Ellen Hillegass - Essentials of Cardiopulmonary Physical Therapy-Saunders (2016)

Essentials of Cardiopulmonary Physical Therapy FOURTH EDITION

Ellen Hillegass, PT, EdD, CCS, FAACVPR, FAPTA President, Cardiopulmonary Specialists, Inc, A Consulting Corporation, Partner in PT CARDIOPULMONARY EDUCATORS, LLC, A webinar-based continuing education company, http://www.ptcardiopulmonaryeducators.com Adjunct Professor, Department of Physical Therapy, Mercer University, Atlanta, Georgia Adjunct Professor, Department of Physical Therapy, Western Carolina University, Cullowhee, North Carolina

Table of Contents Cover image Title page Copyright Dedication Contributors Preface Acknowledgments

Section 1. Anatomy and Physiology 1. Anatomy of the cardiovascular and pulmonary systems Thorax The Respiratory System The Cardiovascular System Cardiac and Pulmonary Vessels Systemic Circulation Summary

2. Physiology of the cardiovascular and pulmonary systems The Pulmonary System The Cardiovascular System Summary

Section 2. Pathophysiology 3. Ischemic cardiovascular conditions and other vascular pathologies Anatomy of the Coronary Arteries Myocardial Perfusion Atherosclerosis Hypertension Cerebrovascular Disease Peripheral Arterial Disease Other Vascular Disorders Summary

4. Cardiac muscle dysfunction and failure Causes and Types of Cardiac Muscle Dysfunction Cardiac Muscle Specific Pathophysiologic Conditions Associated with Congestive Heart Failure Clinical Manifestations of Congestive Heart Failure Medical Management Mechanical Management Surgical Management Prognosis Physical Therapy Assessment Physical Therapy Interventions Ventilation Summary

5. Restrictive lung dysfunction Etiology Pathogenesis Clinical Manifestation Maturational Causes of Restrictive Lung Dysfunction

Interstitial Causes Environmental/Occupational Causes Asbestosis Infectious Causes Neoplastic Causes Pleural Diseases Cardiovascular Causes Neuromuscular Causes Musculoskeletal Causes Connective Tissue Causes of RLD Immunologic Causes Pregnancy as Cause Nutritional and Metabolic Causes Traumatic Causes Therapeutic Causes Pharmaceutical Causes Radiologic Causes Summary

6. Chronic obstructive pulmonary diseases Overall Etiology, Pathology, and Pathophysiology of COPD Lung Function in Obstructive Lung Diseases Symptoms Associated with Obstructive Lung Diseases Physical and Psychological Impairments Associated with Obstructive Lung Diseases Quantification of Impairment in Obstructive Lung Diseases Disease-Specific Obstructive Lung Conditions Pediatric Obstructive Lung Conditions

7. Cardiopulmonary implications of specific diseases Obesity Diabetes Mellitus Clinical Implications for Physical Therapy

Chronic Kidney Disease and Failure Other Specific Diseases and Disorders Cardiopulmonary Toxicity of Cancer Treatment Summary

Section 3. Diagnostic Tests and Procedures 8. Cardiovascular diagnostic tests and procedures Diagnostic Test Interpretation and Probability of Disease Sensitivity/Specificity of Testing Clinical Laboratory Studies Other Noninvasive Diagnostic Tests Other Imaging Modalities Exercise Testing Pharmacologic Stress Testing Cardiac Catheterization: Coronary Angiography and Ventriculography Digital Subtraction Angiography Endocardial Biopsy Vascular Diagnostic Testing for Aortic, Peripheral, and Carotid Disease Peripheral Arterial Disease and Dysfunction and Diagnosis Carotid Artery Disease and Diagnosis Summary

9. Electrocardiography Basic Electrophysiologic Principles Heart Rhythm: Assessment of Single-Lead Electrocardiogram Heart Blocks Ventricular Arrhythmias Other Findings on a 12-Lead Electrocardiogram Summary

10. Pulmonary diagnostic tests and procedures Chest Imaging Bronchoscopy Pulmonary Function Testing Blood Gas Analysis Oximetry Cytologic and Hematologic Tests Summary

Section 4. Surgical Interventions, Monitoring, and Support 11. Cardiovascular and thoracic interventions Cardiovascular and Thoracic Surgical Procedures Gene Therapy for the Stimulation of Angiogenesis Radiation Chest Tube Placement Pacemaker Implantation Implantable Cardioverter Defibrillator Summary

12. Thoracic organ transplantation: Heart and lung History Evaluation Preoperative Rehabilitation Alternative Therapies to Transplantation Donor Selection and Matching Criteria Surgical Techniques Medications Postoperative Treatment Lung Transplantation

Future Trends in Transplantation Care161 Summary

13. Monitoring and life support Monitoring Equipment Temperature Monitoring Intracranial Pressure Monitoring Life Support Equipment Summary

Section 5. Pharmacology 14. Cardiovascular medications Pharmacokinetics Pharmacodynamics General Considerations of Pharmacologic Management Cardiac Drugs Used in Critical Care Cardiac Pharmacology in the Geriatric Population Cardiac Pharmacology in the Neonate and Pediatric Populations Pharmacologic Management of Diabetes Heart Transplantation Vascular Pharmacology Summary

15. Pulmonary medications Physiology Bronchomotor Tone Rationale for Bronchodilators Bronchodilators New Drug Development New Antifibrotic Medications (for the Treatment of Idiopathic Pulmonary Fibrosis)

Pulmonary Arterial Hypertension Medications Ancillary Pulmonary Medications Summary

Section 6. Cardiopulmonary Assessment and Intervention 16. Examination and assessment procedures Elements of Patient Management Patient History Medical Chart Review Interview with the Patient and the Family Systems Review Physical Examination Evaluation Summary

17. Interventions for acute cardiopulmonary conditions Airway Clearance Techniques Breathing Strategies, Positioning, and Facilitation Breathing Exercises Special Considerations for Mechanically Ventilated Patients Exercise Injury Prevention and Equipment Provision Patient Education Discharge Planning Pediatric Considerations Summary

18. Interventions and prevention measures for individuals with cardiovascular disease, or risk of disease Primary Prevention

Rehabilitation of Patients with Documented Cardiovascular Disease Management and Evaluation of Patients during the Acute Phase Postacute Phase Rehabilitation Candidacy Home-Based Cardiac Rehabilitation Rehabilitation/Secondary Prevention in the Outpatient Setting Secondary Prevention: Management of Risk Factors Administrative Considerations Summary

19. Pulmonary rehabilitation Choosing Goals and Outcomes in Pulmonary Rehabilitation Structure of the Pulmonary Rehabilitation Program Physical Therapy Management Patient Evaluation Procedures Treatment Intervention Physical Conditioning Summary

20. Pediatric cardiopulmonary physical therapy Respiratory System Development Cardiac Development Congenital Heart Defects Respiratory Conditions of Infancy Pediatric Conditions with Secondary Cardiopulmonary Issues Pediatric Conditions with Decreased Activity Levels and/or Altered Posture Physical Therapy Examination Physical Therapy Evaluation, Diagnosis, and Prognosis Physical Therapy Intervention Summary

21. The lymphatic system

Anatomy and Physiology Pathophysiology The Role of the Lymphatic System in the Cardiovascular System and in Cardiovascular Disease Medical Management Lipedema Summary

22. Outcome measures: A guide for the evidence-based practice of cardiopulmonary physical therapy Outcomes Defined Importance of Measuring Outcomes Selection of Data to Measure Functional Performance Measures Quality-of-Life Measures Summary

Index

ISBN: 978-0-323-43054-8

Copyright © 2017 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 Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their

patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability 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 2011, 2001, and 1994. Library of Congress Cataloging-in-Publication Data Names: Hillegass, Ellen A., editor. Title: Essentials of cardiopulmonary physical therapy / [edited by] Ellen Hillegass. Other titles: Cardiopulmonary physical therapy Description: Fourth edition. | St. Louis, Missouri : Elsevier, [2017] | Includes bibliographical references and index. Identifiers: LCCN 2016002395 | ISBN 9780323430548 (hardcover : alk. paper) Subjects: | MESH: Cardiovascular Diseases--physiopathology | Cardiovascular Diseases--rehabilitation | Lung Diseases--physiopathology | Lung Diseases--rehabilitation | Physical Therapy Modalities Classification: LCC RC702 | NLM WG 166 | DDC 616.1/062--dc23 LC record available at http://lccn.loc.gov/2016002395 Executive Content Strategist: Kathy Falk Content Development Manager: Jolynn Gower Senior Content Development Specialist: Brian Loehr Publishing Services Manager: Julie Eddy Project Manager: Abigail Bradberry Design Direction: Miles Hitchen Printed in China Last digit is the print number: 9

Dedication This book is dedicated to my beloved family for all their love and support as well as their understanding during my endless hours of working on this edition: To my husband Dan, who is my rock and my constant support whom I could not live without; To my three wonderful children: Patrick, Jamie, and Christi who give me moral support, make me laugh, and who constantly try to keep me up to date on all the modern technologies that have helped me communicate with them, communicate with my colleagues, and write this book. They keep me young with their ideas and assistance; they constantly have a “joie de vivre”; To my two dogs: Sparky and Bear who kept my feet warm while I sat for hours at the computer working on this edition but demanded daily play, and provided a wonderful mental break from writing; To my brother-in-law George, who was an inspiration to everyone he knew and met with his positive attitude and fighting spirit that he had up until the day he died from pancreatic cancer. And, In loving memory of my parents, John and Norma, who kept me busy as their daughter and caregiver while they were alive, and were always proud of everything I did. In addition, I dedicate this edition: To my colleagues who keep me informed, give me moral and intellectual support, and who keep me inspired to maintain my passion for the field of cardiovascular and pulmonary physical therapy. I have enjoyed being a mentor to many rising cardiopulmonary specialists as well as all my students, and have especially enjoyed being a resident mentor to my first resident, Erica

Colclough, and my current residents Tiffany Haney and Stephen Ramsey. I also especially rely on the support and inspiration of some very dear friends/colleagues including Dianne Jewell, Andrew Ries, Claire Rice, and Joanne Watchie. And finally, I can never forget my very special friends/mentors to whom I am forever grateful and whose memories and teachings are with me always: Michael Pollock (1937–1998), Linda Crane (1951–1999), and Gary Dudley (1952–2006).

Contributors Erinn Barker, DPT, Cardiovascular and Pulmonary Physical Therapist Resident, Department of Physical Therapy, Duke University Hospital, Durham, North Carolina Pamela Bartlo, PT, DPT, CCS Clinical Associate Professor, Physical Therapy, D’Youville College, Buffalo, New York Staff PT in Cardiac and Pulmonary Rehabilitation, Rehabilitation Department, Mount St. Mary’s Hospital, Lewiston, New York Traci Tiemann Betts, PT, DPT, CCS, Physical Therapist - Cardiopulmonary Clinical Specialist, Physical Medicine and Rehabilitation, Baylor Institute for Rehabilitation Baylor University Medical Center - Baylor Scott & White Healthcare, Dallas, Texas Tamara L. Burlis, PT, DPT, CCS, Associate Director of Clinical Education, Assistant Professor, Program in Physical Therapy and Internal Medicine, Washington University, St. Louis, Missouri Rohini K. Chandrashekar, PT, MS, CCS Guest Lecturer, Physical Therapy, Texas Woman’s University, Houston, Texas Physical Therapist, Rehabilitation, Triumph Hospital Clear Lake, Webster, Texas Meryl Cohen, DPT, MS, CCS Assistant Professor, Department of Physical Therapy, Miller School of Medicine, University of Miami, Coral Gables, Florida Adjunct Instructor, Massachusetts General Hospital, Institute of Health Professions, Boston, Massachusetts Kelley Crawford, DPT, Center, Portland, Maine

Level III Clinician, Rehabilitation, Medicine, Maine Medical

Rebecca Crouch, PT, DPT, CCS Adjunct Faculty, Doctoral Program in Physical Therapy, Duke University, Durham, North Carolina Coordinator of Pulmonary Rehabilitation, PT/OT Duke University Medical Center, Durham, North Carolina Nicole DeLuca, DPT, CCS, Program Coordinator, Cardiopulmonary Rehabilitation, Physical Medicine and Rehabilitation, Miami VA Healthcare System, Miami, Florida Konrad J. Dias, PT, DPT, CCS, Associate Professor, Physical Therapy Program, Maryville University, St. Louis, Missouri

Christen DiPerna, PT, DPT, Physical Therapist, Indiana University Health Methodist Hospital, Indianapolis, Indiana Anne Mejia-Downs, PT, CCS Assistant Professor, Krannert School of Physical Therapy, University of Indianapolis, Indianapolis, Indiana Physical Therapist, Department of Rehabilitation Services, Clarian Health Partners, Indianapolis, Indiana Jennifer Edelschick, PT, DPT, Coordinator of Pediatric Acute PT/OT Services Physical and Occupational Therapy, Duke Medicine, Durham, North Carolina Tara Marie Dickinson Fahrner, PT, DPT, CCS, Sacred Heart Hospital, Pensacola, Florida

Physical Therapist, Physical Medicine,

Ann Winkel Fick, PT, DPT, MS, CCS Director of Clinical Education Associate Professor, Physical Therapy, Maryville University, St. Louis, Missouri PRN Physical Therapist, Physical Therapy, Barnes-Jewish Hospital, St. Louis, Missouri Danielle L. Fioriello, PT, MPT, CCS, Physical Therapist, Cardiac and Pulmonary Rehabilitation, Mount Sinai Beth Israel, New York, New York Courtney Frankel, PT, MS, CCS, Clinical Research Coordinator II, Department of Medicine, Duke University, Durham, North Carolina Susan L. Garritan, PT, PhD, CCS, Clinical Assistant Professor, Rehabilitation Medicine, Acute Care Physical Therapy Coordinator, Tisch Hospital, New York University, Langone Medical Center, New York, New York Natalie M. Goldberg, PT, DPT, CCS Adjunct Professor, Department of Physical Therapy, University of Hartford, Hartford, Connecticut Physical Therapist, Department of Rehabilitation, Hartford Hospital, Hartford, Connecticut Kate Grimes, MS, PT, CCS, Clinical Assistant Professor, Massachusetts General Hospital, Institute of Health Professions, Boston, Massachusetts Ellen Hillegass, PT, EdD, CCS, FAACVPR, FAPTA President, Cardiopulmonary Specialists, Inc, A Consulting Corporation, Partner in PT CARDIOPULMONARY EDUCATORS, LLC, A webinar-based continuing education company, http://www.ptcardiopulmonaryeducators.com Adjunct Professor, Department of Physical Therapy, Mercer University, Atlanta, Georgia Adjunct Professor, Department of Physical Therapy, Western Carolina University,

Cullowhee, North Carolina Morgan Johanson, PT, MSPT, CCS Coordinator of Inpatient and Outpatient, Cardiac and Pulmonary Physical Therapy Co-Director, Cardiovascular and Pulmonary Physical Therapy Residency Program, Physical Medicine and Rehabilitation, Ann Arbor VA Healthcare System, Ann Arbor, Michigan Tamara Klintwork-Kirk, PT, CCS, Clinical Services Coordinator, Department of Physical and Occupational Therapy, Duke University Hospital, Durham, North Carolina Meghan Lahart, PT, DPT, CCS, Physical Therapist II, Rehabilitation Services, Advocate Christ Medical Center, Oak Lawn, Illinois Kristin M. Lefebvre, PT, PhD, CCS, Assistant Professor, Institute for Physical Therapy Education, Widener University, Chester, Pennsylvania Ana Lotshaw, PT, PhD, CCS, Rehabilitation Supervisor, Physical Medicine and Rehabilitation, Baylor University Medical Center, Dallas, Texas Sean T. Lowers, PT, DPT, CCS, Senior Physical Therapist, Department of Physical Therapy and Occupational Therapy, Duke University Health System, Durham, North Carolina Kate MacPhedran, PT, PhDc, CCS Instructor, Doctor of Physical Therapy, Gannon University, Erie, Pennsylvania Frailty Consultant, Consultants in Cardiovascular Diseases, Inc., Saint Vincent Hospital, Erie, Pennsylvania Susan Butler McNamara, MMSc, PT, CCS, Team Leader, Division of Rehabilitation Medicine, Maine Medical Center, Portland, Maine Harold Merriman, PT, PhD, CLT, Associate Professor, Department of Physical Therapy, University of Dayton, Dayton, Ohio Andrew Mills, PT, DPT, Assistant Professor, School of Physical Therapy, Touro University Nevada, Henderson, Nevada Amy Pawlik, PT, DPT, CCS, Program Coordinator, Cardiopulmonary Rehabilitation Therapy Services The University of Chicago Hospitals, Chicago, Illinois Christiane Perme, PT, CCS, Senior Physical Therapist, Department of Physical Therapy and Occupational Therapy, The Methodist Hospital, Houston, Texas Karlyn J. Schiltgen, PT, DPT, OCS, CCS,

Physical Therapist, Department of Inpatient

PT/OT, Duke University Hospital, Durham, North Carolina Alexandra Sciaky, PT, DPT, MS, CCS Adjunct Faculty, Department of Physical Therapy, University of Michigan-Flint, Flint, Michigan Senior Physical Therapist, Coordinator of Clinical Education, Physical Medicine and Rehabilitation, Physical Therapy Section, Veterans Affairs Ann Arbor Healthcare System Ann Arbor, Michigan Debra Seal, PT, DPT, Senior Pediatric Physical Therapist, Acute Therapy, Cedars-Sinai Medical Center, Los Angeles, California Joanne Watchie, MA, PT, CCS,

Owner, Joanne’s Wellness Ways, Pasadena, California

Preface Originally this text was developed to meet the needs of the physical therapy community, as cardiopulmonary was identified as one of the four clinical science components in a physical therapy education program as well as in clinical practice. Those aspects of physical therapy commonly referred to as “cardiovascular and pulmonary physical therapy” are recognized as fundamental components of the knowledge base and practice base of all entry-level physical therapists. Therefore this text was developed for entrylevel physical therapists, as well as individuals in practice who need more in-depth knowledge of cardiopulmonary content. This text is also utilized by many clinicians studying for advanced practice board certification as well as those involved in residency programs. Although intended primarily for physical therapists, this text has been useful to practitioners in various disciplines who teach students or who work with patients who suffer from primary and secondary cardiopulmonary dysfunction. This fourth edition can also be used by all practitioners who teach entry-level clinicians, work with residents as well as to help in clinical practice of patients with cardiopulmonary dysfunction. This fourth edition has gone through update and revision from the third edition to make the text more user friendly and provide more interactive learning. The same six sections exist: Anatomy and Physiology; Pathophysiology; Diagnostic Tests and Procedures; Surgical Interventions, Monitoring and Support; Pharmacology; and Cardiopulmonary Assessment and Intervention. The six sections were kept as they facilitate the progression of understanding of the material in order to be able to perform a thorough assessment and provide an optimal intervention as well as provide measurable outcomes to assess change. The revisions you should notice include both major and minor changes. All chapters have been revised as well as supplemented with many figures and tables and some videos to help the learner visualize the written information. Additional figures, case studies, and resource material can also be found on the Evolve website that accompanies this text. The number of clinical notes was increased to help clinicians and students understand certain clinical findings and help them relate them to the pathophysiology of cardiovascular and pulmonary disease. All chapters were updated with new information, technology, and research. Each chapter had specific revisions that should be highlighted. Chapters 1 and 2, which explain anatomy and physiology, increased the number of figures to help the learner relate the pathophysiology to the normal anatomy and physiology. In addition, the developmental and maturational anatomy was moved to the pediatrics chapter (Chapter 20) to help the learner compare the pathophysiology to the normal in this population. Chapter 3, Ischemic Cardiovascular Conditions and Other Vascular Pathologies, underwent revision particularly in areas that were lacking such as venous dysfunction including deep vein thrombosis. New material was added, so that you will now find

hypertension, peripheral arterial disease, cerebrovascular disease, renal disease, and aortic aneurysm in this chapter, in addition to ischemic disease. Chapter 4, Cardiac Muscle Dysfunction and Failure, was restructured and revised to improve the flow and understanding of this important pathologic condition as well as all new figures and tables to help understand heart dysfunction and failure. Due to the complexities and number of conditions of restrictive lung dysfunction many more tables were created in Chapter 5 to separate the material and assist the learner to identify key information quickly. Chapter 6, Chronic Obstructive Pulmonary Diseases, was updated and revised to emphasize the importance of this disease and the fact that COPD is the third leading cause of death. Revisions in Chapter 7, Cardiopulmonary Implications of Specific Diseases, emphasize information on obesity, diabetes, and metabolic syndrome, as well as cancer and neuromuscular diseases. New technologies and advancements in diagnostic tests and surgical procedures were added to Chapters 8, 9, 10, and 11. Chapter 11, Cardiovascular and Thoracic Interventions underwent major overhaul with many new figures and text. The advances in transplantation were discussed in Chapter 12 and Monitoring and Life Support (Chapter 13) was revised to increase the depth of information on ventilators as well as other monitoring equipment found in intensive care units and used by PTs when mobilizing patients earlier. As advances in health care and diagnostics occur, so do improvements and changes in medications, so both Cardiovascular Medications (Chapter 14) and Pulmonary Medications (Chapter 15) required updating. Chapter 16 (Examination and Assessment Procedures) was revised with addition of new tables to help organize assessments and improve the understanding of this material. Chapter 17, Interventions for Acute Cardiopulmonary Conditions added a greater emphasis on early mobility and Chapter 18, Interventions and Prevention Measures for Individuals with Cardiovascular Disease, or Risk of Disease had major updating and revision, new clinical notes and many new figures and tables. Chapter 19, Pulmonary rehabilitation was revised to correspond with changes in the new pulmonary rehabilitation (PR) definition and in the changing practice since Medicare revised payment for PR. Chapter 20, Pediatric Cardiopulmonary Physical Therapy and Chapter 21, The Lymphatic System were two wonderful additions to the third edition of Cardiopulmonary Physical Therapy and were updated with some new figures. And, finally, the text ends with the outcomes chapter which was totally revamped and provides great information for measurement of improvement in the cardiopulmonary patient population. Whenever possible, case studies are provided to exemplify the material being presented. Additional case studies are found on Evolve. No matter how well you understand the material in this book, it will not make you a master clinician, skilled in the assessment and treatment of cardiovascular and pulmonary disorders. To become even a minimally competent clinician, you will have to practice physical therapy under the tutelage of an experienced clinician. Essentials of

Cardiopulmonary Physical Therapy cannot provide you with everything there is to know about the assessment and treatment of cardiovascular and pulmonary disorders. It will provide the essentials as the title indicates. Learning is a continuous process, and technology and treatment are forever improving; therefore this text provides clinicians as well as educators with the most current information at the time of publication. It is my true hope that you appreciate this edition and are able to learn from all the wealth of information provided by such wonderful contributors. Without heart and breath there is no therapy!

