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Rose Ann Urdiales Baker, PhD RN,
PMHCNS-BC
Assistant Professor
College of Health Professions
The University of Akron
Akron, Ohio
Barbara Boss, PhD, APRN, FNP-BC,
ANP-BC
Professor of Nursing and Director of DNP
Program
University of Mississippi Medical Center
Jackson, Mississippi
Valentina L. Brashers, MD, FACP, FNAP
Professor of Nursing and Woodard Clinical
Scholar
Attending Physician in Internal Medicine
University of Virginia Health System
Charlottesville, Virginia
Kristen Lee Carroll, MD
Associate Professor, Orthopedics
University of Utah
Salt Lake City, Utah
Shriner’s Intermountain Unit
Shriner’s Hospital for Children
Salt Lake City, Utah
Dennis Cheek, RN, PhD, FAHA
Abell-Hanger Professor of Gerontology
Nursing
Harris College of Nursing and Health
Sciences
Texas Christian University
Fort Worth, Texas
Margaret F. Clayton, PhD, APRN
Associate Professor, College of Nursing
University of Utah
Salt Lake City, Utah
Christy L. Crowther-Radulewicz, MS,
CRNP
Nurse Practitioner
Anne Arundel Orthopedic Surgeons
Annapolis, Maryland
Adjunct Faculty
Johns Hopkins University School of Nursing
Baltimore, Maryland
*The authors also would like to thank the
previous edition contributors.
C ONTR IB UTO R S *
Susanna G. Cunningham, BSN, MA, Gwen Latendresse, PhD, CNM
PhD, FAAN, FAHA Assistant Professor
Professor University of Utah College of Nursing
School of Nursing Salt Lake City, Utah
University of Washington
Seattle, Washington Linda L. Martin, DNP, RN, CFNP
Assistant Professor of Professional Practice
Alexa K. Doig, PhD, RN Texas Christian University
Associate Professor Harris College of Nursing and Health
College of Nursing Sciences
University of Utah Fort Worth, Texas
Salt Lake City, Utah
Sue A. McCann, MSN, RN, DNC
Todd C. Grey, MD Programmatic Nurse Specialist
Chief Medical Examiner—State of Utah University of Pittsburgh Medical Center
Associate Clinical Professor Pittsburgh, Pennsylvania
Department of Pathology
University of Utah School of Medicine Nancy L. McDaniel, MD
Salt Lake City, Utah Associate Professor of Pediatrics
University of Virginia
Mary Fran Hazinski, RN, MSN, FAAN, Charlottesville, Virginia
FAHA, FERC
Professor, Vanderbilt University School of Mary A. Mondozzi, MSN, RN
Nursing Burn Center Education/Outreach
Assistant, Departments of Surgery and Coordinator
Pediatrics, Vanderbilt University School Akron Children’s Hospital
of Medicine The Paul and Carol David Foundation Burn
Clinical Nurse Specialist Institute
Monroe Carell, Jr. Children’s Hospital at Akron, Ohio
Vanderbilt
Nashville, Tennessee Stephen E. Morris, MD
Associate Professor of Surgery
Robert E. Jones, MD, FACP, FACE Director, University of Utah Burn Center
Professor of Medicine Salt Lake City, Utah
University of Utah School of Medicine
Salt Lake City, Utah Noreen Heer Nicol, PhD, RN, FNP,
NEA-ABC
Lynn B. Jorde, PhD Associate Professor
H.A. and Edna Benning Presidential University of Colorado, College of Nursing
Professor and Chair Director, Children’s Hospital Colorado
Department of Human Genetics Denver, Colorado
University of Utah School of Medicine
Salt Lake City, Utah Julia Phillippi, PhD, CNM, FACNM
Assistant Professor
Lynne M. Kerr, MD, PhD Vanderbilt University School of Nursing
Associate Professor Nashville, Tennessee
Departments of Pediatrics and Neurology
University of Utah Medical Center Patricia Ring, RN, PNP-BC
Salt Lake City, Utah Pediatric Nephrology Nurse Practitioner
Children’s Hospital of Wisconsin
Nancy E. Kline, PhD, RN, CPNP, FAAN Milwaukee, Wisconsin
Director, Nursing Research, Medicine
Patient Services/Emergency Department George W. Rodway, PhD, RN, ANP
Boston Children’s Hospital Assistant Professor
Boston, Massachusetts Orvis School of Nursing
University of Nevada—Reno
Reno, Nevada
v
vi CONTRIBUTORS

Neal S. Rote, PhD
Academic Vice-Chair and Director of
Research
Department of Obstetrics and Gynecology
University Hospitals Case Medical Center
William H. Weir, MD. Professor of
Reproductive Biology and Professor of
Pathology
Case Western Reserve University School of
Medicine
Cleveland, Ohio
Anna L. Schwartz, PhD, FNP-BC, FAAN
Associate Professor
School of Nursing
Northern Arizona University
Flagstaff, Arizona
Richard A. Sugerman, PhD
Professor of Anatomy, Emeritus
Director of Service Learning Projects
College of Osteopathic Medicine of the
Pacific
Pomona, California
Lorey K. Takahashi, PhD
Professor of Psychology
University of Hawaii at Manoa
Honolulu, Hawaii
Gillian Tufts, DNP, FNP-C
Associate Professor
Clinical College of Nursing
University of Utah College of Nursing
Salt Lake City, Utah
 R EV IEW E R S

Nancy M. Burruss, PhD, RN, CNE Carol Anne Marchetti, PhD, RN, CNS, Abby Saunders, MS, PA-C
Associate Professor NP Physician Assistant
Bellin College Assistant Professor School of Health and Medical Sciences
Green Bay, Wisconsin Bouve College of Health Sciences Seton Hall University
School of Nursing South Orange, New Jersey
David J. Derrico, RN, MSN Northeastern University
Clinical Assistant Professor Boston, Massachusetts Lorna L. Schumann, PhD, NP-C, ACNS,
Adult and Elderly Department BC, ACNP, BC, CCRN-R, FAANP
University of Florida College of Nursing Denise Morita, MD Associate Professor
Gainesville, Florida Assistant Professor College of Nursing
Department of Pediatrics Washington State University
Diane P. Genereux, PhD Division of Pediatric Neurology Spokane, Washington
Assistant Professor University of Utah School of Medicine
Department of Biology Salt Lake City, Utah Karin C. VanMeter, PhD
Westfield State University Lecturer
Westfield, Massachusetts Jason Mott, PhD, RN Department of Biomedical Sciences
Instructor of Nursing College of Veterinary Medicine
Sandra L. Kaminski, MS, PA-C Nursing Department Iowa State University
Assistant Professor Bellin College Ames, Iowa
School of Health and Medical Sciences Green Bay, Wisconsin
Seton Hall University
South Orange, New Jersey Jane Cross Norman, PhD, RN, CNE
Masters of Science in Nursing
Fei Li, PhD Program Director
Assistant Professor Tennessee State University
Department of Biology Nashville, Tennessee
New York University
New York, New York

vii
This page intentionally left blank

     

