already existing homeostatic system—is

known as acclimatization

Let us take sweating in response to heat exposure as

an example and perform a simple experiment On day 1, we

expose a person for 30 minutes (min) to an elevated

tempera-ture and ask her to do a standardized exercise test Body

tem-perature increases, and sweating begins after a certain period

of time The sweating provides a mechanism for increasing

heat loss from the body and therefore tends to minimize the

increase in body temperature in a hot environment The

vol-ume of sweat produced under these conditions is measured

Then, for a week, our subject enters the heat chamber for 1 or

2 hours (h) per day and exercises On day 8, her body

temper-ature and sweating rate are again measured during the same

exercise test performed on day 1 The striking finding is that

the subject begins to sweat sooner and much more profusely

than she did on day 1 As a consequence, her body

tempera-ture does not increase to nearly the same degree The subject

has become acclimatized to the heat She has undergone an

adaptive change induced by repeated exposure to the heat and

is now better able to respond to heat exposure

Acclimatizations are usually reversible If, in the example just described, the daily exposures to heat are discontinued, our

subject’s sweating rate will revert to the preacclimatized value

within a relatively short time

The precise anatomical and physiological changes that bring about increased capacity to withstand change during

acclimatization are highly varied Typically, they involve an

increase in the number, size, or sensitivity of one or more of

the cell types in the homeostatic control system that mediates

the basic response

Biological Rhythms

As noted earlier, a striking characteristic of many body

functions is the rhythmic changes they manifest The most

common type is the circadian rhythm , which cycles

approx-imately once every 24 h Waking and sleeping, body

temper-ature, hormone concentrations in the blood, the excretion of

ions into the urine, and many other functions undergo

cir-cadian variation; an example of one type of rhythm is shown

What do biological rhythms have to do with stasis? They add an anticipatory component to homeostatic

homeo-control systems, in effect, a feedforward system

operat-ing without detectors The negative feedback homeostatic

responses we described earlier in this chapter are corrective

responses They are initiated after the steady state of the

indi-vidual has been perturbed In contrast, biological rhythms

enable homeostatic mechanisms to be utilized immediately

and automatically by activating them at times when a

For example, body temperature increases prior to waking

in a person on a typical sleep–wake cycle This allows the

metabolic machinery of the body to operate most efficiently

immediately upon waking, because metabolism (chemical

reactions) is to some extent temperature dependent During

38 Lights on Lights off

2:00 P.M.

10:00 P.M.

6:00 A.M.

2:00 P.M.

10:00 P.M.

Figure 1.10 Circadian rhythm of body temperature in a human subject with room lights on (open bars at top) for 16 h, and off (blue bars at top) for 8 h Note the increase in body temperature that occurs just prior to lights on, in anticipation of the increased activity and metabolism that occur during waking hours

Adapted from Moore-Ede and Sulzman.

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