Acknowledgments “Change is good and change equals opportunity!” This statement explains how I have approached each edition, but most especially this edition! Hopefully you will gain knowledge and insight from all the changes as there are many excellent contributions from my colleagues, who are THE experts in cardiovascular and pulmonary physical therapy and who poured their passion into their chapters. This edition is what I consider the “Mentoring” edition….many of the co-authors in the chapters are newly recognized cardiopulmonary specialists and past Residents of Cardiopulmonary Residency programs and new to writing. They were mentored along the way, and what they provided to this edition was amazing content, figures, videos, and updated material that makes this text stand out. We can all learn from these experts and you will as you dig into the material in the following pages. Learning does not stop with this text. Continuing education is a vital component of lifelong learning so I would also encourage all of my readers to continue their lifelong learning in cardiopulmonary physical therapy by utilizing always updated webinars from www.ptcardiopulmonaryeducators.com. During the publication phase of the first edition of the Essentials of Cardiopulmonary Physical Therapy, I was always worried about new developments in the field of Cardiovascular and Pulmonary diagnosis and treatment that were not going to be covered in the book. My very first editor, Margaret Biblis, kept saying “that’s what the next edition is for ” and that is how I approached the second edition and again the third and fourth edition. I have saved comments and suggestions along the way as well as attended conferences regularly to stay current with new developments in the field. And, with the age of the internet, you have access to the new Evolve site that accompanies this text. Instructional material including PowerPoint presentations and a test bank are available to instructors in the course, as well as updated information. So, I would like to thank all the amazing experts who have helped with this fourth edition, including each of the wonderful contributors as well as all those clinicians, students, and faculty members who provided feedback on previous editions and who continue to use this book in their courses and their every day practice. I would like to especially thank the contributors for their ability to work under my constant nagging to achieve their deadlines and for providing great material including figures, tables, and clinical notes. I would also like to acknowledge and thank Angela Campbell and Meryl Cohen, who kept pressing me to get this edition going and make it interactive, as it was their comments that pushed me to finally initiate the fourth edition. Of course my family and my dogs need to be acknowledged for all the time I spent at the computer working on this edition instead of spending time with them. Lastly, this edition truly would not be published were it not for my wonderful editor,

Brian Loehr, who called me weekly, joked with me about content and figures, and learned a lot of cardiopulmonary along the way while pushing this edition to a timely completion. He has become a friend and the best editor ever! Thanks, Brian!

SECT ION 1

Anatomy and Physiology OUT LINE 1. Anatomy of the cardiovascular and pulmonary systems 2. Physiology of the cardiovascular and pulmonary systems

Anatomy of the cardiovascular and pulmonary systems Konrad J. Dias

CHAPTER OUTLINE Thorax 1 Sternum 1 Ribs 2 The Respiratory System 3 Muscles of Ventilation 3 Muscles of Expiration 7 Pulmonary Ventilation 7 The Cardiovascular System 15 Mediastinum 15 Heart 15 Innervation 19 Cardiac and Pulmonary Vessels 19 Aorta 19 Right Coronary Artery 19 Left Coronary Artery 20 Pulmonary Artery 20 Pulmonary Veins 21 Vena Cava and Cardiac Veins 21 Systemic Circulation 21 Arteries 21 Endothelium 22 Veins 22 Summary 22 References 22

This chapter describes the anatomy of the cardiovascular and pulmonary systems as it is relevant to the physical therapist. Knowledge of the anatomy of these systems provides clinicians with the foundation to perform the appropriate examination and provide optimal treatment interventions for individuals with cardiopulmonary dysfunction. An effective understanding of cardiovascular and pulmonary anatomy allows for comprehension of function and an appreciation of the central components of oxygen and nutrient transport to peripheral tissue. A fundamental assumption is made; namely, that the reader already possesses some knowledge of anatomic terms and cardiopulmonary anatomy.

Thorax The bony thorax covers and protects the major organs of the cardiopulmonary system. Within the thoracic cavity exist the heart, housed within the mediastinum centrally, and laterally are two lungs. The bony thorax provides a skeletal framework for the attachment of the muscles of ventilation. The thoracic cage (Fig. 1-1) is conical at both its superior and inferior aspects and somewhat kidney shaped in its transverse aspect. The skeletal boundaries of the thorax are the 12 thoracic vertebrae dorsally, the ribs laterally, and the sternum ventrally.

Sternum The sternum, or breastbone, is a flat bone with three major parts: manubrium, body, and xiphoid process (see Fig. 1-1). Superiorly located within the sternum, the manubrium is the thickest component articulating with the clavicles and first and second ribs. A palpable jugular notch or suprasternal notch is found at the superior border of the manubrium of the sternum. Inferior to the manubrium lies the body of the sternum, articulating laterally with ribs three to seven. The sternal angle, or “angle of Louis,” is the anterior angle formed by the junction of the manubrium and the body of the sternum. This easily palpated structure is in level with the second costal cartilage anteriorly and thoracic vertebrae T4 and T5 posteriorly. The most caudal aspect of the sternum is the xiphoid process, a plate of hyaline cartilage that ossifies later in life. The sternal angle marks the level of bifurcation of the trachea into the right and left main stem bronchi and provides for the pump-handle action of the sternal body during inspiration.1

FIGURE 1-1 A, Anterior. B, Posterior views of the bones of the thorax. (From Hicks GH: Cardiopulmonary Anatomy and Physiology, Philadelphia, 2000, Saunders.)

Pectus excavatum is a common congenital deformity of the anterior wall of the chest in which several ribs and the sternum grow abnormally (see Fig. 5-25). This produces a caved-in or sunken appearance of the chest. It is present at birth, but rapidly progresses during the years of bone growth in the early teenage years. These patients have several pulmonary complications, including shortness of breath caused by altered mechanics of the inspiratory muscles on the caved-in sternum and ribs, and often have cardiac complications caused by the restriction (compression) of the heart.2 To gain access to the thoracic cavity for surgery, including coronary artery bypass grafting, the sternum is split in the median plane and retracted. This procedure is known

as a median sternotomy. Flexibility of the ribs and cartilage allows for separation of the two ends of the sternum to expose the thoracic cavity.3

Ribs The ribs, although considered “flat” bones, curve forward and downward from their posterior vertebral attachments toward their costal cartilages. The first seven ribs attach via their costal cartilages to the sternum and are called the true ribs (also known as the vertebrosternal ribs); the lower five ribs are termed the false ribs—the eighth, ninth, and tenth ribs attach to the rib above by their costal cartilages (the vertebrochondral ribs), and the eleventh and twelfth ribs end freely (the vertebral ribs; see Fig. 1-1). The true ribs increase in length from above downward, and the false ribs decrease in length from above downward. Each rib typically has a vertebral end separated from a sternal end by the body or shaft of the rib. The head of the rib (at its vertebral end) is distinguished by a twin-faceted surface for articulation with the facets on the bodies of two adjacent thoracic vertebrae. The cranial facet is smaller than the caudal, and a crest between these permits attachment of the interarticular ligament. Fig. 1-2 displays the components of typical ribs three to nine, each with common characteristics, including a head, neck, tubercle, and body. The neck is the 1-inch long portion of the rib extending laterally from the head; it provides attachment for the anterior costotransverse ligament along its cranial border. The tubercle at the junction of the neck and the body of the rib consists of an articular and a nonarticular portion. The articular part of the tubercle (the more medial and inferior of the two) has a facet for articulation with the transverse process of the inferior-most vertebra to which the head is connected. The nonarticular part of the tubercle provides attachment for the ligament of the tubercle.

FIGURE 1-2 Typical middle rib as viewed from the posterior. The head end articulates with the vertebral bones, and the distal end is attached to the costal cartilage of the sternum. (From Wilkins RL: Egan’s Fundamentals of Respiratory Care, ed 9, St. Louis, 2009, Mosby.)

The shaft, or body, of the rib is simultaneously bent in two directions and twisted about its long axis, presenting two surfaces (internal and external) and two borders (superior and inferior). A costal groove for the intercostal vessels and nerve extends along the inferior border dorsally but changes to the internal surface at the angle of the rib. The sternal end of the rib terminates in an oval depression into which the costal cartilage makes its attachment. Although rib fractures may occur in various locations, they are more common in the weakest area where the shaft of the ribs bend—the area just anterior to its angle. The first rib does not usually fracture, as it is protected posteroinferiorly by the clavicle. When it is injured, the brachial plexus of nerves and subclavian vessel injury may occur.4 Lower rib fractures may cause trauma to the diaphragm resulting in a diaphragmatic hernia. Rib fractures are extremely painful because of their profound nerve supply. It is important for all therapists to recommend breathing, splinting, and coughing strategies for patients with rib fractures. Paradoxical breathing patterns and a flail chest may also need to be evaluated in light of multiple rib fractures in adjacent ribs.3 Chest tubes are inserted above the ribs to avoid trauma to vessels and nerves found within the costal grove. A chest tube insertion involves the surgical placement of a hollow, flexible drainage tube into the chest. This tube is used to drain blood, air, or fluid around the lungs and effectively allow the lung to expand. The tube is placed between the ribs and into the space between the inner lining and the outer lining of the lung

(pleural space). The first, second, tenth, eleventh, and twelfth ribs are unlike the other, more typical ribs. The first rib is the shortest and most curved of all the ribs. Its head is small and rounded and has only one facet for articulation with the body of the first thoracic vertebra. The sternal end of the first rib is larger and thicker than it is in any of the other ribs. The second rib, although longer than the first, is similarly curved. The body is not twisted. There is a short costal groove on its internal surface posteriorly. The tenth through twelfth ribs each have only one articular facet on their heads. The eleventh and twelfth ribs (floating ribs) have no necks or tubercles and are narrowed at their free anterior ends. The twelfth rib sometimes is shorter than the first rib.

The Respiratory System The respiratory system includes the bony thorax, the muscles of ventilation, the upper and the lower airways, and the pulmonary circulation. The many functions of the respiratory system include gas exchange, fluid exchange, maintenance of a relatively lowvolume blood reservoir, filtration, and metabolism, and they necessitate an intimate and exquisite interaction of these various components. Because the thorax has already been discussed, this section deals with the muscles of ventilation, the upper and lower airways, and the pulmonary circulation.

Muscles of Ventilation Ventilation, or breathing, involves the processes of inspiration and expiration. For air to enter the lungs during inspiration, muscles of the thoracic cage and abdomen must move the bony thorax to create changes in volume within the thorax and cause a concomitant reduction in the intrathoracic pressure. Inspiratory muscles increase the volume of the thoracic cavity by producing bucket-handle and pump-handle movements of the ribs and sternum, as depicted in Fig. 1-3. The resultant reduced intrathoracic pressure generated is below atmospheric pressure, forcing air into the lungs to help normalize pressure differences. The essential muscles to achieve the active process of inspiration at rest are the diaphragm and internal intercostals. To create a more forceful inspiration during exercise or cardiopulmonary distress, accessory muscles assist with the inspiration. The accessory muscles include the sternocleidomastoid, scalenes, serratus anterior, pectoralis major and minor, trapezius, and erector spinae muscles.

Diaphragm The diaphragm is the major muscle of inspiration. It is a musculotendinous dome that forms the floor of the thorax and separates the thoracic and abdominal cavities (Fig. 1-4). The diaphragm is divided into right and left hemidiaphragms. Both hemidiaphragms are visible on radiographic studies from the front or back. The right hemidiaphragm is protected by the liver and is stronger than the left. The left hemidiaphragm is more often subject to rupture and hernia, usually because of weaknesses at the points of embryologic fusion. Each hemidiaphragm is composed of three musculoskeletal components, including the sternal, costal, and lumbar portions that converge into the central tendon. The central tendon of the diaphragm is a thin but strong layer of tendons (aponeurosis) situated anteriorly and immediately below the pericardium. There are three major openings to enable various vessels to traverse the diaphragm. These include the vena caval opening for the inferior vena cava; the esophageal opening for the esophagus and gastric vessels; and the aortic opening containing the aorta, thoracic duct, and azygos veins. The phrenic nerve arises from the third, fourth, and fifth cervical spinal nerves (C3 to C5) and is involved in contraction of the diaphragm.

FIGURE 1-3 A-C, Actions of major respiratory muscles. (From Boron WF: Medical Physiology, updated ed, St. Louis, 2005, Saunders.)

The resting position of the diaphragm is an arched position high in the thorax. The level of the diaphragm and the amount of movement during inspiration vary as a result of factors such as body position, obesity, and size of various gastrointestinal organs present below the diaphragm. During normal ventilation or breathing, the diaphragm contracts to pull the central tendon down and forward. In doing so, the resting dome shape of the diaphragm is reversed to a flattening of the diaphragm. Contraction of this muscle increases the dimensions of the thorax in a cephalocaudal, anterior posterior, and lateral direction.1 The increase in volume decreases pressure in the thoracic cavity and simultaneously causes a decrease in volume and an increase in pressure within the abdominal cavity. The domed shape of the diaphragm is largely maintained until the abdominal muscles end their extensibility, halting the downward displacement of the abdominal viscera, essentially forming a fixed platform beneath the central tendon. The central tendon then becomes a fixed point against which the muscular fibers of the diaphragm contract to elevate the lower ribs and thereby push the sternum and upper ribs forward. The right hemidiaphragm meets more resistance than the left during its descent, because the liver underlies the right hemidiaphragm and the stomach underlies the left; it is therefore more substantial than the left. In patients with chronic obstructive pulmonary disease (COPD), there is compromised ability to expire. This results in a flattening of the diaphragm as a result of the presence of hyperinflated lungs.1,5 It is essential for therapists to reverse hyperinflation and restore the normal resting arched position of the diaphragm using any exercise aimed at

strengthening the diaphragm muscle. A flat and rigid diaphragm cannot be strengthened and will cause an automatic firing of the accessory muscles to trigger inspiration. Body position in supine, upright, or side lying alters the resting position of the diaphragm, resulting in concomitant changes in lung volumes.6 In the supine position, without the effects of gravity, the level of the diaphragm in the thoracic cavity rises. This allows for a relatively greater excursion of the diaphragm. Despite a greater range of movement of the diaphragm, lung volumes are low as a consequence of the elevated position of the abdominal organs within the thoracic cavity. In an upright position, the dome of the diaphragm is pulled down because of the effects of gravity. The respiratory excursion is less in this position; however, the lung volumes are larger. In the side-lying position, the hemidiaphragms are unequal in their positions: the uppermost side drops to a lower level and has less excursion than that in the sitting position; the lowermost side rises higher in the thorax and has a greater excursion than in the sitting position. In quiet breathing, the diaphragm normally moves about two-thirds of an inch; with maximal ventilatory effort, the diaphragm may move from 2.5 to 4 inches.5

Clinical tip Stomach fullness, obesity with presence of a large pannus, ascites with increased fluid in the peritoneal space from liver disease, and pregnancy are additional factors affecting the normal excursion of the diaphragm during inspiration.

FIGURE 1-4 The diaphragm originates from the lumbar vertebra, lower ribs, xiphoid process, and abdominal wall and converges in a central tendon. Note the locations of the phrenic nerves and openings for the inferior vena cava, esophagus, and abdominal aorta. (From Hicks GH: Cardiopulmonary Anatomy and Physiology, Philadelphia, 2000, Saunders.)

External Intercostal Muscles The external intercostal muscles originate from the lower borders of the ribs and attach to the upper border of the ribs below (Fig. 1-5). There are 11 external intercostal muscles on each side of the sternum. Contraction of these muscles pull the lower rib up and out

toward the upper rib, thereby elevating the ribs and expanding the chest.

Accessory Muscles Fig. 1-6 explains the anatomy of the accessory muscles.

Sternocleidomastoid Muscle The sternocleidomastoid arises by two heads (sternal and clavicular from the medial part of the clavicle), which unite to extend obliquely upward and laterally across the neck to the mastoid process. For this muscle to facilitate inspiration, the head and neck must be held stable by the neck flexors and extensors. This muscle is a primary accessory muscle and elevates the sternum, increasing the anteroposterior diameter of the chest.

Scalene Muscle The scalene muscles lie deep to the sternocleidomastoid, but may be palpated in the posterior triangle of the neck. These muscles function as a unit to elevate and fix the first and second ribs: ▪ The anterior scalene muscle passes from the anterior tubercles of the transverse processes of the third or fourth to the sixth cervical vertebrae, attaching by tendinous insertion into the first rib. ▪ The middle scalene muscle arises from the transverse processes of all the cervical vertebrae to insert onto the first rib (posteromedially to the anterior scalene, the brachial plexus and subclavian artery pass between the anterior scalene and middle scalene). ▪ The posterior scalene muscle arises from the posterior tubercles of the transverse processes of the fifth and sixth cervical vertebrae, passing between the middle scalene and levator scapulae, to attach onto the second or third rib.

Upper Trapezius The trapezius (upper fibers) muscle arises from the medial part of the superior nuchal line on the occiput and the ligamentum nuchae (from the vertebral spinous processes between the skull and the seventh cervical vertebra) to insert onto the distal third of the clavicle. This muscle assists with ventilation by helping to elevate the thoracic cage.

FIGURE 1-5 The external intercostal muscles lift the inferior ribs and enlarge the thoracic cavity. The internal intercostal muscles compress the thoracic cavity by pulling together the ribs. (From Hicks GH: Cardiopulmonary Anatomy and Physiology, Philadelphia, 2000, Saunders.)

Pectoralis Major and Minor The pectoralis major arises from the medial third of the clavicle, from the lateral part of the anterior surface of the manubrium and body of the sternum, and from the costal cartilages of the first six ribs to insert upon the lateral lip of the crest of the greater tubercle of the humerus. When the arms and shoulders are fixed, by leaning on the elbows or grasping onto a table, the pectoralis major can use its insertion as its origin and pull on the anterior chest wall, lifting the ribs and sternum, and facilitate an increase in the anteroposterior diameter of the thorax. The pectoralis minor arises from the second to fifth or the third to sixth ribs upward to insert into the medial side of the coracoid process close to the tip. This muscle assists in forced inspiration by raising the ribs and increasing intrathoracic volume.

Serratus Anterior and Rhomboids The serratus anterior arises from the outer surfaces of the upper eight or nine ribs to attach along the costal aspect of the medial border of the scapula. The primary action of the serratus is to abduct, rotate the scapula, and hold the medial border firmly over the rib cage. The serratus can only be utilized as an accessory muscle in ventilation, when the rhomboids stabilize the scapula in adduction.7 The action of the rhomboids fixes the insertion, allowing the serratus to expand the rib cage by pulling the origin toward the insertion.

FIGURE 1-6 Musculature of the chest wall. (From Ravitch MM, Steichen FM: Atlas of General Thoracic Surgery, Philadelphia, 1988, Saunders.)

Latissimus Dorsi The latissimus dorsi arises from the spinous processes of the lower six thoracic, the lumbar, and the upper sacral vertebrae, from the posterior aspect of the iliac crest, and slips from the lower three or four ribs to attach to the intertubercular groove of the humerus.7 The posterior fibers of this muscle assist in inspiration as they pull the trunk into extension.

Serratus Posterior Superior The serratus posterior superior passes from the lower part of the ligamentum nuchae and the spinous processes of the seventh cervical and first two or three thoracic vertebrae downward into the upper borders of the second to fourth or fifth ribs. This muscle assists

in inspiration by raising the ribs to which it is attached and expanding the chest.

Thoracic Erector Spinae Muscles The erector spinae is a large muscle group extending from the sacrum to the skull. The thoracic erector spinae muscles extend the thoracic spine and raise the rib cage to allow greater expansion of the thorax.

Muscles of Expiration Abdominal Muscles The abdominal muscles include the rectus abdominis, transversus abdominis, and internal and external obliques. These muscles work to raise intraabdominal pressure when a sudden expulsion of air is required in maneuvers such as huffing and coughing. Pressure generated within the abdominal cavity is transmitted to the thoracic cage to assist in emptying the lungs.

Internal Intercostal Muscles Eleven internal intercostal muscles exist on each side of the sternum. These muscles arise on the inner surfaces of the ribs and costal cartilages and insert on the upper borders of the adjacent ribs below (see Fig. 1-5). The posterior aspect on the internal intercostal muscles is termed the interosseus portion and depresses the ribs to aid in a forceful expiration. The intercartilaginous portion of the internal intercostals elevates the ribs and assists in inspiration.

