Vander's Human Physiology: The

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Sixteenth Edition

HUMAN
Vander’s

PHYSIOLOGY The Mechanisms of Body Function

Eric P. Widmaier | Hershel Raff | Kevin T. Strang

ISTUDY
 SIXTEENTH EDITION VA N D E R ’ S

Human
Physiology
The Mechanisms of Body Function

ERIC P. WIDMAIER
B O S TO N U N I V E R S I T Y

HERSHEL RAFF
M E D I C A L CO L L E G E O F W I S CO N S I N
AU R O R A S T. LU K E ’ S M E D I C A L C E N T E R /
A DVO C AT E AU R O R A R E S E A R C H I N S T I T U T E

KEVIN T. STRANG
U N I V E R S I T Y O F W I S CO N S I N – M A D I S O N

ISTUDY
 VANDER’S HUMAN PHYSIOLOGY

Published by McGraw Hill LLC, 1325 Avenue of the Americas, New York, NY 10019. Copyright ©2023 by McGraw Hill LLC.
All rights reserved. Printed in the United States of America. No part of this publication may be reproduced or distributed in
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ISTUDY
 BRIEF CONTENTS
MEET THE AUTHORS IV ■ FROM THE AUTHORS V ■ INDEX OF EXERCISE PHYSIOLOGY XV ■ GUIDED TOUR THROUGH A CHAPTER XVI
■ UPDATES AND ADDITIONS XX ■ ACKNOWLEDGMENTS XXI ■ CONNECT XXII

■ 1 Homeostasis: A Framework ■ 10 Control of Body ■ 16 Regulation of Organic

for Human Physiology 1 Movement 300 Metabolism and Energy
Balance 574
■ 2 Chemical Composition of ■ 11 The Endocrine System 319 ■ 
Control and Integration of
the Body and Its Relation to Carbohydrate, Protein, and Fat
■ 
General Characteristics of
Physiology 21 Hormones and Hormonal Control
Metabolism 575
Systems 320 ■ 
Regulation of Total-Body Energy
■ 3 Cellular Structure, ■ 
The Hypothalamus and
Balance 589

Proteins, and Metabolic Pituitary Gland 332 ■ 

Regulation of Body
Temperature 594
Pathways 45 ■ The Thyroid Gland 338

■ Cell Structure 46
■ 
T he Endocrine Response to
Stress 343
■ 17 Reproduction 604
■ 
Protein Synthesis, Degradation, ■ 
■ 
Endocrine Control of Growth 347 Overview and Gametogenesis,
and Secretion 57 Sex Determination, and Sex
■  Endocrine Control of Ca2+
■  Differentiation; General
Interactions Between Proteins and
Homeostasis 351 Principles of Reproductive
Ligands 66
■ 
Chemical Reactions and
Enzymes 71
■ 12 Cardiovascular
Endocrinology 605
■ 
Male Reproductive
Physiology 361 Physiology 614
■ Metabolic Pathways 78
■ 
General Features of the ■ 
Female Reproductive
■ 4 Movement of Solutes Circulatory System 362 Physiology 624
and Water Across Cell ■ The Heart 371 ■ 
P regnancy, Contraception,
Infertility, and Hormonal Changes
Membranes 95 ■ The Vascular System 389 Through Life 637

■ 5 Cell Signaling in
■ 
Integration of Cardiovascular
Function: Regulation of Systemic ■ 18 The Immune System 659
Physiology 118 Arterial Pressure 409
■ 
Cardiovascular Patterns in Health ■ 19 Medical Physiology:
■ 6 Neuronal Signaling and the
and Disease 417
■ 
Hemostasis: The Prevention of
Integration Using Clinical
Structure of the Nervous Blood Loss 430
Cases 697
System 136
■ Cells of the Nervous System 137
■ 13 Respiratory APPENDIX A A-1
Physiology 445
■ Membrane Potentials 143 APPENDIX B A-42
■ Synapses 158 ■ 14 The Kidneys and APPENDIX C A-46
■ 
Structure of the Nervous Regulation of Water
System 172
and Inorganic Ions 490 GLOSSARY/INDEX GI-1

■ 7 Sensory Physiology 190 ■ 

Basic Principles of Renal
Physiology 491
■ General Principles 191
■ 
Regulation of Ion and Water
■ Specific Sensory Systems 201 Balance 505

■ 8 Consciousness, the Brain, ■ 

Hydrogen Ion Regulation 523
and Behavior 234 ■ 15 The Digestion and
Absorption of Food 534
■ 9 Muscle 257
■ Skeletal Muscle 258
■ Smooth and Cardiac Muscle 286

iii

ISTUDY
 MEET THE AUTHORS
ERIC P. WIDMAIER received his Ph.D. in 1984 in Endocrinology from the University of
California at San Francisco. His postdoctoral training was in molecular endocrinology, neuroscience,
and physiology at the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts,
and The Salk Institute in La Jolla, California. His research was 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 Emeritus Professor of Biology at Boston
University, where he has taught Human Physiology for many years, and he has been recognized with
the Gitner Award for Distinguished Teaching by the College of Arts and Sciences as well as the Metcalf
Prize for Excellence in Teaching by Boston University. He is the author of many scientific and lay
Photo courtesy of: Maria
publications, including books about physiology for the general reader. He has two grown children, Rick
Widmaier
and Carrie; he and his wife Maria divide their time between New Hampshire and Florida.

H ER SH EL R AFF 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 and Molecular Medicine),
Surgery, and Physiology in the School of Medicine at the Medical College of Wisconsin. He is
Director of the Endocrine Research Laboratory at Aurora St. Luke’s Medical Center/Advocate
Aurora Research Institute. He teaches physiology and pathophysiology to medical, pharmacy,
and graduate students as well as clinical fellows. At the Medical College of Wisconsin, he is
the Endocrinology/Reproduction Course Director for second-year medical students. He was an
inaugural inductee into the Society of Teaching Scholars, elected as a faculty member to Alpha
Omega Alpha (AOA Honor Medical Society), received the Beckman Basic Science Teaching Award
Photo courtesy of: Tonya from the senior MD class five times, and has been one of the MCW’s Outstanding Medical Student
Limberg Teachers in multiple years. He is also an Adjunct Professor of Biomedical Sciences at Marquette
University. Dr. Raff’s basic research focuses on the adaptation to stress. 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.

Photo courtesy of: Kevin Strang
K EVI N T. STR ANG received both his Master’s Degree in Zoology (1988) and his Ph.D.
in Physiology (1994) from the University of Wisconsin–Madison, where he is now an emeritus
Distinguished Faculty Associate in the Departments of Neuroscience and Kinesiology. His thesis
research focused on cellular mechanisms of contractility modulation in cardiac muscle. For over
30 years he taught a large undergraduate systems physiology course as well as the first-year medical
physiology course 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 has been a frequent guest speaker at colleges and high schools on the physiology of alcohol
consumption. Twice awarded the UW Medical Alumni Association’s Distinguished Teaching
Award for Basic Sciences, he 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 physiology animations, some of which were adopted for use with Vander’s Human
Physiology. He has two adult children, Jake and Amy, and lives in Madison with his wife Sheryl.

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

iv

ISTUDY
 FROM THE AUTHORS
Lifeline to success in physiology

We are pleased to offer an integrated package of textual and

digital material to deliver basic and clinical content, real-
life applications, and educational technologies to students of
physiology. With the sixteenth edition of Vander’s Human
Physiology, all these pieces come together to facilitate learn-
ing and enthusiasm for understanding the mechanisms of
body function.
The cover of this edition reflects several areas of focus
of the book, including homeostasis, exercise, and human
health. These and other areas of interest are elaborated
upon, beginning with Chapter 1, where the key “General
Principles of Physiology,” an underlying theme in the book,
is first introduced. Unifying themes, such as homeostasis,
are explored throughout the book at all levels of system,
organ, tissue, and cellular function. As in previous editions,
these themes are always related to pathophysiology through
the use of compelling clinical case studies in all chapters,
and a final chapter with several cases that integrate material
across the entire book.
We are certain that you will find the sixteenth edition
of this textbook to be the most up-to-date and comprehen-
sive book available for students of physiology. Thank you
and happy reading!

Cover Image: Jacob Lund/Shutterstock

ISTUDY
 CONTENTS
MEET THE AUTHORS IV ■ FROM THE AUTHORS V ■ INDEX OF EXERCISE PHYSIOLOGY XV ■ GUIDED TOUR THROUGH A CHAPTER XVI
■ UPDATES AND ADDITIONS XX ■ ACKNOWLEDGMENTS XXI ■ CONNECT XXII

Hydrogen Bonds 27

1
Molecular Shape 27
Homeostasis: A Framework Ionic Molecules 27
for Human Physiology 1 2.3 Solutions 28
Water 28
1.1 The Scope of Human Physiology 2 Molecular Solubility 29
Concentration 30
1.2 How Is the Body Organized? 2
Hydrogen Ions and Acidity 30
Muscle Cells and Tissue 3
2.4 Classes of Organic Molecules 31
Neurons and Nervous Tissue 3
Epithelial Cells and Epithelial Tissue 3 Carbohydrates 31
Connective-Tissue Cells and Connective Tissue 4 Lipids 33
Organs and Organ Systems 4 Proteins 35
Nucleic Acids 39
1.3 Body Fluid Compartments 5
Chapter 2 Clinical Case Study 42
1.4 Homeostasis: A Defining Feature of Physiology 7
1.5 General Characteristics of Homeostatic Control ASSESSMENT QUESTIONS 43
Systems 8
Feedback Systems 9

3
Resetting of Set Points 9
Feedforward Regulation 10 Cellular Structure, Proteins, and
1.6 Components of Homeostatic Control Systems 11 Metabolic Pathways 45
Reflexes 11
Local Homeostatic Responses 13
1.7 The Role of Intercellular Chemical Messengers in Cell Structure 46
Homeostasis 13 3.1 Microscopic Observations of Cells 46
1.8 Processes Related to Homeostasis 14 3.2 Membranes 48
Adaptation and Acclimatization 14 Membrane Structure 48
Biological Rhythms 14 Membrane Junctions 50
Balance of Chemical Substances in the Body 15 3.3 Cell Organelles 52
1.9 General Principles of Physiology 16 Nucleus 52
Chapter 1 Clinical Case Study 17 Ribosomes 52
Endoplasmic Reticulum 53
ASSESSMENT QUESTIONS 20
Golgi Apparatus 53
Endosomes 53
Mitochondria 53

2
Chemical Composition of Lysosomes 54
the Body and Its Relation to Peroxisomes 55
Physiology 21 Cytoskeleton 55

Protein Synthesis, Degradation, and Secretion 57

2.1 Atoms 22
3.4 Genetic Code 57
Components of Atoms 22
Atomic Number 23 3.5 Protein Synthesis 58
Atomic Mass 23 Transcription: mRNA Synthesis 59
Ions 24 Translation: Polypeptide Synthesis 60
Atomic Composition of the Body 24 Regulation of Protein Synthesis 62
2.2 Molecules 25 Mutation 64
Covalent Chemical Bonds 25 3.6 Protein Degradation 65
Ionic Bonds 26

vi

ISTUDY
 3.7 Protein Secretion 65 4.4 Endocytosis and Exocytosis 110
Endocytosis 111
Interactions Between Proteins and Ligands 66 Exocytosis 112
4.5 Epithelial Transport 113
3.8 Binding Site Characteristics 66
Chemical Specificity 66 Chapter 4 Clinical Case Study 115
Affinity 67 ASSESSMENT QUESTIONS 116
Saturation 68
Competition 69
3.9 Regulation of Protein-Binding Activity 69
Allosteric Modulation 70
Covalent Modulation 71
5 Cell Signaling in Physiology 118

Chemical Reactions and Enzymes 71

3.10 Chemical Reactions 71
Determinants of Reaction Rates 72
Reversible and Irreversible Reactions 72
Law of Mass Action 73
3.11 Enzymes 74
Cofactors 74
3.12 Regulation of Enzyme-Mediated
Reactions 75
Substrate Concentration 75
Enzyme Concentration 75
Enzyme Activity 76
3.13 Multienzyme Reactions 76
5.1 Receptors 119
Types of Receptors 119
Interactions Between Receptors and Ligands 119
Regulation of Receptors 122
5.2 Signal Transduction Pathways 122
Pathways Initiated by Lipid-Soluble Messengers 123
Pathways Initiated by Water-Soluble Messengers 124
Major Second Messengers 126
Other Messengers 130
Cessation of Activity in Signal Transduction Pathways 132
Chapter 5 Clinical Case Study 133
ASSESSMENT QUESTIONS 134

Metabolic Pathways 78

3.14 Cellular Energy Transfer 78
Glycolysis 78
Krebs Cycle 80
Oxidative Phosphorylation 82
3.15 Carbohydrate, Fat, and Protein Metabolism 84
Carbohydrate Metabolism 84
Fat Metabolism 86
Protein and Amino Acid Metabolism 88
Metabolism Summary 89
3.16 Essential Nutrients 90
Vitamins 91
Chapter 3 Clinical Case Study 91
ASSESSMENT QUESTIONS 93
6
Neuronal Signaling and
the Structure of the Nervous
System 136
Cells of the Nervous System 137
6.1 Structure and Maintenance of Neurons 137
6.2 Functional Classes of Neurons 138
6.3 Glial Cells 141
6.4 Neural Growth and Regeneration 142
Growth and Development of Neurons 142
Regeneration of Axons 142
Membrane Potentials 143
6.5 Basic Principles of Electricity 143

4
Movement of Solutes and Water
Across Cell Membranes 95
4.1 Diffusion 96
Magnitude and Direction of Diffusion 96
Diffusion Rate Versus Distance 97
Diffusion Through Membranes 97
4.2 Mediated-Transport Systems 100
Facilitated Diffusion 102
Active Transport 102
4.3 Osmosis 106
Extracellular Osmolarity and Cell Volume 108
6.6 The Resting Membrane Potential 144
Nature and Magnitude of the Resting Membrane Potential 144
Contribution of Ion Concentration Differences 145
Contribution of Different Ion Permeabilities 147
Contribution of Ion Pumps 148
Summary of the Development of a Resting Membrane
Potential 148
6.7 Graded Potentials and Action Potentials 149
Graded Potentials 149
Action Potentials 151
Synapses 158
6.8 Functional Anatomy of Synapses 158
Contents vii

ISTUDY
 Electrical Synapses 158 7.4 Association Cortex and Perceptual Processing 200
Chemical Synapses 159 Factors That Affect Perception 200
6.9 Mechanisms of Neurotransmitter Release 159
6.10 Activation of the Postsynaptic Cell 160 Specific Sensory Systems 201
Binding of Neurotransmitters to Receptors 160 7.5 Somatic Sensation 201
Removal of Neurotransmitter from the Synapse 160
Touch and Pressure 201
Excitatory Chemical Synapses 160
Posture and Movement 202
Inhibitory Chemical Synapses 161
Temperature 202
6.11 Synaptic Integration 162 Pain and Itch 202
6.12 Synaptic Strength 163 Neural Pathways of the Somatosensory System 206
Presynaptic Mechanisms 163 7.6 Vision 207
Postsynaptic Mechanisms 164 Light 207
Modification of Synaptic Transmission by Drugs and Overview of Eye Anatomy 208
Disease 164 The Optics of Vision 208
6.13 Neurotransmitters and Neuromodulators 166 Photoreceptor Cells and Phototransduction 210
Acetylcholine 166 Neural Pathways of Vision 213
Biogenic Amines 167 Color Vision 214
Amino Acid Neurotransmitters 168 Color Blindness 216
Neuropeptides 170 Eye Movement 216
Gases 171 Common Diseases of the Eye 217
Purines 171 7.7 Audition 218
Lipids 171 Sound 218
6.14 Neuroeffector Communication 171 Sound Transmission in the Ear 219
Hair Cells of the Organ of Corti 222
Structure of the Nervous System 172 Neural Pathways in Hearing 223
7.8 Vestibular System 224
6.15 Central Nervous System: Brain 172
The Semicircular Canals 224
Forebrain: The Cerebrum 172
The Utricle and Saccule 225
Forebrain: The Diencephalon 175
Vestibular Information and Pathways 225
Hindbrain: The Cerebellum 175
Brainstem: The Midbrain, Pons, and Medulla Oblongata 175 7.9 Chemical Senses 226
6.16 Central Nervous System: Spinal Cord 176 Gustation 226
Olfaction 228
6.17 Peripheral Nervous System 176
Chapter 7 Clinical Case Study 229
6.18 Autonomic Nervous System 179
ASSESSMENT QUESTIONS 232
6.19 Protective Elements Associated with the Brain 183
Meninges and Cerebrospinal Fluid 183
The Blood–Brain Barrier 184

8
Chapter 6 Clinical Case Study 185
Consciousness, the Brain,
ASSESSMENT QUESTIONS 188 and Behavior 234

8.1 States of Consciousness 235

7 Sensory Physiology 190 Electroencephalogram 235

The Waking State 236
Sleep 236
Neural Substrates of States of Consciousness 238
General Principles 191 Coma and Brain Death 240
8.2 Conscious Experiences 241
7.1 Sensory Systems and Receptors 191
Selective Attention 242
The Receptor Potential 192
Neural Mechanisms of Conscious Experiences 242
7.2 Primary Sensory Coding 193
8.3 Motivation and Emotion 244
Stimulus Type 194
Motivation 244
Stimulus Intensity 194
Emotion 245
Stimulus Location 195
Central Control of Afferent Information 197 8.4 Altered States of Consciousness 246
7.3 Ascending Neural Pathways in Sensory Systems 198 Schizophrenia 246
The Mood Disorders: Depression and Bipolar Disorders 247

viii Contents

ISTUDY
 Psychoactive Substances, Tolerance, and Substance
Use Disorders 248
8.5 Learning and Memory 249
Memory 249
The Neural Basis of Learning and Memory 250
8.6 Cerebral Dominance and Language 251
Chapter 8 Clinical Case Study 253
ASSESSMENT QUESTIONS 255
9 Muscle 257
Skeletal Muscle 258
9.1 Structure 258
Cellular Structure 258
Connective Tissue Structure 259
Filament Structure 259
Sarcomere Structure 260
Other Myofibril Structures 261
9.2 Molecular Mechanisms of
Skeletal Muscle Contraction 262
Membrane Excitation:
The Neuromuscular Junction 262
Excitation–Contraction Coupling 265
Sliding-Filament Mechanism 267
9.3 Mechanics of Single-Fiber Contraction 270
Twitch Contractions 271
Load–Velocity Relation 272
Frequency–Tension Relation 272
Length–Tension Relation 274
9.4 Skeletal Muscle Energy Metabolism
Creatine Phosphate 276
Oxidative Phosphorylation 276
Glycolysis 276
Muscle Fatigue 277
9.5 Types of Skeletal Muscle Fibers 278
9.6 Whole-Muscle Contraction 279
Control of Muscle Tension 280
Control of Shortening Velocity 281
Muscle Adaptation to Exercise 281
Lever Action of Muscles and Bones 282
9.7 Skeletal Muscle Disorders 285
Muscle Cramps 285
Hypocalcemic Tetany 285
Muscular Dystrophy 285
Myasthenia Gravis 286
Smooth and Cardiac Muscle 286
9.8 Structure of Smooth Muscle 286
9.9 Smooth Muscle Contraction and Its Control 287
Cross-Bridge Activation 287
Sources of Cytosolic Ca2+ 289
ISTUDY
Membrane Activation 289
Types of Smooth Muscle 291
9.10 Cardiac Muscle 292
Cellular Structure of Cardiac Muscle 292
Excitation–Contraction Coupling
in Cardiac Muscle 293
Chapter 9 Clinical Case Study 295
ASSESSMENT QUESTIONS 297
10 Control of Body
Movement 300
10.1 Motor Control Hierarchy 301
Voluntary and Involuntary Actions 303
10.2 Local Control of Motor Neurons 303
Interneurons 303
Local Afferent Input 304
10.3 The Brain Motor Centers and the Descending Pathways
They Control 308
Cerebral Cortex 308
Subcortical and Brainstem Nuclei 310
Cerebellum 310
Descending Pathways 311
10.4 Muscle Tone 313
Abnormal Muscle Tone 313
10.5 Maintenance of Upright Posture and Balance 313
10.6 Walking 315
Chapter 10 Clinical Case Study 315
ASSESSMENT QUESTIONS 317
275
11
The Endocrine System 319
General Characteristics of Hormones and Hormonal Control
Systems 320
11.1 Hormones and Endocrine
Glands 320
11.2 Hormone Structures and Synthesis 322
Amine Hormones 322
Peptide and Protein Hormones 322
Steroid Hormones 323
11.3 Hormone Transport in the Blood 326
11.4 Hormone Metabolism and Excretion 327
11.5 Mechanisms of Hormone Action 327
Hormone Receptors 327
Events Elicited by Hormone–Receptor Binding 328
Pharmacological Effects of Hormones 328
11.6 Inputs That Control Hormone Secretion 329
Contents ix
 Control by Plasma Concentrations of Mineral Ions or Organic

12
Nutrients 329
Control by Neurons 329
Cardiovascular
Control by Other Hormones 330 Physiology 361
11.7  Types of Endocrine Disorders 330
Hyposecretion 331 General Features of the Circulatory System 362
Hypersecretion 331
Hyporesponsiveness and Hyperresponsiveness 331 12.1  Components of the Circulatory System 362
Blood 362
The Hypothalamus and Pituitary Gland 332 Plasma 363
The Blood Cells 363
11.8  Control Systems Involving the Hypothalamus and Blood Flow 367
Pituitary Gland 332 Circulation 367
Posterior Pituitary Hormones 332 12.2  Pressure, Flow, and Resistance 369
Anterior Pituitary Gland Hormones and the Hypothalamus 334

