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Reviewers

We gratefully acknowledge the generous assistance of Mark Lafferty

the reviewers whose names appear in the list that fol- Science Department Chair
lows. These individuals were kind enough to provide Delaware Technical and Community College
input on different aspects of this text; their comments Wilmington, DE
helped shape its final form.
Rene Lapierre
Margy Blankenship Coordinator, “Soins Paramédicaux”
Chair, Health Division Collège Boréal
Kentucky Community & Technical College System Ontario, Quebec, Canada
Somerset, KY
Susan Leftwich Sale
Gerald Callahan Level Coordinator, Faculty
Associate Professor Riverside School of Professional Nursing, Riverside
Microbiology, Immunology, and Pathology School of Health Careers
Colorado State University Newport News, VA
Fort Collins, CO
Steve Moon
David Derrico Instructor, Allied Medicine
Assistant Clinical Professor, Nursing College of Medicine, The Ohio State University
University of Florida Columbus, OH
Gainesville, FL
John Olson
Bertha C. Escobar-Poni Lecturer
Associate Professor, Pathology and Human Anatomy Arizona State University
School of Medicine Phoenix, AZ
Loma Linda University
Loma Linda, CA Alisa Petree
Instructor/Clinical Coordinator
Jacquelyn Harris Medical Laboratory Technician
Medical Department Chair McLennan Community College
Bryan College Waco, TX
Springfield, MO
Christine Recktenwald
Lisa Hight Assistant Teaching Professor
Associate Profesor, Biology College of Nursing at University of Missouri—
Baptist College of Health Sciences St. Louis
Memphis, TN St. Louis, MO

Jody LaCourt Vickie Roettger

Senior Teaching Specialist Profesor
University of Minnesota Missouri Southern State University
Minneapolis, MN Joplin, MO

vi
 Reviewers vii

Sandra A. Sieck Wanda Thuma-McDermond

Program Director Associate Professor of Nursing
UW-L-Gunderson-Mayo PA Program Messiah College
LaCrosse, WI Mechanicsburg, PA

J. Steve Smith Karen Tombs-Harling

Biology Department Dean, Academic Affairs
Universityof West Florida Harrisburg Area Community College
Pensacola, FL Harrisburg, PA

Becky J. Socha, Sheila Trahan

Adjunct Faculty Academic Department Chair, Allied Health
Merrimack College Lamar Institute of Technology
North Andover, MA Beaumont, TX

Gina Stephens
Program Chair, Medical Business Administrative
Technologies
Georgia Northwester Technical Colleage
Rome, GA
Preface
This Second Edition of The Nature of Disease (TNOD)
is, like the first edition, written for a particular audi-
ence: students in the health professions.
In this edition, I combine three important features to
bring students a unique learning experience.
• First, my writing style is deliberately casual. It is a nar-
rative (storyteller) style, which is less formal than the
stiff prose that populates similar textbooks. My expe-
rience shows that it makes reading and learning easier.
• Second, each chapter opens with a review of normal
anatomy and physiology. Given that pathology and
pathophysiology are nothing more than normal
anatomy and physiology gone wrong, a brief review
prepares the reader for the disease discussions that
follow.
• Third, each chapter focuses on one or more case stud-
ies, which bind the material together and make it
more memorable.
Classroom Vetted
TNOD literally grew out of a classroom. When I joined
the academic community in 1997 after a career in the
laboratory business, the classroom was an alien place to
me. I puzzled over the fact that the students I taught,
who were of the very highest quality, still had trouble
grasping the material. I began to pay more attention
to the textbooks available, and learned the student
perspective of most pathology texts: they are difficult
to read.
Much of the difficulty springs from the fact that
most pathology books are compilations written by mul-
tiple authors, each with a certain writing style and with
differing views about the relative importance of things.
Their style is generally formal. The text doesn’t flow,
and reading is bare of enjoyment. I avoid these prob-
lems by bringing a single point of view and a natural
writing style that is easy to read and remember.
Approach
Having spent much of my professional life commu-
nicating with busy physicians buried in a blizzard of
viii
paper, I know that brevity, manner, and style are the
essence of written communication. TNOD adopts a
deliberately casual narrative style, which served me well
in medical practice. It makes reading easier, holds the
reader’s attention, and enhances understanding and
recall of important points without sacrificing scientific
relevance.
TNOD focuses on answering the most important
questions that students have about every disease—
definition of the condition, its cause, how the anatomy
and physiology change and evolve, how it is diagnosed
and treated, and the outlook. Along the way, the text
uses a number of devices to deepen understanding,
retain interest, and enhance recall:
• Much of the molecular and microscopic detail typically
found in similar textbooks has been eliminated. Each
chapter focuses on the essentials necessary to build a
broad, fundamental understanding, with supporting
detail where relevant.
• New terms are boldfaced and defined at their first use
in the narrative. This practice alerts the reader to the
importance of the new term, which is defined in the
same sentence, or the one immediately following.
Terms of secondary importance are italicized.
• Selected important phrases are italicized for emphasis.
For example, in Chapter 7, Disorders of Blood Cells,
the following italicized phrase emphasizes the threat
of colon cancer: . . . until proven otherwise, the cause
of iron deficiency anemia in adult men or postmeno-
pausal women is occult (undetected) bleeding from the
gastrointestinal tract.
• The narrative is sprinkled with quotations—serious,
whimsical, or humorous—to humanize the material
and make the subject matter more memorable. For
example, Chapter 9, Disorders of the Heart, begins
with a line from country and western singer Tim
McGraw’s tune, “Where the Green Grass Grows”:
“. . . another supper from a sack, a ninety-nine cent
heart attack. . . .” This snippet of lyric speaks vol-
umes about the American diet and heart disease, and
students invariably enjoy and remember it.
• History of Medicine boxes further humanize the nar-
rative by presenting historical anecdotes that put in its
historical perspective. For example, in Chapter 23,

Disorders of Daily Life, the box titled French Food,
Fast Food, Fat Food discusses the history of res-
taurants, the development of fast food in America,
and the devastating rise of obesity in America since
World War II. Study of the history of medicine
makes the scienctific points memorable in a way not
achievable otherwise.
Cases
Each chapter is built around one or more real-life cases.
Learning about disease, its development, and its effects
is an academic exercise, which requires orderly study
using textbooks, lectures, seminars, journals, lab ex-
periments, and so on.
Another important tool in understanding this sub-
ject is case studies. The case-study method for learning
medicine is as old as medical science. A case study is
the “story” of a particular patient and the course of
their condition over a period of time. Cases human-
ize and particularize medicine in a way that no other
method can. Diseases occur in people, and people vary
greatly from one to another. Every disease occurs in
someone of a certain age, sex, and ethnicity; someone
who lives a certain lifestyle, and who, for good or ill,
has found a certain niche in life. Every one of these
characteristics relates in some way to the condition
from which they are suffering when we meet them in
the chapters.
Cases are chosen to illustrate a point, usually about
disease behavior, diagnosis, or treatment. Typically they
are written in the past tense, do not use the patient’s
real name, and follow a certain form, (discussed in
detail below). Individualizing disease by presenting it
in living, breathing, flesh-and-blood form enhances
learning.
The idea is to make the story memorable, the better
from which to learn, by telling the story as it actually
happened and by including the unadorned facts, some
of which may not be flattering to patients or c­ aregivers.
In this book, we have condensed cases to their essence,
which means I have eliminated unimportant detail.
And in some cases, I have added a bit of fiction to the
illness to add teaching value. I am confident you will
find these memorable, because all of them are real
people in some disguise.
Many TNOD cases are supplemented by “What
if . . .?” alternative scenarios that are posted online
at thePoint.com. This feature is entitled The Road Not
Taken—An Alternative Scenario. Because most of the
cases are derived from autopsy material, I have added a
Preface ix
twist to some of them, which imagines a better outcome
for the patient had the case unfolded in a different way.
For example, in Chapter 8, Disorders of Blood Vessels,
the case is that of a man found dead in his office. He
had a history of high blood pressure, obesity, lack of
exercise and tended not to take his antihypertension
prescription drugs. The alternative scenario imagines
the patient behaving differently—losing weight, taking
his blood pressure medicine regularly, exercising, and
watching his diet—and living happily ever after.
Organization
Although this textbook is unique in many ways, it
is organized in a familiar fashion: it presents general
pathology and pathophysiology first and follows with
discussions of disorders of organ systems.
Part 1, Mechanisms of Health and Disease, opens with
a chapter titled Health and Disease, which discusses the
nature of d ­ isease—that is, the intimate relationship be-
tween form and function in health and in illness. This
chapter also emphasizes the difference between the dis-
ease itself and the signs and symptoms it produces. The
failure of healthcare professionals and their patients to
appreciate this distinction accounts for a great deal of
medical misdirection and misunderstanding. The re-
maining chapters in Part 1 deal with pathologic forces
that can affect any part of the body: the life and death
of cells, inflammation and repair, immune disorders,
infections, neoplasia, and aberrations of fluid balance
and blood flow.
Part 2, Dis­orders of Organ Systems, expands on the
understanding established in Part 1 by discussing con-
ditions of the various organs and organ systems. Along
the way, the narrative is stitched together with liberal
use of cross-references to other material. In early chap-
ters cross-references steer the reader to more detailed
discussion in later chapters. In later chapters they r­ ecall
earlier discussion of basic concepts. For ­example, in
Chapter 17, Disorders of the Female ­Genital Tract and
Breast, the discussion of dysplasia of the cervix calls
on the reader to understand the concept of metaplasia,
which was defined and discussed initially in Chapter 2.
Part 3, Disorders of the Stages and States of Life, fuses
knowledge gained in Parts 1 and 2 into discussions
of disorders associated with states of being. We suffer
­differently as we progress from fetus, to neonate, to
child, to adult, and to old age. Foremost we are prison-
ers of our genes—some grant partial exemption from
risk, others are the outright cause of disease. To a lesser
extent we are prisoners of environment and habit.
x Preface
We benefit from careful diet, exercise and helpful stress.
Or we suffer from harmful stress malnutrition, obesity, in-
dolence, tobacco use or illicit drug abuse. We are always
at risk of trauma and the problem of pain is universal.
Art Program
No textbook of pathology can succeed without a first-
rate art program. Line art simplifies the structures and
concepts depicted by distilling them to their basic,
most easily recognizable forms, while photographs
show anatomic structures as they appear in real life.
The Nature of Disease is richly illustrated with both.
Text discussions are augmented by more than 560
full-color figures. In keeping with the core notion that
anatomic form and function go hand in hand, this text-
book contains more gross clinical photographs of pa-
tients and pathologic photographs of organs, tissues and
cells than comparable texts. Each photograph illustrates
a critical point and is intended to speak for itself. The
guiding principle in developing medical line art is that
good art should be understandable at a glance, or with
minimal study. Our line drawings have been designed to
be esthetically pleasing and to guide the reader’s thought
without refering to the text or to read a lengthy legend.
A full description of each of the text’s features as
well as the online resources can be found in Chapter
Features: A Guided Tour, which begins on the next page.
Instructor Resources
In addition to the student resources (see Digital Con-
nections on page xiii) instructors also have access to the
following teaching tools:
• PowerPoint slides with accompanying lecture notes
• Image bank of figures from the text
• Answers to Chapter Challenge review questions in
the text
• Test generator with more than 2,000 questions
Summary
I trust you will learn by study of the material. But more
than that, I hope you will enjoy reading it. I have spent
a great deal of time and energy to make the science
clear and the reading easy. This book is larded with hu-
manity in order to make the science easy to grasp and
retain. My hope is that this distinctive approach will
entertain and will give disease a human face.
So, here it is; judge for yourself. And after you have
judged, I want you to tell me what you think. This is
no idle invitation—please send your comments, sug-
gestions, praise, or criticism to me at thmiii@gmail.com
Thomas H. McConnell, MD, FCAP
Dallas, Texas
Chapter Features: A Guided Tour

Each chapter content begins with a discussion of normal anatomy and physiology, provid-
ing just the right amount of information to support the disease discussions that follow.
The disease discussions are the core of each chapter and consist of a narrative examina-
tion of the many disorders that may arise.
The discussion of normal anatomy and physiology and of diseases and disorders is
enhanced by the following features:

The Contents list outlines major

headings and subheadings—
providing an at-a-glance look
at the material covered and its
organization.

Chapter Objectives follow the

chapter outline and are sorted
and displayed according to the
headings under which they
are discussed.

The Case Study that opens each chapter’s content

(some chapters contain more than one) is pre-
sented in the usual clinical fashion:
• Chief Complaint. The problem that stimulated
the patient to seek care.
• Clinical History. The timeline of signs and
symptoms relating to the current illness.
• Physical Examination and Othe Data. Physical,
laboratory and imaging data.
• Clinical Course. The story of treatment, further
diagnosis, and recovery or death.

Brief Quotations help to illustrate

the main idea of each chapter in an
entertaining and informative way.

xi
xii Chapter Features: A Guided Tour

Case Study Revisited. The case and its outcome is re-

viewed discussed at the end of the chapter to reinforce
the science discussed in the chapter.

Chapter Challenge. Finally, each chapter ends with the

Chapter Challenge, a comprehensive list of noncase
questions and tasks that covers all of the chapter mate-
rial. Answers are provided in the instructor’s material.

Chapters are sprinkled with two types of questions, visual reminders of key points, and
special boxed features.

Case notes. These are case-related questions that pertain to the re-
lationship between the case and the topic at hand. For example, in
Chapter 9, Disorders of the Heart, there is a discussion on the prin-
ciple mechanisms of heart disease (e.g., pump failure, obstructed
flow, etc.). The patient, ­Willard, suffered from stenosis of the aortic
valve. Case Note 9.3 is “Which of the five principle mechanisms of
heart disease did Willard have?” Answers are posted online.

Pop Quiz. At the end of each major chapter heading is a list of

questions related to the material covered under the heading.
These are short, straightforward queries designed to solidify
knowledge while it is fresh and readily available by quick restudy.
Answers are posted online.

Remember This. Within narrative sections,these highlighted state-

ments emphasize the most important ideas, or suggest other ways
to hep you remember key facts.

The Clinical Side presents supplemental information designed to high-

light the patient side of a topic. For example, in Chapter 9, Disorders of
the Heart, the box title is Lifestyle and Coronary ­Artery Disease. The box
asks, What Can the Average Joe or Jane Do to Prevent a Heart A ­ ttack?, then
briefly provides an answer, elements of which are sprinkled throughout
the chapter narrative.
 Chapter Features: A Guided Tour xiii

Molecular Medicine presents additional insight into disease at the mo-

lecular level. Topics are simple molecular mechanisms that are easy to
grasp and supplment understanding of chapter material. For example, in
Chapter 8, Disorders of Blood Vessels, the box title is A Tale of Two Sources
of Cholesterol. The box briefly discusses the sources of blood cholesterol
and the molecular mechanisms of cholesterol-lowering drugs.

History of Medicine boxes present interesting stories about the de-

velopment of medical science. For example, it is well-­established
today that coronary artery disease is common and fatal and is
accompanied by clinical signs and symptoms known even to the
average person on the street. It is easy to assume this has always
been the case, but the History of Medicine box in Chapter 9,
Disorders of the Heart, points out that chest pain and death were
attributed to coronary artery disease only 100 years ago.