Pulmonary Ventilation Pulmonary ventilation, commonly referred to as breathing, is the process in which air is moved in and out of the lungs. Inspiration, an active process at rest and during exercise, involves contraction of the diaphragm and external intercostal muscles. The muscle that contracts first is the diaphragm, with a caudal movement and resultant increase within the volume of the thoracic cavity. The diaphragm eventually meets resistance against the abdominal viscera, causing the costal fibers of the diaphragm to contract and pull the lower ribs up and out—the bucket-handle movement. The outward movement is also facilitated by the external intercostal muscles. In addition, a pump-handle movement of the upper ribs is achieved through contraction of the external intercostals and the intercartilaginous portion of the internal intercostal muscles. The actions of the inspiratory muscles expand the dimensions of the thoracic cavity and concomitantly reduce the pressure in the lungs (intrathoracic pressure) below the air pressure outside the body. With the respiratory tract being open to the atmosphere, air rushes into the lungs to normalize the pressure difference, allowing inspiration to occur and the lungs to fill with air. During forced or labored breathing, additional accessory muscles need to be used to

increase the inspiratory maneuver. The accessory muscles raise the ribs to a greater extent and promote extension of the thoracic spine. These changes facilitate a further increase in the volume within the thoracic cavity and a subsequent drop in the intrathoracic pressure beyond that caused by the contraction of the diaphragm and external intercostals. This relatively lower intrathoracic pressure will promote a larger volume of air entering the lung. At rest, expiration is a passive process and achieved through the elastic recoil of the lung and relaxation of the external intercostal and diaphragm muscle. As the external intercostals relax, the rib drops to its preinspiratory position and the diaphragm returns to its elevated dome position high in the thorax. To achieve a forceful expiration, additional muscles can be used, including the abdominals and internal intercostal muscles. The internal intercostals actively pull the ribs down to help expel air out of the lungs. The abdominals contract to force the viscera upward against the diaphragm, accelerating its return to the dome position.

Clinical tip The changes in intraabdominal and intrathoracic pressure that occur with forced breathing assist with venous return of blood back to the heart. The drop in pressure allows for a filling of the veins, and the changing pressure within the abdomen and thorax cause a milking effect to help return blood back to the heart.

Pleurae Two serous membranes, or pleurae, exist that cover each lung (Fig. 1-7). The pleura covering the outer surface of each lung is the visceral pleura and is inseparable from the tissue of the lung. The pleura covering the inner surface of the chest wall, diaphragm, and mediastinum is called the parietal pleura. The parietal pleura is frequently described with reference to the anatomic surfaces it covers: the portion lining the ribs and vertebrae is named the costovertebral pleura; the portion over the diaphragm is the diaphragmatic pleura; the portion covering the uppermost aspect of the lung in the neck is the cervical pleura; and that overlying the mediastinum is called the mediastinal pleura.8 Parietal and visceral pleurae blend with one another where they come together to enclose the root of the lung. Normally, the pleurae are in intimate contact during all phases of the ventilatory cycle, being separated only by a thin serous film. There exists a potential space between the pleurae called the pleural space or pleural cavity. A constant negative pressure within this space maintains lung inflation. The serous fluid within the pleural space serves to hold the pleural layers together during ventilation and reduce friction between the lungs and the thoracic wall.6,8

FIGURE 1-7 Pleurae of the lungs. (From Craven J: The lungs and their relations. Anaesth Intensive Care Med, 9(11):459-512, 2008.)

The parietal pleura receives its vascular supply from the intercostal, internal thoracic, and musculophrenic arteries. Venous drainage is accomplished by way of the systemic veins in the adjacent parts of the chest wall. The bronchial vessels supply the visceral pleura. There exists no innervation to the visceral pleura and therefore no sensation.5 The phrenic nerve innervates the parietal pleura of the mediastinum and central diaphragm, whereas the intercostal nerves innervate the parietal pleura of the costal region and peripheral diaphragm. Irritation of the intercostally innervated pleura may result in the referral of pain to the thoracic or abdominal walls, and irritation of the phrenic-supplied pleura can result in referred pain in the lower neck and shoulder.9 Several complications can affect pleural integrity. Infection with resultant inflammatory response within the pleura is termed pleuritis or pleurisy and is best appreciated through the presence of pleural chest pain and an abnormal pleural friction rub on auscultation.9 A pleural effusion refers to a buildup of fluid in the pleural space commonly seen after cardiothoracic surgery or with cancer. This is evidenced by diminished or absent breath sounds in the area of the effusion, is more likely to be in gravity-dependent areas, and is accompanied by reduced lung volumes. Blood in the pleural space is termed a hemothorax, whereas air in the pleural space from a collapsed lung is termed a pneumothorax. Finally, a bacterial infection with resultant pus in the pleural space is referred to as empyema. Management for several of these complications of the pleural space is achieved through insertion of a chest tube into the pleural space to drain pleural secretions or to restore a negative pressure within the space and allow for lung inflation. A needle

aspiration of fluid from the space, a thoracocentesis, may be performed for patients with large pleural effusions.

Lungs The lungs are located on either side of the thoracic cavity, separated by the mediastinum. Each lung lies freely within its corresponding pleural cavity, except where it is attached to the heart and trachea by the root and pulmonary ligament. The substance of the lung— the parenchyma—is normally porous and spongy in nature. The surfaces of the lungs are marked by numerous intersecting lines that indicate the polyhedral (secondary) lobules of the lung. The lungs are basically cone shaped and are described as having an apex, a base, three borders (anterior, inferior, and posterior), and three surfaces (costal, medial, and diaphragmatic). The apex of each lung is situated in the root of the neck, its highest point being approximately 1 inch above the middle third of each clavicle. The base of each lung is concave, resting on the convex surface of the diaphragm. The inferior border of the lung separates the base of the lung from its costal surface; the posterior border separates the costal surface from the vertebral aspect of the mediastinal surface; the anterior border of each lung is thin and overlaps the front of the pericardium. Additionally, the anterior border of the left lung presents a cardiac notch. The costal surface of each lung conforms to the shape of the overlying chest wall. The medial surface of each lung may be divided into vertebral and mediastinal aspects. The vertebral aspect contacts the respective sides of the thoracic vertebrae and their intervertebral disks, the posterior intercostal vessels, and nerves. The mediastinal aspect is notable for the cardiac impression; this concavity is larger on the left than on the right lung to accommodate the projection of the apex of the heart toward the left. Just posterior to the cardiac impression is the hilus, where the structures forming the root of the lung enter and exit the parenchyma. The extension of the pleural covering below and behind the hilus from the root of the lung forms the pulmonary ligament.

FIGURE 1-8 Topography of the lung demonstrating the lobes, segments, and fissures. The fissures (or chasms) demarcate the lobes in each lung. Numbers refer to specific bronchopulmonary segments. SVC, Superior vena cava. (From Koeppen B, Stanton B: Berne and Levy Physiology, ed 6, Philadelphia, 2010, Mosby.)

Hila and Roots The point at which the nerves, vessels, and primary bronchi penetrate the parenchyma of each lung is called the hilus. The structures entering the hila of the lungs and forming the roots of each of the lungs are the principal bronchus, the pulmonary artery, the pulmonary veins, the bronchial arteries and veins, the pulmonary nerve plexus, and the lymph vessels. They lie next to the vertebral bodies of the fifth, sixth, and seventh thoracic vertebrae. The right root lies behind the superior vena cava and a portion of the right atrium, below the end of the azygos vein; the left root lies below the arch of the aorta and in front of the descending thoracic aorta. The pulmonary ligament lies below the root; the phrenic nerve and the anterior pulmonary plexus lie in front of the root; the vagus nerve and posterior pulmonary plexus lie behind the root.

Lobes, Fissures, and Segments

The right lung consists of three lobes, including the right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL). Two fissures separate these three lobes from one another. The upper and middle lobes of the right lung are separated from the lower lobe by the oblique (major) fissure (Fig. 1-8). Starting on the medial surface of the right lung at the upper posterior aspect of the hilus, the oblique fissure runs upward and backward to the posterior border at about the level of the fourth thoracic vertebra; it then descends anteroinferiorly across the anterior costal surface to intersect the lower border of the lung approximately 5 inches from the median plane and then passes posterosuperiorly to rejoin the hilus just behind and beneath the upper pulmonary vein. The RML is separated from the RUL by the horizontal (minor) fissure that joins the oblique fissure at the midaxillary line at about the level of the fourth rib and runs horizontally across the costal surface of the lung to about the level of the fourth costal cartilage; on the medial surface, it passes backward to join the hilus near the upper-right pulmonary vein. Each lobe of the right lung is further subdivided into segments. The RUL has three segments, including the apical, posterior, and anterior segments. This lobe extends to the level of the fourth rib anteriorly and is adjacent to ribs three to five posteriorly. The RML is subdivided into the lateral and medial lobes. This lobe is the smallest of the three lobes. Its inferior border is adjacent to the fifth rib laterally and the sixth rib medially. The lowermost lobe, the RLL, consists of four segments (anterior basal, superior basal, lateral basal, and posterior basal). The superior border of the RLL is at the level of the sixth thoracic vertebra and extends inferiorly down to the diaphragm. During maximal inspiration, the inferior border of the RLL may extend to the second lumbar vertebra and superimpose over the superior aspects of the kidney. The left lung is relatively smaller than the right lung and has only two lobes, including the left upper lobe (LUL) and left lower lobe (LLL). The left lung is divided into upper and lower lobes by the oblique fissure, which is somewhat more vertically oriented than that of the right lung; there is no horizontal fissure. The portion of the left lung that corresponds to the right lung is termed the lingular segment and is a part of the LUL. Posteriorly, the inferior border of the LUL is at the level of the sixth rib, and the LLL is at the level of the eleventh rib. Table 1-1 describes the topographic boundaries for the bronchopulmonary segments of each lung.

Clinical tip An understanding of the various lobes and segments and their anatomic orientation is essential for appropriate positioning and removal of secretions from various aspects of the lung during bronchopulmonary hygiene procedures.

Table 1-1 Topographic boundaries for the bronchopulmonary lung segments Lobe Upper Lobe

Segment Anterior segment (right or left)

Borders Upper border: c lavic le Lower border: a horizontal line at the level of the third interc ostal spac e (ICS ), or fourth rib, anteriorly Apic al segment (R) or apic al aspec t, Anteroinferior border: c lavic le apic oposterior segment (L) Posteroinferior border: a horizontal line at the level of the upper lateral border of the spine of the sc apula Posterior segment (R) or posterior Upper border: a horizontal line at the level of the upper lateral border of the spine of the sc apula aspec t, apic oposterior segment (L) Lower border: a horizontal line at, or approximately 1 inc h below, the inferomedial aspec t of the spine of the sc apula Middle Lobe Upper border: a horizontal line at the level of the third ICS , or fourth rib, anteriorly (R) or Lower and lateral borders: the oblique fissure (a horizontal line at the level of the sixth rib anteriorly) Lingula (L) extending to the anterior axillary line; from the anterior axillary line, angling upward to approximately the fourth rib at the posterior axillary line The midc lavic ular line separates the medial and lateral segments of the right middle lobe A horizontal line at the level of the fifth rib, anteriorly, separates the superior and inferior lingular segments Lower Lobe S uperior (basal) segment (right or Upper border: a horizontal line at, or approximately 1 inc h below, the inferomedial aspec t of the spine of the left) sc apula Lower border: a horizontal line at, or approximately 1 inc h above, the inferior angle of the sc apula Posterior (basal) segment (right or Upper border: a horizontal line at, or approximately 1 inc h above, the inferior angle of the sc apula left) Lateral border: a “plumb line” bisec ting the inferior angle of the sc apula Lower border: a horizontal line at the level of the tenth ICS , posteriorly Lateral (basal) segment (right or Upper border: a horizontal line at, or approximately 1 inc h above, the inferior angle of the sc apula left) Medial border: a “plumb line” bisec ting the inferior angle of the sc apula Lateral border: the midaxillary line Lower border: a horizontal line at the level of the tenth ICS , posteriorly Anterior (basal) segment (R) or Upper border: the oblique fissure (a horizontal line at the level of the sixth rib anteriorly, extending to the anterior aspec t, anteromedial (basal) anterior axillary line; from the anterior axillary line, angling upward to approximately the fifth rib at the segment (L) midaxillary line Lateral border: the midaxillary line

Upper Respiratory Tract Nose. The nose is a conglomerate of bone and hyaline cartilage. The nasal bones (right and left), the frontal processes of the maxillae, and the nasal part of the frontal bone combine to form the bony framework of the nose. The septal, lateral, and major and minor alar cartilages combine to form the cartilaginous framework of the nose. The periosteal and perichondral membranes blend to connect the bones and cartilages to one another. Three major muscles assist with movement of the bony framework of the nose. The procerus muscle wrinkles the skin of the nose. The nasalis muscle has two parts, including the transverse and alar portions, and assists in flaring the anterior nasal aperture.8 Finally, the depressor septi muscle works with the nasalis muscle to flare the nostrils.8 Skin covers the external nose. The nasal cavity is a wedge-shaped passageway divided vertically into right and left halves by the nasal septum and compartmentalized by the paranasal sinuses (Fig. 1-9). Opening anteriorly via the nares (nostrils) to the external environment, the nasal cavity blends posteriorly with the nasopharynx. The two halves are essentially identical, having a floor, medial and lateral walls, and a roof divided into three regions: the vestibule, the olfactory region, and the respiratory region. The primary respiratory functions of the nasal cavity include air conduction, filtration, humidification, and temperature control; it also plays a role in the olfactory process. Three nasal conchae project into the nasal cavity from the lateral wall toward the medial

wall; they are named the superior, middle, and inferior conchae. The conchae serve to increase the respiratory surface area of the nasal mucous membrane for greater contact with inspired air. The vestibule of the nasal cavity is lined with skin containing many coarse hairs and sebaceous and sweat glands. Mucous membrane lines the remainder of the nasal cavity. Fig. 1-10 depicts examples of some selected types of mucosal coverings in the upper and lower respiratory tracts. The olfactory region of the nasal cavity is distinguished by specialized mucosa. This pseudostratified olfactory epithelium is composed of ciliated receptor cells, nonciliated sustentacular cells, and basal cells that help to provide a sense of smell.8 Sniffing increases the volume of inspired air entering the olfactory region, allowing the individual to smell something specific.4 The respiratory region is lined with a mixture of columnar or pseudostratified ciliated epithelial cells, goblet cells, nonciliated columnar cells with microvilli, and basal cells. Serous and mucous glands, which open to the surface via branched ducts, underlie the basal lamina of the respiratory epithelium.10 The submucosal glands and goblet cells secrete an abundant quantity of mucus over the mucosa of the nasal cavity, making it moist and sticky. Turbulent airflow, created by the conchae, causes inhaled dust and other particulate matter larger than approximately 10 µm to “rain out” onto this sticky layer, which is then moved by ciliary action backward and downward out of the nasal cavity into the nasopharynx at an average rate of about 6 mm per minute.11,12

FIGURE 1-9 A, Positions of the frontal, maxillary, sphenoid, and ethmoid sinuses; the nasal sinuses are named for the bones in which they occur. B, Midsagittal section through the upper airway. (From Wilkins RE: Fundamentals of Respiratory Care, ed 9, St. Louis, 2009, Mosby.)

FIGURE 1-10 Types of cells composing the mucosal lining of the upper and lower respiratory tracts. (Modified from Williams PL, Warwick R, Dyson M, et al, editors: Gray’s Anatomy, ed 37, New York, 1989, Churchill Livingstone.)

Clinical tip Nasotracheal suctioning must be performed with caution in individuals with low platelet counts because of the likelihood of trauma and bleeding to superficial nasal conchae and cells within the nasal cavity. The placement of a nasopharyngeal airway or nasal trumpet may reduce trauma with recurrent blind suctioning procedures in these patients. Individuals with seasonal allergies who are prone to developing sinus infections are also prone to developing bronchitis if the infection leaves the sinus cavities and drops down the throat to the bronchioles. Pharynx.

The pharynx is a musculomembranous tube approximately 5 to 6 inches long and located posterior to the nasal cavity. It extends from the base of the skull to the esophagus that corresponds with a line extending from the sixth cervical vertebra to the lower border of the cricoid cartilage. The pharynx consists of three parts: the nasopharynx, the oropharynx, and the laryngopharynx. Nasopharynx. The nasopharynx is a continuation of the nasal cavity, beginning at the posterior nasal apertures and continuing backward and downward. Its roof and posterior wall are continuous; its lateral walls are formed by the openings of the eustachian tubes; and its floor is formed by the soft palate anteriorly and the pharyngeal isthmus (the space between the free edge of the soft palate and the posterior wall of the pharynx), which marks the transition to the oropharynx. The epithelium of the nasopharynx is composed of ciliated columnar cells. Oropharynx. The oropharynx extends from the soft palate and pharyngeal isthmus superiorly to the upper border of the epiglottis inferiorly. Anteriorly, it is bounded by the oropharyngeal isthmus (which opens into the mouth) and the pharyngeal part of the tongue. The posterior aspect of the oropharynx is at the level of the body of the second cervical vertebra and upper portion of the body of the third cervical vertebra. The epithelium in the oropharynx is composed of stratified squamous cells. Laryngopharynx. The laryngopharynx extends from the upper border of the epiglottis to the inferior border of the cricoid cartilage and the esophagus. The laryngeal orifice and the posterior surfaces of the arytenoid and cricoid cartilages form the anterior aspect of the laryngopharynx. The posterior aspect is at the level of the lower portion of the third cervical vertebra, the bodies of the fourth and fifth cervical vertebrae, and the upper portion of the body of the sixth cervical vertebra. The epithelium in the laryngopharynx is composed of stratified squamous cells. Larynx. The larynx, or voice box, is a complex structure made up of several cartilages and forms a connection between the pharynx and the trachea. The position of the larynx depends on the age and sex of the individual, being opposite the third to sixth cervical vertebrae in the adult male and somewhat higher in adult females and children. The larynx consists of the endolarynx and its surrounding cartilaginous structures. The endolarynx is made of two sets of folds, including the false vocal cords (supraglottis) and true vocal cords.8 Between the true cords are slit-shaped spaces that form the glottis. A space exists above the false vocal cords and is termed the vestibule. Six supporting cartilages, including three large (epiglottis, thyroid, cricoid) and three smaller (arytenoid, corniculate, cuneiform), prevent food, liquids, and foreign objects from entering the

airway. Two sets of laryngeal muscles (internal and external) play important roles in swallowing, ventilation, and vocalization. The larynx controls airflow and closes to increase intrathoracic pressure to generate an effective cough. Sounds with speech are created as expired air vibrates over the contracting vocal cords.

Clinical tip Endotracheal intubation may cause damage to structures within the larynx, producing an inflammatory response—laryngitis—where patients present with hoarseness and pain during speech.

Lower Respiratory Tract The lower respiratory tract extends from the level of the true vocal cords in the larynx to the alveoli within the lungs. Generally, the lower respiratory tract may be divided into two parts: the tracheobronchial tree, or conducting airways, and the acinar or terminal respiratory units.

FIGURE 1-11 Structure of the airways. The number of the various structures is reported for two lungs. (From Costanzo LS: Physiology, ed 3, St. Louis, 2007, Saunders.)

Tracheobronchial tree or conducting airways. The conducting airways are not directly involved in the exchange of gases in the lungs. They simply conduct air to and from the respiratory units. Airway diameter progressively decreases with each succeeding generation of branching, starting at approximately 1 inch in diameter at the trachea and reaching 1 mm or less at the terminal bronchioles. The cartilaginous rings of the larger airways give way to irregular cartilaginous plates, which become smaller and more widely spaced with each generation of branching, until they disappear at the bronchiolar level.13 There may be as many as 16 generations of branching in the conducting airways from the mainstem bronchi to the terminal bronchioles (Fig. 1-11).14 Trachea. The trachea is a tube approximately 4 to 4.5 inches long and approximately 1 inch in diameter, extending downward along the midline of the neck, ventral to the esophagus.

As it enters the thorax, it passes behind the left brachiocephalic vein and artery and the arch of the aorta. At its distal end, the trachea deviates slightly to the right of midline before bifurcating into right and left mainstem bronchi. Between 16 and 20 incomplete rings of two or more hyaline cartilages are often joined together along the anterior twothirds of the tracheal circumference, forming a framework for the trachea. Fibrous and elastic tissues and smooth muscle fibers complete the ring posteriorly. The first and last tracheal cartilages differ somewhat from the others: the first is broader and is attached by the cricotracheal ligament to the lower border of the cricoid cartilage of the larynx. The last is thicker and broader at its middle, where it projects a hook-shaped process downward and backward from its lower border—the carina—between the two mainstem bronchi. The carina is located at the fifth thoracic vertebra or sternal notch and represents the cartilaginous wedge at the bifurcation of the trachea into the right and left mainstem bronchi.

Clinical tip During suctioning procedures, the catheter is inserted to the level of the carina. When the catheter is in contact with the carina, a cough ensues along with a strong parasympathetic response. Therapists must monitor for adverse responses in heart rate and provide supplemental oxygen as needed. Mainstem and lobar bronchi. The right mainstem bronchus is wider and shorter than its left counterpart, and it diverges at approximately a 25-degree angle from the trachea. It passes laterally downward behind the superior vena cava for approximately 1 inch before giving off its first branch—the upper lobe bronchus—and entering the root of the right lung. Approximately 1 inch farther, it gives off its second branch—the middle lobe bronchus— from within the oblique fissure. Thereafter, the remnant of the mainstem bronchus continues as the lower lobe bronchus. The left mainstem bronchus leaves the trachea at an angle of approximately 40 to 60 degrees and passes below the arch of the aorta and behind the left pulmonary artery, proceeding for a little more than 2 inches before it enters the root of the left lung, giving off the upper lobe bronchus and continuing on as the lower lobe bronchus. The left lung has no middle lobe, which is a major distinguishing feature in the general architecture of the lungs.