The Heart 371

The Thyroid Gland 338
12.3  Anatomy 371
11.9  Synthesis of Thyroid Hormone 338
Cardiac Muscle 372
11.10 Control of Thyroid Function 340
12.4  Heartbeat Coordination 373
11.11 Actions of Thyroid Hormone 341 Sequence of Excitation 374
Metabolic Actions 341 Cardiac Action Potentials and Excitation of the SA Node 375
Permissive Actions 341 The Electrocardiogram 377
Growth and Development 341 Excitation–Contraction Coupling 377
11.12 Hypothyroidism and Hyperthyroidism 342 Refractory Period of the Heart 378
12.5  
Mechanical Events
The Endocrine Response to Stress 343 of the Cardiac Cycle 380
11.13 Physiological Functions of Cortisol 343 Mid-Diastole to Late Diastole 382
Systole 382
11.14 Functions of Cortisol in Stress 344 Early Diastole 383
11.15 Adrenal Insufficiency and Cushing’s Syndrome 345 Pulmonary Circulation Pressures 383
11.16 Other Hormones Released During Stress 346 Heart Sounds 384
12.6   The Cardiac Output 384
Endocrine Control of Growth 347 Control of Heart Rate 385
Control of Stroke Volume 385
11.17 Bone Growth 347
12.7  Measurement of Cardiac Function 389
11.18 Environmental Factors Influencing Growth 348
11.19 Hormonal Influences on Growth 348 The Vascular System 389
Growth Hormone and Insulin-Like Growth Factors 348
12.8  Overview of the Vascular System 389
Thyroid Hormone 350
Insulin 350 12.9  Arteries 391
Sex Steroids 350 Arterial Blood Pressure 391
Cortisol 350 Measurement of Systemic Arterial Pressure 392
12.10 Arterioles 394
Endocrine Control of Ca2+ Homeostasis 351 Local Controls 395
11.20 Effector Sites for Ca 2+
Homeostasis 351 Extrinsic Controls 396
Endothelial Cells and Vascular Smooth Muscle 397
Bone 351
Arteriolar Control in Specific Organs 398
Kidneys 352
Gastrointestinal Tract 352
12.11 Capillaries 399
11.21 Hormonal Controls 352 Anatomy of the Capillary Network 400
Velocity of Capillary Blood Flow 400
Parathyroid Hormone 353
Diffusion Across the Capillary Wall: Exchanges of Nutrients and
1,25-Dihydroxyvitamin D 353
Metabolic End Products 401
Calcitonin 354
Bulk Flow Across the Capillary Wall: Distribution of the
11.22 Metabolic Bone Diseases 354 Extracellular Fluid 402
Hypercalcemia 355 12.12 Venules and Veins 405
Hypocalcemia 355 Determinants of Venous Pressure 406
Chapter 11 Clinical Case Study 356 12.13 The Lymphatic System 407
ASSESSMENT QUESTIONS 359 Mechanism of Lymph Flow 409

x Contents

ISTUDY
 Integration of Cardiovascular Function: Regulation of Inspiration 453
Systemic Arterial Pressure 409 Expiration 455
12.14 Overview of Regulation of Systemic Arterial 13.3  Lung Mechanics 456
Pressure 409 Lung Compliance 456
Airway Resistance 458
12.15 Baroreceptor Reflexes 413
Lung Volumes and Capacities 459
Arterial Baroreceptors 413
13.4  Alveolar Ventilation 460
The Medullary Cardiovascular Center 414
Operation of the Arterial Baroreceptor Reflex 415 Dead Space 461
Other Baroreceptors 415 13.5  Exchange of Gases in Alveoli and Tissues 462
12.16 Blood Volume and Long-Term Regulation of Arterial Partial Pressures of Gases 462
Pressure 416 Alveolar Gas Pressures 464
Gas Exchange Between Alveoli and Blood 465
12.17 Other Cardiovascular Reflexes and Responses 417
Matching of Ventilation and Blood Flow in Alveoli 466
Cardiovascular Patterns in Health and Disease 417 Gas Exchange Between Tissues and Blood 467
13.6  Transport of Oxygen in Blood 468
12.18 Hemorrhage and Other Causes of Hypotension 417
What Is the Effect of PO2 on Hemoglobin Saturation? 468
Shock 419 Effects of Other Factors on Hemoglobin Saturation and Oxygen-
12.19 The Upright Posture 419 Carrying Capacity 470
12.20 Exercise 420 13.7  Transport of Carbon Dioxide in Blood 473
Maximal Oxygen Consumption and Training 422 13.8  Transport of Hydrogen Ion Between Tissues and
12.21 Hypertension 424 Lungs 474
12.22 Heart Failure 425 13.9   Control of Respiration 475
12.23 Hypertrophic Cardiomyopathy 427 Neural Generation of Rhythmic Breathing 475
Control of Ventilation by PO2 , PCO2, and H+ Concentration 476
12.24 Coronary Artery Disease and Heart Attacks 428
Control of Ventilation During Exercise 480
Causes and Prevention 428
Other Ventilatory Responses 482
Drug Therapy 430
13.10 Hypoxia 483
Interventions 430
Stroke and TIA 430 Why Do Ventilation–Perfusion Abnormalities Affect O2 More
Than CO2? 483
Hemostasis: The Prevention of Blood Loss 430 Emphysema 484
Acclimatization to High Altitude 484
12.25 Overview of Hemostasis 430 13.11 Nonrespiratory Functions of the Lungs 485
12.26 Formation of a Platelet Plug 431 Chapter 13 Clinical Case Study 486
12.27 Blood Coagulation: Clot Formation 432
ASSESSMENT QUESTIONS 488
12.28 Anticlotting Systems 436
Factors That Oppose Clot Formation 436
The Fibrinolytic System 436

14
12.29 Anticlotting Drugs 437 The Kidneys and
Chapter 12 Clinical Case Study 438 Regulation of Water
and Inorganic Ions 490
ASSESSMENT QUESTIONS 442

Basic Principles of Renal Physiology 491

13
14.1  Renal Functions 491
Respiratory Physiology 445
14.2  Structure of the Kidneys and Urinary System 492
14.3   Basic Renal Processes 496
Glomerular Filtration 497
13.1  Organization of the Respiratory System 446 Tubular Reabsorption 499
The Airways and Blood Vessels 446 Tubular Secretion 501
Site of Gas Exchange: The Alveoli 448 Metabolism by the Tubules 501
Relation of the Lungs to the Thoracic (Chest) Wall 449 Regulation of Membrane Channels and Transporters 501
“Division of Labor” in the Tubules 502
13.2   Principles of Ventilation 450
14.4  The Concept of Renal Clearance 502
Ventilation 450
Boyle’s Law 451 14.5  Micturition 504
Transmural Pressures 451 Involuntary (Spinal) Control 504
How Is a Stable Balance of Transmural Pressures Achieved Voluntary Control 504
Between Breaths? 452 Incontinence 505
Contents xi

ISTUDY
 Regulation of Ion and Water Balance 505 15.6 The Small Intestine 551
14.6  Total-Body Balance of Sodium and Water 505 Anatomy 551
Secretions 552
14.7  Basic Renal Processes for Sodium and Water 506
Digestion and Absorption in the Small Intestine 557
Primary Active Na+ Reabsorption 506 Motility of the Small Intestine 563
Coupling of Water Reabsorption to Na+ Reabsorption 507 15.7 The Large Intestine 564
Urine Concentration: The Countercurrent Multiplier
System 509 Anatomy 564
Secretion, Digestion, and Absorption in the Large Intestine 565
14.8   Renal Sodium Regulation 513
Motility of the Large Intestine and Defecation 565
Control of GFR 513
15.8 Pathology of the Digestive System 567
Control of Na+ Reabsorption 514
Ulcers 567
14.9   Renal Water Regulation 517
Vomiting 567
Osmoreceptor Control of Vasopressin Secretion 517 Gallstones 569
Baroreceptor Control of Vasopressin Secretion 518 Lactose Intolerance 569
14.10 A Summary Example: The Response to Sweating 519 Constipation and Diarrhea 569
14.11 Thirst and Salt Appetite 519 Chapter 15 Clinical Case Study 570
14.12 Potassium Regulation 520 ASSESSMENT QUESTIONS 573
Renal Regulation of K+ 520
14.13 Renal Regulation of Calcium and Phosphate Ions 522
14.14 Summary—Division of Labor 522

16
Regulation of Organic
14.15 Diuretics 523 Metabolism and Energy
Balance 574
Hydrogen Ion Regulation 523
14.16 Sources of Hydrogen Ion Gain or Loss 523 Control and Integration of Carbohydrate, Protein,
14.17 Buffering of Hydrogen Ion in the Body 524 and Fat Metabolism 575
14.18 Integration of Homeostatic Controls 525 16.1 Events of the Absorptive and Postabsorptive States 575
14.19 Renal Mechanisms 525 Absorptive State 575
HCO3− Handling 526 Postabsorptive State 579
Addition of New HCO3− to the Plasma 526 16.2 Endocrine and Neural Control of the Absorptive
14.20 Classification of Acidosis and Alkalosis 527 and Postabsorptive States 581
Chapter 14 Clinical Case Study 529 Insulin 581
Glucagon 585
ASSESSMENT QUESTIONS 532
Epinephrine and Sympathetic Nerves to Liver and Adipose
Tissue 585
Cortisol 586

15
Growth Hormone 586
The Digestion and Hypoglycemia 587
Absorption of Food 534 16.3 Energy Homeostasis in Exercise and Stress 588

Regulation of Total-Body Energy Balance 589

15.1  Overview of the Digestive System 535 16.4 General Principles of Energy Expenditure 589
15.2  Structure of the Gastrointestinal Tract Wall 538 Metabolic Rate 589
15.3  How Are Gastrointestinal Processes Regulated? 539 16.5 Regulation of Total-Body Energy Stores 591
Neural Regulation 540 Regulation of Food Intake 591
Hormonal Regulation 540 Overweight and Obesity 593
Phases of Gastrointestinal Control 541 What Should We Eat? 593
15.4  Mouth, Pharynx, and Esophagus 542
Regulation of Body Temperature 594
Saliva 542
Chewing 543 16.6 General Principles of Thermoregulation 594
Swallowing 543 Mechanisms of Heat Loss or Gain 595
15.5  The Stomach 545 Temperature-Regulating Reflexes 595
Anatomy 545 Temperature Acclimatization 597
Secretions of the Stomach 545 16.7 Fever and Hyperthermia 598
Gastric Motility 549 Chapter 16 Clinical Case Study 600
ASSESSMENT QUESTIONS 602

xii Contents

ISTUDY
 17.16 Additional Effects of Gonadal Steroids 635

17 Reproduction 604 17.17 Puberty (Female) 636

17.18 Female Sexual Response 637
17.19 Menopause 637
Overview and Gametogenesis, Sex Determination,
and Sex Differentiation; General Principles of Pregnancy, Contraception, Infertility, and Hormonal
Reproductive Endocrinology 605 Changes Through Life 637
17.1   Overview and Gametogenesis 605 17.20 Fertilization and Early Development 637
Gametogenesis 605 Egg Transport 637
17.2  Sex Determination 607 Intercourse, Sperm Transport, and Capacitation 638
Fertilization 638
17.3  Sex Differentiation 608 Early Development, Implantation, and Placentation 639
Differentiation of the Gonads 608 17.21 Hormonal and Other Changes During Pregnancy 643
Differentiation of Internal
Preeclampsia and the Nausea and Vomiting of Pregnancy 645
and External Genitalia 608
Fetal and Neonatal Programming 611 17.22 Parturition and Lactation 645
Sexual Differentiation of the Brain 612 Parturition 645
17.4  General Principles of Reproductive Endocrinology 612 Lactation 646
Androgens 612 17.23 Contraception and Infertility 650
Estrogens and Progesterone 612 Contraception 650
Effects of Gonadal Steroids 613 Infertility 651
Hypothalamo–Pituitary–Gonadal Control 613 17.24 Summary of Reproductive Hormones
Through Life 652
Male Reproductive Physiology 614 Fetal Life 652
17.5  Anatomy of the Male Reproductive System 614 Infancy: The Minipuberty 652
17.6  Spermatogenesis 616 Puberty 652
Adult 652
Sertoli Cells 617
Aging 652
Leydig Cells 617
Production of Mature Sperm 617 Chapter 17 Clinical Case Study 654
17.7   Transport of Sperm 618 ASSESSMENT QUESTIONS 657
Erection 619
Ejaculation 619
17.8  Hormonal Control of Male Reproductive Functions 620
Control of the Testes 620
Testosterone 620
17.9  Puberty (Male) 622
18 The Immune System 659

Secondary Sex Characteristics and Growth 622

Behavior 622 18.1  Cells and Secretions Mediating Immune Defenses 660
Anabolic Steroid Use 622 Immune Cells 660
17.10 Hypogonadism 623 Immune Cell Secretions: Cytokines 661
17.11 Andropause 624 18.2   Innate Immune Responses 663
Defenses at Body Surfaces 663
Female Reproductive Physiology 624 Inflammation 663
Interferons 667
17.12 Overview and Anatomy of the Female Reproductive
Toll-Like Receptors 668
System 624
18.3   Adaptive Immune Responses 669
Anatomy of the Female Reproductive System 624
Overview 669
17.13 Ovarian Functions 625
Lymphoid Organs and Lymphocyte Origins 669
Oogenesis 625 Humoral and Cell-Mediated Responses: Functions of B Cells
Follicle Growth 626 and T Cells 672
Formation of the Corpus Luteum 627 Lymphocyte Receptors 672
Sites of Synthesis of Ovarian Hormones 627 Antigen Presentation to T Cells 675
17.14 Control of Ovarian Function 628 NK Cells 677
Follicle Development and Estrogen Development of Immune Tolerance 677
Synthesis During the Early and Middle Follicular Phases 629 Antibody-Mediated Immune Responses: Defenses Against
LH Surge and Ovulation 630 Bacteria, Extracellular Viruses, and Toxins 677
The Luteal Phase 632 Defenses Against Virus-Infected Cells and Cancer Cells 681
17.15 Uterine Changes in the Menstrual Cycle 633 18.4  Systemic Manifestations of Infection 684
Contents xiii

ISTUDY
 18.5 Factors That Alter the Resistance to Infection 685 Diagnosis 703
Acquired Immune Deficiency Syndrome (AIDS) 685 Physiological Integration 704
Antibiotics 686 Therapy 705
18.6 Harmful Immune Responses 687 19.3 Case Study of a Man with Abdominal Pain, Fever, and
Graft Rejection 687
Circulatory Failure 705
Transfusion Reactions 687 Case Presentation 705
Hypersensitivities 688 Physical Examination 705
Autoimmune Disease 690 Laboratory Tests 706
Excessive Inflammatory Responses 690 Diagnosis 706
Chapter 18 Clinical Case Study 693 Physiological Integration 707
Therapy 708
ASSESSMENT QUESTIONS 695 19.4 Case Study of a College Student with Nausea, Flushing,
and Sweating 709
Case Presentation 709

19
Physical Examination 709
Medical Physiology: Integration Laboratory Tests 710
Using Clinical Cases 697 Diagnosis 710
Physiological Integration 710
Therapy 712
19.1 Case Study of a Woman with Palpitations and Heat
Intolerance 698 APPENDIX A ANSWERS TO TEST AND REVIEW QUESTIONS A-1
Case Presentation 698 APPENDIX B INDEX OF CLINICAL TERMS A-42
Physical Examination 698
APPENDIX C CONCENTRATION RANGES OF COMMONLY MEASURED
Laboratory Tests 698
VARIABLES IN BLOOD A-46
Diagnosis 699
Physiological Integration 701
Therapy 701 GLOSSARY/INDEX GI-1
19.2 Case Study of a Man with Chest Pain After a Long
Airplane Flight 702
Case Presentation 702
Physical Examination 702
Laboratory Tests 703

Table of Contents credits: Ch. 1 Andre Schoenherr/Stone/Getty Images; Ch. 2 Andrew Dunn/Alamy Stock Photo; Ch. 3 Professors Pietro
M. Motta & Tomonori Naguro/Science Source; Ch. 4 VVG/Science Photo Library/Science Source; Ch. 5 Dr. Mark J. Winter/Science
Source; Ch. 6 David Becker/Science Source; Ch. 7 Dr. Robert Fettiplace; Ch. 8 Sherbrooke Connectivity Imaging Lab (SCIL)/Getty Images;
Ch. 9 Steve Gschmeissner/Science Source; Ch. 10 Blend Images - Erik Isakson/Brand X Pictures/Getty Images; Ch. 11 Living Art
Enterprises/Science Source; Ch. 12 SPL/Science Source; Ch. 13 SPL/Science Source; Ch. 14 Steve Gschmeissner/Science Photo Library/
Getty Images; Ch. 15 Steve Gschmeissner/Science Photo Library/Science Source; Ch. 16 The Rockefeller University/AP Images; Ch. 17
David M. Phillips/Science Source; Ch. 18 Corona Borealis Studio/Shutterstock; Ch. 19 Comstock Images/Getty Images

xiv Contents

ISTUDY
 INDEX OF EXERCISE PHYSIOLOGY
EFFECTS ON CARDIOVASCULAR SYSTEM, 421–24 Respiratory rate (increases), 460, 475
Atrial pumping (atrial fibrillation), 377 Role of Hering-Breuer reflex, 475
Cardiac output (increases), 384–85, 388–89, 407, 409–11, 411f–12f,
413, 414–16, 418–20 EFFECTS ON SKELETAL MUSCLE
Distribution during exercise, 411, 411f
Adaptation to exercise, 281–82
Control mechanisms, 539, 542
Arterioles (dilate), 414, 421–23, 422f
Coronary blood flow (increases), 428
Changes with aging, 282
Gastrointestinal blood flow (decreases), 419
Cramps, 285
Heart attacks (protective against), 428
Fatigue, 277, 277f
Heart rate (increases), 388, 388f, 389, 415f, 423, 423t
Glucose uptake and utilization (increase), 276, 582–83, 582f
Lymph flow (increases), 409
Hypertrophy, 262, 341
Maximal oxygen consumption (increases), 422
Local blood flow (increases), 277, 398, 417, 421–22, 421f
Mean arterial pressure (increases), 393, 411t, 413, 414f
Local metabolic rate (increases), 396
Renal blood flow (decreases) 491–92
Local temperature (increases), 295–96, 423
Skeletal muscle blood flow (increases), 277, 396, 412, 421, 421f,
Nutrient utilization, 580–81
422–23
Oxygen extraction from blood (increases), 467
Skin blood flow (increases), 423t
Recruitment of motor units, 280–81
Stroke volume (increases), 419, 421–23, 422f, 423t, 424f
Soreness, 282
Summary, 430
Summary, 286t
Venous return (increases), 419–21
Role of respiratory pump, 407, 421, 423
Role of skeletal muscle pump, 409, 423 OTHER EFFECTS
Aging, 282
EFFECTS ON ORGANIC METABOLISM, 581–85 Body temperature (increases), 75, 594
Central command fatigue, 277
Cortisol secretion (increases), 586
Exercise-related activity thermogenesis (EAT), 590
Diabetes mellitus (protects against), 600
Gastrointestinal blood flow (decreases), 419
Epinephrine secretion (increases), 585
Immune function, 685
Fuel homeostasis, 588–89
Menstrual function, 633
Glucagon secretion (increases), 582–83, 582f
Metabolic acidosis, 525t
Glucose mobilization from liver (increases), 581–82
Metabolic rate (increases), 589
Glucose uptake by muscle (increases), 276, 581–83, 582f
Muscle fatigue, 277
Growth hormone secretion (increases), 585
Non-exercise activity thermogenesis (NEAT), 590
Insulin secretion (decreases), 581–83, 582f
Osteoporosis (protects against), 355
Metabolic rate (increases), 586
Stress, 346
Plasma glucose changes, 276, 580–82, 582f
Sweating, 519
Plasma lactic acid (increases), 276, 479
Weight loss, 570–71, 601
Sympathetic nervous system activity (increases), 586

TYPES OF EXERCISE
EFFECTS ON RESPIRATION, 477, 478
Aerobic, 281
Airflow (increases), 446
Endurance exercise, 281–82, 422–23, 601
Alveolar gas pressures (no change in moderate exercise), 464–65,
Long-distance running, 277, 281–82
480, 480f
Moderate exercise, 422–23, 465, 481–83
Capillary diffusion, 463
Swimming, 482, 638
Control of respiration in exercise, 475–85
Weightlifting, 281, 282, 422, 590
Oxygen debt, 277
Ventilation (increases), 477, 478f
Breathing depth (increases), 277, 461
Expiration, 454f, 473f

xv

ISTUDY
 GUIDED TOUR THROUGH A CHAPTER

12
Chapter Outline

CHAPTER
Cardiovascular Physiology Every chapter starts with an introduction giving the reader a brief
overview of what is to be covered in that chapter. Included in the
introduction for the sixteenth edition is a feature that provides
General Features of the Circulatory students with a preview of those General Principles of Physiology
System
12.1 Components of the Circulatory System
(introduced in Chapter 1) that will be covered in the chapter.
12.2 Pressure, Flow, and Resistance

General Principles of Physiology

The Heart
12.3 Anatomy
12.4 Heartbeat Coordination
12.5 Mechanical Events of the Cardiac Cycle First introduced in the thirteenth edition to wide acclaim, General
12.6 The Cardiac Output
12.7 Measurement of Cardiac Function Principles of Physiology have been integrated throughout each
The Vascular System chapter in order to continually reinforce their importance. Each
12.8
12.9
Overview of the Vascular System
Arteries chapter opens with a preview of those principles that are particularly
12.10
12.11
Arterioles
Capillaries
Color-enhanced angiographic image of coronary arteries. SPL/Science Source
relevant for the material covered in that chapter. The principles
12.12
12.13
Venules and Veins
The Lymphatic System
12.19 The Upright Posture are then reinforced when specific examples arise within a chapter,
Integration of Cardiovascular
12.20 Exercise
12.21 Hypertension
including Dig Deeper inquiries associated with certain figures.
Function: Regulation of Systemic
Arterial Pressure 12.22 Heart Failure
General Features of the Circulatory System
12.23 Hypertrophic Cardiomyopathy
12.14 Overview of Regulation of Systemic
Arterial Pressure 12.24 Coronary Artery Disease and Heart Attacks
12.1 Components of the the erythrocytes (red blood cells) and the leukocytes (white blood
cells), and the cell fragments are the platelets. More than 99% of
12.15 Baroreceptor Reflexes
Hemostasis: The Prevention of Blood Loss Circulatory System blood cells are erythrocytes that carry oxygen to the tissues and
12.16 Blood Volume and Long-Term carbon dioxide from the tissues. The leukocytes protect against
Beyond a distance of a few cell diameters, the random movement
Regulation of Arterial Pressure infection and cancer, and the platelets function in blood clot-
12.25 Overview of Hemostasis of substances from a region of higher concentration to one of
ting. The constant motion of the blood keeps the cells dispersed
12.17 Other Cardiovascular Reflexes and lower concentration (diffusion) is too slow to meet the metabolic
12.26 Formation of a Platelet Plug throughout the plasma.
Responses requirements of cells. Because of this, our large, multicellular bod-
The hematocrit is defined as the percentage of blood
ies require an organ system to transport molecules and other sub-
12.27 Blood Coagulation: Clot Formation stances rapidly over the long distances between cells, tissues, and
volume that is erythrocytes. It is measured by centrifugation (spin-
Cardiovascular Patterns in Health organs. This is achieved by the circulatory system (also known as
ning at high speed) of a sample of blood. The erythrocytes are
and Disease 12.28 Anticlotting Systems forced to the bottom of the centrifuge tube, the plasma remains
the cardiovascular system), which includes a pump (the heart);
on top, and the leukocytes and platelets form a very thin layer
12.29 Anticlotting Drugs a set of interconnected tubes (blood vessels or vascular system);
between them called the buffy coat (Figure 12.1). The hematocrit
12.18 Hemorrhage and Other Causes of and a fluid connective tissue containing water, solutes, and cells
is normally about 45% in men and 42% in women.
Hypotension Chapter 12 Clinical Case Study that fills the tubes (the blood). Chapter 9 described the detailed
The volume of blood in a 70 kg (154 lb) person is approxi-
361 mechanisms by which the cardiac and smooth muscle cells found
mately 5.5 L. If we take the hematocrit to be 45%, then
in the heart and blood vessel walls, respectively, contract and gen-
erate force. In this chapter, you will learn how these contractions
Erythrocyte volume = 0.45 × 5.5 L = 2.5 L
create pressures and move blood within the circulatory system.
The general principles of physiology described in Chap-
ter 1 are abundantly represented in this chapter. In Section 12.2,

Clinical Case Studies

The authors have drawn from their teaching and research experiences
In contrast to aspirin, the fibrinogen blockers, the oral antico-
and the clinical experiences of colleagues to provide students with
agulants, and heparin, all of which prevent clotting, the fifth type of
drug—plasminogen activators—dissolves a clot after it is formed.
The use of such drugs is termed thrombolytic therapy. Intravenous
you will learn about the relationships between blood pressure,
blood flow, and resistance to blood flow, a classic illustration of
the general principle of physiology that physiological processes
are dictated by the laws of chemistry and physics. The general
principle of physiology that structure is a determinant of—and has
coevolved with—function is apparent throughout the chapter; as
one example, you will learn in the section on the vascular system
Stu d y an d Rev iew 12 .29 how the structures of different types of blood vessels determine
■ Aspirin: inhibits platelet cyclooxygenase activity (decreases
prostaglandin and thromboxane production)
whether they participate in fluid exchange, regulate blood pres-
sure, or provide a reservoir of blood.
Plasma = 55%

real-life applications through clinical case studies in each chapter.

administration of recombinant t-PA within a few hours after myo- The general principle of physiology that most physiological
∙ inhibits platelet aggregation
cardial infarction significantly reduces myocardial damage and mor- functions are controlled by multiple regulatory systems, often
■ Oral anticoagulants: inhibit clot formation
tality. Recombinant t-PA has also been effective in reducing brain working in opposition, is exemplified by the hormonal and neural

They have been redesigned to incorporate the format of Chapter 19.

damage following a stroke caused by blood vessel occlusion. ∙ interfere with vitamin K action or inactivate factor Xa
regulation of blood vessel diameter and blood volume (sections Leukocytes
■ Heparin: inhibits clot formation on the vascular system and the integration of cardiovascular func- and buffy coat
∙ interferes with antithrombin III from endothelial cells tion), as well as by the opposing mechanisms that create and dis- platelets

You will now find “Reflect and Review” questions and at least one Recombinant tissue plasminogen activator (t-PA): solve blood clots (section on hemostasis). The sections on the
■
thrombolytic (see Study and Review 12.28) integration of cardiovascular function and cardiovascular patterns Erythrocytes = 45%
(hematocrit = 45%)
Review Question: What is the main risk of using heparin? in health and disease explain how the regulation of arterial blood

figure or table in every case study.