Digital Connections: Reinforcing and Enhancing Learning

Visit thePoint.lww.com and reinforce your Chapter 4:
learning with the following:
• Answers to Case Note questions • Animation: The Chain of Infection
• Answers to Case Note and Pop Quiz questions • The Road Not Taken: Case Study Alternative Scenario
• Glossary of Key Terms • Supplemental Case Study: “A spider bit me.” The
Animations, supplemental box content, supplemental case of D.W.
case studies, and “The Road Not Taken” (an alternative • History of Medicine: Who was Syphilus?
ending for selected chapter case studies) enhance your • History of Medicine: The Tuskegee Syphilis Experiment
learning and expand your understanding. In addition • Lab Tools: How Do I Know If a Patient with a Genital
to the resources above, you can access the following on Ulcer Has Syphilis?
thePoint.com • Lab Tools: Serologic Tests for Syphilis (STS)
• History of Medicine: The Discovery of Antibiotics
Chapter 1: • History of Medicine: The History of Tuberculosis

• Animation: Acute Inflammation Chapter 5:

• Animation: The Cell Cycle
• Animation: Wound Healing • The Road Not Taken: Case Study Alternative Scenario
• Supplemental Case Study: “I have a chest cold that
Chapter 3: won’t go away.” The Case of Tina D.
• History of Medicine: Where There’s Smoke, There’s Cancer
• Animation: The Immune Response
• The Road Not Taken: Case Study Alternative Scenario Chapter 6:
• Molecular Medicine: Detecting Autoimmune
Antibodies • Animation: Hemostatis
• The Clinical Side: Coombs Test • The Road Not Taken: Case Study Alternative Scenario
xiv Chapter Features: A Guided Tour

• Supplemental Case Study: “She’s gone.” The case of Rita B. • The Clinical Side: Measurement of Glomerular Fil-
• Lab Tools: Mixing Blood and Water tration Rate

Chapter 7: Chapter 17:

• Animation: Oxygen Transport • The Road Not Taken: Case Study Alternative Scenario
• The Road Not Taken: Case Study Alternative Scenario • The Clinical Side: The Difference Between Absolute
• Lab Tools: Measurement of Total Red Cell Mass and Relative Risk
• History of Medicine: “The Royal Disease” • The Clinical Side: Long-Term Estrogen Replacement
Therapy
Chapter 8:
Chapter 19:
• Animation: Hypertension
• The Road Not Taken: Case Study Alternative Scenario • Animation: Action Potential
• Animation: Nerve Synapse, Stroke
Chapter 9: • History of Medicine: Strokes in United States
Presidents
• Animation: The Cardia Cycle
• Animation: Congestive Heart Failure (CHF) Chapter 20:
Chapter 10: • History of Medicine: Braille
• The Clinical Side: Diagnosing Glaucoma
• Animation: Asthma, Gas Exchange
• The Road Not Taken: Case Study Alternative Scenario
Chapter 21:
Chapter 11:
• Animation: The Immune Response
• The Road Not Taken: Case Study Alternative Scenario
• Animation: Digestion of CHO
• History of Medicine: John D. Rockefeller, Sr.’s Hair
• Animation: General Digestion

Chapter 12: Chapter 22:

• Animation: Cirrhosis • The Road Not Taken: Case Study Alternative Scenario
• History of Medicine: The History of DNA
Chapter 13: • Lab Tools: Laboratory Diagnosis in Genetic Disease
• Molecular Medicine: Meiosis—From 46 Chromo-
somes to 23 and Back Again
• Animations: Diabetes, Hormone Control (Insulin
• The Clinical Side: Diagnosis of Cytogenetic Defects
and Glucose Metabolism)
• The Road Not Taken: Case Study Alternative Scenario
• Supplemental Case Study: “He drinks; I don’t.” The Chapter 23:
case of Charisa M.
• The Road Not Taken: Case Study Alternative Scenario
Chapter 14: • History of Medicine: Benjamin Franklin and Lead
Toxicity
• History of Medicine: President John F. Kennedy and • The Clinical Side: Metabolic Rate and Aging
Addison Disease
Chapter 24:
Chapter 15:
• The Clinical Side: Eat Less, Live Longer?
• Animation: Renal Function
Acknowledgments
There was a time when I paid little attention to Ac-
knowledgments pages in books. That was before I
became an author and realized how critical are the con-
tributions of people whose names are not on the cover.
The first edition of TNOD would not have occurred
but for a chain of unlikely events that led me into aca-
demia after a career as a practicing pathologist. It began
in June 1997 when I answered the phone to hear the
voice of Lynn Little, a former employee I’d not heard
from in years. He was calling in his capacity as Chair-
man of the Medical Laboratory Sciences department
in the UT Southwestern Allied Health Sciences School
(now the School of Health Professions). Lynn asked if I
would be interested in teaching the required pathology
course. Being somewhat at loose ends at the time, and
having narrowly chosen private practice over academia
30 years earlier, I leapt at the chance.
Then came the task of assembling course materials
from the archives in the pathology department of UT
Southwestern Medical School. Beni Stewart, guru in
the photography lab, and Beverly Shackelford, Supervi-
sor of Education Programs, guided me through a huge
collection of microscopic slides and photo images and
helped me assemble the rudiments of a course.
Next I created an outline for students, which after
a few years evolved into a ring-bound textbook. Soon
word spread, other institutions began wanting to use
my materials and before long I found myself in the
publishing business. This was time-consuming, so I
decided to mail copies to about two dozen publishers.
One landed at Lippincott Williams and Wilkins. Several
other publishers were interested, but it didn’t take long
for Lippincott to rise to the top of the heap by virtue of
plainly evident professionalism.
Then came the formal editorial process, completely
new to me, which proved to be one of the best educa-
tional experiences in a lifetime of learning. David Troy,
executive acquisition editor, oversaw the first edition
and continued his role with this second edition.
In publishing a medical textbook many people are
working independently on pieces of the whole. There
are the text documents (in successive versions), the art
and photographs (in separate successive versions), the
design team and its work products, the compositors
who assembled all into the final layout you are now
examing, and the printers. Eve Klein, Senior Product
Development Editor, kept us and our work organized
and on time. This was no mean feat.
I fancied myself good with words until I got into
the hands of professional editors. To an extent that
would surprise those not familiar with the editorial
process, this second edition is the product of the superb
editorial skills of Development Editor Laura Bonaz-
zoli. Laura collected and codified critiques of the first
edition and suggested structural reorganization of the
content of this second edition. On a smaller scale she
made chapter-by-chapter detailed recommendations
about sequence, organization, and emphasis. Later, as
draft chapters emerged, her medical knowledge added
materially to chapter scientific accuracy and complete-
ness, and her skill with words and grammar greatly
improved text flow and comprehension.
Finally, a few words about Vera Paulson, MD, PhD,
and Mark Valasek, MD, PhD, products of the MD/PhD
program at UT Southwestern. Their work is embed-
ded on every page. I wrote the first and final drafts
of each chapter, but they independently combed the
intermediate drafts for scientific completeness and
accuracy. Each also has knack for organizing thoughts
and a way with words that greatly improved the final
product.
Thomas H. McConnell, MD, FCAP
Dallas, Texas
xv
Contents

Dedication v 11 Disorders of the Gastrointestinal Tract 305

Reviewers vi
12 Disorders of the Liver and Biliary Tract 351
Preface viii
Chapter Features: A Guided Tour xi
13 Disorders of the Pancreas 384

Acknowledgments xv 14 Disorders of the Endocrine Glands 409

Part 1 15 Disorders of the Urinary Tract 445

Mechanisms of Health and Disease 16 Disorders of the Male Genitalia 488

1 Health and Disease 2 17 Disorders of the Female Genitalia

and Breast 507
2 Cellular Pathology: Injury, Inflammation,
and Repair 16 18 Disorders of Bones, Joints, and Skeletal
Muscle 556
3 Disorders of the Immune System 43
19 Disorders of the Nervous System 595
4 Infectious Disease 79
20 Disorders of the Senses 638
5 Neoplasia 114
21 Disorders of the Skin 671
6 Disorders of Fluid, Electrolyte and Acid-Base
Balance, and Blood Flow 140
Part 3
Part 2 Disorders of the Stages
and States of Life
Disorders of the Organ Systems
22 Congenital and Childhood Disorders 706
7 Disorders of Blood Cells 177
23 Disorders of Daily Life 741
8 Disorders of Blood Vessels 210
24 Aging, Stress, Exercise, and Pain 768
9 Disorders of the Heart 237
Index 788
10 Disorders of the Respiratory Tract 276

xvi
Expanded Contents
Dedication v
Reviewers vi
Preface viii
Chapter Features: A Guided Tour xi
Acknowledgments xv
Part 1
Mechanisms of Health and Disease
1 Health and Disease 2
What Is Disease? 3
How Do Scientists Study Disease? 5
What Causes and Influences Disease? 6
How Is Disease Expressed? 7
How Are Medical Tests Interpreted? 9
2 Cellular Pathology: Injury, Inflammation,
and Repair 16
Cell Reproduction and Differentiation 17
Cell Injury, Disease, and Death 20
The Inflammatory Response to Injury 26
Repair 35
3 Disorders of the Immune System 43
Non-Immune Defense Mechanisms 46
Lymphoid Organs and the Lymphatic System 48
Innate and Adaptive Immunity 48
Cells of the Immune System 51
B Lymphocyte (Antibody)-Mediated Immunity 51
T Lymphocyte (Delayed)-Mediated Immunity 53
Hypersensitivity Reactions 54
Allergic Disorders and Atopy 57
Autoimmune Disorders 60
Amyloidosis 64
Immunity in Tissue Transplantation and Blood
Transfusion 65
Immunodeficiency Disorders 69
4 Infectious Disease 79
The Biology of Infectious Disease 82
Virus Infections 89
Bacterial Infections 92
Fungus Infections 101
Parasite Infections 102
Sexually Transmitted Infections 105
Laboratory Tools 110
5 Neoplasia 114
Characteristics and Definitions of Neoplasia 116
The Causes of Cancer 118
The Molecular Basis of Neoplasia 120
The Biology of Neoplastic Growth 121
Clinical Manifestations 127
Clinical and Laboratory Assessment
of Neoplasms 129
Cancer Treatment 134
Early Detection and Prevention of Cancer 136
6 Disorders of Fluid, Electrolyte and Acid-Base
Balance, and Blood Flow 140
Pressure and the Movement of Body Fluids 142
Fluid Flow in Blood Vessels and Lymphatics 145
Water and Fluid Compartments 145
Fluid Imbalance 148
Electrolyte Imbalances 152
Acid-Base Imbalance 154
Hyperemia and Congestion 157
Hemostasis 158
Hemorrhage 160
Thrombosis 163
Disseminated Intravascular Coagulation 166
Embolism 166
Infarction 167
The Collapse of Circulation: Shock 169
Part 2
Disorders of the Organ Systems
7 Disorders of Blood Cells 177
The Formed Elements of Blood 179
Laboratory Assessment of Formed
Elements 183
Anemia 183
Polycythemia 194
Leukopenia, Leukocytosis, and Lymphadenopathy 194
Overview of Malignancies of White Blood Cells 195
Myeloid Malignancies 197
Lymphoid Malignancies 200
Disorders of the Spleen and Thymus 206
xvii
xviii Expanded Contents

8 Disorders of Blood Vessels 210 Viral Hepatitis 363

Non-Viral Inflammatory Liver Disease 370
Overview of Vascular Structure
and Functioning 212 Toxic Liver Injury 370
Hypertensive Vascular Disease 218 Metabolic Liver Disease 373
Atherosclerosis 222 Disease of Intrahepatic Bile Ducts 375
Aneurysms and Dissections 227 Circulatory Disorders 376
Vasculitis 230 Tumors of the Liver 377
Raynaud Syndrome 231 Disorders of the Gallbladder and Extrahepatic Bile
Ducts 378
Diseases of Veins 231
Tumors of Blood and Lymphatic Vessels 232
13 Disorders of the Pancreas 384
9 Disorders of the Heart 237 Normal Pancreatic Physiology 387
Pancreatitis 388
The Uniqueness of the Heart 239
Diabetes 394
Heart Failure 244
Pancreatic Neoplasms 403
Coronary Artery Disease 248
Valvular Heart Disease 255
Diseases of the Myocardium 260 14 Disorders of the Endocrine Glands 409
Pericardial Disease 262 The Normal Endocrine System 411
Congenital Heart Disease 263 Disorders of the Pituitary Gland 417
Tumors of the Heart 266 Disorders of the Thyroid Gland 422
Cardiac Arrhythmias 267 Disorders of the Adrenal Cortex 431
Disorders of the Adrenal Medulla 438

10 Disorders of the Respiratory Tract 276 Disorders of the Parathyroid Glands 439
Multiple Endocrine Neoplasia Syndromes (MEN) 441
The Normal Respiratory Tract 278
Lung Volume, Air Flow, and Gas Exchange 281
Diseases of the Upper Respiratory Tract 283 15 Disorders of the Urinary Tract 445
Atelectasis 284 The Normal Urinary Tract 447
Pulmonary Edema 285 Urine 453
Acute Respiratory Distress Syndrome 285 Urinary Obstruction 457
Obstructive Lung Diseases 286 Urolithiasis 460
Restrictive Lung Diseases (Diffuse Interstitial Disease) 291 Neoplasms of the Urinary Tract 461
Vascular and Circulatory Lung Disease 293 Congenital Anatomic Abnormalities 465
Pneumonia 294 Infection and Inflammation 466
Lung Neoplasms 298 Voiding Disorders 466
Diseases of the Pleura 301 Clinical Presentations of Renal Disorder 470
Inherited, Congenital, and Developmental Disorder 471

11 Disorders of the Gastrointestinal Tract 305 Glomerular Disorders 472

The Normal Gastrointestinal Tract 307
Signs and Symptoms of Gastrointestinal Disorder 314
Diseases of the Oral Cavity 318
Diseases of the Esophagus 322
Diseases of the Stomach 323
Congenital Anomalies of the Small and Large Bowel 328
Vascular Diseases of the Small and Large Bowel 329
Infectious Diseases Affecting the Small and Large
Bowel 331
Malabsorption Syndromes 333
Inflammatory Bowel Disease 335
Neoplasms of the Large and Small Bowel 339
Colonic Diverticulosis and Anorectal Conditions 345
Diseases of the Appendix and Peritoneum 347
12 Disorders of the Liver and Biliary Tract 351
The Normal Liver 353
The Liver Response to Injury 357
Tubular and Interstitial Disorders 479
Pyelonephritis 481
Vascular Disorder 483
16 Disorders of the Male Genitalia 488
The Normal Male Genital System 490
Disorders of Reproductive Function 493
Disorders of the Penis, Scrotum, and Groin 494
Disorders of the Epididymis and Testis 496
Disorders of the Prostate 499
17 Disorders of the Female Genitalia and
Breast 507
The Normal Female Genitalia 510
The Pituitary-Ovarian-Endometrial Cycle 512
Pregnancy 515
Infertility 521
Vulvar Disorder and Vaginitis 522
 Expanded Contents xix

