B R I E F C O N T E N T S
UNIT I Pathophysiologic Processes
1 Introduction to Pathophysiology, 1
2 Homeostasis, Allostasis, and Adaptive Responses to Stressors, 12
UNIT II Cellular Function
3 Cell Structure and Function, 26
4 Cell Injury, Aging, and Death, 59
5 Genome Structure, Regulation, and Tissue Differentiation, 77
6 Genetic and Developmental Disorders, 94
7 Neoplasia, 117
UNIT III Defense
8 Infectious Processes, 141
9 Inflammation and Immunity, 158
10 Alterations in Immune Function, 194
11 Malignant Disorders of White Blood Cells, 215
12 HIV Disease and AIDS, 233
UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
13 Alterations in Oxygen Transport, 259
14 Alterations in Hemostasis and Blood Coagulation, 298
15 Alterations in Blood Flow, 313
16 Alterations in Blood Pressure, 337
UNIT V Cardiac Function
17 Cardiac Function, 354
18 Alterations in Cardiac Function, 382
19 Heart Failure and Dysrhythmias: Common Sequelae of Cardiac Diseases, 411
20 Shock, 434
UNIT VI Respiratory Function
21 Respiratory Function and Alterations in Gas Exchange, 451
22 Obstructive Pulmonary Disorders, 478
23 Restrictive Pulmonary Disorders, 499
UNIT VII Fluid, Electrolyte, and Acid-Base Homeostasis
24 Fluid and Electrolyte Homeostasis and Imbalances, 521
25 Acid–Base Homeostasis and Imbalances, 541
UNIT VIII Renal and Bladder Function
26 Renal Function, 551
27 Intrarenal Disorders, 575
28 Acute Kidney Injury and Chronic Kidney Disease, 593
29 Disorders of the Lower Urinary Tract, 609
UNIT IX Genital and Reproductive Function
30 Male Genital and Reproductive Function, 626
31 Alterations in Male Genital and Reproductive Function, 641
32 Female Genital and Reproductive Function, 656
33 Alterations in Female Genital and Reproductive Function, 671
34 Sexually Transmitted Infections, 689
UNIT X Gastrointestinal Function
35 Gastrointestinal Function, 697
36 Gastrointestinal Disorders, 720
37 Alterations in Function of the Gallbladder and Exocrine Pancreas, 742
38 Liver Diseases, 754
UNIT XI Endocrine Function, Metabolism, and Nutrition
39 Endocrine Physiology and Mechanisms of Hypothalamic-Pituitary Regulation, 783
40 Disorders of Endocrine Function, 799
41 Diabetes Mellitus, 815
42 Nutritional and Metabolic Disorders, 838
UNIT XII Neural Function
43 Structure and Function of the Nervous System, 850
44 Acute Disorders of Brain Function, 891
45 Chronic Disorders of Neurologic Function, 915
46 Alterations in Special Sensory Function, 936
47 Pain, 955
UNIT XIII Neuropsychological Function
48 Neurobiology of Psychotic Illnesses, 971
49 Neurobiology of Nonpsychotic Illnesses, 989
UNIT XIV Musculoskeletal Support and Movement
50 Structure and Function of the Musculoskeletal System, 1001
51 Alterations in Musculoskeletal Function: Trauma, Infection, and Disease, 1020
52 Alterations in Musculoskeletal Function: Rheumatic Disorders, 1042
UNIT XV Integumentary System
53 Alterations in the Integumentary System, 1058
54 Burn Injuries, 1093
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• Glossary with audio pronunciations.
• Answers to key questions.
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PATHOPHYSIOLOGY TH EDITION6
JACQUELYN L. BANASIK, PhD, ARNP Associate Professor College of Nursing
Washington State University Spokane, Washington
LEE-ELLEN C. COPSTEAD, PhD, RN Professor Emerita
Department of Nursing College of Nursing and Health Sciences
University of Wisconsin—Eau Claire Eau Claire, Wisconsin
3251 Riverport Lane St. Louis, Missouri 63043
PATHOPHYSIOLOGY, SIXTH EDITION ISBN: 978-0-323-35481-3
Copyright © 2019 by Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).
Notices
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
Previous editions copyrighted 2013, 2010, 2005, 2000, and 1995.
International Standard Book Number: 978-0-323-35481-3
Executive Content Strategist: Kellie White Content Development Specialist: Jennifer Wade Publishing Service Manager: Jeffrey Patterson Book Production Specialist: Carol O’Connell Book Designer: Renee Duenow
Printed in Canada
Last digit is the print number: 9 8 7 6 5 4 3 2 1
http://www.elsevier.com/permissions
To:
Loved ones, past and present,
who give meaning to the work.
JLB
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vii
Brent A. Banasik, PhD, MA, BS Scientist Chemistry Banasik Consulting Seattle, Washington
Brianne N. Banasik, BS Environmental Science, MS Marine Resources Management
Research Associate Pediatric Vaccinology University of Texas Medical Branch Galveston, Texas
Jacquelyn L. Banasik, PhD, ARNP Associate Professor College of Nursing Washington State University Spokane, Washington
Robin Y. Beeman, BSN, MSN, PhD Chair and Professor Nursing University of Wisconsin—Eau Claire Eau Claire, Wisconsin
Cheryl L. Brandt, PhD, RN, ACNS-BC Professor College of Nursing and Health Sciences University of Wisconsin—Eau Claire Eau Claire, Wisconsin
Ann Futterman Collier, PhD Associate Professor and Chair Psychological Sciences Northern Arizona University Flagstaff, Arizona
Lee-Ellen C. Copstead, PhD, RN Professor Emerita Department of Nursing College of Nursing and Health Sciences University of Wisconsin—Eau Claire Eau Claire, Wisconsin
Carol L. Danning, MD Staff Rheumatologist Rheumatology Department Gundersen Health Systems La Crosse, Wisconsin
Michael R. Diestelmeier, MD Fellow American Academy of Dermatology Dermatologist, Retired Mayo Clinic Health System Eau Claire, Wisconsin
Ruth E. Diestelmeier, RN, MSN Clinical Instructor Department of Nursing University of Wisconsin—Eau Claire Eau Claire, Wisconsin
C O N T R I B U T O R S
Roberta J. Emerson, PhD, RN Associate Professor, Retired Washington State University College of Nursing Spokane, Washington
Linda Felver, PhD, RN Associate Professor School of Nursing Oregon Health & Science University Portland, Oregon
Rosemary A. Jadack, PhD, RN Professor Nursing University of Wisconsin—Eau Claire Eau Claire, Wisconsin
Debra A. Jansen, PhD, RN Associate Dean, Professor College of Nursing and Health Sciences University of Wisconsin—Eau Claire Eau Claire, Wisconsin
Marie L. Kotter, PhD, MS, BS Professor Emeritus Health Sciences Weber State University Ogden, Utah
Teresa Grigsby Loftsgaarden, MSN, RN, OCN,ONN-CG
Oncology Nurse Navigator Regional Cancer Center Sacred Heart Hospital Eau Claire, Wisconsin
Joni D. Marsh, BSN, MN Advanced Registered Nurse Practitioner Medical Oncology Summit Cancer Centers Spokane, Washington
Benjamin J. Miller, PhD, ARNP, FNP-C, ACNPC, ENP-C
Assistant Professor Seattle University Seattle, Washington
Sarah Ogle, DO, MS Banner University Medical Center-Phoenix University of Arizona College of Medicine
Phoenix Phoenix, Arizona
Nirav Patel, MD Assistant Professor, Infectious Diseases and
Critical Care Medicine Internal Medicine Saint Louis University School of Medicine; Chief Medical Officer SSM Health Saint Louis University Hospital; Infection Control Officer/Director of
Antibiotic Stewardship SSM Health Saint Louis University Hospital Saint Louis, Missouri
Faith Young Peterson, BSN, MSN, MPA, CFNP
Family Nurse Practitioner Marsing, Idaho
Cheryl Rockwell, RN, MSN Clinical Assistant Professor Nursing Department Indiana University-Purdue University at
Fort Wayne; Staff/Clinical Nurse Surgical Trauma Intensive Care Unit Parkview Health Systems Fort Wayne, Indiana
Samantha Cody Russell, Psychology, MA Graduate Student Psychological Sciences Northern Arizona University Flagstaff, Arizona
Jeffrey S. Sartin, MD Consulting Physician Infectious Diseases Infectious Disease and Epidemiology
Associates; Consulting Physician Infectious Diseases Nebraska Medicine; Consulting Physician Infectious Diseases CHI Hospitals Omaha, Nebraska
Lorna L. Schumann, PhD Heritage UGM Women and Children’s
Clinic Medical Clinic Heritage Health Coeur d’Alene, Idaho
Susan G. Trevithick, RN, MS, NE-BC Compliance Officer VA Salt Lake City Healthcare System Salt Lake City, Utah
Marvin Van Every, MD Staff Urologist Urology Department Gundersen Health Systems La Crosse, Wisconsin
Linda D. Ward, PhD, FNP-C Assistant Professor College of Nursing Washington State University Spokane, Washington
viii
Brianne N. Banasik, MS Research Associate Pediatric Vaccinology University of Texas Medical Branch Galveston, Texas
Deb Cipali, RN, BSN, MSN, EdD(c) Des Moines Area Community College Nursing Lab Coordinator/Adjunct Professor Ankeny, Iowa
Janie Corbitt, RN, MLS Milledgville, Georgia
Maria Fleurdeliz Cuyco, BS Instructor Preferred College of Nursing Los Angeles, California
Abimbola Farinde, PhD Professor Columbia Southern University Orange Beach, Alabama
Annette Gunderman, DEd, MSN, RN Associate Professor of Nursing Bloomsburg University Bloomsburg, Pennsylvania
Barbara Hunter, RN, MSN School of Nursing, Klamath Falls Campus Oregon Health & Science University Klamath Falls, Oregon
Sandra L. Kaminski, MS, PA-C Assistant Professor Seton Hall University School of Health and Medical Sciences; Physician Assistant VA NJ Healthcare System Medical Service/Infections Disease Clark, New Jersey
Steven Krau, PhD, RN, CNE Associate Professor Vanderbilt School of Nursing Nashville, Tennessee
Clarice Perry, MS Research Associate Pediatric Vaccinology University of Texas Medical Branch Galveston, Texas
R E V I E W E R S
Janet Pinkelman, MSN, RNC-Maternal Newborn Nursing
Professor of Nursing Owens Community College Toledo, Ohio
Linda Turchin, RN, MSN, CNE Associate Professor of Nursing Fairmont State University Fairmont, West Virginia
Kim Webb, MN, RN Adjunct Nursing Instructor Pioneer Technology Center Ponca City, Oklahoma
Janice Williams, RN, ACNS-BC, CDE Professor of Nursing and Program Director Armstrong McDonald School of Nursing College of the Ozarks Point Lookout, Missouri
ix
The pace of scientific discovery in health and medicine continues to transform our understanding of physiology and disease. To be clinically relevant and useful to health care students and professionals, a text must synthesize a vast amount of detailed knowledge into overarching concepts that can be applied broadly. As in previous editions, the goal of the sixth edition of Pathophysiology is to include recent and relevant information on anatomy, biochemistry, cell physiology, genomics, and pathophysiology while not overwhelming the reader. Attention is given to major concepts relevant to clinical practice while still providing enough detail for deep understanding.