Clinical tip The angulation of the right mainstem bronchus relative to the position of the trachea predisposes foreign objects, food, and fluids to enter the right lung. Consequently, aspiration is relatively more common in the right lung compared with the left lung.

Segmental and subsegmental bronchi. Each of the lobar bronchi gives off two or more segmental bronchi; an understanding of their anatomy is essential to the appropriate assessment and treatment of pulmonary disorders (Fig. 1-12). The RUL bronchus divides into three segmental bronchi about a half inch from its own origin: the first—the apical segmental bronchus—passes superolaterally toward its distribution in the apex of the lung; the second—the posterior segmental bronchus—proceeds slightly upward and posterolaterally to its distribution in the posteroinferior aspect of the upper lobe; the third—the anterior segmental bronchus —runs anteroinferiorly to its distribution in the remainder of the upper lobe. The RML bronchus divides into a lateral segmental bronchus, which is distributed to the lateral aspect of the middle lobe, and a medial segmental bronchus to the medial aspect. The RLL bronchus first gives off a branch from its posterior surface—the superior segmental bronchus—which passes posterosuperiorly to its distribution in the upper portion of the lower lobe. Then, after continuing to descend posterolaterally, the lower lobe bronchus yields the medial basal segmental bronchus (distributed to a small area below the hilus) from its anteromedial surface. The next offshoots from the lower lobe bronchus are the anterior basal segmental bronchus, which continues its descent anteriorly, and a very small trunk that almost immediately splits into the lateral basal segmental bronchus (distributed to the lower lateral area of the lower lobe) and the posterior basal segmental bronchus (distributed to the lower posterior area of the lower lobe).

FIGURE 1-12 Anterior and lateral views of the bronchopulmonary segments as seen projected to the surface of the lungs.

The LUL bronchus extends laterally from the anterolateral aspect of the left mainstem bronchus before dividing into correlates of the right upper and middle lobar bronchi. However, these two branches remain within the LUL because there is no left middle lobe. The uppermost branch ascends for approximately one-third of an inch before yielding the anterior segmental bronchus, and then continues its upward path as the apicoposterior segmental bronchus before subdividing further into its subsegmental

distribution. The caudal branch descends anterolaterally to its distribution in the anteroinferior area of the LUL, a region called the lingula. This lingular bronchus divides into the superior lingular and inferior lingular segmental bronchi. The LLL bronchus descends posterolaterally for approximately one-third of an inch before giving off the superior segmental bronchus from its posterior surface (its distribution is similar to that of the RLL superior segmental bronchus). After another one-half to two-thirds of an inch, the lower lobe bronchus splits in two: the anteromedial division is called the anteromedial basal segmental bronchus, and the posterolateral division immediately branches into the lateral basal and posterior basal segmental bronchi. The distributions of these segmental bronchi are similar to those of their right-lung counterparts. The epithelium of the upper regions of the conducting airways is pseudostratified and, for the most part, ciliated. The epithelium of the terminal and respiratory bronchioles is single layered and more cuboidal in shape, and many of the cells are nonciliated. The lamina propria, to which the epithelial basal lamina is attached, contains longitudinal bands of elastin throughout the length of the tracheobronchial tree that spread into the elastin network of the terminal respiratory units. The framework thus created is responsible for much of the elastic recoil of the lungs during expiration. The most abundant types of cells in the bronchial epithelium are the ciliated cells. Ciliated cells are found in all levels of the tracheobronchial tree down to the level of the respiratory bronchioles. The cilia projecting from their luminal surfaces are intimately involved in the removal of inhaled particulate matter from the airways via the “mucociliary escalator ” mechanism. Two of the bronchial epithelial cells are mucus secreting: the mucous cells and serous cells.15 Mucous cells, formerly called goblet cells, are normally more numerous in the trachea and large airways, becoming less numerous with distal progression, until they are infrequently found in the bronchioles. Serous cells are much less numerous than mucous cells and are confined predominantly to the extrapulmonary bronchi. Both types of cells are nonciliated, although both exhibit filamentous surface projections.

Clinical tip Smoking paralyzes ciliated epithelial cells. These cilia will be paralyzed for 1 to 3 hours after smoking a cigarette, or will be permanently paralyzed in chronic smokers.16 The inability of the mucociliary escalator to work increases the individual’s risk for developing respiratory infections. Terminal respiratory (acinar) units. The conducting airways terminate in gas-exchange airways made up of respiratory bronchioles, alveolar ducts, and alveoli (Fig. 1-13). These structures together are termed the acinus and participate in gas exchange. The functional unit of the lung is the alveoli, where gas exchange occurs. The acinus is connected to the interstitium through a dense

network of fibers. Two major types of epithelial cells exist along the alveolar wall. Squamous pneumocytes (type I) cells are flat and thin and cover approximately 93% of the alveolar surface. Granular pneumocytes (type II) cells are thick, are cuboidal shaped, cover 7% of the alveolar wall, and are involved in the production of surfactant.13 Surfactant is a lipoprotein that lowers alveolar surface tension at end expiration and thereby prevents the lung from collapsing. The alveoli, like the bronchi, contain cellular components of inflammation and immunity. The alveolar macrophage engulfs and ingests foreign material in the alveoli and provides a protective function against disease.

FIGURE 1-13 A view of the terminal respiratory unit showing the alveolar sac and blood supply surrounding. (From Malamed SF: Sedation, ed 4, Mosby, St. Louis, 2010.)

Capillaries composed of a single layer of endothelial cells deliver blood in close proximity to the alveoli. Capillaries can distend and accommodate to the volume of blood being delivered to the lung. The alveolar capillary interface is where exchange of gases occurs. The thickness of the alveolar capillary membrane is between 0.5 and 1.0 µm.

Innervation of the Lungs The lungs are invested with a rich supply of afferent and efferent nerve fibers and specialized receptors. Parasympathetic fibers are supplied by preganglionic fibers from the vagal nuclei via the vagus nerves to ganglia around the bronchi and blood vessels. Postganglionic fibers innervate the bronchial and vascular smooth muscle, as well as the mucous cells and submucosal bronchial glands. The parasympathetic postganglionic fibers from thoracic sympathetic ganglia innervate essentially the same structures. Posterior and anterior pulmonary plexuses are formed by contributions from the postganglionic sympathetic and parasympathetic fibers at the roots of the lungs. Generally, stimulation of the vagus nerve results in bronchial constriction, dilation of pulmonary arterial smooth muscle, and increased glandular secretion.17 Stimulation of the sympathetic nerves causes bronchial relaxation, constriction of pulmonary arterial smooth muscle, and decreased glandular secretion.17 Bronchodilators enhance sympathetic stimulation to the lungs to cause relaxation of bronchial smooth muscle cells and reduce secretions.

The Cardiovascular System Mediastinum The mediastinum lies between the right and left pleura of the lungs and near the median sagittal plane of the chest. From an anteroposterior perspective, it extends from the sternum in front to the vertebral column behind and contains all the thoracic viscera except the lungs.8 It is surrounded by the chest wall anteriorly, the lungs laterally, and the spine posteriorly. It is continuous with the loose connective tissue of the neck and extends inferiorly onto the diaphragm. It is the central compartment of the thoracic cavity and contains the heart, the great vessels of the heart, esophagus, trachea, phrenic nerve, cardiac nerve, thoracic duct, thymus, and lymph nodes of the central chest.8,13 A shifting of the structures within the mediastinum (mediastinal shift) is appropriate to consider and examine on the chest radiograph in patients who have air trapped in the pleural space (pneumothorax) or after removal of a lung (pneumonectomy).3 In a tension pneumothorax or pneumonectomy, the mediastinum shift away from the affected or operated side.

Heart The heart is the primary pump that circulates blood through the entire vascular system. It is closely related to the size of the body and is roughly the size of the individual’s closed fist. It lies obliquely (diagonally) in the mediastinum, with two-thirds lying left of the midsagittal plane. The superior portion of the heart formed by the two atria is termed the base of the heart. It is broad and exists at the level of the second intercostal space in adults. The apex of the heart, defined by the tip of the left ventricle, projects into the fifth intercostal space at the midclavicular line. The heart moves freely and changes its position during its contraction and relaxation phase, as well as during breathing. As the heart contracts, it moves anteriorly and collides with the chest wall. The portion of the heart that strikes the chest wall is the apex of the heart and is termed the point of maximum impulse.1 Normally, this point is evidenced at the anatomic landmark of the apex, which is the fifth intercostal space at the midclavicular line. In terms of ventilation, quiet resting breathing does not alter the point of maximum impulse because of minimal excursion of the diaphragm. However, with deep inspiration, there is more significant inferior depression of the diaphragm, causing the heart to descend and rotate to the right, displacing the point of maximum impulse away from the normal palpable position.1

Clinical tip The point of maximum impulse is relatively more lateral in patients with left ventricular hypertrophy caused by an increase in left ventricular mass. Also, patients with a pneumothorax and resultant mediastinal shift will demonstrate an altered point

of maximum impulse away from the normal anatomic position of the apex of the heart.

Tissue Layers Pericardium The heart wall is made up of three tissue layers (Fig. 1-14). The outermost layer of the heart is a double-walled sac termed the pericardium, anchored to the diaphragm inferiorly and the connective tissue of the great vessels superiorly. The two layers of the pericardium include an outer parietal pericardium and an inner visceral pericardium, also referred to as the epicardium.8 The parietal pericardium is a tough, fibrous layer of dense, irregular connective tissue, whereas the visceral pericardium is a thin, smooth, and moist serous layer. Between the two layers of the pericardium is a closed space termed the pericardial space or pericardial cavity filled with approximately 10 to 20 mL of clear pericardial fluid.18 This fluid separates the two layers and minimizes friction during cardiac contraction. In patients with inflammation of the pericardium, fluid may accumulate in the closed pericardial space, producing cardiac tamponade, evidenced as compromised cardiac function and contractility caused by buildup of fluid in the pericardial space. Finally, pericarditis is also commonly noted after a coronary artery bypass grafting procedure.

FIGURE 1-14 Layers of the heart wall. (From Applegate E: The Anatomy and Physiology Learning System, ed 3, St. Louis, 2007, Saunders.)

Myocardium The middle layer of the heart is termed the myocardium. It is the layer of the heart that facilitates the pumping action of the heart as a result of the presence of contractile elements. Myocardial cells are unique, as they demonstrate three important traits: automaticity (the ability to contract in the absence of stimuli); rhythmicity (the ability to contract in a rhythmic manner); and conductivity (the ability to transmit nerve impulses).17 Myocardial cells may be categorized into two groups based on their function: mechanical cells contributing to mechanical contraction and conductive cells contributing to electrical conduction.1,17 Mechanical cells, also termed myocytes, are large cells containing a larger number of actin and myosin myofilaments, enabling a greater capacity for mechanical shortening needed for pump action. In addition, these cells have a large number of mitochondria (25% of cellular volume) to provide sufficient energy in the form of adenosine triphosphate (ATP) to the heart, an organ that can never rest.5,17 The conducting myocardial cells are joined by intercalated disks forming a structure

known as a syncytium. A syncytium characterizes a group of cells in which the protoplasm of one cell is continuous with that of adjacent cells.8 Intercalated disks contain two junctions: desmosomes attaching one cell to another and connexins that allow the electrical flow to spread from one cell to another. These two junctions work together to move the impulse through a low-resistance pathway.

Clinical tip Injured myocardial cells cannot be replaced, as the myocardium is unable to undergo mitotic activity. Thus death of cells from an infarction or a cardiomyopathy may result in a significant reduction in contractile function.

Endocardium The innermost layer of the heart is termed the endocardium. This layer consists of simple squamous endothelium overlying a thin areolar tissue layer.18 The tissue of the endocardium forms the inner lining of the chambers of the heart and is continuous with the tissue of the valves and the endothelium of the blood vessel. Because the endocardium and valves share similar tissue, patients with endocarditis must be ruled out for valvular dysfunction. Endocardial infections can spread into valvular tissue, developing vegetations on the valve.19 Bronchopulmonary hygiene procedures, including percussions and vibrations, are contraindicated for patients with unstable vegetations, as they may dislodge, move as emboli, and cause an embolic stroke.

Chambers of the Heart The heart is divided into right and left halves by a longitudinal septum (Fig. 1-15). The right side of the heart receives deoxygenated venous blood (returning from the body), and the left side of the heart receives oxygenated blood (returning from the lungs). Each half of the heart is made up of two chambers: superiorly the atria and inferiorly the ventricles. Thus the four chambers of the heart include the right atrium (Fig. 1-16, A), right ventricle (see Fig. 1-16, A), left atrium (see Fig. 1-16, B), and left ventricle (see Fig. 116, B). The atria receive blood from the systemic and pulmonary veins and eject blood into the ventricles. The ventricles eject blood that is received from the atria into arteries that deliver blood to the lungs and the systemic circulation.

Right Atrium The chamber of the right atrium (see Fig. 1-16, A) consists of a smooth posterior and medial inner wall. Parallel muscle bundles known as pectinate muscles exist anteriorly and laterally. Both right and left atria have small earlike extensions called auricles that help to increase volume within the chambers. The right atrium receives deoxygenated blood from three major vessels. The superior vena cava collects venous blood from the head

and upper extremities; the inferior vena cava collects blood from the trunk and lower extremities; and the coronary sinus collects venous blood specifically from the heart. The coronary sinus empties into the right atrium above the tricuspid valve. Normal diastolic pressure to enable filling ranges from 0 to 8 mm Hg and is clinically referred to as the central venous pressure.

FIGURE 1-15 View of heart showing all four chambers and forward blood flow through right and left sides. (From Khanna N: Illustrated Synopsis of Dermatology and Sexually Transmitted Diseases, New Delhi, 2005, Peepee Publishers and Distributors.)

The effective contraction of the pectinate muscles of the atria accounts for approximately 15% to 20% of cardiac output—the atrial kick.19 In patients with abnormal electrical conduction causing a quivering of the atria (atrial fibrillation), the mechanical contractile ability of the pectinate muscles is reduced, resulting in a low atrial kick and compromised cardiac output.1,5

Right Ventricle The right ventricle is shaped like a crescent or triangle, enabling it to eject large volumes of blood through a small valve into a low-pressure pulmonary system. Blood within the right ventricle is received from the right atrium through a one-way valve present between the atrium and ventricle termed the tricuspid atrioventricular valve. It ejects blood to the lungs via the pulmonic semilunar valve into the pulmonary artery. The right ventricle (see Fig. 1-16, A), like the right atrium, may be considered in two parts: (1) a posteroinferior inflow tract, termed the body, which contains the tricuspid valve, chordae tendineae, papillary muscles, and trabeculated myocardium; and (2) an anterosuperior outflow tract, called the infundibulum, from which the pulmonary trunk arises.8 Four muscular bands

separate the inflow and outflow portions of the right ventricle, including the infundibular septum, the parietal band, the septal band, and the moderator band. Pressures within the right ventricle are relatively lower compared with the left ventricle, with diastolic pressures ranging from 0 to 8 mm Hg and systolic pressures ranging from 15 to 30 mm Hg.17 During periods of exacerbation, patients with chronic lung pathologies, including COPD and pulmonary fibrosis, often present with hypoxemia and increased pressure within the pulmonary vasculature, termed pulmonary artery hypertension, caused by compromised perfusion capacity to the lung.19,20 The increased pressure within the pulmonary artery increases the workload on the right ventricle, causing cor pulmonale, or right ventricular hypertrophy, and resultant right ventricular failure.

Left Atrium The left atrium is divided from the right atrium by an interatrial septum. It has a relatively thicker wall compared with the right atrium to adapt to higher pressures of blood entering the chamber from the lung. Oxygenated blood from the lungs enters the left atrium posteriorly via the pulmonary veins. These vessels have no valves; instead, pectinate muscles extend from the atria into the pulmonary veins and exert a sphincterlike action to prevent backflow of blood during contraction of the atria. The normal filling pressure of the left ventricle is between 4 and 12 mm Hg. Oxygenated blood is ejected out of the left atrium through the mitral atrioventricular (bicuspid) valve to enter the left ventricle.

FIGURE 1-16 Schematic of the heart. A, Right atrium and ventricle. The arrows indicate the flow of blood from the venae cavae to the right atrium and from the right atrium to the right ventricle. B, Left atrium and ventricle. The blood flows from the pulmonary veins to the left atrium, through the mitral valve into the left ventricle, and from there into the systemic circulation. (From Snopek AM: Fundamentals of Special Radiographic Procedures, ed 5, St. Louis, 2007, Saunders.)

Regurgitation, or insufficiency of the mitral valve, causes blood to accumulate in the left atrium and elevate left atrial pressures. These chronically elevated pressures alter the

integrity of the atrial wall and predispose the individual to developing a quivering of the atria wall (atrial fibrillation) and potential blood clots within the left atrium.

Left Ventricle The almost conical left ventricle (see Fig. 1-16, B) is longer and narrower than the right ventricle. The walls of the left ventricle are approximately three times thicker than those of the right, and the transverse aspect of the cavity is almost circular. In contrast to the inflow and outflow orifices of the right ventricle, those of the left are located adjacent to one another, being separated only by the anterior leaflet of the mitral valve and the common fibrous ridge to which it and the left and posterior cusps of the aortic valve are attached. The interventricular septum forms the medial wall of the left ventricle and creates a separation between the left and right ventricle. This chamber receives oxygenated blood from the left atrium via the mitral valve and ejects blood through the aortic valve and into the aorta to the peripheral systemic vasculature. Normal systolic pressures within the left ventricle are 80 to 120 mm Hg, and diastolic pressures are 4 to 12 mm Hg. Because of the elevated pressures within this chamber, the wall thickness of the left ventricle is the greatest compared with the three other chambers of the heart.

FIGURE 1-17 Nomenclature for the leaflets and cusps of the principal valves of the heart.

Pathologic thickening of the left ventricular wall is evidenced in patients with various

cardiovascular complications, including but not limited to, hypertension, aortic stenosis, and heart failure, as a consequence of an increase in the afterload. This pathologic thickening alters the contractile ability of the ventricle and reduces its filling capacity, causing a reduction in cardiac output.

Heart Valves Four heart valves (Fig. 1-17) ensure one-way blood flow through the heart. Two atrioventricular valves exist between the atria and the ventricle, including the tricuspid valve on the right and the mitral or bicuspid valve on the left between the left atrium and ventricle. The semilunar valves lie between the ventricles and arteries and are named based on their corresponding vessels: pulmonic valve on the right in association with the pulmonary artery, and aortic valve on the left relating to the aorta. Flaps of tissue called leaflets or cusps guard the heart valve openings. The right atrioventricular valve has three cusps and therefore is termed tricuspid, whereas the left atrioventricular valve has only two cusps and hence is termed bicuspid. These leaflets are attached to the papillary muscles of the myocardium by chordae tendineae. The primary function of the atrioventricular valves is to prevent backflow of blood into the atria during ventricular contraction or systole, and the semilunar valves prevent backflow of blood from the aorta and pulmonary artery into the ventricles during diastole. Opening and closing of each valve depends on pressure gradient changes within the heart created during each cardiac cycle. An initial disturbance of valvular function may be picked up through auscultation of the heart sounds and evidenced by variety of murmurs. It must be noted that the identification of a murmur would warrant the need for additional testing, including echocardiography, to accurately diagnose pathology within a particular valve.

Conduction System In a normal conduction system (Fig. 1-18), electrical impulses arise in the sinoatrial (SA), or sinus, node. The SA node is located at the junction of the right atrium and superior vena cava. The P cells of the SA node are the sites for impulse generation; consequently, the SA node is termed the pacemaker of the heart, as it makes or creates the impulses that pace the heart.8 The normal pacing ability of the SA node is between 60 and 100 beats per minute (bpm) at rest. The impulse generated at the SA node travels down one of three internodal tracts to the atrioventricular (AV) node. The three conduction pathways that exist between the SA and AV node include an anterior tract of Bachman, a middle tract of Wenckebach, and a posterior tract of Thorel.8

FIGURE 1-18 Conduction system of the heart. The electrical impulse originates in the heart, and contraction of the heart’s chambers is coordinated by specialized heart tissues. (From Leonard PC: Building a Medical Vocab ulary: With Spanish Translations, ed 7, St. Louis, 2009, Saunders.)

The AV node is located at the inferior aspect of the right atrium, near the opening of the coronary sinus and above the tricuspid valve. Posterior to the AV node are several parasympathetic autonomic ganglia that serve as receptors for the vagus nerve and cause slowing of the cardiac cycle. The major function of the AV node during each cardiac cycle is to slow down the cardiac impulse to mechanically allow time for the ventricles to fill. Conducting fibers from the AV node converge to form the bundle of His to carry the impulse into the ventricles. The bundle of His appears as a triangle of nerve fibers within the posterior border of the interventricular septum. The bundle bifurcates to give rise to the right and left bundle branches carrying the impulse to the right and left ventricles, respectively. The right bundle branch (RBB) is thin, with relatively fewer branches proceeding inferiorly to the apex of the right ventricle. The left bundle branch (LBB) arises perpendicularly and divides into two branches or fascicles.8 The left anterior bundle branch crosses the left anterior papillary muscle and proceeds along the base of the left ventricle toward the aortic valve. The left posterior bundle branch advances posteriorly through the posterior papillary muscle toward the posterior inferior left ventricular wall. Both bundles terminate into a network of nerve fibers called the Purkinje fibers. These fibers extend from the apex of each ventricle and penetrate the heart wall to the outer myocardium. Electrical stimulation of the Purkinje fibers causes mechanical contraction of the ventricles. It may be important to appreciate that normal electrical conduction through the heart allows for appropriate mechanical activity and maintenance of cardiac output to sustain activity. An alteration in the conduction pathway subsequently alters the mechanical activity of the heart and reduces cardiac output.