Disorders of the Cervix 523 Disorders of the Inner Ear 665

Disorders of the Endometrium and Myometrium 532 Normal Taste and Smell 666
Disorders of the Ovary 538 Disorders of Taste and Smell 667
The Normal Breast 543 Normal Somatic Senses 667
Evaluation of Breast Disorders 544 Disorders of Somatic Senses 668
Benign Breast Conditions 545
Breast Cancer 547 21 Disorders of the Skin 671
Normal Skin 675
18 Disorders of Bones, Joints, and Skeletal General Conditions of Skin 677
Muscle 556 Infections, Infestations, Bites, and Stings 680
The Normal Skeleton 557 Disorders of Hair Follicles and Sebaceous Glands 683
Normal Joints 561 Dermatitis 684
Normal Skeletal Muscle 562 Diseases of the Dermis and Subcutis 689
Disorders of Bone Growth, Maturation, Modeling, Blistering Diseases 689
and Maintenance 565 Disorders of Pigmentation and Melanocytes 690
Fractures 570 Neoplasms of Skin Not Including Melanoma 696
Bone Infarction and Infection 572 Disorders of Hair and Nails 700
Bone Tumors and Tumor-Like Lesions 573
Arthritis 577
Injuries to Joints and Periarticular Tissues 583 Part 3
Periarticular Pain Syndromes 584 Disorders of the Stages
Tumors and Tumor-Like Lesions of Joints and Soft and States of Life
Tissues 586
Pathologic Reactions of Muscle 588
Myopathies 589
22 Congenital and Childhood Disorders 706
Normal Pregnancy and Gestation 708
Myasthenia Gravis 592
Overview of Congenital Defects 711
Defects Caused by Environmental Factors 712
19 Disorders of the Nervous System 595 Genetic Disorders An Introduction 716
The Normal Nervous System 597
Single-Gene Defects Transmitted According to Mendel’s
Increased Intracranial Pressure 610 Rules 719
CNS Congenital and Perinatal Disorder 613 Single-Gene Defects Transmitted According to Non-­
CNS Trauma 613 Mendelian Rules 725
Cerebrovascular Disease 617 Disorders Influenced by Multiple Genes 726
CNS Infections 622 Disorders Caused by Large-Scale Chromosome
CNS Demyelinating Diseases 624 Abnormalities 726
CNS Metabolic Disorders 625 Genetic Diagnosis 729
CNS Degenerative Disorders 627 Perinatal and Neonatal Disease 731
CNS Neoplasms 630 Infections of Infants and Children 735
Diseases of Peripheral Nerves 632 Sudden Infant Death Syndrome (SIDS) 737
Tumors and Tumor-Like Conditions in Children 737
20 Disorders of the Senses 638
The Normal Eye and Orbit 641 23 Disorders of Daily Life 741
Disorders of Alignment and Movement 646 Injury from Physical Agents 743
Trauma 646 Toxic Exposures 748
Disorders of Refraction 647 Tobacco Use 752
Disorders of the Eyelid, Conjunctiva, Sclera, and Lacrimal Alcohol Use and Abuse 754
Apparatus 648 Illicit Drug Abuse 756
Disorders of the Cornea 649 Nutritional Disease 759
Disorders of the Lens 651
Disorders of the Uveal Tract 652 24 Aging, Stress, Exercise, and Pain 768
Disorders of the Vitreous Humor and Retina 653 Aging and the Decline of Body Functions 770
Disorders of the Optic Nerve 656 Stress 775
Ocular Neoplasms 659 Exercise 778
The Normal Ear 661 Pain 783
Disorders of the External Ear 663
Disorders of the Middle Ear 664 Index 788

Mechanisms of Health and Disease
These chapters discuss basic disease processes and pathophysiology that can affect any tissue,
organ, or system of organs.
Chapter 1 Health and Disease
• Pathology, epidemiology, signs, symptoms, syndromes, and
other concepts of disease
• The effects of genetics and environment
• The meaning of “normal” and “abnormal”; test sensitivity
and specificity; false-positive and false-negative tests; the
effect of prevalence on test interpretation
Chapter 2 Cellular Pathology: Injury, Inflammation,
and Repair
• Labile, stable, and permanent tissues; the role of stem cells
• Necrosis, apoptosis, and other cell changes in health and
diseaase
• Acute and chronic inflammation and the body’s response
to injury
• Regeneration, scarring, and repair in the recovery from
injury
Chapter 3 Disorders of the Immune System
• Epithelial barriers and other nonimmune protection; alien
antigens and the reactions of the immune system
• Cells and organs of the lymphoid and immune systems
• Anaphylaxis, delayed immunity, and other immune reactions
• Allergy and autoimmune disease
• AIDS and other immunodeficiencies; avian tuberculosis and
other opportunistic infections
Chapter 4 Infectious Disease
• Prions, viruses, bacteria, worms, ticks, and other varieties
of infectious agents
• Leukocytosis, fever, and other effects of infection
PART
1
• Leukocytosis, lymphocytosis, eosinophilia, and other
characteristics of infections by particular agents
• Gonorrhea, Chlamydia, syphilis, hepatitis, and other
transmitted infections
Chapter 5 Neoplasia
• Definitions of adenoma, sarcoma, carcinoma, lymphoma,
and other types of neoplasms
• DNA mutations, proto-oncogenes, tumor suppressor
genes, the importance of apoptosis
• Premalignant states, malignant clones, growth fraction,
degrees of differentiation, tumor blood supply, invasion
and metastasis, immune surveillance
• The importance of clinical history; grading, staging, biopsy,
cytology, cell markers, paraneoplastic syndromes, other
aspects of clinical behavior and assessment
• Surgery, radiation, chemotherapy, vaccination, and other
immune treatments
Chapter 6 Disorders of Fluid, Electrolyte and Acid–Base
Balance, and Blood Flow
• Hydrodynamic pressure, osmotic pressure, and the
movement of fluid and blood
• Intracellulular and extracellular fluid, plasma and blood
volume, other body fluid compartments
• Edema, acidosis, dehydration, electrolyte imbalances
• Hemostasis, hemorrhage, congestion, thrombosis
• Thromboembolism and infarction
• Hypovolemic, cardiac, and septic shock; collapse of blood
circulation
1
CHAPTER
1 Health and Disease
Contents
Case Study “My daughter has a fever and an earache.”
The case of Anne M.
WHAT IS DISEASE?
HOW DO SCIENTISTS STUDY DISEASE?
Pathology Is the Study of Disease in Individuals
Epidemiology Is the Study of Disease in Populations
WHAT CAUSES AND INFLUENCES DISEASE?
All Disease Is Due to Environmental Injuries and/or
Genetic Defects
Determinants of Health Can Indirectly Influence
Disease
Chapter Objectives
After studying this chapter, you should be able to
complete the following tasks:
WHAT IS DISEASE?
1. Define disease, and compare and contrast acute and
chronic disease.
2. Describe the relationship between structure and
function.
3. Discuss disease progression from latent period to
complications/sequelae.
HOW DO SCIENTISTS STUDY DISEASE?
4. Compare and contrast the terms “etiology,”
“pathogenesis,” and “pathophysiology.” Also
compare and contrast the terms “idiopathic,”
“iatrogenic,” and “nosocomial.”
5. Define “epidemiology,” “incidence,” and
“prevalence.”
2
HOW IS DISEASE EXPRESSED?
Symptoms Are Subjective, and Signs Are Objective
Medical Tests Provide Data about Disease
A Syndrome Is a Collection of Symptoms, Signs, and Data
HOW ARE MEDICAL TESTS INTERPRETED?
The Terms Normal and Abnormal Describe Observations
and Measurements
Test Sensitivity and Specificity Are Key Considerations
Tests Vary in Their Predictive Value
Disease Prevalence Influences a Test’s Usefulness
Case Study Revisited “My daughter has a fever and an
earache.” The case of Anne M.
WHAT CAUSES AND INFLUENCES DISEASE?
6. Discuss the roles of environmental factors, genetic
factors, and determinants of health in the disease
process.
HOW IS DISEASE EXPRESSED?
7. Compare and contrast symptoms and signs.
8. List the types of tests that are used to study disease
(consider anatomical and clinical pathology).
HOW ARE MEDICAL TESTS INTERPRETED?
9. Explain the meaning of the terms “mean,” “normal
range,” and “standard deviation” as they relate
to medical tests and the concepts of normal and
abnormal.
10. List the factors that influence the use of diagnostic
tests. How does disease prevalence and incidence af-
fect a diagnostic test? How should these tests be ad-
ministered (e.g., why administer a sensitive test first)?
 Case Study
“My daughter has a fever and an earache.” The case of Anne M.
Chief Complaint: Fever and earache
Clinical History: Anne M. was a 21-month-old girl
sitting in her mother’s lap. Her mother told the nurse
practitioner that Anne had had a runny nose for sev-
eral days but no fever. She became feverish, however,
during the afternoon and had been crying and tug-
ging at her left ear. This is when her mother brought
her to the emergency room.
Physical Examination and Other Data: The nurse
practitioner found that Anne had a temperature of
103°F and a perforated left eardrum with pus in the
external auditory canal. Crusted mucus was present in
and around the nostrils. The remainder of the exam
was unremarkable—there was no skin rash, the chest
was clear, the neck was flexible and moving the head
produced no reaction from the child, and the anterior
cranial fontanel was flat and soft. The practitioner
made a diagnosis of acute rhinitis (a “cold”) and acute
otitis media (a middle ear infection), swabbed the pus
for culture by the lab, and wrote a prescription for an
antibiotic.
Be careful about reading health books. You may die of a misprint.
MARK TWAIN (SAMUEL LANGHORNE CLEMENS), 1835–1910, AMERICAN NOVELIST AND HUMORIST
In this chapter we are going to introduce you to disease,
how it develops from beginning to end, and how it affects
our anatomy and the functioning of our organs. But what
exactly is disease? How does it differ from health? What’s
more, how can you know if someone is unhealthy, and if
unhealthy, how can you discover the cause? Then, once
you know the cause, what can you do to correct the situ-
ation safely; what can you say about the patient’s future?
What Is Disease?
A young man visits his physician for a routine checkup.
He feels fine and has a completely normal physical
exam—despite the fact that an undetected malignant tu-
mor is growing in his lungs. Although this young man and
his physician perceive him as healthy, he is certainly sick.
That’s because the terms sickness and health refer to a state
characterized, not according to how a person feels, but
Clinical Course: The next evening Anne’s mother
returned her to the clinic. She said Anne was still
feverish but seemed strangely sleepy and “jumpy”
at the same time. The nurse practitioner called in a
pediatrician for consultation who found that Anne’s
neck was now stiff and she cried when her head was
moved. The anterior fontanel had become tense and
bulging. The pediatrician inserted a needle between
two lumbar vertebrae to collect a sample of spinal
fluid (a spinal tap). The cerebrospinal fluid was milky.
Lab microscopic examination revealed that it con-
tained many white blood cells and a few rod-shaped
bacteria. A call to the laboratory revealed that the ear
culture obtained the day before was growing a pure
growth of the bacterium Haemophilus influenzae. The
diagnosis became acute bacterial meningitis. Anne was
admitted to the hospital and placed on high doses of
intravenous antibiotics. She made a prompt recovery.
After you have read this chapter, you should be
able to discuss this case in proper scientific terms
and explain why the physical examination did not
detect meningitis on the first visit, and why diagnosis
became certain the next day.
according to whether or not disease is actually present. So
what, precisely, is disease?
Disease is really nothing more than healthy anatomy
(structure) and physiology (function) gone wrong. Put
another way, disease is a condition resulting from ana-
tomical distortion or physiologic dysfunction. This defi-
nition holds whether or not the distortion or dysfunction
is perceptible. Sometimes disease will cause no obvious
dysfunction or “dis-ease,” especially in the early stages,
as we saw with the young man above. Moreover, some
distortions occur at the molecular level and may not be
detectable even under a microscope. Another example is
high blood pressure, which is a famously silent killer.
Structure and function are inseparably locked together.
For example, bacterial infection of the mitral heart valve
may erode a hole (a structural abnormality) in the valve
(Fig. 1.1). With each ventricular contraction, the hole
allows backflow of blood (a dysfunction) into the left
atrium. This inefficiency causes the heart to perform extra
3
4 Part 1 • Mechanisms of Health and Disease
Holes in mitral valve
Figure 1.1 Initial structural disorder. Holes eaten into the mitral
valve by bacteria are the initial structural defect. The result is regurgita-
tion (backflow) of blood into the atrium—a functional disorder.
work to move the required amount of blood. This extra
labor can lead to heart muscle exhaustion (heart failure),
a functional disorder discussed in Chapter 9.
Likewise, a functional disorder may lead to structural
change. For example, high blood pressure is a functional
disorder that puts excessive strain on heart muscle as
it struggles to eject blood against the elevated pressure
in the arterial tree. This stress causes the left ventricu-
lar muscle to enlarge just like the skeletal muscles of a
weightlifter doing gym exercises. The abnormally en-
larged heart muscle is a structural disorder that has arisen
from a functional disorder (Fig. 1.2).
Case Notes
1.1 Is the hole in Anne’s eardrum a functional
or a structural disorder?
Occasionally, medical science is unable to demonstrate
a distortion or dysfunction responsible for a particular
disease. When this occurs, it does not necessarily reflect
the actual state of things in the body, but rather the lim-
its of our technology. Patients with mental disorders, for
Normal Thickened
thickness heart muscle
Figure 1.2 Initial functional disorder. High blood pressure is the initial
functional disorder. Pumping against abnormally high pressure puts ex-
cess strain on the left ventricle. The result is thickening of heart muscle—a
structural disorder.
example, have brain tissue that malfunctions in ways that
are largely invisible to science. This is also true of certain
other disorders. Fibromyalgia, for example, is a condition
characterized by muscle and periarticular pain, tenderness,
and stiffness that is not associated with any objective abnor-
mality on medical imaging, blood analyses, or other inves-
tigations. Irritable bowel syndrome is another condition that
illustrates the point. Patients suffer from diarrhea or consti-
pation, abdominal pain, and bloating, but do not have any
of the objective abnormalities associated with disease; labs,
imaging studies, and physical findings are normal.
Apart from these exceptions, diseases present them-
selves by causing observable and measurable changes in
the appearance (form) or performance (function) of cells,
tissues, and organs. Alterations of form (such as a mass
in the neck) and function (such as difficulty breathing)
are assessed by collecting a medical history, performing
a physical examination, and gathering objective data by
laboratory tests, X-rays, and other means. We discuss this
process later in this chapter, but you’ve already seen it
reflected in the opening case study. Notice that the nurse
practitioner first took a clinical history, and then per-
formed a physical examination. She also sent a sample of
tissue fluid to the laboratory for analysis.
All disease is either acute or chronic. Acute disease
arises rapidly, is accompanied by distinctive clinical mani-
festations, and lasts a short time. For example, the bacterial
infection in Anne’s middle ear, acute otitis media, begins
suddenly, is accompanied by characteristic ear pain and
fever, and lasts a few days. Chronic disease usually begins
slowly, with manifestations that are difficult to interpret. It
persists for a long time, and generally cannot be prevented
by vaccines or cured by medication. For example, the onset
of wear and tear arthritis (called osteoarthritis) begins with

