eTextbook 978-0323088541

Pathophysiology: The Biologic Basis

for Disease in Adults and Children
(Pathophysiology the Biologic Basis)
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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
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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.
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 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
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 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
xxiv CONTENTS

UNIT X The Pulmonary System Acute Lung Injury/Acute Respiratory Distress

34 Structure and Function of the Pulmonary System, Syndrome, 1310
1225 Cystic Fibrosis, 1310
Valentina L. Brashers Sudden Infant Death Syndrome, 1313
Structures of the Pulmonary System, 1225 UNIT XI The Renal and Urologic Systems
Conducting Airways, 1225
37 Structure and Function of the Renal and Urologic
Gas-Exchange Airways, 1229
Systems, 1319
Pulmonary and Bronchial Circulation, 1229
Alexa K. Doig and Sue E. Huether
Chest Wall and Pleura, 1231
Structures of the Renal System, 1319
Functions of the Pulmonary System, 1232
Structures of the Kidney, 1319
Ventilation, 1232
Urinary Structures, 1325
Gas Transport, 1238
Renal Blood Flow, 1326
Tests of Pulmonary Function, 1243
Autoregulation of Renal Blood Flow, 1326
AGING and the Pulmonary System, 1244
Neural Regulation, 1326
35 Alterations of Pulmonary Function, 1248
Hormones and Other Factors, 1327
Valentina L. Brashers and Sue E. Huether
Kidney Function, 1327
Clinical Manifestations of Pulmonary Alterations,
Nephron Function, 1327
1248
Concentration and Dilution of Urine, 1331
Signs and Symptoms of Pulmonary Disease, 1248
Renal Hormones, 1333
Conditions Caused by Pulmonary Disease or
Tests of Renal Function, 1334
Injury, 1251
The Concept of Clearance, 1334
Disorders of the Chest Wall and Pleura, 1253
Blood Tests, 1335
Disorders of the Chest Wall, 1253
Urinalysis, 1335
Pleural Abnormalities, 1254
AGING and Renal Function, 1336
Pulmonary Disorders, 1255
38 Alterations of Renal and Urinary Tract Function,
Restrictive Lung Disorders, 1255
1340
Obstructive Pulmonary Disease, 1263
Alexa K. Doig and Sue E. Huether
Respiratory Tract Infections, 1271
Urinary Tract Obstruction, 1340
Viral Pneumonia, 1273
Upper Urinary Tract Obstruction, 1340
Pulmonary Vascular Disease, 1275
Lower Urinary Tract Obstruction, 1344
Malignancies of the Respiratory
Tumors, 1347
Tract, 1278
Urinary Tract Infection, 1349
36 Alterations of Pulmonary Function
Causes of Urinary Tract Infection, 1349
in Children, 1290
Types of Urinary Tract Infection, 1350
Valentina L. Brashers and Sue E. Huether
Glomerular Disorders, 1352
Structure and Function, 1290
Glomerulonephritis, 1352
Upper Airway, 1290
Nephrotic and Nephritic Syndromes, 1358
Lower Airways and Lung Parenchyma, 1290
Acute Kidney Injury, 1359
Chest Wall Dynamics, 1292
Classification of Kidney Dysfunction, 1359
Metabolic Characteristics, 1292
Acute Kidney Injury, 1360
Immunologic Incompetence, 1292
Chronic Kidney Disease, 1364
Physiologic Control of Respiration, 1293
Creatinine and Urea Clearance, 1366
Disorders of the Upper Airways, 1293
Fluid and Electrolyte Balance, 1367
Upper Airway Obstruction, 1293
Calcium, Phosphate, and Bone, 1368
Disorders of the Lower Airways, 1301
39 Alterations of Renal and Urinary Tract Function in
Respiratory Distress Syndrome of the Newborn,
Children, 1376
1301
Patti Ring and Sue E. Huether
Bronchopulmonary Dysplasia, 1303
Structure and Function of the Urinary System in
Respiratory Tract Infections, 1305
Children, 1376
Aspiration Pneumonitis, 1308
Development of the Urinary System, 1376
Bronchiolitis Obliterans, 1308
Fluid and Electrolyte Balance in Children, 1377
Asthma, 1308

Alterations in Renal and Bladder Function in
Children, 1378
Congenital Abnormalities, 1378
Glomerular Disorders, 1381
Kidney Injury, 1385
Wilms Tumor, 1385
Bladder Disorders, 1386
Urinary Incontinence, 1388
UNIT XII The Digestive System
40 Structure and Function of the Digestive System, 1393
Alexa K. Doig and Sue E. Huether
The Gastrointestinal Tract, 1393
Mouth and Esophagus, 1395
Stomach, 1396
Small Intestine, 1400
Large Intestine, 1407
Intestinal Bacteria, 1408
Accessory Organs of Digestion, 1409
Liver, 1409
Gallbladder, 1413
Exocrine Pancreas, 1413
Tests of Digestive Function, 1415
Gastrointestinal Tract, 1415
Liver, 1416
Gallbladder, 1416
Exocrine Pancreas, 1416
AGING and the Gastrointestinal System, 1417
41 Alterations of Digestive Function, 1423
Alexa K. Doig and Sue E. Huether
Disorders of the Gastrointestinal Tract, 1423
Clinical Manifestations of Gastrointestinal
Dysfunction, 1423
Disorders of Motility, 1428
Gastritis, 1434
Peptic Ulcer Disease, 1435
Malabsorption Syndromes, 1439
Inflammatory Bowel Disease, 1440
Intestinal Vascular Insufficiency, 1446
Disorders of Nutrition, 1446
Disorders of the Accessory Organs of Digestion, 1451
Common Complications of Liver Disorders, 1451
Disorders of the Liver, 1457
Disorders of the Gallbladder, 1463
Disorders of the Pancreas, 1464
Cancer of the Digestive System, 1466
Cancer of the Gastrointestinal Tract, 1466
Cancer of the Accessory Organs of Digestion, 1472
42 Alterations of Digestive Function in Children, 1486
Sue E. Huether
Disorders of the Gastrointestinal Tract, 1486
Congenital Impairment of Motility, 1486
CONTENTS xxv
Esophageal Malformations, 1487
Acquired Impairment of Motility, 1492
Impairment of Digestion, Absorption, and
Nutrition, 1494
Diarrhea, 1499
Disorders of the Liver, 1500
Disorders of Biliary Metabolism and Transport,
1500
Inflammatory Disorders, 1502
Portal Hypertension, 1502
Metabolic Disorders, 1503
UNIT XIII The Musculoskeletal System
43 Structure and Function of the Musculoskeletal
System, 1510
Christy L. Crowther-Radulewicz
Structure and Function of Bones, 1510
Elements of Bone Tissue, 1511
Types of Bone Tissue, 1517
Characteristics of Bone, 1517
Maintenance of Bone Integrity, 1519
Structure and Function of Joints, 1520
Fibrous Joints, 1520
Cartilaginous Joints, 1520
Synovial Joints, 1522
Structure and Function of Skeletal Muscles, 1526
Whole Muscle, 1527
Components of Muscle Function, 1533
Tests of Musculoskeletal Function, 1535
Tests of Bone Function, 1535
Tests of Joint Function, 1535
Tests of Muscular Function, 1535
AGING and The Musculoskeletal System, 1536
44 Alterations of Musculoskeletal Function, 1540
Christy L. Crowther-Radulewicz and Kathryn L. McCance
Musculoskeletal Injuries, 1540
Skeletal Trauma, 1540
Support Structure Trauma, 1545
Disorders of Bones, 1550
Metabolic Bone Diseases, 1550
Infectious Bone Disease: Osteomyelitis, 1558
Bone Tumors, 1560
Disorders of Joints, 1565
Osteoarthritis, 1565
Classic Inflammatory Joint Disease, 1568
Disorders of Skeletal Muscle, 1578
Secondary Muscular Dysfunction, 1578
Muscle Membrane Abnormalities, 1581
Metabolic Muscle Diseases, 1582
Inflammatory Muscle Diseases: Myositis, 1583
Myopathy, 1585
Muscle Tumors, 1585
xxvi CONTENTS