Clinical tip An evaluation of electrocardiographic (ECG) changes is necessary to help a clinician recognize and differentially diagnose reduced exercise tolerance caused from an electrical disturbance producing mechanical alterations that reduce cardiac output and exercise tolerance and not a true mechanical problem within the heart.

Innervation Although the SA node and conduction pathway have an intrinsic rate of depolarization causing contraction of the myocardium, the autonomic nervous system influences the rate of impulse generation, contraction, relaxation, and strength of contraction.6,17 Thus autonomic neural transmission creates changes in the heart rate and contractility to allow adjustments in cardiac output to meet metabolic demands. A cardiac plexus contains both sympathetic and parasympathetic nerve fibers and is located anterior to the tracheal bifurcation. The cardiac plexus receives its parasympathetic input from the right and left vagus nerves.17 Subsequently, nerves branch off the plexus, follow the coronary vessels, and innervate the SA node and other components of the conduction system. There is relatively less parasympathetic innervation to the ventricles, resulting in a sympathetic dominance on ventricular function. Vagal stimulation is inhibitory on the cardiovascular system and is evidenced by decreased heart rate and blood pressure.6 The neurohormone involved with parasympathetic stimulation is acetylcholine. The sympathetic input to the plexus arises from the sympathetic trunk in the neck. Cardiac nerves from the cervical and upper four to five thoracic ganglia feed into the cardiac plexus.6,17 Sympathetic stimulation releases catecholamines (epinephrine and norepinephrine) that interact with β-adrenergic receptors on the cardiac cell membrane, causing an excitation of the cardiovascular system. This is evidenced by an increase in heart rate, increased contractility through a greater influx of calcium into myocytes, increased blood pressure, a shortening of the conduction time through the AV node, and an increase in rhythmicity of the AV pacemaker fibers. Sympathetic nervous system stimulation is cardioexcitatory and increases heart rate and contractility—the fight-or-flight response. Conversely, parasympathetic stimulation is cardioinhibitory and slows down heart rate and contractility.

Cardiac and Pulmonary Vessels Aorta The ascending aorta begins at the base of the left ventricle and is approximately 2 inches long. From the lower border of the third costal cartilage at the left of the sternum, it passes upward and forward toward the right as high as the second right costal cartilage. The aorta exhibits three dilations above the attached margins of the cusps of the aortic valve at the root of the aorta—the aortic sinuses (of Valsalva). The coronary arteries (Fig. 1-19) open near these aortic sinuses of Valsalva. Three branches typically arise from the upper aspect of the arch of the aorta: the brachiocephalic trunk (innominate artery), the left common carotid artery, and the left subclavian artery. The openings of the coronary arteries block blood from entering into the arteries when the aortic valve is open (during systole). Therefore the part of the cardiac cycle when the coronary arteries receive their blood is during diastole, when the aortic valves are closed.

Right Coronary Artery The right coronary artery arises from the right anterolateral surface of the aorta and passes between the auricular appendage of the right atrium and the pulmonary trunk, typically giving off a branch to the sinus node and yielding two or three right anterior ventricular rami as it descends into the coronary sulcus to come around the right (acute) margin of the heart into the posterior aspect of the sulcus. As the right coronary artery crosses the right margin of the heart, it gives off the right (acute) marginal artery before continuing as far as the posterior interventricular sulcus, where it usually turns to supply the diaphragmatic surfaces of the ventricles as the posterior interventricular (posterior descending) artery. In approximately 70% of hearts, an atrioventricular nodal artery is given off just before the posterior interventricular artery.21

FIGURE 1-19 Typical distributions of the right and left coronary arteries and veins (From Herlihy B: The Human Body in Health and Illness, ed 4, St. Louis, 2011, Saunders.)

Left Coronary Artery The left coronary artery originates from the left anterolateral aspect of the aorta and splits into two major branches: the anterior interventricular and circumflex arteries. The anterior interventricular, or left anterior descending artery (LAD), traverses the anterior interventricular groove to supply sternocostal aspects of both ventricles. In its course, the anterior interventricular artery gives off right and left anterior ventricular and anterior septal branches. The larger left anterior ventricular branches vary in number from two to nine, with the first being designated the diagonal artery. Approximately 70% of the left ventricle is fed by the LAD artery. The circumflex artery runs in the coronary sulcus between the left atrium and ventricle, crosses the left margin of the heart, and usually continues to its termination, just short of the junction of the right coronary and the posterior interventricular arteries. In many instances, as the circumflex artery crosses the left margin of the heart, it gives off a large branch that supplies this area—the left marginal (obtuse) artery. The right coronary artery is the primary supply route for blood to the majority of the right ventricle and the inferior and posterior portions of the left ventricle. In addition, specialized conduction tissue within the right atrium, including the SA node and AV node, are nourished by the right coronary artery. The LAD supplies blood to the anterior and septal aspects of the left ventricle, and the circumflex artery supplies blood to the lateral aspect of the left ventricle. Occlusion of a coronary artery produces an infarction in a defined region within the

heart. Right coronary artery occlusions cause inferior or posterior infarctions and affect the functioning of the SA node in the right atrium. Left anterior descending artery occlusions produce anterior septal infarctions, also termed the widow maker, whereas circumflex occlusions are responsible for generating lateral infarctions. Distribution of blood supply within the heart is variable from one individual to another because of the presence of collateral circulation involving the formation of new blood vessels (angiogenesis) in areas of the heart that are partially occluded.

Pulmonary Artery The pulmonary trunk runs upward and backward (first in front of and then to the left of the ascending aorta) from the base of the right ventricle; it is approximately 2 inches in length. At the level of the fifth thoracic vertebra, it splits into right and left pulmonary arteries. The right pulmonary artery runs behind the ascending aorta, superior vena cava, and upper pulmonary vein, but in front of the esophagus and right primary bronchus to the root of the lung. The left pulmonary artery runs in front of the descending aorta and the left primary bronchus to the root of the left lung. It is attached to the arch of the aorta by the ligamentum arteriosum.

Clinical tip A saddle embolus is life threatening and involves an embolus dislodged at the bifurcation of the right and left pulmonary arteries.

Pulmonary Veins The pulmonary veins, unlike the systemic veins, have no valves. They originate in the capillary networks and join together to ultimately form two veins—a superior and an inferior pulmonary vein—from each lung, which open separately into the left atrium (see Fig. 1-19).

Vena Cava and Cardiac Veins The superior vena cava is approximately 3 inches long from its termination in the upper part of the right atrium opposite the third right costal cartilage to the junction of the two brachiocephalic veins. The inferior vena cava extends from the junction of the two common iliac veins, in front of the fifth lumbar vertebra, passing through the diaphragm to open into the lower portion of the right atrium. The vena cavae have no valves. The cardiac veins can be categorized into three groups: the coronary sinus and its supplying veins, the anterior cardiac veins, and the thebesian veins. Most of the veins of the heart drain into the coronary sinus, which runs into the posterior aspect of the coronary sulcus and empties through the valve of the coronary sinus, a semilunar flap,

into the right atrium between the opening of the inferior vena cava and the tricuspid valve. As Fig. 1-19 shows, the small and middle cardiac veins, the posterior vein of the left ventricle, the left marginal vein, and the great cardiac vein feed the coronary sinus. The anterior cardiac veins are fed from the anterior part of the right ventricle. They originate in the subepicardial tissue, crossing the coronary sulcus as they terminate directly into the right atrium. The right marginal vein runs along the right border of the heart and usually opens directly into the right atrium. Occasionally, it may join the small cardiac vein. The thebesian veins (venae cordis minimae) vary greatly in their number and size. These tiny veins open into all the cavities of the heart, but are most numerous in the right atrium and ventricle, are found occasionally in the left atrium, and are rare in the left ventricle.

Systemic Circulation Oxygenated blood ejected out of the heart flows through the aorta into systemic arteries. These arteries branch into smaller vessels called arterioles, which further branch into the smallest vessels, the capillaries primarily involved in the exchange of nutrients and gases. Deoxygenated blood from the capillaries enters venules that join together to form larger veins that return blood back to the right heart and lungs. Blood vessels have three layers: the innermost tunica intima, middle tunica media, and outermost tunica adventitia.

Arteries The wall of the artery is composed of elastic and fibrous connective tissue and smooth muscle. Anatomically, arteries can be categorized into two types depending on the structural components along their wall. Elastic arteries, including the aorta and pulmonary trunk, have a thick tunica media with more elastic fibers than smooth muscle cells, allowing for a greater stretch as blood is ejected out of the heart. During diastole, the elasticity of the vessel promotes recoil of the artery and maintains blood pressure within the vessel. Muscular arteries are present in medium and small arteries and contain more smooth muscle cells within the middle tunica media layer. These arteries have the ability of vasoconstriction and vasodilation as a result of the presence of smooth muscles cells to control the amount of blood flow to the periphery.6 These smooth muscle cells are under autonomic nervous system influence through the presence of α-receptors. As the artery becomes more distal, a greater amount of smooth muscle is evidenced. Arterioles have primarily smooth muscle along their walls, enabling their diameter to alter significantly as needed. Arterioles empty into capillary beds. The density of capillaries within a capillary bed is greater in active tissue, including the muscle. Exchange of nutrients and gases occur within the capillary bed. Fig. 1-20 depicts the major arterial tree within the human body.

FIGURE 1-20 Anterior view of the aorta and its principal arterial branches. Labels for the ascending, arch, thoracic, and abdominal aorta and their corresponding arteries are shown. (From Leonard PC: Building a Medical Vocab ulary: With Spanish Translations, ed 7, St. Louis, 2009, Saunders.)

Endothelium Endothelial cells form the endothelium, or endothelial lining, of the blood vessel. These cells have the ability to adjust their number and arrangement to accommodate local requirements. Endothelial cells serve several important functions, including filtration and permeability, vasomotion, clotting, and inflammation.19 Atherosclerosis is initiated through endothelial dysfunction, evidenced by endothelial cells that are extensively permeable to fat cells and white blood cells.

Veins Compared with arteries, veins have thinner walls and a larger diameter. Veins also have less elastic tissue and hence are not as distensible. In the lower extremity, veins have valves to assist with unidirectional flow of blood back to the heart. Blood is transferred back to the heart through muscle pump activity, which causes a milking effect on the veins. Patients with incompetent valves in their veins develop varicosities in their lower extremities. Also, patients on prolonged bed rest are likely to develop deep vein thrombosis from a lack of muscle activity, resulting in a pooling of blood and clot formation within the venous vasculature.

Summary This chapter provides the reader with an understanding of the anatomy of the cardiovascular and pulmonary systems and its relevance for the therapist. This content provides the basis for an understanding of the pathophysiology of these systems and lays a foundation for the development of relevant examination and treatment strategies to use when managing patients with cardiopulmonary dysfunction. A comprehensive understanding of anatomy is fundamental to the knowledge base of the therapist in understanding the central components involved in the delivery of oxygen and nutrients to peripheral tissue.

References 1. DeTurk W, Cahalin L. Cardiovascular and Pulmonary Physical Therapy: An Evidenced-Based Approach. New York: McGraw-Hill; 2004. 2. Townsend C.M, Beauchamp R.D, Evers B.M, et al. Sabiston Textbook of Surgery. ed 18. Philadelphia: Saunders; 2008. 3. Paz J, West M. Acute Care Handbook for Physical Therapists. ed 3. Philadelphia: Saunders; 2009. 4. Ganong W.F. Review of Medical Physiology. ed 21. New York: McGraw-Hill; 2003. 5. Frownfelter D, Dean E. Cardiovascular and Pulmonary Physical Therapy: Evidence and Practice. ed 4. St. Louis: Mosby; 2006. 6. Fox S. Human Physiology. ed 11. Boston: McGraw-Hill; 2009. 7. Kendall F.P, McCreary E.P, Provance P.G, et al. Muscles: Testing and Function. ed 5. Baltimore: Lippincott Williams and Wilkins; 2005. 8. Gray H, Bannister L.H, Berry M.M, et al. Gray’s Anatomy: The Anatomical Basis of Medicine and Surgery. ed 38. New York: Churchill Livingstone; 1996. 9. Goodman C, Fuller K. Pathology: Implications for the Physical Therapist. ed 3. St. Louis: Saunders; 2009. 10. Lund V.J. Nasal physiology: Neurochemical receptors, nasal cycle and ciliary action. Allergy Asthma Proc. 1996;17(4):179–184. 11. Richerson H.B. Lung defense mechanisms. Allergy Proc. 1990;11(2):59–60. 12. Janson-Bjerklie S. Defense mechanisms: Protecting the healthy lung. Heart Lung. 1983;12(6):643–649. 13. Moore K, Dalley A. Clinically Oriented Anatomy. ed 5. Baltimore: Lippincott, Williams and Wilkins; 2006. 14. Berend N, Woolcock A.J, Marlin G.E. Relationship between bronchial and arterial diameters in normal human lungs. Thorax. 1979;34(3):354–358. 15. Mason R.J, Broaddus V.C, Murray J.F, et al. Textbook of Respiratory Medicine. ed 4. Philadelphia: Saunders; 2006. 16. Heuther S.E, McCance K.L. Understanding Pathophysiology. ed 3. St. Louis: Mosby; 2004. 17. Guyton A.C, Hall J.E. Textbook of Medical Physiology. ed 11. Philadelphia: Saunders; 2006. 18. Moore K, Dalley A. Clinically Oriented Anatomy. ed 5. Baltimore: Lippincott Williams and Wilkins; 2006. 19. Cheitlin M.D. Clinical Cardiology. ed 7. Stamford, CT: Appleton & Lange; 2004. 20. Berne R.M, Levy M.N. Cardiovascular Physiology. ed 8. Philadelphia: Mosby; 2002. 21. Abuin G, Nieponice A. New findings on the origin of the blood supply to the atrioventricular node. Clinical and surgical significance. Tex Heart Inst J. 1998;25(2):113–117.

Physiology of the cardiovascular and pulmonary systems Konrad J. Dias

CHAPTER OUTLINE The Pulmonary System 23 Ventilation 23 Respiration 30 The Cardiovascular System 34 The Cardiac Cycle 34 Physiology of Cardiac Output 36 Summary 40 References 40

This chapter reviews concepts relating to the physiology of the cardiovascular and pulmonary systems and its relevance in physical therapy practice. The cardiopulmonary systems not only share a close spatial relationship in the thoracic cavity, but also have a close functional relationship to maintain homeostasis. Physiologically, these systems must work collaboratively to provide oxygen required for energy production and assist in removing carbon dioxide manufactured as a waste product. A disorder affecting the lungs has a direct effect on the heart and vice versa. An understanding of normal physiology helps the reader better appreciate pathophysiologic changes associated with diseases and dysfunction of these systems that will be discussed in subsequent chapters.

The Pulmonary System The pulmonary system has several important functions. The most important function of the pulmonary system is to exchange oxygen and carbon dioxide between the environment, blood, and tissue. Oxygen is necessary for the production of energy. If a cell has oxygen, a single molecule of glucose can undergo aerobic metabolism and produce 36 adenosines triphosphate (ATP). However, if a cell is devoid of oxygen, each molecule of glucose undergoes anaerobic metabolism, yielding only 2 ATP. Thus pathology of the pulmonary system will result in reduced energy production because of decreased oxygen within the tissue and a concomitant reduction in the exercise tolerance of the individual. Carbon dioxide is another gas that must be effectively exchanged at the level of the lung. Through the release of carbon dioxide from the body, the pulmonary system plays an important role in regulating the acid–base balance and maintaining normal blood pH. The second function of the pulmonary system is temperature homeostasis, which is achieved through evaporative heat loss from the lungs. Finally, the pulmonary system helps to filter and metabolize toxic substances, as it is the only organ that receives all blood coming from the heart. To facilitate comprehension of the physiology of the pulmonary system, three major physiologic components are discussed in this chapter, including (1) the process of ventilation or breathing; (2) the process of gas exchange or respiration; and (3) the transport of gases to peripheral tissue.

Ventilation Ventilation, or breathing, often misnamed respiration, involves the mechanical movement of gases into and out of the lungs.1 At rest, an adult breathes at a rate of 10 to 15 breaths/minute, termed the ventilatory rate or respiratory rate. Approximately 350 to 500 mL of air is inhaled or exhaled at rest with each breath and is termed the tidal volume (TV or VT). The amount of effective ventilation, termed the minute ventilation, expressed in liters per minute, is calculated by multiplying the ventilatory rate and tidal volume. The minute ventilation represents the total volume of air that is inhaled or exhaled in 1 minute. At rest, the minute ventilation is approximately 5 L/min, whereas at maximum exercise, it increases to a level between 70 and 125 L/min.2

Additional Lung Volumes Before considering the mechanical properties of the lungs during ventilation or breathing, it is helpful to consider the static volumes of the lungs measured via spirometry studies (Fig. 2-1).2–4 As mentioned earlier, the volume of air normally inhaled and exhaled with each breath during quiet breathing is called the tidal volume (TV or VT). The additional volume of air that can be taken into the lungs beyond the normal tidal inhalation is called the inspiratory reserve volume (IRV). The additional volume of air that can be let out beyond the normal tidal exhalation is called the expiratory reserve volume (ERV). The volume of air that remains in the lungs after a forceful expiratory effort is

called the residual volume (RV). The inspiratory capacity (IC) is the sum of the tidal and inspiratory reserve volumes; it is the maximum amount of air that can be inhaled after a normal tidal exhalation. The functional residual capacity (FRC) is the sum of the expiratory reserve and RV; it is the amount of air remaining in the lungs at the end of a normal tidal exhalation. The importance of FRC cannot be overstated; it represents the point at which the forces tending to collapse the lungs are balanced against the forces tending to expand the chest wall. The vital capacity (VC) is the sum of the inspiratory reserve, tidal, and expiratory reserve volumes; it is the maximum amount of air that can be exhaled following a maximum inhalation. The total lung capacity (TLC) is the maximum volume to which the lungs can be expanded; it is the sum of all the pulmonary volumes.

Control of Ventilation Breathing requires repetitive stimulation from the brain, as skeletal muscles required for ventilation are unable to contract without nervous stimulation.5 Although breathing usually occurs automatically and involuntarily, there are circumstances when individuals hold their breath, take deep breaths, or change ventilation, such as when singing or laughing. In light of this, it is important to review the mechanisms involved in helping to control breathing. This section describes the neural mechanisms that regulate ventilation. Neurons in parts of the brainstem, including the medulla oblongata and pons, provide control for automatic breathing and adjust ventilatory rate and tidal volume for normal gas exchange (Fig. 2-2).5 The medulla oblongata contains inspiratory neurons that produce inspiration and expiratory neurons that are triggered with forced expiration. Inspiratory neurons are located in the inspiratory center, or dorsal respiratory group, of the medulla. An enhanced frequency of firing of these neurons increases the motor units recruited and results in a deeper breath.6 An elongation in the time of firing prolongs each breath and results in a slower respiratory rate.6 A cessation of neural stimulation of these neurons causes elastic recoil of the lungs and passive expiration.

FIGURE 2-1 Lung volumes and capacities as displayed by a time-versus-volume spirogram. Values are approximate. The tidal volume is measured under resting conditions. (From Seeley RR, Stephens TD, Tate P: Anatomy & Physiology, ed 3, New York, 1995, McGraw-Hill.)

The expiratory center, or ventral respiratory group, in the medulla contains inspiratory neurons in the midregion and expiratory neurons in the anterior and posterior zones. Neural stimulation of the expiratory neurons causes inhibition of the inspiratory center when a deeper expiration is warranted. The pons has two major centers that assist with ventilation, including the pneumotaxic center in the upper pons and the apneustic center in the lower pons.5 The pneumotaxic center maintains the rhythm of ventilation, balancing the time periods of inspiration and expiration by inhibiting the apneustic center or the inspiratory center of the medulla. The apneustic center facilitates apneustic or prolonged breathing patterns when it is uninhibited from the pneumotaxic center. Breathing concerning a conscious change in pattern involves control from the motor cortex of the frontal lobe of the cerebrum.6 Here impulses are sent directly down to the corticospinal tracts to the respiratory neurons in the spinal cord, bypassing the respiratory centers in the brainstem to trigger changes in ventilation.

Afferent Connections to the Brainstem The respiratory centers of the brainstem receive afferent input from various locations, including the limbic system, hypothalamus, chemoreceptors, and lungs.5

Hypothalamic and Limbic Influence Sensations of pain and alterations in emotion alter ventilation through input coming to

the brainstem from the limbic system and hypothalamus.7 For example, anxiety triggers hyperventilation and a concomitant reduction in carbon dioxide levels in blood, as the rate of carbon dioxide elimination out of the lungs exceeds the rate of carbon dioxide production in the body.

Clinical tip Patients with injuries within the central nervous system from an acute brain injury or stroke demonstrate altered ventilatory patterns following neurologic insult. These patients lose the normal response to breathing, resulting in altered ventilatory rates and volumes.