vague stiffness or aches in certain joints, progresses slowly,
cannot be cured (but can be treated), and lasts a lifetime.
The beginning of a disease is its onset, which may be
facilitated by certain predisposing factors. These factors
can be genetic or environmental. For example, heart disease
may be promoted by certain genes inherited from an ances-
tor or by exposure to environmental toxins such as those
in tobacco smoke. As discussed earlier, disease may be pres-
ent but cause no apparent problems. This subclinical state
may also be called the latent period. In infectious diseases,
it is called the incubation period to reflect the fact that,
although the person feels well, the infecting microorgan-
ism is rapidly reproducing within the body. Some disease,
especially infectious disease, begins with a period of minor,
nonspecific aches, dizziness, or other indications called the
prodromal period that heralds the coming of more intense,
specific indications of disease. For example, viral hepatitis
often presents with loss of appetite, malaise, and mild fever
that may persist for several days or longer before jaundice
and other findings reveal the true nature of the problem.
After revealing itself, the condition may resolve with or
without treatment. Alternatively, the condition may linger
as chronic disease, which may wax and wane. When the
disease is quiet, it is in remission; when it reappears, it
is a recurrence. For example, after apparently successful
treatment, breast cancer may disappear clinically only to
reappear years, or decades, after initial treatment. A period
of increased intensity of disease is an exacerbation. After
the main illness has subsided, the patient enters a period
of recovery during which health improves.
Sometimes a disease may quickly give rise to adverse
consequences, which are called complications. For ex-
ample, severe skin burns are often complicated by bacte-
rial infections. In like manner, a disease may be associated
with adverse outcomes at a later time, which are called
sequelae. For example, repeated head trauma may lead to
dementia later in life.
Case Notes
1.2 Is Anne’s meningitis an exacerbation or a
complication of otitis media?
Pop Quiz
1.1 True or false? A functional disorder
can lead to a structural change.
1.2 True or false? Acute disease typically begins
with manifestations that are difficult to
interpret.
Chapter 1 • Health and Disease 5
1.3 What is the scientific name for a period of
vague, early manifestations that herald the
coming of more pronounced disease?
1.4 What is the name for a short period of
increased intensity of disease?
How Do Scientists Study Disease?
Two branches of medicine study disease as it occurs in
individuals and in populations. Study of individuals elu-
cidates functional and anatomic detail. Study of popu-
lations elucidates broad ethnic and geographic trends,
modes of transmission, the influences of habits such as
smoking, and the effects of age and sex, little of which
can be gained by the study of individuals.
Pathology Is the Study of Disease
in Individuals
Pathology is the scientific study of changes in bodily
structure and function that occur as a result of disease.
The term is derived from the Greek pathos meaning suf-
fering, and logos indicating word or reason. The discipline
of pathology has four main goals:
• To describe the lesion (the anatomic abnormality pro-
duced by the disease)
• To discover the etiology (cause) of the disease
• To understand the pathogenesis (natural history and
development) of the disease process
• To explain the pathophysiology (the manner in which
the incorrect function is expressed)
If the etiology is unknown, the disease is said to be
idiopathic (from Greek idio meaning personal, thus of a
personal, not commonly known, cause). For example, if
a patient has a failing heart because of weak heart muscle
and the cause of the weakness cannot be identified, the
patient can be said to have idiopathic cardiomyopathy. In
contrast, if the disease is a byproduct of medical diagnosis
or treatment, it is said to be iatrogenic (from Greek iatros
meaning physician). For example, if a patient develops
a bladder infection after a catheter is inserted into the
urinary bladder, the patient can be said to have iatrogenic
cystitis. Finally, if a disease—especially an infection—
originates while a patient is hospitalized, it is described as
nosocomial, from Greek words meaning “to take care of
disease.” For example, a form of pneumonia caused by the
Staphylococcus bacterium is commonly hospital acquired.
As an example of how these concepts fit together, con-
sider an ordinary sunburn. The lesion is red, swollen, hot,
painful skin. The etiology is excessive exposure to sun-
light. The pathogenesis is absorption of high-energy ultra-
violet (UV) rays, which injure skin. The pathophysiology
6 Part 1 • Mechanisms of Health and Disease
is characterized by skin pain, swelling, redness, and
warmth due to blood vessel dilation and increased blood
flow, all of which are part of the reaction to the injury.
Case Notes
1.3 Is Anne’s disease idiopathic?
Epidemiology Is the Study of Disease
in Populations
Epidemiology is a discipline of medicine that studies
the broad behavior of disease in large populations. One
goal of epidemiology is to determine the incidence of a
disease, which is the number of new cases of a particular
disease that appear in a year, as well as the prevalence,
which is the number of people with a certain disease at
a given moment. For example, in 2009 the incidence of
new prostate cancers in American men was approximately
192,000 cases. The prevalence of prostate cancer in Ameri-
can men was about 1.5%; that is, somewhat more than 1
in every 100 men had a history of prostate cancer. The
morbidity rate is the number of people with an illness
or complication of an illness and can be stated as either
incidence or prevalence. The mortality rate is the number
of people dying from a particular disease in a particular
period of time.
Epidemiological methods are also used to identify
factors that may increase an individual’s likelihood of
developing a specific disease. These factors are known as
risk factors. For example, careful population studies have
revealed that cigarette smoking is a risk factor for heart
disease, and use of oral contraceptives is a risk factor for
cervical cancer after five years of use. In contrast, protec-
tive factors are those that decrease risk. Engaging in regu-
lar physical activity is a protective factor in heart disease.
In addition, an epidemiologist may study a group of pa-
tients with a particular disease to determine what happens
to them over time. This type of study helps epidemiolo-
gists establish a prognosis—the probability of recovery,
death, or another outcome, for a disease. Probabilities are
statistical likelihoods, and are often expressed as percent-
ages. For example, the prognosis for many cancers is the
percentage of patients expected to survive for a period of
five, ten, or twenty years.
Pop Quiz
1.5 What is the scientific name for the
cause of a disease?
1.6 What is the scientific name for a structural
abnormality of disease?
1.7 True or false? The incidence of a disease
is the number of new cases of a particular
disease that appear in a year.
What Causes and Influences
Disease?
When considering the origin of disease, it’s important to
distinguish between two types of factors: those that are ca-
pable of directly causing disease, and those that indirectly
influence the initiation and progression of disease.
All Disease Is Due to Environmental
Injuries and/or Genetic Defects
The causes of disease can be conceived of as a continuum.
At one end of the continuum are diseases caused solely
by environmental injury. At the opposite end are those
caused solely by our genetic makeup. In the middle are
the majority of diseases, those resulting from some com-
bination of the two.
Environmental Injuries
The term injuries typically brings to mind physical trauma
(burns, broken bones, etc.). But toxic molecules––from
chemical poisonings to molecules released by infectious
organisms––also commonly cause injuries. Cancer is also
due to molecular injury: all cancers originate from dam-
aged DNA. Such injurious forces are environmental fac-
tors; that is, they arise from the world in which we live.
As we discuss below, our genetic makeup, age, gender,
nutrition, and other factors can play a role in how we
respond to injurious forces.
Genetic Defects
A genetic defect can be the sole cause of disease, such as
cystic fibrosis, hemophilia, or sickle cell anemia. One of
the most common genetic disorders is red–green color-
blindness, which affects fully 7% of all males and is due
to a defect in a clearly identified single gene. But most
single gene (monogenic) diseases are rare. Diseases
caused by the interaction of multiple genes (polygenic)
are much more common, much less visible, and much
more difficult to study. Not only certain diseases, but
most human characteristics (traits) are polygenic. Hair
and eye color, height, weight, intelligence, and facial
features are examples. Important though they are, it is
very difficult to identify the individual genes that make
up the combination influencing, for example, intel-
ligence. We don’t know if it is closer to 100 or 1,000
genes, much less which genes are responsible and what
role each plays. (See The Clinical Side, “The New Age of
Personal Genomics.”)

The Clinical Side
THE NEW AGE OF PERSONAL GENOMICS
In recent years, genetic technology companies have
begun offering consumers an analysis of their personal
genome that can identify genes that may predispose
them to certain diseases. Even though anyone can
purchase these genetic screenings, doing so may or may
not be a good idea. In some ways it’s like playing with
dynamite. There is a lesson to be learned among families
with Huntington chorea, an invariably fatal monogenic
disease that begins to manifest in early to middle adult-
hood. Statistically speaking, the children of affected
patients have a 50% chance of inheriting the disorder.
Although these children could learn their fate from ge-
netic analysis, many prefer not to know. For them there
is wisdom in the saying, “Ignorance is bliss.”
Consumers who do opt for genetic screening should
have a thorough understanding of the benefits and draw-
backs. It is advisable to speak with a doctor or genetic
counselor before purchase of such tests and especially af-
ter results become available. Consumers should also have
realistic expectations: studies show that most people who
purchase personal gene tests do so with the expectation
that they will change their evil ways if they are found to
have a tendency to develop a certain disease. But the
same studies show they don’t change.
Multifactorial Diseases
Although genes are solely responsible for a few diseases
and the environment accounts solely for many others,
on the whole, both genetics and environment play a role
in most. That is, the majority of disease is multifactorial.
For example, some cancers develop because of inherited
genetic mutations that predispose the patient to develop
cancer, provided that environmental factors—like expo-
sure to cigarette smoke—injure the patient’s DNA. The
fact that most disease is multifactorial means that most
disease is not completely preventable in any individual.
Again, cigarette smoking and lung cancer provide an ex-
cellent illustration of this tricky concept. Although 85%
of all lung cancer deaths occur in smokers, 15% occur in
lifelong nonsmokers, some of whom have had no signifi-
cant exposure to secondhand smoke. So although elimi-
nating all smoking would dramatically reduce lung cancer
mortality within a population, avoiding smoking is not
guaranteed to prevent lung cancer in any one individual.
Determinants of Health Can Indirectly
Influence Disease
In addition to direct environmental and genetic causes,
literally hundreds of factors in an individual’s life can in-
directly influence the initiation and progression of disease.
Chapter 1 • Health and Disease 7
Recall Anne, from our case study, whose mother sought
care for Anne’s fever and ear pain. How do you think
Anne’s disease process might have been affected if her
mother did not have access to the clinic—if, for example,
she were a single mother working a minimum-wage job
with no health insurance, and had waited a day or two to
see if Anne’s condition might resolve on its own, without
the expense of medical care?
Access to quality healthcare is just one of many factors
known to influence the development and progression of
disease. Called determinants of health, these include per-
sonal, social, economic, and environmental factors that
may not directly cause disease, but certainly play a role
in its behavior. For instance, having social support—such
as a loving family member who encourages you to see
the doctor about that nagging cough—is a protective
factor against disease, whereas living in a high-crime
area—with limited options for safely engaging in walk-
ing, jogging, biking, and other types of outdoor physical
activity—may promote obesity.
Pop Quiz
1.8 True or false? The majority of
disease is monogenic.
1.9 True or false? A patient’s ability to read and
comprehend prescription-drug information
is a determinant of health.
How Is Disease Expressed?
The nature of a disease is expressed by its symptoms, which
are subjective and described by the patient during the med-
ical history, and its signs, which are objective and are re-
vealed during the physical, lab, X-ray, or other examination.
The assembled facts then suggest the diagnosis, which is a
name for the cause of the patient’s problem. In considering
the diagnostic process, it’s important to keep in mind that
although symptoms, signs, and test results may suggest a
diagnosis, they may or may not suggest the correct diagno-
sis. It is helpful to think of such data as a roadmap, and the
disease as the actual road. The roadmap may be incorrect,
and the road may differ from what the map suggests.
Symptoms Are Subjective, and Signs
Are Objective
Symptoms are complaints reported by the patient or by
someone else on behalf of the patient. They therefore
reflect a subjective experience of the disease. One of the
most commonly reported symptoms is, of course, pain.
Typically, the examiner asks the patient to describe the
onset, duration, quality, and intensity of the pain, as well as
what seems to exacerbate it and relieve it. Other common
symptoms include fatigue, nausea, sensory impairment,
8 Part 1 • Mechanisms of Health and Disease
and bowel dysfunction. All symptoms become part of the
medical history.
Signs are objective data: observations by an examiner
(e.g., registered nurse, nurse practitioner, physician assis-
tant, or physician), lab data, imaging studies, electrocar-
diogram, and so on. For example, diarrhea reported by the
patient is a symptom, but diarrhea observed by the examiner
is a sign. Similarly, hearing loss reported by the patient is a
symptom, but hearing loss demonstrated upon examination
is a sign. Many signs can be detected only by the examiner.
For instance, auscultation with a stethoscope may reveal
heart, lung, or bowel sounds not detectible by the patient.
Notice that both symptoms and signs are detectible
manifestations of disease. For example, a person may have
a liver tumor that produces no symptoms and is too small
to be palpated or seen. As noted earlier, in such cases the
disease is said to be latent (or subclinical).
Case Notes
1.4 Name some symptoms and signs present on
Anne’s second visit.
Medical Tests Provide Data about Disease
Assessment of body tissues, fluids, and other components
is a third way in which disease may make itself known.
These studies are either anatomic or clinical.
Anatomic Pathology
Anatomic pathology is the study of structural changes
caused by disease. Assessment of tissue specimens by the
unaided eye is gross examination; assessment of magni-
fied images of small structures is microscopic examina-
tion. The most basic and extensive gross examination is an
autopsy, an after-death (postmortem) dissection of a body
to determine the cause of death and other facts about the
condition of the patient at the time of death. On a smaller
scale, a biopsy is examination of living tissue, usually via
microscope. For example, the study of tissues and cells in
a breast biopsy or a Pap smear is an anatomic pathology
procedure. Refer to The Clinical Side, “What Happens to
a Biopsy Specimen,” to see how tissue specimens are pre-
pared for study.
The Clinical Side
WHAT HAPPENS TO A BIOPSY SPECIMEN?
The word biopsy derives from Greek bios = life + opsis =
sight. It is the obtaining of a piece of living tissue to
discover the presence, cause, or extent of disease. The
biopsy specimen is submitted to a pathologist or other
medical professional for examination and diagnosis.
Typically the specimen is placed in a fixative solution
(usually formaldehyde) to prevent degeneration or bacte-
rial growth and to ready the specimen for further study.
Examination occurs in two stages: gross and micro-
scopic. The gross examination is study of the specimen
with the unaided eye and includes the weight, size,
shape, texture, color, and other features. The gross exam
is followed by a microscopic study of all or carefully se-
lected small pieces of the specimen.
In microscopic study of a biopsy, light shines upward
from below the specimen and through it to the micros-
copist’s eye. Microscopic study, therefore, requires slices
of tissue thin enough to be transparent, usually less than
one cell thick. But, just as a glass of water from the deep
blue sea is almost colorless, in such thin slices there is not
enough natural color present to make cells clearly visible.
To solve this problem, dyes (stains) are added to color
the cells. The finished result is somewhat like looking at
a flag with the sun shining through from the backside.
Consider a specimen from a breast biopsy. The surgeon
puts the raw lump of tissue in formaldehyde to preserve
it and kill any bacteria that might cause decay during lab
processing. A small sample is selected by the pathologist
for further processing and is placed in a series of chemicals
to soak out the fat and water, both of which render tissue
fuzzy and blurry under the microscope. Next, the piece is
immersed in hot paraffin wax, which soaks into the speci-
men to take the place of the missing fat and water. The
paraffinized piece is chilled and becomes hard enough for
very thin slicing by a highly precise instrument. A slice is
laid flat on a slide and dipped in a series of chemicals to
remove the paraffin, leaving behind on the slide surface
an exceedingly thin layer of waterless, fat-free tissue; all
that remains is protein, carbohydrate, and minerals. This
is then dipped in a series of dyes that stain cell nuclei
blue and cytoplasm red. Collagen, calcium, and other
interstitial materials stain red or blue or a mixture of the
two colors depending on individual characteristics. Places
where fat and water used to be are empty and colorless.
Pathologists, or other specialists with microscopic ex-
pertise, study the tissue searching for patterns of disease—
inflammation, degeneration, peculiar-looking cells, and so on.
In addition to ordinary microscopic study, special
techniques can highlight certain cell characteristics and
make them microscopically visible. An example is detec-
tion of estrogen-receptor molecules in breast cancer
cells. The presence or absence of estrogen receptors is
important in crafting the best therapy for breast can-
cer. The technique (called “immunohistochemistry”)
requires treating a thin slice of raw tumor tissue with
antibodies and chemicals, the combination of which
causes a colored precipitate to accumulate in breast
cancer cells if estrogen receptors are present in them.