45 Alterations of Musculoskeletal Function in 47 Alterations of the Integument in Children, 1653

Children, 1591 Noreen Heer Nicol and Sue E. Huether
Kristen Lee Carroll and Lynn M. Kerr Acne Vulgaris, 1653
Musculoskeletal Development in Children, 1591 Dermatitis, 1654
Bone Formation, 1591 Atopic Dermatitis, 1654
Bone Growth, 1592 Diaper Dermatitis, 1655
Skeletal Development, 1593 Infections of the Skin, 1656
Muscle Growth, 1593 Bacterial Infections, 1656
Musculoskeletal Alterations in Children, 1593 Fungal Infections, 1657
Congenital Defects, 1593 Viral Infections, 1658
Abnormal Density or Modeling of the Skeleton, Insect Bites and Parasites, 1661
1597 Scabies, 1661
Bone Infection: Osteomyelitis, 1601 Pediculosis (Lice Infestation), 1661
Juvenile Idiopathic Arthritis, 1603 Fleas, 1662
Avascular Diseases of the Bone: Osteochondrosis, Bedbugs, 1662
1604 Hemangiomas and Cutaneous Vascular
Cerebral Palsy, 1606 Malformations, 1662
Muscular Dystrophy, 1606 Hemangiomas, 1662
Musculoskeletal Tumors in Children, 1609 Vascular Malformations, 1663
Nonaccidental Trauma, 1612 Other Skin Disorders, 1664
Miliaria, 1664
UNIT XIV The Integumentary System
Erythema Toxicum Neonatorum, 1664
46 Structure, Function, and Disorders of the Stevens-Johnson Syndrome and Toxic Epidermal
Integument, 1616 Necrolysis, 1664
Sue Ann McCann and Sue E. Huether
Structure and Function of the Skin, 1616 UNIT XV Multiple Interacting Systems
Layers of the Skin, 1616 48 Shock, Multiple Organ Dysfunction Syndrome, and
Subcutaneous Layer, 1618 Burns in Adults, 1668
AGING and Skin Integrity, 1619 Linda L. Martin, Dennis J. Cheek, and Stephen E. Morris
Tests of Skin Function, 1619 Shock, 1668
Clinical Manifestations of Skin Dysfunction, 1619 Cellular Alterations and Impairment of Cellular
Disorders of the Skin, 1627 Metabolism, 1669
Inflammatory Disorders, 1627 Types of Shock, Clinical Manifestations, and
Papulosquamous Disorders, 1629 Treatment, 1671
Vesiculobullous Disorders, 1632 Multiple Organ Dysfunction Syndrome, 1679
Infections, 1634 Burns, 1685
Vascular Disorders, 1638 Epidemiology and Etiology, 1685
Tick Bites, 1640 Burn Wound Depth, 1685
Benign Tumors, 1640 49 Shock, Multiple Organ Dysfunction Syndrome, and
Skin Cancer, 1641 Burns in Children, 1699
Cold Injury, 1646 Mary Fran Hazinski, Mary A. Mondozzi, and
Disorders of the Hair, 1646 Rose A. Urdiales Baker
Alopecia, 1646 Shock and Multiple Organ Dysfunction
Hirsutism, 1647 Syndrome, 1699
Disorders of the Nail, 1647 Types of Shock, 1700
Paronychia, 1647 Clinical Manifestations of Shock, 1700
Onychomycosis, 1647 Reperfusion and Inflammatory Injury, 1710
Evaluation and Treatment of Shock, 1710
Burns, 1715
Severity of Injury, 1716
Interactive Review – Pathophysiology

e1
 Interactive Review – Unit I

e2
 CHAPTER

1
Cellular Biology
Kathryn L. McCance

http://evolve.elsevier.com/McCance/
• Review Questions and Answers

CHAPTER OUTLINE
Prokaryotes and Eukaryotes, 2 Cellular Metabolism, 25
Cellular Functions, 2 Role of Adenosine Triphosphate, 25
Structure and Function of Cellular Components, 2 Food and Production of Cellular Energy, 26
Nucleus, 2 Oxidative Phosphorylation, 27
Cytoplasmic Organelles, 4 Membrane Transport: Cellular Intake and Output, 28
Plasma Membranes, 11 Movement of Water and Solutes, 28
Cellular Receptors, 16 Transport by Vesicle Formation, 33
Cell-to-Cell Adhesions, 17 Movement of Electrical Impulses: Membrane Potentials, 36
Extracellular Matrix, 17 Cellular Reproduction: The Cell Cycle, 37
Specialized Cell Junctions, 18 Phases of Mitosis and Cytokinesis, 37
Cellular Communication and Signal Transduction, 20 Rates of Cellular Division, 37
Signal Transduction, 21 Growth Factors, 38
Extracellular Messengers and Channel Regulation, 22 Tissues, 39
Second Messengers, 22 Tissue Formation, 39
Types of Tissues, 39