Chemoreceptors Chemoreceptors are located in the brainstem and peripheral arteries. These receptors are responsible for sensing alterations in blood pH, carbon dioxide, and oxygen levels.7 There primarily exist two types of chemoreceptors, including central and peripheral chemoreceptors. The receptors found along the anterior lateral surfaces of the upper medulla of the brainstem are called central chemoreceptors. These receptors are stimulated when carbon dioxide concentrations rise in the cerebrospinal fluid. Central chemoreceptors facilitate an increased depth and rate of ventilation so as to restore normal carbon dioxide levels and pH in the body.5,7 Peripheral chemoreceptors are found within the carotid artery and aortic arch. These receptors help to increase ventilation in response to increasing levels of carbon dioxide in blood (hypercapnia), as well as low oxygen levels in blood (hypoxia).5,7 In a small percentage of patients with chronically high carbon dioxide levels in blood, such as in patients with severe chronic obstructive pulmonary disease (COPD), the body begins to rely more on oxygen receptors and less on carbon dioxide receptors to regulate breathing. This is termed the hypoxic drive to breathe and is a form of respiratory drive in which the body uses oxygen receptors instead of carbon dioxide receptors to regulate the respiratory cycle.8 Normal ventilation is driven mostly by the levels of carbon dioxide in the arteries, which are detected by peripheral chemoreceptors, and very little by oxygen levels. An increase in carbon dioxide triggers the chemoreceptors and causes a resultant increase in ventilatory rate. In these few patients with COPD who demonstrate the hypoxic drive, oxygen receptors serve as the primary means of regulating breathing rate. For these patients, oxygen supplementation must be prudently administered, as an increase in oxygen within blood (hyperoxemia) suppresses the hypoxic drive and results in a reduced drive to breathe.8

FIGURE 2-2 Neurochemical respiratory control system. (From McCance KL, Huether SE, Brashers VL, et al, editors: Pathophysiology: The Biologic Basis for Disease in Adults and Children, ed 6, St. Louis, 2010, Mosby.)

Lung Receptors There exist three types of receptors on the lung that send signals to the respiratory centers within the brainstem: 1. Irritant receptors: These receptors are found within the epithelial layer of the conducting airways and respond to various noxious gases, particulate matter, and irritants, causing them to initiate a cough reflex. When stimulated, these receptors also cause bronchial constriction and increase ventilatory rate.5 2. Stretch receptors: These receptors are located along the smooth muscles lining the airways and are sensitive to increasing size and volume within the lung.6 Hering and

Breuer discovered that ventilatory rate and volume was reduced following distention of anesthetized animal lungs. This stimulation of the ventilatory changes in response to increased volume and size is termed the Hering–Breuer reflex and is more active in newborns. In adults, this reflex is only active with large increases in the tidal volume, which is especially seen during exercise, and protects the lung from excessive inflation.6 3. J receptor: The juxtapulmonary receptors (J receptors) are located near the pulmonary capillaries and are sensitive to increased pulmonary capillary pressures. On stimulation, these receptors initiate a rapid, shallow breathing pattern.7 Additionally, the interstitial J receptors produce a cough reflex with fluid accumulation within the lung in patients with pulmonary edema and pleural effusions.

Clinical tip In patients with acute left-side congestive heart failure and resultant pulmonary edema, the interstitial J receptors within the lung are stimulated. The firing of these receptors causes the patient to breathe in a shallow, tachypneic pattern. This breathing pattern causes a milking of the lymphatic vasculature to facilitate a removal of fluid out of the lungs.9

Joint and Muscle Receptors Receptors within peripheral joints and muscles of the extremities respond to changes in movement and increase ventilation. During exercise, a twofold increase in minute ventilation is noted—an initial abrupt increase in ventilation followed by a secondary gradual increase in ventilation (Fig. 2-3).10 The initial abrupt increase in ventilation is a result of sensory input conveyed from receptors within peripheral joints and muscles, whereas the secondary gradual increase in ventilation is a result of changes in pH within the blood caused by increased lactic acid production. This is conveyed to the brainstem by the chemoreceptors.

Mechanics of Breathing Movement of air into and out of the lungs occurs as a result of pressure differences between the two ends of the airway. Airflow through the conducting airway is directly proportional to the pressure difference created between the ends of the airway and inversely proportional to the resistance within the airway. In addition, ventilation is affected by various physical properties of the lungs, including compliance, elasticity, and surface tension. This section focuses on pressure changes that allow breathing to occur and explains how lung compliance, elasticity, and surface tension affect breathing. The physiologic importance for pulmonary surfactant is also discussed.

FIGURE 2-3 Ventilatory response during exercise.

Intrapulmonary and Atmospheric Pressures Inspiration is always an active process and involves contraction of the respiratory muscles. When the diaphragm and external intercostals contract they increase the volume of the thoracic cavity and lung. This in turn causes a concomitant reduction in the intrapulmonary pressure, or pressure within the lung (Fig. 2-4).11 The pressure within the lung is reduced in accordance with Boyle’s law, which states that the pressure of a given quantity of gas is inversely proportional to its volume. During inspiration, an increase in lung volume within the thoracic cavity decreases intrapulmonary pressures below atmospheric levels. This is termed a subatmospheric or negative intrapulmonary pressure. This difference in pressure between the atmosphere and the lungs facilitates the flow of air into the lungs to normalize pressure differences. Conversely, expiration occurs when the intrapulmonary pressure exceeds the atmospheric pressure, allowing the lungs to recoil inward and expel air into the atmosphere. There exists a primary difference between normal ventilation and mechanical ventilation. In normal ventilation, air is pulled into the lungs because of a negative pressure created through activation of the respiratory muscles. Patients placed on mechanical ventilation lack the ability to generate an effective negative or subatmospheric pressure. In light of this, the mechanical ventilator forces air into the lungs through creation of a positive pressure greater than the atmospheric pressure that exists within the lung. It is also important to note that patients on mechanical ventilation often demonstrate

reduced strength of the inspiratory muscles (including the diaphragm), as the ventilator assists with breathing. These patients may benefit from breathing exercises, positioning, and the use of an inspiratory muscle trainer to improve functioning of the inspiratory muscles.

FIGURE 2-4 A-C, Ventilation: Changes in pressure with inspiration and expiration. (From Gould BE: Pathophysiology for the Health Professions, ed 3, St. Louis, 2007, Saunders.)

Intrapleural and Transmural Pressures Two layers cover each lung, including the outer parietal pleura and inner visceral pleura, separated by an intrapleural space containing a thin layer of viscous fluid. A small amount of viscous fluid within the intrapleural space serves as a lubricant and allows for the lungs to slide relative to the chest during breathing. With ventilation, there exist two opposing forces, including an inward pull from the elastic tension of the lung tissue trying to collapse the lung and an outward pull of the thoracic wall trying to expand the lungs.1,2,5 These two opposing forces give rise to a subatmospheric (negative) pressure within the intrapleural space, termed the intrapleural pressure. This intrapleural pressure is normally lower than the intrapulmonary pressure developed during both inspiration and expiration. In light of these two pressure differences, a transpulmonary or transmural pressure is developed across the wall of the lung.1,2,5 The transmural pressure considers the difference between the intrapulmonary and intrapleural pressure. The inner intrapulmonary pressure is relatively greater than the outer intrapleural pressure, allowing the difference in pressure (the transmural pressure) to maintain the lung near the chest wall. It is the transmural or transpulmonary pressure that allows changes in lung volume to parallel changes in thoracic excursion during inspiration and expiration. When changes in lung volume do not parallel the normal outward and inward pull during inspiration and expiration, respectively, and are, in fact, opposite, the breathing pattern is said to be paradoxical. This breathing pattern is often seen in patients with multiple rib fractures and a resultant flail chest.

Physical Properties of Lungs The processes of inspiration and expiration are facilitated by three physical properties of lung tissue. Compliance allows lung tissue to stretch during inspiration; the elastic recoil of the lung allows passive expiration to occur; and surface tension forces with the alveoli allow the lung to get smaller during expiration. Compliance The lung can be compared with a balloon during inspiration, where there exists a tendency to collapse or recoil while inflated. To maintain inflation, the transmural pressure, or pressure difference between the intrapulmonary pressure and intrapleural pressure, must be maintained. A distending force is needed to overcome the inward recoil forces of the lung. This outward force is provided by the elastic properties of the lung and through the action of the inspiratory muscles. Compliance describes the distensibility of lung tissue. It is defined as the change in lung volume per change in transmural or transpulmonary pressure, expressed

symbolically as ΔV/ΔP (Fig. 2-5).12 In other words, a given transpulmonary pressure will cause a greater or lesser degree of lung expansion, depending on the distensibility or compliance of the lung. The compliance of the lung is reduced by factors that produce a resistance to distension. Also, the compliance is reduced as the lung approaches its TLC, where it becomes relatively stiffer and less distensible. In patients with emphysema, the chronicity of the disease leads to progressive destruction of the elastic recoil, making the compliance high.13 A reduced inward pull from low recoil allows small changes in transmural pressure to cause large changes in lung volumes and resultant hyperinflation of the lung. The changes seen in individuals with emphysema include a barrel chest and flattened diaphragms. These negative sequelae result in less diaphragm use with breathing, more accessory muscle, and an increase in the work of breathing.

FIGURE 2-5 A-C, Lung compliance changes associated with disease.

In patients with pulmonary fibrosis, the lung is fibrotic and stiff and thereby has reduced compliance.13 In these patients, despite large changes in transmural pressure, only small changes in lung volume will occur as a result of the stiffness or lack of distensibility of lung tissue. Consequently, clinically one sees individuals with increased respiratory rates and accessory muscle use because of decreased lung volumes. The work of breathing with activity is greatly increased as a consequence of the inability to increase lung volumes. Elasticity Elasticity refers to the tendency of a structure to return to its initial size after being distended. A network of elastin and collagen fibers within the alveolar wall and surrounding bronchi and pulmonary capillaries provides for the elastic properties of the

lung. Surface tension Although the elastic characteristics of the lung tissue itself play a role in resisting lung distension or compliance, the surface tension at the air–liquid interface on the alveolar surface has a greater influence. Anyone who has ever attempted to separate two wet microscope slides by lifting (not sliding) the top slide from the bottom has firsthand experience with the forces of surface tension. In the lung, a thin film of fluid on the alveolus has a surface tension, which is caused by water molecules at the surface being relatively more attracted to other water molecules than to air. This surface tension acts to collapse the alveolus and increase the pressure of air within the alveolus. The law of Laplace states that the pressure created within the alveolus is directly proportional to the surface tension and inversely proportional to the radius of the alveolus. For example, consider two alveoli of different sizes, one at either end of a bifurcated respiratory bronchiole (Fig. 2-6); because of the size difference, the smaller alveolus must have a higher pressure than the larger alveolus if the surface tension of each is the same. To keep the air in the smaller alveolus from emptying into the larger, a surface-active agent is needed to decrease the overall surface tension of the alveoli so as to lower wall tension in proportion to the radius of the alveolus (see Fig. 2-6). Moreover, it must do so almost in anticipation of diminishing alveolar size. Only if such a surface-active agent were present could alveoli with different radii coexist in the lungs. The surface-active agent in the human lung that performs this function is called surfactant.14,15 Pulmonary surfactant is not composed of a single class of molecules, but, rather, is a collection of interrelated macromolecular lipoprotein complexes that differ in composition, structure, and function.14,15 Nonetheless, the principal active ingredient of surfactant is dipalmitoyl phosphatidylcholine (DPPC). The structure of the surfactant molecule is such that it presents a nonpolar end of fatty acids (two palmitate residues) that is insoluble in water, and a smaller, polar end (a phosphatidylcholine group) that dissolves readily in water. Thus surfactant orients itself perpendicularly to the surface in the alveolar fluid layer, with its nonpolar end projecting toward the lumen. If surfactant were uniformly dispersed throughout the alveoli, its concentration at the air–fluid interface would vary in accordance with the surface area of any individual alveolus. Thus the molecules would be compressed in the smaller alveoli, as depicted in Fig. 2-6. Compressing the surfactant molecules increases their density and builds up a film pressure that counteracts much of the surface tension at the air–fluid interface. The rate of change in the surface tension resulting from compression of the surfactant molecules as the alveolus gets smaller is faster than the rate of change of the decreasing alveolar radius, so that a point is rapidly reached in which the pressure in the small alveolus equals the pressure in the big alveolus.

FIGURE 2-6 Two pairs of unequally filled alveoli arranged in parallel illustrate the effect of a surfaceactive agent. One pair of alveoli is shown without surfactant (A) and the other is shown with surfactant (B). In the alveoli without surfactant, if Tsml were the same as Tbig, Psml would have to be many times greater than Pbig; otherwise, the smaller alveolus would empty into the larger one. In the alveoli with surfactant, Tsml is reduced in proportion to the radius of the alveolus, which permits Psml to equal Pbig. Thus alveoli of different radii can coexist. Refer to the text for details.

FIGURE 2-7 Laminar and turbulent airflow in the airways. A, At low flow rates, air flows in a laminar pattern, and the resistance to airflow is proportional to the flow rate. B, At airway bifurcation, eddy formation creates a transitional flow pattern. C, At high flow rates, when a great deal of turbulence is created, the resistance to airflow is proportional to the square of the flow rate. (Redrawn from West JB: Respiratory Physiology: The Essentials, ed 9, Baltimore, 2012, Lippincott Williams & Wilkins.)

Surfactant begins to develop in late fetal life. Premature babies may be born with less surfactant, resulting in collapsed alveoli and respiratory distress. In an effort to reduce complications in women likely to go into premature labor (150 mg/dL), particularly when they are associated with low levels of HDL (200 mm Hg or DBP >110 mm Hg), physician clearance must be obtained. Exercise testing should be terminated if blood pressure becomes excessively high (SBP >250 mm Hg or DBP >115 mm Hg).237 The risk of myocardial ischemia during exercise is enhanced in individuals with HTN, especially those with evidence of LVH, and angina may occur. Furthermore, if left ventricle function is impaired, LV end-diastolic volume and pressure, and therefore intrapulmonary pressures, will rise during exercise, resulting in shortness of breath (Box 3-6).

Clinical tip Orthostatic hypotension is defined as a systolic pressure drop of more than 20 mm Hg or a diastolic drop of more than 10 mm Hg when assuming an upright position, which often renders the individual symptomatic (dizzy, lightheaded, or cognitive changes). It is not the same as a hypotensive blood pressure response to activity.

BO X 3- 6 Guide line s for e x e rcise in individua ls wit h

hype rt e nsion • Exercise testing • If resting BP >200 mm Hg systolic, >100 mm Hg diastolic: obtain physician

clearance • Discontinue exercise if >250 mm Hg systolic, >115 mm Hg diastolic • Exercise training • If resting BP is uncontrolled and severe, ≥180 mm Hg systolic, ≥110 mm Hg diastolic: medical clearance needed. • Consider side effects of medications • Particularly watch for hypotension with: • Change of position • Postexercise • Long-term standing • Warm environments • Avoid breath hold and Valsalva, especially with resistive exercises • Low weights, high repetitions in deconditioned/high risk; 60% to 80% one repetition maximum others • Endurance training at moderate intensity Data from American College of Sports Medicine: Guidelines for Exercise Testing and Prescription, ed 9, Baltimore, Williams & Wilkins, 2014.

Cerebrovascular Disease Approximately 795,000 individuals experience a new or recurrent cerebrovascular accident (stroke) in the United States each year. It is estimated that 87% of these events result from ischemia and the remaining from a hemorrhage.1 Stroke is the leading cause of disability and the fourth leading cause of death after CAD, cancer, and chronic lung disease in the United States.1 Fig. 3-13 shows the actual anatomy of the vascular supply to the brain, demonstrating two internal carotid arteries and two vertebral arteries that come together at the base of the skull to form the circle of Willis. There is a vast amount of individual variability in the circle of Willis, and some individuals do not even have a complete circle. A cerebrovascular event is defined as a transient ischemic attack (TIA) if symptoms resolve completely within 24 hours, and as a stroke if deficit results after 24 hours. Patients with a TIA have a higher chance of stroke within 90 days, with many of these occurring within the first 2 days.253 Individuals who have involvement of a carotid artery may experience hemispheric symptoms such as contralateral hemiparesis, contralateral sensory loss, aphasia, and/or a visual field deficit. Individuals who have vertebrobasilar or circle of Willis arterial involvement may have nonhemispheric symptoms, which include ataxia, dysarthria, diplopia, vertigo, syncope, and/or cranial nerve involvement. Many of the risk factors for stroke are the same as those of cardiac and peripheral vascular disease, yet stroke presents with a variety of different conditions and pathophysiologic processes. The treatment interventions for stroke are too numerous to present in this chapter, but the interventions for stroke prevention as outlined by the American Stroke Association/American Heart Association are presented in the following sections.1,254–258

FIGURE 3-13 Extracranial and intracranial arterial supply to the brain. Vessels forming the circle of Willis are highlighted. ACA, Anterior cerebral artery; AICA, anterior inferior cerebellar artery; Ant. Comm., anterior communicating artery; CCA, common carotid artery; ECA, external carotid artery; E-I anast., extracranial–intracranial anastomosis; ICA, internal carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; PICA, posterior inferior cerebellar artery; Post. Comm., posterior communicating artery; SCA, superior cerebellar artery. (Modified from Lord K: Surgery of the occlusive cerebrovascular disease, St. Louis, 1986, Mosby. In Goodman CC: Pathology: Implications for the Physical Therapist, ed 3, St. Louis, 2009, Saunders.)

Treatment for Stroke Prevention: Primary and Secondary Prevention According to the American Stroke Association, primary and secondary prevention includes risk factor reduction and medical management. Medical management includes platelet antiaggregants (primarily aspirin), anticoagulants, lipid-lowering medications, glycemic control, antihypertensive medications, and appropriate interventional methods.254,255,258 The benefit of the use of aspirin outweighs the risk of bleeding in all individuals who are at moderate to high risk of stroke based upon risk factors, especially women. Women who were defined as having a moderate to high risk of stroke demonstrated a 17% reduction in risk with the inclusion of aspirin in their daily regimen as defined in the Women’s Health Study.259 Aspirin in combination with sustained-release

dipyridamole was found to reduce risk of a second stroke by 37%.255,260 Anticoagulation (warfarin/Coumadin) has been used for years to reduce the risk of a first event of embolism due to conditions like mechanical heart valves, atrial fibrillation, and cardiomyopathy; however, the Warfarin-Aspirin Recurrent Stroke Study (WARSS) found a slight advantage with the use of aspirin compared with warfarin for prevention of a second stroke because of the risk of bleeding complications with warfarin and the need for additional monitoring.261 The role of statins is well documented in the management of patients with CAD and is also well documented in the primary prevention of stroke. The HPS was the first large study to document the use of statins for secondary prevention of stroke.128 Individuals with a prior history of stroke showed a 20% reduction in frequency of major vascular events (MI, stroke, revascularization procedure, or vascular death) with the use of statins. Finally, the American Stroke Association and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) agree that the reduction in blood pressure is far more important than the actual medications used to achieve the reduction and that with a reduction in blood pressure, risk for stroke is reduced between 28% and 35%.207,254 Therefore a combination of aspirin, lipid-lowering medication, glycemic control, and antihypertensive medication may be the optimal regimen for primary and secondary prevention of stroke in addition to risk factor modification. Chapter 11 discusses other treatments for those with documented carotid disease in greater detail.

Implications for Physical Therapy Intervention Because of the incidence of atherosclerotic disease in this patient population, patients with a diagnosis of carotid or vertebral disease should have their blood pressure monitored at rest and with all new activities, should be educated about primary or secondary prevention of stroke (medical management as outlined earlier), and should be taught the symptoms of instability (signs of TIAs) and the need for immediate medical treatment should these symptoms appear. The earlier a patient receives emergency medical management for an impending stroke, the lower the risk of permanent brain injury.