ORGANIZATION Pathophysiology uses a systems approach to content, beginning with a review of normal anatomy and physiology, followed by pathophysiology and application of concepts to specific disorders. The text is organized into 15 units, each of which includes a particular body system or group of interrelated body systems and the pertinent pathophysiologic concepts and disorders.
FEATURES An understanding of normal structure and function of the body is necessary for any detailed understanding of its abnormalities and pathophysiology. The first chapter in most units includes a fully illustrated review of normal physiology. Age-related concepts are highlighted in boxes titled Geriatric Considerations and Pediatric Considerations.
Each chapter opens with Key Questions, which are designed to alert the reader to important conceptual questions that will be discussed in the chapter. Although the chapters are meant to be read from beginning to end to develop an understanding of the material, the text also serves as a reference for looking up specific content. Chapter Outlines are included at the beginning of each chapter to help the reader locate specific content. Within every chapter, Key Points are identified at the end of every major discussion and are presented in short bulleted lists. These recurring summaries help readers to focus on the main points.
Nearly 900 illustrations elucidate both normal physiology and pathophysiologic changes. The entire book is in full color, with color
used generously in the illustrations to better explain pathophysiologic concepts.
A study of pathophysiology requires a new vocabulary, and many of these terms are defined in a comprehensive Glossary, which appears at the end of the text. Common prefixes and suffixes as well as root words are included in the back matter to help with basic understanding of the language of pathophysiology.
ANCILLARIES Student Learning Resources on Evolve The student section of the book’s website hosted on Evolve offers nearly 700 Student Review Questions in a variety of question formats, an Audio Glossary, Animations to help readers visualize pathophysiologic processes, Case Studies with questions, and Key Points Review. Visit the Evolve website at http://evolve.elsevier.com/Banasik/pathophysiology.
Study Guide Pathophysiology can be a daunting subject for students because of the large volume of factual material to be learned. The student Study Guide is designed to help students focus on important pathophysiologic concepts. Questions to check recall of normal anatomy and physiology are included for each chapter. A number of activities that help the student focus on similarities and differences between often-confused pathologic processes are included. More than 1500 self-assessment test questions with answers are included to help students check their understanding and build confidence for examinations. Case studies, with more than 250 questions including rationales for correct and incorrect answers, are used to help students begin to apply pathophysi- ologic concepts to clinical situations.
Instructor Learning Resources on Evolve The Instructor Learning Resources on Evolve provide a number of teaching aids for instructors who require the text for their students. The materials include a Test Bank presented in Exam View with approximately 1200 test items, a Teach for Nurses instructor manual detailing the resources available to instructors for their lesson planning, a PowerPoint lecture guide with more than 4000 slides with integrated case studies and audience response questions to facilitate classroom presentations, and an Image Collection of more than 900 color images from the text.
P R E F A C E
http://evolve.elsevier.com/Banasik/pathophysiology
x
Revising this 6th edition of the text has been possible because of the tremendous dedication of authors, artists, reviewers, and editors. Sincere gratitude goes to all who helped with this and previous editions. In particular, grateful appreciation is extended to all of the contributing authors who have given exhaustively of their time over many editions over the decades. Thank you to the many thoughtful experts who gave their time to read and critique manuscripts and help ensure excellence in chapter content throughout the text.
Grateful recognition is made to the staff at Elsevier: Kellie White, Executive Content Strategist; Jennifer Wade, Content Development Specialist; Jeffrey Patterson, Publishing Service Manager; Carol O’Connell, Book Production Specialist; Renee Duenow, Book Designer; and Vikraman Palani, Multimedia Producer.
We would like to recognize those who provided a foundation for the revised text through their contributions to earlier editions: Arnold A. Asp, Donna Bailey, Barbara Bartz, Linda Belsky-Lohr, Tim Brown, Carolyn Spenee Cagle, Karen Carlson, Katherina P. Choka, Arnold Norman Cohen, Cynthia F. Corbett, Lorri Dawson, Leslie Evans, Patricia Garber, Jane Georges, Karen Groth, Christine M. Henshaw, Carolyn Hoover, Jo Annalee Irving, Marianne Genge Jagmin, Debby Kaaland, Naomi Lungstrom, Rick Madison, Anne Roe Mealey, David Mikkelsen, Carrie Miller, Linda Denise Oakley, Maryann Pranulis, Mark Puhlman, Edith Randall, Bridget Recker, Cleo Richard, Dawn Rondeau, Mary Sanguinetti-Baird, Billie Marie Severtsen, Jacqueline Siegel, Gary Smith, Sheila Smith, Martha Snider, Pam Springer, Angela Starkweather, Patti Stec, Julie Symes, Lorie Wild, and Debra Winston-Heath.
A C K N O W L E D G M E N T S
xixi
C O N T E N T S
UNIT I Pathophysiologic Processes
1 Introduction to Pathophysiology, 1 Lee-Ellen C. Copstead
Framework for Pathophysiology, 2 Etiology, 2 Pathogenesis, 2 Clinical Manifestations, 3 Treatment Implications, 3
Concepts of Normality in Health and Disease, 4 Statistical Normality, 4 Individual Factors Influencing Normality, 5
Patterns of Disease in Populations, 6 Concepts of Epidemiology, 6
2 Homeostasis, Allostasis, and Adaptive Responses to Stressors, 12 Debra A. Jansen and Roberta J. Emerson
Homeostasis and Allostasis, 12 Homeostasis, 12 Allostasis, 13
Stress as a Concept, 13 The General Adaptation Syndrome and
Allostasis, 14 Stressors, Gender and Developmental Influences,
and Risk Factors, 16 Neurohormonal Mediators of Stress and
Adaptation, 17 Catecholamines: Norepinephrine and
Epinephrine, 17 Adrenocortical Steroids: Cortisol and
Aldosterone, 18 Endorphins, Enkephalins, and Immune
Cytokines, 19 Sex Hormones: Estrogen, Testosterone, and
Dehydroepiandrosterone, 19 Growth Hormone, Prolactin, and
Oxytocin, 19 Adaptation, Coping, and Illness, 20
Adaptation, Coping, and Resilience, 20 Allostatic Overload and Illness, 21
UNIT II Cellular Function
3 Cell Structure and Function, 26 Jacquelyn L. Banasik and Brianne N. Banasik
Plasma Membrane, 27 Membrane Structure, 27 Lipid Bilayer, 27 Membrane Proteins, 29
Organization of Cellular Compartments, 30 Cytoskeleton, 30 Nucleus, 30 Endoplasmic Reticulum, 31 Golgi Apparatus, 32 Lysosomes and Peroxisomes, 33 Mitochondria, 34
Cellular Metabolism, 34 Glycolysis, 36 Citric Acid Cycle, 36 Oxidative Phosphorylation, 36
Functions of the Plasma Membrane, 39 Membrane Transport of Macromolecules, 39 Membrane Transport of Small Molecules, 40 Cellular Membrane Potentials, 45
Intercellular Communication and Growth, 48 Cell Signaling Strategies, 48 Cell Surface Receptor–Mediated Responses, 49 Intracellular Receptor–Mediated Responses, 53 Regulation of Cellular Growth and Proliferation, 54
4 Cell Injury, Aging, and Death, 59 Jacquelyn L. Banasik
Reversible Cell Injury, 59 Hydropic Swelling, 60 Intracellular Accumulations, 60
Cellular Adaptation, 63 Atrophy, 63 Hypertrophy, 63 Hyperplasia, 63 Metaplasia, 63 Dysplasia, 64
Irreversible Cell Injury, 64 Necrosis, 64 Apoptosis, 66
Etiology of Cellular Injury, 68 Ischemia and Hypoxic Injury, 68 Nutritional Injury, 70 Infectious and Immunologic Injury, 70 Chemical Injury, 72 Physical and Mechanical Injury, 72
Cellular Aging, 74 Cellular Basis of Aging, 74 Physiologic Changes of Aging, 75
Somatic Death, 75 5 Genome Structure, Regulation, and Tissue
Differentiation, 77 Jacquelyn L. Banasik
Structure and Function of DNA, 78 Structure of DNA, 78 DNA Replication, 79 Genetic Code, 80 Transcription, 81 Translation, 82
Regulation of the Genome, 84 Transcriptional Controls, 84
Differentiation of Tissues, 86 Cell Diversification and Cell Memory, 86 Mechanisms of Development, 86 Differentiated Tissues, 87
6 Genetic and Developmental Disorders, 94 Linda D. Ward
Principles of Inheritance, 95 DNA Mutation and Repair, 96
xii CoNTeNTs
GENETIC DISORDERS, 98 Chromosomal Abnormalities, 99
Aberrant Number of Chromosomes, 99 Abnormal Chromosome Structure, 100 Examples of Autosomal Chromosome
Disorders, 100 Examples of Sex Chromosome Disorders, 101