All body functions depend on the integrity of cells. Therefore,
an understanding of cellular biology is intrinsically necessary for
an understanding of disease. An overwhelming amount of infor-
mation is revealing how cells behave as a multicellular “social”
organism. At the heart of cellular biology is cellular communi-
cation (“cellular crosstalk”)—how messages originate and are
transmitted, received, interpreted, and used by the cell. Fossil
records suggest that unicellular organisms resembling bacteria
were present on earth 3.5 billion years ago, yet it took another 2.5
billion years for the first multicellular organisms to appear. This
delay was seemingly slow because elaborate signaling mechanisms
had to evolve that would allow cells to crosstalk. This streamlined
conversation between, among, and within cells maintains cellular
function and specialization. Intercellular signals allow each cell
to determine its position and specialized role. Cells must demon-
strate a “chemical fondness” for other cells and their surround-
ing environment to maintain the integrity of the entire organism.
When they no longer tolerate this fondness, the conversation
breaks down and cells either adapt (sometimes altering function)
or become vulnerable to isolation, injury, or disease.
1
2 UNIT I The Cell
PROKARYOTES AND EUKARYOTES
Living cells generally are divided into two major classes—
eukaryotes and prokaryotes. The cells of higher animals and
plants are eukaryotes, as are the single-celled organisms fungi,
protozoa, and most algae. Prokaryotes include cyanobacteria
(blue-green algae), bacteria, and rickettsiae. Prokaryotes tra-
ditionally were studied as core subjects of molecular biology.
Current emphasis is on the eukaryotic cell; much of its structure
and function has no counterpart in bacterial cells.
Eukaryotes (eu = good; karyon = nucleus) are larger and
have more extensive intracellular anatomy and organization
than do prokaryotes. Eukaryotic cells have a characteristic set
of membrane-bound intracellular compartments, called organ-
elles, that includes a well-defined nucleus. Prokaryotes contain
no organelles, and their nuclear material is not encased by a
nuclear membrane. Prokaryotic cells are characterized by lack
of a distinct nucleus.
Besides having structural differences, prokaryotic and
eukaryotic cells differ in chemical composition and biochemi-
cal activity. The nuclei of prokaryotic cells carry genetic infor-
mation in a single circular chromosome, and they lack a class
of proteins called histones, which in eukaryotic cells bind with
deoxyribonucleic acid (DNA) and are involved in the super-
coiling of DNA (see Figure 1-2, p. 4). We now understand that
the loops and coiling of DNA are important for many diseases
(see Chapter 6). Eukaryotic cells have several chromosomes.
Protein production, or synthesis, in the two classes of cells also
differs because of major structural differences in ribonucleic
acid (RNA)–protein complexes. Other distinctions include dif-
ferences in mechanisms of transport across the outer cellular
membrane and differences in enzyme content.
CELLULAR FUNCTIONS
Cells become specialized through the process of differentia-
tion, or maturation, so that some cells eventually perform one
kind of function and other cells perform other functions. Cells
with a highly developed function, such as movement, often lack
some other property, such as hormone production, which is
more highly developed in some other type of specialized cell.
The eight chief cellular functions follow:
1. Movement. Muscle cells can generate forces that produce
motion. Muscles that are attached to bones produce limb
movements, whereas those that enclose hollow tubes or
cavities move or empty contents when they contract. For
example, the contraction of smooth muscle cells sur-
rounding blood vessels changes the diameter of the ves-
sels; the contraction of muscles in walls of the urinary
bladder expels urine.
2. Conductivity. Conduction as a response to a stimulus is
manifested by a wave of excitation, an electrical potential
that passes along the surface of the cell to reach its other
parts. Conductivity is the chief function of nerve cells.
3. Metabolic absorption. All cells take in and use nutrients
and other substances from their surroundings. Cells of
the intestine and the kidney are specialized to carry out
absorption. Cells of the kidney tubules reabsorb fluids
and synthesize proteins. Intestinal epithelial cells reab-
sorb fluids and synthesize protein enzymes.
4. Secretion. Certain cells, such as mucous gland cells, can
synthesize new substances from substances they absorb
and then secrete the new substances to serve as needed
elsewhere. Cells of the adrenal gland, testis, and ovary can
secrete hormonal steroids.
5. Excretion. All cells can rid themselves of waste products
resulting from the metabolic breakdown of nutrients.
Membrane-bound sacs (lysosomes) within cells contain
enzymes that break down, or digest, large molecules, turn-
ing them into waste products that are released from the cell.
6. Respiration. Cells absorb oxygen, which is used to trans-
form nutrients into energy in the form of adenosine
triphosphate (ATP). Cellular respiration, or oxidation,
occurs in organelles called mitochondria.
7. Reproduction. Tissue growth occurs as cells enlarge and
reproduce themselves. Even without growth, tissue main-
tenance requires that new cells be produced to replace
cells that are lost normally through cellular death. Not all
cells are capable of continuous division (see Chapter 2).
8. Communication. Communication is vital for cells to survive
as a society of cells. Pancreatic cells, for instance, secrete and
release insulin necessary to signal muscle cells to absorb
sugar from the blood for energy. Constant communication
allows the maintenance of a dynamic steady state.
STRUCTURE AND FUNCTION OF CELLULAR
COMPONENTS
Figure 1-1 shows a “typical” eukaryotic cell. It consists of three
components: an outer membrane called the plasma membrane,
or plasmalemma; a fluid filling called cytoplasm; and the intra-
cellular “organs,” or organelles, which are membrane bound
and include the nucleus.
Nucleus
The nucleus, which is surrounded by the cytoplasm and
generally is located in the center of the cell, is the largest
membrane-bound organelle. Two membranes comprise the
nuclear envelope (Figure 1-2, A). The outer membrane is
continuous with membranes of the endoplasmic reticulum.
The inner membrane encloses the neoplasm. The nucleus
contains the nucleolus, a small dense structure composed
largely of RNA; most of the cellular DNA; and the DNA-
binding proteins, the histones, that regulate its activity. The
DNA chain in eukaryotic cells is so extensive that the risk of
breakage is high. Therefore, the histones that bind to DNA
cause DNA to fold into chromosomes (Figure 1-2, C). The
wrapping of DNA into tight packages of chromosomes is
essential for cell division in eukaryotes.
The primary functions of the nucleus are cell division and
control of genetic information. Other functions include the
replication and repair of DNA and the transcription of the
information stored in DNA. Genetic information is transcribed
into RNA, which can be processed into messenger, transport,
 CHAPTER 1 Cellular Biology 3

Nuclear Smooth
Nucleolus membrane endoplasmic
Centrioles Rough
Nucleus reticulum endoplasmic
Plasma reticulum
membrane
Microfilaments

Peroxisome

Lysosome
Cilia

Cytoplasm
Mitochondrion
Vault

Cell junction Cell junction

(desmosome) (gap junction)

Golgi
Free ribosome
apparatus

Ribosome

Microtubule

Vesicle
Microvilli
A

Mitochondrion

Plasma
membrane

Nuclear
membrane
Centrosome

Golgi
apparatus
Chromatin

Nucleus

Ribosomes

Lysosomes
B
FIGURE 1-1 Typical or Composite Cell. A, Artist’s interpretation of cell structure. B, Color-enhanced electron micrograph
of a cell. Both show the many mitochondria known as the “power plants of the cell.” Note, too, the innumerable dots bordering
the endoplasmic reticulum. These are ribosomes, the cell’s “protein factories.” (B courtesy of A. Arlan Hinchee. From Patton KT,
Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
4 UNIT I The Cell

Nucleoplasm
Nuclear pores
Nucleolus

PORE

Chromosome

B
Supercoil within
chromosome
Nuclear envelope

A
Chromatin

FIGURE 1-2 The Nucleus. The nucleus is composed of a double mem- Human
Coiling
brane, called a nuclear envelope, that encloses the fluid-filled interior, called chromosomes within
nucleoplasm. The chromosomes are suspended in the nucleoplasm (illustrated supercoil
here much larger than actual size to show the tightly packed DNA strands).
Swelling at one or more points of the chromosome, shown in A, occurs at a
nucleolus where genes are being copied into RNA. The nuclear envelope is
studded with pores. B, The pores are visible as dimples in this freeze etch of a Chromatin fiber
nuclear envelope. C, Histone-folding DNA in chromosomes. (B from Raven PH,
Johnson GB: Biology, St Louis, 1992, Mosby.)
DNA
Nucleosome
Histone

DNA double helix (duplex)

C Histone DNA

and ribosomal RNA and introduced into the cytoplasm, where
it directs cellular activities. Most of the processing of RNA
occurs in the nucleolus. (The role of DNA and RNA in protein
synthesis is discussed in Chapter 4.)
Cytoplasmic Organelles
Cytoplasm is an aqueous solution (cytosol) that fills the cyto-
plasmic matrix—the space between the nuclear envelope and
the plasma membrane. The cytosol represents about half the
volume of a eukaryotic cell. It contains thousands of enzymes
involved in intermediate metabolism and is crowded with ribo-
somes making proteins. Newly synthesized proteins remain in
the cytosol if they lack a signal for transport to a cell organelle.1
The organelles suspended in the cytoplasm are enclosed in bio-
logic membranes, which enables them to simultaneously carry
out functions that require different biochemical environments.
These functions, many of which are directed by coded messages
carried from the nucleus by RNA, include synthesis of proteins
and hormones and their transport out of the cell, isolation and
elimination of waste products from the cell, metabolic pro-
cesses, breakdown and disposal of cellular debris and foreign
proteins (antigens), and maintenance of cellular structure and
motility. Also the cytosol functions as a storage unit for fat, car-
bohydrate, and secretory vesicles.
Ribosomes
Ribosomes are RNA-protein complexes (nucleoproteins) that
are synthesized in the nucleolus and secreted into the cyto-
plasm through pores in the nuclear envelope called nuclear
pore complexes (NPCs).2 These tiny ribosomes may float
free in the cytoplasm or attach themselves to the outer mem-
branes of the endoplasmic reticulum (see Figure 1-1, A).
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 DANCE ON STILTS AT THE GIRLS’ UNYAGO, NIUCHI

Newala, too, suffers from the distance of its water-supply—at least

the Newala of to-day does; there was once another Newala in a lovely
valley at the foot of the plateau. I visited it and found scarcely a trace
of houses, only a Christian cemetery, with the graves of several
missionaries and their converts, remaining as a monument of its
former glories. But the surroundings are wonderfully beautiful. A
thick grove of splendid mango-trees closes in the weather-worn
crosses and headstones; behind them, combining the useful and the
agreeable, is a whole plantation of lemon-trees covered with ripe
fruit; not the small African kind, but a much larger and also juicier
imported variety, which drops into the hands of the passing traveller,
without calling for any exertion on his part. Old Newala is now under
the jurisdiction of the native pastor, Daudi, at Chingulungulu, who,
as I am on very friendly terms with him, allows me, as a matter of
course, the use of this lemon-grove during my stay at Newala.
 FEET MUTILATED BY THE RAVAGES OF THE “JIGGER”
(Sarcopsylla penetrans)