Peripheral Arterial Disease Peripheral arterial disease, or more specifically atherosclerotic occlusive disease (AOD), involves atheromatous plaque obstruction of the large- or medium-size arteries supplying blood to one or more of the extremities (usually lower). Atherosclerotic occlusive disease is a result of the same atherosclerotic process previously described and causes symptoms when the atheroma becomes so enlarged that it interferes with blood flow to the distal tissues, it ruptures and extrudes its contents into the bloodstream or obstructs the arterial lumen, or it encroaches on the media, causing weakness of that layer and aneurysmal dilation of the arterial wall. The hemodynamic significance of the disease depends on the location and number of lesions in an artery, the rapidity with which the atherosclerotic process progresses, and the presence and extent of any collateral arterial system. When blood flow is not adequate to meet the demand of the peripheral tissues (i.e., during activity), the patient may experience symptoms of ischemia, such as intermittent claudication of a lower extremity. As the disease progresses, the patient experiences more severe symptoms, such as rest pain and skin changes. Complete obstruction to flow will cause tissue necrosis and possibly loss of the limb (Fig. 3-14). Individuals with lower extremity PAD should be assumed to have ASHD, which is the main cause of higher morbidity and mortality rates in these individuals.262 Studies report up to 60% to 80% of those with PAD have significant coronary atherosclerosis in at least one coronary artery.263 Individuals with asymptomatic disease appear to have the same increased risk of cardiovascular events and death found in those with symptoms of claudication.264 Further information on PAD and medical diagnostic testing and interventions can be found in the American College of Cardiology Foundation and American Heart Association’s Guidelines for the management of patients with PAD, updated in 2011.265

Exercise and Peripheral Arterial Disease Individuals with PAD are unable to produce the normal increases in peripheral blood flow essential for enhanced oxygen supply to exercising muscles. If the oxygen supply is inadequate to meet the increasing demand of the exercising muscles, ischemia develops and leads to the production of lactic acid. When excessive lactic acid accumulates in the muscle, pain is experienced (this symptom is known as intermittent claudication); when it reaches the central circulation, respiration is further stimulated and patients may experience shortness of breath (Table 3-7). Patients with intermittent claudication have moderate to severe impairment in walking ability that usually comes on with a particular amount of activity and is relieved with rest. Their peak exercise capacity during graded treadmill exercise is severely limited, allowing for only light to very-light activities;266–268 the energy requirements of many leisure and work-related activities usually exceed their capacity. Metabolic measurements during exercise testing reveal that maximal oxygen consumption and anaerobic threshold

are reduced in patients with AOD.266,268 Yet, even though the anaerobic threshold may be so low that it cannot be detected, evidence of systemic lactic acidosis may be minimal because of the reduced muscle perfusion. Several studies have documented the efficacy of exercise training in the management of patients with AOD. Increases in both pain-free and maximal walking tolerance on level ground and during constant-load treadmill exercise achieved during exercise testing have been reported.269–277 A recent Cochrane Review found patients healthy enough to participate in exercise programs can improve the time and distance of walking, with results lasting for approximately 2 years.278 Studies even have concluded that greater symptomatic relief and functional improvement in patients with mild to moderate claudication not requiring immediate therapeutic interventions is achieved through supervised exercise therapy rather than PTCA.270,279 Some studies have demonstrated the benefit of exercise for patients with rest pain.280 Several mechanisms have been postulated to account for these improvements: increased walking efficiency, increased peripheral blood flow through changes in the collateral circulation, reduced blood viscosity, regression of atherosclerotic disease, raising of the pain threshold, and improvements in skeletal muscle metabolism. There is evidence that periods of brief repetitive walking can successfully improve oxygenation in the feet of limbs with more severe arterial obstruction.281

FIGURE 3-14 Signs and symptoms of arterial insufficiency. (From Goodman CC: Pathology: Implications for the Physical Therapists, ed 3, St. Louis, 2009, Saunders.)

Table 3-7 Subjective gradation of claudication discomfort Grade I II III IV

P ain Description Initial disc omfort (established, but minimal) Moderate disc omfort but attention c an be diverted Intense pain (attention c annot be diverted) Exc ruc iating and unbearable pain

From American College of Sports Medicine: Guidelines for Exercise Testing and Prescription, ed 3, Baltimore, 2009, Williams & Wilkins.

Implications for Physical Therapy Intervention Because of the high prevalence of ASHD in patients with PAD, all patients should be monitored during physical therapy evaluation and initial treatment, including the monitoring of heart rate and blood pressure. Such monitoring is especially needed when working with patients who have undergone amputation, which implies severe disease.

Notably, patients with PAD may exhibit precipitous rises in blood pressure during exercise due to their atherosclerosis and diminished vascular bed. Physical therapists can also use SBP measurements to predict the severity of PAD by performing an ankle–brachial index (ABI). Systolic blood pressures should be higher in the lower extremities; if the upper extremity SBPs are higher than the lower extremity SBPs, one should suspect PAD. If an ABI (SBP of ankle/SBP of arm) is 0.90 or less, it is considered abnormal (see Chapters 8 and 22). Physical therapists should also look for other signs of PAD in the extremity, including dry, shiny skin; hair loss; thick toenails; muscle atrophy; impaired sensation; and decreased pulses. Intermittent claudication is considered a classic symptom during activity. Claudication in the calf is associated with stenosis of the femoral and/or popliteal artery, whereas thigh, hip, or buttock claudication is usually caused by aortoiliac arterial disease. However, studies state that less than half of individuals with PAD express any type of leg symptoms, and many others describe other various leg symptoms, whereas only 10% actually report classic claudication.1,237,282 Still, including a subjective gradation of pain for expressing claudication discomfort, as described in Table 3-8, can be useful during exercise.237,282 Patients should exercise to levels of maximal tolerable pain—that is, to grade III discomfort—in order to obtain optimal symptomatic benefit over time, possibly through enhanced collateral circulation or increased muscular efficiency.237,281,283 And, in order to achieve as much benefit as possible, an individual should consider a supervised exercise program. A recent Cochrane Review reported that people in supervised exercise programs improved their distance of walking significantly more (up to 180 meters) than those in unsupervised exercise programs.284 Box 3-7 provides additional exercise recommendations.

Table 3-8 Two-level DVT wells score

Other Vascular Disorders Venous Disease Venous disease comprises the major categories of venous problems, including venous insufficiency, venous stasis ulcers, and venous thromboembolism (VTE). Prevalence of venous insufficiency varies depending on the age and ethnic population studied; however, mild forms have been reported in more than 40% of individuals. In more serious venous disease, it is estimated that 300,000 to 600,000 Americans are affected yearly by VTE, resulting in approximately 60,000 to 100,000 deaths despite advances in medical care.285,286 Venous stasis ulcers affects half a million people. These venous conditions are thought to be underdiagnosed and often preventable.

Venous Insufficiency Approximately 65% to 70% of the blood is housed in the veins at one time, thus the term capacitance vessels for veins. Veins have the job of being the body’s “clean-up crew,” carrying carbon dioxide and other cellular waste back to the heart and liver. The walls of veins are thinner and less rigid with a larger lumen diameter than arteries. They are equipped with one-way valves that, when open, function to move blood back toward the heart and liver and, when closed, prevent blood from flowing backward. If damage occurs to the valves, the blood pools and flows backward, causing the veins to become enlarged and weak. Tension can then build up, leading to venous HTN, obstruction of venous flow, and overall failure of the pump.

BO X 3- 7 Ex e rcise re com m e nda t ions for individua ls wit h

pe riphe ra l a rt e ria l dise a se Perform exercise in intervals as short as 1 to 5 minutes, alternating with rest periods. Increase the length of exercise intervals and decrease the length of rest periods. Most convenient and functional mode is walking. Non–weight-bearing activities may allow for longer duration and higher intensities, but progressive walking should be encouraged. Longer warm-up time required in colder environments because of peripheral vasoconstriction. Sensory examination should be performed before providing an exercise prescription because of the possibility of peripheral neuropathy. Footwear and foot hygiene should be emphasized. Muscle action is also essential to help the valves move venous blood toward the heart. When inadequate muscle action, incompetent venous valves, or venous obstruction occurs, venous insufficiency can result. Risk factors for venous insufficiency include, but are not limited to, advancing age,

genetics, obesity, prolonged standing, sedentary lifestyle, smoking, and female hormones. Symptoms may include complaints of dull ache, heaviness, swelling, itching, tingling, or cramping in the extremity (typically in the leg). Types of venous insufficiency range from mild forms of spider veins (telangiectasias) and varicose veins to chronic venous insufficiency. Spider veins are dilated veins in the dermal layer of the skin (Fig. 3-15). Varicose veins are superficial subcutaneous veins appearing knotted, swollen, and/or twisted. Chronic venous insufficiency leads to skin changes caused by a “chronic release of inflammatory mediators,”287 swelling, and wounds. Dermatitis and hemosiderin staining are typically visible skin changes caused by venous insufficiency. Hemosiderin staining is thought to happen when red blood cells “leak” into the tissues secondary to venous HTN. These red blood cells later break down, leaving behind a rusty brown skin color due to iron contained in the blood (Fig. 3-16). Venous wounds can also develop. These wounds are typically described as beefy red in color, with moderate to severe exudate and irregular borders, and are usually seen in the lower one-third of the leg.

FIGURE 3-15 Spider veins. (From Travers R, Hsu J: Skin in the spotlight: Cosmetic treatments, Sexuality, Reproduction and Menopause Volume 4, Issue 2, October 2006, Pages 80–85.)

FIGURE 3-16 Venous insufficiency. (From James WD, Berger TG, and Elston DM: Andrews’ Diseases of the Skin: Clinical Dermatology, ed 10, St. Louis, 2006, Elsevier.)

Venous Thromboembolic Disease Venous thromboembolism includes both deep venous thrombosis (DVT) and pulmonary embolism (PE). Deep vein thrombosis usually refers to the development of a clot in a deep vein of the lower extremity or pelvis, with a smaller percentage occurring in the arm (Fig. 3-17). A PE is a clot that reaches the lungs. In both cases, the thrombosis obstructs blood flow in the affected area.286 Major risk factors for the development of VTE are thought to arise from one or more of three main categories described as Virchow’s triad; hypercoagulability, venous stasis, and endothelial injury.288 A hypercoagulable state encompasses any situation where there is an increased propensity of developing blood clots, such as with cancer, hormonal replacement, and inherited clotting disorders such as factor V Leiden mutation.289 Venous stasis is a condition in which blood flow is slowed or congested such as what happens with prolonged bed rest, travel, and paralysis. Endothelial injury, or injury to the

inner lining of the vein, can occur from surgery, trauma, or insertion of a central venous catheter. Pain, ipsilateral swelling, a palpable cord, and redness are signs of a DVT. The Wells Decision Tool can assist the therapist in assessing the probability of a DVT (see Chapters 8 and 16). Medical testing, including D dimer, a Doppler assessment, compression ultrasonography, or MRI, can be used to confirm the presence of lower extremity or upper extremity DVT. Signs and symptoms of a PE are shortness of breath, decreased SpO2, pleuritic chest pain, cough, and tachycardia. However, one systematic review found one-third of patients with a DVT to have had an asymptomatic, or “silent,” PE.290 Therefore it is crucial to assess for these warning signs, especially when patients have a history of a proximal DVT (above the knee), previous PE, or other significant risk factors. Medical testing consisting of ventilation/perfusion scan or computed tomography (CT) pulmonary angiogram can be used for medical diagnosis of a PE.

Implications for Physical Therapy Through effective screening, examination, and interventions, physical therapists can be instrumental in prevention and further development of complications from venous disease experienced in patients. When obtaining the patient’s history, the risk factors and signs/symptoms for venous insufficiency and VTE are important to consider (utilization of the Wells Prediction Model for VTE is important and found in Chapters 8 and 16; see Table 3-8).291 When examining the lower extremity for a DVT, the therapist must distinguish a DVT from other medical problems that can mimic a DVT, such as a baker ’s cyst or muscle injury. And throughout the session, it is essential to assess vital signs as well as for signs and symptoms of a PE.

FIGURE 3-17 Development of deep venous thrombosis with arrows indicating direction of blood flow. A, Thrombus in valve pocket of a deep vein with blood flowing beside thrombus. B, Thrombi tend to form at bifurcations of deep veins with some slowing of blood flow. C, Complete occlusion of vein by thrombus forcing backflow of blood. D, Embolus that has broken off from a thrombus and is floating in bloodstream could migrate to lungs and cause pulmonary embolus. (From Monahan FD, Sands JK, Neighbors M: Phipps’ Medical-Surgical Nursing, ed 8, St. Louis, 2007, Mosby.)

Interventions for venous insufficiency comprise exercise, elevation of the extremity,

avoiding long periods of sitting or standing, compression, and aggressive wound management, along with education to prevent further progression of the disorder. Mechanical compression, early mobility, and anticoagulation are vital for the prevention and further progression of venous thromboembolic disease.292 Anticoagulation, such as heparin, low-molecular-weight heparin, or a new oral anticoagulant is a key treatment for individuals at risk for or diagnosed with a DVT. These medications work by blocking proteins needed for clot formation, which in turn slows and/or prevents this process. The clot gradually dissolves and is reabsorbed by the body as healing occurs. This process can take weeks to months (see Chapter 14 for further information about anticoagulation used in VTE).293 It has been found that anticoagulation therapy is best continued for 3 to 6 months to avoid recurrence or progression of VTE. In these individuals, especially if balance is impaired, fall prevention education is vital for those taking anticoagulation medication because of an increased risk of complications related to bleeding.292 Research supports early ambulation as soon as possible.294 Patients who have a documented lower extremity DVT and have reached therapeutic levels of the prescribed anticoagulant should be mobilized out of bed and encouraged to ambulate to prevent venous stasis, as well as deconditioning, a lengthened hospital stay, and other adverse effects of bed rest.292 A common concern of mobilizing a patient with a lower extremity DVT is that the clot will dislodge and embolize to the lungs, causing a potentially fatal PE. However, mobilization has been shown to lead to no greater risk of PE than bed rest for those with a diagnosed DVT who have been treated with anticoagulants.294 In the metaanalysis by Aissaoui in 2009, the authors concluded there is no increased risk of PE/DVT with early ambulation after anticoagulation.294 Similar findings were reported in a systematic review reporting strong prospective evidence that early walking did not increase the risk of PE in the days after diagnosis of DVT and initiation of anticoagulation therapy.295 Early mobilization of lower extremity DVT patients has also demonstrated a potentially reduced risk of extension of proximal DVT and reduced longterm symptoms of postthrombotic syndrome (PTS).295 Ambulation postdocumented lower extremity DVT after initiation of an anticoagulant has been reported to be safe as soon as an individual has reached the therapeutic dosing of the anticoagulant. Different anticoagulants have different times to therapeutic levels, but in general, heparin will be prescribed for individuals with renal dysfunction and a creatinine clearance of less than 30 mL/min, and it achieves a therapeutic level within 12 to 24 hours; low-molecular-weight heparins usually achieve therapeutic levels within 3 to 5 hours, and the new oral anticoagulants achieve therapeutic levels within 2 to 3 hours.296–301 The time frames allow earlier mobility based upon the time to achieve a level in the blood to dissolve any larger clots floating in the blood or that break off from the original clot that would cause problem with the lungs.296–301 These time frames are based upon the documented therapeutic levels and give some guidance for mobility, yet all physical therapists should still be watching for signs/symptoms of PE in all patients with a documented lower extremity DVT. Physical therapists should continue to assess for

DVT/PE in these individuals since they will often be prescribed anticoagulant medications for 3 to 6 months or more. Individuals with a proximal lower extremity DVT or a PE may require different anticoagulation or time before mobilization, as these are more unstable clots. Mechanical compression, in addition, is important to utilize for prevention of DVT as well as postthrombotic syndrome.292,301,302 A Cochrane Systematic Review showed evidence that graduated compression stockings worn by hospitalized surgical patients were effective in reducing the risk of DVT.302 Another systematic review found compression stockings decreased the incidence of DVT in airline passengers.303 Postthrombotic syndrome is the most frequent complication of lower extremity DVT and develops in up to 50% of these patients even when appropriate anticoagulant therapy is used; therefore physical therapists should evaluate all patients who have a diagnosis of lower extremity DVT for PTS.304–306 A clot remaining in the vein of the LE can obstruct blood flow, leading to venous hypertension. Additionally, damage to the vein itself occurs and leads to inflammation and tissue damage within the vein, which may compromise return of blood flow. As a result, PTS symptoms may develop, including chronic, aching pain; edema; limb heaviness; and leg ulcers.304 In summary, anticoagulation, ambulation, and even mechanical compression have been shown to decrease the incidence of progression of DVT, as well as development of PTS.

Renal Artery Disease Renal artery stenosis (RAS) results from atherosclerosis of the renal artery and is associated with increased cardiovascular events and mortality. The prevalence of RAS is approximately 20% to 30% in the high-risk population.307 Renal artery stenosis is a progressive disease that is associated with loss of renal mass, progressing to renal insufficiency, refractory HTN, and renal failure. Approximately 20% of individuals older than 50 years of age who begin renal dialysis have atherosclerotic RAS as the cause of their renal failure. Renal dialysis patients with RAS have a 56% 2-year survival rate, 18% 5-year survival, and 5% 10-year survival.308 Clearly, the early diagnosis of RAS and the prevention of end-stage renal disease (ESRD) are important goals.

Aortic Aneurysm The aorta is the largest artery in the body and is divided anatomically into the thoracic and abdominal aorta. An aneurysm of the aorta is a pathologic permanent dilation of the aortic wall that is at least 50% greater than the expected normal diameter (>3 cm is considered aneurysmal in adults). Aneurysms are typically described in terms of their location, size, morphologic appearance, and origin. An aortic aneurysm is usually uniform in shape, although some form a sac or outpouching of a portion of the aorta (Table 3-9). The large majority of abdominal aortic aneurysms (AAAs) arise below the renal arteries and are known as infrarenal aneurysms. Only a small minority, known as

suprarenal aneurysms, arise between the level of the diaphragm and the renal arteries.309 Table 3-9 Risk factors of aneurysms Risk Factors S moking (c urrent or past) Age Gender Family history Hypertension Hyperlipidemia Atherosc lerosis

Complications Fivefold inc rease vs. nonsmokers Most oc c ur in individuals >60 years of age 5–10× higher inc idenc e in men than in women Women with aneurysm have a higher risk of rupture First-degree relative has an inc reased risk

Data from Braverman A, Thompson R, Sanchez L: Diseases of the aorta. In Braunwald E, editor: Heart Disease: A Textbook of Cardiovascular Medicine, ed 9, Philadelphia, 2012, Saunders.

A thrombus may form as a result of stagnate blood flow along the wall of the aneurysmal section. This thrombus has the potential to break off and impede circulation of the distal arteries. However, rupture is the major risk of AAAs and is usually fatal. Rupture into the retroperitoneum is most common. When there is rupture into the peritoneal cavity, uncontrolled hemorrhage and rapid circulatory collapse occur. Because most AAAs expand over time at an average increase of 0.3 to 0.5 cm per year, the risk of rupture tends to increase with time. A sudden increase in enlargement can also predict the possibility of aneurysm rupture, especially for AAAs 5.5 cm or greater in diameter (Fig. 3-18).309

Implications for Physical Therapy Although individuals with AAAs often have no symptoms, the most common signs/symptoms include: ▪ Pulsating tumor or mass in abdominal area (although often not reliable) ▪ Bruit heard over swollen area in abdomen ▪ Abdominal, back, or flank pain ▪ Leg pain/claudication pain ▪ Numbness in the lower extremities ▪ Excessive fatigue, especially with walking ▪ Poor distal pulses, especially the dorsalis pedis ▪ Low back pain with elevated pressure that may indicate renal artery aneurysm During the initial assessment, the therapist should identify risk factors for aneurysm, especially age (>60 years) and immediate family history (see Table 3-9). According to Braverman et al, moderate activity in individuals with small AAAs has not been shown to influence the risk of rupture; therefore regular exercise should be promoted.309

FIGURE 3-18 Abdominal aortic aneurysm. (From Frazier M: Essentials of Human Diseases and Conditions, ed 6, St. Louis, 2016, Saunders.)

Summary ▪ Coronary heart disease is the most common disease in the industrialized world. ▪ The presence of CHD in a given individual is dependent on the presence of any of the following risk factors for the disease and the susceptibility of the individual to those factors: • Cigarette smoking • Hypertension • Elevated cholesterol levels • Physical inactivity • Diabetes • Obesity • Poor dietary habits • Family history • Age • Gender • Stress ▪ The risk factors of CAD are the same risk factors of PAD, carotid and vertebral vascular disease, and other vascular diseases. Therefore individuals with any of these diseases should be examined for all other diseases. ▪ The plaques that obstruct the coronary arteries are a combination of atheroma and thrombus, and they begin to form early in life, probably in the second decade. ▪ The majority of the risk factors for CAD are modifiable. ▪ Through control of these risk factors, the progress of CAD can be arrested and in some cases reversed. ▪ Patients with diabetes have a relatively high 10-year risk for developing CVD. ▪ Premature or early coronary disease is defined as men older than age 50 years and women older than age 60 years, but the AHA defines family history as significant if either parent (genetic linked parents) had a diagnosis of heart disease (first event of MI, angina, CABG, or PTCA) at an age earlier than 60 years. ▪ Psychosocial distress is also associated with increased mortality and morbidity rates after MI. In addition, social isolation and depression are associated with a poor prognosis after MI. ▪ Individuals with elevated CRP and Lp-PLA2 levels might benefit from more aggressive long-term dietary, lifestyle, and coronary risk factor modification than would be the standard of care in a primary prevention population. ▪ In 40% to 50% of patients with CHD, SCD (death within 1 hour of onset of symptoms) is the initial presenting syndrome. ▪ The term acute coronary syndrome is used to describe patients who present with either unstable angina or AMI, which includes STEMI and non-STEMI. ▪ A third universal definition of AMI has been adopted to include criteria of a rise or drop of troponin plus evidence of symptoms of ischemia, ECG changes (pathologic Q wave, ST-segment changes, and/or new left bundle branch block), or new cardiac

muscle damage or wall motion abnormalities seen on imaging. ▪ If arterial reperfusion of the myocardium occurs within 20 minutes of myocardial ischemia, necrosis can be prevented. Beyond this phase, the extent of damage varies depending on factors such as the total time of coronary artery occlusion, possible collateral blood flow, and myocardial oxygen requirements. ▪ An individual’s prognosis post-MI is related to the complications, infarction size, presence of disease in other coronary arteries, and, most importantly, left ventricle function. ▪ Standards of physical therapy practice should include the assessment of resting and activity vital signs during an initial examination as part of the systems review. ▪ Systolic dysfunction refers to an impairment of ventricular contraction, resulting in decrease in stroke volume and decrease in ejection fraction. Diastolic dysfunction refers to changes in ventricular diastolic properties that lead to an impairment in ventricular filling (reduction in ventricular compliance) and an impairment in ventricular relaxation. ▪ A cerebrovascular event is defined as a TIA if symptoms resolve completely within 24 hours, and as a stroke if deficit results after 24 hours. ▪ Medical management includes platelet antiaggregants (aspirin), anticoagulants, lipidlowering medications, glycemic control, antihypertensive medications, and appropriate interventional methods. ▪ Studies report up to 60% to 80% of those with PAD have significant coronary atherosclerosis in at least one coronary artery. ▪ Renal artery stenosis results from atherosclerosis of the renal artery and is associated with increased cardiovascular events and mortality. ▪ An aneurysm of the aorta is a pathologic permanent dilation of the aortic wall that is higher than 50% of the expected normal diameter (>3 cm is considered aneurysmal in adults). Aneurysms are usually described in terms of their location, size, morphologic appearance, and origin.