Pathophysiology incorporates basic, translational, and clinical
research to advance understandings of disease and dysfunction.
The study of pathophysiology involves many biomedical sciences
and a wide range of research activities. Multiple aspects of cellu-
lar physiology are progressing rapidly, generating vast amounts of
data to understand. The information expansion involves a greater
understanding of the behavior of individual cells, of their neigh-
boring microenvironment, and of the molecules that not only
make up those cells but also communicate with their surroundings.
Importantly, the forward movement of biomedical sciences occurs
within the context of social, economic, and political processes that
determine how disease is defined, experienced, and treated.
Interdisciplinary research has led to significant advancements
in genetics, epigenetics, cell signaling and communication, con-
trol of cell behavior, metabolism, and cell fate. Knowledge about
normal cell structures and signaling pathways is at the forefront
of translational science. Advancements in tools to observe cells
have provided new understanding of cellular processes includ-
ing migration of tumor cells, responses of the immune system,
and influences of the microenvironment. Investigators are
studying if or how early life events affect health and disease into
adulthood and across generations. A wide range of research is
centered on microbial mechanisms of pathogenesis, immune
responses, epidemiology, and drug efficacy and resistance.
Although these advancements have created an ever-increasing
state of excitement, they have also created the problem of how
students, teachers, and clinicians can cope with the expanding
new information. Compressing these data into simplified dis-
cussions for students and clinicians is challenging. Our approach
in this book has been to present an organized, logical sequence
of content based on current literature and research reports with
understandable explanations and accompanied by illustrations
and summary tables. The primary focus is on pathophysiology,
and there is less emphasis on the evaluation and treatment that is
found in clinical management textbooks. As in previous editions,
the following is a list of our specific goals for the textbook:
• Draw attention to differences in etiology, epidemiology,
pathophysiology, clinical manifestations, and treatment
according to gender and age.
• Pay careful attention to presentations of emerging new data
on controversial topics.
• Integrate health promotion and disease prevention by updat-
ing risk factors, explaining certain relationships between
nutrition and disease, and referencing screening recommen-
dations and other therapeutic approaches.
ORGANIZATION AND CONTENT: WHAT’S NEW
IN THE SEVENTH EDITION
The book is organized into two parts. Part One presents the cel-
lular and tissue responses common to disease. The pathophysi-
ology of disease, organized by body systems, is presented in Part
PR EFAC E
Two. All content has been reviewed and updated with extensive
new references and two new chapters.
Part One: Central Concepts of Pathophysiology:
Cells and Tissues
Part One begins with an in-depth study of the cell and pro-
gresses to cover the underlying processes of disease. Concepts
covered include cell signaling and cell communication pro-
cesses; genes and common genetic diseases; epigenetics and
disease; fluid, electrolyte, and acid-base balance; inflammation,
cytokines and their biologic functions, and normal and altered
immunity; infection, stress, coping, and immunity; tumor biol-
ogy, epidemiology of cancer, and cancer in children. Particu-
larly important revisions and additions to Part One include the
following:
• Updated content on cellular organelles, the plasma mem-
brane, cell signaling, and communication (Chapter 1)
• Updated content on agents of cell injury, oxidative stress,
apoptosis, autophagy, and aging (Chapter 2)
• A new chapter on epigenetics and disease (Chapter 6)
• Updated content on normal innate and adaptive immunity
(Chapters 7 and 8)
• Updated content on alterations of immunity and inflamma-
tion (Chapter 9)
• Updated content on infection (Chapter 10)
• Reorganization and updated content on stress and disease
(Chapter 11)
• Extensive revisions and reorganization of tumor biology and
invasion and metastases (Chapter 12)
• Extensive revisions and reorganization of epidemiology of
cancer (Chapter 13)
Part Two: Pathophysiologic Alterations:
Organs and Systems
Part Two is a systematic survey of diseases within body systems.
Each unit focuses on a specific body system and begins with an
anatomy and physiology chapter to provide a basis of compari-
son for understanding the alterations created by disease. A brief
summary of normal aging is included at the end of the section
on anatomy and physiology. The discussion of each disease in
the alterations’ chapters is developed in a logical manner that
begins with an introductory paragraph on etiology and epide-
miology, followed by pathophysiology, clinical manifestations,
and evaluation and treatment. Separate chapters are dedicated
to pediatric pathophysiology, and sensitivity is paid to gender
and age. Especially significant revisions and additions to Part
Two include the following:
• Updated information on chronic pain syndromes and clas-
sification of sleep disorders (Chapter 16)
• Updated content on concepts of alterations in consciousness,
memory, delirium syndromes, and dementia. New infor-
mation related to motor neuron and movement disorders
ix
x PREFACE
including Parkinson disease and amyotrophic lateral sclero-
sis (Chapter 17)
• Updated information on traumatic brain and spinal cord
injury, degenerative disorders of the spine, stroke and head-
ache syndromes, and multiple sclerosis (Chapter 18)
• Updated content on schizophrenia, mood disorders, and
anxiety (Chapter 19)
• Updates on childhood cerebrovascular disease, seizure dis-
orders, and brain tumors (Chapter 20)
• Extensive updates on diabetes mellitus, insulin resistance,
and thyroid and adrenal gland disorders (Chapter 22)
• Extensively rewritten material on female reproductive dis-
orders including cancer, benign breast diseases, and breast
cancer (Chapter 24)
• A separate chapter on male reproductive disorders and
­cancer with extensive updating and reorganization (Chap-
ter 25)
• Extensive updating of sexually transmitted infections (Chap-
ter 26)
• Updated content on normal blood cells, hemostasis, platelet
function, and coagulation (Chapter 27)
• Revised and updated content on alterations of leukocyte,
lymphoid, and hemostatic function (Chapter 29)
• Extensively rewritten chapter on the anatomy and physiol-
ogy of the cardiovascular and lymphatic systems (Chapter
31)
• Extensively updated coverage of atherosclerosis, endothelial
injury and dysfunction, coronary artery disease, myocardial
infarction, and heart failure (Chapter 32)
• M ajor revisions to the immune mechanisms of asthma,
chronic lung disease; and updates for respiratory tract infec-
tion, pulmonary hypertension, pulmonary embolism, and
lung cancers (Chapters 35)
• Major updates for childhood asthma, respiratory distress
syndrome, cystic fibrosis, lung infections, and sudden infant
death syndrome (Chapter 36)
• Updates on kidney stones, urinary tract infection, glomer-
ulopathies, chronic renal failure, and bladder and kidney
tumors (Chapter 38)
• New information for urinary tract infection, glomerulone-
phritis, and renal failure in children (Chapter 39)
• Updates on gastroesophageal reflux disease, peptic ulcer dis-
ease, irritable bowel syndrome, inflammatory bowel disease,
intestinal obstruction, obesity, colon cancer, and liver dis-
ease (Chapter 41)
• New information on gluten-sensitive enteropathy, necrotiz-
ing enterocolitis, bowel obstruction, infections of the intes-
tine, and liver disease in children (Chapter 42)
• Updated content on alterations of the musculoskeletal sys-
tem (Chapter 44)
• Updated content on pressure ulcers, dermatitis and psoria-
sis, vesicular disorder, scleroderma, and skin cancer (Chap-
ter 46)
• Updated content on childhood atopic dermatitis, skin infec-
tions, and immune drug reactions (Chapter 47)
• Extensive updating and reorganization of content on septic
shock, multiple organ dysfunction syndrome, and burns for
adults and children (Chapters 48 and 49)

FEATURES TO PROMOTE LEARNING
Ease of learning has been enhanced by designing a number of
features that guide and support understanding, including:
• Each chapter opener notes the corresponding module in
the Online Review Course. The course is available as a
separate purchase. Details of the course can be reviewed at
www.us.elsevierhealth.com.
• Chapter Outlines for each chapter
• Special Headings to underscore the consistent treatment of
each disease—Pathophysiology, Clinical Manifestations,
and Evaluation and Treatment
• More than 85 What’s New? boxes review the most current
research and clinical developments; a list of these is included
on the inside front cover
• Nutrition & Disease boxes to emphasize nutrition as a
health promotion strategy that may alter disease risk or
pathogenesis
• End-of-chapter Summary Review sections summarize the
content in each chapter and serve as built-in content review
guides
• Boldface Key Terms with end-of-chapter term lists and page
numbers for rapid access
• A comprehensive Glossary with approximately 1000 terms
helps students with the often-difficult terminology related to
pathophysiology
ART PROGRAM
The art program was carefully crafted. It received as much
attention as the narrative. Nearly 200 new or revised full-color
illustrations were created and strategically placed throughout
the textbook. Also included are many new high-quality, full-
color photographs of clinical manifestations, pathologic speci-
mens, and clinical imaging techniques. The combination of
illustrations, algorithms, and photographs and the use of color
for tables and boxes allow clarification for complex concepts
and the emergence of easily recognized essential information.
PREFACE xi
ANCILLARIES
For Students
On Evolve, at http://evolve.elsevier.com/McCance/, students
can access 550 review questions, 100 animations to help stu-
dents master the text content, 28 case studies with questions
and answers, and downloadable chapter Key Point documents
for each chapter.
The newly rewritten Study Guide includes many different
question types, aiming to help all different types of student
learners. Question types include the following:
• Choose the Correct Words
• Complete These Sentences
• Categorize These Clinical Examples
• Explain the Pictures
• Teach These People about Pathophysiology
• Plus many more…
Answers are found in the back of the Study Guide for easy
reference for students.
For Instructors
The Evolve Instructor Resources for this textbook provide the
following teaching aids:
• Teach for Nurses instructor manual, broken down by chap-
ter, detailing the resources available to instructors for their
lesson planning, and including unique case studies and class
activities they can share with students
• Test Bank in ExamView with approximately 1900 ques-
tions (in multiple choice, multiple response, and match-
ing ­formats) with answers, rationales, and textbook page
references
• Image Collection with all of the approximately 1200 figures
from the text
• PowerPoint lecture slides for each chapter (approximately
3400 slides and 420 images total), including integrated Audi-
ence Response Questions in each chapter (218 total), and
integrated case studies at the end of each unit (15 total)
Evolve is an Internet-based learning environment that
works in coordination with the text. This resource enables you
to publish your class syllabus, outline, and lecture notes; set up
“virtual office hours” and e-mail communication; share impor-
tant dates and information through the online class calendar;
and encourage student participation through chat rooms and
discussion boards. Free with qualified adoption. Contact your
sales representative or visit http://evolve.elsevier.com for more
information about integrating Evolve into your curriculum.
This page intentionally left blank

     
 A C K NOW LED GM EN T S
The enormous task of keeping this book current and readable
greatly depends on our contributors; several new writers have
joined our team for this edition. We thank them for their knowl-
edge and tremendous labor of reviewing relevant literature,
synthesizing it, and writing and revising chapters to make them
highly readable for others. This edition includes a new chapter
on epigenetics and disease and separate chapters for female and
male alterations of reproduction. Several chapters were com-
pletely rewritten for this edition. We have a special appreciation
for Neal Rote and Tina Brashers, section editors, for their tire-
less editing, writing, and development of new art. Neal man-
aged the immunity, infection, and hematology chapters. For
this edition, he completely updated the tumor biology chapter.
Neal also fully updated the glossary. Tina managed the endo-
crine, pulmonary, and cardiovascular alterations chapters. Both
Neal and Tina have exceptional ability to integrate, simplify,
and illustrate the complex content of pathophysiology. Always
motivated to really help students and clinicians, we thank you
both. In addition, Tina Brashers, Samantha Greed, Lori Kelly,
Kathleen Whalen, Diane Young, and Linda Turchin developed
modules for the Online Review Course. There were also many
faculty and clinicians who provided reviews for content revision
and we are grateful for their insight and recommendations.
We extend gratitude to those who contributed to the book
supplements. Linda Felver has created an all new inventive and
resourceful Study Guide. Thank you Linda for very astute edits.
For the Student Evolve website, Blaine Winters and Gaye Ray
wrote the review questions. For the Instructor Evolve website,
Linda Turchin updated and revised the Test Bank. Joanna Cain
and Stacy June Breedlove Shaffer created unique case studies
for the Teach for Nurses Instructor’s Manual and PowerPoints.
Kim Webb fully updated the PowerPoint presentations and
supplemental audience response questions. Former Content
Development Specialist on our book, Charlene ­Ketchum, cre-
ated the Teach for Nurses Instructor’s Manual. Also thank you
to freelancer Allison Smith, who aided in the update of the glos-
sary. We would also like to acknowledge Nancy Blasdell, Diane
Young, Margaret Clayton, Susan Frazier, and Linda Turchin for
their previous contributions to the Evolve resources. Thank you
all for your help.
The process of completing this book is dependent on the
“behind the scenes work” of numerous people. Manuscript
management and final word processing is a huge and complex
effort and was completed by our “rock” Sue Meeks, who has
worked with us for more than 30 years. Her extraordinary tal-
ent, unwavering dedication to excellence, and detail kept us
sane and on track. Every edition is monumental work—and she
retypes and recounts endlessly—and unruffled. As always, our
deepest appreciation for your continuing skill and patience.
Our Senior Content Development Editor at Elsevier is
Karen Turner. This job is key. Karen monitored closely with
an eagle eye! Karen was especially helpful with illustrations and
exacting surveillance necessary for staying consistent and clear.
Her questions were thoughtful and critically timed. She is very
organized and practical and kept this project on target. Thank
you Karen. Senior Content Strategist Sandra Clark helped with
the overall structure of the book and all the business needed
for contributors, designers, artists, and other editors. This is a
big job and Sandra made sure that we had all resources neces-
sary to complete this book. Thank you, Sandra. Senior Content
Coordinator Brooke Kannady, a delight to work with, coor-
dinated all reviewer projects, was quick to respond to any of
the production needs, and is very conscientious. Thank you,
Brooke. To Sally Schrefer, endless thanks for constant inspira-
tion over 24 years.
The project manager for a book of this size and complexity
of content has an enormous responsibility. The Senior Project
Manager was Jeanne Genz. From copy edit to final page proofs,
she is exacting and a gem to work with. Thank you, Jeanne, espe-
cially for your early morning consultations. Our book designer
was Amy Buxton and she did an outstanding job guiding the
design of the interior portion of the book—we are especially
pleased with the layout, dynamic colors, and presentation of
pedagogy. She also coordinated the work that went into creat-
ing the striking cover design. Thank you, Amy.
The newly drawn and revised artwork for this edition was
completed by George Barile of Accurate Art Inc. The art is
key and challenging and our drawings are often pathetic, but
George was persistent to get it right and creative. Thank you
so much George for the conceptual arrangements, labels, and
beautiful colors.
We thank Ramón Andrade Candelario at 3Dciencia for
allowing us to use the beautiful cover image. We also thank the
Department of Dermatology at the University of Utah School
of Medicine, which provided numerous photos of skin lesions.
Thanks to Dr. Arthur R. Brothman, University of Utah School
of Medicine, for the N-myc gene amplification slides used to
illustrate the discussion of neuroblastoma, and to Dr. John
Hoffman for the PET scan images of non–small cell lung cancer.
We are grateful to the many colleagues and friends at the
University of Utah Health Sciences Center for their assistance
with references and consultation on content. Thanks for the
outstanding extra help—Ruth Weinberg, your experience and
editorial skill are exceptional.
Special thanks are given to students, particularly nursing and
other health science students, for the e-mails and phone calls we
receive. Your questions and suggestions are inspiring and guide
us in our efforts to prepare a clear and up-to-date manuscript
with much visual input.
Sincerely and with great affection we thank our families,
especially John, Mae, and Dorothy. Although disentangling cer-
tain data is inconvenient at times, we thank those committed
to “getting it right”—increasing patient-centered quality care,
safety, and satisfaction.
xiii
This page intentionally left blank