CHAPTER 12 Clinical Case Study: Shortness of Breath on Exertion in a
72-Year-Old Man
A 72-year-old man saw his primary
care physician; he was complaining
of shortness of breath when doing
his 15 min daily walk. His shortness of
breath with walking had been wors-
ening over the past four weeks. He
(Answer found in Appendix A.)
pressure exemplifies that homeostasis is essential for health and
survival, yet another general principle of physiology. Finally, mul-
tiple examples demonstrate the general principle of physiology that
the functions of organ systems are coordinated with each other—
for example, the circulatory and urinary systems work together to Figure 12.1 Measurement of the hematocrit by
control blood pressure, blood volume, and sodium balance.
We will begin with an overview of the components of the
centrifugation. The values shown are typical for a healthy male.
Due to the presence of a thin layer of leukocytes and platelets
circulatory system and a discussion of some of the physical factors between the plasma and red cells, the value for plasma is actually
Reflect and Review #2 that determine its function. slightly less than 55%.
■ What is the patient’s current pulse pressure and what most common symptomatic heart valve abnor-
150
are the main determinants of pulse pressure? (Hint: See Blood mality in adults. It is more common in men and,
when occurring in the elderly, is usually due to
DIG DEEPER
Figures 12.32, 12.33, and 12.34.) Increased pressure gradient
Blood is composed
across stenotic valve
of formed
calcification of theelements (cells
aortic valve. The and cell fragments)
decreased ■ Estimate the hematocrit of a person with a plasma volume of 3 L
Examination of his neck revealed that his jugular veins were
distended and had very prominent pulses. Auscultation of his chest
suspended in a liquid called plasma.
—Continued
pulse pressure Dissolved
arises because in the plasma are
the narrowed and total blood volume of 4.5 L. Begin
Pressure (mmHg)

did not complain of chest pain dur- Left ventricular pressure

revealed a prominent systolic murmur (see description of heart a large number of proteins,
aortic nutrients,
valve reduces metabolic
the pressure wastes,
in the aorta, and other
Answer found in Appendix A. Aortic stenosis
ing his walks. However, he did expe-
Comstock Images/Getty Images
100
sounds in Section 12.5). When the physician felt the patient’s carotid molecules beingdespite higher pressures generated in the
transported between organ systems. The cells are
rience a pressure-like chest pain left ventricle (shaded area of Figure 12.78).
arteries, the strength of the upstroke of the pulse during systole Aortic pressure
under the sternum (angina pectoris) 362 Chapter 12Therefore, the magnitude of the ejection frac- Progressive narrowing of aortic valve
seemed to be decreased.
when walking up several flights of tion of the left ventricle was reduced.
stairs. He had also felt light-headed and as if he were going to faint Reflect and Review #3 As the aortic valve becomes increasingly
when walking up the stairs, but both the pain and light-headedness ■ What clinical condition could explain all of the findings in narrowed, the heart has to work harder and Heart
50this
passed when he sat down and rested. For the past few months, he patient? (Hint: See Section 12.22.) harder to eject a normal stroke volume; this is damage
Myocyte Contractility Stroke volume (pulse pressure)
has had to prop his head up using three pillows to keep from feeling exemplified by the increase in systolic left ven- Cardiac output
The patient was showing all of the symptoms of congestive
short of breath when lying in bed. Occasionally the breathlessness tricular pressure shown in Figure 12.78. As a
heart failure (see Figure 12.68). The shortness of breath on walking
would wake him up at night. This symptom was relieved by sitting result of this increased work, the Left left ventricular
ventricle hypertrophy Progressive heart failure
suggested that the failure of cardiac output to keep up with need Left atrial pressure
upright and letting his legs hang off the side of the bed. His feet got becomes hypertrophied. In fact, this patient
caused a backup of blood in the lungs leading to accumulation 0 of
swollen, particularly at the end of the day when he had been stand- was referred to a cardiologist who performed a
fluid that reduced the capacity for air exchange in the lungs. This
ing quite a bit. He had never smoked cigarettes and was not taking Doppler echocardiographic examination of the
was not a problem at rest but was with the increase in whole-body Pulse pressure and
any prescription medications. patient’s heart: The left ventricle was clearly
oxygen consumption that occured with even mild exercise like walk- ECG mean arterial blood
hypertrophied and the aortic valve was dra-
Reflect and Review #1 ing. The feeling of light-headedness during more strenuous exer- Systolic ejection murmur pressure
1st 2nd
matically calcified and not opening properly.
■ What are the potential causes of his swollen feet after cise suggested that the brain was not receiving sufficient blood flow
The progression of heart failure in this
standing for a significant portion of the day? (Hint: See to maintain oxygen delivery and adequate removal of carbon diox- Heart sounds Sympathetic input
patient is an example of harmful positive feed- Arterial baroreflexes
Figures 12.48 and 12.63.) ide. This is additional evidence of the inability of the failing heart Parasympathetic input
back (Figure 12.79). As the aortic valve narrowed
to adequately increase cardiac output and maintain cerebral bloodDiastole Systole Diastole
Phase of cardiac cycle
The physician performed a complete physical exam. The man 1 2 3 4 1 and the stroke volume decreased, barorecep-
flow during exercise.
did not have a fever. His heart rate was 86 bpm, which was increased tor reflexes were activated to try to normalize Renal fluid retention Venous and capillary pressure
The swelling of his feet and the more prominent jugular pulses
1 = Ventricular filling
compared to a year before when it was 78 bpm. His systolic/ cardiac output and restore blood pressure (see
suggested that venous blood was having difficulty returning to 2 = Isovolumetric ventricular contraction
the
diastolic blood pressure was 115/92 mmHg; a year previously, 3 = Ventricular ejection Figures 12.58 and 12.59). At first, this worked
heart. The difficulty sleeping may have also been related to con- 4 = Isovolumetric ventricular relaxation
before his symptoms had started, it had been 139/75 mmHg (normal and the mean arterial blood pressure was main- Edema (peripheral and pulmonary)
gestive heart failure, because of the associated breathing problems.
for a 72-year-old man). His resting respiratory rate was increased tained fairly close to normal. However, the heart
This suggested the possibility of pulmonary edema, which arose
at 16 breaths per minute, compared to 13 breaths per minute a year had to work harder and harder to eject a stroke
Figure
when the failing left ventricle did not adequately eject blood, 12.78 The effect of aortic stenosis on left ventricular and aortic pressures during
creat- Figure 12.79 Aortic stenosis leading to heart failure: The narrowing of the aortic valve decreases pulse pressure and eventually mean arterial
before. volume and the myocardium started to fail while reflexes that increase stimulation of the heart to work harder. However, the increased workload causes the
the cardiac cycle. Compare to a normal-functioning heart in Figure 12.22 to see the dramatic
ing a “back pressure” into the pulmonary circulation and subsequent pressure. This activates baroreceptor
increase in the difference between left ventricular and aortic pressure during ejection (shaded becoming hypertrophied due tothen
heart to fail, which the further
increased decreases cardiac output and blood pressure. At the same time, increases in venous and capillary pressure and
area). Because of the reduction of the aortic outflow, the aortic pulse pressure is decreased. workload. This failure isofcaused
activation at first by
neurohumoral myo-that increase fluid retention lead to the development of pulmonary and peripheral edema.
factors
438 Chapter 12
Also notice the systolic ejection murmur in the heart sounds. cyte (ventricular wall) stress, which leads to
left ventricular hypertrophy, which eventually
results in increases
myocyte the filtration
damage. The of fluid into the interstitial space leading to
barorecep- An exciting new approach to valve replacement is called
leakage of fluid from pulmonary capillaries. All of these factors indi-
tor reflex increased the stimulation the of
development
the heart (see of Figure
edema.12.58). percutaneous (through the skin) transcatheter aortic valve
cated that the patient may have had fluid retention (see explanation
of Figure 12.68). As described in Section 12.22, this was likely due, However, like any fatiguing muscle, what The
the best
hearttreatment
needed wasfor patients with aortic stenosis is sur-
rest, replacement (TAVR). In this technique, the cardiologist inserts a
at least in part, to decreased baroreceptor afferent activity that trig- gical replacement
not increased work. This excess stimulation worsenedof thethe poorly functioning aortic valve as soon
condition catheter containing a collapsed artificial aortic valve into the outflow
gered the neuroendocrine components of the baroreceptor reflex; of the heart, and a vicious cycle as symptoms
ensued. develop.
As shown Because
in Figure 12.79, our patient was in good physical from the left ventricle into the aorta. When the catheter is in proper
this increased the retention of fluid by the kidney. Although his mean condition
as the patient’s heart failure worsens, his before the symptoms
mean arterial pressure started and he sought treatment position, the valve is deployed and expanded to its full size from the
arterial pressure was not decreased at the time he first presented will likely decrease significantly,quickly,
making he thewas
baroreceptor reflex
a good candidate for surgical valve replace- catheter and then anchored in place. When TAVR was developed, it
to his physician, the smaller pulse pressure resulted in decreased response even greater, which will worsen
ment. In the condition.
patients whoThe key ishave surgical valve replacement
cannot was primarily used in patients who were not candidates for standard
baroreceptor firing (see Figure 12.57b). The baroreceptor reflex also to intervene with appropriate therapy before thisthe
immediately, occurs.
stenotic valve can be enlarged by balloon surgical valve replacement. The FDA recently approved TAVR for
accounted for the increased heart rate of this patient. The combination of increased venous backInpressure
valvuloplasty. due to a cardiologist inserts a cathe-
this procedure, lower risk patients with aortic stenosis.
heart failure and baroreceptor reflex stimulation of fluid retention by
ter (hollow tube) across the valve and inflates a balloon to try to Our patient underwent a surgical valve replacement and is
Reflect and Review #4 the kidneys led to the propensity to develop pulmonary and periph-
■ Explain how an increase in venous pressure can result in the
break up the calcifications on the valve. This typically is only a currently doing well.
eral edema. Remember that the rate of fluid filtration from the capil-
development of peripheral edema. (Hint: See Figure 12.45.) temporary treatment as the valve usually calcifies again or leaks Source: Adapted from Toy EC: McGraw Hill Medical Case Files, Access Medicine
laries into the interstitial fluid is a balance between forces favoring
after the procedure. (online): Case 73.
The history and physical findings (particularly the shortness filtration (capillary hydrostatic pressure and interstitial fluid protein
of breath on exertion, systolic murmur, decreased pulse pressure, osmotic pressure) and forces favoring absorption (interstitial fluid
and angina pectoris) of this patient suggested that the heart failure hydrostatic pressure and plasma protein osmotic pressure; see Fig-
may have been due to stenosis (narrowing) of the aortic valve (see ure 12.45). The increase in venous pressure is reflected back into
description of heart sounds in Section 12.5). Aortic stenosis is the the capillaries, increasing the capillary hydrostatic pressure, which See Chapter 19 for complete, integrative case studies.

xvi
—Continued next page

Cardiovascular Physiology 439

ISTUDY
 10 10
Answer found in Appendix A.
(b) Effect of tube diameter on flow
5 5
R _1
r4

1
___ 1 1 1 1 1
RA = __ = __ RB ___ = __ = __ = 1
(rA)4 24 16 (rB)4 14 1

P
TABLE 12.3 Because flow = ___ andSystem
The Circulatory RB = 16 x RA,
R
Component Function
1
flow in B = __ of flow in A.
16
Heart
(b) Effect of tube diameter on flow
Atria Chambers through which blood flows from veins to ventricles. Atrial contraction adds to ventricular filling but
is not essential for it.

Summary Tables Ventricles Chambers whose contractions produce the pressures that drive blood through the pulmonary and systemic
vascular systems and back to the heart.

Summary tables are used to bring together large amounts of Vascular system
Arteries Low-resistance tubes conducting blood to the various organs with little loss in pressure. They also act as
information that may be scattered throughout the book or to pressure reservoirs for maintaining blood flow during ventricular relaxation.

summarize small or moderate amounts of information. The Arterioles Major sites of resistance to flow; responsible for regulating the pattern of blood-flow distribution to the various
organs; participate in the regulation of arterial blood pressure.
tables complement the accompanying figures to provide a Capillaries Major sites of nutrient, gas, metabolic end product, and fluid exchange between blood and tissues.

rapid means of reviewing the most important material in the Venules Capacitance vessels that are sites of migration of leukocytes from the blood into tissues during inflammation
and infection.

chapter. Veins Low-resistance, high-capacitance vessels carrying blood back to the heart. Their capacity for blood is adjusted to
facilitate this flow.

Blood
Plasma Liquid portion of blood that contains dissolved nutrients, ions, wastes, gases, and other substances. Its
composition equilibrates with that of the interstitial fluid at the capillaries.
Cells Includes erythrocytes that function mainly in gas transport, leukocytes that function in immune defenses, and
platelets (cell fragments) for blood clotting.

370 Chapter 12

Begin Figure 12.66 Control of

Dig Deeper Inquiries
Brain Exercising skeletal muscles
the cardiovascular system
during exercise. The primary The authors have continued to refine and expand the number
outflow to the sympathetic
“Exercise centers” Contractions
and parasympathetic neurons of higher Bloom’s-level critical thinking questions linked
is via pathways from “exercise
Afferent Stimulate
mechanoreceptors
Local chemical
centers” in the brain. Afferent
input from mechanoreceptors and
with many figures from all chapters. These concept checks
input
were introduced in a different form in the eleventh edition and
Arterial baroreceptors Medullary changes
in the muscles chemoreceptors in the exercising
Reset upward cardiovascular
center
muscles and from reset arterial
Afferent
input Stimulate Dilate
baroreceptors also influences the
autonomic neurons by way of the
continue to prove extremely popular with users of the textbook.
They are designed to help students become more engaged
chemoreceptors arterioles medullary cardiovascular center.
Parasympathetic output to heart in the muscles in the muscle
Sympathetic output to heart, veins,
and arterioles in abdominal
organs and kidneys Muscle blood flow
DIG DEEPER: General
Principle of Physiology
in learning a concept or process depicted in the art. These
■ How do the homeostatic questions challenge a student to analyze the content of the figure
Cardiac output responses during exercise
Vasoconstriction in
abdominal organs
highlight the general principle of
physiology described in Chapter
and, occasionally, to recall information from previous chapters.
and kidneys
1 that the functions of organ
systems are coordinated with
Many of the questions also require quantitative skills. Many
each other?
Answer found in Appendix A.
instructors find that these Dig Deeper inquiries make great
exam questions. Numerous Dig Deeper inquiries are linked with
General Principles of Physiology, providing students with two
higher brain centers. The result is a further increase in heart
rate, myocardial contractility, and vascular resistance in the non-
the contracting muscles exceed 10% to 15% of their maximal force,
the blood flow to the muscle is greatly reduced because the muscles
great learning tools in one!
active organs. Such a system permits a fine degree of match- are physically compressing the blood vessels that run through them.
ing between cardiac pumping and total oxygen and nutrients In other words, the arteriolar vasodilation is overcome by the physi-
required by the exercising muscles. Mechanoreceptors in the cal compression of the blood vessels. Therefore, the cardiovascular
exercising muscles are also stimulated and provide input to the changes are ineffective in causing increased blood flow to the mus-
medullary cardiovascular center. cles, and these contractions can be maintained only briefly before
Finally, the arterial baroreceptors also have a function in the fatigue sets in. Moreover, because of the compression of blood ves-
altered autonomic outflow. Knowing that the mean and pulsatile sels, total peripheral resistance may increase considerably (instead of
pressures increase during exercise, you may logically assume that decreasing as it does in endurance exercise), contributing to a large
the arterial baroreceptors will respond to these increased pres- increase in mean arterial pressure during the contraction. Frequent
sures and signal for increased parasympathetic and decreased exposure of the heart to only this type of exercise can cause harmful
sympathetic outflow, a pattern designed to counter the increase in changes in the left ventricle, including wall hypertrophy and dimin-
arterial pressure. In reality, however, exactly the opposite occurs: ished chamber volume. 4.3 mm
Large vein Large artery
The arterial baroreceptors are involved in increasing the arterial low resistance, low resistance,
pressure over that existing at rest. The reason is that one neural high-capacitance vessels conducting vessels

component of the central command output travels to the arte- Maximal Oxygen Consumption and
Anatomy and Physiology Training
rial baroreceptors and “resets” them upward as exercise begins.
This resetting causes the baroreceptors to respond as though arte-
As the intensity of any endurance exercise increases, oxygen Several elastic

REVEALED® (APR) Icon

Few elastic
rial pressure had decreased, and their output (decreased action layers
layers
potential frequency) signals for decreased parasympathetic and consumption also increases proportionally until reaching a point
Lumen
increased sympathetic outflow. Table 12.10 summarizes the when it fails to increase despite a further increment in workload.
. Endothelium
Endothelium
changes that occur during moderate exercise—that is, exercise This is known as maximal oxygen consumption (Vo2 max).
APR icons are found in figure legends. These icons indicate that
(like jogging, swimming, or fast walking) that involves large mus- After this point has been reached, work can be increased and
Wide lumen

Many layers of
cle groups for an extended period of time. sustained only briefly by anaerobic metabolism in the exercising
APR-related content is available to reinforce and enhance learning
Few layers of smooth muscle
smooth muscle
In closing, we return to the other major category of exercise, muscles. and connective
Inferior
Aorta
and connective
vena cava tissue
Theoretically, Vo2 max could be limited by:
.
tissue
which involves maintained high-force, slow-shortening-velocity con-
of the material.
tractions, as in weight lifting. Here, too, cardiac output and arterial
■ the cardiac output
blood pressure increase, and the arterioles in the exercising muscles ■ the respiratory system’s ability to deliver oxygen to the
undergo vasodilation due to local metabolic factors. However, there blood Venule Arteriole

Descriptive Art Style

is a crucial difference. During maintained contractions, once ■ the exercising muscles’ ability to use oxygen WBCs released into tissues during main resistance vessels,
inflammation and infection; controls distribution of
capacitance vessels blood flow
422 Chapter 12

A realistic three-dimensional perspective is included in many Smooth Endothelium

of the figures for greater clarity and understanding of concepts

muscle
Endothelium cells

presented.
Lumen Lumen

Connective
tissue
Endothelial
cells

Lumen

Capillary
exchange of gases, fluid, nutrients;
uptake of waste and secretory
products from cells

Figure 12.31 Comparative features of blood vessels. Sizes are not drawn to scale. Inset: Light micrograph (enlarged four times) of a
medium-sized artery near a vein. Note the difference between the two vessels in wall thickness and lumen diameter. Refer back to Table 12.3 for more
details on function. Biophoto Associates/Science Source

We have previously described the pressures in the aorta and has completed its journey back to the atrium in each circuit, most
pulmonary arteries during the cardiac cycle. Figure 12.32 illus- of the pressure originally generated by the ventricular contraction
trates the pressure changes that occur along the rest of the sys- Guided Tour
has dissipated. Through
The reason a Chapter
the average pressure at any point in xvii
temic and pulmonary circuits. Sections dealing with the individual the pulmonary and systemic circuits is lower than that upstream
vascular segments will describe the reasons for these changes in toward the heart is that the blood vessels offer resistance to the
pressure. For the moment, note only that by the time the blood flow from one point to the next (review Figure 12.8).
ISTUDY 390 Chapter 12
 kinase, which Figure 12.30 integrates the factors that determine stroke
the following volume and heart rate into a summary of the control of cardiac
output.
e During
During stimulation
stimulation
Sympathetic
Sympathetic
s in the stimulation
stimulation of
of sympathetic
sympathetic

during contraction
200
200 nerves
nerves to
to heart
heart

Force developed
Increased
Increased

Stroke volume (mL)

n
Flow Diagrams
contractility
contractility
Begin
Control
Control
100
100 Control
Control

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

End-diastolic Activity of sympathetic
he ventricular volume nerves to heart
Normal
Normal
resting
resting
value
value

tion increases this edition. They have been updated to assist in learning.TABLE 12.5 Effects of Autonomic Nerves on the Heart
00 100
100 200
200 300
300 400
400
Time
Time
xcitation, Ca2+ Plasma Activity of
Ventricular
Ventricular end-diastolic
end-diastolic volume
volume (mL)
(mL)
Sympathetic Nerves (Norepinephrine Parasympat

Key to Flow Diagrams

(a)
(a) Stroke
Stroke volume
volume increased
increased by
by increased
increased end-diastolic
end-diastolic volume
volume
Area Affected (b)
(b) Effect
Effect of
of sympathetic
sympathetic stimulation
stimulation on
on ventricular
ventricular on Beta-Adrenergic Receptors) Muscarinic
lowing excita- epinephrine parasympathetic and
and sympathetic
sympathetic stimulation
stimulation force
force development
development
ling are accel- nerves to heart
Figure 12.28 SA node
Sympathetic stimulation causes increased contractility of ventricular muscle. (a) Stroke volume is increased at any given end- Increased heart rate Decreased h
ction observed
■ The beginning boxes of the diagrams are color-coded AV
green.
diastolic volume. (b) Both the rate of force development and the rate of relaxation increase, as does the maximum force developed.
node Increased conduction rate Decreased c

■ Other boxes are consistently color-coded throughout the

Atrial book.
DIG DEEPER
the ventricles, muscle Increased contractility Decreased c
Cardiac muscle SA node ■ Estimate the ejection fraction and end-systolic volumes under control and under sympathetic-stimulated conditions at an end-diastolic volume
gligible direct of 140 mL.
■ Structures are always shown in three-dimensional form.
Stroke volume Heart rate
Ventricular muscle Increased contractility No significa
Answer found in Appendix A.
onomic nerves

Cardiac output

Cardiac output = Stroke volume × Heart rate Extracellular fluid Adrenergic receptors activate a G-protein-coupled cascade that alterations in vascular resis
Norepinephrine Epinephrine
that includes the production of cAMP and activation of a in arterial pressure can weaken
troke volume. protein kinase. A number of proteins involved in excitation– stroke volume.
ight, the arte- Figure 12.30 Major factors involved in increasing cardiac output. L-type Ca2+ channel contraction coupling are phosphorylated by the kinase, which Figure 12.30 integrates th
Reversal of all arrows in the boxes would illustrate how cardiac enhances contractility. These proteins include the following volume and heart rate into a sum
ng ventricular
output can be decreased. β-adrenergic Adenylyl (numbers keyed in figure): output.
lood. A term receptor
β
α α cyclase
Plasma membrane

to eject blood γ β
γ
1 L-type Ca2+ channels in the plasma membrane
acting muscle DIG DEEPER 1 Intracellular fluid
2 the ryanodine receptor and associated proteins in the
Ca2+ Ryanodine receptor
sarcoplasmic reticulum membrane
w Figure 9.17). ■ Recall from Figure 12.12 that parasympathetic nerves do not Inactive
cAMP ATP
cAMP-dependent 3 thin filament proteins—in particular, troponin
in the normal innervate the ventricles. Does this make it impossible for protein kinase +
2
4 thick filament proteins associated with the Begin
Active
overall influ- parasympathetic activity to influence stroke volume? cAMP-dependent cross-bridges
protein kinase End-diastolic Activi
wever, in the Answer found in Appendix A.
Sarcoplasmic 5 proteins involved in pumping Ca2+ back into the ventricular volume ne
Ca2+ reticulum
e, we will see sarcoplasmic reticulum
4 3 Due to these alterations, cytosolic Ca2+ concentration increases
Thin filament
Cross-bridge cycling,
activation more quickly and reaches a greater value during excitation, Ca2+ Plasma
thick and thin filament sliding,
force generation (Ca2+–troponin) returns to its pre-excitation value more quickly following excita- epinephrine
tion, and the rates of cross-bridge activation and cycling are accel-
5
erated. The net result is the stronger, faster contraction observed
Force and Velocity of Contraction during sympathetic activation of the heart.
There is little parasympathetic innervation of the ventricles,
Cardiac muscle
Figure 12.29 Mechanisms of sympathetic effects on cardiac muscle cell contractility. In some of the pathways, the kinase phosphorylates so the parasympathetic system normally has a negligible direct Stroke volume
accessory proteins that are not shown. effect on ventricular contractility.
Cardiovascular Physiology 387 Table 12.5 summarizes the effects of the autonomic nerves
on cardiac function.
Cardia

Afterload Cardiac output = Stroke

An increased arterial pressure tends to reduce stroke volume.