Mendelian Single-Gene Disorders, 102 Autosomal-Dominant Disorders, 103 Autosomal-Recessive Disorders, 104 Sex-Linked (X-Linked) Disorders, 106
Nonmendelian Single-Gene Disorders, 107 Anticipation, 109 Mitochondrial Gene Mutations, 109 Genomic Imprinting, 110
Polygenic and Multifactorial Disorders, 110 Environmentally Induced Congenital
Disorders, 111 Periods of Fetal Vulnerability, 111 Teratogenic Agents, 111 Other Disorders of Infancy, 113
Diagnosis, Counseling, and Gene Therapy, 113 Prenatal Diagnosis and Counseling, 113 Genetic Analysis and Therapy, 114 Recombinant DNA Technology, 114
7 Neoplasia, 117 Jacquelyn L. Banasik
Benign Versus Malignant Growth, 118 Characteristics of Benign and Malignant
Tumors, 118 Tumor Terminology, 118 The Malignant Phenotype, 118
Epidemiology and Cancer Risk Factors, 120 Tobacco Use, 120 Nutrition, 120
Genetic Mechanisms of Cancer, 123 Proto-Oncogenes, 124 Tumor Suppressor Genes, 127
Multistep Nature of Carcinogenesis, 129 Initiation, 129 Promotion, 131 Progression, 131
Metastasis, 132 Patterns of Spread, 132 Angiogenesis, 133 Grading and Staging of Tumors, 134
Effects of Cancer on the Body, 136 Cancer Therapy, 137
Surgery, 137 Radiation Therapy, 138 Drug Therapy, 138 Immunotherapy, 138 Gene and Molecular Therapy, 138 Stem Cell Transplantation, 139
UNIT III Defense
8 Infectious Processes, 141 Brent A. Banasik
Host–Microbe Relationship, 142 The Human Microbiome, 142
Host Characteristics, 142 Pathogen Characteristics, 144
Transmission of Infection, 147 Routes of Transmission, 148 Emerging Infectious Diseases, 148 Weapons of Bioterrorism, 149
Types of Pathogenic Organisms, 149 Bacteria, 149 Viruses, 150 Fungi, 151 Parasites, 152
9 Inflammation and Immunity, 158 Jacquelyn L. Banasik
COMPONENTS OF THE IMMUNE SYSTEM, 159
Epithelial Barriers, 159 Mononuclear Phagocyte System, 159 Lymphoid System, 160
Primary Lymphoid Organs, 160 Secondary Lymphoid Organs, 161
Leukocytes, 162 Neutrophils, 162 Eosinophils, 163 Basophils and Mast Cells, 164 Monocytes and Macrophages, 164 Dendritic Cells, 165 Lymphocytes, 165
Chemical Mediators of Immune Function, 167 Complement, 167 Kinins, 169 Clotting Factors, 169 Cytokines and Chemokines, 169
INNATE DEFENSES AND INFLAMMATION, 169 Inflammation, 171
Increased Vascular Permeability, 171 Emigration of Leukocytes, 172 Phagocytosis, 172 Chronic Inflammation, 174
Healing, 174 Inflammatory Exudates, 175 Systemic Manifestations of Inflammation, 175 SPECIFIC ADAPTIVE IMMUNITY, 176 Major Histocompatibility Complex, 176 Antigen Presentation by MHC, 176
MHC Class I Presentation, 177 MHC Class II Presentation, 177
Mechanisms of Cell-Mediated Immunity, 178 T Helper Cells (CD4+), 178 Cytotoxic T Cells (CD8+), 181
Mechanisms of Humoral Immunity, 181 Antigen Recognition by B Cells, 181
Antibody Structure, 183 Class Switching and Affinity Maturation, 185 Antibody Functions, 186
Passive and Active Immunity, 187 Passive Immunity, 187 Active Immunity, 187
INTEGRATED FUNCTION AND REGULATION OF THE IMMUNE SYSTEM, 189
Integrated Response to Microbial Antigen, 189 Integrated Response to Viral Antigen, 191 Regulation of Immune Function, 192
CoNTeNTs xiii
10 Alterations in Immune Function, 194 Faith Young Peterson
EXCESSIVE IMMUNE RESPONSES, 195 Autoimmunity, 195
Genetic Factors, 196 Environmental Triggers, 196 Pharmacotherapies, 197
Hypersensitivity, 198 Type I Hypersensitivity, 199 Type IIa Hypersensitivity, 201 Type IIb Hypersensitivity, 204 Type III Hypersensitivity, 204 Type IV Hypersensitivity, 207
DEFICIENT IMMUNE RESPONSES, 210 Primary Immunodeficiency Disorders, 210
B-Cell and T-Cell Combined Disorders, 210 T-Cell Disorders, 211 B-Cell Disorders, 212
Secondary Immunodeficiency Disorders, 212 11 Malignant Disorders of White Blood Cells, 215
Marie L. Kotter and Jacquelyn L. Banasik Classification of Hematologic Neoplasms, 215 Etiology of Myeloid and Lymphoid Neoplasms, 216 General Principles of Management, 217
Diagnosis of Hematologic Neoplasms, 217 Principles of Treatment, 218 Prevention and Management of Complications, 219
Myeloid Neoplasms, 221 Chronic Myeloid Leukemia, 221 Acute Myeloid Leukemia, 222
Lymphoid Neoplasms, 223 Chronic Lymphoid Leukemia, 223 Acute Lymphoblastic Leukemia/Lymphoma, 223 Hairy Cell Leukemia, 224 Plasma Cell Myeloma (Multiple Myeloma), 224 Hodgkin Disease, 227 B-Cell, T-Cell, and NK-Cell Lymphoma
(Non-Hodgkin), 229 12 HIV Disease and AIDS, 233
Faith Young Peterson Epidemiology, 234
History, 234 Types of HIV, 234 Transmission, 236 Prevention of Transmission, 238
Etiology, 239 HIV Structure, 239 HIV Binding and Infection, 239
Pathogenesis, 242 Effect of HIV on Immune Cells at the Cellular
Level, 242 Viral Production and Cell Death, 242 Progression of HIV Infection From Seroconversion
to AIDS, 244 CDC HIV Classification System, 245
Diagnostic Testing, 245 Monitoring the Progression of HIV, 246 Clinical Manifestations, 248
Systemic Manifestations, 248 Gastrointestinal Manifestations, 249 Pulmonary Manifestations, 249 Mucocutaneous Manifestations, 250
Gynecologic Manifestations, 251 Neurologic Manifestations, 252 Ocular Manifestations, 253 Cardiovascular Manifestations, 253 Manifestations in Other Systems, 253 Manifestations in Children, 254
Treatment, 254 Antiretroviral Therapy Recommendations, 254 Nucleoside Reverse Transcriptase Inhibitors, 255 Nucleotide Reverse Transcriptase Inhibitors, 255 Nonnucleoside Reverse Transcriptase
Inhibitors, 255 Protease Inhibitors, 257 Fusion Inhibitors, 257 CCR5 Inhibitors, 257 Integrase Strand Transfer Inhibitors, 257 Other Treatments and Vaccines, 257
UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
13 Alterations in Oxygen Transport, 259 Susan G. Trevithick
Composition of Blood, 260 Organic and Inorganic Components, 261 Cellular Components, 261
Structure and Function of Red Blood Cells, 262 Hematopoiesis, 263 Hemoglobin Synthesis, 265 Nutritional Requirements for Erythropoiesis, 266 Energy and Maintenance of Erythrocytes, 267 Red Cell Production, 267 Red Cell Destruction, 268
Gas Transport and Acid–Base Balance, 268 Oxygen Transport, 268 Carbon Dioxide Transport, 270 Alterations in Oxygen Transport, 270
Anemia, 272 General Effects of Anemia, 272
Anemia Related to Decreased Red Cell Production, 277 Aplastic Anemia, 277 Anemia of Chronic Renal Failure, 277 Anemia Related to Vitamin B12 (Cobalamin)
or Folate Deficiency, 278 Iron Deficiency Anemia, 279
Anemia Related to Inherited Disorders of the Red Cell, 279 Thalassemia, 279 Sickle Cell Anemia, 281 Hereditary Spherocytosis, 282 Glucose-6-Phosphate Dehydrogenase
Deficiency, 282 Anemia Related to Extrinsic Red Cell Destruction or
Loss, 284 Hemolytic Disease of the Newborn, 284 Antibody-Mediated Drug Reactions, 284 Acute Blood Loss, 285 Other Extrinsic Abnormalities, 285
Transfusion Therapy, 286 Polycythemia, 286
xiv CoNTeNTs
Polycythemia Vera, 286 Secondary Polycythemia, 292 Relative Polycythemia, 293
14 Alterations in Hemostasis and Blood Coagulation, 298 Cheryl Rockwell
The Process of Hemostasis, 298 Stages of Hemostasis, 298 Platelets, 299 Blood Coagulation Factors, 299 Fibrin Clot, 299 Fibrinolysis, 301
Evaluation of Hemostasis and Coagulation, 301 Clinical Assessment, 301 Laboratory Tests, 304
Vascular and Platelet Disorders, 304 Vascular Disorders, 304 Platelet Disorders, 306
Coagulation Disorders, 308 15 Alterations in Blood Flow, 313
Teresa Grigsby Loftsgaarden Organization of the Circulatory and Lymphatic
Systems, 315 Vessel Structure, 315 Lymphatic Structure, 317
Principles of Flow, 317 Hemodynamics of the Circulatory System, 317
Control of Flow, 322 Control of Blood Flow, 322 Control of Lymphatic Flow, 323
General Mechanisms That Cause Altered Flow, 323 Blood Vessels: Obstructions, 323 Blood Vessels: Structural Alterations, 325 Lymphatic Vessels, 326
Alterations in Arterial Flow, 326 Arteriosclerosis/Atherosclerosis, 326 Thromboangiitis Obliterans (Buerger Disease), 330 Raynaud Syndrome, 330 Aneurysms, 330 Acute Arterial Occlusion, 331
Alterations in Venous Flow, 332 Valvular Incompetence, 332 Varicose Veins, 332 Chronic Venous Insufficiency, 333 Deep Vein Thrombosis, 333
Alterations in Lymphatic Flow, 333 Lymphedema, 333
16 Alterations in Blood Pressure, 337 Benjamin J. Miller
Arterial Blood Pressure, 337 Determinants of Systemic Blood Pressure, 337 Measurement of Blood Pressure, 338
Mechanisms of Blood Pressure Regulation, 341 Short-Term Regulation of Systemic Blood
Pressure, 341 Long-Term Regulation of Systemic Blood Pressure, 341 Normal Fluctuations in Systemic Blood Pressure, 343
Hypertension, 343 Definition and Classification, 343 Primary Hypertension, 344 Secondary Hypertension, 348 Hypertensive Emergencies and Urgency, 349
Low Blood Pressure, 350
UNIT V Cardiac Function
17 Cardiac Function, 354 Jacquelyn L. Banasik
Cardiovascular Anatomy, 355 Heart, 355 Circulatory System, 356