The water-supply of New Newala is in the bottom of the valley,

some 1,600 feet lower down. The way is not only long and fatiguing,
but the water, when we get it, is thoroughly bad. We are suffering not
only from this, but from the fact that the arrangements at Newala are
nothing short of luxurious. We have a separate kitchen—a hut built
against the boma palisade on the right of the baraza, the interior of
which is not visible from our usual position. Our two cooks were not
long in finding this out, and they consequently do—or rather neglect
to do—what they please. In any case they do not seem to be very
particular about the boiling of our drinking-water—at least I can
attribute to no other cause certain attacks of a dysenteric nature,
from which both Knudsen and I have suffered for some time. If a
man like Omari has to be left unwatched for a moment, he is capable
of anything. Besides this complaint, we are inconvenienced by the
state of our nails, which have become as hard as glass, and crack on
the slightest provocation, and I have the additional infliction of
pimples all over me. As if all this were not enough, we have also, for
the last week been waging war against the jigger, who has found his
Eldorado in the hot sand of the Makonde plateau. Our men are seen
all day long—whenever their chronic colds and the dysentery likewise
raging among them permit—occupied in removing this scourge of
Africa from their feet and trying to prevent the disastrous
consequences of its presence. It is quite common to see natives of
this place with one or two toes missing; many have lost all their toes,
or even the whole front part of the foot, so that a well-formed leg
ends in a shapeless stump. These ravages are caused by the female of
Sarcopsylla penetrans, which bores its way under the skin and there
develops an egg-sac the size of a pea. In all books on the subject, it is
stated that one’s attention is called to the presence of this parasite by
an intolerable itching. This agrees very well with my experience, so
far as the softer parts of the sole, the spaces between and under the
toes, and the side of the foot are concerned, but if the creature
penetrates through the harder parts of the heel or ball of the foot, it
may escape even the most careful search till it has reached maturity.
Then there is no time to be lost, if the horrible ulceration, of which
we see cases by the dozen every day, is to be prevented. It is much
easier, by the way, to discover the insect on the white skin of a
European than on that of a native, on which the dark speck scarcely
shows. The four or five jiggers which, in spite of the fact that I
constantly wore high laced boots, chose my feet to settle in, were
taken out for me by the all-accomplished Knudsen, after which I
thought it advisable to wash out the cavities with corrosive
sublimate. The natives have a different sort of disinfectant—they fill
the hole with scraped roots. In a tiny Makua village on the slope of
the plateau south of Newala, we saw an old woman who had filled all
the spaces under her toe-nails with powdered roots by way of
prophylactic treatment. What will be the result, if any, who can say?
The rest of the many trifling ills which trouble our existence are
really more comic than serious. In the absence of anything else to
smoke, Knudsen and I at last opened a box of cigars procured from
the Indian store-keeper at Lindi, and tried them, with the most
distressing results. Whether they contain opium or some other
narcotic, neither of us can say, but after the tenth puff we were both
“off,” three-quarters stupefied and unspeakably wretched. Slowly we
recovered—and what happened next? Half-an-hour later we were
once more smoking these poisonous concoctions—so insatiable is the
craving for tobacco in the tropics.
Even my present attacks of fever scarcely deserve to be taken
seriously. I have had no less than three here at Newala, all of which
have run their course in an incredibly short time. In the early
afternoon, I am busy with my old natives, asking questions and
making notes. The strong midday coffee has stimulated my spirits to
an extraordinary degree, the brain is active and vigorous, and work
progresses rapidly, while a pleasant warmth pervades the whole
body. Suddenly this gives place to a violent chill, forcing me to put on
my overcoat, though it is only half-past three and the afternoon sun
is at its hottest. Now the brain no longer works with such acuteness
and logical precision; more especially does it fail me in trying to
establish the syntax of the difficult Makua language on which I have
ventured, as if I had not enough to do without it. Under the
circumstances it seems advisable to take my temperature, and I do
so, to save trouble, without leaving my seat, and while going on with
my work. On examination, I find it to be 101·48°. My tutors are
abruptly dismissed and my bed set up in the baraza; a few minutes
later I am in it and treating myself internally with hot water and
lemon-juice.
Three hours later, the thermometer marks nearly 104°, and I make
them carry me back into the tent, bed and all, as I am now perspiring
heavily, and exposure to the cold wind just beginning to blow might
mean a fatal chill. I lie still for a little while, and then find, to my
great relief, that the temperature is not rising, but rather falling. This
is about 7.30 p.m. At 8 p.m. I find, to my unbounded astonishment,
that it has fallen below 98·6°, and I feel perfectly well. I read for an
hour or two, and could very well enjoy a smoke, if I had the
wherewithal—Indian cigars being out of the question.
Having no medical training, I am at a loss to account for this state
of things. It is impossible that these transitory attacks of high fever
should be malarial; it seems more probable that they are due to a
kind of sunstroke. On consulting my note-book, I become more and
more inclined to think this is the case, for these attacks regularly
follow extreme fatigue and long exposure to strong sunshine. They at
least have the advantage of being only short interruptions to my
work, as on the following morning I am always quite fresh and fit.
My treasure of a cook is suffering from an enormous hydrocele which
makes it difficult for him to get up, and Moritz is obliged to keep in
the dark on account of his inflamed eyes. Knudsen’s cook, a raw boy
from somewhere in the bush, knows still less of cooking than Omari;
consequently Nils Knudsen himself has been promoted to the vacant
post. Finding that we had come to the end of our supplies, he began
by sending to Chingulungulu for the four sucking-pigs which we had
bought from Matola and temporarily left in his charge; and when
they came up, neatly packed in a large crate, he callously slaughtered
the biggest of them. The first joint we were thoughtless enough to
entrust for roasting to Knudsen’s mshenzi cook, and it was
consequently uneatable; but we made the rest of the animal into a
jelly which we ate with great relish after weeks of underfeeding,
consuming incredible helpings of it at both midday and evening
meals. The only drawback is a certain want of variety in the tinned
vegetables. Dr. Jäger, to whom the Geographical Commission
entrusted the provisioning of the expeditions—mine as well as his
own—because he had more time on his hands than the rest of us,
seems to have laid in a huge stock of Teltow turnips,[46] an article of
food which is all very well for occasional use, but which quickly palls
when set before one every day; and we seem to have no other tins
left. There is no help for it—we must put up with the turnips; but I
am certain that, once I am home again, I shall not touch them for ten
years to come.
Amid all these minor evils, which, after all, go to make up the
genuine flavour of Africa, there is at least one cheering touch:
Knudsen has, with the dexterity of a skilled mechanic, repaired my 9
× 12 cm. camera, at least so far that I can use it with a little care.
How, in the absence of finger-nails, he was able to accomplish such a
ticklish piece of work, having no tool but a clumsy screw-driver for
taking to pieces and putting together again the complicated
mechanism of the instantaneous shutter, is still a mystery to me; but
he did it successfully. The loss of his finger-nails shows him in a light
contrasting curiously enough with the intelligence evinced by the
above operation; though, after all, it is scarcely surprising after his
ten years’ residence in the bush. One day, at Lindi, he had occasion
to wash a dog, which must have been in need of very thorough
cleansing, for the bottle handed to our friend for the purpose had an
extremely strong smell. Having performed his task in the most
conscientious manner, he perceived with some surprise that the dog
did not appear much the better for it, and was further surprised by
finding his own nails ulcerating away in the course of the next few
days. “How was I to know that carbolic acid has to be diluted?” he
mutters indignantly, from time to time, with a troubled gaze at his
mutilated finger-tips.
 Since we came to Newala we have been making excursions in all
directions through the surrounding country, in accordance with old
habit, and also because the akida Sefu did not get together the tribal
elders from whom I wanted information so speedily as he had
promised. There is, however, no harm done, as, even if seen only
from the outside, the country and people are interesting enough.
The Makonde plateau is like a large rectangular table rounded off
at the corners. Measured from the Indian Ocean to Newala, it is
about seventy-five miles long, and between the Rovuma and the
Lukuledi it averages fifty miles in breadth, so that its superficial area
is about two-thirds of that of the kingdom of Saxony. The surface,
however, is not level, but uniformly inclined from its south-western
edge to the ocean. From the upper edge, on which Newala lies, the
eye ranges for many miles east and north-east, without encountering
any obstacle, over the Makonde bush. It is a green sea, from which
here and there thick clouds of smoke rise, to show that it, too, is
inhabited by men who carry on their tillage like so many other
primitive peoples, by cutting down and burning the bush, and
manuring with the ashes. Even in the radiant light of a tropical day
such a fire is a grand sight.
Much less effective is the impression produced just now by the
great western plain as seen from the edge of the plateau. As often as
time permits, I stroll along this edge, sometimes in one direction,
sometimes in another, in the hope of finding the air clear enough to
let me enjoy the view; but I have always been disappointed.
Wherever one looks, clouds of smoke rise from the burning bush,
and the air is full of smoke and vapour. It is a pity, for under more
favourable circumstances the panorama of the whole country up to
the distant Majeje hills must be truly magnificent. It is of little use
taking photographs now, and an outline sketch gives a very poor idea
of the scenery. In one of these excursions I went out of my way to
make a personal attempt on the Makonde bush. The present edge of
the plateau is the result of a far-reaching process of destruction
through erosion and denudation. The Makonde strata are
everywhere cut into by ravines, which, though short, are hundreds of
yards in depth. In consequence of the loose stratification of these
beds, not only are the walls of these ravines nearly vertical, but their
upper end is closed by an equally steep escarpment, so that the
western edge of the Makonde plateau is hemmed in by a series of
deep, basin-like valleys. In order to get from one side of such a ravine
to the other, I cut my way through the bush with a dozen of my men.
It was a very open part, with more grass than scrub, but even so the
short stretch of less than two hundred yards was very hard work; at
the end of it the men’s calicoes were in rags and they themselves
bleeding from hundreds of scratches, while even our strong khaki
suits had not escaped scatheless.