This is because, like a skeletal muscle lifting a weight, the arte- Figure 12.30 Major factors inv
Reversal of all arrows in the boxes
rial pressure constitutes a “load” that contracting ventricular
output can be decreased.
muscle must work against when it is ejecting blood. A term
Uniform Color-Coded Illustrations Keyed to the Text used to describe how hard the heart must work to eject blood
is afterload. The greater the load, the less contracting muscle DIG DEEPER
fibers can shorten at a given contractility (review Figure 9.17).
Color-coding is effectively used to promote learning. For example, there are specific colors
■ Recall from Figure 12.12 that pa
This factor will not be dealt with further because in the normal innervate the ventricles. Does th
heart several inherent adjustments minimize the overall influ- parasympathetic activity to influ
for extracellular fluid, intracellular fluid, muscle filaments, and transporter molecules. ence of arterial pressure on stroke volume. However, in the Answer found in Appendix A.
sections on high blood pressure and heart failure, we will see
In addition, in figures with complex processes the color-coded numerals associated with
each step are keyed using the same coding in the main text. 388 Chapter 12

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

End of Section Study and Review

At the end of numbered sections throughout the book, you will
find a feature that is new to the sixteenth edition called Study
and Review. These are bulleted lists of the major points covered Atherosclerotic
plaque
Superior
vena cava Aortic arch

in a section, followed by an assessment. Many of the latter are Lipid-rich core

of plaque

multipart, critical thinking questions, asking students first to Abnormal connective

tissue, smooth muscle,
Right
coronary
Pulmonary
trunk
artery
recall information and then to apply it.
(divided)
and macrophages
Circumflex
artery

Left anterior

St u d y a n d Revi ew 12. 2 chambers, as well as the inner wall of all blood vessels, is lined by descending
coronary
artery
a thin layer of cells known as endothelial Normal bloodcells, orMarginal endothelium. Great cardiac
vessel wall artery
■ Blood flow between two points: analogous to electrical As noted, the human heart is divided intoInferior right and left vein

current in Ohm’s law describing electrical circuits halves, each consistingEndothelium

of an atrium and a ventricle. The two ven-
vena cava
Anterior
interventricular
artery
∙ directly proportional to pressure difference tricles are separated by a muscular wall, the interventricular
(a) Atherosclerotic plaque

∙ inversely proportional to resistance septum. Located between the atrium and ventricle in each half
of the heart are the one-way atrioventricular (AV) valves,
■ Resistance
which permit blood to flow from atrium to ventricle but not
∙ directly proportional to the viscosity of the blood and length backward from ventricle to atrium. The right AV valve is called
of the blood vessel the tricuspid valve because it has three fibrous flaps, or cusps
∙ inversely proportional to the fourth power of the vessel radius (Figure 12.10). The left AV valve has two flaps and is therefore
(most important determinant of resistance and blood flow to called the bicuspid valve. Its resemblance to a bishop’s headgear
each organ)
(a “mitre”) has earned the ofleft
(b) Occlusion AV
coronary arteryvalve another commonly
(c) Balloon angioplasty used (d) Restoration of blood flow
and stent placement

Review Question: What are the three determinants of resistance name, mitral valve.
Figure 12.69 Coronary artery disease and its treatment. (a) Anterior view of the heart showing the major coronary vessels. Inset
demonstrates narrowing due to atherosclerotic plaque. (b) Dye-contrast x-ray angiography performed by injecting radiopaque dye shows a significant
to flow, and which is varied physiologically to alter blood flow? The opening and
occlusion of the closing
right coronary of
arterythe AV
(arrow). (c) Avalves
guide wire isare
used topassive pro-a dye-filled balloon in the narrow region, and a wire-
position and inflate
mesh stent is inserted. (d) Blood flows freely through the formerly narrowed region after the procedure.
(Answer found in Appendix A.) cesses resulting from pressure differences across the valves.
Madison
(b. c, d) Matthew R. Wolff, M.D., University of Wisconsin,

When the blood pressure in an

Regular exercise atrium
is protective is greater
against heart attacksthanfor a in regular
the cor-consumption of fruits, vegetables, whole grains, and fish
variety of reasons. Among other things, it induces: may help by reducing the concentration of “bad” cholesterol
xviii Guided Tour Through a Chapter responding ventricle, the valve is pushed open and blood flows
The Heart ■ decreased myocardial oxygen demand due to decreases in
from atrium to ventricle.
resting heartIn contrast,
rate and blood pressurewhen a contractingterol
(LDLs, discussed in Chapter 16) in the blood. This form of choles-
ventri-
contributes to the buildup of atherosclerotic plaques in blood
vessels. Supplements like folic acid (a B vitamin; also called folate
■ increased diameter of coronary arteries
ISTUDY cle achieves an internal pressure greater than
■ decreased severity of hypertension and diabetes, two major
the pressure in its
or folacin) may also be protective, in this case because folic acid
helps reduce the blood concentration of the amino acid homocys-
connected atrium, risk thefactors
AVfor valve between them is forcedteine,
atherosclerosis closed.
one of the risk factors for heart attacks. Homocysteine is
 internodal pathways P wave
K EY A N D CL INICA L T ER M S
End of Chapter 12.1 Components of the Circulatory System
L-type Ca2+ channels
(dihydropyridine [DHP]
channels)
QRS complex
sinoatrial (SA) node
T-type Ca2+ channels

At the end of the chapters, you will find

pacemaker potential T wave
albumins iron-deficiency anemia
Purkinje fibers
anemia leukocytes
aorta lymphocytes
■ An alphabetized list of all key terms and clinical arteries
arterioles
macrophages
malaria
12.5 Mechanical Events of the Cardiac Cycle
atrial fibrillation isovolumetric ventricular

terms in the chapter, organized by numbered atrium megakaryocytes cardiac cycle relaxation
basophils microcirculation diastole laminar flow
bilirubin monocytes dicrotic notch septal defect
section. blood
blood vessels
multipotent hematopoietic stem
cells
end-diastolic volume (EDV)
end-systolic volume (ESV)
stenosis (of heart valves)
stroke volume (SV)

Recall
■ 12.12 and Comprehend Questions that are designed
Venules and Veins 12.24 Coronary Artery Disease and Heart Attacks
bone marrow
bulk flow
neutrophils
pernicious anemia
heart murmurs
heart sounds
systole
ventricular ejection
capillaries plasma insufficiency (of heart valves) ventricular filling
to test
capacitance student
vessels
peripheral veins
comprehension
respiratory pump
skeletal muscle pump
of key concepts. atherosclerosis
automatic electronic
defibrillation
embolism
cardiovascular system
circulatory system
plasma proteins
platelets
isovolumetric ventricular
contraction

Apply,
■ 12.13 Analyze,
The Lymphatic System
and Evaluate Questions that defibrillators (AEDs)
cardiopulmonary resuscitation
embolus
heart attack
eosinophils
erythrocytes
polycythemia
portal system 12.6 The Cardiac Output

challenge the student to go beyond the memorization (CPR) ischemia erythropoiesis pulmonary arteries afterload Frank–Starling mechanism
lymph lymphatic vessels erythropoietin pulmonary circulation
coronary artery bypass grafting myocardial infarction cardiac output (CO) inotropic
lymphatic capillaries lymphedema ferritin pulmonary trunk chronotropic preload
of facts to solve problems and to encourage thinking
lymphatic system coronary artery disease nitroglycerin
fibrinogen pulmonary veins contractility venous return
coronary balloon angioplasty transient ischemic attacks (TIAs)
folic acid reticulocyte dromotropic ventricular-function curve
coronary stents ventricular fibrillation
about the meaningtotalorperipheral
12.14 Overview
hemorrhage
broader significance of what
resistance (TPR)
coronary thrombosis
formed elements
globulins
serum
sickle-cell disease
ejection fraction (EF)

heart superior vena cava

has just been read. [systemic
12.7 Measurement of Cardiac Function
vascular resistance 12.25 Overview hematocrit systemic circulation
(SVR)] cardiac angiography echocardiography
hematopoietic growth factors transferrin
hematoma hemostasis
General
■ 12.15 BaroreceptorPrinciples
Reflexes Assessments that test a student’s (HGFs)
hemochromatosis
vascular system
veins 12.9 Arteries
12.26 Formation of a Platelet Plug hemoglobin ventricle arteriosclerosis mean arterial pressure (MAP)
ability to relate thebaroreceptors
aortic arch baroreceptor
arterial baroreceptors
material covered in a given
medullary cardiovascular center nitric oxide prostacyclin inferior vena cava
intrinsic factor
venules
vitamin B12
compliance
diastolic pressure (DP)
pulse pressure
sphygmomanometer
platelet activation prostaglandin I2 (PGI2)
chapter
12.17 to one Reflexes
Other Cardiovascular or more of the Generalplatelet
and Responses Principles
aggregation of thromboxane A 2
iron deficiency Korotkoff’s sounds systolic pressure (SP)

platelet plug von Willebrand factor (vWF)

Physiology described in Chapter 1. This provides 12.2 Pressure, Flow, and Resistance 12.10 Arterioles
Cushing’s phenomenon
hemodynamics resistance (R) active hyperemia myogenic responses
12.27 Blood Coagulation: Clot Formation angiotensin II nitric oxide
acardiogenic
powerful unifying theme to understanding
blood coagulation all
12.18 Hemorrhage and Other Causes of Hypotension hydrostatic pressure viscosity
platelet factor (PF) Poiseuille’s law atrial natriuretic peptide prekallikrein
shock low-resistance shock clot prothrombin bradykinin prostacyclin
of physiology andvasovagal
hypotension
hypovolemic shock
is also
shock
an excellentclotting
syncope
gauge of a
extrinsic pathway
thrombin
thrombus
12.3 Anatomy
3. Which of the following contains blood with the lowest oxygen content?
aortic valves epicardiumveins
endothelin-1 (ET-1) prostaglandin I2 (PGI2)
10. Which of the following pressures is closest to the mean arterial blood
flow autoregulation reactive hyperemia
a. aorta d. pulmonary pressure in a person whose systolic blood pressure is 135 mmHg and pulse
student’s progress from the beginning to the end of a
hyperemia sildenafil (Viagra)
fibrin tissue factor b. leftatrioventricular
atrium (AV) valves interventricular
e. systemic septum
arterioles pressure is 50 mmHg?
intrinsic tone tadalafil (Cialis)
12.20 Exercise hemophilia vitamin K bicuspid
c. right valve
ventricle mitral valve a. 110 mmHg
kallekrein vasoconstriction
term or semester.
maximal oxygen consumption intrinsic pathway chordae tendineae myocardium b. 78 mmHg
4. If other factors are equal, which of the following vessels would have the kininogen vasodilation
conducting system papillary muscles c. controls
102 mmHg
(Vo max) lowest resistance? local vasopressin
.
2 coronary arteries pericardium d. 152 mmHg
12.28 Anticlotting Systems a. length = 1 cm, radius = 1 cm
coronary blood flow prolapse e. 85 mmHg
b. length = 4 cm, radius = 1 cm 12.11 Capillaries
12.21 Hypertension antithrombin III plasminogen activators endothelial cells pulmonary valve
c. length = 8 cm, radius = 1 cm 11.absorption
Which of the following would help restore homeostasis
intercellular clefts in the first few
angiotensin-converting enzyme left ventricular hypertrophy fibrinolytic system protein C endothelium tricuspid valve
d. length = 1 cm, radius = 2 cm moments after a person’s mean arterial
angiogenesis pressure became elevated?
kwashiorkor
(ACE) inhibitors primary hypertension heparin thrombomodulin e. length = 0.5 cm, radius = 2 cm a. a decrease in baroreceptor actionmetarterioles
potential frequency
12.4 Heartbeat Coordination angiogenic factors
hypercoagulability tissue factor pathway inhibitor b. a decrease in action potential frequency along pressure
parasympathetic
beta-adrenergic receptor blockers renal hypertension 5. Which of the following correctly ranks pressures during isovolumetric angiostatin net filtration (NFP) neurons
calcium channel blockers secondary hypertension plasmin (TFPI) absolute refractory period ECG leads to the heart
contraction of a normal cardiac cycle? colloids precapillary sphincter
diuretics stroke plasminogen tissue plasminogen activatora.(t-PA)
artificial pacemaker
left ventricular > aortic > left atrial
ectopic pacemakers c. an increase in action potential frequency
crystalloids Starling along
forcessympathetic neurons to
atrioventricular (AV) node electrocardiogram (ECG, EKG)
hypertension b.
aortic > left atrial > left ventricular edemathe heart
automaticity F-type channels d. a decrease in action potential frequency along sympathetic neurons to
12.29 Anticlotting Drugs c.
left atrial > aortic > left ventricular fused-vesicle channels
AV conduction disorder (hyperpolarization-activated arterioles
12.22 Heart Failure d.
aortic > left ventricular > left atrial
aspirin recombinant t-PA bundle branches cyclic nucleotide-gated e. an increase in total peripheral resistance
e.
left ventricular > left atrial > aortic
beta-adrenergic receptor blockers diuretics oral anticoagulants thrombolytic therapy bundle of His [HCN] channels)
6. Considered as a whole, (DHP)
the body’s capillaries have 12. Which is false about L-type Ca2+ channels in cardiac ventricular muscle cells?
cardiac inotropic drugs heart failure dihydropyridine channels heart rate
a. smaller cross-sectional area than the arteries. a. They are open during the plateauCardiovascular
of the actionPhysiology
potential. 441
congestive heart failure pulmonary edema Clinical Case Study b. They allow Ca2+ entry that triggers sarcoplasmic reticulum Ca2+ release.
b. less total blood flow than in the veins.
diastolic dysunction systolic dysfunction balloon valvuloplasty percutaneous transcatheterc.aortic
greater total resistance than the arterioles. c. They are found in the T-tubule membrane.
digitalis vasodilator drugs d. slower blood velocity than in the arteries.
valve replacement (TAVR) d. They open in response to depolarization of the membrane.
e. greater total blood flow than in the arteries. e. They contribute to the pacemaker potential.
12.23 Hypertrophic Cardiomyopathy 7. Which of the following would not result in tissue edema? 13. Which correctly pairs an ECG phase with the cardiac event responsible?
a. an increase in the concentration of plasma proteins a. P wave: depolarization of the ventricles
angina pectoris hypertrophic cardiomyopathy
b. an increase in the pore size of systemic capillaries b. P wave: depolarization of the AV node
c. an increase in venous pressure c. QRS wave: depolarization of the ventricles
d. QRS wave: repolarization of the ventricles
CHAPTER 1 2 TE ST Q UE ST I O NS Recall and Comprehend Answers appear in Appendixblockage
d. A. of lymph vessels
e. a decrease in the protein concentration of the plasma e. T wave: repolarization of the atria
These questions test your recall of important details covered in this chapter. They also help prepare you for the type of questions
8. Which statement comparing the systemic and pulmonary circuits is true? 14. When a person engages in strenuous, prolonged exercise,
encountered in standardized exams. Many additional questions of this type are available on Connect and LearnSmart. a. The blood flow is greater through the systemic. a. blood flow to the kidneys is reduced.
b. The blood flow is greater through the pulmonary. b. cardiac output is reduced.
c. The absolute pressure is higher in the pulmonary. c. total peripheral resistance increases.
1. Hematocrit is increased 2. The principal site of erythrocyte production is d. The blood flow is the same in both. d. systolic arterial blood pressure is reduced.
a. when a person has a vitamin B12 deficiency. a. the liver. e. The pressure gradient is the same in both. e. blood flow to the brain is reduced.
b. by an increase in secretion of erythropoietin. b. the kidneys. 15. Which is not part of the cascade leading to formation of a blood clot?
9. What is mainly responsible for the delay between the atrial and ventricular
c. when the number of white blood cells is increased. c. the bone marrow. a. contact between the blood and collagen found outside the blood vessels
contractions?
d. by a hemorrhage. d. the spleen. b. prothrombin converted to thrombin
a. the shallow slope of AV node pacemaker potentials
e. in response to excess oxygen delivery to the kidneys. e. the lymph nodes. c. formation of a stabilized fibrin mesh
b. slow action potential conduction velocity of AV node cells
c. slow action potential conduction velocity along atrial muscle cell d. activated platelets
membranes e. secretion of tissue plasminogen activator (t-PA) by endothelial cells
d. slow action potential conduction in the Purkinje network of the ventricles
e. greater parasympathetic nerve firing to the ventricles than to the atria

9. A person is given a drug that doubles the blood flow to her kidneys but does
not change the mean arterial pressure. What must the drug be doing?
Hint: See Figure 12.36 and remember how parallel resistances add up.
10. A blood vessel removed from an experimental animal dilates when exposed to
acetylcholine. After the endothelium is scraped from the lumen of the vessel, it
no longer dilates in response to this mediator. Explain. Hint: See Table 12.6.
11. A person is accumulating edema throughout the body. Average capillary
pressure is 25 mmHg, and lymphatic function is normal. What is the most
likely cause of the edema? Hint: See Figure 12.45.
12. A person’s cardiac output is 7 L/min and mean arterial pressure is 140
mmHg. What is the person’s total peripheral resistance? Hint: See
Table 12.8 and recall the equation relating MAP, CO, and TPR.
13. The following data are obtained for an experimental animal before and after
administration of a drug:
Before: Heart rate = 80 beats/min; Stroke volume = 80 mL/beat
After: Heart rate = 100 beats/min; Stroke volume = 64 mL/beat
Total peripheral resistance remains unchanged.
What has the drug done to mean arterial pressure?
Hint: Recall the relationship between heart rate, stroke volume, and cardiac
output.
14. When the afferent nerves from all the arterial baroreceptors are cut in an
experimental animal, what happens to mean arterial pressure? Hint: What
will the brain “think” the arterial pressure is?
15. What happens to the hematocrit within several hours after a hemorrhage?
Hint: See Table 12.9 and remember what happens to interstitial fluid volume.
16. If a woman’s mean arterial pressure is 85 mmHg and her systolic pressure
is 105 mmHg, what is her pulse pressure? Hint: See Figure 12.34Cand
HAPTER 12 TEST QU ESTION S Apply, Analyze, and Evaluate Answers appear in Appendix A.
Table 12.8.
17. When a heart is transplanted into a patient, it is not possible toThese
connectquestions, which are designed to be challenging, require you to integrate concepts covered in the chapter to draw your own
autonomic neurons from the medullary cardiovascular centersconclusions.
to the new See if you can first answer the questions without using the hints that are provided; then, if you are having difficulty, refer
backexercise?
heart. Will such a patient be able to increase cardiac output during to the figures or sections indicated in the hints.
Hint: Recall the effects of circulating catecholamines and changes in
venous return on cardiac output.
1. A person is found to have a hematocrit of 35%. Can you conclude that there 5. A person has a left ventricular systolic pressure of 180 mmHg and an
18. The P wave records the spread of depolarization of the atria on a lead I
is a decreased volume of erythrocytes in the blood? Explain. Hint: See aortic systolic pressure of 110 mmHg. What is the explanation? Hint: See
ECG as an upright wave form. Referring to the orientation of the ECG Figure 12.1 and remember the formula for hematocrit. Figure 12.22.
leads in Figure 12.18, what difference in the shape of the P wave might
you expect when recording with lead aVR? Hint: See Figures 12.18 2. Which would cause a greater increase in resistance to flow: a doubling of blood 6. A person has a left atrial pressure of 20 mmHg and a left ventricular
viscosity or a halving of tube radius? Hint: See equation 12-2 in Section 12.2. pressure of 5 mmHg during ventricular filling. What is the explanation?
and 12.19.
2+ Hint: See Figures 12.21 and 12.22.
19. Calculate the ejection fraction (EF), given the following cardiac 3. If all plasma membrane Ca channels in contractile cardiac muscle cells
were blocked with a drug, what would happen to the muscle’s action 7. A patient is taking a drug that blocks beta-adrenergic receptors. What
performance data:
potentials and contraction? Hint: See Figure 12.15. changes in cardiac function will the drug cause? Hint: See Figure 12.29
Cardiac output (CO) = 5400 mL/min and Table 12.5 and think about the effect of these receptors on heart rate
4. A person with a heart rate of 40 has no P waves but normal QRS complexes
Heart rate (HR) = 75 beats/min on the ECG. What is the explanation? Hint: See Figures 12.19 and 12.22 and and contractility.
End-systolic volume (ESV) = 60 mL remember the source of the P wave. 8. What is the mean arterial pressure in a person with a systolic pressure of
Hint: See Figure 12.22 and the description of ejection fraction associated 160 mmHg and a diastolic pressure of 100 mmHg? Hint: See Figure 12.34a.
with Figure 12.28.
Cardiovascular Physiology 443

CHAPTER 1 2 TE ST Q UE ST I O NS General Principles Assessment Answers appear in Appendix A.

These questions reinforce the key theme first introduced in Chapter 1, that general principles of physiology can be applied across all
levels of organization and across all organ systems.

1. A general principle of physiology states that information flow between cells,
tissues, and organs is an essential feature of homeostasis and allows for
integration of physiological processes. How is this principle demonstrated
by the relationship between the circulatory and endocrine systems?
2. The left AV valve has only two large leaflets, while the right AV valve has
three smaller leaflets. It is a general principle of physiology that structure
is a determinant of—and has coevolved with—function. Although it is
unknown why the two valves differ in structure in this way, what difference
in the functional demands of the left side of the heart might explain why
there is one less valve leaflet than on the right side?
3. Two of the body’s important fluid compartments are those of the
interstitial fluid and plasma. How does the liver’s production of plasma
proteins interact with those compartments to illustrate the general
principle of physiology, Controlled exchange of materials occurs between
compartments and across cellular membranes?

Guided Tour Through a Chapter xix

ISTUDY
 UPDATES AND ADDITIONS
N E W TO TH I S E D ITI O N
The sixteenth edition of Vander’s Human Physiology has been
thoroughly revised with an eye toward updating information
and presenting that information in a format that is most readily
assimilated and retained by the reader. To that end, several new
design elements that improve the effectiveness of the text as a
learning tool have been developed. These elements include:
■ offset, bulleted lists of such items as anatomical features, to
provide an immediate visual reference and study guide
■ offset, numbered lists of processes that are best understood
in stepwise fashion
■ reduction of long segments of text into smaller, more
manageable chunks
■ artwork that is keyed by color-coded symbols to the text
■ standardization of artwork across chapters (for example, the
inclusion and style of captions in multipart figures)
■ the inclusion of over 200 brief, bulleted lists of major
concepts at the end of each numbered section. These
lists are called Study and Review, which reflects their
purpose. An assessment at the end of each of these handy
study guides is usually a mix of recall and application
and is designed to encourage readers to stop and think
about that section’s material before proceeding to the
next section.

Selected Chapter-by-Chapter Changes in This Edition

In general, every chapter has been carefully and thoroughly updated and edited for new content, improved illustrations, accuracy, and
readability. A few examples of some specific changes are given below as representative of the overall approach to the sixteenth edition.