     
 INTR OD UC TION T O
PA TH OPH Y S IOLO G Y
The word root “patho” is derived from the Greek word pathos,
which means suffering. The Greek word root “logos” means
discourse or, more commonly, system of formal study, and
“physio” pertains to functions of organisms. Generally, patho-
physiology is the systematic study of the functional changes
in cells, tissues, and organs altered by disease and/or injury.
Important, however, is the inextricable component of suffering.
Knowledge of cellular biology as well as anatomy and physi-
ology and the various organ systems of the body is an essential
foundation for the study of pathophysiology. To understand
pathophysiology the student must also use principles, concepts,
and basic knowledge from other fields of study, including biol-
ogy, genetics, immunology, pathology, and epidemiology. A
number of terms are used to focus the discussion of pathophysi-
ology; they may be used interchangeably at times, but that does
not necessarily indicate that they have the same meaning. These
terms are reviewed in Table I-1.
Pathophysiology is one of the most important bridging sci-
ences between preclinical and clinical courses for students in
the health sciences and it requires in-depth study at an early
stage in the curriculum. The definitions or conceptual models
of pathophysiology that we carry in our minds influence what
we do with our observations and the rationale that we provide
for our actions. Therefore, the clinician must understand that
TABLE I-1 TERMS AND DEFINITIONS
RELATED TO
PATHOPHYSIOLOGY
Pathology Study of structural alterations in cells, tissues, and
organs that help to identify the cause of disease
Pathogenesis Pattern of tissue changes associated with the
development of disease
Etiology Study of the cause(s) of disease and/or injury
Idiopathic Diseases with no identifiable cause
Iatrogenic Diseases and/or injury as a result of medical
intervention
Clinical Signs and symptoms
manifestations
Nosocomial Diseases acquired as a consequence of being in a
hospital environment
Diagnosis Naming or identification of a disease
Prognosis Expected outcome of a disease
Acute disease Sudden appearance of signs and symptoms lasting
a short time
Chronic disease Develops more slowly, lasting a long time or a
lifetime
Remissions Periods when clinical manifestations disappear or
diminish significantly
Exacerbations Periods when clinical manifestations become
worse or more severe
Sequelae Any abnormal conditions that follow and are the
result of a disease, treatment, or injury
although pathophysiology is a science, it also designates suffer-
ing in people; the clinician should never lose sight of this aspect
of its definition.
As students study clinically-related sciences, they learn to
recognize and categorize disease. From the formulation of a dif-
ferential diagnosis one understands the different clinical mani-
festations, the signs, and the symptoms of certain pathologies.
These understandings structure further investigations, treat-
ment plans, and evaluation. The interaction of these activities
determines clinical outcomes and treatment success. Still, the
concept of disease can be inherently ambiguous and elusive;
many pathologies remain hidden and resist easy classification.
One should appreciate that the naming and diagnosing of dis-
eases involve evaluative judgments as well as scientific fact, and
that the process is as much a social endeavor as it is a scien-
tific one. Some diseases, such as tuberculosis, identify a highly
specific causative or etiologic agent or process. Others, such as
Alzheimer disease or arthritis, indicate pathologic changes of
unclear cause. There is considerable need for more research
to validate mental health diagnoses. In addition, syndromes
and functional disorders simply describe multiple symptoms
and signs that frequently occur together. Does commonality
exist in all of these labels? The answer is “yes” and “no” and
depends on our conception of health and disease. In the strict-
est sense, objective scientific facts help us know if an individual
is healthy or suffering from disease. Critical to attaining health
in the United States are nine domains particularly worrisome
and include adverse birth outcomes, injuries and homicides,
adolescent pregnancy and sexually transmitted infections, HIV
and AIDS, drug-related mortality, obesity and diabetes, heart
disease, chronic lung disease, and disability.1
An individual’s conception of disease is based on personal
beliefs and histories, professional and lay healers who interact
with that individual, and society at large. Each idea or construct
has the power to influence other ideas and constructs, and each
relationship has the ability to shape the way disease is under-
stood and experienced.2 In short, defining and understanding
disease are tremendously ambiguous. Although a discerning
mind is key, perhaps an important trait for the new student of
pathophysiology is an open and tolerant mind. To believe that
science alone can overcome ignorance and that clinical training
and technology can overcome ineptitude only encourages arro-
gance and undermines the scientific purpose.
Pathophysiology has had great success in explaining the
mechanisms and clinical manifestations associated with infec-
tious diseases. Syndromes of unclear etiology, such as headache
and fibromyalgia, have proven to be troublesome. Even more
difficult are multifactorial conditions, such as atherosclerosis
or type 2 diabetes mellitus, in which several interacting fac-
tors contribute to the etiology. Learning how interacting fac-
tors relate to one another to increase morbidity or actually
cause disease contributes to an appreciation of how emerging
xv
xvi INTRODUCTION TO PATHOPHYSIOLOGY
concepts revolutionize current understandings. One revolution
in thought that has driven intensive research is that low levels
of chronic inflammation cause or contribute to many diseases.
The language that clinicians use to discuss diseases and their
manifestations is powerful. Lives are altered by a few words
uttered by a clinician in a white coat or uniform. “AIDS,” “can-
cer,” and “heart attack” have become culturally ingrained sym-
bols that portend an individual’s future. Although some futures
are determined by scientific evidence, others are determined by
subjective experience.3 For example, a person diagnosed with
a familial disease may ask, “Will I suffer like my mother did?”
This questioning influences individuals’ suffering.
In conclusion, pathophysiology—the understanding of
disease—requires descriptive evidence as well as an evaluative
component regarding suffering and the language we use to
describe it. Combining objective and subjective perspectives
requires new conceptual models that take into account the
complex interactions among the body, mind, environment, and
spirit.
REFERENCES
1. Woolf SH, Aron L, editors: Panel on understanding cross-national
health differences among high-income countries, Committee on
Population, Division of Behavioral and Social Sciences and Educa-
tion, National Research Council, Board on Population Health
and Public Practice, Institute of Medicine, Bethesda, MD, 2013,
Author.
2. Magid C: Developing tolerance for ambiguity, JAMA 285(1):88,
2001.
3. Goldstein J: In the twilight: life in the margins between sick and
well, JAMA 285(1):92, 2001.
 C ONTEN T S

Introduction to Pathophysiology, xv Hypertrophy, 51

Hyperplasia, 51
Dysplasia: Not a True Adaptive Change, 53
PART ONE CENTRAL CONCEPTS Metaplasia, 54
OF PATHOPHYSIOLOGY: Cellular Injury, 54
CELLS AND TISSUES General Mechanisms of Cell Injury, 55
Hypoxic Injury, 56
Free Radicals and Reactive Oxygen
UNIT 1 The Cell
Species—Oxidative Stress, 59
1 Cellular Biology, 1 Chemical Injury, 62
Kathryn L. McCance Unintentional and Intentional Injuries, 70
Prokaryotes and Eukaryotes, 2 Injury from Errors in Health Care, 71
Cellular Functions, 2 Infectious Injury, 75
Structure and Function of Cellular Components, 2 Immunologic and Inflammatory Injury, 75
Nucleus, 2 Injurious Genetic/Epigenetic Factors, 75
Cytoplasmic Organelles, 4 Injurious Nutritional Imbalances, 75
Plasma Membranes, 11 Injurious Physical Agents, 75
Cellular Receptors, 16 Manifestations of Cellular Injury, 83
Cell-to-Cell Adhesions, 17 Cellular Manifestations: Accumulations, 83
Extracellular Matrix, 17 Systemic Manifestations, 88
Specialized Cell Junctions, 18 Cellular Death, 88
Cellular Communication and Signal Transduction, 20 Necrosis, 88
Signal Transduction, 21 Apoptosis, 91
Extracellular Messengers and Channel Autophagy: Death but Also Survival, 92
Regulation, 22 AGING and Altered Cellular and Tissue Biology, 93
Second Messengers, 22 Normal Life Span and Life Expectancy, 94
Cellular Metabolism, 25 Somatic Death, 97
Role of Adenosine Triphosphate, 25 3 The Cellular Environment: Fluids and Electrolytes,
Food and Production of Cellular Energy, 26 Acids and Bases, 103
Oxidative Phosphorylation, 27 Alexa K. Doig and Sue E. Huether
Membrane Transport: Cellular Intake and Output, 28 Distribution of Body Fluids, 103
Movement of Water and Solutes, 28 AGING and Distribution of Body Fluids, 104
Transport by Vesicle Formation, 33 Water Movement Between ICF and ECF, 105
Movement of Electrical Impulses: Membrane Water Movement Between Plasma and
Potentials, 36 Interstitial Fluid, 105
Cellular Reproduction: The Cell Cycle, 37 Alterations in Water Movement, 105
Phases of Mitosis and Cytokinesis, 37 Edema, 105
Rates of Cellular Division, 37 Sodium, Chloride, and Water Balance, 108
Growth Factors, 38 Sodium and Chloride Balance, 108
Tissues, 39 Water Balance, 109
Tissue Formation, 39 Alterations in Sodium, Chloride, and Water
Types of Tissues, 39 Balance, 109
2 Altered Cellular and Tissue Biology, 49 Isotonic Alterations, 109
Kathryn L. McCance, Todd Cameron Grey, and Hypertonic Alterations, 110
George Rodway Hypotonic Alterations, 112
Cellular Adaptation, 50 Alterations in Potassium, Calcium, Phosphate, and
Atrophy, 50 Magnesium Balance, 114