Clinical Pathology
Clinical pathology is the study of the functional aspects of
disease by laboratory study of tissue, blood, urine, or other
body fluids. Examples include blood glucose measurement
to diagnose diabetes, or a culture of urine to detect bacterial
infection. Clinical pathology extends from the lab to the bed-
side, too. A pathologist is practicing clinical pathology when
he or she supervises the performance of a laboratory test,
such as a blood aldosterone assay, and consults with another
physician about the results.
A Syndrome Is a Collection of Symptoms,
Signs, and Data
A distinctive collection of symptoms, signs, and data
(anatomic or clinical) is a syndrome. For example, ac-
quired immunodeficiency syndrome (AIDS) commonly
includes profound fatigue (a symptom), and abnormally
low counts of a particular type of T cell (a sign).
Sometimes, a particular syndrome may be caused by
any of several different diseases. For example, Cushing
syndrome (Chapter14) is a collection of symptoms, signs,
and data attributable to chronic adrenocortical hormone
(steroid hormone) excess. It is characterized by truncal
obesity, a moon face, excess facial hair, easy bruising, skin
striae (stretch marks), brittle bones, high blood glucose,
and high blood cortisol, among many other features.
Cushing syndrome is often due to medical treatment, but
it can be due to adrenal, pituitary, or other disease.
Remember This! A syndrome is a distinctive
collection of symptoms, signs, and test data.
Pop Quiz
1.10 Is an abnormality observed by a
nurse a sign or a symptom?
1.11 True or false? A biopsy is an examination of
a tissue specimen to determine the cause of
death.
1.12 What is the name for a distinctive collection
of symptoms, signs, and data?
How Are Medical Tests Interpreted?
We’ve said that one way disease expresses itself is by caus-
ing alterations in body tissues and chemicals that can be
detected by medical tests. But when test results are in,
how do clinicians interpret them in relation to disease? To
answer that question, we first need to understand how to
distinguish between normal and abnormal.
Chapter 1 • Health and Disease 9
The Terms Normal and Abnormal Describe
Observations and Measurements
In everyday conversation, we may refer to cancer or de-
mentia as “abnormal,” but clinicians do not use the terms
normal and abnormal to describe health and disease. Rather,
they use them to characterize observations and measure-
ments. That’s because medical test results vary greatly
among healthy people, just as do height, weight, and other
physical features. For example, a shoe size 15 EEE might be
normal for a 6′10′, 350-lb man, but for a 5′2′, 105-lb woman
it would be abnormal in the extreme. Neveretheless, even in
a small woman, such a foot, though of a very abnormal size,
would not necessarily indicate disease—it may function
normally and be perfectly healthy. In the same way, healthy
people may have unusually low, high, or otherwise abnor-
mal test results even though they do not have a disease—the
abnormal results merely reflect variation among individuals.
These variations of normal require that clinicians use
an established definition of normal. For these purposes,
normal means the usual result in healthy people. Like-
wise, abnormal means not the usual result in healthy
people. It is true that most sick patients have abnormal
test results, and most healthy patients have normal results.
Nevertheless, sometimes sick patients have normal test
results and sometimes healthy patients have abnormal test
results; thus, applying the terms normal and abnormal only
to observations and measurements is essential. Figure 1.3
depicts these concepts.
Qualitative versus Quantitative Tests
Qualitative tests are used to describe qualities, most com-
monly the presence, absence, or characteristics of a com-
ponent, such as the shape of the heart as seen in a chest
X-ray. For qualitative tests, the result is either normal
(the expected result in healthy people) or abnormal (not
the expected result in healthy people). For example, if a
patient is suspected of having intestinal bleeding, stool
can be tested for the presence or absence of blood. Either
blood is present (abnormal) or it is not present (normal)
and decisions can be made accordingly.
More commonly, a determination of normal or ab-
normal must be made for the results of quantitative tests,
which measure quantities (amounts or numbers) of a
component. For example, a quantitative test of kidney
function might measure the amount of nitrogen in a pa-
tient’s blood. This numerical data must then be compared
to a standard. That is, for quantitative tests, a normal
range must be established. Recall from above that normal
is defined as the usual result in healthy people. But how
do clinicians know what is usual?
Establishing Normal for Quantitative Tests
To establish normal for any particular quantity, epidemi-
ologists perform statistical analysis of many results in a
large number of presumably healthy people. These results
10 Part 1 • Mechanisms of Health and Disease

Sick with Sick with

normal tests abnormal tests

Healthy with Healthy with

normal tests abnormal tests
A B C

Healthy Normal
test
Sick Abnormal
test
Figure 1.3 Healthy or sick, normal or abnormal, and how they combine. A. All patients are either healthy or sick. B. All measurements (tests)
are either normal or abnormal. C. Some healthy patients have abnormal test results, and some sick patients have normal test results.

are averaged to determine the mean (average). Statistical
formulas are also applied to the data to determine the
standard deviation, a measure of the degree of natural
variability of results; that is, the degree of variation from
one normal person to another. When test results cluster
tightly around the mean, the standard deviation is small.
The test results for blood calcium levels, for example,
have a small standard deviation because the body tightly
controls blood calcium, and levels vary little from one
person to another. On the other hand, when test results
are widely scattered above and below the mean, as they are
with blood glucose levels, the standard deviation is large.
To accommodate the natural variability of test results,
epidemiologists use the mean and standard deviation
to establish a normal range. By widespread agreement,
the lower limit of the normal range is always set at two
standard deviations below the mean, and the upper
limit is set at two standard deviations above the mean.
A graphic display of a hypothetical normal range study
for blood glucose is shown in Figure 1.4. When normal
is defined this way, the lowest 2.5% and highest 2.5% of
results in presumably healthy persons are so far from the
(average) and standard deviations are calculated for the
group. If the average glucose in our group is 90 mg/dL, and
one standard deviation (SD) is 10 mg/dL, then the normal
range for fasting blood glucose levels would be from 90
minus 20 to 90 plus 20, or 70 to 110 mg/dL, as shown in
Figure 1.4.
Positive versus Negative Results
When referring to tests for a particular disease, results
are often referred to as positive if abnormal and negative if
normal. The presumption is that positive suggests disease
may be present, while negative suggests it is not. Presum-
ing we know by other methods whether the patient is sick
or well, test results for a particular disease are referred to
as true positive if the test is positive and the patient actu-
ally has the disease. Conversely, the test is referred to as
false positive if the test is positive but the patient does
not have the disease. That is to say, a true positive test
Mean
particular blood glucose level
Number of people with a

average that they are considered abnormal even though

by definition the patient is healthy. Thus, by definition, One standard
deviation
5% of presumably healthy people will have an abnormal
test result.
Abnormally Abnormally
Remember This! Healthy is not the same as low high
normal; sick is not the same as abnormal. Normal = mean ± 2
standard deviations
As an example, let’s presume we want to establish a
normal range for blood glucose. We therefore ask 100 pre-
sumably healthy young adults to volunteer to have a blood 60 70 80 90 100 110 120
glucose test. Those with signs or symptoms that suggest Blood glucose levels (mg/dL) in presumably healthy people
diabetes or those with a family history of diabetes are
Figure 1.4 The normal distribution curve. Among healthy people
rejected. Those who are accepted are instructed not to eat
who do not have diabetes, the greatest numbers of blood glucose
or drink anything for four hours before the test. A blood levels are near the mean (90 mg/dL). A few people will have a blood
glucose test is performed on each person, and the mean glucose level below 70 mg/dL or greater than 110 mg/dL.

Table 1.1 Test Results: True and False Positive; True and False Negative
Normal Test
HEALTHY Healthy patient with normal test result:
True negative
Example: People without Normal fasting blood glucose level:
diabetes Diagnosis—no diabetes
SICK Sick patient with normal test result:
False negative
Example: People with untreated Normal fasting blood glucose level:
diabetes Perhaps lab error
correctly indicates that disease is present, whereas a false
positive test incorrectly suggests disease is present when,
in fact, it is not. Likewise, negative results are referred to
as true negative or false negative, depending on whether
the test result correctly or incorrectly indicates that disease
is absent. These combinations are depicted in grid form in
Table 1.1.
Case Notes
1.5 Presuming that Anne’s meningitis was
present but not severe on the first visit, was
Anne’s soft, flat fontanel a true positive, false
positive, true negative, or false negative test for
meningitis?
The Extent of Abnormality
If a test is abnormal, the degree of abnormality is
important—markedly abnormal results are more signifi-
cant than are mildly abnormal ones. Disease is a contin-
uum from mildly ailing to desperately ill, and test results
vary accordingly. The greater the degree of abnormality,
the more likely it is that the result means disease is present
(the test is truly positive). For example, if the upper limit
of normal blood glucose levels is 110 mg/dL, a patient with
a fasting blood glucose level of 190 mg dL is much more
likely to have diabetes than is a patient with a fasting blood
glucose level of 120 mg/dL.
Test Sensitivity and Specificity
Are Key Considerations
In addition to interpreting the values of test results as nor-
mal and abnormal, clinicians must be able to appreciate a
test’s sensitivity and specificity. The ability of a test to be
positive in the presence of disease is test sensitivity. For
example, a test is 99% sensitive if it is positive in 99 of
100 patients known to have the disease. Similarly, speci-
ficity is the ability of a test to be negative in the absence of
the disease. A test is said to be 99% specific if it is negative
in 99 of 100 persons known not to have the disease.
Chapter 1 • Health and Disease 11
Abnormal Test
Healthy patient with abnormal test result:
False positive
High fasting blood glucose level: Perhaps
patient not really fasting
Sick patient with abnormal test result:
True positive
High fasting blood glucose level:
Diagnosis—diabetes
Case Notes
1.6 Presuming Anne had mild meningitis on the
first visit, as a test for meningitis did the neck
manipulation test lack sensitivity or specificity?
There is a trade-off between sensitivity and specificity.
Highly sensitive tests are likely to be positive in patients
with the condition or disease (truly positive), but they
also have a tendency to be positive (falsely positive) in
some healthy people, too. That is to say, if you screen for
a certain condition using a highly sensitive test, the group
with positive results will include most of the patients with
the condition (you won’t miss many), but mixed in will be
a fairly large number of healthy patients who do not have
the condition (their tests are falsely positive). Although
this is less than ideal, the flip side is that you can be confi-
dent that those who had negative results are healthy (truly
negative). That is to say, a negative result using a highly
sensitive test is a very reliable indicator that the condition
for which you are testing is not present. In the group with
positive tests, you can sort out the false positives from the
true positives by doing additional tests.
The opposite is true for highly specific tests—the test
is likely to be negative in healthy patients who, of course,
do not have the condition for which you are testing. The
test may be negative, however, in some patients with the
condition (their test is falsely negative). It follows that if
you screen a group of patients using a highly specific test,
you can be confident that those with positive tests have
the condition (their test is likely to be a true positive, not
a false positive). Nevertheless, the group with negative
results will include some patients with disease, whom you
can identify by further testing later.
Again, as a rule, highly sensitive tests are not very spe-
cific, and highly specific tests are not very sensitive. By
way of example, consider home burglar alarms as a test
for burglars. Alarms are very sensitive but not very spe-
cific—so although they do not miss many burglars, there
are lots of false alarms. That is to say, burglar alarms have
12 Part 1 • Mechanisms of Health and Disease
many false positives but few false negatives. By contrast,
having a personal observer at home is much more specific
but it is less sensitive. Rarely would an observer in the
house falsely accuse someone of being a burglar unless
they were unknown or unwelcome, but if the observer is
out working in the back garden, then a burglar might not
be detected.
Given that both sensitive and specific tests have draw-
backs, which type of test does a clinician choose, and
why? In the diagnostic process, the most effective strategy
is this: first use a very sensitive test, and then follow up on
patients who test positive by administering a very specific
test. This is precisely the strategy used in many types of
cancer screening. For example, sexually active women are
routinely screened for cervical cancer using a Pap smear,
which is a highly sensitive test; that is, it misses very few
cases of cervical cancer (Fig. 1.5). A Pap smear is inex-
pensive, painless, and minimally invasive. The clinician
collects a sample of cervical cells in a matter of seconds
during a woman’s routine pelvic exam. Nevertheless,
because it is highly sensitive, Pap smear screening will
result in false positives. So a diagnosis of—and treatment
for—cervical cancer is not yet warranted for those women
who test positive. Instead, these women undergo a sec-
ond, highly specific test, a tissue biopsy. This second test
is more invasive, more painful, more time consuming, and
more expensive, so it is not practical as a screening test for
Highly sensitive test
Population False positive
Positive
test
Pap
smear
Negative
test
Resmear
in one
year
= Cervical cancer
= No cancer
False negative
Figure 1.5 Test sensitivity and specificity in the search for cancer of the cervix. To detect cancer of the cervix, first use a highly sensitive test,
the Pap smear, which is not likely to miss many cancers. Those who test positive by Pap smear are further investigated by cervical biopsy, a more
specific test. Those who tested negative by Pap smear are retested by Pap smear the next year, which will likely identify false negatives missed on
the first smear.
presumably healthy women; it is, however, very useful to
distinguish the true-positive smears (women with cancer)
from the false-positive smears (women without cancer).
Remember This! Test first with highly sensitive
tests; retest positives with highly specific tests.
Tests Vary in Their Predictive Value
The purpose of testing is to determine who has disease and
who does not. The best test has high predictive value; that
is, it accurately predicts who has and who does not have
disease. Highly sensitive tests tend to have a lot of false
positives, but very few false negatives. Therefore, a nega-
tive result in a highly sensitive test has high predictive value.
Highly specific tests tend to have a lot of false negatives, but
few false positives. Therefore, a positive result in a highly spe-
cific test has high predictive value. Another way to say this is
that if a test has many true positives and few false positives,
the predictive value of a positive test is high. Likewise, if a
test has a great number of true negatives and few false nega-
tives, the predictive value of a negative test is high.
For example, cardiac troponin I, a heart muscle protein
that increases in blood as a result of a heart attack, nor-
mally circulates in blood in small amounts. Therefore, in a
patient with chest pain and possible heart attack, increased
cardiac troponin I is considered a positive test for cardiac
Highly specific test
Diagnosis:
Cancer
Biopsy
Diagnosis:
No cancer
Biopsy
Diagnosis:
Cancer