NATIVE PATH THROUGH THE MAKONDE BUSH, NEAR

MAHUTA

I see increasing reason to believe that the view formed some time
back as to the origin of the Makonde bush is the correct one. I have
no doubt that it is not a natural product, but the result of human
occupation. Those parts of the high country where man—as a very
slight amount of practice enables the eye to perceive at once—has not
yet penetrated with axe and hoe, are still occupied by a splendid
timber forest quite able to sustain a comparison with our mixed
forests in Germany. But wherever man has once built his hut or tilled
his field, this horrible bush springs up. Every phase of this process
may be seen in the course of a couple of hours’ walk along the main
road. From the bush to right or left, one hears the sound of the axe—
not from one spot only, but from several directions at once. A few
steps further on, we can see what is taking place. The brush has been
cut down and piled up in heaps to the height of a yard or more,
between which the trunks of the large trees stand up like the last
pillars of a magnificent ruined building. These, too, present a
melancholy spectacle: the destructive Makonde have ringed them—
cut a broad strip of bark all round to ensure their dying off—and also
piled up pyramids of brush round them. Father and son, mother and
son-in-law, are chopping away perseveringly in the background—too
busy, almost, to look round at the white stranger, who usually excites
so much interest. If you pass by the same place a week later, the piles
of brushwood have disappeared and a thick layer of ashes has taken
the place of the green forest. The large trees stretch their
smouldering trunks and branches in dumb accusation to heaven—if
they have not already fallen and been more or less reduced to ashes,
perhaps only showing as a white stripe on the dark ground.
This work of destruction is carried out by the Makonde alike on the
virgin forest and on the bush which has sprung up on sites already
cultivated and deserted. In the second case they are saved the trouble
of burning the large trees, these being entirely absent in the
secondary bush.
After burning this piece of forest ground and loosening it with the
hoe, the native sows his corn and plants his vegetables. All over the
country, he goes in for bed-culture, which requires, and, in fact,
receives, the most careful attention. Weeds are nowhere tolerated in
the south of German East Africa. The crops may fail on the plains,
where droughts are frequent, but never on the plateau with its
abundant rains and heavy dews. Its fortunate inhabitants even have
the satisfaction of seeing the proud Wayao and Wamakua working
for them as labourers, driven by hunger to serve where they were
accustomed to rule.
But the light, sandy soil is soon exhausted, and would yield no
harvest the second year if cultivated twice running. This fact has
been familiar to the native for ages; consequently he provides in
time, and, while his crop is growing, prepares the next plot with axe
and firebrand. Next year he plants this with his various crops and
lets the first piece lie fallow. For a short time it remains waste and
desolate; then nature steps in to repair the destruction wrought by
man; a thousand new growths spring out of the exhausted soil, and
even the old stumps put forth fresh shoots. Next year the new growth
is up to one’s knees, and in a few years more it is that terrible,
impenetrable bush, which maintains its position till the black
occupier of the land has made the round of all the available sites and
come back to his starting point.
The Makonde are, body and soul, so to speak, one with this bush.
According to my Yao informants, indeed, their name means nothing
else but “bush people.” Their own tradition says that they have been
settled up here for a very long time, but to my surprise they laid great
stress on an original immigration. Their old homes were in the
south-east, near Mikindani and the mouth of the Rovuma, whence
their peaceful forefathers were driven by the continual raids of the
Sakalavas from Madagascar and the warlike Shirazis[47] of the coast,
to take refuge on the almost inaccessible plateau. I have studied
African ethnology for twenty years, but the fact that changes of
population in this apparently quiet and peaceable corner of the earth
could have been occasioned by outside enterprises taking place on
the high seas, was completely new to me. It is, no doubt, however,
correct.
The charming tribal legend of the Makonde—besides informing us
of other interesting matters—explains why they have to live in the
thickest of the bush and a long way from the edge of the plateau,
instead of making their permanent homes beside the purling brooks
and springs of the low country.
“The place where the tribe originated is Mahuta, on the southern
side of the plateau towards the Rovuma, where of old time there was
nothing but thick bush. Out of this bush came a man who never
washed himself or shaved his head, and who ate and drank but little.
He went out and made a human figure from the wood of a tree
growing in the open country, which he took home to his abode in the
bush and there set it upright. In the night this image came to life and
was a woman. The man and woman went down together to the
Rovuma to wash themselves. Here the woman gave birth to a still-
born child. They left that place and passed over the high land into the
valley of the Mbemkuru, where the woman had another child, which
was also born dead. Then they returned to the high bush country of
Mahuta, where the third child was born, which lived and grew up. In
course of time, the couple had many more children, and called
themselves Wamatanda. These were the ancestral stock of the
Makonde, also called Wamakonde,[48] i.e., aborigines. Their
forefather, the man from the bush, gave his children the command to
bury their dead upright, in memory of the mother of their race who
was cut out of wood and awoke to life when standing upright. He also
warned them against settling in the valleys and near large streams,
for sickness and death dwelt there. They were to make it a rule to
have their huts at least an hour’s walk from the nearest watering-
place; then their children would thrive and escape illness.”
The explanation of the name Makonde given by my informants is
somewhat different from that contained in the above legend, which I
extract from a little book (small, but packed with information), by
Pater Adams, entitled Lindi und sein Hinterland. Otherwise, my
results agree exactly with the statements of the legend. Washing?
Hapana—there is no such thing. Why should they do so? As it is, the
supply of water scarcely suffices for cooking and drinking; other
people do not wash, so why should the Makonde distinguish himself
by such needless eccentricity? As for shaving the head, the short,
woolly crop scarcely needs it,[49] so the second ancestral precept is
likewise easy enough to follow. Beyond this, however, there is
nothing ridiculous in the ancestor’s advice. I have obtained from
various local artists a fairly large number of figures carved in wood,
ranging from fifteen to twenty-three inches in height, and
representing women belonging to the great group of the Mavia,
Makonde, and Matambwe tribes. The carving is remarkably well
done and renders the female type with great accuracy, especially the
keloid ornamentation, to be described later on. As to the object and
meaning of their works the sculptors either could or (more probably)
would tell me nothing, and I was forced to content myself with the
scanty information vouchsafed by one man, who said that the figures
were merely intended to represent the nembo—the artificial
deformations of pelele, ear-discs, and keloids. The legend recorded
by Pater Adams places these figures in a new light. They must surely
be more than mere dolls; and we may even venture to assume that
they are—though the majority of present-day Makonde are probably
unaware of the fact—representations of the tribal ancestress.
 The references in the legend to the descent from Mahuta to the
Rovuma, and to a journey across the highlands into the Mbekuru
valley, undoubtedly indicate the previous history of the tribe, the
travels of the ancestral pair typifying the migrations of their
descendants. The descent to the neighbouring Rovuma valley, with
its extraordinary fertility and great abundance of game, is intelligible
at a glance—but the crossing of the Lukuledi depression, the ascent
to the Rondo Plateau and the descent to the Mbemkuru, also lie
within the bounds of probability, for all these districts have exactly
the same character as the extreme south. Now, however, comes a
point of especial interest for our bacteriological age. The primitive
Makonde did not enjoy their lives in the marshy river-valleys.
Disease raged among them, and many died. It was only after they
had returned to their original home near Mahuta, that the health
conditions of these people improved. We are very apt to think of the
African as a stupid person whose ignorance of nature is only equalled
by his fear of it, and who looks on all mishaps as caused by evil
spirits and malignant natural powers. It is much more correct to
assume in this case that the people very early learnt to distinguish
districts infested with malaria from those where it is absent.
This knowledge is crystallized in the
ancestral warning against settling in the
valleys and near the great waters, the
dwelling-places of disease and death. At the
same time, for security against the hostile
Mavia south of the Rovuma, it was enacted
that every settlement must be not less than a
certain distance from the southern edge of the
plateau. Such in fact is their mode of life at the
present day. It is not such a bad one, and
certainly they are both safer and more
comfortable than the Makua, the recent
intruders from the south, who have made USUAL METHOD OF
good their footing on the western edge of the CLOSING HUT-DOOR
plateau, extending over a fairly wide belt of
country. Neither Makua nor Makonde show in their dwellings
anything of the size and comeliness of the Yao houses in the plain,
especially at Masasi, Chingulungulu and Zuza’s. Jumbe Chauro, a
Makonde hamlet not far from Newala, on the road to Mahuta, is the
most important settlement of the tribe I have yet seen, and has fairly
spacious huts. But how slovenly is their construction compared with
the palatial residences of the elephant-hunters living in the plain.
The roofs are still more untidy than in the general run of huts during
the dry season, the walls show here and there the scanty beginnings
or the lamentable remains of the mud plastering, and the interior is a
veritable dog-kennel; dirt, dust and disorder everywhere. A few huts
only show any attempt at division into rooms, and this consists
merely of very roughly-made bamboo partitions. In one point alone
have I noticed any indication of progress—in the method of fastening
the door. Houses all over the south are secured in a simple but
ingenious manner. The door consists of a set of stout pieces of wood
or bamboo, tied with bark-string to two cross-pieces, and moving in
two grooves round one of the door-posts, so as to open inwards. If
the owner wishes to leave home, he takes two logs as thick as a man’s
upper arm and about a yard long. One of these is placed obliquely
against the middle of the door from the inside, so as to form an angle
of from 60° to 75° with the ground. He then places the second piece
horizontally across the first, pressing it downward with all his might.
It is kept in place by two strong posts planted in the ground a few
inches inside the door. This fastening is absolutely safe, but of course
cannot be applied to both doors at once, otherwise how could the
owner leave or enter his house? I have not yet succeeded in finding
out how the back door is fastened.