xvii
xviii CONTENTS
Potassium, 114
Calcium and Phosphate, 119
Magnesium, 122
Acid-Base Balance, 122
Hydrogen Ion and pH, 122
Buffer Systems, 123
Acid-Base Imbalances, 126
UNIT II Genes and Gene-Environment
­Interaction
4 Genes and Genetic Diseases, 135
Lynn B. Jorde
DNA, RNA, and Proteins: Heredity
at the Molecular Level, 136
DNA, 136
From Genes to Proteins, 141
Chromosomes, 142
Chromosome Aberrations and Associated
Diseases, 143
Elements of Formal Genetics, 151
Phenotype and Genotype, 151
Dominance and Recessiveness, 151
Transmission of Genetic Diseases, 151
Autosomal Dominant Inheritance, 152
Autosomal Recessive Inheritance, 154
X-Linked Inheritance, 156
Evaluation of Pedigrees, 159
Linkage Analysis and Gene Identification, 159
Classical Pedigree Analysis, 159
Assigning Loci to Specific Chromosomes, 160
5 Genes, Environment-Lifestyle, and Common
Diseases, 164
Lynn B. Jorde
Factors Influencing Incidence of Disease in
Populations, 164
Concepts of Incidence and Prevalence, 164
Analysis of Risk Factors, 165
Principles of Multifactorial Inheritance, 165
Basic Model, 165
Threshold Model, 166
Recurrence Risks and Transmission Patterns,
167
Nature and Nurture: Disentangling the Effects of
Genes and Environment, 169
Twin Studies, 169
Adoption Studies, 170
Genetics of Common Diseases, 171
Congenital Malformations, 171
Multifactorial Disorders in the Adult Population,
171
6 Epigenetics and Disease, 183
Lynn B. Jorde
Epigenetics and Development, 184
Twin Studies Provide Insights on Epigenetic
Modification, 185
Epigenetics and Cancer, 186
DNA Methylation and Cancer, 186
miRNAs and Cancer, 186
Strategies for Treating Epigenetic Disease, 186
Genomic Imprinting, 187
Prader-Willi and Angelman Syndromes, 187
Beckwith-Wiedemann Syndrome, 188
Russell-Silver Syndrome, 188
Future Directions, 188
UNIT III Mechanisms of Self-Defense
7 Innate Immunity: Inflammation, 191
Neal S. Rote, Sue E. Huether, and
Kathryn L. ­McCance
Human Defense Mechanisms, 192
First Line of Defense: Physical, Mechanical, and
Biochemical Barriers, 192
Physical and Mechanical Barriers, 192
Biochemical Barriers, 192
Second Line of Defense: The Inflammatory
Response, 195
Vascular Response, 195
Plasma Protein Systems, 197
Cellular Mediators of Inflammation, 201
Local Manifestations of Inflammation, 213
Systemic Manifestations of Acute Inflammation, 213
Fever, 213
Leukocytosis, 213
Plasma Protein Synthesis, 214
Chronic Inflammation, 214
Resolution and Repair, 215
Reconstructive Phase, 216
Maturation Phase, 218
Dysfunctional Wound Healing, 218
PEDIATRICS and Mechanisms of Self-Defense,
220
AGING and Mechanisms of Self-Defense, 220
8 Adaptive Immunity, 224
Neal S. Rote and Kathryn L. McCance
General Characteristics of Adaptive Immunity, 225
Humoral and Cell-Mediated Immunity, 226
Active vs. Passive Immunity, 227
Recognition and Response, 227
Antigens and Immunogens, 228
Molecules That Recognize Antigen, 229
Molecules That Present Antigen, 233
Molecules That Hold Cells Together, 235
Cytokines and Their Receptors, 235
Generation of Clonal Diversity, 236
T-Cell Maturation, 237
B-Cell Maturation, 240

Induction of an Immune Response: Clonal Selection,
241
Secondary Lymphoid Organs, 242
Antigen Processing and Presentation, 242
T-Helper Lymphocytes, 245
B-Cell Activation: The Humoral Immune
Response, 247
T-Cell Activation: The Cellular Immune
Response, 249
Effector Mechanisms, 251
Antibody Function, 251
T-Lymphocyte Function, 255
FETAL and NEONATAL Immune Function, 257
AGING and Immune Function, 257
9 Alterations in Immunity and Inflammation, 262
Neal S. Rote and Kathryn L. McCance
Hypersensitivity: Allergy, Autoimmunity, and
Alloimmunity, 262
Mechanisms of Hypersensitivity, 263
Antigenic Targets of Hypersensitivity Reactions,
270
Autoimmune and Alloimmune Diseases, 277
Deficiencies in Immunity, 281
Initial Clinical Presentation, 281
Primary Immune Deficiencies, 281
Secondary Immune Deficiencies, 289
Evaluation and Care of Those with Immune
Deficiency, 292
Replacement Therapies for Immune Deficiencies,
293
10 Infection, 298
Neal S. Rote and Sue E. Huether
Emerging Infections, 299
Microorganisms and Humans: A Dynamic
Relationship, 300
Microorganisms and Infections, 300
Process of Infection, 300
Clinical Infectious Disease, 301
Classes of Infectious Microorganisms, 302
Acquired Immunodeficiency Syndrome
(AIDS), 322
Transmission, 322
Pathogenesis, 324
Clinical Manifestations, 326
Treatment and Prevention, 327
Pediatric AIDS and Central Nervous System
Involvement, 327
Countermeasures Against Pathogens, 329
Infection Control Measures, 329
Antimicrobials, 330
Active Immunization: Vaccines, 332
Passive Immunotherapy, 333
CONTENTS xix
11 Stress and Disease, 338
Margaret F. Clayton and Kathryn L. McCance
Historical Background and General Concepts, 338
Concepts of Stress, 339
Psychoneuroimmunologic Mediators of Stress,
342
Stress Response, 343
Central Stress Response, 343
Neuroendocrine Regulation, 344
Stress and the Immune System, 353
Stress, Personality, Coping, and Illness, 355
Coping, 357
AGING and Stress: Stress-Age Syndrome, 358
UNIT IV Cellular Proliferation: Cancer
12 Cancer Biology, 363
Neal S. Rote and David M. Virshup
Cancer Characteristics and Terminology, 363
Tumor Classification and Nomenclature, 364
The Biology of Cancer Cells, 368
The Genetic Basis of Cancer, 372
Cancer-Causing Mutations in Genes, 372
Oncogenes and Tumor-Suppressor Genes:
Accelerators and Brakes, 373
Gene Changes That Occur in Cancer, 375
Guardians of the Genome, 379
Types of Genes Misregulated in Cancer, 380
Inflammation, Immunity, and Cancer, 382
Cancer Invasion and Metastasis, 387
Only Rare Cells in a Cancer Are Able to
Metastasize, 388
Detachment and Invasion, 388
Survival and Spread in the Circulation, 389
Selective Adherence in Favorable Sites, 389
Escape from the Circulation and Development of
a New Microenvironment, 390
Clinical Manifestations and Treatment of Cancer, 392
Clinical Manifestations of Cancer, 392
Cancer Treatment, 395
13 Cancer Epidemiology, 402
Kathryn L. McCance
Genetics, Epigenetics, and Tissue, 403
Incidence and Mortality Trends, 409
Incidence Trends, 409
Mortality Trends, 410
In Utero and Early Life Conditions, 410
Environmental-Lifestyle Factors, 413
Tobacco Use, 413
Diet, 414
Infection, Sexual and Reproductive Behavior,
Human Papillomaviruses, 423
Other Viruses and Microorganisms, 424
Ionizing Radiation, 424
xx CONTENTS
Ultraviolet Radiation, 431
Electromagnetic Radiation, 431
Chemicals and Occupational Hazards as
Carcinogens, 432
Air Pollution, 433
14 Cancer in Children, 442
Nancy E. Kline
Incidence and Types of Cancer, 442
Etiology, 443
Genetic Factors, 444
Environmental Factors, 444
Prognosis, 445
PART TWO PATHOPHYSIOLOGIC
­ALTERATIONS: ORGANS
AND ­SYSTEMS
UNIT V The Neurologic System
15 Structure and Function of the Neurologic System,
447
Richard A. Sugerman
Overview and Organization of the Nervous System,
447
Cells of the Nervous System, 448
Neurons, 448
Neuroglia and Schwann Cells, 449
Nerve Injury and Regeneration, 450
Nerve Impulse, 451
Synapses, 451
Neurotransmitters, 452
Central Nervous System, 454
Brain, 454
Spinal Cord, 460
Motor Pathways (Tracts), 463
Sensory Pathways, 464
Protective Structures, 464
Blood Supply, 467
Peripheral Nervous System, 469
Autonomic Nervous System, 470
Anatomy of the Sympathetic Nervous System, 470
Anatomy of the Parasympathetic Nervous System,
473
AGING and the Nervous System, 477
Tests of Nervous System Function, 477
Skull and Spine Roentgenograms, 477
Computed Tomography, 478
Magnetic Resonance Imaging, 478
Magnetic Resonance Angiography, 478
Positron-Emission Tomography Scan, 478
Brain Scan, 478
Cerebral Angiography, 480
Myelography, 480
Echoencephalography (Ultrasound), 480
Electroencephalography, 480
Evoked Potentials, 480
Cerebrospinal Fluid Analysis, 480
16 Pain, Temperature Regulation, Sleep, and Sensory
Function, 484
Sue E. Huether, George Rodway, and Curtis DeFriez
Pain, 485
Theories of Pain, 485
Neuroanatomy of Pain, 485
Pain Modulation, 487
Clinical Descriptions of Pain, 491
PEDIATRICS and Perception of Pain, 495
AGING and Perception of Pain, 495
Temperature Regulation, 495
Hypothalamic Control of Temperature, 496
PEDIATRICS and Temperature Regulation, 498
AGING and Temperature Regulation, 498
Pathogenesis of Fever, 498
Benefits of Fever, 498
Disorders of Temperature Regulation, 500
Sleep, 502
Non–Rapid Eye Movement (NREM) Sleep, 502
Rapid Eye Movement Sleep, 503
PEDIATRICS and Sleep Patterns, 503
AGING and Sleep Patterns, 504
Sleep Disorders, 504
Sleep Disorders Associated with Mental,
Neurologic, or Medical Disorders, 505
Somatosensory Function and the Special Senses,
506
Touch, 506
Proprioception, 506
Vision, 507
AGING and Vision, 509
Hearing, 514
AGING and Hearing, 515
Olfaction and Taste, 517
AGING and Olfaction and Taste, 518
17 Alterations in Cognitive Systems, Cerebral
Hemodynamics, and Motor Function, 527
Barbara J. Boss and Sue E. Huether
Alterations in Cognitive Systems, 527
Alterations in Arousal, 528
Alterations in Awareness, 535
Data Processing Deficits, 539
Seizure Disorders, 550
Alterations in Cerebral Hemodynamics, 555
Increased Intracranial Pressure, 555
Cerebral Edema, 557
Hydrocephalus, 558