muscle damage and a reliable sign of a heart attack. Normal
levels of cardiac troponin I suggest no cardiac muscle dam-
age has occurred and the cause of the pain must be found
elsewhere. Diagnostic use of cardiac troponin I as a tool to
predict the presence or absence of heart muscle damage
has shown that most patients with abnormally high cardiac
troponin I have heart muscle damage. Conversely, the great
majority of patients with normal cardiac troponin I do not
have heart muscle damage. Thus, the predictive value of
cardiac troponin I as an indicator of the presence or ab-
sence of heart muscle damage is high for both positive and
negative tests, making cardiac troponin I a very widely used
diagnostic test when heart muscle damage is suspected.
As discussed above, the degree of test abnormality is
important—the greater the abnormality, the more likely is
it that the result correctly suggests that disease is present.
This means that a patient with very high cardiac troponin
I is much more likely to have heart muscle damage (and
more extensive damage) than is a patient with mildly el-
evated cardiac troponin I.
Disease Prevalence Influences a Test’s
Usefulness
How well a test performs (whether it has high or low
predictive value) depends to a surprising degree on how
many cases exist (the prevalence) in the group being
tested. For example, consider the cardiac troponin I test
just mentioned. The number of people having an acute
heart attack is near zero among asymptomatic persons
entering a shopping mall. Any positive test in such a
group is very likely a false positive. On the other hand,
the same test will be much more useful if performed in pa-
tients who present with chest pain to an emergency room
Case Study Revisited
“My daughter has a fever and an earache.” The case of Anne M.
Reviewing this case gives us an opportunity to review
many of the terms and concepts covered in this
chapter.
Anne’s primary symptom on her first visit was
pain, which she “reported” (through her mother) by
crying and tugging on her ear. The nurse practitioner
examined Anne and found the following signs,
each of which can be thought of as a positive test:
elevated temperature, runny nose and crusted
nostrils, perforated left eardrum, and pus in the
external auditory canal. Knowing that meningitis
Chapter 1 • Health and Disease 13
because among such patients there are many having a
heart attack. Therefore, in an emergency room population,
a positive result is much more likely to be truly positive.
In medical diagnostic terms, a positive test is more likely
to be truly positive (to have a high predictive value; to be a
correct indication of disease) if there are a lot of people in
the tested population who have the disease; that is, if the
prevalence of disease is high in the tested population.
Case Notes
1.7 Is the prevalence of meningitis likely to be
low or high in a group of infants with a tense,
bulging fontanel?
Pop Quiz
1.13 True or false? All sick patients will
have at least one abnormal test.
1.14 What percentage of the test results in
healthy people fall within the mean plus
and minus two standard deviations?
1.15 The ability of a test to be positive in the
presence of disease is __________.
1.16 True or false? The best testing strategy is to
start with highly sensitive tests and follow
with highly specific ones.
can be a complication of ear infection, the nurse also
checked the flexibility of Anne’s neck and the softness
of her anterior fontanel. Both were normal; that
is, they were negative tests. After examination the
nurse practitioner concluded that the diagnosis was
acute bacterial infection of the left middle ear (otitis
media) with perforation of the tympanic membrane.
The initial etiology was acute viral upper respiratory
infection. The pathogenesis was swelling and mucus
obstruction of the eustachian tube (abnormal form),
which caused accumulation of fluid in the left middle
(continued)
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alcancem. Tratase hūa Historia de hum Ermitão, et hum
Salteador de caminhos» (Está en Braga, n. 151).
Cont. II. «Que as filhas devem tomar o conselho da sua boa may,
e fazer seus mandamentos. Trata de hūa que o não fez, e a
morte desastrada que ouve» (Braga, n. 152).
Cont. III. «Que as donzellas, obedientes, devotas e virtuosas, que
por guardar sua honra se aventurão a perigo da vida, chamando
por Deos, elle les acode. Trata de hūa donzella tal que he digno
de ser lido» (Braga, n. 153).
Cont. IV. «Que diz que as zombarias são perjudiciaes, e que he
bom não usar delles, concluesse autorizado con hum dito grave».
Es meramente un dicho sentencioso de un caballero de la Corte
de D. Juan III: «Senhor, não zombo, porque o zombar tem
resposta».
Cont. V. «Trata do que aconteceo en hūa barca zombando, e hūa
resposta sotil».
Son zumbas y motejos entre un corcobado y un narigudo, que
acabaron mal.
Cont. VI. «Que en toda parceria se deve tratar verdade, porque o
engano ha se de descobrir, e deixa envergonhado seu mestre.
Trata de dous rendeiros».
Historia insulsa que tiende á recomendar la buena fe en los
contratos.
Cont. VII. «Que aos Principes convem olhar por seus vassalos,
para lhe fazer merce. E os despachadores sempre devem folgar
disso, e não impedir o bõ despacho das partes. Trata hum dito
gravissimo de hum Rey que Deos tem».
Un Rey justiciero da á un mancebo de Tras os Montes el cargo
de contador del almojarifazgo que tenía su padre, y haciéndole
alguna observación su veedor de Hacienda sobre la inutilidad del
cargo, le replica: «Se nos não havemos mister o contador, o
mancebo ha mister o officio».
Cont. VIII. «Que os Prelados socorram com suas esmolas a seus
subditos, e os officiaes de sua casa lhe ajudem. Trata de hum
Arcebispo e seu veador».
El Arzobispo de Toledo de quien se trata es D. Alonso Carrillo, y
el cuento procede de la Floresta Española, como decimos en el
texto: «Vos faço saber que estes que me servem ham de ficar em
casa, porque eu os ey mister, e estes que me não servem,
tambem ficarão, porque elles me ham mister a mi».
Cont. IX. «Que ha hum genero de odios tam endurecido que
parece enxerido pello demonio. Trata de dous vezinhos
envejosos hum do outro» (Braga, II, 154).
Cont. X. «Que nos mostra como os pobres com pouca cousa se
alegram. E he hum dito que disse hum homen pobre a seus
filhos» (Braga, II).
Cont. XI. «Do que acontece a quem quebranta os mandamentos
de seu pay, e o proveyto que vem de dar esmolla, e o dano que
socede aos ingratos. Trata de hum velho e seu filho» (Braga, II,
157, con el título de O segredo revelado).
Cont. XII. «Que offerecendosemos gostos ou perda, o sentimento
ou nojo seja conforme a causa, concluindo con elle. Trata hum
dito de hum Rey que mandou quebrar hūa baixella».
Cont. XIII. «Que os que buscam a Deos sempre o achão. Trata
de hum hermitan, e hum pobre lavrador que quis antes un real
bem ganhado que cento mal ganhados» (Braga, n. 156).
Cont. XIV. «Que todo tabellião e pessoa que da sua fe em juizo,
deve attentar bem como a da. Trata hūa experiencia que fez hum
senhor para hum officio de Tabellião» (Braga, n. 158).
Cont. XV. «Que os pobres não desesperem nas demandas que
lhe armão tyrannos. Trata de dous irmãos que competiam em
demanda hum com outro, e outras pessoas» (Braga, 159).
Cont. XVI. «Que as molheres honradas e virtuosas devem ser
calladas. Trata de hūa que fallou sem tempo e da reposta que lhe
derão.
Anécdota insignificante, fundado en el dicho de una mujer de
Llerena.
Cont. XVII. «Como castiga Deos accusadores, e liura os
innocentes. Trata de hum Comendador que foy com falsidade
accusado diante del Rey» (Braga, n. 160, con el título de Don
Simão).
Cont. XVIII. «De quam bom he tomar conselho com sabedores e
usar delle. Trata de hum mancebo que tomou tres conselhos, e o
sucesso» (Braga, n. 161).
Cont. XIX. «Que he hūa carta do Autor a hūa senhora, com que
acaba a primeira parte destas historias e contos de proveito e
exemplo. E logo começa segunda, em que estão muitas historias
notaveis, graciosas, e de muito gosto, como se vera nella».
Parte 2.ª.
Cont. I. «Que trata quanto val a boa sogra, e como por industria
de hūa sogra esteve a nora bem casada com o filho que a
aborrecia» (Braga, n. 162).
Cont. II. «Que diz que honrar os Sanctos e suas Reliquias, e
fazerlhe grandes festas he muito bem, e Deos e os Sanctos o
pagão. Trata de hum filho de hum mercador, que con ajuda de
Deos e dos Sanctos veo a ser Rey de Inglaterra».
Cont. III. «Que diz nos conformemos com a vontade do Senhor.
Trata de hum Medico que dizia: Tudo o que Deos fez he por
melhor» (Braga, n. 163).
Cont. IV. «Que diz que ninguem arme laço que não caya nelle.
Trata de hum que armou hūa trampa para tomar a outro, e cahio
elle mesmo nella».
Cont. V. «Que diz que a boa mulher he joya que não tem preço, e
he mellior para o homen que toda a fazenda e saber do mundo
como se prova claro ser assi no discorso do conto».
Es un largo ejemplo moral.
Cont. VI. «Que nāo confie ninguem em si que sera bom, porque
ja o tem promettido: mas andemos sobre aviso fugindo das
tentações. Trata hum dito de hum arraez muito confiado».
Cont. VII. «Que nāo desesperemos nos trabalhos, e confiemos
em Deos que nos proverá, como fez a huma Rainha virtuosa con
duas irmãas que o nāo erão, do que se trata no conto seguinte»
(Braga, n. 164).
Cont. VIII. «Que o poderoso nāo seja tyranno, porque querendo
tudo, nāo alcança o honesto e perde o que tem. Como se ve em
hūa sentença sotil em caso semelhante» (Braga, n. 165).
Cont. IX. «Que diz que conformes com a vontade de Deos nosso
Senhor lhe demos louvores e graças por tudo o que faz. Trata de
hum dito do Marquez de Pliego, em tempo del Rey Don Fernando
Quinto de Castella».
Terceira parte.
Cont. I. «Que todos sejamos sojeitos a razam, e por alteza de
estado nāo ensoberbeçamos, nem por baixeza desesperamos.
Trata de hū Principe, que por soberbo hum seu vassallo pos as
mãos nelle, e o sucesso do caso he notavel» (Braga, n. 166).
Cont. II. «Que quem faz algum bem a outro, nāo lho deve lançar
em rosto, e que sempre se deve agradecer a quem nos da
materia de bem obrar».
Trátase de una carestía de Córdoba. Este cuento, ó más bien
dicho sentencioso y grave contra los que echan en cara los
beneficios recibidos, parece de origen castellano.
Cont. III. «Que diz quanto val o juizo de hum homen sabio, e
como por hum Rey tomar con elle, o tirou de huma duvida en que
estava com hum seu barbeiro» (Braga, n. 168).
El Rey invita á su barbero á que le pida cualquier merced,
prometiendo concedérsela. El barbero le pide la mano de la
princesa su hija. Sorprendido el rey de tal petición, consulta con
un sabio, el cual le aconseja que mande abrir la tierra en el sitio
donde había estado el barbero, porque sin duda habría puesto
los pies sobre un gran tesoro, que le daba humos para aspirar
tan alto. El tesoro aparece en efecto, y el rey lo reparte entre el
barbero y el letrado que dió tan buen consejo. Ignoro el origen de
este absurdo cuento.
Cont. IV. «Trata como dous mancebos se quiseran em estremo
grao, e como hum delles por guardar amizade se vio em grandes
necessidades, e como foy guardado do outro amigo».
Cont. V. «Que inda que nos vejamos em grandes estados nāo
nos ensoberbeçamos, antes tenhamos os olhos onde nacemos
para merecer despois a vir a ser grandes senhores, como
aconteceo a esta Marqueza de que he o conto seguinte». (Braga,
n. 107, con el título de Constancia de Griselia).
Cont. VI. «Em que mostra de quanto preço he a virtude nas
molheres, especialmente nas donzelas, e como hūa pobre
lavradora por estimar sua honra em muyto, veo a ser grande
senhora».
Cont. VII. «Neste conto atraz tratei hūa grandeza de animo que
por comprir justiça usou Alexandro de Medices Duque de
Florença com hūa pobre Donzela, e porque este he de outra
nobreza sua que usou com hūa pobre viuva, a qual he o
seguinte» (Braga, n. 169, O achado da bolsa).
Cont. VIII. «Em que se conta que estando hūa Raynha muyto
perseguida e sercada em seu Reyno, foy liurada por hum
cavaleyro de quem ella era en estremo enemiga, e ao fim veio a
casar com elle».
Cont. IX. «Que mostra de quanta perfeição he o amor nos bōs
casados, e como hum homen nobre se pos em perigo da morte
por conservar a hōra de sua molher, e por a liurar das miserias
em que vivia, e como lhe pagou com o mesmo amor».
Cont. X. «Em o qual se trata de hum Portuguez chegar a cidade
de Florença, e o que passou com o Duque senhor della, com hūa
peça que lhe den a fazer, o qual he exemplo muy importante para
officiaes».]
[199] Página 11 de la edición de Francisco Asensio.
[200] Vid. E. Cosquin, La Légende du Page de Sainte Elisabeth
de Portugal et le conte indien des «Bons Conseils», en la Revue
de Questions Historiques, enero de 1903.
[201] Á las comparaciones hechas por el primero en sus notas á
los Awarische Texte de A. Schiefner (n. 12) hay que añadir la
monografía del segundo sobre Quatro Novelline popolari livornesi
(Spoleto, 1880). Una nota de Teófilo Braga, que excuso repetir (II,
192-195), resume estas indagaciones. Pero para estudiarlas á
fondo, habrá que recurrir siempre a los fundamentales trabajos
de Köhler (Kleinere Schriften zur Märchenforschung von Köhler
Herausgegeben von Iohannes Bolte, Weimar, 1898, pp. 118, 143,
565 y ss.).
[202] Basque Legends: collected, chiefly in the Labourd, by Rev.
Wentworth Webster... Londres, 1879, pág. 176.
[203] Recuérdese lo que hemos dicho en la página LVII, nota 2.ª.
[204] Part. 1.ª, nov. XIV. «Alessandro duca di Firenze fa che
Pietro sposa una mugnaja che aveva rapita, e le fa far molto ricca
dote».
En el cuento siguiente de Trancoso (VII de la 3.ª Parte) hay
alguna reminiscencia (pero sólo al principio) de la novela XV,
parte 2.ª, de Bandello («Bell' atto di giustizia fatto da Alessandro
Medici, duca di Firenze contra un suo favorito cortegiano»),
[205] En las notas de Valentin Schmidt á su traducción alemana
de algunas novelas de Straparola puede verse, una indicación de
ellas.
Märchen-Saal. Sammlung alter Märchen mit Anmerkungen;
herausgegeben von Dr. Friedr. Wilh-Val. Schmidt. Erster Band.
Die Märchen des Straparola, Berlín, 1817.
Pero es mucho más completo el trabajo de G. Rua, Intorno alle
«Piacevoli dello Straparola (Giornale Storico della letteratura
italiana, vol. XV y XVI, 1890).
[206] Cap. 124. «Quod mulieribus non est credendum, neque
archana committendum, quoniam tempore iracundiae celare non
possunt». Ed. Oesterley, p. 473. Trae copiosa lista de paradigmas
en la página 732.
[207] «Pisti è dannato per micidiale, e gli è levato tutto l' hauere, e
son promessi premii a chi l' uccide, o vivo il dà nelle mani della
giustitia; Egli si fà offerire a' Signori, e libera la familia da disagio,
e se da pericolo. (Novella 5, prima deca de Gli Hecatommithi).
[208] «Caritea ama Pompeo, Diego innamorato della giouane, l'
uccide; Ella promette di darsi per moglie a chi le da il capo di
Diego. Le moue guerra il Re di Portogallo. Diego la difende, e fa
prigione il Re, poscia si pone in podestà della Donna, e ella lo
pliglia per marito» (Novella 1ª seconda deca).
[209]