Chapter 1 The description of reflexes has been expanded. Chapter 11 The use of anti-inflammatory glucocorticoids in
the treatment of COVID-19 is now included.
Chapter 3 The formation of lactate and its role in metabolism
has been further elucidated. Chapter 12 New discussion and figure on lymphedema has
been included.
Chapter 4 The process of primary active transport is now
illustrated in a color-coded figure that is keyed to the text. Chapter 13 The use of anti-inflammatory glucocorticoids in the
An expanded description of osmosis, its similarities and treatment of lung inflammation in COVID-19 is discussed.
differences from simple diffusion, and its relation to entropy
Chapter 14 Sections on incontinence and on kidney
has now been included.
transplantation have been updated.
Chapter 6 Figures illustrating the processes involved in the
Chapter 17 New and updated information has been added
establishment of a resting membrane potential, action potentials,
to sections on opiate suppression of the hypothalamic-
EPSPs, and IPSPs have been redrawn for greater quantitative
pituitary-gonadal axis; nausea and vomiting of pregnancy and
accuracy, with color-coded numbers keyed to the text.
hyperemesis gravidum; contraception; minipuberty, including
Chapter 7 The response of single opponent color ganglion cells effects of estrogen in the female infant; and factors involved in
to different wavelengths of light has been redrawn for clarity. development of a dominant follicle. A new figure and updated
text have been added to the section on spermatogenesis.
Chapter 8 The classes and names of anti-anxiety and antidepressant
drugs have been updated to reflect current trends in medicine. Chapter 18 A new illustration of SARS-CoV-2 is included.
New information regarding pathological effects of SARS-
Chapter 9 Figures illustrating the cross-bridge cycle in skeletal
CoV-2, and the role of interferons in combatting the virus,
muscle cells, the mechanism of action of Ca2+ in the cross-
are also included. New subsections for myeloid cells
bridge cycle, and contraction of smooth muscle cells have
and lymphoid cells have been added. The description of
been color-coded and keyed to the text.
regulatory T-cells has been expanded.
Chapter 10 The description of Parkinson’s disease and
Chapter 19 Updated information has been added on
treatments has been updated.
glioblastoma multiforme.
xx

ISTUDY
 ACKNOWLEDGMENTS
In this sixteenth edition of Vander’s Human Physiology, we are very excited to have been able to use real student data
points derived from thousands of users to help guide our revision path. We are also deeply thankful to the following
individuals for their contributions to the sixteenth edition. Any errors that may remain are solely the responsibility of
the authors.

David Adelson The authors are also indebted to the editors and staff at McGraw
East Los Angeles College Hill Education who contributed to the development and publication
Douglas Danforth of this text, particularly Senior Product Developer Krystal Faust,
Ohio State University–College of Medicine Portfolio Manager Matthew Garcia, Marketing Manager Valerie
Sumana Koduri Kramer, Content Project Managers, Ann Courtney/Brent dela
Medical College of Wisconsin Cruz, Buyer Sandy Ludovissy, Designer David Hash, and Content
Monica McCullough Licensing Specialist Lori Hancock. We also thank freelance
Western Michigan University copy editor Heath Lynn Silberfeld. We are especially grateful
Cassandra Nelson for outstanding proofreading that was provided by freelance
Rutgers University proofreaders Jennifer Grubba and Sharon O’Donnell. As always,
we are grateful to the many students and faculty who have provided
The authors are indebted to the many individuals who assisted with us with critiques and suggestions for improvement.
the numerous digital and ancillary products associated with this Eric P. Widmaier
text. Thank you to Janet Brodsky, Ivy Tech Community College, Hershel Raff
and Justin York, Glendale Community College.
Kevin T. Strang

xxi

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 1

CHAPTER
Homeostasis:
A Framework for Human Physiology

1.1 The Scope of Human Physiology

1.2 How Is the Body Organized?
1.3 Body Fluid Compartments
1.4 Homeostasis: A Defining Feature
of Physiology
1.5 General Characteristics of
Homeostatic Control Systems
1.6 Components of Homeostatic Control
Systems
1.7 The Role of Intercellular Chemical
Messengers in Homeostasis
1.8 Processes Related to Homeostasis
1.9 General Principles of Physiology
Chapter 1 Clinical Case Study
Coping with changes in external temperature and oxygen levels even in extreme
conditions are examples of homeostasis. Andre Schoenherr/Stone/Getty Images

T
he purpose of this chapter is to provide an orientation to the
subject of human physiology and the central role of homeostasis—
the maintenance of a stable internal environment—in the study
of this science. The mountain climbers shown here are experiencing
numerous challenges that must be met by their hearts, lungs, and other
organs. For example, their hearts need to work harder to pump more
blood each minute to their muscles, their lungs must maximize the
amount of oxygen brought into the blood, and they must maintain their
body temperature in the cold environment. An understanding of these
processes 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, organ systems, and fluid
compartments. Lastly, several “General Principles of Physiology” are
introduced. These serve as unifying themes throughout the textbook,
and the reader is encouraged to return to them often to see how they
apply to the material covered in subsequent chapters. ■

ISTUDY
 1.1 The Scope of Human Fertilized egg

Physiology Cell
Physiology is the study of how living organisms function. At division
and
one end of the spectrum, it includes the study of individual growth
molecules—for example, how a particular protein’s shape and
electrical charge, if any, allow it to function as a channel for ions
Cell
to move into or out of a cell. At the other end, it is concerned with differentiation
complex processes that depend on the integrated functions of
many organs in the body—for example, how the heart, kidneys, Specialized
and several glands all function together to cause the excretion of cell types
more sodium ions in the urine when a person has eaten salty food.
Epithelial Connective- Neuron Muscle
Physiologists are interested in function and integration— cell tissue cell cell
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-
Tissues
vidual molecules, the intention is ultimately to apply the informa-
tion 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 recon-
struct our physiological synthesis, so as to see the joint action of Epithelial Connective Nervous Muscle
tissue tissue tissue tissue
all the parts we have isolated.”
In many areas of this text, we will relate physiology to human
health. 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 physiologists are actively engaged in research on the physi-
ological bases of a wide range of diseases. In this text, we will give
many examples of the pathophysiology that underlies disease. A Organ
handy index of all the diseases and medical conditions discussed in (kidney) Functional
this text, and their causes and treatments, appears in Appendix B. unit
A related field of science is anatomy, which is the study of (nephron)
the structures of body parts. Throughout this text, we will typically
provide an overview of the anatomy of body parts, such as the
lungs, kidneys, brain, and others. Without a basic understanding of
structures, it would be difficult to understand physiology because,
as we will see, the structures of objects determine their functions.
For this reason, we turn first to an overview of the anatomical
Kidney
organization of the human body, including the ways in which the
cells of the body are organized into higher levels of structure.
Ureter

Stu d y a n d Revi ew 1.1

■ Physiology: study of the functions of the body parts Bladder

■ Pathophysiology: study of disease states (physiological Urethra

dysfunction)
Organ system
Review Question: Distinguish between anatomy, physiology,
(Urinary system)
and pathophysiology. How are they related? (Answer found in
Appendix A.) Figure 1.1 Levels of cellular organization. The nephron is not drawn
to scale.

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

1.2 How Is the Body Organized?
The simplest structural units into which a complex multicellular
organism can be divided and still retain the functions charac-
teristic of life are called cells (Figure 1.1). Each human being
2 Chapter 1
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 develop-
ment, however, each cell becomes specialized for the performance

ISTUDY
 of a particular function, such as producing force and movement or
generating electrical signals. The process of transforming an unspe-
cialized cell into a specialized cell is known as cell differentiation,
one of the most exciting areas of study in biology today.
About 200 distinct kinds of cells can be identified in the
body in terms of differences in structure and function. When cells
are classified according to the broad types of function they per-
form, however, four major categories emerge:
■■ muscle cells
■■ neurons
■■ epithelial cells
■■ 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 control-
ling 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 locations
during development and form selective adhesions with other cells
to produce multicellular structures. In this manner, the cells of the
body arrange themselves in various combinations to form a hierarchy
of organized structures. Differentiated cells with similar properties
aggregate to form tissues. Corresponding to the four general catego-
ries of differentiated cells, there are four general types of tissues:
■■ muscle tissue
■■ nervous tissue
■■ epithelial tissue
■■ 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 cellular 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.
As you will see shortly, 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 discus-
sion 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, 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 producing facial expres-
sions. Contraction of skeletal muscle is under voluntary control,
which means that you can choose to contract a skeletal muscle
whenever you wish.
Cardiac muscle cells are found only in the heart. When car-
diac muscle cells generate force, the heart contracts and conse-
quently pumps blood into the circulation.
Smooth muscle cells make up part of the walls of many of
the tubes in the body—blood vessels, for example, or the tubes
ISTUDY
of the gastrointestinal tract—and their contraction decreases the
diameter or shortens the length of these tubes. For example, con-
traction of smooth muscle cells along the esophagus—the tube
leading from the pharynx to the stomach—helps “squeeze” swal-
lowed food down to the stomach.
Cardiac and smooth muscle tissues are said to be “involun-
tary” muscle, because you cannot consciously alter the activity
of these types of muscle. You will learn about the structure and
function of each of the three types of muscle cells in Chapters 9
and 12.
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 neu-
rons underlies such phenomena as consciousness and perception.
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 consisting of numerous
layers of cells, called a stratified epithelium. The type of epithe-
lium 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 trachea (just
mentioned). Epithelial cells rest on an extracellular protein layer called
the basement membrane, which (among other functions) anchors
the tissue (Figure 1.2). The side of the cell anchored to the basement
membrane is called the basolateral side; the opposite side, which typi-
cally faces the interior (called the lumen) of a structure such as the
trachea or the tubules of the kidneys, is called the apical side.
A defining feature of many epithelia is that the two sides
of all the epithelial cells in the tissue may perform different
physiological functions. In addition, the cells are held together
Homeostasis: A Framework for Human Physiology 3

Blood vessel
Epithelial cell
Glucose
molecule
Basolateral
membranes
(transport glucose
out of cell)
Tight junction
Tubular
lumen Apical
membrane
(transports glucose
into cell)
Basement
membrane
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 transported across the epithelium, first
directed into the cell, and then directed out of the cell.
along their lateral surfaces between the apical and basolateral
membranes by extracellular barriers called tight junctions (look
ahead to Figure 3.9, b and c, for a depiction of tight junctions).
Tight junctions function as selective barriers regulating the
exchange of molecules. For example, as shown in Figure 1.2 for
a kidney tubule, the apical membranes transport useful solutes
such as the sugar glucose from the tubule lumen into the epithe-
lial 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 leaking
“backward.”
Connective-Tissue Cells and Connective Tissue
Connective-tissue cells, as their name implies, connect, 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 tis-
sue 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 connec-
tive tissue, 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 ECM consists
4 Chapter 1
ISTUDY
of a mixture of proteins; polysaccharides (chains of sugar mol-
ecules); and, in some cases, minerals, specific for any given tissue.
The ECM serves two general functions:
■■ provides a scaffold for cellular attachments
■■ transmits information in the form of chemical messengers
to the cells to help regulate their activity, migration,
growth, and differentiation
Some of the proteins of the ECM are known as fibers, insolu-
ble proteins including ropelike collagen fibers and ­rubberband-like
elastin fibers. Others are a mixture of nonfibrous proteins that
contain carbohydrate. In some ways, the ECM is analogous
to reinforced concrete. The fibers of the matrix, particularly
collagen, which constitutes as much as one-third of all bodily
proteins, are like the reinforcing iron mesh or rods in the concrete.
The carbohydrate-­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 adhe-
sion or recognition molecules between cells. Thus, they are links
in the communication between extracellular messenger 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:
■■ a series of small tubes, each composed of a simple
epithelium
■■ blood vessels, whose walls contain varying quantities of
smooth muscle and connective tissue
■■ extensions from neurons that end near the muscle and
epithelial cells
■■ 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 comprised of small, similar subunits
often referred to as functional units, each performing the func-
tion 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 (see Figure 1.1). For
example, the urinary system consists of the kidneys; the uri-
nary bladder; the ureters, the tubes leading from the kidneys
to the bladder; and the urethra, the tube leading from the
bladder to the exterior. Table 1.1 lists the components and
functions of the organ systems in the body. It is critical to
recognize, however, that organ systems do not function “in a
vacuum.” That is, they function together to maintain a healthy
body. As just one example, blood pressure is controlled by the
circulatory, urinary, nervous, and endocrine systems working
together.
 TABLE 1.1 Organ Systems of the Body
System Major Organs or Tissues Primary Functions
Circulatory Heart, blood vessels, blood Transport of blood throughout the body

Digestive Mouth, salivary glands, pharynx, esophagus, stomach, small Digestion and absorption of nutrients and water;
and large intestines, anus, pancreas, liver, gallbladder elimination of wastes

Endocrine All glands or organs secreting hormones: pancreas, testes, Regulation and coordination of many activities in the
ovaries, hypothalamus, kidneys, pituitary, thyroid, parathyroids, body, including growth, metabolism, reproduction, blood
adrenals, stomach, small intestine, liver, adipose tissue, heart, pressure, water and electrolyte balance, and others
and pineal gland; and endocrine cells in other organs

Immune White blood cells and their organs of production Defense against pathogens

Integumentary Skin Protection against injury and dehydration; defense

against pathogens; regulation of body temperature

Lymphatic Lymph vessels, lymph nodes Collection of extracellular fluid for return to blood;
participation in immune defenses; absorption of fats from
digestive system

Musculoskeletal Cartilage, bone, ligaments, tendons, joints, skeletal muscle Support, protection, and movement of the body;
production of blood cells

Nervous Brain, spinal cord, peripheral nerves and ganglia, sense organs Regulation and coordination of many activities in
the body, including most of those regulated by the
endocrine system; detection of and response to changes
in the internal and external environments; states of
consciousness; learning; memory; emotion; others

Reproductive Male: testes, penis, and associated ducts and glands Male: production of sperm; transfer of sperm to female
Female: ovaries, fallopian tubes, uterus, vagina, mammary Female: production of eggs; provision of a nutritive
glands environment for the developing embryo and fetus;
nutrition of the infant

Respiratory Nose, pharynx, larynx, trachea, bronchi, lungs Exchange of carbon dioxide and oxygen; regulation of
hydrogen ion concentration in the body fluids

Urinary Kidneys, ureters, bladder, urethra Regulation of plasma composition through controlled
excretion of ions, water, and organic wastes

St u d y an d Review 1.2 St udy and Review 1 . 2 —c o ntinue d

■ Cells: simplest structural units into which a complex
multicellular organism can be divided and still retain the
functions characteristic of life
■ Cell differentiation: formation of four general types of
specialized cells
∙∙ Muscle cells: generate the mechanical activities that produce
force and movement; 3 types include skeletal, cardiac, and
smooth muscle cells
∙∙ Neurons: initiate and conduct electrical signals
∙∙ Epithelial cells: form barriers and selectively secrete and
absorb ions and organic molecules; basolateral surface rests
on a basement membrane
∙∙ Connective-tissue cells: connect, anchor, and support
the structures of the body; form the extracellular
matrix, which consists of fibers such as collagen and
elastin
■ Tissues: aggregates of differentiated cells with similar
properties; correspond to the four general types of specialized
cells
■ Organs: composed of two or more of the four kinds of tissues
∙∙ Many organs contain multiple, small, similar functional units.
■ Organ system: group of organs that perform an overall function
Review Question: It is a simplification to refer to organ systems
as if they function independently from each other. Why? Refer to
Table 1.1 and give two or three examples of how the functions of
different organ systems overlap. (Answer found in Appendix A.)
1.3 Body Fluid Compartments
Another useful way to think about how the body is organized
is to consider body fluid compartments. When we refer to
“body fluid,” we are referring to a watery solution of dissolved
Homeostasis: A Framework for Human Physiology 5

ISTUDY
 substances such as oxygen, nutrients, and wastes. This solution
is present within and around all cells of the body, and within
blood vessels, and is known as the internal environment. Body
fluids exist in three compartments:
■■ Intracellular fluid is the fluid contained within all the
cells of the body and accounts for about 67% of all the
water in the body.
■■ Plasma is the fluid portion of blood in which blood cells
are suspended, and accounts for about 7% of total-body
water.
■■ Interstitial fluid is the fluid that lies around and between
cells (in the space known as the interstitium) and makes
up about 26% of total-body water.
Together, the plasma and interstitial fluid comprise the extracell­
ular fluid of the body. Therefore, the total volume of extracel-
lular fluid is the sum of the plasma and interstitial fluid volumes.
Figure 1.3 summarizes the relative volumes of water in the dif-
ferent 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 ves-
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 intersti-
tial fluid). With this major exception, the entire extracellular
fluid may be considered to have an essentially homogeneous
Intracellular fluid
28 L
Red blood
cell
Plasma 3 L
Capillary
Interstitial fluid
11 L
(a) Movements of water between body fluid
compartments
Figure 1.3 Fluid compartments of the body. Volumes are for a typical 70-kilogram (kg) (154-pound) 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.
DIG DEEPER
■ What fraction of total-body water is extracellular? Assume that water constitutes 60% of a person’s body weight. What fraction of a person’s
body weight is due to extracellular body water?
Answer found in Appendix A.
6 Chapter 1
ISTUDY
solute composition. In contrast, the composition of the extra-
cellular fluid is very different from that of the intracellular
fluid.
Maintaining differences in fluid composition between
intracellular and extracellular fluid compartments is an impor-
tant 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 intracel-
lular 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 from each
other by the walls of the blood vessels. Chapter 12 discusses
how this barrier normally keeps most of the extracellular fluid
in the interstitial compartment and restricts proteins mainly to
the plasma.
With this understanding of the structural organization of the
body, we turn to a description of how balance is maintained in the
internal environment of the body.
70 (67%)
Percentage of total-body water
60
50
40
30 (26%)
20
10 (7%)
Plasma Interstitial Intracellular
fluid fluid
(b) Relative amounts of water in body fluid
compartments
 St u d y an d Review 1.3
■ Extracellular fluid: composed of the interstitial fluid (the fluid
between cells [within the space called the interstitium]) and
the plasma (noncellular portion of blood)
∙∙ Interstititial fluid: ~75%–80% of the extracellular fluid
∙∙ Plasma: ~20%–25% of the extracellular fluid
■ Interstitial fluid and plasma have similar composition except
plasma contains a much greater concentration of protein.
■ Intracellular fluid: the fluid inside cells
■ Internal environment: total-body fluid, made up of 2/3
intracellular fluid and 1/3 extracellular fluid
■ Different compositions of the compartments reflect the
activities of the barriers separating them.
Review Question: If a person were to receive a wound that resulted
in significant loss of blood, which body fluid compartment would
be immediately affected? How might a health care professional
restore fluid to that compartment? (Answer found in Appendix A.)
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 some-
how associated with a balance among the multiple 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 ordinary microscope, led to the discov-
ery that the human body is composed of trillions of cells, each
of which can permit movement of certain substances—but not
others—across the plasma 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 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 interiors and the blood in nearby capillaries (see Figure 1.3a).
It was further determined by careful observation that most
of the common physiological variables found in healthy organ-
isms such as humans—blood pressure; body temperature; 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 physiolo-
gist Walter Cannon, who coined the term homeostasis.
Originally, homeostasis was defined as a state of reason-
ably stable balance between physiological variables such as those
just described. However, this simple definition does not provide a
full 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 during the course of a day, yet are
still considered to be in balance. That is because homeostasis is a
dynamic, not a static, process.
ISTUDY
Consider swings in the concentration of glucose in the blood
over the course of a day (Figure 1.4). After a typical meal, car-
bohydrates in food are broken down in the intestines into glucose
molecules, which are then absorbed across the intestinal epithe-
lium and released into the blood. As a consequence, the blood
­glucose concentration increases 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 inter-
nal environment. What is important is that once the concentra-
tion of glucose in the blood increases, compensatory ­mechanisms
restore it toward the concentration it was before the meal.
These homeostatic compensatory mechanisms do not, how-
ever, overshoot to any significant degree in the opposite direction.
That is, the blood glucose usually does not decrease below the pre-
meal concentration, or does so only slightly. In the case of glucose,
the endocrine system is primarily responsible for this adjustment, by
regulating the uptake of glucose from the blood into organs such as
muscles. However, a wide variety of control systems may be initiated
to regulate other homeostatic processes. In later chapters, we will
see how every organ of the human body contributes to homeostasis,
sometimes in multiple ways, and usually in concert with each other.
Homeostasis, therefore, does not imply that a given physiologi-
cal 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 normal range, it is restored to normal.
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 and carbon dioxide levels in the arterial blood of a healthy
person are measured, they barely change over the course of time,
even if the person exercises. Such a system is said to be tightly con-
trolled and to demonstrate very little variability or scatter around an
average value. Blood glucose concentrations, as we have seen, may
vary considerably over the course of a day. Yet, if the daily average
glucose concentration was determined in the same person on many
consecutive days, it would be much more predictable over days or
even years than random, individual measurements of glucose 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 time. This has led to the con-
cept 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 predictable when averaged over the long term.
160
concentration (mg/dL)
140
Blood glucose
Breakfast Lunch Dinner
120
100
80
60
12:00 A.M. 6:00 A.M. 12:00 P.M. 6:00 P.M. 12:00 A.M.
Time of day
Figure 1.4 Changes in blood glucose concentration 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.
Homeostasis: A Framework for Human Physiology 7
 It is also important to realize that a person may be homeo-
static for one variable but not homeostatic for another. Homeosta-
sis must be described differently, therefore, for each variable. For
example, as long as the concentration of sodium ions (Na+) in the
blood remains within its normal range, Na+ homeostasis exists.
However, a person whose Na+ concentration is homeostatic may
suffer from other disturbances, such as an abnormally low pH in
the blood resulting from kidney disease, a condition that could be
fatal. Just one nonhomeostatic variable, among the many that can
be described, can have life-threatening consequences.
Often, when one variable becomes significantly out of bal-
ance, other variables in the body become nonhomeostatic as a
consequence. For example, when you exercise strenuously and
begin to get warm, you perspire, which helps maintain body
temperature homeostasis. This is important, because many cells
(notably neurons) malfunction 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”).
Stu d y a n d Revi ew 1.4
■ Internal environment: the extracellular fluid
■ Homeostasis: the process of maintaining a stable internal
environment
∙∙ When homeostasis is disturbed for one variable, other
variables will compensate.
■ Dynamic constancy: a given variable may fluctuate in the body
in the short term, but is stable and predictable in the long term
Review Question: What is meant by “dynamic constancy”?
How does it relate to homeostasis, and what is one physiological
variable described in this section that illustrates this concept?
(Answer found in Appendix A.)
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 internal envi-
ronment initiates a reaction to correct the change. The compen-
sating mechanisms that mediate such responses are performed by
homeostatic control systems.
Consider again an example of the regulation of body tempera-
ture. This time, our subject is a resting, lightly clad man in a room
at a temperature of 20°C and moderate humidity. His internal body
temperature is 37°C, and he is losing heat to the external environment
because the room 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 undergoes no net gain or loss of heat, and the body temperature
8 Chapter 1
ISTUDY
remains more or less 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 stable, homeostatic 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 temperature in our example is known as
the set point of the thermoregulatory system.
All homeostatic control systems operate around a set point.
There are set points for blood pressure, plasma ion concentrations,
total-body water, and so on. Stability of an internal environmental
variable is achieved by the balancing of inputs and outputs. In the
previous example, the variable (body temperature) remains constant
because metabolic heat production (input) equals heat loss from the
body (output).
Now imagine that we rapidly decrease the temperature of the
room, say to 5°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
responses occur to limit the decrease. Figure 1.5 summarizes these
responses. The reader is urged to study Figure 1.5 and its legend
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.
Begin
Room temperature
Heat loss from body
Body temperature
(Body’s responses)
Constriction of skin
Curling up Shivering
blood vessels
Heat loss from body Heat production
Return of body temperature toward original value
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.
 The first homeostatic response is that blood vessels to the
skin become constricted (narrowed), reducing the amount of blood
flowing through the skin. This decreases heat loss from the warm
blood across the skin and out to the environment and helps slow the
loss of heat from the body. At a room temperature of 5°C, however,
blood vessel constriction cannot by itself eliminate the extra heat
loss from the body. 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 heat loss still continues, 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 mus-
cle contractions that constitute shivering produce large quantities of
heat, thereby restoring body temperature homeostasis.
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, therefore, 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 mechanisms and characteristics of
negative feedback in different systems will be addressed in later chap-
ters. For now, it is important to recognize that negative feedback has 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 Figure 1.6.
(An enzyme is a protein that catalyzes chemical reactions.)
In this example, the product formed from a substrate 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 of the reaction. The production of
adenosine triphosphate (ATP) within cells is a good example of a
chemical process regulated by feedback. Normally, glucose mol-
ecules are enzymatically broken down inside cells to release some
of the chemical energy that was contained in the bonds of the mol-
ecule. 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 mol-
ecules 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 feedback. Conversely, if ATP concentrations decrease
within a cell, negative feedback is removed and more glucose is
broken 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 “explosive”
system. In other words, an initial change in a particular variable
subsequently leads to an even greater change in that variable.
ISTUDY
SUBSTRATE
Enzyme A
Inactive intermediate 1
Enzyme B
Inactive intermediate 2
Enzyme C
Active product
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.
DIG DEEPER
■ What would be the effect on this pathway if negative feedback
was removed?
Answer found in Appendix A.
This is counter to homeostasis, because positive feedback has no
obvious means of stopping. Not surprisingly, therefore, positive
feedback is much less 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 detail in Chapter 12, is the process of blood
clotting (Figure 1.7). When a blood vessel is ruptured, damaged
cells in the vessel wall release chemicals into the blood that attract
platelets to the injury site and activate them. Platelets are frag-
ments of cells that stick together and form clots that seal a wound.
Once activated, platelets themselves then release additional acti-
vating chemicals, which activate more platelets, and so on. The
cycle finally stops once the wound is fully sealed with a clot.
Resetting of Set Points
As we have seen, changes in the external environment can displace a
variable from its set point. In addition, the set points for many regu-
lated variables can be reset to a new value. A common example is
fever, the increase in body temperature 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 main-
tain the temperature at an increased value. This regulated increase
in body temperature 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 as the
presence of pathogens, but this is not the case. Indeed, the set points
for many regulated variables change on a rhythmic basis every day.
Homeostasis: A Framework for Human Physiology 9
 Damaged Chemical
endothelial cell signals

1 Wounded cells secrete

chemical signals that
attract and activate
platelets.