Alterations in Neuromotor Function, 559
Alterations in Muscle Tone, 559
Alterations in Movement, 561
Extrapyramidal Motor Syndromes, 573
Alterations in Complex Motor Performance, 574
18 Disorders of the Central and Peripheral Nervous
Systems and the Neuromuscular Junction, 581
Barbara J. Boss and Sue E. Huether
Central Nervous System Disorders, 581
Traumatic Brain and Spinal Cord Injury, 581
Degenerative Disorders of the Spine, 594
Cerebrovascular Disorders, 598
Headache Syndromes, 607
Infection and Inflammation of the Central
Nervous System, 609
Demyelinating Disorders, 618
Peripheral Nervous System and Neuromuscular
Junction Disorders, 621
Peripheral Nervous System Disorders, 621
Neuromuscular Junction Disorders, 624
Tumors of the Central Nervous System, 626
Cranial Tumors, 626
Spinal Cord Tumors, 633
19 Neurobiology of Schizophrenia, Mood Disorders,
and Anxiety Disorders, 641
Lorey K. Takahashi
Schizophrenia, 642
Etiology and Pathophysiology, 642
Clinical Manifestations, 644
Treatment, 646
Mood Disorders: Depression and Bipolar
Disorder, 647
Etiology and Pathophysiology, 647
Clinical Manifestations, 650
Treatment, 651
Anxiety Disorders, 654
Panic Disorder, 654
Generalized Anxiety Disorder, 655
Posttraumatic Stress Disorder, 655
Obsessive-Compulsive Disorder, 656
20 Alterations of Neurologic Function
in Children, 660
Lynne M. Kerr and Sue E. Huether
Structure and Function of the Nervous System in
Children, 660
Brain Development, 661
Structural Malformations, 663
Defects of Neural Tube Closure, 663
Craniosynostosis, 666
Malformations of Cortical Development, 667
Alterations in Function: Encephalopathies, 670
Static Encephalopathies, 670
Acute Encephalopathies, 674
CONTENTS xxi
Cerebrovascular Disease in Children, 677
Perinatal Stroke, 677
Childhood Stroke, 677
Epilepsy, 678
Childhood Tumors, 681
Brain Tumors, 681
Embryonal Tumors, 684
UNIT VI The Endocrine System
21 Mechanisms of Hormonal Regulation, 689
Valentina L. Brashers, Robert E. Jones,
and Sue E. Huether
Mechanisms of Hormonal Regulation, 689
Regulation of Hormone Release, 690
Hormone Transport, 691
Hormone Receptors, 691
Plasma Membrane Receptors and Signal
Transduction, 692
Hormone Effects, 696
Structure and Function of the Endocrine
Glands, 696
Hypothalamic-Pituitary Axis, 696
Thyroid and Parathyroid Glands, 700
Endocrine Pancreas, 704
Adrenal Glands, 706
Neuroendocrine Response to Stressors, 710
Tests of Endocrine Function, 710
AGING and the Endocrine System, 711
22 Alterations of Hormonal Regulation, 717
Valentina L. Brashers, Robert E. Jones, and
Sue E. Huether
Mechanisms of Hormonal Alterations, 717
Alterations of the Hypothalamic-Pituitary
System, 718
Diseases of the Posterior Pituitary, 718
Diseases of the Anterior Pituitary, 720
Alterations of Thyroid Function, 724
Hyperthyroidism, 725
Hypothyroidism, 728
Alterations of Parathyroid Function, 731
Hyperparathyroidism, 731
Hypoparathyroidism, 733
Dysfunction of the Endocrine Pancreas: Diabetes
Mellitus, 734
Types of Diabetes Mellitus, 735
Acute Complications of Diabetes Mellitus, 743
Chronic Complications of Diabetes Mellitus, 746
Alterations of Adrenal Function, 752
Disorders of the Adrenal Cortex, 752
Disorders of the Adrenal Medulla, 758
xxii CONTENTS
UNIT VII The Reproductive Systems
23 Structure and Function of the Reproductive
Systems, 768
Gillian Tufts, George Rodway, Sue E. Huether,
and Angela Deneris
Development of the Reproductive Systems, 768
Sexual Differentiation and Hormone Production
In Utero, 768
Puberty and Reproductive Maturation, 770
The Female Reproductive System, 771
External Genitalia, 771
Internal Genitalia, 772
Female Sex Hormones, 776
The Menstrual (Ovarian) Cycle, 778
Structure and Function of the Breast, 782
The Female Breast, 782
The Male Breast, 784
The Male Reproductive System, 784
External Genitalia, 784
Internal Genitalia, 787
Spermatogenesis, 789
Male Sex Hormones, 789
Tests of Reproductive Function, 791
AGING and Reproductive Function, 791
24 Alterations of the Female Reproductive System, 800
Julia C. Phillippi, Gwen A. Latendresse, and
Kathryn L. McCance
Abnormalities of Reproductive Tract Development,
800
Alterations of Sexual Maturation, 802
Delayed Puberty, 802
Precocious Puberty, 803
Disorders of the Female Reproductive System, 804
Hormonal and Menstrual Alterations, 804
Infection and Inflammation, 813
Pelvic Organ Prolapse, 817
Benign Growths and Proliferative
Conditions, 820
Cancer, 825
Sexual Dysfunction, 834
Impaired Fertility, 835
Disorders of the Breast, 836
Galactorrhea, 836
Benign Breast Disease, 837
Cancer, 843
25 Alterations of the Male Reproductive System, 885
George Rodway and Kathryn L. McCance
Alterations of Sexual Maturation, 885
Delayed Puberty, 886
Precocious Puberty, 886
Disorders of the Male Reproductive System, 888
Disorders of the Urethra, 888
Disorders of the Penis, 888
Disorders of the Scrotum, Testis, and Epididymis,
891
Disorders of the Prostate Gland, 897
Sexual Dysfunction, 911
Impairment of Sperm Production and Quality, 912
Disorders of the Male Breast, 913
Gynecomastia, 913
Cancer, 914
26 Sexually Transmitted Infections, 918
Julia C. Phillippi and Gwen A. Latendresse
Sexually Transmitted Urogenital Infections, 919
Bacterial Infections, 919
Chlamydial Infections, 929
Viral Infections, 932
Parasitic Infections, 937
Sexually Transmitted Infections of Other Body
Systems, 940
Hepatitis B Virus, 940
Acquired Immunodeficiency Syndrome, 941
UNIT VIII The Hematologic System
27 Structure and Function of the Hematologic System,
945
Neal S. Rote and Kathryn L. McCance
Components of the Hematologic System, 945
Composition of the Blood, 945
Lymphoid Organs, 951
Development of Blood Cells, 954
Hematopoiesis, 954
Development of Erythrocytes, 959
Development of Leukocytes, 964
Development of Platelets, 965
Mechanisms of Hemostasis, 965
Function of Blood Vessels, 965
Function of Platelets, 967
Function of Clotting Factors, 969
Control of Hemostatic Mechanisms, 970
Lysis of Blood Clots, 971
Clinical Evaluation of the Hematologic System, 973
Tests of Bone Marrow Function, 973
Blood Tests, 975
PEDIATRICS and the Hematologic System, 975
AGING and the Hematologic System, 975
28 Alterations of Erythrocyte Function, 982
Neal S. Rote and Kathryn L. McCance
Anemia, 982
Classification, 982
Macrocytic-Normochromic Anemias, 987
Microcytic-Hypochromic Anemias, 989
Normocytic-Normochromic Anemias, 993
Myeloproliferative Red Blood Cell Disorders, 1002
Polycythemia Vera, 1003
Iron Overload, 1004

29 Alterations of Leukocyte, Lymphoid, and
Hemostatic Function, 1008
Anna L. Schwartz and Neal S. Rote
Alterations of Leukocyte Function, 1008
Quantitative Alterations of Leukocytes, 1009
Infectious Mononucleosis, 1011
Leukemias, 1013
Alterations of Lymphoid Function, 1023
Lymphadenopathy, 1023
Malignant Lymphomas, 1023
Plasma Cell Malignancies, 1030
Alterations of Splenic Function, 1036
Alterations of Platelets and Coagulation, 1037
Disorders of Platelets, 1037
Disorders of Coagulation, 1042
30 Alterations of Hematologic Function in
Children, 1055
Nancy E. Kline
Fetal and Neonatal Hematopoiesis, 1055
Postnatal Changes in the Blood, 1056
Erythrocytes, 1057
Leukocytes and Platelets, 1057
Disorders of Erythrocytes, 1058
Acquired Disorders, 1058
Inherited Disorders, 1062
Disorders of Coagulation and Platelets, 1070
Inherited Hemorrhagic Disease, 1070
Antibody-Mediated Hemorrhagic Disease, 1073
Leukemia and Lymphoma, 1074
Leukemia, 1074
Lymphomas, 1078
UNIT IX The Cardiovascular and Lymphatic
Systems
31 Structure and Function of the Cardiovascular and
Lymphatic Systems, 1083
Susanna G. Cunningham, Valentina L. Brashers, and
Kathryn L. McCance
Circulatory System, 1083
The Heart, 1085
Structures That Direct Circulation Through the
Heart, 1085
Structures That Support Cardiac Metabolism:
The Coronary Vessels, 1090
Structures That Control Heart Action, 1092
Factors Affecting Cardiac Output, 1101
Systemic Circulation, 1106
Structure of Blood Vessels, 1106
Factors Affecting Blood Flow, 1109
Regulation of Blood Pressure (Arterial Pressure),
1114
CONTENTS xxiii
Regulation of Coronary Circulation, 1117
Lymphatic System, 1118
Tests of Cardiovascular Function, 1119
Cardiac and Coronary Artery Evaluation, 1119
Systemic Vascular Evaluation, 1122
AGING and the Cardiovascular System, 1123
32 Alterations of Cardiovascular Function, 1129
Valentina L. Brashers
Diseases of the Veins, 1129
Varicose Veins and Chronic Venous Insufficiency,
1129
Deep Venous Thrombosis, 1130
Superior Vena Cava Syndrome, 1131
Diseases of the Arteries, 1132
Hypertension, 1132
Orthostatic (Postural) Hypotension, 1140
Aneurysm, 1140
Arterial Thrombus Formation, 1142
Embolism, 1143
Peripheral Vascular Diseases, 1144
Atherosclerosis, 1145
Peripheral Artery Disease, 1148
Coronary Artery Disease, Myocardial Ischemia,
and Acute Coronary Syndromes, 1148
Disorders of the Heart Wall, 1163
Disorders of the Pericardium, 1163
Disorders of the Myocardium: The
Cardiomyopathies, 1165
Disorders of the Endocardium, 1167
Cardiac Complications in Acquired
Immunodeficiency Syndrome, 1175
Manifestations of Heart Disease, 1175
Heart Failure, 1175
Dysrhythmias, 1182
33 Alterations of Cardiovascular Function in
Children, 1194
Nancy L. McDaniel
Development of the Cardiovascular System, 1194
Developmental Anatomy, 1194
Transitional Circulation, 1196
Postnatal Development, 1198
Congenital Heart Defects, 1198
Classification of Congenital Heart Defects and
Associated Conditions, 1199
Defects Increasing Pulmonary Blood Flow, 1202
Defects Decreasing Pulmonary Blood Flow, 1207
Obstructive Defects, 1210
Mixing Defects, 1214
Acquired Cardiovascular Disorders, 1218
Kawasaki Disease, 1218
Systemic Hypertension, 1218
Childhood Obesity, 1221
Another random document with
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 CHAPTER XXV.