Jupiter ambiguas hominum praediscere mentes,

Ad terras Phoebum misit ab arce poli.
Tunc duo diversis poscebant numina votis;
Namque alter cupidus, invidus alter erat.
His sese medium Titan; scrutatus utrumque,
Obtulit, et precibus ut peteretur, ait:
Praestabit facilis; nam quae speraverit unus,
Protinus haec alter congeminata feret.
Sed cui longa jecur nequeat satiare cupido,
Distulit admotas in nova lucra preces:
Spem sibi confidens alieno crescere voto,
Seque ratus solum munera ferre duo.
Ille ubi captantem socium sua praemia vidit,
Supplicium proprii corporis optat ovans.
Nam petit extincto ut lumine degeret uno,
Alter ut, hoc duplicans, vivat utroque carens.
Tunc sortem sapiens humanam risit Apollo,
Invidiaeque malum rettulit inde Jovi.
Quae dum proventis aliorum gaudet iniquis,
Laetior infelix et sua damna cupit.
[210] Vid. T. Braga, II, 27.
[211] Sigo, con algún ligero cambio, la antigua traducción
castellana de Juan Bautista de Morales, impresa por primera vez
en 1622.
Corte en aldea y noches de invierno de Francisco Rodríguez
Lobo... En Valencia: en la oficina de Salvador Fauli, año 1793.
Diálogo X. «De la materia de contar historias en conversación».
Diálogo XI. «De los cuentos y dichos graciosos y agudos en la
conversación». PP. 276-355.
[212] Vid. Serrano y Morales, La Imprenta en Valencia, pp. 285-
327. En la pág. 323 de este precioso libro está publicado el
testamento de Felipe Mey, que nombra entre sus hijos á
Sebastián, con lo cual queda plenamente confirmado lo que
sobre este punto conjeturó D. Nicolás Antonio.
[213] Fabulario en que se contienen fabulas y cuentos diferentes,
algunos nueuos y parte sacados de otros autores; por Sebastian
Mey. En Valencia. En la impression de Felipe Mey. A costa de
Filipo Pincinali a la plaça de Vilarasa.
8.º, 4 hs. prls. y 184 pp.
Aprobación del Pavorde Rocafull, 20 de enero de 1613.—Escudo
de Mey.—Prólogo.
«Harto trillado y notorio es, a lo menos a quien tiene mediana
licion, lo que ordena Platon en su Republica, encargando que las
madres y amas no cuenten a los niños patrañas ni cuentos que
no sean honestos. Y de aqui es que no da lugar a toda manera
de Poetas. Cierto con razon, porque no se habitue a vicios
aquella tierna edad, en que facilmente, como en blanda cera, se
imprime toda cosa en los animos, haviendo de costar despues
tanto y aun muchas vezes no haviendo remedio de sacarlos del
ruin camino, a seguir el cual nos inclina nuestra perversa
naturaleza. A todas las personas de buen juicio, y que tienen zelo
de bien comun, les quadra mucho esta dotrina de aquel Filosofo:
como quepa en razon, que pues tanta cuenta se tiene en que se
busque para sustento del cuerpo del niño la mejor leche, no se
procure menos el pasto y mantenimiento que ha de ser de mayor
provecho para sustentar el alma, que sin proporcion es de muy
mayor perficion y quilate. Pero el punto es la execucion, y este es
el fin de los que tanto se han desvelado en aquellas
bienaventuradas republicas, que al dia de hoy se hallan
solamente en los buenos libros. Por lo qual es muy acertada y
santa cosa no consentir que lean los niños toda manera de libros,
ni aprendan por ellos. Uno de los buenos para este efeto son las
fabulas introduzidas ya de tiempo muy antigo, y que siempre se
han mantenido: porque a mas de entretenimiento tienen dotrina
saludable. Y entre otros libros que hay desta materia, podra
caber este: pues tiene muchas fabulas y cuentos nuevos que no
están en los otros, y los que hay viejos estan aqui por diferente
estilo. Nuestro intento ha sido aprovechar con él a la republica.
Dios favorezca nuestro deseo».
Cada una de las fábulas lleva un grabadito en madera, pero
algunos están repetidos.
[214] Modern Language Notes, Baltimore, junio y noviembre de
1906.
[215] Para que nada falte á la descripción de tan raro libro,
pondremos los títulos de estas fábulas, con sus moralidades
respectivas:
Fábula I. El labrador indiscreto. Es la fábula del molinero, su hijo
y el asno, tornada probablemente de El Conde Lucanor, cap. 24
de la edición de Argote.

Quien se sujeta á dichos de las gentes,

Ha de caer en mil inconvenientes.
Fáb. II. El gato y el gallo. Hipócritas pretextos
del gato para matar al gallo y comérsele.
Con el ruin son por demás razones,
Que al cabo prevalecen sus pasiones.
Es la fábula 4.ª del «Isopo de la traslacion
nueva de Remigio» en la colección del infante
Don Enrique.
Fáb. III. El viejo y la muerte.
Los hombres llaman á la muerte ausente,
Mas no la quieren ver quando presente.
Fáb. IV. La hormiga y la cigala.
Quando estés de tu edad en el verano,
Trabaja, porque huelgues cuando anciano.
Fáb. VI. El álamo y la caña.
 Mas alcanza el humilde con paciencia,
Que no el soberbio haziendo resistencia.
Fáb. VII. La raposa y la rana.
De la voz entonada no te admires,
Sin que primero de quien sale mires.
Fáb. IX. La raposa y las uvas.
Quando algo no podemos alcançar,
Cordura dizen que es dissimular.
Fáb. XI. El leon, el asno y la raposa.
Quando vemos el daño del vecino,
No escarmentar en él es desatino.
Fáb. XII. La mujer y el lobo.
La muger es mudable como el viento:
De sus palabras no hagas fundamento.
Fáb. XIV. El gallo y el diamante.
No se precia una cosa, ni codicia,
Si no es donde hay de su valor noticia.
Fáb. XV. El cuervo y la raposa.
Cuando alguno te loa en tu presencia,
Piensa que es todo engaño y apariencia.
Fáb. XVII. El leon y el raton.
No quieras al menor menospreciar,
Pues te podrá valer en su lugar.
Fáb. XIX. La liebre y el galápago.
Hazienda y honra ganarás obrando,
Y no con presuncion emperezando.
Fáb. XXI. La rana y el buey.
Con los mayores no entres en debate,
Que se paga muy caro tal dislate.
Fáb. XXII. El asno y el lobo.
Entienda cada qual en su exercicio,
Y no se meta en el ageno oficio.
Fáb. XXIV. El consejo de los ratones.
 Ten por consejo vano y de indiscreto,
Aquel del qual no puede verse efeto.
Fáb. XXV. El grillo y la abeja.
De su trabajo el hombre se alimente,
Y á gente vagamunda no sustente.
Si fueres docto, y no seras discreto,
Seran tus letras de muy poco efeto.
Fáb. XXIX. Las liebres y las ranas.
Aunque tengas miseria muy notable,
Siempre hallarás quien es más miserable.
Fáb. XXX. El asno, el gallo y el leon.
Quien presume de sí demasiado,
Del que desprecia viene á ser hollado.
Fáb. XXXI. La raposa y el leon.
En aprender no tomes pesadumbre,
pues lo hace fácil todo la costumbre.
Fáb. XXXIII. El asno, el cuervo y el lobo.
Para bien negociar, favor procura:
Con él tu causa casi está segura.
Fáb. XXXIV. El asno y el lobo.
Uno que haziendo os mal ha envejecido,
Si hazeros bien ofrece, no es creido.
Fáb. XXXV. El raton de ciudad y el del campo.
Ten por mejor con quietud pobreza,
Que no desasosiegos con riqueza.
Fáb. XXXVI. La raposa y el vendimiador.
Si con las obras el traydor te vende,
En vano con palabras te defiende.
Fáb. XXXVII. La vieja, las moças y el gallo.
Huir de trabajar, es claro engaño,
Y de poco venir á grande daño.
Fáb. XXXIX. El asno y las ranas.
Quando un poco de mal te quita el tino.
Mira el que tienen otros de contino.
 Fáb. XL. El pastor y el lobo.
Al que en mentir por su plazer se emplea.
Quando dize verdad, no hay quien le crea.
Fáb. XLII. El labrador y la encina.
Si favoreces al ruin, haz cuenta
Que en pago has de tener dolor y afrenta.
Fáb. XLIII. El leon enamorado.
Los casamientos hechos por amores
Muchas vezes son causa de dolores.
Fáb. XLIV. La raposa y el espino.
Acudir por socorro es grande engaño
A quien vive de hazer á todos daño.
Fáb. XLVIII. El Astrólogo.
¿Qué certidumbre puede dar del cielo
El que á sus pies aun ver no puede el suelo?
Fáb. L. El leon enfermo, el lobo y la raposa.
Algunas vezes urde cosa el malo
Que viene á ser de su castigo el palo.
Fáb. LII. La raposa y la gata.
Un arte vale más aventajada
Que muchas si aprovechan poco ó nada.
Fáb. LIV. Los ratones y el cuervo.
Algunos, por inútiles contiendas,
Pierden la posesion de sus haziendas.

[216] Es la fábula XLI de Mey y termina con estos versos:

Harta ceguera tiene la cuytada

Que tuvo hazienda y no ve suyo nada.

[217] Fábula XXIII:

Si no he de aprovecharme del dinero,

Una piedra enterrada tanto quiero.
 [218] Fábula XXVI de Mey. Corresponde á la XVII del
«Isopo de la traslacion nueva de Remigio», en la del
infante D. Enrique.

[219] Calila é Dymna, p. 33 en la edición de Gayangos

(Escritores en prosa anteriores al siglo XV).
[220] Así en Firenzuola: «il buon uomo, o pur come dicemmo, lo
sciocco». En Mey: «el hombre bueno, o si se sufre llamarle
bovo».
También pudo consultar La moral filosophia del Doni (Venecia,
1552), que es una refundición del libro de Firenzuola.
[221] Del falso e del torpe.
Dixo Calila: «Dos homes eran en una compaña, et el uno dellos
era torpe, e el otro falso, e ficieron aparceria en una mercaderia;
et yendo por un camino fallaron una bolsa en que habia mil
maravedis, e tomáronla, e ovieron por bien de le tornar a la
cibdat. Et quando fueron cerca de la cibdat, dixo el torpe al falso:
«Toma la metad destos dineros, et tornaré yo la otra meatad». Et
dixo el falso, pensándose levar todos los maravedis: «Non
fagamos asi, que metiendo los amigos sus faziendas en manos
de otri fazen más durar el amor entre ellos; mas tome cada uno
de nos para gastar, e soterremos los otros que fincaren en algun
logar apartado, et quando hobiéremos menester dellos, tomarlos
hemos». E acordóse el torpe en aquello, et soterraron los
maravedis so un arbol muy grande, e fuéronse ende, e despues
tornó el falso por los maravedis, e levólos; e cuando fue dias,
dixo el falso al torpe: «Vayamos por nuestros maravedis, que yo
he menester que despienda». E fuéronse para el logar que los
posieron, e cavaron e non fallaron cosa; e comenzóse a mesar el
falso et a ferir en sus pechos, et comenzó a dezir: «Non se fie
home en ninguno desde aqui, nin se crea por él». E dixo al torpe:
«Tú tornaste aqui et tomaste los maravedis». Et comenzó el torpe
a jurar e confonderse que lo non feciera, e el falso diciendo: «Non
sopo ninguno de los maravedis salvo yo et tú, e tú los tomaste».
E sobre esto fuéronse pora la cibdat, e pora el alcall, e el falso
querellóse al alcall cómo el torpe le habia tomado los maravedis,
e dixo el alcall: «¿Tú has testigos?» Dixo el torpe: «Sí, que fio por
Dios que el arbol me será testigo, e me afirmará en lo que yo
digo». E sobre esto mandó el alcall que se diesen fiadores, et
díxoles: «Venid vos para mí e iremos al arbol que decides». E
fuese el falso a su padre et fízogelo saber e contóle toda su
fazienda, et díxole: «Yo no dixe al alcall esto que te he contado,
salvo por una cosa que pensé; si tú acordares comigo, habremos
ganado el haber». Dixo el padre: «¿Qué es?» Dixo el falso: «Yo
busqué el mas hueco arbol que pude fallar, e quiero que te vayas
esta noche allá e que te metas dentro aquel logar y donde
puedas caber, et cuando el alcall fuere ende, e preguntare quién
tomó los maravedis, responde tú dentro que el torpe los tomó...
«Et non quedó de le rogar que lo fiziese fasta que gelo otorgó. Et
fuese a meter en el arbol, e otro dia de mañana llegó el alcall con
ellos al arbol, e preguntóle por los maravedis, e respondió el
padre del falso que estaba metido en el arbol, et dixo: «El torpe
tomó los maravedis». E maravillóse de aquello el alcall e cuantos
ende estaban, e andudo alrededor del arbol, e non vió cosa en
que dudase, e mandó meter y mucha leña e ponerla en derredor
del arbol, e fizo poner fuego. E cuando llegó el fumo al viejo, e le
dió la calor, escomenzó de dar muy grandes voces e demandar
acorro; et entonces sacáronle de dentro del arbol medio muerto,
e el alcall fizo su pesquisa e sopo toda la verdat, e mandó
justiciar al padre e al fijo e tornar los maravedis al torpe; e así el
falso perdió todos los maravedis, e su padre fué justiciado por
cabsa de la mala cobdicia que ovo et por la arteria que fizo».
(Calila e Dymna, ed. Gayangos, pp. 32-33).
Cf. Johannis de Capua Directorium vitae humanae... ed. de
Derenbourg, París, 1887, pp. 90-92.
Agnolo Firenzuola, La prima veste de' discorsi degli animali, ed.
Camerini, pp. 241-242.
[222] The Facetiae or jocose tales of Poggio..., París, 1879, I,
187.
[223] Diporto de' Vindanti, nel quale si leggono Facetie, Motti e
Burle, raccolte da diversi e gravi autori. Pavia, Bartoli, 1589, 8.º.
Ésta es la más antigua de las ediciones mencionadas por Gamba
en su bibliografía novelística.
[224] Cento Novelle de' più nobili scrittori della lingua volgare
scelte da Francesco Sansovino... Venezia, appresso Francesco
Sansovino, 1561.
Hállase también en las ediciones de 1562, 1563, 1566, 1571,
1598, 1603 y 1610.
[225] Ancona, Le fonti del Novellino, p. 319.
[226] En Sansovino no es el Gobernador sino el Arzobispo.
[227] «En un gran banquete, que hizo un señor á muchos
caballeros, despues de haber servido muy diversos manjares,
sacaron barbos enteros, y pusieron á un capitan de una Nao, que
estaba al cabo de la mesa, un pez muy pequeño, y mientras que
los otros comian de los grandes, tomó él el pececillo y púsole á la
oreja. El señor que hacia el banquete, paróse mientes, y
preguntóle la causa. Respondió: «Señor, mi padre tenia el mismo
oficio que yo tengo, y por su desdicha y mía anegóse en el mar y
no sabemos adónde, y desde entonces á todos los peces que
veo, pregunto si saben de él. Díceme éste, que era chiquito, que
no se acuerda».
(Floresta Española... Sexta parte, Capítulo VIII, n. XII de «dichos
de mesa», pág. 254 de la ed. de 1790.)
Pequeñas variantes tiene el cuento de Garibay:
«Sirvieron a la mesa del Señor unos peces pequeños y al Señor
grandes. Estaba a la mesa un fraile, y no hacia más que tomar de
los peces chicos y ponellos al oido y echallos debajo de la mesa.
El Señor miró en ello, y díjole: «Padre ¿huelen mal esos peces?»
Respondió: «No, señor, sino que pasando mi padre un rio, se
ahogó, y preguntábales si se habian hallado a la muerte de mi
padre. Ellos me respondieron que eran pequeños, que no, que
esos de V. S.ª que eran mayores, podría ser que se hubiesen
hallado». Entendido por el Señor, dióle de los peces grandes,
diciéndole: «Tome, y pregúntesle la muerte de su padre» (Sales
Españolas, de Paz Melia, II, p. 52).
[228] Fáb. XVI.