Erythrocyte Platelets

2 Clotting begins as
activated platelets
adhere to the wound
site. Activated platelets
3 These signals then secrete more
attract and activate chemical signals.
yet more platelets.
Positive
feedback

4 Cycle ends once the

wound is fully sealed.

Figure 1.7 Positive feedback as illustrated by the clotting process in blood. Damaged endothelial cells (a type of epithelial cells) in the lining of a blood
vessel secrete chemical signals that attract and activate platelets, tiny cell fragments that form clots. As clotting begins, the activated platelets produce
chemical signals of their own, attracting and activating more platelets to the wound site, which then produce yet more chemical signals, and so on. The
cycle ends when the wound is fully sealed. (Most details of the clotting process are omitted for clarity; you can look ahead to Figure 12.71 for details.)

For example, the set point for body temperature is higher during
the day, when we are active, than at night.
Although the resetting of a set point is adaptive in some
cases, in others it simply reflects the clashing demands of differ-
ent regulatory systems. This brings us to one more generalization:
It is not possible for everything to be held constant by homeo-
static 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. More-
over, because so many properties of the internal environment are
closely interrelated, it is often possible to keep one property rela-
tively stable only by moving others away from their usual set point.
This is what we mean by “clashing demands,” which explains the
phenomenon mentioned earlier about the interplay between body
temperature and water balance during exercise.
The generalizations we have given about homeostatic con-
trol systems are summarized in Table 1.2. One additional point is
that, as is illustrated by the regulation of body temperature, multi-
ple systems usually control a single parameter. The adaptive 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 is feedforward regulation, in
which changes in regulated variables are anticipated and prepared
for before they actually occur. Control of body temperature is a

TABLE 1.2 Some Important Generalizations About Homeostatic Control Systems

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.

10 Chapter 1

ISTUDY
 good example of a feedforward process. The temperature-sensitive
neurons that trigger negative feedback regulation of body tempera-
ture when it begins to decrease are located inside the body. In addi-
tion, 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, resulting in heat conser-
vation 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 diges-
tive system. The effect is to prepare the digestive system for the
arrival of food before we even consume it—for example, by induc-
ing saliva to be secreted in the mouth and causing the stomach to
churn and produce acid. Thus, feedforward regulation 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 probably cause
relatively large changes in regulated internal environmental fac-
tors, and in responding to these changes the central nervous sys-
tem 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.
St ud y an d Review 1.5
■ Homeostasis results from the operation of compensatory
control systems.
∙∙ Homeostasis is a steady state in which a variable is
unchanging but only as long as energy is provided
(equilibrium does not require input of energy).
■ Negative feedback control system: minimizes changes from
the set point of a system, leading to stability
∙∙ A change in a regulated variable brings about responses that
move the variable in the direction opposite to the original
change.
■ Positive feedback: accelerates a process by moving a variable
further from a set point
■ Homeostatic control systems minimize changes but cannot
maintain complete constancy of a regulated variable.
■ Feedforward regulation:
∙∙ anticipates changes in a regulated variable
∙∙ fine-tunes homeostatic responses
∙∙ minimizes fluctuations in the regulated variable
Review Question: Distinguish between negative feedback,
positive feedback, and feedforward regulation. Which of the three
is least likely to contribute to homeostasis, and why? (Answer
found in Appendix A.)
ISTUDY
1.6 Components of Homeostatic
Control Systems
Reflexes
The thermoregulatory system we used as an example in the previ-
ous section and many of the other homeostatic control systems
belong to the general category of stimulus–response sequences
known as reflexes. In the narrowest sense of the word, a reflex is
a specific, involuntary, “built-in” response to a particular stimu-
lus. Some reflexes involve muscular activity, such as the famil-
iar knee-jerk reflex, or the startle reflex that follows when we are
surprised by a loud noise. Other reflexes occur without our con-
scious awareness and involve internal homeostatic responses such
as those described in this chapter. For example, you are generally
not aware of reflexive changes in blood pressure.
Many responses appear automatic and stereotyped but are
actually the result of learning and practice. For example, an expe-
rienced driver performs many complicated acts in operating a car.
To the driver, these motions are, in large part, automatic, stereo-
typed, 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 altera-
tion by learning.
The pathway mediating a reflex is known as the reflex arc,
and its components are shown in Figure 1.8. A stimulus is defined
as a detectable change in the internal or external environment,
such as a change in temperature, plasma potassium concentration,
or blood pressure. A receptor detects 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 integra-
tion of numerous bits of information.
Integrating center
(Compare to set point)
Afferent Efferent
pathway pathway
Receptor Effector
Begin
Stimulus Response
Negative
feedback
Figure 1.8 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.
Homeostasis: A Framework for Human Physiology 11
 The output of an integrating center is sent to the last compo-
nent of the system, known as an effector. The actions of the effector
constitute the overall response of the system. The information going
from an integrating center to an effector is like a command direct-
ing 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 pro-
duced 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 feed-
back. For example, the smell of food stimulates the stomach to
secrete molecules that are important for digestion, but these mol-
ecules do not eliminate our perception of the smell of food (the
stimulus).
Figure 1.9 demonstrates the components of a negative
feedback homeostatic reflex arc in the process of thermoregu-
lation. The temperature receptors are the endings of certain
neurons in various parts of the body. These receptors gener-
ate electrical signals in the neurons at a rate determined 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 regula-
tion is located. The integrating center, in turn, sends signals out
along neurons in other nerves that cause skeletal muscles and
the muscles in skin blood vessels to contract. The nerves to the
muscles are the efferent pathway, and the muscles are the effec-
tors. The dashed arrow and the negative sign indicate the nega-
tive 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 example, the
effector may be a hormone secreted into the blood. As will be
described in detail in Chapter 11, a hormone is a type of chemical
messenger secreted into the blood by cells of the endocrine system
(see Table 1.1). Hormones may act on many different cells simulta-
neously because they circulate throughout the body.
Traditionally, the term reflex was restricted to situations in
which the receptors, afferent pathway, integrating center, and effer-
ent pathway were all parts of the nervous system, as in the thermo-
regulatory 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 in more
than one way in a reflex. For example, when the glucose concen-
tration in the blood is increased, this is detected by gland cells

INTEGRATING CENTER

Specific neurons in brain

Compare to set point; alter rates of firing

AFFERENT PATHWAY
(Nerves) EFFERENT PATHWAY
(Nerves)
Temperature-sensitive Smooth muscle in Skeletal muscle
RECEPTORS neurons skin blood vessels EFFECTORS
Contraction
Signaling rate Contraction (Shivering)
(Decreases blood flow)

Begin
Decreased body
STIMULUS temperature

Heat loss Heat RESPONSES

production

Figure 1.9 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 ⊝ 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 boxes).

DIG DEEPER
■ What might happen to the efferent pathway in this control system if body temperature increased above normal?
Answer found in Appendix A.

12 Chapter 1

ISTUDY
 in the pancreas (receptor). These same cells then release the hor- Hormone-secreting Neuron
gland cell
mone insulin (effector) into the blood, which decreases the blood
glucose concentration.

Local Homeostatic Responses Electrical

Hormone signal
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 Blood Neurotransmitter
induce an alteration of cell activity with the net effect of coun- vessel
teracting 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 Target cells in Neuron or effector
one or more cell in close proximity
become very metabolically active, they secrete substances into distant places in to site of neuro-
the interstitial fluid that dilate (widen) local blood vessels. the body transmitter release
The resulting increased blood flow increases the rate at which
nutrients and oxygen are delivered to that area, and the rate at Local cell Local cell
which wastes are removed. The significance of local responses
is that they provide individual areas of the body with mecha-
nisms for local self-regulation.
Paracrine substance Autocrine substance

St u d y an d Review 1.6 Target cells in close

■ Reflex: specific, involuntary, unpremeditated response to a
stimulus
∙∙ typically innate but some can be learned or acquired
■ Reflex arc: stimulus → receptor → afferent pathway →
integrating center → efferent pathway → effector → response
■ Local homeostatic responses:
∙∙ involve stimulus–response sequences
∙∙ occur only in the area of the stimulus (no nerves or hormones
directly involved)
Review Question: What might happen to a reflex arc in an
individual in whom the effectors for that reflex were not
functional? (Answer found in Appendix A.)
1.7 The Role of Intercellular
Chemical Messengers in
Homeostasis
Essential to reflexes and local homeostatic responses—and there-
fore 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
communication is performed by chemical messengers. There are
four categories of such messengers: hormones, neurotransmitters,
paracrine substances, and autocrine substances (Figure 1.10).
As noted earlier, a hormone is a chemical messenger that
enables the hormone-secreting cell to communicate with other cells,
proximity to site of Autocrine substance
release of paracrine acts on same cell
substance that secreted the
substance
Figure 1.10 Categories of chemical messengers. With the exception
of autocrine messengers, all messengers act between cells—that is,
intercellularly.
with the blood acting as the delivery system. The cells on which hor-
mones act are called the hormone’s target cells. Hormones are pro-
duced in and secreted from endocrine glands—such as the gonads,
pancreas, and thyroid gland—or in scattered cells that are distributed
throughout an organ. They have important functions in essentially all
physiological processes, including growth, reproduction, metabolism,
mineral balance, and blood pressure, and several of them are pro-
duced whenever homeostasis is threatened.
In contrast to hormones, neurotransmitters are chemical mes-
sengers that are released from the endings of neurons onto other neu-
rons, muscle cells, or gland cells. A neurotransmitter 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
functions in neuronal signaling and brain function will be covered
in Chapter 6. In the context of homeostasis, they form the signaling
basis of many reflexes, as well as having a vital role in the compensa-
tory 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 extracell­
ular fluid. They then diffuse to neighboring cells, some of which
are their target cells. Given this broad definition, neurotransmitters
Homeostasis: A Framework for Human Physiology 13

ISTUDY
 could be classified as a subgroup of paracrine substances, but by
convention they are not. Once they have performed their func-
tions, paracrine substances are generally inactivated by locally
existing enzymes and therefore they do not enter the bloodstream
in large quantities. Paracrine substances are produced throughout
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 response to eating food.
There is one category of local chemical messengers that
are not intercellular messengers—that is, they do not communi-
cate between cells. Rather, the chemical is secreted by a cell into
the extracellular fluid and then acts upon the very cell that secreted
it. Such messengers are called autocrine substances (or agents) (see
Figure 1.10). Frequently, a messenger may serve both paracrine and
autocrine functions simultaneously—that is, molecules of the mes-
senger released by a cell may act locally on adjacent cells as well as
on the same cell that released the messenger. This type of signaling
is commonly found in cells of the immune system (Chapter 18).
A point of great importance must be emphasized here to avoid
later confusion. A neuron, endocrine gland cell, and other cell types
may all secrete the same chemical messenger. In some cases, a par-
ticular messenger may sometimes function as a neurotransmitter,
a hormone, or a paracrine or autocrine substance. Norepinephrine,
for example, is not only a neurotransmitter in the brain; it is also
produced as a hormone 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. The first type occurs via gap junctions, which are physical
linkages connecting the cytosol between two cells (see Chapter 3).
Molecules can move directly from one cell to an adjacent cell
through gap junctions 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. For example, the messenger may be a plasma mem-
brane protein with part of its structure extending into the extracel-
lular space. When the cell encounters another cell type capable of
responding to the message, the two cells link up via the membrane-
bound protein. This type of signaling, sometimes 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). It is one way in which similar types
of cells “recognize” each other and form tissues.
Stu d y a n d Revi ew 1.7
■ Intercellular communication: cell-to-cell communication
facilitates homeostasis
∙∙ essential to reflexes and local responses
∙∙ achieved by neurotransmitters, hormones (many of which
are secreted from endocrine glands), paracrine substances,
or autocrine substances
∙∙ also occurs to a lesser extent through gap junctions or cell-
bound messengers
Review Question: Explain how intercellular communication facilitates
the maintenance of homeostasis. (Answer found in Appendix A.)
14 Chapter 1
ISTUDY
1.8 Processes Related to
Homeostasis
Adaptation and Acclimatization
The term adaptation denotes a characteristic that favors survival
in specific environments. Common examples in humans include
the ability of certain individuals to digest lactose in milk, and the
protection against the dangerous effects of ultraviolet light con-
ferred by dark skin. Homeostatic control systems are also inher-
ited biological adaptations and allow an individual to adapt to
encountered environmental changes. In addition, in some cases
the effectiveness of such systems can be enhanced by prolonged
exposure to an environmental change. This type of adaptation—
the improved functioning of an already existing homeostatic
system—is known as acclimatization.
Let us take sweating in response to heat exposure as an
example of an adaptation and perform a simple experiment. On
day 1, we expose a person for 30 minutes (min) to an elevated
temperature and ask her to do a standardized exercise test. Body
temperature 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 volume 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 temperature 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 temperature does not increase to nearly the same degree. The
subject has become acclimatized to the heat. She has undergone a
beneficial 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 accli-
matization 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, a striking characteristic of many body functions is the
rhythmic changes they manifest. The most common type is the
circadian rhythm, which cycles approximately once every 24 h.
Waking and sleeping, body temperature, hormone concentrations
in the blood, the excretion of ions into the urine, and many other
functions undergo circadian variation; an example of one type of
rhythm is shown in Figure 1.11.
What do biological rhythms have to do with homeosta-
sis? They add an anticipatory component to homeostatic control
systems—in effect, a feedforward system operating without detec-
tors. The negative feedback homeostatic responses we described ear-
lier in this chapter are corrective responses. They are initiated after
 exerted by the external environment. In turn, the pacemaker sends

temperature (°C)
Lights on Lights off
38
out neural signals to other parts of the brain, which then influence
the various body systems, activating some and inhibiting others. One

Body
37 output of the pacemaker goes to the pineal gland, a gland within
the brain, which secretes the hormone melatonin. These neural sig-
36 nals from the pacemaker cause the pineal gland to secrete melatonin
6:00 2:00 10:00 6:00 2:00 10:00 during darkness but not during daylight. It has been hypothesized,
A.M. P.M. P.M. A.M. P.M. P.M. therefore, that melatonin may act as an important mediator to influ-
Time of day ence other organs either directly or by altering the activity of the
parts of the brain that control these organs.
Figure 1.11 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
Balance of Chemical Substances in the Body
just prior to lights on, in anticipation of the increased activity and Many homeostatic systems regulate the balance between addition
metabolism that occur during waking hours. Source: Moore-Ede, Martin C., and removal of a chemical substance from the body. Figure 1.12
Sulzman, Frank M., and Fuller, Charles A., The Clocks that Time Us. Harvard University Press, 1982. is a generalized schema of the possible pathways involved in
maintaining such balance. The pool occupies a position of central
importance in the balance sheet. It is the body’s readily available
the steady state of the individual has been perturbed. In contrast,
quantity of the substance and is often identical to the amount pres-
biological rhythms enable homeostatic mechanisms to be utilized
ent in the extracellular fluid. The pool receives substances and
immediately and automatically by activating them at times when
redistributes them to all the pathways.
a challenge is likely to occur but before it actually does occur—for
The pathways on the left of Figure 1.12 are sources of net
example, body temperature increases prior to waking in a person on
gain to the body. A substance may enter the body through the gas-
a typical sleep–wake cycle. This allows the metabolic machinery
trointestinal (GI) tract or the lungs. Alternatively, a substance may
of the body to operate most efficiently immediately upon waking,
be synthesized within the body from other materials.
because metabolism (chemical reactions) is to some extent temper-
The pathways on the right of the figure are causes of net loss
ature dependent. During sleep, metabolism is slower than during
from the body. A substance may be lost in the urine, feces, expired
the active hours, and therefore body temperature decreases at that
air, or menstrual fluid, as well as from the surface of the body as
time. A crucial point concerning most body rhythms is that they are
skin, hair, nails, sweat, or tears. The substance may also be chemi-
internally driven. Environmental factors do not drive the rhythm
cally altered by enzymes and thus removed by metabolism.
but rather provide the timing cues important for entrainment, or
The central portion of Figure 1.12 illustrates the distribu-
setting of the actual hours of the rhythm. A classic experiment will
tion of the substance within the body. The substance may be
clarify this distinction.
taken from the pool and accumulated in storage depots—such
Subjects were put in experimental chambers that completely
as the accumulation of fat in adipose tissue. Conversely, it may
isolated them from their usual external environment, including
leave the storage depots to reenter the pool. Finally, the substance
knowledge of the time of day. For the first few days, they were
may be incorporated reversibly into some other molecular struc-
exposed to a 24 h rest–activity cycle in which the room lights
ture, such as fatty acids into plasma membranes. Incorporation
were turned on and off at the same times each day. Under these
is reversible because the substance is liberated again whenever the
conditions, their sleep–wake cycles were 24 h long. Then, all
more complex structure is broken down. This pathway is distin-
environmental time cues were eliminated, and the subjects were
guished from storage in that the incorporation of the substance into
allowed to control the lights themselves. Immediately, their sleep–
other molecules produces new molecules with specific functions.
wake patterns began to change. On average, bedtime began about
Substances do not necessarily follow all pathways of this
30 min later each day, and so did wake-up time. Thus, a sleep–
generalized schema. For example, minerals such as Na+ cannot be
wake cycle persisted in the complete absence of environmental
synthesized, do not normally enter through the lungs, and cannot
cues. Such a rhythm is called a free-running rhythm. In this
be removed by metabolism.
case, it was approximately 24.5 h rather than 24. This indicates
that cues are required to entrain or set a circa-
NET GAIN TO BODY DISTRIBUTION WITHIN NET LOSS FROM
dian rhythm to 24 h. BODY BODY
What is the neural basis of body rhythms?
In the part of the brain called the hypothalamus a Food GI tract Storage depots Metabolism
specific collection of neurons (the suprachiasmatic
nucleus) functions as the principal pacemaker, or
time clock, for circadian rhythms. How it keeps Air Lungs POOL
time independent of any external environmen-
tal cues is not fully understood, but it appears to Excretion from body
Reversible via lungs, GI tract,
involve the rhythmic turning on and off of critical Synthesis in body kidneys, skin,
incorporation
genes in the pacemaker cells. into other menstrual flow
The pacemaker receives input from the molecules
eyes and many other parts of the nervous system,
and these inputs mediate the entrainment effects Figure 1.12 Balance diagram for a chemical substance.
Homeostasis: A Framework for Human Physiology 15

ISTUDY
 The orientation of Figure 1.12 illustrates two important gen-
eralizations concerning the balance concept: (1) During any period
of time, total-body balance depends upon the relative rates of net
gain and net loss to the body; and (2) the pool concentration depends
not only upon the total amount of the substance in the body but also
upon exchanges of the substance within the body.
For any substance, three states of total-body balance
are possible:
■■ Loss exceeds gain, so that the total amount of the substance
in the body is decreasing, and the person is in negative
balance.
■■ Gain exceeds loss, so that the total amount of the substance
in the body is increasing, and the person is in ­positive
balance.
■■ Gain equals loss, and the person is in stable balance.
Clearly, a stable balance can be upset by a change in the
amount being gained or lost in any single pathway in the schema.
For example, increased sweating can cause severe negative water
balance. Conversely, stable balance can be restored by homeo-
static control of water intake and output.
Let us take the balance of calcium ions (Ca2+) as another
example. The concentration of Ca2+ in the extracellular fluid is crit-
ical for normal cellular functioning, notably muscle cells and neu-
rons, but also for the formation and maintenance of the skeleton.
The vast majority of the body’s Ca2+ is present in bone. The control
systems for Ca2+ balance target the intestines and kidneys such that
the amount of Ca2+ absorbed from the diet is balanced with the
amount excreted in the urine. During infancy and childhood, how-
ever, the net balance of Ca2+ is positive, and Ca2+ is deposited in
growing bone. In later life, especially in women after menopause
(see Chapter 17), Ca2+ is released from bones faster than it can
be deposited, and that extra Ca2+ is lost in the urine. Consequently,
the bone pool of Ca2+ becomes smaller, the rate of Ca2+ loss from
the body exceeds the rate of intake, and Ca2+ balance is negative.
In summary, homeostasis is a complex, dynamic process
that regulates the adaptive responses of the body to changes in the
external and internal environments. To work properly, homeostatic
systems require a sensor to detect the environmental change as well
as a means to produce a compensatory response. Because compen-
satory responses require muscle activity, behavioral changes, or
synthesis of chemical messengers such as hormones, homeostasis
is achieved by the expenditure of energy. The nutrients that provide
this energy, as well as the cellular structures and chemical reactions
that release the energy stored in the chemical bonds of the nutrients,
are described in the following two chapters.
Stu d y a n d Revi ew 1.8
■ Adaptation: any characteristic that favors survival in a specific
environment; many are inheritable, such as homeostatic control
systems
■ Acclimatization: improved functioning of an already existing
homeostatic system
∙∙ induced by prolonged exposure to a stress with no change in
genetic endowment
∙∙ typically reversible
16 Chapter 1
ISTUDY
St udy and Review 1.8 — co ntinue d
■ Circadian rhythms: biological functions with a cycle of
approximately 24 h
∙∙ feedforward component to homeostatic control systems
∙∙ internally driven by pacemakers
∙∙ entrained by light
∙∙ free run without entrainment
■ Total-body (mass) balance: matching inputs and outputs of a
substance in the body
∙∙ can be negative (net loss), positive (net gain), or stable (loss = gain)
Review Question: Distinguish between acclimatization and
adaptation. Considering organ systems and referring back to
Table 1.1 if necessary, what are one or two general adaptations
that are important for our ability to survive in a terrestrial
environment? (Answer found in Appendix A.)
1.9 General Principles
of Physiology
This chapter has highlighted several fundamental and recurring
themes or principles in physiology. Recognizing these principles
and how they manifest in the different organ systems can provide
a deeper understanding of the integrated function of the human
body. To help you gain this insight, beginning with Chapter 2, the
introduction to each chapter will highlight the general principles
demonstrated in that chapter. Your understanding of how to apply
the following general principles of physiology to a given chapter’s
content will then be assessed at the end of the chapter and in Dig
Deeper questions associated with certain figures.
1. Homeostasis is essential for health and survival. The
ability to maintain physiological variables such as body
temperature and blood sugar concentrations within
normal ranges is the underlying principle upon which all
physiology is based. Keys to this principle are the processes
of feedback and feedforward. Challenges to homeostasis
may result from disease or from environmental factors such
as famine or exposure to extremes of temperature.
2. The functions of organ systems are coordinated with
each other. Physiological mechanisms operate and
interact at the levels of cells, tissues, organs, and organ
systems. Furthermore, the different organ systems in
the human body do not function independently of each
other. Each system typically interacts with one or more
others to control a homeostatic variable. A good example
that you will learn about in Chapters 12 and 14 is the
coordinated activity of the circulatory and urinary systems
in regulating blood pressure. This type of coordination is
often referred to as “integration” in physiological contexts.
3. Most physiological functions are controlled by multiple
regulatory systems, often working in opposition. Typically,
control systems in the human body operate such that a given
variable, such as heart rate, receives both stimulatory and
inhibitory signals. As you will learn in detail in Chapter 6,
for example, the nervous system sends both types of signals
to the heart; adjusting the ratio of stimulatory to inhibitory
 signals allows for fine-tuning of the heart rate under
changing conditions such as rest or exercise.
4. Information flow between cells, tissues, and organs is an
essential feature of homeostasis and allows for integration
of physiological processes. Cells can communicate with
nearby cells via locally secreted chemical signals; a good
example of this is the signaling between cells of the stomach
that results in acid production, a key feature of the digestion
of proteins (see Chapter 15). Cells in one structure can
also communicate long distances using electrical signals
or chemical messengers such as hormones. Electrical
and hormonal signaling will be discussed throughout the
textbook and particularly in Chapters 6, 7, and 11.
5. Controlled exchange of materials occurs between
compartments and across cellular membranes. The
movement of water and solutes—such as ions, sugars, and
other molecules—between the extracellular and intracellular
fluid is critical for the survival of all cells, tissues, and organs.
In this way, important biological molecules are delivered to
cells and wastes are removed and eliminated from the body.
In addition, regulation of ion movements creates the electrical
properties that are crucial to the function of many cell types.
These exchanges occur via several different mechanisms,
which are introduced in Chapter 4 and are reinforced where
appropriate for each organ system throughout the book.
6. Physiological processes are dictated by the laws of
chemistry and physics. Throughout this textbook, you
will encounter some simple chemical reactions, such as
the reversible binding of oxygen to the protein hemoglobin
in red blood cells (Chapter 13). The basic mechanisms
that regulate such reactions are reviewed in Chapter 3.
Physical laws, too, such as gravity, electromagnetism, and
the relation between the diameter of a tube and the flow of
liquid through the tube, help explain things like why we may
feel light-headed upon standing too suddenly (Chapter 12,
but also see the Clinical Case Study that follows in this
chapter), how our eyes detect light (Chapter 7), and how we
inflate our lungs with air (Chapter 13).
7. Physiological processes require the transfer and balance
of matter and energy. Growth and the maintenance of
homeostasis require regulation of the movement and
transformation of energy-yielding nutrients and molecular
building blocks between the body and the environment and
between different regions of the body. Nutrients are ingested
(Chapter 15), stored in various forms (Chapter 16), and
ultimately metabolized to provide energy that can be stored
in the bonds of ATP (Chapters 3 and 16). The concentrations
of many inorganic molecules must also be regulated to
maintain body structure and function—for example, the
Ca2+ found in bones (Chapter 11). One of the most important
functions of the body is to respond to changing demands,
such as the increased requirement for nutrients and oxygen
in exercising muscle. This requires a coordinated allocation
of resources to regions that most require them at a particular
time. The mechanisms by which the organ systems of the
body recognize and respond to changing demands is a theme
you will encounter repeatedly in Chapters 6 through 19.
8. Structure is a determinant of—and has coevolved
with—function. The form and composition of cells,
tissues, organs, and organ systems determine how they
interact with each other and with the physical world.
Throughout the text, you will see examples of how different
body parts converge in their structure to accomplish similar
functions. For example, enormous elaborations of surface
areas to facilitate membrane transport and diffusion can
be observed in the circulatory (Chapter 12), respiratory
(Chapter 13), urinary (Chapter 14), digestive (Chapter 15),
and reproductive (Chapter 17) systems.
St udy and Review 1 . 9
■ General principles of physiology: include homeostasis;
information flow; coordination between the functions of
different organ systems; transfer of matter and energy; structure
determines function; physiological processes follow the laws of
chemistry and physics
Review Question: Refer back to Figure 1.9. Which general
principles of physiology are depicted by the reflexes that control
body temperature homeostasis? (Answer found in Appendix A.)