A bove the fountain is a building which contains some paintings of

Polygnotus, it is the votive offering of the people of Cnidos, and
is called The Lounge by the people of Delphi, because they used to
assemble there in old times and discuss both serious and trifling
subjects. That there were many such places throughout Greece
Homer has shown in Melantho’s reviling of Odysseus:
“For you will not go to sleep at a smithy or at some lounge, but you
will keep talking here.”[118]
On the right as you enter the building is a painting of the capture of
Ilium and the return of the Greeks. And they are making preparations
for Menelaus’ hoisting sail, and his ship is painted with boys and
sailors all mixed up together on board: and in the middle of the ship
is Phrontis the pilot with two punting poles. Homer[119] has
represented Nestor among other things telling Telemachus about
Phrontis, how he was the son of Onetor, and pilot of Menelaus, and
most able in his art, and how he died as he sailed past Sunium in
Attica. And Menelaus, who was up to this time sailing with Nestor,
was now left behind, that he might discharge all due funeral rites for
Phrontis. Beneath Phrontis in the painting of Polygnotus is
Ithæmenes carrying some garment, and Echœax descending the
gangway-ladder with a brazen water-pot. And Polites and Strophius
and Alphius are represented taking down the tent of Menelaus,
which is not far from the ship. And Amphialus is taking down another
tent, a boy is sitting at his feet, but there is no inscription on him, and
Phrontis is the only person with a beard. His was the only name in
the group that Polygnotus got out of the Odyssey: the others I
imagine he invented. There too stands Briseis, and Diomede near
her, and Iphis in front of them both, they all appear to be gazing at
Helen’s beauty. And Helen is seated, and near her is Eurybates, who
has no beard, and was I suppose the herald of Odysseus. And
Helen’s handmaids are by, Panthalis standing at her side, and
Electra fastening her sandals: these names are different however
from those Homer gives in the Iliad, when he describes Helen and
her maids going on to the walls.[120] And above Helen sits a man
clothed in purple, looking very dejected: before reading the
inscription one would conjecture that it is Helenus the son of Priam.
And near Helenus is Meges, who is wounded in the shoulder, as he
is described by Lescheos of Pyrrha, the son of Æschylinus, in his
Capture of Ilium, he was wounded he says by Admetus the son of
Augeas in the night-attack of the Trojans. And next to Meges is
Lycomedes the son of Creon, who is wounded on the wrist, as
Lescheos says he was by Agenor. It is manifest that Polygnotus
must have read Lescheos’ poem, or he would not have painted their
wounds so accurately. He has also depicted Lycomedes with a third
wound in the ankle, and a fourth on the head. Euryalus also the son
of Mecisteus is represented as wounded in the head and wrist. All
these are above Helen in the painting: and next Helen is Æthra the
mother of Theseus with her head shaven, and Theseus’ son
Demophon apparently wondering whether he could save her. And
the Argives say that Melanippus was the son of Theseus by the
daughter of Sinis, and that he won the prize in the race, when the
Epigoni restored the Nemean games which were originally
introduced by Adrastus. Lescheos has stated that Æthra escaped
when Ilium was taken, and got to the Greek camp, and was
recognized by the sons of Theseus, and Demophon asked her of
Agamemnon. And he said he would willingly gratify Demophon, but
could not do so before he obtained the consent of Helen, so a
messenger was sent to Helen and she gave her consent. I think
therefore the picture represents Eurybates coming to Helen on this
errand, and delivering the message of Agamemnon. And the Trojan
women in the painting look in sad dejection as if they were captives
already. There is Andromache, with a babyboy at her breast.
Lescheos says that this babyboy was hurled from a tower, not in
consequence of any decree of the Greeks, but simply from the
private hatred of Neoptolemus. There too is Medesicaste, one of the
illegitimate daughters of Priam, of whom Homer says that she dwelt
in the town of Pedæum, and married Imbrius the son of Mentor.[121]
Andromache and Medesicaste are represented veiled: but Polyxena
has her hair plaited after the manner of maidens. The Poets
represent her to have been slain at the tomb of Achilles, and I have
seen paintings both at Athens and Pergamus beyond the river
Caicus of her death. Polygnotus has also introduced Nestor into the
same painting, with a hat on his head and a spear in his hand: and a
horse near seems to be rolling in the dust. Near the horse is the sea-
shore, and you can see the pebbles, but the rest of the scene does
not resemble a sea view.
[118] Odyssey, xviii. 328, 329. See Dr. Hayman’s admirable note
on this passage.
[119] Odyssey, iii. 276 sq.
[120] Iliad, iii. 144. Their names there are Æthra and Clymene.
[121] Iliad, xiii. 171-173.
 CHAPTER XXVI.

A bove the women between Æthra and Nestor are the captives,
Clymene, and Creusa, and Aristomache, and Xenodice.
Clymene is enumerated among the captives by Stesichorus in his
Fall of Ilium: Aristomache likewise is represented in the poem called
The Return from Ilium as the daughter of Priam, and wife of Critolaus
the son of Hicetaon: but I do not remember either poet or prose-
writer making mention of Xenodice: and as to Creusa, they say that
the Mother of the Gods and Aphrodite rescued her from slavery to
the Greeks, and that she was the wife of Æneas, though Lescheos
and the author of the Cyprian Poems represent Eurydice as the wife
of Æneas. Above these are painted Deinome Metioche Pisis and
Cleodice reclining on a couch: Deinome is the only one of these
mentioned in the poem called The Little Iliad, so I think Polygnotus
must have invented the other names. Here too is Epeus naked
knocking down the walls of Troy, and above the walls is the head
only of the Wooden Horse. Here too is Polypœtes, the son of
Pirithous, with his head bound by a fillet, and near him Acamas, the
son of Theseus, with a helmet on his head, and a crest on the
helmet. Here too is Odysseus with a coat of mail on. And Ajax the
son of Oileus is standing near the altar with a shield in his hand,
taking his oath in connection with the violation of Cassandra:
Cassandra is seated on the ground and holding fast the wooden
statue of Athene, for she tore it from its base, when Ajax dragged her
away from the altar. And the sons of Atreus are painted with their
helmets on: and on Menelaus’ shield is a representation of the
dragon that appeared to him as an omen during the sacrifice at Aulis.
They are administering the oath to Ajax. And near the painting of the
horse by Nestor’s side[122] is Neoptolemus killing Elasus, whoever
he was;[123] his dying agony is well depicted: and Astynous, who is
mentioned by Lescheos, has fallen on to his knee, and Neoptolemus
is in the act of smiting him with the sword. And Polygnotus has
represented Neoptolemus alone of all the Greeks continuing to
butcher the Trojans, that the painting should correspond with the
scenes depicted on the tomb of Neoptolemus. Homer indeed calls
Achilles’ son everywhere by the name of Neoptolemus, but the
Cyprian Poems say he was called Pyrrhus by Lycomedes, and that
the name Neoptolemus was given him by Phœnix, because he[124]
was very young when he first went to the wars. Here too is the
painting of an altar, and a little boy clinging to it in dire fear: a brazen
coat of mail lies on the altar, such as was worn in old times, for in our
days we seldom see such. It consisted of two pieces called Gyala,
one a protection for the breast and belly, the other for the back, both
joined together by clasps. And such coats of mail would afford
sufficient protection without a shield: and so Homer represented
Phorcys the Phrygian without a shield, because he was armed with
this kind of coat of mail.[125] In Polygnotus’ painting I recognize a
coat of mail of this kind: and in the temple of Ephesian Artemis
Calliphon of Samos has painted some women fitting this kind of coat
of mail on Patroclus. And Polygnotus has represented Laodice
standing on the other side of the altar. I do not find her name
mentioned by any poet among the captive Trojan women: and it
seems probable enough that the Greeks let her go. For Homer has
represented in the Iliad that Menelaus and Odysseus were
entertained by Antenor, and that Laodice was the wife of Antenor’s
son Helicaon.[126] And Lescheos states that Helicaon was wounded
in the night-engagement, and recognized by Odysseus, and rescued
out of the battle alive. It follows therefore, from the affection of
Menelaus and Odysseus for the family of Antenor, that Agamemnon
and Menelaus would have offered no violence to Helicaon’s wife.
What Euphorion of Chalcis therefore has written about Laodice is
very improbable. And next Laodice is a stone prop, and a bronze
laver on it. And Medusa sits on the ground holding this prop with
both her hands. Whoever has read the Ode of Himeræus will include
her among the daughters of Priam. And near Medusa is an old
woman closely shaven, (or possibly a eunuch), with a naked child in
his or her arms: the child’s hand is before its eyes for fear.
[122] See ch. 26 nearly at the end.
[123] An Elasus is mentioned in Iliad, xvi. 696.
[124] He (i.e. Neoptolemus). Siebelis very ingeniously suggests ὁ
Ἀχιλλέως. I accept that suggestion as necessary to the sense.
[125] See Iliad, xvii. 314. Pausanias goes a little beyond Homer
methinks.
[126] See Iliad, iii. 205-207. Also 122-124.
 CHAPTER XXVII.