Cardiac Cycle, 358 Isovolumic Contraction, 359 Ventricular Ejection, 360 Isovolumic Relaxation, 360 Atrial Events, 360 Aortic and Pulmonary Artery Events, 360
Coronary Circulation, 360 Anatomy of the Coronary Vessels, 360 Regulation of Coronary Blood Flow, 361
Cardiac Myocytes, 363 Myocyte Structure, 363 Structure of the Contractile Apparatus, 363 Characteristics of Contractile Filaments, 365
Molecular Basis of Contraction, 366 Overview of Contraction, 366 Sliding Filament/Cross-Bridge Theory of Muscle
Contraction, 366 Role of Calcium in Muscle Contraction, 367 Energy of Muscle Relaxation, 367
Cardiac Energy Metabolism, 368 Oxygen Utilization, 368 Substrate Utilization, 369
Cardiac Electrophysiology, 369 Cardiac Resting Potential, 369 Cardiac Action Potential, 369 Rhythmicity of Myocardial Cells, 370 Specialized Conduction System of the Heart, 371 Autonomic Regulation of Rhythmicity, 372
Electrocardiography, 372 Determinants of Cardiac Output, 374
Determinants of Heart Rate, 374 Determinants of Stroke Volume, 375 Cardiac Workload, 376
Endocrine Function of the Heart, 376 Tests of Cardiac Function, 376
Electrocardiography, 376 Magnetic Resonance Imaging and Computed
Tomography, 378 Echocardiography, 378 Nuclear Cardiography, 379 Cardiac Catheterization/Coronary
Angiography, 379 18 Alterations in Cardiac Function, 382
Jacquelyn L. Banasik Coronary Heart Disease, 383
Etiology of Coronary Heart Disease, 383 Risk Factors and Mechanisms of Coronary
Atherosclerosis, 383 Pathophysiology of Ischemia, 385 Clinical Features and Management of Coronary
Syndromes, 388 Endocardial and Valvular Diseases, 394
Disorders of the Mitral Valve, 394 Disorders of the Aortic Valve, 397 Diseases of the Endocardium, 398
CoNTeNTs xv
Myocardial Diseases, 399 Myocarditis, 399 Cardiomyopathy, 400
Pericardial Diseases, 402 Pericardial Effusion, 402 Pericarditis, 402
Congenital Heart Diseases, 403 Embryologic Development, 403 Etiology and Incidence of Congenital Heart
Disease, 404 Pathophysiology of Congenital Heart
Disease, 405 Acyanotic Congenital Defects, 406 Cyanotic Congenital Defects, 408
19 Heart Failure and Dysrhythmias: Common Sequelae of Cardiac Diseases, 411 Benjamin J. Miller and Jacquelyn L. Banasik
Heart Failure, 412 Pathogenesis and Diagnosis, 412 Compensatory Mechanisms, Remodeling,
and Progression, 413 Clinical Manifestations, 417 Class and Stage of Heart Failure, 420 Treatment, 421
Cardiac Dysrhythmias, 421 Dysrhythmia Mechanisms, 421 Dysrhythmia Analysis, 423 Abnormal Rates of Sinus Rhythm, 424 Abnormal Site of Impulse Initiation, 425 Conduction Pathway Disturbances, 428 Treatment, 431
20 Shock, 434 Benjamin J. Miller
Pathogenesis of Shock, 434 Impaired Tissue Oxygenation, 435 Compensatory Mechanisms and Stages of
Shock, 437 Types of Shock, 439
Cardiogenic Shock, 439 Obstructive Shock, 441 Hypovolemic Shock, 442 Distributive Shock, 443
Assessment and Hemodynamic Monitoring, 447 Cardiac Output, 447 Arterial Oxygen Content, 447 Distribution of Blood Flow, 448 Hemodynamic Monitoring, 448
Complications of Shock, 449 Acute Respiratory Distress Syndrome, 449 Disseminated Intravascular Coagulation, 449 Acute Renal Failure, 449 Multiple Organ Dysfunction Syndrome, 449
UNIT VI Respiratory Function
21 Respiratory Function and Alterations in Gas Exchange, 451 Lorna L. Schumann
Functional Anatomy, 452 Development of the Pulmonary System, 452 Upper Airway Structures, 452
Lower Airway Structures, 453 Pulmonary Circulation, 457 Age-Related Variations, 457
Ventilation, 460 Lung Volumes and Capacities, 460 Dead Space, 460 Minute Ventilation, 460 Alveolar Ventilation/Oxygenation, 461 Mechanics of Breathing, 461 Airway Resistance, 461 Lung Compliance, 462 Distribution of Ventilation, 462 Neurologic Control of Ventilation, 462
Pulmonary Blood Flow, 465 Pulmonary Vasculature, 465 Distribution of Blood Flow, 465 Ventilation–Perfusion Ratios, 465 Hypoxic Vasoconstriction, 466
Diffusion and Transport of Respiratory Gases, 466 Barriers to Diffusion, 466 Oxygen Transport, 467 Carbon Dioxide Transport, 467
Alterations in Pulmonary Function, 468 Hypoventilation and Hyperventilation, 468 Hypoxemia and Hypoxia, 468 Acute Respiratory Failure, 469
Diagnostic Tests, 471 Pulmonary Function Testing, 471 Bronchial Provocation Tests, 472
Alterations in Pulmonary Vasculature, 472 Pulmonary Hypertension, 472 Pulmonary Venous Thromboembolism, 473
Pulmonary Malignancies, 475 Etiology, 475 Pathogenesis, 475 Clinical Manifestations, 476 Diagnosis, 476 Treatment, 476
22 Obstructive Pulmonary Disorders, 478 Benjamin J. Miller and Lorna L. Schumann
Obstruction From Conditions in the Wall of the Lumen, 479 Asthma, 479 Acute Bronchitis, 483 Chronic Bronchitis, 485
Obstruction Related to Loss of Lung Parenchyma, 488 Emphysema, 488
Obstruction of the Airway Lumen, 491 Bronchiectasis, 491 Bronchiolitis, 493 Cystic Fibrosis, 494 Acute Tracheobronchial Obstruction, 495 Epiglottitis, 496 Croup Syndrome, 496
23 Restrictive Pulmonary Disorders, 499 Lorna L. Schumann and Benjamin J. Miller
Lung Parenchyma Disorders, 500 Fibrotic Interstitial Lung Diseases, 500
Atelectatic Disorders, 504 Pleural Space Disorders, 508
xvi CoNTeNTs
Neuromuscular, Chest Wall, and Obesity Disorders, 511 Neuromuscular Disorders, 511 Chest Wall Deformities, 511 Disorders of Obesity, 513
Infection or Inflammation of the Lung, 514
UNIT VII Fluid, Electrolyte, and Acid-Base Homeostasis
24 Fluid and Electrolyte Homeostasis and Imbalances, 521 Linda Felver
Body Fluid Homeostasis, 522 Fluid Intake and Absorption, 522 Fluid Distribution, 523 Fluid Excretion, 524 Fluid Loss Through Abnormal Routes, 524
Fluid Imbalances, 525 Extracellular Fluid Volume, 525 Body Fluid Concentration, 526 Both Volume and Concentration, 528 Interstitial Fluid Volume, 528
Principles of Electrolyte Homeostasis, 529 Electrolyte Intake and Absorption, 529 Electrolyte Distribution, 531 Electrolyte Excretion, 531 Electrolyte Loss Through Abnormal Routes, 531
Electrolyte Imbalances, 531 Plasma Potassium, 531 Plasma Calcium, 533 Plasma Magnesium, 534 Plasma Phosphate, 535
25 Acid–Base Homeostasis and Imbalances, 541 Linda Felver
Acid–Base Homeostasis, 541 Buffers, 542 Respiratory Contribution, 542 Renal Contribution, 543
Acid–Base Imbalances, 545 Mixed Acid–Base Imbalances, 549
UNIT VIII Renal and Bladder Function
26 Renal Function, 551 Jacquelyn L. Banasik
Renal Anatomy, 552 Renal Parenchyma, 552 Renal Lymphatics and Innervation, 552 Renal Blood Supply, 553
Overview of Nephron Structure and Function, 554 Glomerulus, 555 Proximal Convoluted Tubule, 557 Loop of Henle, 558 Distal Convoluted Tubule, 559 Collecting Duct, 559
Regulation of Glomerular Filtration, 560 Physics of Filtration, 560 Factors Affecting Filtration Pressure, 562 Tubuloglomerular Feedback, 563
Effects of Glucose and Amino Acids, 563 Role of Mesangial Cells, 564
Transport Across Renal Tubules, 565 Reabsorption of Glucose, 565 Regulation of Acid–Base Balance, 565 Secretion of Potassium, 566
Regulation of Blood Volume and Osmolality, 567 Antidiuretic Hormone, 567 Aldosterone, Angiotensin II, Natriuretic
Peptides, Urodilatin, Uroguanylin, and Guanylin, 568
Diuretic Agents, 569 Endocrine Functions, 570
Erythropoietin, 570 Vitamin D, 570
Age-Related Changes in Renal Function, 570 Infant, 570 Adult and Elderly, 570
Tests of Renal Structure and Function, 570 Urine and Blood Studies, 570 Diagnostic Tests, 572
27 Intrarenal Disorders, 575 Jacquelyn L. Banasik and Roberta J. Emerson
Common Manifestations of Kidney Disease, 575 Pain, 575 Abnormal Urinalysis Findings, 576 Other Diagnostic Tests, 576
Congenital Abnormalities, 577 Renal Agenesis and Hypoplasia, 577 Cystic Kidney Diseases, 578
Neoplasms, 579 Infection, 581 Obstruction, 583 Glomerular Disorders (Glomerulopathies), 586
Glomerulonephritis, 587 Nephrotic Syndrome, 589
28 Acute Kidney Injury and Chronic Kidney Disease, 593 Cheryl Rockwell and Robin Y. Beeman
Acute Kidney Injury, 593 Etiology and Pathophysiology, 594 Clinical Presentation of Acute Kidney Injury, 596
Chronic Kidney Disease, 601 Risk Factors, 601 Pathophysiology of Progression of Chronic
Kidney Disease, 602 Stages of Chronic Kidney Disease, 602 Complications of Chronic Kidney Disease, 602
Clinical Management, 604 29 Disorders of the Lower Urinary Tract, 609
Cheryl L. Brandt Lower Urinary Tract, 609
Functional Anatomy, 609 Physiology of Micturition, 610 Diagnostic Tests, 611
Lower Urinary Tract Symptoms and Syndromes, 611
Neurogenic Bladder, 614 Congenital Disorders, 615 Neoplasms, 617 Inflammation and Infection, 619 Obstruction, 622
Lower Urinary Tract Calculi, 622
CoNTeNTs xvii
UNIT IX Genital and Reproductive Function
30 Male Genital and Reproductive Function, 626 Marvin Van Every
Anatomy, 626 Upper Genitourinary Tract, 626 Lower Genitourinary Tract, 627 Auxiliary Genital Glands, 628 External Genitalia, 629