CHAPTER 1 Clinical Case Study: L oss of Consciousness in a 64-Year-Old Man

Comstock Images/Getty Images
Throughout this text, you will find a fea-
ture at the end of each chapter called
the “Clinical Case Study.” These seg-
ments reinforce what you have learned
in that chapter by applying it to real-life
examples of different medical condi-
tions. The clinical case studies will
increase in complexity as you progress
through the text and will enable you to
integrate recent material from a given
chapter with information learned in
While Gardening on a Hot Day
previous chapters. In this first clinical case study, we examine a seri-
ous and potentially life-threatening condition that can occur in individ-
uals in whom body temperature homeostasis is disrupted. All of the
material presented in this clinical case study will be explored in depth
in subsequent chapters, as you learn the mechanisms that underlie
the pathologies and compensatory responses illustrated here in brief.
Notice as you read that the first two general principles of physiology
described earlier are particularly relevant to this case. It is highly rec-
ommended that you return to this case study as a benchmark at the
end of your semester; we are certain that you will be amazed at how
your understanding of physiology has grown in that time.
—Continued next page

Homeostasis: A Framework for Human Physiology 17

ISTUDY
 —Continued
A 64-year-old, fair-skinned man in good overall health spent
a very hot, humid summer day gardening in his backyard. After
several hours in the sun, he began to feel light-headed and con-
fused as he knelt over his vegetable garden. Although earlier he
had been perspiring profusely and appeared flushed, his sweating
had eventually stopped. Because he also felt confused and dis-
oriented, he could not recall for how long he had not been per-
spiring, or even how long it had been since he had taken a drink
of water. He called to his wife, who was alarmed to see that his
skin had since turned a pale-blue color. She asked her husband
to come indoors, but he fainted as soon as he tried to stand. The
wife called for an ambulance, and the man was taken to a hospital
and diagnosed with a condition called heatstroke. What happened
to this man that would explain his condition? How does it relate to
homeostasis?
Reflect and Review #1
■■ Review the homeostatic control of body temperature in
Figure 1.5. Based on that, what would you expect to occur
to skin blood vessels when a person first starts feeling
warm?
As you learned in this chapter, body temperature is a physi-
ological function that is under homeostatic control. If body tem-
perature decreases, heat production increases and heat loss
decreases, as illustrated in Figures 1.5 and 1.9. Conversely, as in
our example here, if body temperature increases, heat produc-
tion decreases and heat loss increases. When our patient began
gardening on a hot, humid day, his body temperature began to
increase. At first, the blood vessels in his skin dilated, making
him appear flushed and helping him dissipate heat across his
skin. In addition, he perspired heavily. As you will learn in Chap-
ter 16, perspiration is an important mechanism by which the body
loses heat; it takes considerable heat to evaporate water from
the surface of the skin, and the source of that heat is from the
body. However, as you likely know from personal experience,
evaporation of water from the body is less effective in humid
environments, which makes it more dangerous to exercise when
it is not only hot but also humid.
The sources of perspiration are the sweat glands, which
are located beneath the skin and which secrete a salty solu-
tion through ducts to the surface of the skin. The fluid in sweat
comes from the extracellular fluid compartment, which, as you
have learned, consists of the plasma and interstitial fluid compart-
ments (see Figure 1.3). Consequently, the profuse sweating that
initially occurred in this man caused his extracellular fluid levels to
decrease. In fact, the fluid levels decreased so severely that the
amount of blood available to be pumped out of his heart with each
heartbeat also decreased. The relationship between fluid volume
and blood pressure is an important one that you will learn about in
detail in Chapter 12. Generally speaking, if extracellular fluid lev-
els decrease, blood pressure decreases as a consequence. This
explains why our subject felt light-headed, particularly when he
tried to stand up too quickly. As his blood pressure decreased, the
18 Chapter 1
ISTUDY
ability of his heart to pump sufficient blood against gravity up to
his brain also decreased; when brain cells are deprived of blood
flow, they begin to malfunction. Suddenly standing only made mat-
ters worse. Perhaps you have occasionally experienced a little
of this light-headed feeling when you have jumped out of a chair
or bed and stood up too quickly. Normally, your nervous system
quickly compensates for the effects of gravity on blood flowing up
to the brain, as will be described in Chapters 6 and 12. In a person
with decreased blood volume and pressure, however, this com-
pensation may not happen and the person can lose conscious-
ness. After fainting and falling, the man’s head and heart were at
the same horizontal level; consequently, blood could more easily
reach his brain.
Another concern is that the salt (ion) concentrations in the
body fluids changed. If you have ever tasted the sweat on your
upper lip on a hot day, you know that it is somewhat salty. That
is because sweat is derived from extracellular fluid, which as you
have learned is a watery solution of ions (derived from salts, such
as NaCl) and other substances. Sweat, however, is slightly more
dilute than extracellular fluid because more water than ions is
secreted from sweat glands. Consequently, the more heavily one
perspires, the more concentrated the extracellular fluid becomes.
In other words, the total amount of water and ions in the extra-
cellular fluid decreases with perspiration, but the remaining fluid
is “saltier.” Heavy perspiration, therefore, not only disrupts fluid
balance and blood pressure homeostasis but also has an impact
on the balance of the ions in the body fluids, notably Na +, K+,
and Cl −. A homeostatic balance of ion concentrations in the body
fluids is absolutely essential for normal heart and brain function,
as you will learn in Chapters 4 and 6. As the man’s ion concentra-
tions changed, therefore, the change affected the activity of the
cells of his brain.
Reflect and Review #2
■■ Refer to Figure 1.12. Was the man in a positive or negative
balance for total-body Na+?
Why did the man stop perspiring, and why did his skin turn pale?
To understand this, we must consider that several homeostatic vari-
ables were disrupted by his activities. His body temperature increased,
which initially resulted in heavy sweating. As the sweating continued,
it resulted in decreased fluid levels and a negative balance of key ion
concentrations in his body; this contributed to a decrease in mental
function, and he became confused. As his body fluid levels continued
to decrease, his blood pressure also decreased, further endangering
brain function. At this point, the homeostatic control systems were
essentially in competition. Though it is potentially life threatening for
body temperature to increase too much, it is also life threatening for
blood pressure to decrease too much. Eventually, many of the blood
vessels in regions of the body that are not immediately required for
survival—such as the skin—began to constrict, or close off. By doing
so, the more vital organs of the body—such as the brain—could receive
sufficient blood. This is why the man’s skin turned a pale blue, because
the amount of oxygen-rich blood flowing to the surface of his skin was
decreased. Unfortunately, although this compensatory mechanism
 helped protect the man’s brain and other vital organs by providing the Begin
necessary blood flow to them, the reduction in blood flow to the skin
Body temperature
made it increasingly more difficult to dissipate heat from the body to
the environment. It also made it more difficult for sweat glands in the
skin to obtain the fluid required to produce sweat. The man gradually Sweat glands
decreased perspiring and eventually stopped sweating altogether. At
Heavy sweating
that point, his body temperature spiraled out of control and he was hos-
pitalized (Figure 1.13).
This case illustrates a critical feature of homeostasis that you Volume of body fluids
will encounter throughout this textbook and that was emphasized in
this chapter. Often, when one physiological variable—such as body
temperature—is disrupted, the compensatory responses initiated to Blood pressure
correct that disruption cause, in turn, imbalances in other variables.
These secondary imbalances must also be compensated for, and
the significance of each imbalance must be “weighed” against the Constriction of skin
blood vessels
others. In this example, the man was treated with intravenous fluids
made up of a salt solution to restore his fluid levels and concentra-
tions, and he was immersed in a cool bath and given cool compresses Heat loss and sweating
to help reduce his body temperature. Although he recovered, many
people do not survive heatstroke because of its profound impact on Rapid increase in
homeostasis. body temperature

Figure 1.13 Sequence of events that occurred in the man

described in this case study.

See Chapter 19 for complete, integrative case studies.

1.5 General Characteristics of Homeostatic Control Systems

K EY A N D CL INICA L T ER M S
equilibrium positive feedback
1.1 The Scope of Human Physiology feedforward regulation set point
homeostatic control systems steady state
pathophysiology physiology
negative feedback
1.2 How Is the Body Organized?
1.6 Components of Homeostatic Control Systems
basement membrane fibers
acquired reflexes learned reflexes
cell differentiation functional units
afferent pathway local homeostatic responses
cells muscle cells
effector receptor
collagen fibers muscle tissue
efferent pathway reflex
connective tissue nerve
hormone reflex arc
connective-tissue cells nervous tissue
integrating center stimulus
elastin fibers neuron
epithelial cells organs
epithelial tissue organ system 1.7 The Role of Intercellular Chemical Messengers
epithelium tissues in Homeostasis
extracellular matrix (ECM) autocrine substances neurotransmitters
endocrine glands paracrine substances
1.3 Body Fluid Compartments
extracellular fluid interstitium 1.8 Processes Related to Homeostasis
internal environment intracellular fluid acclimatization negative balance
interstitial fluid plasma adaptation pacemaker
circadian rhythm pineal gland
1.4 Homeostasis: A Defining Feature of Physiology entrainment pool
free-running rhythm positive balance
dynamic constancy homeostasis
melatonin stable balance

Homeostasis: A Framework for Human Physiology 19

ISTUDY
 CHAPTER 1 TEST QU E ST ION S Recall and Comprehend Answers appear in Appendix A.

These questions test your recall of important details covered in this chapter. They also help prepare you for the type of questions
encountered in standardized exams. Many additional questions of this type are available on Connect and LearnSmart.

1. Which of the following is one of the four basic cell types in the body? d. Drinking an excess of water will create a negative balance of water in
a. respiratory the body.
b. epithelial e. Acclimatization requires a modification of a person’s genetic makeup.
c. endocrine 5. Most of the water in the human body is found in
d. integumentary a. the interstitial fluid compartment.
e. immune b. the intracellular fluid compartment.
2. Which of the following is incorrect? c. the plasma compartment.
a. Equilibrium requires a constant input of energy. d. the total extracellular fluid compartment.
b. Positive feedback is less common in nature than negative feedback. 6. The type of tissue involved in many types of transport processes, and
c. Homeostasis does not imply that a given variable is unchanging. which often lines the inner surfaces of tubular structures, is called    .
d. Fever is an example of resetting a set point.
7. All the fluid found outside cells is collectively called     fluid, and
e. Efferent pathways carry information away from the integrating center
consists of     and     fluid.
of a reflex arc.
8. Physiological changes that occur in anticipation of a future change to a
3. In a reflex arc initiated by touching a hand to a hot stove, the effector
homeostatic variable are called     processes.
belongs to which class of tissue?
a. nervous c. muscle 9. A     is a chemical factor released by cells that acts on neighboring
b. connective d. epithelial cells without having to first enter the blood.
4. Which is correct? 10. When loss of a substance from the body exceeds its gain, a person is said to
a. Circadian rhythms can only free-run; they cannot be fixed to some be in     balance for that substance.
environmental cue.
b. Being able to perceive color is an example of an acclimatization.
c. Eating a very salty meal will create a period of positive sodium balance
in the blood.

CHAPTER 1 TEST QU E ST ION S Apply, Analyze, and Evaluate Answers appear in Appendix A.

These questions, which are designed to be challenging, require you to integrate concepts covered in the chapter to draw your own
conclusions. See if you can first answer the questions without using the hints that are provided; then, if you are having difficulty, refer
back to the figures or sections indicated in the hints.

1. The Inuit of Alaska and Canada have a remarkable ability to work in the
cold without gloves and not suffer decreased skin blood flow. Does this
prove that there is a genetic difference between the Inuit and other people
with regard to this characteristic? Hint: Refer back to “Adaptation and
Acclimatization” in Section 1.8.
2. Explain how an imbalance in any given physiological variable may produce
a change in one or more other variables. Hint: For help, see Section 1.4 and
Figure 1.13.