O f the dead in the painting are Pelis naked,[127] lying on his back,
and underneath him Eioneus and Admetus both in their coats of
mail. According to Lescheos Eioneus was slain by Neoptolemus, and
Admetus by Philoctetes. And above these are others, near the laver
Leocritus, the son of Polydamas, who was killed by Odysseus, and
near Eioneus and Admetus Corœbus the son of Mygdon. This
Mygdon has a famous tomb on the borders of the Stectorenian
Phrygians, and poets have given those Phrygians the name of
Mygdones after him. Corœbus came to wed Cassandra, and was
killed by Neoptolemus according to the prevalent tradition, but by
Diomede according to Lescheos. And above Corœbus are Priam
and Axion and Agenor. Lescheos says that Priam was not slain at
the altar of Household Zeus, but was torn away from the altar and
killed by Neoptolemus with no great difficulty at the doors of the
palace. As to Hecuba, Stesichorus in his Fall of Ilium has stated that
she was taken to Lycia by Apollo. And Lescheos says that Axion was
the son of Priam, and killed by Eurypylus the son of Euæmon. The
same poet states that Agenor was killed by Neoptolemus. And
Echeclus, Agenor’s son, seems to have been slain by Achilles. And
Sinon, the companion of Odysseus, and Anchialus are carrying out
the corpse of Laomedon for burial. There is another dead person in
the painting, Eresus by name; no poet, so far as my knowledge
goes, has sung either of Eresus or Laomedon. There is a painting
also of the house of Antenor, and a leopard’s skin hung up over the
porch, as a sign to the Greeks not to meddle with the family of
Antenor. And Theano, Antenor’s wife, is painted with her sons,
Glaucus seated on his armour, and Eurymachus seated on a stone.
Near him stands Antenor with his daughter Crino, who is carrying her
baby boy. All these are depicted with sorrowful countenances. The
servants are placing a chest and other articles on the back of an ass,
on which a little boy also sits. And under this painting is the following
Elegiac couplet by Simonides.
“Polygnotus of Thasos, the son of Aglaophon, painted
these incidents in the capture of Ilium.”
[127] Naked here, and in connection with Epeus in ch. 26,
probably only means without armour on. Cf. “Nudus ara, sere
nudus.” Virg. Georg. i. 299.
 CHAPTER XXVIII.

T he other part of the painting, that on the left, represents

Odysseus descending to Hades, to consult the soul of Tiresias
about his return home. In the painting is a river, which is obviously
Acheron, and there are some reeds growing in it, and some fishes so
indistinct that they look like the ghosts of fishes. And there is a boat
on the river, and a ferryman with his oars. Polygnotus has followed (I
think) here the description, in the poem called the Minyad, about
Theseus and Pirithous.
“Unwillingly did old Charon admit these living persons into his boat
meant for the use of the dead.”
Polygnotus has accordingly represented Charon as old. The persons
on board are not very easy to trace. But there is Tellis, looking like a
youth, and Cleobœa still a virgin, with a cist on her knees such as
they use in the worship of Demeter. Of Tellis I know nothing more
than that Archilochus was his greatgrandson. And Cleobœa they say
first introduced the mysteries of Demeter from Paros to Thasos. And
on the bank of the Acheron near Charon’s boat a son, who had not
treated his father well, is being strangled by his father. For the
ancients reverenced fathers exceedingly,[128] as one may infer
among other things from the conduct of those called Pious at
Catana, who, when Catana was consumed by fire from Mount Ætna,
took no account of silver or gold, but the one took up his mother, the
other his father, and fled for their lives. And as they advanced with
great difficulty for the flame gathered on them, (but they would not
for all that set their parents down), the flames they say divided so as
to let them pass without hurt. These young men are still honoured at
Catana. And in Polygnotus’ painting near the man who ill-treated his
father, and has consequently a bad time of it in Hades, is a
sacrilegious wretch suffering punishment. The woman[129] who is
punishing him seems well acquainted with poison, and other things
that can do man harm. Men were also in those days remarkable for
piety to the gods, as the Athenians shewed when they captured the
temple of Olympian Zeus at Syracuse, for they removed none of the
votive offerings, and left the former priest still in charge. Datis the
Mede also showed the same piety both in word and in deed, in word
to the Delians, and in deed when, finding a statue of Apollo on a
Phœnician ship, he gave it back to the people of Tanagra to take to
Delium. In those days all men honoured the deity, and so Polygnotus
introduced into his painting the sacrilegious wretch suffering
punishment. Above those I have described is Eurynomus, who
according to the Antiquarians at Delphi is a demon in Hades, and
eats the flesh of the dead clean to the bones. No such person
however is mentioned in the Odyssey, or in the Minyad, or in The
Return from Ilium, though these poems contain accounts of Hades
and its horrors. I shall therefore describe Eurynomus’ appearance in
this painting. His colour is a blueish-black, like that of the flies that
infest meat,[130] and he shows his fangs, and sits on a vulture’s skin.
And next him are Auge and Iphimedea from Arcadia. Auge came to
Teuthras in Mysia, and, of all the women who consorted with
Hercules, bare a son most like him. And Iphimedea is treated with
very great honour by the Carians who dwell at Mylasa.
[128] See for example Hesiod, Works and Days, 331, 332, with
context.
[129] Boettiger takes this woman to be Punishment personified.
[130] Our “bluebottles.”
 CHAPTER XXIX.

A bove those I have already mentioned are Perimedes and

Eurylochus,[131] the comrades of Odysseus, with the victims
which are black rams. And next them is a man seated, whom the
inscription states to be Ocnus. He is representing rope-making, and
a she-ass near him eats the rope as fast as he makes it. This Ocnus
they say was an industrious man, who had an extravagant wife: and
whatever he got together by industry was very soon spent by her.
This picture therefore of Polygnotus is supposed to be a skit on
Ocnus’ wife. And I know that the Ionians, when they see anyone
labouring hard to no profit, say that he is weaving Ocnus’ rope.[132]
However those who divine by the flight of birds give the name of
Ocnus to a very rare kind of heron, both large and handsome. Tityus
too is in the picture, no longer being tortured, but worn out by his
continuous punishment to a mere shadow. And if you look at the next
part of the picture, you will see Ariadne very near the man who is
ropemaking: she is sitting on a rock, and looking at her sister
Phædra, who is suspended to a rock by a rope which she holds in
both hands. She is so represented to make her end appear more
decorous. And Dionysus took Ariadne from Theseus either by some
chance, or purposely preparing an ambush for him, sailing against
him with a larger armament. This was the same Dionysus, I take it,
who was the first to invade India, and the first to throw a bridge over
the river Euphrates; the place where he built this bridge was called
Zeugma, and a rope is preserved to this day, wreathed with tendrils
of the vine and ivy, which was used in the construction of the bridge.
Both Greeks and Egyptians have many legends about Dionysus.
And below Phædra Chloris is reclining on the knees of Thyia: no one
will err who states that there was a great friendship between these
two women in their lifetime: and both came from the same
neighbourhood, Orchomenus in Bœotia.[133] There are other
traditions about them, as that Poseidon had an intrigue with Thyia,
and that Chloris was married to Poseidon’s son Neleus. And next
Thyia is Procris the daughter of Erechtheus, and next her, with her
back towards her, is Clymene, who is represented in The Return
from Ilium to have been the daughter of Minyas, and the wife of
Cephalus the son of Deion, and mother by him of Iphiclus. All the
poets agree that Procris was Cephalus’ wife before Clymene was,
and that she was murdered by her husband. And beyond Clymene in
the interior of the painting is the Theban Megara, who was Hercules’
wife, but eventually repudiated by him, because he lost all his
children by her, and so did not think his marriage with her a lucky
one. Above the head of those women I have mentioned is the
daughter of Salmoneus sitting on a stone, and beside her Eriphyle is
standing, lifting her fingers through her dress to her neck. You may
conjecture that she is holding the famous necklace in the hand which
is concealed by the folds of her dress. And above Eriphyle is
Elpenor, and Odysseus kneeling, holding his sword over a ditch: and
Tiresias the prophet is approaching the ditch, and near Tiresias is
Anticlea, the mother of Odysseus, sitting on a stone. And Elpenor is
wearing the coarse plaited coat usual among sea-faring men. And
below Odysseus Theseus and Pirithous are seated on the
enchanted rock, Theseus has both his own sword and that of
Pirithous, and Pirithous is looking at his like one indignant that
swords are useless for their present venture. Panyasis has
represented Theseus and Pirithous as not fastened to their seat, but
that the rock grew to them instead of fetters. The friendship between
Theseus and Pirithous has been alluded to by Homer both in the
Iliad and Odyssey. In the latter Odysseus says to the Phæacians,
“I then perhaps had seen the heroes of former times,
whom I fain would have seen, as Theseus and Pirithous,
the famous sons of the gods.”[134]
And in the Iliad, in his chiding of Agamemnon and Achilles, Nestor
uses the following words:[135]
“I never before saw such heroes nor shall I e’er again, as Pirithous,
and Dryas shepherd of his people, and Cæneus and Exadius and
divine Polyphemus, and Theseus son of Ægeus like to the
Immortals.”
[131] Odyssey, xi. 23 sq.
[132] Propertius has an allusion to this, v. iii. 21, 22.
[133] It will be seen that I adopt the suggestion of Siebelis. The
reading is doubtful.
[134] Odyssey, xi. 630, 631. The last line is in brackets in modern
editions.
[135] Iliad, i. 262-265. The last line here is in brackets in modern
editions.
 CHAPTER XXX.