Embryology, 632 Nephric System, 632 Vesicourethral Unit, 633 Gonads, 633 Genital Duct System, 633 External Genitalia, 633
Male Reproductive Physiology, 633 Hypothalamic-Pituitary-Testicular Axis, 633 Spermatogenesis, 637 Anatomy of Spermatozoa, 637 Transport of Spermatozoa, 637
31 Alterations in Male Genital and Reproductive Function, 641 Marvin Van Every
Disorders of the Penis and Male Urethra, 641 Congenital Anomalies, 641 Acquired Disorders, 643 Infectious Disorders, 645 Neoplastic Disorders, 647
Disorders of the Scrotum and Testes, 647 Congenital Disorders, 647 Acquired Disorders, 648 Infectious Disorders, 650 Neoplastic Disorders, 650
Disorders of the Prostate, 651 32 Female Genital and Reproductive Function, 656
Rosemary A. Jadack Reproductive Structures, 656
Organization of the Female Reproductive Organs, 656
Menstrual Cycle, 659 Breast, 662
Structure of the Breast, 662 Breast Development, 662 Lactation, 663
Pregnancy, 663 Early Human Development, 663 Implantation, 663 Fetal Membranes and Placenta, 663 Development of the Human Embryo and Fetus, 664 Parturition, 665 Response of the Mother’s Body to Pregnancy, 667
Menopause, 668 33 Alterations in Female Genital and Reproductive
Function, 671 Rosemary A. Jadack
Menstrual Disorders, 672 Alterations in Uterine Position and Pelvic
Support, 674 Inflammation and Infection of the Female
Reproductive Tract, 676 Benign Growths and Aberrant Tissue of the Female
Reproductive Tract, 678
Cancer of the Female Genital Structures, 679 Disorders of Pregnancy, 681 Disorders of the Breast, 682
Reactive-Inflammatory Breast Disorders, 682 Benign Breast Disorders, 683 Malignant Disorder of the Breast, 684
34 Sexually Transmitted Infections, 689 Rosemary A. Jadack
Urethritis, Cervicitis, Salpingitis, and Pelvic Inflammatory Disease, 690
Diseases With Systemic Involvement, 691 Diseases With Localized Lesions, 694
Ulcerative Lesions, 694 Nonulcerative Lesions, 694
Enteric Infections, 695
UNIT X Gastrointestinal Function
35 Gastrointestinal Function, 697 Jeffrey S. Sartin
Structure and Organization of the Gastrointestinal Tract, 698 Embryology, 698 Functional Anatomy, 699
Gastrointestinal Motility, 704 Characteristics of the Intestinal Wall, 704 Neural Control, 704 Hormonal Control, 706 Movement in the Gastrointestinal Tract, 706 Movement of Nutrients, 707
Secretory Function, 712 Secretion of Gastrointestinal Juices, 712 Gastrointestinal Hormones, 712
Digestion and Absorption, 712 Digestion of Carbohydrates, 713 Digestion of Lipids, 713 Digestion of Proteins, 714 Absorption, 715
Gastrointestinal Function Across the Life Span, 717 Maturation, 717 Age-Related Changes, 717
36 Gastrointestinal Disorders, 720 Jeffrey S. Sartin
Manifestations of Gastrointestinal Tract Disorders, 721 Dysphagia, 721 Esophageal Pain, 721 Abdominal Pain, 721 Vomiting, 723 Intestinal Gas, 723 Alterations in Bowel Patterns, 723
DISORDERS OF THE MOUTH AND ESOPHAGUS, 724
Oral Infections, 724 Esophageal Disorders, 724 ALTERATIONS IN THE INTEGRITY OF
THE GASTROINTESTINAL TRACT WALL, 726
Inflammation of the Stomach and Intestines, 726
xviii CoNTeNTs
Inflammatory Bowel Disease, 728 Enterocolitis, 731 ALTERATIONS IN MOTILITY OF THE
GASTROINTESTINAL TRACT, 733 Motility Disorders, 733 Disorders of Malabsorption, 735 Mucosal Disorders, 735 Malabsorption Disorders After Surgical
Intervention, 735 NEOPLASMS OF THE GASTROINTESTINAL
TRACT, 737 Esophageal, Gastric, and Small Intestinal
Cancers, 737 Colonic Polyps and Colon Cancer, 738 Psychosocial Aspects of Gastrointestinal
Disorders, 739 Stress of Lifestyle Changes, 739
37 Alterations in Function of the Gallbladder and Exocrine Pancreas, 742 Jeffrey S. Sartin
Structure and Function of the Pancreaticobiliary System, 742
Embryology of the Pancreaticobiliary System, 743
Physiology of Bile, 743 Functional Anatomy of the Pancreas, 744 Disorders of the Gallbladder, 744
Pathophysiology of Cholesterol Gallstone Formation, 744
Cholelithiasis and Cholecystitis, 745 Disorders of the Pancreas, 748
Pancreatitis, 748 38 Liver Diseases, 754
Jeffrey S. Sartin Structure and Function of the Liver, 755 General Manifestations of Liver Disease, 755
Hepatocellular Failure, 755 Portal Hypertension, 759 Portal Systemic Encephalopathy, 763 Complications of Advanced Liver
Disease, 764 Disorders of the Liver, 767
Hepatitis, 767 Chronic Hepatitis, 772
Cirrhosis, 773 Alcoholic Liver Disease, 773
Toxic Liver Disorders, 774 Metal Storage Diseases, 774 Toxic Metabolic Agents, 775
Other Structural Liver Conditions, 775 Transplantation, 776
Evaluation of the Transplantation Patient, 777
Posttransplantation Management, 777 Age-Related Liver Disorders, 778
Liver Diseases and Pediatric Considerations, 778 Abnormal Bilirubin Metabolism in the Neonatal
Period, 778 Infectious and Acquired Hepatitides in
Children, 778 Congenital Liver Disease, 779
Liver Diseases and Geriatric Considerations, 780
UNIT XI Endocrine Function, Metabolism, and Nutrition
39 Endocrine Physiology and Mechanisms of Hypothalamic-Pituitary Regulation, 783 Jacquelyn L. Banasik
Hormone Structure and Action, 784 Chemical Structure of Hormone Classes, 784 Mechanisms of Hormone Action, 784
Hormone Regulation, 786 Hormone Synthesis, Secretion, and
Metabolism, 786 Regulation of Receptor Responses, 787
Hypothalamic-Pituitary Endocrine System, 788 Hormones of the Posterior Pituitary Gland, 788 Hormones of the Hypothalamus and Anterior
Pituitary Gland, 790 Thyroid Hormones, 793
Thyroid Hormone Synthesis and Secretion, 793 Thyroid Action on Target Cells, 793
Steroid Hormones, 794 Steroid Hormone Synthesis and Secretion, 794 Steroid Action on Target Cells, 795
Categories of Endocrine Disease, 797 Hyposecretion, 797 Hypersecretion, 797 Hyporesponsiveness, 797
40 Disorders of Endocrine Function, 799 Jacquelyn L. Banasik
Basic Concepts of Endocrine Disorders, 799 Etiology of Endocrine Disorders, 799 Classification of Endocrine Disorders, 800
Growth Hormone Disorders, 801 Thyroid Hormone Disorders, 803 Adrenocortical Hormone Disorders, 806 Adrenal Medulla Disorder, 810 Parathyroid Gland Disorders, 811
Regulation and Actions of Parathyroid Hormone, 811
Antidiuretic Hormone Disorders, 812 41 Diabetes Mellitus, 815
Benjamin J. Miller Regulation of Glucose Metabolism, 816
Hormonal Regulation, 816 Neural Regulation, 817 Exercise, 818 Stress, 818
Glucose Intolerance Disorders, 820 Classification of Glucose Intolerance
Disorders, 820 Prediabetes, 820 Diabetes Mellitus, 821 Screening for Diabetes, 824
Clinical Manifestations and Complications, 825 Acute Hyperglycemia, 825 Diabetic Ketoacidosis, 825 Nonketotic Hyperglycemic Hyperosmolar
Syndrome, 826 Chronic Hyperglycemia, 826 Vascular Complications, 826 Neuropathic Complications, 827 Complications in Pregnancy, 827
CoNTeNTs xix
Treatment and Education, 827 Nutrition, 828 Obesity and Eating Disorders, 828 Exercise, 829 Pharmacologic Agents, 829 Stress Management, 831 Assessment of Efficacy, 831
Pediatric Considerations, 833 Goals of Therapy, 834 Acute Complications, 834 Chronic Complications, 834 Treatment, 834
Geriatric Considerations, 834 Goals of Therapy, 835 Acute Complications, 835 Chronic Complications, 835 Treatment, 835
42 Nutritional and Metabolic Disorders, 838 Brent A. Banasik
Metabolic Processes, 838 Anabolism and Catabolism, 839 Metabolic Rate, 839
Nutrient Metabolism, 839 Carbohydrates, 839 Lipids, 840 Proteins, 841
Regulation of Appetite and Nutrient Metabolism, 841 Role of Genetics, Epigenetics, and
Environment, 841 Hormonal Regulation of Nutrient Intake and
Appetite, 842 Hormonal Regulation of Nutrient Storage,
Distribution, and Metabolism, 843 Obesity and Metabolic Syndrome, 844
Obesity, 844 Metabolic Syndrome, 844
Metabolic Responses to Starvation and Physiologic Stress, 844 Starvation and Protein-Energy Malnutrition, 845 Physiologic Stress, 845
Nutritional Considerations for Aging and Altered Health States, 846 Aging, 846 Infection, Sepsis, and Fever, 846 Surgery, 848 Trauma, 848 Burns, 848 Cancer, 848 Immobility, 848
UNIT XII Neural Function
43 Structure and Function of the Nervous System, 850 Jacquelyn L. Banasik
STRUCTURAL ORGANIZATION, 851 Central Nervous System, 851
Support and Protection of the Central Nervous System, 851
The Brain, 853 The Spinal Cord, 861
Peripheral Nervous System, 863 Cranial Nerves, 863 Spinal Nerves, 864
Autonomic Nervous System, 867 NEURONAL STRUCTURE AND FUNCTION, 868 Neurons and Supportive Cells, 868
Neurons, 868 Glia, 868
Neuronal Communication, 872 Membrane Potentials, 872 Synaptic Transmission, 874 Neurotransmitters, 875 Neuronal Circuits, 880
Neural Development, Aging, and Injury, 880 Development, 880 Aging, 881 Injury, 881
SENSORY FUNCTION, 882 Sensory Receptors, 882 Sensory Pathways, 883 Somatosensory Cortex, 883 MOTOR FUNCTION, 883 Motor Neurons, 884 Spinal Reflexes, 884 Central Control of Motor Function, 885 CONSCIOUSNESS, MEMORY, AND SLEEP, 886 Consciousness and Memory, 886 Sleep, 888