De ser cantor no tenga presuncion

El que no sabe más de una cancion.

[229] Fáb. XIII. Es cuento de mentiras de cazadores.

No disimules con quien mucho miente,

Porque delante de otros no te afrente.

[230] Fáb. XXXII.

Hablale de ganancia al codicioso,

 Si estás de hazerle burla deseoso.

[231] Fáb. XLVI.

Si hizieres al ingrato algun servicio,

Publicará que le hazes maleficio.

[232] Fáb. LI.

Harás que tu muger de ti se ria,

Si la dexas salir con su porfia.

[233] Fáb. LVII. El Maestro de escuela

Encomiendate a Christo y a Maria,

A tu Angel y a tu Santo cada dia.

[234] Fáb. XXXIV.

No cases con mochacha si eres viejo;

Pesarte ha si no tomas mi consejo.

[235] Il Novellino di Masuccio Salernitano, ed. de Settembrini,

Nápoles, 1874. Págs. 519 y ss.
[236] Cercando ultimamente tra virtuosi gesti, de prossimo me è
già stato da uno nobile oltramontano per autentico recontato, che
è ben tempo passato che in Toleto cità notevole de Castiglia fu un
cavaliero d' antiqua e generosa famiglia chiamato misser Piero
Lopez d' Aiala, il quale avendo un suo unico figliolo molto
leggiadro e bello e de gran core, Aries nominato...
En el exordio dice también que su novela ha sido «de virtuosi
oltramontani gesti fabbricata».
[237] Le Comte Lucanor... París, 1854, pág. 149.
[238] Dialogos de apacible entretenimiento, que contiene vnas
Carnestolendas de Castilla, Diuidido en las tres noches del
Domingo, Lunes, y Martes de Antruexo. Compvesto por Gaspar
Lucas Hidalgo. Procvra el avtor en este libro entretener al Letor
con varias curiosidades de gusto, materia permitida Para recrear
penosos cuydados a todo genero de gentes. Barcelona, en casa
de Sebastian Cormellas. Año 1605.
8.º, 3 hs. prls. y 108 folios.
Según el Catálogo de Salvá (n. 1.847), hay ejemplares del mismo
año y del mismo impresor, con diverso número de hojas, pero
con igual contenido.
Una y otra deben de ser copias de una de Valladolid (¿1603?),
según puede conjeturarse por la aprobación de Gracián Dantisco
y el privilegio, que están fechados en aquella ciudad y en aquel
año.
—Diálogos... Con licencia. En Logroño, en casa de Matias Mares,
año de 1606.
8.º, 3 hs. prls. y 108 folios. (N.º 2 520 de Gallardo.)
—Barcelona, 1606. Citada por Nicolás Antonio.
—Barcelona, en casa de Hieronimo Margarit, en la calle de
Pedrixol, en frente Nuestra Señora del Pino. Año 1609.
8.º, 5 hs. prls., 120 pp. dobles y una al fin, en que se repiten las
señas de la impresión.
—Brusselas, por Roger Velpius, impressor jurado, año 1610.
8.º, 2 hs. prls., 135 folios y una hoja más sin foliar.
—Año 1618. En Madrid, por la viuda de Alonsso Martin. A costa
de Domingo Gonçalez, mercader de libros.
8.º, 4 hs. prls. sin foliar y 112 pp. dobles.
—Con menos seguridad encuentro citadas las ediciones de
Amberes, 1616, y Bruselas, 1618, que nunca he visto.
D. Adolfo de Castro reimprimió estos Diálogos en el tomo de
Curiosidades Bibliográficas de la Biblioteca de Rivadeneyra, y
también se han reproducido (suprimiendo el capítulo de las
bubas) en un tomo de la Biblioteca Clásica Española de la Casa
Cortezo, Barcelona, 1884, que lleva el título de Extravagantes.
Opúsculos amenos y curiosos de ilustres autores.
[239] Tiene este vejamen una curiosa alusión al Brocense: «el
maestro Sánchez, el retórico, el griego, el hebreo, el músico, el
médico y el filósofo, el jurista y el humanista tiene una cabeza,
que en todas estas ciencias es como Ginebra, en la diversidad de
profesiones». «Este maestro (añade, á modo de glosa, Gaspar
Lucas Hidalgo), aunque sabía mucho, tenía peregrinas opiniones
en todas estas facultades».
La alusión á Ginebra no haría mucha gracia al Brocense, que ya
en 1584 había tenido contestaciones con el Santo Oficio y que
volvió á tenerlas en aquel mismo año de 1600, postrero de su
vida.
[240] Actus gallicus ad magistrum Franciscum Sanctium, «en el
grado de Aguayo», per fratrem Ildephonsum de Mendoza
Augustinum.
Está en el famoso códice AA-141-4 de la Biblioteca Colombina,
que dio ocasión á D. Aureliano Fernández Guerra para escribir
tanto y tan ingeniosamente en el apéndice al primer tomo de la
bibliografía de Gallardo.
El Maestro Francisco Sánchez, de quien se trata, es persona
distinta del Brocense, que asistió á su grado juntamente con Fr.
Luis de León y otros maestros famosos.
[241] Über eine spanische Handschrift der Wiener Hofbibliothek
(1867), pág. 89. Mussafia formó un pequeño glosario para
inteligencia de esta composición.
También la reproduce el Sr. Paz y Melia en sus Sales Españolas
(I, p. 249): «Carta increpando de corto en lenguaje castellano, ó
la carta del monstruo satírico de la lengua española».
[242] Hállase en el códice antes citado de la Biblioteca
Colombina.
[243] El Sr. Paz y Melia (Sales Españolas, I, pág. VIII) cita un
inventario manuscrito de los cuadros propios de D. Luis Méndez
de Haro y Guzmán que pasaron á la Casa de Alba, en el cual se
lee lo siguiente:
«Un cuadro de un Duque de Alba enfermo, echando mano á la
espada, y un médico con la jeringa en la mano y en la otra el
bonete encarnado de doctor. Es de mano de Diego Velázquez.
De dos varas y cuarta de alto y vara y cuarta de ancho».
Todavía se menciona este cuadro en otro inventario de 1755,
pero luego se pierde toda noticia de él.
[244] Parte primera del libro intitulado Noches de Inuierno.
Compuesto por Antonio de Eslaua, natural de la villa de
Sangüessa. Dedicado a don Miguel de Nauarra y Mauleon,
Marques de Cortes, y señor de Rada y Treybuenos. En
Pamplona. Impresso: por Carlos de Labayen, 1609.
8.º, 12 hs. prls., 239 pp. dobles y una en blanco.
Aprobaciones de Fr. Gil Cordon y el Licdō. Juan de Mendi
(Pamplona, 27 de noviembre de 1608 y 26 de junio de 1609).—
Dedicatoria al Marqués de Cortes:... «He procurado siempre de
hablar con los muertos, leyendo diversos libros llenos de historias
Antiguas, pues ellos son testigos de los tiempos, y imagenes de
la vida; y de los mas dellos y de la oficina de mi corto
entendimiento, he sacado con mi poco caudal, estos toscos y mal
limados Dialogos: y viendo tambien quan estragado está el gusto
de nuestra naturaleza, los he guisado con un saynete de
deleytacion, para que despierte el apetito, con título de Noches
de Invierno: llevando por blanco de aliviar la pesadumbre dellas;
alagando los oydos al Lector, con algunas preguntas de la
Philosophia natural y moral, insertas en apacibles historias».
Prólogo al discreto lector: «Advierte... una cosa que estás
obligado a disimular conmigo, mas que con ningun Autor, las
faltas, los yerros, el poco ornato y retorica de estos mis Dialogos,
atento que mi voluntad con el exercicio della, se ha opuesto a
entretenerte y aliviarte de la gran pesadumbre de las noches del
Invierno».
Soneto del autor á su libro. Véanse los tercetos:

Acogete a la casa del discreto,

Del curioso, del sabio, del prudente
Que tienen su morada en la alta cumbre.
Que ellos te ternan con gran respeto,
Vestiran tu pobreza ricamente,
Y asiento te daran junto a la lumbre.

Soneto de D. Francisco de Paz Balboa, en alabanza del autor.—

De un amigo al autor (redondillas).—Sonetos laudatorios del
Licenciado Morel y Vidaurreta, relator del Consejo Real de
Navarra; de Hernando Manojo; de Miguel de Hureta, criado del
Condestable de Navarra y Duque de Alba; de Fr. Tomás de Avila
y Paz, de la Orden de Santo Domingo; de un fraile francisco (que
pone el nombre de Eslava en todos los versos); de D. Juan de
Eslava, racionero de la catedral de Valladolid y hermano del autor
(dos sonetos).—Texto.—Tabla de capítulos.—Tabla de cosas
notables.—Nota final.
—Parte primera del libro intitvlado Noches de Inuierno.
Compuesto... (ut supra). Dirigido a don Ioan Iorge Fernandez de
Heredia Conde de Fuentes, señor de la Casa y varonia de Mora,
Comendador de Villafranca, Gouernador de la orden de
Calatraua... Año 1609. En casa Hieronymo Margarit. A costa de
Miguel Menescal, Mercader de Libros.
8.º, 236 pp. dobles.
Aprobación de Fr. Juan Vicente (Santa Catalina, 16 de setiembre
de 1609).—Licencia del Ordinario (18 de setiembre). Siguen los
preliminares de la primera edición, aunque no completos.
—Parte primera... (ut supra). Dedicado a D. Miguel de Nauarra y
Mauleon, Marquez (sic) de Cortes... En Brvsellas. Por Roger
Velpius y Huberto Antonio, Impressores de sus Altezas, à l'Aguila
de oro, cerca de Palacio. 1610. Con licencia.
12.º, 258 hs. Reproduce todos los preliminares de la de
Pamplona y añade un Privilegio por seis años á favor de Roger
Velpius y Huberto Antonio (Bruselas, 7 de mayo de 1610).
Existe una traducción alemana de las Noches de Invierno
(Winternächte... Aus dem Spanischen in die Teutsche Sprache...)
por Mateo Drummer (Viena, 1649; Nüremberg, 1666). Vid.
Schneider, Spaniens Anteil an der Deutschen Litteratur, p. 256.
Tabla de los capítulos en el libro de Eslava:
«Capitulo Primero. Do se cuenta la perdida
del Navio de Albanio.
Cap. 2. Do se cuenta cómo fue
descubierta la fuente del Desengaño.
Cap. 3. Do se cuenta el incendio del
Galeon de Pompeo Colona.
Cap. 4. Do se cuenta la sobervia del Rey
Niciforo, y incendio de sus Naves, y la Arte
Magica del Rey Dardano.
Cap 5. Do se cuenta la iusticia de Celin
Sultan gran Turco, y la vengaza de Zayda.
Cap. 6. Do se cuenta quien fue el esclavo
Bernart.
Cap. 7. Do se cuenta los trabajos y
cautiverio del Rey Clodomiro y la Pastoral
 de Arcadia.
Cap. 8. Do se cuenta el nacimiento de
Roldan y sus niñerias.
Cap. 9. Do defiende Camila el genero
Femenino.
Cap. 10. Do se cuenta el nacimiento de
Carlo Magno Rey de Francia.
Cap. 11. Do se cuenta el nacimiento de la
Reyna Telus de Tartaria».
[245] Fue publicada por el misionero inglés Henry Callaway, con
otros cuentos de la misma procedencia, en la colonia de Natal,
en 1868. Véase H. Husson, La Chaîne traditionelle. Contes et
légendes au point de vue mythique (París, 1874), p. 115. Este
libro, aunque excesivamente sistemático, sobre todo en la
aplicación del mito solar, contiene, á diferencia de tantos otros,
muchas ideas y noticias en pocas palabras. No es indiferente
para el estudio de los romances castellanos, verbigracia: el de
Delgadina (mito védico de Prajapati—leyenda hagiográfica de
Santa Dina ó Dympna, hija del rey de Irlanda,—novela de
Doralice y Teobaldo, príncipe de Salerno, en Straparola), ó el de
la Infantina, emparentado con el cuento indio de Suria-Bai (pp. 57
y 111).
[246] Histoire poétique de Charlemagne, p. 432.
[247] Les Epopées Françaises, t. III, p. 11.
[248] Ueber die altfranzösischen Heldengedichte aus dem
Karolingischen Sagenkreise, Viena, 1883.
[249] Li Romans de Berte aus grans piés, précedé d'une
Dissertation sur les Romans des douze pairs, par M. Paulin Paris,
de la Bibliothèque du Roi. París, Techener, 1832.
Hay otra edición más correcta, publicada por Augusto Scheler,
conforme al manuscrito de la Biblioteca del Arsenal de París: Li
Roumans de Berte aus grans piés, par Adènes le Roi (Bruselas,
1874).
Mussafia publicó en la Romania (julio de 1874 y enero de 1875)
el texto del poema franco-italiano, anterior quizá en ochenta años
al de Adenet.
[250] Tanto en el poema de Adenès, como en el texto franco-
itálico, lo que distingue á Berta es únicamente el tener los pies