20 Chapter 1

ISTUDY
Another random document with
no related content on Scribd:
But one unlucky day Austin tumbled down, and, though more
frightened than hurt, cried so much that, his own mamma being
away, Sunny’s mamma took him and comforted him, soothing him on
her shoulder till he ceased sobbing. This was more than human
nature could bear. Sunny did nothing at the time, except pull
frantically at her mamma’s gown, but shortly afterward she and
Austin Thomas were found by themselves, engaged in single combat
on the gravel walk. She had seized him by the collar of his frock, and
was kicking him with all her might, while he on his part was
pommelling at her with both his little fat fists, like an infant prize-
fighter. It was a pitched battle, pretty equal on both sides; and
conducted so silently, in such dead earnest, that it would have been
quite funny,—if it had not been so very wrong.
Of course such things could not be allowed, even in babies under
three years old. Sunny’s mamma ran to the spot and separated the
combatants by carrying off her own child right away into the house.
Sunny was so astonished that she did not say a word. And when she
found that her mamma never said a word either, but bore her along
in total silence, she was still more surprised. Her bewilderment was
at its height, when, shutting the bedroom door, her mamma set her
down, and gave her—not a whipping: she objects to whippings under
any circumstances—but the severest scolding the child had ever had
in her life.
When I say “scolding,” I mean a grave, sorrowful rebuke, showing
how wicked it was to kick anybody, and how it grieved mamma that
her good little girl should be so exceedingly naughty. Mamma
grieved is a reproach under which little Sunny breaks down at once.
Her lips began to quiver; she hung her head sorrowfully.
“Sunny had better go into the cupboard,” suggested she.
“Yes, indeed,” mamma replied. “I think the cupboard is the only place
for such a naughty little girl; go in at once.”
So poor Sunshine crept solemnly into a large press with sliding
doors, used for hanging up clothes, and there remained in silence
and darkness all the while her mamma was dressing to go out. At
last she put her head through the opening.
“Sunny quite good now, mamma.”
“Very well,” said mamma, keeping with difficulty a grave
countenance. “But will Sunny promise never to kick Austin Thomas
again?”
“Yes.”
“Then she may come out of the cupboard, and kiss mamma.”
Which she did, with a beaming face, as if nothing at all had
happened. But she did not forget her naughtiness. Some days after,
she came up, and confidentially informed her mamma, as if it were
an act of great virtue, “Mamma, Sunny ’membered her promise.
Sunny hasn’t kicked the little boy again.”
After the eight o’clock breakfast, Sunny, her mamma, and the five
little boys generally took a walk together, or sat telling stories in front
of the house, till the ten o’clock breakfast of the elders. That over, the
party dispersed their several ways, wandering about by land or
water, and meeting occasionally, great folks and small, in boats, or
by hillsides, or indoors at the children’s one o’clock dinner,—almost
the only time, till night, that anybody ever was indoors.
Besides most beautiful walks for the elders, there were, close by the
house, endless play-places for the children, each more attractive
than the other. The pier on the loch was the great delight; but there
was, about a hundred yards from the house, a burn (in fact, burns
were always tumbling from the hillside, wherever you went), with a
tiny bridge across it, which was a charming spot for little people.
There usually assembled a whole parliament of ducks, and hens,
and chickens, quacking and clucking and gobbling together, to their
own great content and that of the children, especially the younger
ones. Thither came Austin Thomas with his nurse Grissel, a
thorough Scotch lassie; and Sunny with her English Lizzie; and there
the baby, the pet of all, tiny “Miss Mary,” a soft, dainty, cuddling thing
of six months old, used to be brought to lie and sleep in the
sunshine, watched by Little Sunshine with never-ending interest. She
would go anywhere with “the dear little baby.” The very intonation of
her voice, and the expression of her eyes, changed as she looked at
it,—for this little girl is passionately fond of babies.
Farther down the mountain-road was another attractive corner, a
stone dike, covered with innumerable blackberries. Though gathered
daily, there were each morning more to gather, and they furnished an
endless feast for both nurses and children. And really, in this sharp
mountain air, the hungriness of both big and little people must have
been alarming. How the house-mother ever fed her household, with
the only butcher’s shop ten miles off, was miraculous. For very often
the usual resort of shooting-lodges entirely failed; the game was
scarce, and hardly worth shooting, and in this weather the salmon
absolutely refused to be caught. Now and then a mournful-looking
sheep was led up to the door, and offered for sale alive, to be
consumed gradually as mutton. But when you have to eat an animal
right through, you generally get a little tired of him at last.
The food that never failed, and nobody ever wearied of, was the
trout; large dishes of which appeared, and disappeared, every
morning at breakfast. A patient guest, who could not go shooting,
used to sit fishing for trout, hour by hour, in the cheerfullest manner;
thankful for small blessings (of a pound or a pound and a half at
most), and always hoping for the big salmon which he had travelled
three hundred miles to fish for, but which never came. Each day,
poor gentleman! he watched the dazzlingly bright sky, and, catching
the merest shadow of a cloud, would say courageously, “It looks like
rain! Perhaps the salmon may bite to-morrow.”
Of afternoons, Sunny and her mamma generally got a little walk and
talk alone together along the hillside road, noticing everything, and
especially the Highland cattle, who went about in family parties,—the
big bull, a splendid animal, black or tawny, looking very fierce, but
really offering no harm to anybody; half a dozen cows, and about
twice that number of calves. Such funny little things these were! not
smooth, like English calves, but with quantities of shaggy hair
hanging about them, and especially over their eyes. Papa used to
say that his little girl, with her incessant activity, and her yellow curls
tossing wildly about on her forehead, was very like a Highland calf.
At first, Sunny was rather afraid of these extraordinary beasts, so
different from Southern cattle; but she soon got used to them, and as
even the big bull did nothing worse than look at her, and pass her by,
she would stand and watch them feeding with great interest, and go
as close to them as ever she was allowed. Once she even begged
for a little calf to play with, but as it ran away up the mountainside as
active as a deer, this was not practicable. And on the whole she liked
the ducks and chickens best.
And for a change she liked to walk with mamma around the old-
fashioned garden. What a beautiful garden it was!—shut in with high
walls, and sloping southward down to the loch. No doubt many a
Highland dame, generations back, had taken great pleasure in it, for
its fruit-trees were centuries old, and the box edging of its straight,
smooth gravel walks was a picture in itself. Also a fuchsia hedge,
thick with crimson blossoms, which this little girl, who is passionately
fond of flowers, could never pass without begging for “a posie, to
stick in my little bosie,” where it was kissed and “loved” until,
generally soon enough, it got broken and died.
Equally difficult was it to pass the apples which lay strewn about
under the long lines of espaliers, where Maurice and Eddie were
often seen hovering about with an apple in each hand, and plenty
more in each pocket. The Highland air seemed to give them
unlimited digestion, but Sunny’s mamma had occasionally to say to
her little girl that quiet denial, which caused a minute’s sobbing, and
then, known to be inevitable, was submitted to.
The child found it hard sometimes that little girls might not do all that
little boys may. For instance, between the terrace and the pier was a
wooden staircase with a hand-rail; both rather old and rickety. About
this hand-rail the boys were for ever playing, climbing up it and
sliding down it. Sunny wanted to do the same, and one day her
mamma caught her perched astride at the top, and preparing to
“slidder” down to the bottom, in imitation of Eddie, who was urging
her on with all his might. This most dangerous proceeding for little
girls with frocks had to be stopped at once; mamma explaining the
reason, and insisting that Sunny must promise never to do it again.
Poor little woman, she was very sad; but she did promise, and,
moreover, she kept her word. Several times mamma saw her stand
watching the boys with a mournful countenance, but she never got
astride on the hand-rail again. Only once, a sudden consolation
occurred to her.
“Mamma, ’posing Sunny were some day to grow into a little boy, then
she might slide down the ladder?”
“Certainly, yes!” answered mamma, with great gravity, and equal
sincerity. In the meantime she perfectly trusted her reliable child,
who never does anything behind her back any more than before her
face. And she let her clamber about as much as was practicable, up
and down rocks, and over stone dikes, and in and out of burns,
since, within certain limitations, little girls should be as active as little
boys. And by degrees, Sunny, a strong, healthy, energetic child,
began to follow the boys about everywhere.
There was a byre and a hay-house, where the children were very
fond of playing, climbing up a ladder and crawling along the roof to
the ridge-tiles, along which Eddie would drag himself, astraddle, from
end to end, throwing Sunny into an ecstasy of admiration. To climb
up to the top of a short ladder and be held there, whence she could
watch Eddie crawl like a cat from end to end of the byre, and wait till
he slid down the tiles again, was a felicity for which she would even
sacrifice the company of “the dear little baby.”
But, after all, the pier was the great resort. From early morning till
dark, two or three of the children were always to be seen there,
paddling in the shallows like ducks, with or without shoes and
stockings, assisting at every embarkation or landing of the elders,
and generally, by force of entreaties, getting—Eddie especially—“a
low” on their own account several times a day. Even Sunny gradually
came to find such fascination in the water, and in Eddie’s company,
that if her mamma had not kept a sharp lookout after her, and given
strict orders that, without herself, Sunny was never under any pretext
to go on the loch at all, the two children, both utterly fearless, would
certainly have been discovered sailing away like the wise men of
Gotham who “went to sea in a bowl.” Probably with the same ending
to their career; that
“If the bowl had been stronger,
My song would have been longer!”
After Little Sunshine’s holiday was done, mamma, thinking over the
countless risks run, by her own child and these other children, felt
thankful that they had all left this beautiful glen alive.
 CHAPTER VIII.
The days sped so fast with these happy people, children and
“grown-ups,” as Sunny calls them, that soon it was already Sunday,
the first of the only two Sundays they had to spend at the glen. Shall
I tell about them both?
These parents considered Sunday the best day in all the week, and
tried to make it so; especially to the children, whom, in order to give
the servants rest, they then took principally into their own hands.
They wished that, when the little folks grew up, Sunday should
always be remembered as a bright day, a cheerful day, a day spent
with papa and mamma; when nobody had any work to do, and
everybody was merry, and happy, and good. Also clean, which was a
novelty here. Even the elders rather enjoyed putting on their best
clothes with the certainty of not getting them wetted in fishing-boats,
or torn with briers and brambles on hillsides. Church was not till
twelve at noon, so most of the party went a leisurely morning stroll,
and Sunny’s papa and mamma decided to have a quiet row on the
loch, in a clean boat, all by their two selves. But, as it happened,
their little girl, taking a walk with her Lizzie, espied them afar off.
Faintly across the water came the pitiful entreaty, “Papa! mamma!
Take her. Take her with you.” And the little figure, running as fast as
her fat legs would carry her, was seen making its way, with Lizzie
running after, to the very edge of the loch.
What heart would not have relented? Papa rowed back as fast as he
could, and took her in, her face quivering with delight, though the big
tears were still rolling down her cheeks. But April showers do not dry
up faster than Sunny’s tears.
No fishing to-day, of course. Peacefully they floated down the loch,
which seemed to know it was Sunday, and to lie, with the hills
standing around it, more restful, more sunshiny, more beautiful than
ever. Not a creature was stirring; even the cattle, that always
clustered on a little knoll above the canal, made motionless pictures
of themselves against the sky, as if they were sitting or standing for
their portraits, and would not move upon any account. Now and then,
as the boat passed, a bird in the bushes fluttered, but not very far off,
and then sat on a bough and looked at it, too fearless of harm to fly
away. Everything was so intensely still, so unspeakably beautiful,
that when mamma, sitting in the stern, with her arm fast around her
child, began to sing “Jerusalem the Golden,” and afterward that other
beautiful hymn, “There is a land of pure delight,” the scene around
appeared like an earthly picture of that Celestial Land.
They rowed homeward just in time to dress for church, and start,
leaving the little girl behind. She was to follow, by and by, with her
Lizzie, and be taken charge of by mamma while Lizzie went to the
English service in the afternoon.
This was the morning service, and in Gaelic. With an English prayer-
book it was just possible to follow it and guess at it, though the words
were unintelligible. But they sounded very sweet, and so did the
hymns; and the small congregation listened as gravely and
reverently as if it had been the grandest church in the world, instead
of a tiny room, no bigger than an ordinary sitting-room, with a
communion-table of plain deal, and a few rows of deal benches,
enough to seat about twenty people, there being about fifteen
present to-day. Some of them had walked several miles, as they did
every Sunday, and often, their good clergyman said, when the glen
was knee-deep in snow.
He himself spent his quiet days among them, winter and summer,
living at a farmhouse near, and scarcely ever quitting his charge. A
lonelier life, especially in winter-time, it was hardly possible to
imagine. Yet he looked quite contented, and so did the little
congregation as they listened to the short Gaelic sermon (which, of
course, was incomprehensible to the strangers), then slowly went
out of church and stood hanging about on the dike-side in the
sunshine, till the second service should begin.
Very soon a few more groups were seen advancing toward church.
There was Maurice, prayer-book in hand, looking so good and gentle
and sweet, almost like a cherub in a picture; and Eddie, not at all
cherubic, but entirely boyish, walking sedately beside his papa;
Eddie clean and tidy, as if he had never torn his clothes or dirtied his
face in all his life. Then came the children’s parents, papa and
mamma and their guests, and the servants of the house following.
While far behind, holding cautiously by her Lizzie’s hand and rather
alarmed at her new position, was a certain little person, who, as
soon as she saw her own papa and mamma, rushed frantically
forward to meet them, with a cry of irrepressible joy.
“Sunny wants to go to church! Sunny would like to go to church with
the little boys, and Lizzie says she mustn’t.”
Lizzie was quite right, mamma explained; afraid that so small a child
might only interrupt the worship, which she could not possibly
understand. But she compromised the matter by promising that
Sunny should go to church as soon as ever she was old enough,
and to-day she should stay with mamma out in the sunshiny road,
and hear the singing from outside.
Staying with mamma being always sufficient felicity, she consented
to part with the little boys, and they passed on into church.
By this time the post, which always came in between the services on
Sundays, appeared, and the postmaster, who was also schoolmaster
and beadle at the church,—as the school, the church, and the post-
office were all one building,—began arranging and distributing the
contents of the bag.
Everybody sat down by the roadside and read their letters. Those
who had no letters opened the newspapers,—those cruel
newspapers, full of the war. It was dreadful to read them, in this
lovely spot, on this calm September Sunday, with the good pastor
and his innocent flock preparing to begin the worship of Him who
commanded “Love your enemies; bless them that curse you, do
good to them that hate you, and pray for them that despitefully use
you and persecute you.”
Oh, what a mockery “church” seemed! You little children can never
understand the pain of it; but you will when you are grown up. May
God grant that in your time you may never suffer as we have done,
but that His mercy may then have brought permanent peace; beating
“swords into ploughshares, and spears into pruning-hooks,” for ever
and ever throughout the world!
Sunny’s mamma prayed so with all her heart, when, the newspaper
laid down, she sat on a stone outside the church, with her child
playing beside her; far enough not to disturb the congregation, but
near enough to catch a good deal of the service, which was the
English Episcopal service; there being few Presbyterians in this
district of Scotland, and not a Presbyterian church within several
miles.
Presently a harmonium began to sound, and a small choir of voices,
singing not badly, began the Magnificat. It was the first time in her life
that the little girl had heard choral music,—several people singing all
together. She pricked up her ears at once, with the expression of
intense delight that all kinds of music bring into her little face.
“Mamma, is that church? Is that my papa singing?”
Mamma did not think it was, but it might be Maurice’s papa, and his
mamma, and Lizzie, and several other people; Sunny must listen
and be quite quiet, so as not to disturb them.
So she did, good little girl! sitting as mute as a mouse all the while
the music lasted, and when it ceased, playing about, still quietly;
building pebble mountains, and gathering a few withered leaves to
stick on the top of them. For she and her mamma were sitting on the
gravel walk of the schoolmaster’s garden, beside a row of
flowerpots, still radiant with geraniums and fuchsias. They were so
close to the open window under which stood the pulpit, that mamma
was able to hear almost every word of the sermon,—and a very
good sermon it was.
When it ended, the friendly little congregation shook hands and
talked a little; then separated, half going up and the other half down
the road. The minister came home to dinner, walking between
Maurice and Eddie, of whom he was a particular friend. They always
looked forward to this weekly visit of his as one of the Sunday
enjoyments, for he was an admirable hand at an oar, and Eddie, who
tyrannised over him in the most affectionate way, was quite sure of
“a low” when the minister was there.
So, after dinner, all went out together, parents and children, pastor
and flock, in two boats, and rowed peacefully up and down the loch,
which had fallen into the cool gray shadow of evening, with the most
gorgeous sunset light, resting on the mountains opposite, and
gradually fading away, higher and higher, till the topmost peaks
alone kept the glow. But that they did to the very last; like a good
man who, living continually in the smile of God, lives cheerfully on to
the end.
Sunny and her mamma watched the others, but did not go out, it
being near the child’s bedtime; and unless it is quite unavoidable,
nobody ever puts Sunny to bed, or hears her say her little prayers,
except her own mamma. She went to sleep quite happily, having
now almost forgotten to ask for Tommy Tinker, or any other story.
The continual excitement of her life here left her so sleepy that the
minute she had her little nightgown on, she was ready to shut her
eyes, and go off into what mamma calls “the land of Nod.”
And so ended, for her, the first Sunday in the glen, which, in its
cheerful, holy peace, was a day long to be remembered. But the little
boys, Maurice and Eddie, who did not go to bed so early, after the
loch grew dark, and the rowing was all done, spent a good long
evening in the drawing-room, climbing on the minister’s knees, and
talking to him about boats and salmon, and all sorts of curious
things: he was so very kind to little children. And after the boys were
gone to bed, he and the elder folk gathered around the not
unwelcome fire, and talked too. This good minister, who spent his life
in the lonely glen, with very little money,—so little that rich Southern
people would hardly believe an educated clergyman could live upon
it at all,—and almost no society, except that of the few cottagers and
farmers scattered thinly up and down, yet kept his heart up, and was
cheerful and kindly, ready to help old and young, rich and poor, and
never complaining of his dull life, or anything else—this gentleman, I
say, was a pattern to both great folk and small.
The one only subject of discontent in the house, if anybody could
feel discontent in such a pleasant place and amid such happy
circumstances, was the continued fine weather. While the sky
remained unclouded, and the loch as smooth as glass, no salmon
would bite. They kept jumping up in the liveliest and most provoking
way; sometimes you could see their heads and shoulders clean out
of water, and of course they looked bigger than any salmon ever
seen before. Vainly did the master of the house and his guests go
after them whenever there was the least cloud on the sky, and coax
them to bite with the most fascinating flies and most alluring hooks;
they refused to take the slightest notice of either. Only trout, and they
not big ones, ever allowed themselves to be caught.
The children and mammas, delighting in the warm sunshiny weather,
did not grieve much, but the gentlemen became quite low in their
spirits, and at last, for their sakes, and especially for the sake of that
one who only cared for fishing, and had come so far to fish, the
whole household began to watch the sky, and with great self-
sacrifice to long for a day—a whole day—of good, settled, pelting
rain.
And on the Monday following this bright Sunday, it seemed likely.
The morning was rather dull, the sunshiny haze which hung over the
mountains melted away, and they stood out sharp and dark and
clear. Toward noon, the sky clouded over a little,—a very little!
Hopefully the elders sat down to their four o’clock dinner, and by the
time it was over a joyful cry arose:
“It’s raining! it’s raining!”
Everybody started up in the greatest delight. “Now we shall have a
chance of a salmon!” cried the gentlemen, afraid to hope too much.
Nevertheless, they hastily put on their greatcoats, and rushed down
to the pier, armed with a rod apiece, and with Donald, the keeper, to
row them; because, if they did hook a salmon, Eddie explained, they
would want somebody to “low” the boat, and follow the fish wherever
he went. Eddie looked very unhappy that he himself had not this
duty, of which he evidently thought he was capable. But when his
father told him he could not go, he obeyed, as he always did. He was
very fond of his father.
The three boys, Maurice, Eddie, and Franky,—Phil, alas! was too ill
to be much excited, even over salmon-fishing,—resigned themselves
to fate, and made the best of things by climbing on the drawing-room
table, which stood in front of the window, and thence watching the
boat as it moved slowly up and down the gray loch, with the four
motionless figures sitting in it,—sitting contentedly soaking. The little
boys, Eddie especially, would willingly have sat and soaked too, if
allowed.
At length, as some slight consolation, and to prevent Eddie’s
dangling his legs out at the open window, letting in the wind and the
rain, and running imminent risk of tumbling out, twenty feet or so,
down to the terrace below, Sunny’s mamma brought a book of
German pictures, and proposed telling stories out of them.
They were very funny pictures, and have been Little Sunshine’s
delight for many months. So she, as the owner, displayed them
proudly to the rest, and it having been arranged with some difficulty
how six pairs of eyes could look over the same book, the party
arranged themselves thus: Sunny’s mamma sat on the hearth-rug,
with her own child on her lap, Austin Thomas on one side, and Phil
on the other; while Maurice, Eddie, and Franky managed as well as
they could to look over her shoulders. There was a general sense of
smothering and huddling up, like a sparrow’s nest when the young
ones are growing a little too big, but everybody appeared happy.
Now and then, Sunshine knitted her brows fiercely, as she can knit
them on occasion, when Austin Thomas came crawling too close
upon her mamma’s lap, with his intrusively affectionate
“Danmamma,” but no open quarrel broke out. The room was so cosy
and bright with firelight, and everybody was so comfortable, that they
had almost forgotten the rain outside, also the salmon-fishing, when
the door suddenly opened, and in burst the cook.
Mary was a kind, warm-hearted Highland woman, always ready to
do anything for anybody, and particularly devoted to the children.
Gaelic was easier to her than English always, but now she was so
excited that she could hardly get out her words.
“Master’s hooked a salmon! He’s been crying” (calling) “on Neil to
get out another boat and come to him. It must be a very big salmon,
for he is playing him up and down the loch. They’ve been at it these
ten minutes and more.”
Mary’s excitement affected the mistress, who laid down her baby.
“Where are they? Has anybody seen them?”
“Anybody, ma’am? Why, everybody’s down at the shore looking at
them. The minister, too; he was passing, and stopped to see.”
As a matter of course, cook evidently thought. Even a minister could
not pass by such an interesting sight. Nor did she seem in the least
surprised when the mistress sent for her waterproof cloak, and,
drawing the hood over her head, went deliberately out into the
pelting rain, Maurice and Franky following. As for Eddie, at the first
mention of salmon, he had been off like a shot, and was now seen
standing on the very edge of the pier, gesticulating with all his might
for somebody to take him into a boat. Alas! in vain.
Never was there such an all-absorbing salmon. As Mary had said,
the whole household was out watching him and his proceedings. The
baby, Austin Thomas, Sunny, and Sunny’s mamma were left alone,
to take care of one another.
These settled down again in front of the fire, and Sunny, who had
been a little bewildered by the confusion, recovered herself, and, not
at all alive to the importance of salmon-fishing, resumed her
entreating whisper:
“’Bout German pictures, mamma; tell me ’bout German pictures.”
And she seemed quite glad to go back to her old ways; for this little
girl likes nothing better than snuggling into her mamma’s lap, on the
hearth-rug, and being told about German pictures.
They came to her all the way from Germany as a present from a kind
German friend, and some of them are very funny. They make regular
stories, a story on each page. One is about a little greedy boy, so like
a pig, that at last, being caught with a sweetmeat by an old witch,
she turns him into a pig in reality. He is put into a sty, and just about
to be killed, when his sister comes in to save him with a fairy rose in
her hand; the witch falls back, stuck through with her own carving-
knife, and poor piggy-wiggy, touched by the magic rose, turns into a
little boy again. Then there is another page, “’bout effelants,” as
Sunny calls them,—a papa elephant and a baby elephant taking a
walk together. They come across the first Indian railway, and the
papa elephant, who has never seen a telegraph wire before, is very
angry at it and pulls it down with his trunk. Then there comes
whizzing past a railway-train, which makes him still more indignant,
as he does not understand it at all. He talks very seriously on the
subject to his little son, who listens with a respectful air. Then,
determined to put an end to such nuisances, this wise papa elephant
marches right in front of the next train that passes. He does not stop
it, of course, but it stops him, cutting him up into little pieces, and
throwing him on either side the line. At which the little elephant is so
frightened that you see him taking to his heels, very solid heels too,
and running right away.
Sunny heard this story for the hundredth time, delighted as ever, and
then tried to point out to Austin Thomas which was the papa
“effelant,” and which the baby “effelant.” But Austin Thomas’s more
infantile capacity did not take it in; he only “scrumpled” the pages
with his fat hands, and laughed. There might soon have been an
open war if mamma had not soothed her little girl’s wounded feelings
by the great felicity of taking off her shoes and stockings, and letting
her warm her little feet by the fire, while she lay back on her
mamma’s lap, sucking her Maymie’s apron.
The whole group were in this state of perfect peace, outside it had
grown dark, and mamma had stirred the fire and promised to begin a
quite new story, when the door again opened and Eddie rushed in.
Maurice and Franky followed, wet, of course, to the skin,—for each
left a little pool of water behind him wherever he stood,—but
speechless with excitement. Shortly after, up came the three
gentlemen, likewise silent, but not from excitement at all.
“But where’s the salmon?” asked Sunny’s mamma. “Pray let us see
the salmon.”
Maurice’s papa looked as solemn as—what shall I say?—the
renowned Buff, when he
“Strokes his face with a sorrowful grace,
And delivers his staff to the next place.”
He delivered his—no, it was not a stick, but a “tommy” hat, all
ornamented with fishing-flies, and dripping with rain, to anybody that
would hang it up, and sank into a chair, saying, mournfully:
“You can’t see the salmon.”
“Why not?”
“Because he’s at the bottom of the loch. He got away.”
“Got away!”
“Yes, after giving us a run of a full hour.”
“An hour and five minutes by my watch,” added Sunny’s papa, who
looked as dejected as the other two. Though no salmon-fisher, he
had been so excited by the sport that he had sat drenched through
and through, in the stern of the boat, and afterward declared “he
didn’t know it had rained.”
“Such a splendid fish he was,—twenty-five pounds at least.”
“Twenty,” suggested some one, who was put down at once with
scorn.
“Twenty-five, I am certain, for he rose several times, and I saw him
plain. So did Donald. Oh, what a fish he was! And he bit upon a
trout-line! To think that we should have had that one trout-line with
us, and he chose it. It could hardly hold him, of course. He required
the tenderest management. We gave him every chance.” (Of being
killed, poor fish!) “The minute he was hooked, I threw the oars to
Donald, who pulled beautifully, humouring him up and down, and you
should have seen the dashes he made! He was so strong,—such a
big fish!”
“Such a big fish!” echoed Eddie, who stood listening with open
mouth and eyes that gradually became as melancholy as his
father’s.
“And, as I said, we played him for an hour and five minutes. He was
getting quite exhausted, and I had just called to Neil to row close and
put the gaff under him, when he came up to the surface,—I declare,
just as if he wanted to have a stare at me,—then made a sudden
dart, right under the boat. No line could stand that, a trout-line
especially.”
“So he got away?”
“Of course he did, with my hook in his mouth, the villain! I dare say
he has it there still.”
It did occur to Sunny’s mamma that the fish was fully as
uncomfortable as the fisherman, but she durst not suggest this for
the world. Evidently, the salmon had conducted himself in a most
unwarrantable manner, and was worthy of universal condemnation.
Even after the confusion had a little abated, and the younger children
were safely in bed, twenty times during tea he was referred to in the
most dejected manner, and his present position angrily speculated
upon,—whether he would keep the hook in his mouth for the
remainder of his natural life, or succeed in rubbing it off among the
weeds at the bottom of the loch.
“To be sure he will, and be just as cheerful as ever, the wretch! Oh,
that I had him,—hook and all! For it was one of my very best flies.”
“Papa, if you would let me ‘low’ you in the boat, while you fished,
perhaps he might come and bite again to-morrow?”
This deep diplomatic suggestion of Eddie’s did not meet with half the
success it deserved. Nobody noticed it except his mother, and she
only smiled.
“Well!” she said, trying to cheer up the mournful company,
“misfortunes can’t be helped sometimes. It is sad. Twenty-five
pounds of fish; boiled, fried into steaks, kippered. Oh, dear! what a
help in the feeding of the household!”
“Yes,” said the patient gentleman, who, being unable to walk, could
only sit and fish, and, having come all the way from London to catch
a salmon, had never yet had a bite except this one. “Yes, twenty-five
pounds at two shillings the pound,—Billingsgate price now. That
makes two-pound-ten of good English money gone to the bottom of
the loch!”
Everybody laughed at this practical way of putting the matter, and
the laugh a little raised the spirits of the gentlemen. Though still they
mourned, and mourned, looking as wretched as if they had lost their
whole families in the loch, instead of that unfortunate—or fortunate—
salmon.
“It isn’t myself I care for,” lamented Maurice’s papa. “It’s you others.
For I know you will have no other chance. The rain will clear off—it’s
clearing off now, into a beautiful starlight night. To-morrow will be
another of those dreadfully sunshiny days. Not a fish will bite, and
you will have to go home at the week’s end,—and there’s that
salmon lying snugly in his hole, with my hook in his mouth!”
“Never mind,” said the patient gentleman, who, though really the
most to be pitied, bore his disappointment better than anybody.
“There’s plenty of fish in the loch, for I’ve seen them every day
jumping up; and somebody will catch them, if I don’t. After all, we
had an hour’s good sport with that fellow to-day,—and it was all the
better for him that he got away.”
With which noble sentiment the good man took one of the boys on
his knee,—his godson, for whom he was planning an alliance with
his daughter, a young lady of four and a half,—and began discussing
the settlements he expected; namely, a large cake on her side, and
on the young gentleman’s, at least ten salmon out of the loch, to be
sent in a basket to London. With this he entertained both children
and parents, so that everybody grew merry as usual, and the lost
salmon fell into the category of misfortunes over which the best dirge
is the shrewd Scotch proverb, “It’s nae use greeting ower spilt milk.”
 CHAPTER IX.
The forebodings of the disappointed salmon-fishers turned out true.
That wet Monday was the first and last day of rain, for weeks.
Scarcely ever had such a dry season been known in the glen.
Morning after morning the gentlemen rowed out in a hopeless
manner, taking their rods with them, under a sky cloudless and hot
as June; evening after evening, if the slightest ripple arose, they
went out again, and floated about lazily in the gorgeous sunset, but
not a salmon would bite. Fish after fish, each apparently bigger than
the other, kept jumping up, sometimes quite close to the boat. Some
must have swum under the line and looked at it, made an
examination of the fly and laughed at it, but as for swallowing it, oh,
dear, no! Not upon any account.
What was most tantalising, the gardener, going out one day, without
orders, and with one of his master’s best lines, declared he had
hooked a splendid salmon! As it got away, and also carried off the fly,
a valuable one, perhaps it was advisable to call it a salmon, but
nobody quite believed this. It might have been only a large trout.
By degrees, as salmon-fishing, never plentiful, became hopeless,
and game scarcer than ever, the gentlemen waxed dull, and began
to catch at the smallest amusements. They grew as excited as the
little boys over nutting-parties, going in whole boat-loads to the other
side of the loch, and promising to bring home large bags of nuts for
winter consumption, but somehow the nuts all got eaten before the
boats reached land.
The clergyman was often one of the nutting-party. He knew every
nook and corner of the country around, was equally good at an oar
or a fishing-rod, could walk miles upon miles across the mountains,
and scramble over rocks as light as a deer. Besides, he was so kind
to children, and took such pleasure in pleasing them, that he earned
their deepest gratitude, as young things understand gratitude. But
they are loving, anyhow, to those that love them, and to have those
little boys climbing over him, and hanging about him, and teasing
him on all occasions to give them “a low,” was, I dare say, sufficient
reward for the good minister.
Sunny liked him, too, very much, and was delighted to go out with
him. But there was such dangerous emulation between her and the
boys in the matter of “fishing” for dead leaves with a stick, which
involved leaning over the boat’s side and snatching at them when
caught, and mamma got so many frights, that she was not sorry
when the minister announced that every nut-tree down the canal had
been “harried” of its fruit, and henceforward people must content
themselves with dry land and blackberries.
This was not an exciting sport, and one day the gentlemen got so
hard up for amusement that they spent half the morning in watching
some gymnastics of Maurice and Eddie, which consisted in climbing
up to their papa’s shoulder and sitting on his head. (A proceeding
which Sunny admired so, that she never rested till she partly imitated
it by “walking up mamma as if she was a tree,” which she did at last
like a little acrobat.)
Children and parents became quite interested in their mutual
performances; everybody laughed a good deal, and forgot to
grumble at the weather, when news arrived that a photographer,
coming through the glen, had stopped at the house, wishing to know
if the family would like their portraits taken.
Now, anybody, not an inhabitant, coming through the glen, was an
object of interest in this lonely place. But a photographer! Maurice’s
papa caught at the idea enthusiastically.
“Have him in, by all means. Let us see his pictures. Let us have
ourselves done in a general group.”
“And the children,” begged their mamma. “Austin Thomas has never
been properly taken, and baby not at all. I must have a portrait of
baby.”
“Also,” suggested somebody, “we might as well take a portrait of the
mountains. They’ll sit for it quiet enough; which is more than can be