MAKONDE LOCK AND KEY AT JUMBE CHAURO

 This is the general way of closing a house. The Makonde at Jumbe
Chauro, however, have a much more complicated, solid and original
one. Here, too, the door is as already described, except that there is
only one post on the inside, standing by itself about six inches from
one side of the doorway. Opposite this post is a hole in the wall just
large enough to admit a man’s arm. The door is closed inside by a
large wooden bolt passing through a hole in this post and pressing
with its free end against the door. The other end has three holes into
which fit three pegs running in vertical grooves inside the post. The
door is opened with a wooden key about a foot long, somewhat
curved and sloped off at the butt; the other end has three pegs
corresponding to the holes, in the bolt, so that, when it is thrust
through the hole in the wall and inserted into the rectangular
opening in the post, the pegs can be lifted and the bolt drawn out.[50]

MODE OF INSERTING THE KEY

With no small pride first one householder and then a second

showed me on the spot the action of this greatest invention of the
Makonde Highlands. To both with an admiring exclamation of
“Vizuri sana!” (“Very fine!”). I expressed the wish to take back these
marvels with me to Ulaya, to show the Wazungu what clever fellows
the Makonde are. Scarcely five minutes after my return to camp at
Newala, the two men came up sweating under the weight of two
heavy logs which they laid down at my feet, handing over at the same
time the keys of the fallen fortress. Arguing, logically enough, that if
the key was wanted, the lock would be wanted with it, they had taken
their axes and chopped down the posts—as it never occurred to them
to dig them out of the ground and so bring them intact. Thus I have
two badly damaged specimens, and the owners, instead of praise,
come in for a blowing-up.
The Makua huts in the environs of Newala are especially
miserable; their more than slovenly construction reminds one of the
temporary erections of the Makua at Hatia’s, though the people here
have not been concerned in a war. It must therefore be due to
congenital idleness, or else to the absence of a powerful chief. Even
the baraza at Mlipa’s, a short hour’s walk south-east of Newala,
shares in this general neglect. While public buildings in this country
are usually looked after more or less carefully, this is in evident
danger of being blown over by the first strong easterly gale. The only
attractive object in this whole district is the grave of the late chief
Mlipa. I visited it in the morning, while the sun was still trying with
partial success to break through the rolling mists, and the circular
grove of tall euphorbias, which, with a broken pot, is all that marks
the old king’s resting-place, impressed one with a touch of pathos.
Even my very materially-minded carriers seemed to feel something
of the sort, for instead of their usual ribald songs, they chanted
solemnly, as we marched on through the dense green of the Makonde
bush:—
 “We shall arrive with the great master; we stand in a row and have
no fear about getting our food and our money from the Serkali (the
Government). We are not afraid; we are going along with the great
master, the lion; we are going down to the coast and back.”
With regard to the characteristic features of the various tribes here
on the western edge of the plateau, I can arrive at no other
conclusion than the one already come to in the plain, viz., that it is
impossible for anyone but a trained anthropologist to assign any
given individual at once to his proper tribe. In fact, I think that even
an anthropological specialist, after the most careful examination,
might find it a difficult task to decide. The whole congeries of peoples
collected in the region bounded on the west by the great Central
African rift, Tanganyika and Nyasa, and on the east by the Indian
Ocean, are closely related to each other—some of their languages are
only distinguished from one another as dialects of the same speech,
and no doubt all the tribes present the same shape of skull and
structure of skeleton. Thus, surely, there can be no very striking
differences in outward appearance.
 Even did such exist, I should have no time
to concern myself with them, for day after day,
I have to see or hear, as the case may be—in
any case to grasp and record—an
extraordinary number of ethnographic
phenomena. I am almost disposed to think it
fortunate that some departments of inquiry, at
least, are barred by external circumstances.
Chief among these is the subject of iron-
working. We are apt to think of Africa as a
country where iron ore is everywhere, so to
speak, to be picked up by the roadside, and
where it would be quite surprising if the
inhabitants had not learnt to smelt the
material ready to their hand. In fact, the
knowledge of this art ranges all over the
continent, from the Kabyles in the north to the
Kafirs in the south. Here between the Rovuma
and the Lukuledi the conditions are not so
favourable. According to the statements of the
Makonde, neither ironstone nor any other
form of iron ore is known to them. They have
not therefore advanced to the art of smelting
the metal, but have hitherto bought all their
THE ANCESTRESS OF
THE MAKONDE
iron implements from neighbouring tribes.
Even in the plain the inhabitants are not much
better off. Only one man now living is said to
understand the art of smelting iron. This old fundi lives close to
Huwe, that isolated, steep-sided block of granite which rises out of
the green solitude between Masasi and Chingulungulu, and whose
jagged and splintered top meets the traveller’s eye everywhere. While
still at Masasi I wished to see this man at work, but was told that,
frightened by the rising, he had retired across the Rovuma, though
he would soon return. All subsequent inquiries as to whether the
fundi had come back met with the genuine African answer, “Bado”
(“Not yet”).
 BRAZIER