44 Acute Disorders of Brain Function, 891 Joni D. Marsh and Jacquelyn L. Banasik
Mechanisms of Brain Injury, 892 Ischemia and Hypoxia, 892 Increased Intracranial Pressure, 895
Manifestations of Brain Injury, 900 Level of Consciousness, 900 Glasgow Coma Scale, 900 Cranial Nerve Reflexes, 901
TRAUMATIC BRAIN INJURY, 902 Epidemiology, 902 Types of Traumatic Brain Injury, 903 Primary Injury, 903
Intracranial Hematomas, 903 Secondary Injury, 905 Treatment, 905 CEREBROVASCULAR DISEASE AND
STROKE, 905 Epidemiology, 906 Ischemic Stroke, 906 Hemorrhagic Stroke, 906 Treatment, 906 Stroke Sequelae, 908
Motor and Sensory Deficits, 908 Language Deficits, 908 Cognitive Deficits, 908
CREBRAL ANEURYSM AND ARTERIOVENOUS MALFORMATION, 909
Cerebral Aneurysm, 909 Etiology, 909 Pathogenesis and Manifestations, 910 Treatment, 910
Arteriovenous Malformation, 911 Etiology, 911
xx CoNTeNTs
Pathogenesis and Manifestations, 911 Treatment, 911
CENTRAL NERVOUS SYSTEM INFECTIONS, 911 Meningitis, 911
Etiology, 911 Pathogenesis and Clinical Manifestations, 911 Treatment, 911
Encephalitis, 912 Etiology, 912 Pathogenesis and Manifestations, 912 Treatment, 912
Brain Abscess, 912 Etiology, 912 Pathogenesis and Manifestations, 912 Treatment, 913
45 Chronic Disorders of Neurologic Function, 915 Joni D. Marsh
Brain and Cerebellar Disorders, 916 Seizure Disorder, 916 Dementia, 918 Parkinson Disease, 920 Cerebral Palsy, 922 Hydrocephalus, 923 Cerebellar Disorders, 924
Spinal Cord and Peripheral Nerve Disorders, 925 Multiple Sclerosis, 925 Spina Bifida, 927 Amyotrophic Lateral Sclerosis, 928 Spinal Cord Injury, 928 Guillain-Barré Syndrome, 931 Bell Palsy, 932
46 Alterations in Special Sensory Function, 936 Joni D. Marsh
HEARING AND BALANCE, 937 Structure and Function of the Ear, 937
External Ear, 937 Middle Ear, 937 Inner Ear, 937 Balance, 938
General Manifestations of Hearing Impairment, 938 Hearing Impairment Disorders, 939
Conductive Hearing Impairment, 939 Sensorineural Hearing Impairment, 939
Otitis Media, 941 Interventions for Individuals With Hearing
Impairment, 942 VISION, 942 Structure of the Eye, 942 Visual Pathways, 943 General Manifestations of Visual Impairment, 944 Disorders of the Eye, 944
Errors of Refraction, 944 Age-Related Disorders, 945 Retinopathy, 947 Glaucoma, 948 Visual Field Deficits, 950
Interventions for Individuals With Vision Impairment, 950
SMELL AND TASTE, 952 47 Pain, 955
Joni D. Marsh Physiology of Pain, 955
Transduction, 956 Transmission, 956 Perception, 958 Modulation, 958
TYPES OF PAIN, 960 Acute Pain, 961
Headache, 962 Chronic Pain, 962
Fibromyalgia Syndrome, 963 Cancer-Related Pain, 964 Neuropathic Pain, 964
Trigeminal Neuralgia, 965 Diabetic Neuropathy, 965 Postherpetic Neuralgia, 966
Ischemic Pain, 966 Referred Pain, 966 Physiologic Responses to Pain, 967 Pain in the Young and the Elderly, 967 TREATMENT MODALITIES, 967 Pharmacologic and Nonpharmacologic Pain
Management, 967 Interrupting Peripheral Transmission of Pain, 968 Modulating Pain Transmission at the Spinal
Cord, 968 Altering the Perception and Integration of
Pain, 968
UNIT XIII Neuropsychological Function
48 Neurobiology of Psychotic Illnesses, 971 Ann Futterman Collier and Samantha Cody Russell
Schizophrenia, 972 Etiology and Neurobiology, 972 Clinical Manifestations, 976 Pharmacologic Treatment, 976 Nonpharmacologic Treatment, 977
Major Depressive and Persistent Depressive Disorders, 978 Etiology and Neurobiology, 979 Clinical Manifestations, 980 Pharmacologic Treatment, 981 Nonpharmacologic Treatment, 981
Bipolar Disorder, 982 Etiology and Neurobiology, 982 Clinical Manifestations, 983 Pharmacologic Treatment, 983 Nonpharmacologic Treatment, 984
Population Considerations, 984 Women and Mental Illness, 984 Cultural Considerations, 984 Geriatric Considerations, 984
49 Neurobiology of Nonpsychotic Illnesses, 989 Ann Futterman Collier and Samantha Cody Russell
Anxiety Disorders, 989 Panic Disorder, 990 Generalized Anxiety Disorder, 991 Obsessive-Compulsive Disorder, 992 Posttraumatic Stress Disorder, 994
Neurodevelopmental Disorders, 995 Attention-Deficit/Hyperactivity Disorder, 996 Autism Spectrum Disorder, 997
CoNTeNTs xxi
UNIT XIV Musculoskeletal Support and Movement
50 Structure and Function of the Musculoskeletal System, 1001 Carol L. Danning
Structure and Function of Bone, 1002 Composition, 1002 Functional Properties, 1003 Response to Injury, Stress, and Aging, 1004
Structure and Function of Joints, 1006 Synarthroses, 1007 Diarthroses, 1007
Structure and Function of Articular Cartilage, 1011 Composition, 1011 Functional Properties, 1011 Response to Injury, Stress, and Aging, 1012
Structure and Function of Tendons and Ligaments, 1012 Composition, 1012 Functional Properties, 1013 Response to Injury, Stress, and Aging, 1013
Structure and Function of Skeletal Muscle, 1013 Composition, 1014
Mechanics of Muscle Contraction, 1015 Sliding Filament Theory, 1015 Role of Calcium, 1015 Electromechanical Coupling, 1015 Types of Muscle Contraction, 1016 Mechanical Principles, 1017 Response to Movement and Exercise, 1017
51 Alterations in Musculoskeletal Function: Trauma, Infection, and Disease, 1020 Carol L. Danning
SOFT TISSUE INJURIES, 1021 Inert Soft Tissue Injuries, 1021
Ligament Injuries, 1021 Joint Capsule Injuries, 1022 Internal Joint Derangement, 1023 Injuries to Fasciae and Bursae, 1023 Injuries to Nerves, Nerve Roots, or Dura
Mater, 1023 Contractile Soft Tissue Injuries, 1023
Injury to Tendons, 1023 Muscle and Tendon Strains, 1024 Blunt Trauma, 1024 Compartment Syndrome, 1024 Soft Tissue Healing After Trauma, 1024
BONE INJURIES AND INFECTIONS, 1026 Bone and Joint Trauma, 1026
Types of Bone, 1026 Fracture, 1026 Dislocations and Subluxations, 1030
Infections of the Bone, 1031 Osteomyelitis, 1031 Tuberculosis, 1032
ALTERATIONS IN BONE STRUCTURE AND MASS, 1032
Bone Structure Disorders, 1032 Scoliosis, 1032
Metabolic Bone Diseases, 1033
Osteoporosis, 1033 Rickets and Osteomalacia, 1035 Paget Disease, 1035
Bone Tumors, 1036 Benign Tumors, 1036 Malignant Bone Tumors, 1037
DISEASES OF SKELETAL MUSCLE, 1038 Idiopathic Inflammatory Myopathy, 1038
Polymyositis and Dermatomyositis, 1038 Muscular Dystrophy, 1039
Duchenne Muscular Dystrophy, 1039 Becker Muscular Dystrophy, 1039 Facioscapulohumeral Muscular Dystrophy, 1039 Myotonic Dystrophies, 1039
OTHER DISORDERS OF MUSCLE, 1039 Myasthenia Gravis, 1039
Treatment, 1039 Chronic Muscle Pain, 1040
Fibromyalgia Syndrome, 1040 52 Alterations in Musculoskeletal Function: Rheumatic
Disorders, 1042 Carol L. Danning
Local Disorders of Joint Function, 1042 Osteoarthritis, 1042 Infectious Arthritis, 1045 Lyme Disease, 1045
Systemic Disorders of Joint Function, 1046 Immune-Mediated Disorders, 1046 Postinfectious Systemic Disorders, 1052
Joint Dysfunction Secondary to Other Diseases, 1053 Psoriatic Arthritis, 1053 Enteropathic Arthritis, 1053 Neuropathic Osteoarthropathy, 1054 Hemophilic Arthropathy, 1054 Gout, 1054 Adult-Onset Still Disease, 1055
Pediatric Joint Disorders, 1056 Nonarticular Rheumatism, 1056 Hypermobility of Joints, 1056 Juvenile Idiopathic Arthritis, 1056
UNIT XV Integumentary System
53 Alterations in the Integumentary System, 1058 Lee-Ellen C. Copstead, Ruth E. Diestelmeier, and Michael R. Diestelmeier
Age-Related Changes, 1059 Epidermis, 1060 Dermis and Subcutaneous Tissue, 1060 Appendages, 1061
Evaluation of the Integumentary System, 1061 Primary and Secondary Lesions, 1061 Lesion Descriptors, 1062
Selected Skin Disorders, 1063 Infectious Processes, 1064
Viral Infections, 1064 Fungal Infections, 1065 Bacterial Infections, 1067
Inflammatory Conditions, 1069 Allergic Skin Responses, 1072 Parasitic Infestations, 1075
xxii CoNTeNTs
Other Disorders of the Dermis, 1076 Scleroderma, 1076 Sunburn and Photosensitivity, 1077 Ulcers, 1078 Altered Cell Growth: Epidermal Proliferation, 1078 Pigmentation Alterations, 1080
Special Characteristics of Dark Skin, 1081 Integumentary Manifestations of Systemic
Disease, 1083 Skin, 1083 Hair, 1084 Nails, 1084
Treatment Implications, 1086 Topical Treatment, 1086 Intralesional Injection, 1086 Selection of a Delivery System, 1087 Corticosteroids, 1087
Developmental Considerations, 1087 Infancy, 1087 Childhood Skin Disorders, 1088 Adolescence and Young Adulthood, 1090 Geriatric Considerations, 1090
54 Burn Injuries, 1093 Sarah Ogle and Nirav Patel
Thermal Injury, 1094 Etiology, Incidence, and Mortality, 1094
Risk Factors, 1094 Integument Effects, 1094 Depth Classification, 1096 Extent of Injury, 1097 Severity Classification, 1097 Acute Management, 1097 Assessment, 1099 Burn Shock and Acute Resuscitation, 1099 Organ Dysfunction, 1101 Metabolic Changes, 1102 Cellular Changes, 1102 Immune Response, 1103 Elements of Burn Injury Survival, 1103 Rehabilitation Phase, 1106