P olygnotus has painted next the daughters of Pandareus, as to

whom Homer says, in a speech of Penelope, that their parents
died through the wrath of the gods when they were still maidens, and
that as they were orphans they were brought up by Aphrodite, and
received gifts from other goddesses, as from Hera prudence and
beauty, from Artemis tallness of stature, from Athene an education fit
for women. But when Aphrodite went up to heaven to obtain a good
match for the girls from Zeus, they were carried off in her absence by
the Harpies and given by them to the Furies. Such at least is
Homer’s account about them.[136] And Polygnotus has painted them
crowned with flowers, and playing with dice. Their names were
Camiro and Clytie. Pandareus was you must know a Milesian from
Cretan Miletus, and an associate of Tantalus both in his theft and
perjury. And next the daughters of Pandareus is Antilochus with one
of his feet on a stone, and his head on both his hands. And next him
is Agamemnon, leaning on his sceptre under his left arm, and with a
staff in his hands. And Protesilaus and Achilles are seated, and
looking at one another. And above Achilles is Patroclus standing.
None of these have beards except Agamemnon. And above them is
painted the stripling Phocus, and Iaseus with a beard, who is trying
to take a ring from Phocus’ left hand. The circumstances are as
follows. When Phocus, the son of Æacus, crossed over from Ægina
to the country now called Phocis, and obtained the sovereignty over
the men in that part of the mainland, and meant to dwell there,
Iaseus was most friendly with him, and offered him various presents,
as was very natural, and among others a stone signet-ring set in
gold: and when Phocus not long after sailed back to Ægina, Peleus
contrived his death: and so in the painting, as a memorial of their
friendship, Iaseus is represented as wishing to look at the signet-
ring, and Phocus letting him take it. Above them is Mæra sitting on a
stone: in The Return from Ilium she is said to have died a virgin, and
to have been the daughter of Prœtus, the son of Thersander and
grandson of Sisyphus. And next Mæra is Actæon, (the son of
Aristæus), and his mother, both seated on a deerskin and holding a
fawn in their hands. And a hound for hunting is near: these are
emblems of the life and death of Actæon. And in the lower part of the
painting next to Patroclus is Orpheus sitting on a hill, with a harp in
his left hand, and with his right hand he is touching the branches of a
willow-tree, and he leans against the tree: the scene looks like the
grove of Proserpine, where Homer tells us poplars and willows grew.
[137] And Orpheus’ dress is Greek, no part of his attire is Thracian,
not even his hat. And Promedon is leaning against the other side of
the willow-tree. Some think Polygnotus introduced Promedon’s name
into legend. Others say he was a Greek who was passionately fond
of music, and especially of that of Orpheus. In the same part of the
painting is Schedius, who led the Phocians to Troy, with a dagger in
his hand, and a garland of grass on his head. And next him sits
Pelias, with beard and head all hoary, gazing at Orpheus. And
Thamyris sitting near Pelias is blind and dejected in mien, with thick
hair and beard, his lyre is broken and the strings torn asunder. Above
him is Marsyas, seated on a stone, and near him Olympus, a
handsome boy, learning to play on the pipe. The Phrygians at
Celænæ represent that the river flowing through their town was
formerly this piper Marsyas, and that the piping in honour of Cybele
was his invention: they say also that they repulsed the army of the
Galati through his aid, as he assisted them both with the water of the
river and his melody.
[136] Odyssey, xx. 63 sq.
[137] Odyssey, x. 509, 510.
 CHAPTER XXXI.

I f you look again at the upper part of the painting, you will see next
Actæon Salaminian Ajax Palamedes and Thersites playing with
dice, which were the invention of Palamedes. And the other Ajax is
looking at them playing: he looks like a shipwrecked man, and his
body is wet with the foam of the sea. Polygnotus seems to have
purposely collected together the enemies of Odysseus. And Ajax the
son of Oileus hated Odysseus, because he urged the Greeks to
stone him for his rape of Cassandra. And I have read in the Cyprian
Poems that Palamedes going a fishing was drowned by Diomede
and Odysseus. And a little above Ajax the son of Oileus is Meleager
painted, looking at Ajax. All these except Palamedes have beards.
As to the death of Meleager, Homer informs us that a Fury heard
Althæa cursing him, and that this was the cause of his death. But the
poems called the Great EϾ and the Minyad agree in stating that
Apollo assisted the Curetes against the Ætolians, and killed
Meleager. As to the famous tradition about the firebrand; how it was
given to Althæa by the Fates, and how Meleager was fated not to die
till it was consumed by fire, and how Althæa set it on fire in a rage,
all this was first described by Phrynichus, the son of Polyphradmon,
in his play called Pleuroniæ:
“He escaped not dread fate, but was consumed by the swift flame,
as soon as the ill-contrived firebrand was set on fire by his stern
mother.”
Phrynichus does not however seem to introduce the legend as his
own invention, but only to allude to it as one well-known throughout
Greece.
In the lower part of the painting next Thracian Thamyris sits Hector,
like a man oppressed with sorrow, with both his hands on his left
knee. And next him is Memnon seated on a stone, and close to
Memnon Sarpedon, who is leaning his head on both his hands, and
one of Memnon’s hands is on Sarpedon’s shoulder. All of these have
beards, and some birds are painted on Memnon’s cloak. These birds
are called Memnonides, and every year the people near the
Hellespont say they come on certain days to Memnon’s tomb, and
sweep all the parts round the tomb that are bare of trees or grass,
and sprinkle them with their wings which they wet in the river
Æsepus. And near Memnon is a naked Ethiopian boy, for Memnon
was king of the Ethiopians. However he did not come to Ilium from
Ethiopia, but from Susa in Persia and the river Choaspes, after
vanquishing all the tribes in that neighbourhood. The Phrygians still
shew the road by which he marched his army, the shortest route
over the mountains.[138]
Above Sarpedon and Memnon is Paris, as yet a beardless youth. He
is clapping his hands like a rustic, apparently to attract the notice of
Penthesilea, who looks at him, but by the toss of her head seems to
despise him, and jeer at him as a boy. She is represented as a
maiden with a Scythian bow, and a leopard’s skin round her
shoulders. Above her are two women carrying water in broken
pitchers, one still in her prime, the other rather advanced in life.
There is no inscription on either of them, except a notification that
they are both among the uninitiated. Above this pair are Callisto the
daughter of Lycaon, and Nomia, and Pero the daughter of Neleus,
from every suitor of whom her father asked the kine of Iphiclus.[139]
Callisto has a bear-skin for her coverlet, and her feet are on the
knees of Nomia. I have before stated that the Arcadians consider
Nomia one of their local Nymphs. The poets say the Nymphs are
long-lived but not immortal. Next to Callisto and the other women
with her is a hill, up which Sisyphus the son of Æolus is laboriously
rolling a stone. There is also a winejar in the painting, and an old
man, and a boy, and two women, a young woman under a rock, and
an old woman near the old man. Some men are bringing water, and
the old woman’s water-pot appears to be broken, and she is pouring
all the water in the pitcher into the winejar. One is inclined to
conjecture that they are people making a mock of the Eleusinian
mysteries. But the older Greeks considered the Eleusinian mysteries
as much above all other religious services, as the gods are superior
to heroes. And under the winejar is Tantalus, undergoing all those
punishments mentioned by Homer,[140] and also terrified lest a stone
overhanging his head should fall on him. It is plain that Polygnotus
followed the account of Archilochus: but I do not know whether
Archilochus invented the addition to the legend about the stone, or
merely related what he had heard from others.
Such is a full account of the various details in this fine painting of the
Thasian painter.
[138] So Corayus. The meaning and reading is very obscure.
[139] See Homer’s Odyssey, xi. 287 sq. Neleus refused the
matchless Pero’s hand to any suitor who would not bring as a
wedding-present these kine of Iphiclus.
[140] Odyssey, xi. 582-592.
 CHAPTER XXXII.

N ear the temple precincts is a handsome theatre. And as you

ascend from the precincts you see a statue of Dionysus, the
offering of the men of Cnidos. In the highest part of the city is a
stadium made of the stone of Mount Parnassus, till the Athenian
Herodes embellished it with Pentelican marble. I have now
enumerated the most remarkable things still to be seen at Delphi.
About 60 stades from Delphi on the road to Mount Parnassus is a
brazen statue, and from thence it is an easy ascent for an active
man, or for mules and horses to the Corycian cavern. It got its name,
as I pointed out a little back,[141] from the Nymph Corycia, and of all
the caverns I have seen is best worth a visit. The various caverns on
sea-coasts are so numerous that one could not easily enumerate
them: but the most remarkable whether in Greece or in foreign lands
are the following. The Phrygians near the river Pencala, who
originally came from Arcadia and the Azanes, show a round and lofty
cavern called Steunos, which is sacred to the Mother of the Gods,
and contains her statue. The Phrygians also, who dwell at
Themisonium above Laodicea, say that when the army of the Galati
harried Ionia and the neighbouring districts, Hercules and Apollo and
Hermes came to their aid: and showed their chief men a cavern in a
dream, and bade them hide there their women and children. And so
in front of this cavern they have statuettes of Hercules and Hermes
and Apollo, whom they call The Cavern-Gods. This cavern is about
30 stades from Themisonium, and has springs of water in it, there is
no direct road to it, nor does the light of the sun penetrate into it, and
the roof in most of the cavern is very near the ground. The
Magnesians also at a place called Hylæ near the river Lethæus have
a cavern sacred to Apollo, not very wonderful for size, but containing
a very ancient statue of Apollo, which supplies strength for any
action. Men made holy by the god leap down rocks and precipices
unhurt, and tear up huge trees by the roots, and carry them with
ease through mountain passes. But the Corycian cavern excels both
of these, and through most of it you can walk without needing
torches: and the roof is a good height from the ground, and water
bubbles up from springs, but still more oozes from the roof, so that
there are droppings from the roof all over the floor of the cavern. And
those that dwell on Mount Parnassus consider it sacred to Pan and
the Corycian Nymphs. It is a feat even for an active man to scale the
heights of Parnassus from it, for they are higher than the clouds, and
on them the Thyiades carry on their mad revels in honour of
Dionysus and Apollo.
Tithorea is about 80 stades from Delphi viâ Mount Parnassus, but
the carriage road by a way less mountainous is many stades longer.
Bacis in his oracles and Herodotus in his account of the invasion of
Greece by the Medes differ as to the name of the town. For Bacis
calls the town Tithorea, but Herodotus calls it Neon, and gives the
name Tithorea to the summit of Parnassus, where he describes the
people of the town fleeing on the approach of the Medes. It seems
probable therefore that Tithorea was originally the name for the
entire district, but as time went on the people, flocking into the town
from the villages, called it Tithorea and no longer Neon. And the
people of the place say it got its name from the Nymph Tithorea, one
of those Nymphs who according to the legendary lore of poets were
born of trees and especially oak-trees.[142] A generation before me
the deity changed the fortunes of Tithorea for the worse. There is the
outline of a theatre, and the precincts of an ancient market-place, still
remaining. But the most remarkable things in the town are the grove
and shrine and statue of Athene, and the tomb of Antiope and
Phocus. In my account of the Thebans I have shewn how Antiope
went mad through the anger of Dionysus, and why she drew on her
the anger of the god, and how she married Phocus the son of
Ornytion, of whom she was passionately fond, and how they were
buried together. I also gave the oracle of Bacis both about this tomb
and that of Zethus and Amphion at Thebes. I have mentioned all the
circumstances worth mention about the town. A river called
Cachales flows by the town, and furnishes water to its inhabitants,
who descend to its banks to draw water.
At 70 stades distance from Tithorea is a temple of Æsculapius, who
is called Archegetes, and is greatly honoured both by the Tithoreans