Some consolation was afforded me by a brassfounder, whom I

came across in the bush near Akundonde’s. This man is the favourite
of women, and therefore no doubt of the gods; he welds the glittering
brass rods purchased at the coast into those massive, heavy rings
which, on the wrists and ankles of the local fair ones, continually give
me fresh food for admiration. Like every decent master-craftsman he
had all his tools with him, consisting of a pair of bellows, three
crucibles and a hammer—nothing more, apparently. He was quite
willing to show his skill, and in a twinkling had fixed his bellows on
the ground. They are simply two goat-skins, taken off whole, the four
legs being closed by knots, while the upper opening, intended to
admit the air, is kept stretched by two pieces of wood. At the lower
end of the skin a smaller opening is left into which a wooden tube is
stuck. The fundi has quickly borrowed a heap of wood-embers from
the nearest hut; he then fixes the free ends of the two tubes into an
earthen pipe, and clamps them to the ground by means of a bent
piece of wood. Now he fills one of his small clay crucibles, the dross
on which shows that they have been long in use, with the yellow
material, places it in the midst of the embers, which, at present are
only faintly glimmering, and begins his work. In quick alternation
the smith’s two hands move up and down with the open ends of the
bellows; as he raises his hand he holds the slit wide open, so as to let
the air enter the skin bag unhindered. In pressing it down he closes
the bag, and the air puffs through the bamboo tube and clay pipe into
the fire, which quickly burns up. The smith, however, does not keep
on with this work, but beckons to another man, who relieves him at
the bellows, while he takes some more tools out of a large skin pouch
carried on his back. I look on in wonder as, with a smooth round
stick about the thickness of a finger, he bores a few vertical holes into
the clean sand of the soil. This should not be difficult, yet the man
seems to be taking great pains over it. Then he fastens down to the
ground, with a couple of wooden clamps, a neat little trough made by
splitting a joint of bamboo in half, so that the ends are closed by the
two knots. At last the yellow metal has attained the right consistency,
and the fundi lifts the crucible from the fire by means of two sticks
split at the end to serve as tongs. A short swift turn to the left—a
tilting of the crucible—and the molten brass, hissing and giving forth
clouds of smoke, flows first into the bamboo mould and then into the
holes in the ground.
The technique of this backwoods craftsman may not be very far
advanced, but it cannot be denied that he knows how to obtain an
adequate result by the simplest means. The ladies of highest rank in
this country—that is to say, those who can afford it, wear two kinds
of these massive brass rings, one cylindrical, the other semicircular
in section. The latter are cast in the most ingenious way in the
bamboo mould, the former in the circular hole in the sand. It is quite
a simple matter for the fundi to fit these bars to the limbs of his fair
customers; with a few light strokes of his hammer he bends the
pliable brass round arm or ankle without further inconvenience to
the wearer.
SHAPING THE POT