Electrical Injury, 1107 Incidence and Mortality, 1107 Pathophysiology, 1107 Management and Complications, 1108
Chemical Injury, 1109 Management and Complications, 1109 Common Agents and Treatment, 1109
Special Populations, 1110 Introduction, 1110
Glossary, 1114 Index, 1143
1
Introduction to Pathophysiology Lee-Ellen C. Copstead
UNIT I Pathophysiologic Processes
1
K E Y Q U E S T I O N S • What is pathophysiology? • How are etiology and pathogenesis used to predict clinical
manifestations and response to therapy? • How are normal and abnormal physiologic parameters defined?
C H A P T E R O U T L I N E Framework for Pathophysiology, 2
Etiology, 2
Pathogenesis, 2
Clinical Manifestations, 3
Stages and Clinical Course, 3
Treatment Implications, 3
Concepts of Normality in Health and Disease, 4 Statistical Normality, 4
Reliability, Validity, and Predictive Value, 5 Individual Factors Influencing Normality, 5
Cultural Considerations, 5
• What general factors affect the expression of disease in a particular person?
• What kinds of information about disease can be gained through understanding concepts of epidemiology?
Pathophysiology derives from the intersection of two older, related disciplines: pathology (from pathos, suffering) and physiology (from physis, nature). Pathology is the study and diagnosis of disease through examination of organs, tissues, cells, and bodily fluids. Physiology is the study of the mechanical, physical, and biochemical functions of living organisms. Together, as pathophysiology, the term refers to the study of abnormalities in physiologic functioning of living beings.
Pathophysiology seeks to reveal physiologic responses of an organism to disruptions in its internal or external environment. Because humans exhibit considerable diversity, healthy structure and function are not precisely the same in any two individuals. However, discovering the common and expected responses to abnormalities in physiologic func- tioning is useful, and it allows a general prediction of clinical progression, identification of possible causes, and selection of interventions that are
most likely to be helpful. Thus pathophysiology is studied in terms of common, or “classic,” presentations of disorders.
Historically, descriptions of diseases were based on observations of those individuals who attracted medical attention because they exhibited abnormal signs or complained of symptoms. Over time, cases with similar presentations were noted and treatments that had been successful before were used again. In some cases, similarities among individuals pointed to possible common causes. With the advent of more sophis- ticated measurements of physiologic and biochemical function, such as blood pressure measurements, blood chemistry values, x-ray images, and DNA analysis, the wide variability in the expression of diseases and disorders in the population became apparent, as did the opportunity to discover diseases at earlier stages, before they were clinically obvious. Screening programs that evaluated large segments of the population
Age Differences, 6 Gender Differences, 6 Situational Differences, 6 Time Variations, 6
Patterns of Disease in Populations, 6 Concepts of Epidemiology, 6
Endemic, Pandemic, and Epidemic Diseases, 7 Aggregate Factors, 7 Levels of Prevention, 9
http://evolve.elsevier.com/Banasik/pathophysiology/ • Review Questions and Answers • Glossary (with audio pronunciations for selected terms) • Animations
• Case Studies • Key Points Review
http://evolve.elsevier.com/Banasik/pathophysiology/
2 UNIT I Pathophysiologic Processes
present, it is termed a risk factor. The identification of risk factors is important for disease prevention, and various levels of prevention provide a focus for the epidemiology section at the end of this chapter.
Some diseases are closely linked with etiologic factors, such that they are said to be the causative agents in the disease. For example, microbial pathogens are considered to be causative agents for infectious diseases: Ebola virus disease—a rare and deadly disease—is caused by infection with a virus of the family Filoviridae, genus Ebolavirus (Fig. 1.1); human immunodeficiency virus causes HIV disease, and Myco- bacterium tuberculosis causes pulmonary tuberculosis. These diseases do not occur unless the pathogen is present in the body; however, this does not mean that the infection will have the same consequences in each case, because many host factors affect the clinical course.
Even when the link between disease and etiologic agent is strong, only a portion of the population exposed to the factor may develop the disease. For example, in persons who consume large quantities of alcohol and develop liver cirrhosis, it is the alcohol consumption that is considered to be the cause, yet only a portion of persons who drink heavily will develop cirrhosis. Thus categorizing the probable etiologies for diseases is a long, difficult research process and, not surprisingly, the exact causes of most disorders remain incompletely understood. Several classification schemes have been proposed to categorize diseases according to etiology. Box 1.1 summarizes an example of an etiologic classification system. No classification system is truly comprehensive, and some diseases fall into multiple categories. Some diseases may receive different designations in the future, as further research reveals new data.
Pathogenesis Pathogenesis refers to the development or evolution of a disease, from the initial stimulus to the ultimate expression of the manifestations of the disease. The sequence of physiologic events that occurs in response to an etiologic agent is a dynamic interplay of changes in cell, tissue, organ, and systemic function. As the ways in which intricate intercellular communication networks control physiologic function are discovered,
revealed the complexity and diversity of disease expression, even in persons with the same genetic defect. Thus although the study of pathophysiology is necessarily a study of the usual and expected responses of the body to a given disruption, individuals often vary significantly from a classic presentation, making the diagnostic process complex and challenging.
Advances in genomic and epigenomic characterization, innovative technologies, and revolutionary approaches to the analysis of genetic variation and function have made studies and treatments possible that were not even imaginable just a few years ago. As a result, definitions of the living world have been virtually transformed and permeate every branch of biological science. Benefits of this new biology include a deeper understanding of evolution, greater insights into immune mechanisms, and advances against cancer and AIDS.
Genetic manipulation also raises sensitive and complex ethical and moral questions that did not exist half a century ago. Scientists are able to experiment with genetic manifestations and their mechanisms of action, dramatically altering medical practice, especially the management of inherited diseases. New capabilities have led to experimental treatments such as gene therapy–molecular surgery powerful enough to cure and alter the next generation. The study of pathophysiology assumes even greater significance as genetic research shows fresh insights and hopeful new treatments for human diseases.
Pathophysiology examines disturbances of normal mechanical, physical, and biochemical functions, either caused by a disease or resulting from a disease or abnormal syndrome or condition. For example, the study of a toxin released by a bacterium has evolved from the science of infectious diseases, as well as the harmful effects of that toxin on the body, with one possible result being sepsis. Another example is the study of the chemical changes that take place in body tissue as the result of inflammation.
Although individual study of specific diseases undertaken in medical pathology textbooks helps students identify subtle differences between similar diseases, the study of pathophysiology is dynamic and conceptual, seeking to explain processes and relationships common to a number of pathologies. For example, the pathophysiology of inflammation, hypotension, fluid volume deficit, hypoxia, and ischemia is important to the understanding of a large number of different pathologies, but each separate process is not necessarily a specific disease.
Pathophysiology includes four interrelated topics: etiology, patho- genesis, clinical manifestations, and treatment implications—the framework used throughout this textbook. Specific diseases will be used as illustrative examples of conditions in which particular pathophysiologic processes may occur.
FRAMEWORK FOR PATHOPHYSIOLOGY Etiology Etiology, in its most general definition, is the study of the causes or reasons for phenomena. A description of etiologic process includes the identification of those causal factors that, acting in concert, provoke a particular disease or injury. When the cause is unknown, a condition is said to be idiopathic. If the cause is the result of an unintended or unwanted medical intervention, the resulting condition is said to be iatrogenic. Most disorders are multifactorial, having several different etiologic factors that contribute to their development. For example, coronary heart disease is a result of the interaction of genetic predisposi- tion, diet, exposure to cigarette smoke, elevated blood pressure, and perhaps numerous other lifestyle and hormonal factors acting in concert. None of these individual factors can be said to cause the disease. When the link between an etiologic factor and development of a disease is less than certain but the probability is increased when the factor is
FIG 1.1 Colorized scanning electron micrograph of filamentous Ebola virus particles (blue) budding from a chronically infected VERO E6 cell (yellow-green). (From National Institute of Allergy and Infectious Diseases at http://flickr.com/photos/54591706@N02/14440817981. March 20, 2017.)
CHAPTER 1 Introduction to Pathophysiology 3
different stages. Knowledge of the possible stages of a disease is helpful in making an appropriate diagnosis and anticipating the clinical course.
Stages and Clinical Course Early in the development of a disease, the etiologic agent or agents may provoke a number of changes in biological processes that can be detected by laboratory analysis, although no recognition of these changes by the patient has occurred. The interval between exposure of a tissue to an injurious agent and the first appearance of signs and symptoms may be called a latent period or, in the case of infectious diseases, an incubation period. The prodromal period, or prodrome, refers to the appearance of the first signs and symptoms indicating the onset of a disease. Prodromal symptoms often are nonspecific, such as headache, malaise, anorexia, and nausea. During the stage of manifest illness, or the acute phase, the disease reaches its full intensity, and signs and symptoms attain their greatest severity. Sometimes during the course of a disease, the signs and symptoms may become mild or even disappear for a time. This interval may be called a silent period or latent period. For example, in the total-body irradiation syndrome, a latent period may occur between the prodrome and the stage of manifest illness. Another example is syphilis, which may have two latent periods: one occurring between the primary and secondary clinical stages and another occurring between the secondary and tertiary stages.
A number of diseases have a subclinical stage, during which the patient functions normally, although the disease processes are well established. It is important to understand that the structure and function of many organs provide a large reserve or safety margin, so that functional impairment may become evident only when organ damage has become advanced. For example, chronic renal disease can completely destroy one kidney and partly destroy the other before any symptoms related to a decrease in renal function are perceived.
The clinical course of a disease is often classified as acute or chronic. An acute condition has relatively severe manifestations but runs a short course measured in hours, days, or a few weeks. A chronic condition lasts for months to years. Sometimes chronic disease processes begin with an acute phase and become prolonged when the body’s defenses are insufficient to overcome the causative agent or stressor. In other cases, chronic conditions develop insidiously and never have an acute phase.
Some diseases (e.g., some types of autoimmune diseases) follow a course of alternating exacerbations and remissions. An exacerbation is a relatively sudden increase in the severity of a disease or any of its signs and symptoms. A remission is an abatement or decline in severity of the signs and symptoms of a disease. If a remission is permanent (sometimes defined as longer than 5 years), the person is said to be cured.
Convalescence is the stage of recovery after a disease, injury, or surgical operation. Occasionally a disease produces a subsequent pathologic condition called a sequela (plural: sequelae). For example, the sequela of an inflammatory process might be scarring. The sequelae of acute rheumatic inflammation of the heart might be scarring and deformation of cardiac valves. In contrast, a complication of a disease is a new or separate process that may arise secondarily because of some change produced by the original problem. For example, bacterial pneumonia may be a complication of viral infection of the respiratory tract.
Treatment Implications An understanding of the etiology, pathogenesis, and clinical consequences of a particular disorder may suggest, or “imply,” that certain treatments could be helpful. For example, understanding that a person with septic shock has excessive dilation of blood vessels that contributes to
pathogenesis is being increasingly understood on the cellular level. One of the best examples of this communication network is the immune system and its interactions with essentially every other cell in the body. A disruption in the delicate system of checks and balances between immune tolerance of normal cells and immune surveillance for abnormal cells and foreign antigens is at the root of a large number of degenerative and inflammatory diseases.
Pathologic disruptions in cellular behavior lead, in turn, to changes in organ and system function that may be detected by clinical or labora- tory examination. Most pathophysiology texts take a systems approach to presenting information. This approach builds on the way in which students learn anatomy and physiology and has its roots in medical specialization. Usually the clinical examination of a patient is also conceptualized by a systems approach. Although the division into systems is useful for dividing the content into conceptual pieces, it is important to remember that the organism functions as an integrated whole and the intercellular communication networks are not confined within single systems. In summary, pathogenesis is a description of how etiologic factors are thought to alter physiologic function and lead to the develop- ment of clinical manifestations that are observed in a particular disorder or disease.
Clinical Manifestations Manifestations of disease that are observed are termed signs of disease. Such objective data may be gathered by clinical examination or by biochemical analysis, diagnostic imaging, and other laboratory tests. The subjective feelings of an abnormality in the body are termed symptoms. By definition, symptoms are subjective and can only be reported by the affected individual to an observer. For example, the feeling of nausea is a symptom, whereas vomiting is objectively observed and is a sign. Some signs and symptoms, such as fever and headache, are nonspecific and, although they designate that something is amiss, they do not indicate a specific cause. In this case further examination and, often, laboratory tests are needed to focus on the possible causes of the signs and symptoms. Many diseases and disorders are characterized by a particular constellation of signs and symptoms, the knowledge of which is essential for accurate detection and diagnosis. When the etiology of a particular set of signs and symptoms has not yet been determined, the disorder may be termed a syndrome. For example, AIDS was originally detected as a set of signs and symptoms related to a deficiency of helper T cells of unknown cause, now known to be a late stage of HIV infection.
The clinical manifestations of some diseases may change significantly over time, resulting in a completely different clinical presentation at
Congenital (inborn) diseases or birth defects Degenerative diseases Iatrogenic diseases Idiopathic diseases Immunologic diseases Infectious diseases Inherited diseases Metabolic diseases Neoplastic diseases Nutritional deficiency diseases Physical agent–induced diseases Psychogenic diseases
BOX 1.1 Etiologic Classification of Diseases
4 UNIT I Pathophysiologic Processes
CONCEPTS OF NORMALITY IN HEALTH AND DISEASE The ability to measure numerous structural, physiologic, biochemical, and genetic parameters in an individual allows the evaluation of information that is helpful in the diagnosis and monitoring of clinical diseases. Many of these same measures are commonly used to screen for disease or to evaluate the risks of a disease occurring in the future. To determine whether a certain finding is indicative of disease or “abnormal,” it must be compared with what is “normal.” The obviousness of this statement belies the difficulty in determining what is normal and the degree of deviation from normal that would be considered abnormal. Many clinical parameters are evaluated by direct observation by the examiner. Skin color and warmth, quality of pulses, briskness of pupil reactions to light, mental acuity, muscle strength, joint mobility, heart sounds, lung sounds, bowel sounds, balance, psychological affect, and level of consciousness are but a few examples of assessments that are subjectively interpreted based on the examiner’s observations. Deciding whether a clinical finding is normal, a normal variation, or an abnormality indicative of a disorder is essential. Reliability of data obtained from observation is dependent on the examiner’s skill and experience. Often the clinical examination is not sufficient to determine definitively the underlying pathophysiologic processes, and diagnostic testing is undertaken to provide more information.
Statistical Normality Some of the variables that are measured to diagnose disease are relatively easy to declare as normal or abnormal because they occur in only two states; for example, a bone is either broken or not broken on x-ray examination. However, most diagnostic variables occur in the population according to a “bell curve,” or normal distribution. This means that a large enough sample taken from the population should give a good estimate of the range of values in the population. Statistics are often used to determine the standard deviation of the variable in question, and then a normal range is suggested as the mean ±2 standard deviations. This means that 95% of the values in the population are expected to fall in the normal range and 5% will be either higher or lower (Fig. 1.2). The “population” chosen to serve as the normal reference population
hypotension implies that fluid administration would likely be helpful. In contrast, most patients with cardiogenic shock have fluid overload, and hypotension in this case is unlikely to improve with fluid administra- tion. Care must be taken not to rely on theoretical implications when evidence-based treatment recommendations are available. When subjected to evaluation by rigorous randomized clinical trials, many treatments that seem as though they should help based on pathophysiology fail to pass the test of application.
The treatment implications discussed in pathophysiology texts usually are general statements rather than specific prescriptions. For example, the pathophysiology of heart failure is characterized by fluid overload, which implies that diuretic therapy would be useful; however, the exact selection of a drug and the dosing schedule would depend on a number of factors particular to the individual patient. Specific treatment recom- mendations are beyond the scope of a pathophysiology text and can be found in pharmacology and clinical practice textbooks.
KEY POINTS • Pathophysiology includes four interrelated topics: etiology, pathogenesis,
clinical manifestations, and treatment implications. • Etiology refers to study of the proposed cause or causes of a particular
disease process. Etiology is a complex notion because most diseases are multifactorial, resulting from interplay between genetic constitution and environmental influences.
• Pathogenesis refers to the proposed mechanisms whereby an etiologic stimulus leads to typically observed clinical manifestations. Pathogenesis describes the direct effects of the initiating event, as well as the usual physiologic responses and compensatory mechanisms.
• Clinical manifestations describe the signs and symptoms that typically accompany a particular pathophysiologic process. Manifestations may vary depending on the stage of the disorder, individual variation, and acuity or chronicity.
• An understanding of the etiology, pathogenesis, and clinical consequences of a particular disorder implies that certain treatments may be helpful.
Normal mean
Mean in those with disease
95% of values Variable values
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FIG 1.2 Representative example of a normal bell curve for a physiologic variable. Many physiologic variables are normally distributed within the population, so the mean ±2 standard deviations include 95% of the normal values in the sample. Approximately 2.5% of values will be above the normal range and 2.5% will be below it. There may be overlap between the values in a normal sample and those in the population with a disease, making interpretation difficult in some cases.