SMOOTHING WITH MAIZE-COB

CUTTING THE EDGE

 FINISHING THE BOTTOM

LAST SMOOTHING BEFORE

BURNING

FIRING THE BRUSH-PILE

 LIGHTING THE FARTHER SIDE OF
THE PILE

TURNING THE RED-HOT VESSEL

NYASA WOMAN MAKING POTS AT MASASI

Pottery is an art which must always and everywhere excite the
interest of the student, just because it is so intimately connected with
the development of human culture, and because its relics are one of
the principal factors in the reconstruction of our own condition in
prehistoric times. I shall always remember with pleasure the two or
three afternoons at Masasi when Salim Matola’s mother, a slightly-
built, graceful, pleasant-looking woman, explained to me with
touching patience, by means of concrete illustrations, the ceramic art
of her people. The only implements for this primitive process were a
lump of clay in her left hand, and in the right a calabash containing
the following valuables: the fragment of a maize-cob stripped of all
its grains, a smooth, oval pebble, about the size of a pigeon’s egg, a
few chips of gourd-shell, a bamboo splinter about the length of one’s
hand, a small shell, and a bunch of some herb resembling spinach.
 Nothing more. The woman scraped with the
shell a round, shallow hole in the soft, fine
sand of the soil, and, when an active young
girl had filled the calabash with water for her,
she began to knead the clay. As if by magic it
gradually assumed the shape of a rough but
already well-shaped vessel, which only wanted
a little touching up with the instruments
before mentioned. I looked out with the
MAKUA WOMAN closest attention for any indication of the use
MAKING A POT. of the potter’s wheel, in however rudimentary
SHOWS THE a form, but no—hapana (there is none). The
BEGINNINGS OF THE embryo pot stood firmly in its little
POTTER’S WHEEL
depression, and the woman walked round it in
a stooping posture, whether she was removing
small stones or similar foreign bodies with the maize-cob, smoothing
the inner or outer surface with the splinter of bamboo, or later, after
letting it dry for a day, pricking in the ornamentation with a pointed
bit of gourd-shell, or working out the bottom, or cutting the edge
with a sharp bamboo knife, or giving the last touches to the finished
vessel. This occupation of the women is infinitely toilsome, but it is
without doubt an accurate reproduction of the process in use among
our ancestors of the Neolithic and Bronze ages.
There is no doubt that the invention of pottery, an item in human
progress whose importance cannot be over-estimated, is due to
women. Rough, coarse and unfeeling, the men of the horde range
over the countryside. When the united cunning of the hunters has
succeeded in killing the game; not one of them thinks of carrying
home the spoil. A bright fire, kindled by a vigorous wielding of the
drill, is crackling beside them; the animal has been cleaned and cut
up secundum artem, and, after a slight singeing, will soon disappear
under their sharp teeth; no one all this time giving a single thought
to wife or child.
To what shifts, on the other hand, the primitive wife, and still more
the primitive mother, was put! Not even prehistoric stomachs could
endure an unvarying diet of raw food. Something or other suggested
the beneficial effect of hot water on the majority of approved but
indigestible dishes. Perhaps a neighbour had tried holding the hard
roots or tubers over the fire in a calabash filled with water—or maybe
an ostrich-egg-shell, or a hastily improvised vessel of bark. They
became much softer and more palatable than they had previously
been; but, unfortunately, the vessel could not stand the fire and got
charred on the outside. That can be remedied, thought our
ancestress, and plastered a layer of wet clay round a similar vessel.
This is an improvement; the cooking utensil remains uninjured, but
the heat of the fire has shrunk it, so that it is loose in its shell. The
next step is to detach it, so, with a firm grip and a jerk, shell and
kernel are separated, and pottery is invented. Perhaps, however, the
discovery which led to an intelligent use of the burnt-clay shell, was
made in a slightly different way. Ostrich-eggs and calabashes are not
to be found in every part of the world, but everywhere mankind has
arrived at the art of making baskets out of pliant materials, such as
bark, bast, strips of palm-leaf, supple twigs, etc. Our inventor has no
water-tight vessel provided by nature. “Never mind, let us line the
basket with clay.” This answers the purpose, but alas! the basket gets
burnt over the blazing fire, the woman watches the process of
cooking with increasing uneasiness, fearing a leak, but no leak
appears. The food, done to a turn, is eaten with peculiar relish; and
the cooking-vessel is examined, half in curiosity, half in satisfaction
at the result. The plastic clay is now hard as stone, and at the same
time looks exceedingly well, for the neat plaiting of the burnt basket
is traced all over it in a pretty pattern. Thus, simultaneously with
pottery, its ornamentation was invented.
Primitive woman has another claim to respect. It was the man,
roving abroad, who invented the art of producing fire at will, but the
woman, unable to imitate him in this, has been a Vestal from the
earliest times. Nothing gives so much trouble as the keeping alight of
the smouldering brand, and, above all, when all the men are absent
from the camp. Heavy rain-clouds gather, already the first large
drops are falling, the first gusts of the storm rage over the plain. The
little flame, a greater anxiety to the woman than her own children,
flickers unsteadily in the blast. What is to be done? A sudden thought
occurs to her, and in an instant she has constructed a primitive hut
out of strips of bark, to protect the flame against rain and wind.
This, or something very like it, was the way in which the principle
of the house was discovered; and even the most hardened misogynist
cannot fairly refuse a woman the credit of it. The protection of the
hearth-fire from the weather is the germ from which the human
dwelling was evolved. Men had little, if any share, in this forward
step, and that only at a late stage. Even at the present day, the
plastering of the housewall with clay and the manufacture of pottery
are exclusively the women’s business. These are two very significant
survivals. Our European kitchen-garden, too, is originally a woman’s
invention, and the hoe, the primitive instrument of agriculture, is,
characteristically enough, still used in this department. But the
noblest achievement which we owe to the other sex is unquestionably
the art of cookery. Roasting alone—the oldest process—is one for
which men took the hint (a very obvious one) from nature. It must
have been suggested by the scorched carcase of some animal
overtaken by the destructive forest-fires. But boiling—the process of
improving organic substances by the help of water heated to boiling-
point—is a much later discovery. It is so recent that it has not even
yet penetrated to all parts of the world. The Polynesians understand
how to steam food, that is, to cook it, neatly wrapped in leaves, in a
hole in the earth between hot stones, the air being excluded, and
(sometimes) a few drops of water sprinkled on the stones; but they
do not understand boiling.
To come back from this digression, we find that the slender Nyasa
woman has, after once more carefully examining the finished pot,
put it aside in the shade to dry. On the following day she sends me
word by her son, Salim Matola, who is always on hand, that she is
going to do the burning, and, on coming out of my house, I find her
already hard at work. She has spread on the ground a layer of very
dry sticks, about as thick as one’s thumb, has laid the pot (now of a
yellowish-grey colour) on them, and is piling brushwood round it.
My faithful Pesa mbili, the mnyampara, who has been standing by,
most obligingly, with a lighted stick, now hands it to her. Both of
them, blowing steadily, light the pile on the lee side, and, when the
flame begins to catch, on the weather side also. Soon the whole is in a
blaze, but the dry fuel is quickly consumed and the fire dies down, so
that we see the red-hot vessel rising from the ashes. The woman
turns it continually with a long stick, sometimes one way and
sometimes another, so that it may be evenly heated all over. In
twenty minutes she rolls it out of the ash-heap, takes up the bundle
of spinach, which has been lying for two days in a jar of water, and
sprinkles the red-hot clay with it. The places where the drops fall are
marked by black spots on the uniform reddish-brown surface. With a
sigh of relief, and with visible satisfaction, the woman rises to an
erect position; she is standing just in a line between me and the fire,
from which a cloud of smoke is just rising: I press the ball of my
camera, the shutter clicks—the apotheosis is achieved! Like a
priestess, representative of her inventive sex, the graceful woman
stands: at her feet the hearth-fire she has given us beside her the
invention she has devised for us, in the background the home she has
built for us.
At Newala, also, I have had the manufacture of pottery carried on
in my presence. Technically the process is better than that already
described, for here we find the beginnings of the potter’s wheel,
which does not seem to exist in the plains; at least I have seen
nothing of the sort. The artist, a frightfully stupid Makua woman, did
not make a depression in the ground to receive the pot she was about
to shape, but used instead a large potsherd. Otherwise, she went to
work in much the same way as Salim’s mother, except that she saved
herself the trouble of walking round and round her work by squatting
at her ease and letting the pot and potsherd rotate round her; this is
surely the first step towards a machine. But it does not follow that
the pot was improved by the process. It is true that it was beautifully
rounded and presented a very creditable appearance when finished,
but the numerous large and small vessels which I have seen, and, in
part, collected, in the “less advanced” districts, are no less so. We
moderns imagine that instruments of precision are necessary to
produce excellent results. Go to the prehistoric collections of our
museums and look at the pots, urns and bowls of our ancestors in the
dim ages of the past, and you will at once perceive your error.
MAKING LONGITUDINAL CUT IN
BARK

DRAWING THE BARK OFF THE LOG

REMOVING THE OUTER BARK

 BEATING THE BARK

WORKING THE BARK-CLOTH AFTER BEATING, TO MAKE IT

SOFT

MANUFACTURE OF BARK-CLOTH AT NEWALA

To-day, nearly the whole population of German East Africa is
clothed in imported calico. This was not always the case; even now in
some parts of the north dressed skins are still the prevailing wear,
and in the north-western districts—east and north of Lake
Tanganyika—lies a zone where bark-cloth has not yet been
superseded. Probably not many generations have passed since such
bark fabrics and kilts of skins were the only clothing even in the
south. Even to-day, large quantities of this bright-red or drab
material are still to be found; but if we wish to see it, we must look in
the granaries and on the drying stages inside the native huts, where
it serves less ambitious uses as wrappings for those seeds and fruits
which require to be packed with special care. The salt produced at
Masasi, too, is packed for transport to a distance in large sheets of
bark-cloth. Wherever I found it in any degree possible, I studied the
process of making this cloth. The native requisitioned for the
purpose arrived, carrying a log between two and three yards long and
as thick as his thigh, and nothing else except a curiously-shaped
mallet and the usual long, sharp and pointed knife which all men and
boys wear in a belt at their backs without a sheath—horribile dictu!
[51]
Silently he squats down before me, and with two rapid cuts has
drawn a couple of circles round the log some two yards apart, and
slits the bark lengthwise between them with the point of his knife.
With evident care, he then scrapes off the outer rind all round the
log, so that in a quarter of an hour the inner red layer of the bark
shows up brightly-coloured between the two untouched ends. With
some trouble and much caution, he now loosens the bark at one end,
and opens the cylinder. He then stands up, takes hold of the free
edge with both hands, and turning it inside out, slowly but steadily
pulls it off in one piece. Now comes the troublesome work of
scraping all superfluous particles of outer bark from the outside of
the long, narrow piece of material, while the inner side is carefully
scrutinised for defective spots. At last it is ready for beating. Having
signalled to a friend, who immediately places a bowl of water beside
him, the artificer damps his sheet of bark all over, seizes his mallet,
lays one end of the stuff on the smoothest spot of the log, and
hammers away slowly but continuously. “Very simple!” I think to
myself. “Why, I could do that, too!”—but I am forced to change my
opinions a little later on; for the beating is quite an art, if the fabric is
not to be beaten to pieces. To prevent the breaking of the fibres, the
stuff is several times folded across, so as to interpose several
thicknesses between the mallet and the block. At last the required
state is reached, and the fundi seizes the sheet, still folded, by both
ends, and wrings it out, or calls an assistant to take one end while he
holds the other. The cloth produced in this way is not nearly so fine
and uniform in texture as the famous Uganda bark-cloth, but it is
quite soft, and, above all, cheap.
Now, too, I examine the mallet. My craftsman has been using the
simpler but better form of this implement, a conical block of some
hard wood, its base—the striking surface—being scored across and
across with more or less deeply-cut grooves, and the handle stuck
into a hole in the middle. The other and earlier form of mallet is
shaped in the same way, but the head is fastened by an ingenious
network of bark strips into the split bamboo serving as a handle. The
observation so often made, that ancient customs persist longest in
connection with religious ceremonies and in the life of children, here
finds confirmation. As we shall soon see, bark-cloth is still worn
during the unyago,[52] having been prepared with special solemn
ceremonies; and many a mother, if she has no other garment handy,
will still put her little one into a kilt of bark-cloth, which, after all,
looks better, besides being more in keeping with its African
surroundings, than the ridiculous bit of print from Ulaya.
MAKUA WOMEN