Case study 3-1 Mr. H is a 38-year-old white male, who, at the age of 30 years, was experiencing angina with low levels of exertion and was found to have severe obstructions of his left anterior descending (LAD), first diagonal (DI), circumflex (CIRC), first obtuse marginal (OMI), and right coronary (RCA) arteries. He underwent five-vessel coronary artery bypass grafting, which relieved his angina. He now has a 2-year history of chronic stable angina, which in the past month has become more frequent, occurring with minimal exertion and occasionally while at rest. Mr. H was admitted to the hospital. He underwent a repeat cardiac catheterization, which revealed total obstructions of his native proximal LAD, mid-CIRC, and RCA. His venous bypass grafts to his LAD and DI were also 100% occluded, whereas the grafts to his OMI and distal RCA were

patent. He has a 20 pack/year (number of packs per day multiplied by the number of years smoked) history of smoking, which he stopped at the time of his bypass surgery. He has a 12-year history of hypertension, which is controlled by medication. He is 67 inches tall and weighs 270 pounds, which is 50 pounds more than he weighed at the time of his bypass surgery. His current blood lipids are TC = 188 mg/dL, triglycerides = 147 mg/dL, HDL = 27 mg/dL, and CHOL/HDL = 6.96 mg/dL. He had been employed as an accountant, but stated that he had to quit his job because he was experiencing frequent angina during stressful situations at work. He has never engaged in an organized exercise program. Study Questions What is this patient’s admitting diagnosis? Why did this patient’s angina return less than 5 years after bypass surgery? Which risk factors did Mr. H modify after his bypass surgery? Which risk factors did he not modify after his surgery? What lifestyle changes should this patient make to keep his remaining grafts patent?

Case study 3-2 Mrs. F is a 65-year-old referred for gait training. Medical history includes PAD, hyperlipidemia, and 40 pack/year of smoking. After ambulating 150 feet, she complains of moderate discomfort in her right calf, which quickly subsides during rest. Study Questions What is this type of pain called? What is the level of pain she is describing? During a visual inspection of the patient’s legs, what signs of PAD can be expected? When the patient arrives the next day, she complains of chest discomfort. Study Questions What type of pain is most likely in her case? What questions should be asked to help differentiate the type of chest discomfort she is experiencing? What patient signs/symptoms should be closely observed? What examination procedures can be performed to help determine the urgency of this matter?

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299. Sanofi US: Lovenox prescribing information. http://products.sanofi.us/lovenox/lovenox.html#Boxed%20Warning. (Accessed December 19, 2014.) 300. Vandiver J.W, Vondracek T.G. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32(6):546–558. 301. Scottish Intercollegiate Guidelines Network. Antithrombotics: Indications and Management: a national clinical guideline. Edinburgh, Scotland: Scottish Intercollegiate Guidelines Network; 2013. 302. Sachdeva A, Dalton M, Amaragiri S.V, et al. Graduated compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2014;12:CD001484. 303. Clarke M.J, Hopewell S, Juszczak E, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2006;2:CD004002. 304. Kahn S.R, Shapiro S, Wells P.S, et al. Compression stockings to prevent postthrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014;383(9920):880–888. 305. Streiff M.B, Brady J.P, Grant A.M, et al. CDC grand rounds: Preventing hospitalassociated venous thromboembolism. MMWR Morb Mortal Wkly Rep. 2014;63(9):190–193. 306. Partsch H, Blättler W. Compression and walking versus bed rest in the treatment of proximal deep venous thrombosis with low molecular weight heparin. J Vasc Surg. 2000;32:861. 307. Weber-Mzell D, Kotanko P, Schumacher M, et al. Coronary anatomy predicts presence or absence of renal artery stenosis. A prospective study in patients undergoing cardiac catheterization for suspected coronary artery disease. Eur Heart J. 2002;23:1684. 308. Safian R.D, Textor S.C. Renal-artery stenosis. N Engl J Med. 2001;344:431. 309. Braverman A, Thompson R, Sanchez L. Diseases of the aorta. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. ed 9. Philadelphia: Saunders; 2012.

Cardiac muscle dysfunction and failure Ellen Hillegass, Sean T. Lowers, and Erinn Barker

CHAPTER OUTLINE Causes and Types of Cardiac Muscle Dysfunction 79 Hypertension 79 Cardiac Arrhythmias 80 Renal Insufficiency 80 Cardiomyopathy 80 Heart Valve Abnormalities and Congenital/Acquired Heart Disease 82 Pericardial Effusion or Myocarditis 83 Pulmonary Embolism 83 Pulmonary Hypertension 83 Spinal Cord Injury 84 Age-Related Changes 84 Cardiac Muscle 86 Pathophysiology 86 Congestive Heart Failure Descriptions 87 Specific Pathophysiologic Conditions Associated with Congestive Heart Failure 88 Cardiovascular Function 88 Renal Function 91 Pulmonary Function 92 Neurohumoral Effects 93 Hepatic Function 94 Hematologic Function 95 Skeletal Muscle Function 95 Pancreatic Function 96 Nutritional and Biochemical Aspects 96 Clinical Manifestations of Congestive Heart Failure 97 Symptoms of Congestive Heart Failure 97 Signs Associated with Congestive Heart Failure 97 Quality of Life in Congestive Heart Failure 102

Cognition 103 Radiologic Findings in Congestive Heart Failure 104 Laboratory Findings in Congestive Heart Failure 104 Echocardiography 104 Medical Management 104 Dietary Changes and Nutritional Supplementation 104 Pharmacologic Treatment 104 Mechanical Management 108 Implantable Cardiac Defibrillator Implantation 108 Cardiac Resynchronization Therapy 108 Special Measures 108 Surgical Management 109 Abandoned Procedures 110 Cardiac Transplantation 110 Prognosis 110 Physical Therapy Assessment 111 Physical Therapy Interventions 112 Exercise Training 112 Guidelines for Exercise Training 112 Exercise Training and Quality of Life 114 Ventilation 115 Ventilatory Muscle Training 115 Instruction in Energy Conservation 116 Self-Management Techniques 116 Summary 117 Case study 4-1 118 References 119

Cardiac muscle dysfunction (CMD) is a term that has gained popularity in describing an apparently common finding in patients with heart and lung disease.1-3 Cardiac muscle dysfunction effectively, yet very simply, describes the most common cause of congestive heart failure (CHF).2 It develops as a result of some underlying abnormality of cardiac structure or function. Those presenting only with CMD (who are at risk of heart failure) may present without symptoms. As the abnormality progresses, the heart begins to fail to function effectively to meet the demands of the system, and heart failure begins. The syndrome of heart failure is accompanied by symptoms of shortness of breath and

fatigue at rest or with activity. It is estimated that 5.7 million or more Americans suffer from CHF and that 670,000 new cases occur yearly, requiring 1.1 million hospitalizations each year.4 In addition, the lifetime risk of developing heart failure for both men and women at age 40 years is 1 in 5, with the annual rate of developing heart failure over the age of 85 years is 65%.4 Individuals with a wide variety of heart and lung diseases very likely will develop CHF at some time during their lives,3 frequently manifested as pulmonary congestion or pulmonary edema.1 This chapter describes the etiology, pathophysiology, clinical manifestations, medical management, prognosis of CMD and CHF, and indications for physical therapy, including patient management.

Causes and Types of Cardiac Muscle Dysfunction Most often, CMD may not present with symptoms, but many of the signs and symptoms of CHF are the result of a “sequence of events with a resultant increase in fluid in the interstitial spaces of the lungs, liver, subcutaneous tissues, and serous cavities.”5 The etiology of CHF is varied, but it is most commonly the result of CMD. The varied causes of CMD and subsequently CHF can be best classified according to 11 specific processes or causes, which are described in Table 4-1.5–7

Hypertension The increased arterial pressure seen in systemic hypertension eventually produces left ventricular hypertrophy. An extremely elevated ventricular and occasionally elevated atrial pressure commonly seen in patients with CMD tend to produce a less effective pump as the myocardial contractile fibers become overstretched, thus increasing the work of each myocardial fiber in an attempt to maintain an adequate cardiac output.8,9 Myocardial work continued in this manner eventually produces left ventricular hypertrophy as the contractile fibers adapt to the increased workload.10,11 The two problems with left ventricular hypertrophy are the increase in afterload and the increased energy expenditure (metabolic cost) required for myocardial contraction because of increased myocardial cell mass.8,10,12 The increased cell mass without an additional increase in vasculature also affects blood supply to the muscle, resulting in a decreased blood supply to some of the new muscle mass. Medical management of hypertension should begin upon diagnosis after echocardiogram is performed for baseline documentation of ventricular involvement. Medical management usually consists of angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, diuretics, or possibly β blockers. Chapter 14 provides detailed information on medications. Exercise training performed regularly has demonstrated changes in systolic pressure of 10 mm Hg and diastolic pressure of 8 mm Hg, but must be maintained throughout an individual’s lifetime to maintain benefits.

Coronary Artery Disease (Myocardial Infarction/Ischemia) Coronary artery disease is the second most common cause of CMD,3 which occurs because of dysfunction of the left or right ventricle or both as a result of injury.13–15 Besides the ischemic injury from disease restricting blood flow to the cardiac muscle, there could be actual injury from infarction resulting in scar formation and decreased contractility, as well as reduced relaxation. In addition, other factors can cause injury, including myocardial damage, or “stunning,” following coronary angioplasty16,17 and postperfusion (postpump) syndrome following cardiopulmonary bypass surgery.18,19 Essentially postpump syndrome results in organ and subsystem dysfunction following abnormal bleeding, inflammation, concomitant renal dysfunction, and peripheral and central vasoconstriction.

Table 4-1 Etiology of congestive heart failure Causes Description Hypertension ↑ Arterial pressure leads to left ventric ular hypertrophy (↑ myoc ardial c ell mass) and ↑ energy expenditure. Coronary artery disease Dysfunc tion of the left or right ventric le or both as a result of injury. S c ar formation and ↓ c ontrac tility may oc c ur, as well as reduc ed (myoc ardial isc hemia) relaxation. Cardiac dysrhythmias Extremely rapid or slow c ardiac arrhythmias impair the func tioning ventric les. Dysfunc tion may be reversible if arrhythmia is c ontrolled. Renal insuffic ienc y Causes fluid overload, whic h frequently progresses to CMD and CHF that may be reversed. Cardiomyopathy Contrac tion and relaxation of myoc ardial musc le fibers are impaired. Primary c auses: pathologic proc esses in the heart musc le itself, whic h impair the heart’s ability to c ontrac t. S ec ondary c auses: systemic disease proc esses. Heart valve abnormality Valvular stenosis or inc ompetent valves (valvular insuffic ienc y bec ause of abnormal or poorly func tioning valve leaflets) c ause myoc ardial hypertrophy and a dec rease in ventric ular distensibility with mild diastolic dysfunc tion. Peric ardial effusion Injury to the peric ardium c an c ause ac ute peric arditis (inflammation of the peric ardial sac surrounding the heart) and progress to peric ardial effusion and c ardiac c ompression as fluid fills the peric ardial sac . May also develop c ardiac tamponade. Pulmonary embolism S evere hypoxemia may result from embolus bloc king a moderate to large amount of lung, resulting in elevated pulmonary artery pressures, a right ventric ular work and right heart. Pulmonary hypertension Elevated pressures in pulmonary artery lead to inc reased afterload for the right ventric le and subsequently, over time, to right ventric ular failure. S pinal c ord injury Transec tion of the c ervic al spinal c ord prevents the sympathetic -driven c hanges nec essary to maintain c ardiac performanc e. Age-related c hanges Aging appears to dec rease c ardiac output by altered c ontrac tion and relaxation of c ardiac musc le. The two most c ommon c ongenital heart defec ts are nonstenotic bic uspid aortic valve and the leaflet abnormality assoc iated with mitral valve prolapse.

Cardiac Arrhythmias Cardiac arrhythmias can also cause CMD for reasons similar to those given for myocardial infarction.5 Extremely rapid or slow cardiac arrhythmias can impair the functioning of the left or right ventricle, or both, and an overall CMD ensues. Prolonged very slow or very fast heart rates are frequently caused by a sick sinus node syndrome or heart block (producing very slow heart rates), prolonged supraventricular tachycardia (i.e., rapid atrial fibrillation or flutter), or ventricular tachycardia (both tachycardias produce very fast heart rates).20,21 (See Chapter 9 for explanation and pictures.) Very slow heart rates or heart blocks are often an adverse reaction or side effect of a specific medication, but when medications are withheld and slow heart rates or a heart block persists, the implantation of a permanent pacemaker is generally performed.20 This type of CMD is readily amenable to treatment and quite reversible. Cardiac muscle dysfunction caused by very rapid heart rates is also reversible. Rapid atrial fibrillation or flutter can produce CMD and is often easily treated by the administration of verapamil or digoxin20 (see Chapter 14). If these drugs fail, electrical cardioversion is usually performed, after which rapid heart rates frequently become much more normal as the cyclic “circus movement” propagating the rapid rhythm is disrupted and the sinoatrial node is allowed to resume control of the heart’s rhythm.20 Ventricular tachycardia and fibrillation are life-threatening cardiac arrhythmias, which, if prolonged, rapid, or both, can also produce CMD and death. The treatment of ventricular tachycardia and fibrillation is dependent on the clinical status of the patient and follows the guidelines set forth by the American Heart Association.20 The use of implantable cardiac defibrillators (ICDs) has been a treatment of choice for patients with recurrent ventricular tachycardia or fibrillation that is unresponsive to antiarrhythmic medications.21,22 Ventricular function is intimately related to cardiac rhythm. Any

abnormally fast, slow, or unsynchronized rhythm can impair ventricular and atrial function quickly and progress to CHF and even death.20 Many patients with CMD have preexisting arrhythmias that must be controlled, typically with medication, but sometimes by other methods (e.g., ablation, ICD)21 to prevent further deterioration of a muscle that is already compromised. Because antiarrhythmic agents act as cardiodepressants and often have proarrhythmic effects, they are not usually indicated in individuals with CHF.23

Renal Insufficiency Acute or chronic renal insufficiency tends to produce a fluid overload, which frequently progresses to CMD and CHF that can often be reversed if it is the only underlying pathophysiologic process. However, other pathophysiologic processes may produce the fluid overload that caused CMD.24 Consequently, CMD is seldom reversed by the correction of fluid volume alone. Nevertheless, the primary treatment is to decrease the reabsorption of fluid from the kidneys so that more fluid is eliminated (in essence, diuresed).24 The diuretic most commonly used is furosemide (Lasix), which can be given intravenously or orally. In addition to and as a result of the administration of a diuretic, electrolyte levels are carefully monitored, ensuring that potassium and sodium levels are within the normal range to prevent further retention of fluid from high levels of potassium and sodium or the detrimental effects of low levels (e.g., cardiac arrhythmias and muscle weakness). Low-dose aldosterone antagonists are also recommended in individuals with moderately severe heart failure symptoms or with left ventricle (LV) dysfunction after acute coronary syndrome (as long as serum creatinine is 28 mm Hg), causing fluid to flood the alveoli and possibly invade the large airways.

▪ Stage II (see Fig. 4-14, B). Accumulation of liquid compromises the small airway

lumina, resulting in a mismatch between ventilation and perfusion, which produces hypoxemia and wasted ventilation. Tachypnea of CHF often ensues.71 In addition, the degree of hypoxemia appears to be correlated to the degree of elevation of the pulmonary capillary wedge pressure.72 ▪ Stage III (see Fig. 4-14, C). As lymph flow continues, edema increases in the vascular system and interstitium, increasing the pulmonary capillary wedge pressure and eventually flooding the alveoli known as pulmonary edema, which significantly compromises gas exchange, producing severe hypoxemia and hypercapnia.71 In addition, severe alveolar flooding can produce the following: (1) filling of the large airways with blood-tinged foam, which can be expectorated; (2) reductions in most lung volumes (e.g., vital capacity); (3) a right-to-left intrapulmonary shunt; and (4) hypercapnia with acute respiratory acidosis.71 Perhaps the most important principle regarding pulmonary edema is that of maintaining pulmonary capillary pressures at the lowest possible levels.71 Pulmonary edema can be decreased by more than 50% when pulmonary capillary wedge pressures are decreased from 12 to 6 mm Hg. The effect of repeated bouts of pulmonary edema (which is common in CHF) upon pulmonary function appears to be profound. More advanced CHF may produce a “global respiratory impairment” that is associated with varying degrees of obstructive and restrictive lung disease.73,74

Neurohumoral Effects The neurohumoral system profoundly affects heart function in physiologic (fight-orflight mechanism) and pathologic states (CMD). In general, the neural effects are much more rapid, whereas humoral effects are slower because the information sent by the autonomic nervous system via efferent nerves travels faster than the information traveling through the vascular system.75

Normal Cardiac Neurohumoral Function Neurohumoral signals to the heart are perceived, interpreted, and augmented by the transmembrane signal transduction systems in myocardial cells.75 The primary signaling system in the heart appears to be the receptor-G-protein-adenylate cyclase (RGC) complex as it regulates myocardial contractility. Fig. 4-15 illustrates the complexity of this system, which consists of (1) membrane receptors; (2) guanine nucleotide–binding regulatory proteins (the G proteins, which transmit stimulatory or inhibitory signals); and (3) adenylate cyclase, which converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). Adenylate cyclase is an effector enzyme activated by a receptor agonist, thus enhancing cAMP synthesis. The lower portion of Fig. 4-10 shows that increased cAMP synthesis ultimately increases the force of myocardial contraction (the inotropic effect).75

FIGURE 4-15 Neural control of cardiopulmonary function. The receptor-G-protein-adenylate cyclase complex and other important receptors, all of which affect the inotropic state of the heart. ATP, Adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Gs, G-stimulatory protein; G1, G-inhibitory protein; IBMX, isobutyl methylxanthine; PDE, phosphodiesterase.

The top portion of Fig. 4-15 shows the receptor agonists responsible for the initial activation of the RGC complex. These agents include norepinephrine, epinephrine, histamine, vasoactive intestinal peptide, adenosine, and acetylcholine. Although Fig. 4-15 shows the complete system, it does not reveal the degree of influence each receptor agonist has on cardiac function. In general, the most influential receptor agonists are the sympathetic neurotransmitters norepinephrine and epinephrine, as they relay excitatory autonomic nervous system stimuli to both postsynaptic α- and β-adrenergic receptors (primarily β for norepinephrine) in the myocardium.75 Inhibitory autonomic nervous system stimuli are transmitted by the parasympathetic nervous system via the vagus nerve and the neurotransmitter acetylcholine. The adrenergic receptors (α1, α2, β1, and β2) are discussed briefly in the next paragraphs so that Fig. 4-15 can be appreciated fully, as are the neurohumoral changes that accompany CMD.

α-Adrenergic Receptors Stimulation of α1-adrenergic receptors appears to activate the phosphodiesterase

transmembrane signaling system,76,77 which increases phosphodiesterase and activates protein kinase, thus marginally increasing the inotropic effect.78 Conversely, stimulation of α2-adrenergic receptors activates the inhibitory G protein and inhibits adenylate cyclase, which decreases the inotropic effect.79

β-Adrenergic Receptors The importance of the β-adrenergic pathway cannot be overemphasized because it has been proposed that the heart is a β-adrenergic organ.80 Two β-adrenergic receptors have been identified, β1 and β2, which are “distinguished by their differing affinities for the agonists epinephrine and norepinephrine.” The β2-adrenergic receptor has a 30-fold greater affinity for epinephrine than for norepinephrine.81 In brief, β2-adrenergic receptor stimulation promotes vasodilation of the capillary beds and muscle relaxation in the bronchial tracts, whereas β1-adrenergic receptor stimulation increases heart rate and myocardial force of contraction.75

Guanine Nucleotide–Binding Regulatory Proteins As briefly discussed, the G proteins transmit stimulatory (Gs) or inhibitory (G1) signals to the catalytic unit (inner membrane sarcolemma) of myocardial contractile tissue. The stimulatory and inhibiting signals are dependent on a very complex, and only partially understood, mechanism of receptor-mediated activation.

Catalytic Unit of Adenylate Cyclase The activation of adenylate cyclase (and subsequent increase in myocardial force of contraction) is, unfortunately, poorly understood but has been observed to be decreased in patients with CHF. This decrease is the result of “a paradoxical diminution in the function of the RGC complex,”75 which alters the receptor–effector coupling and “limits the ability of both endogenous and exogenous adrenergic agonists to augment cardiac contractility.”75 The inability of endogenous (produced in the body) or exogenous (medications) adrenergic agonists to increase the force of myocardial contraction is frequently seen in patients with CHF, and may be a contributing factor in CMD.75,82

Neurohumoral Alterations in the Failing Human Heart Abnormalities in Sympathetic Neural Function The sympathetic neural function of the heart is profoundly affected in CHF. The effects are primarily caused by abnormal RGC complex function, despite interstitial (in the interspaces of the myocardium), intrasynaptic, and systemwide increased concentrations of norepinephrine.75 The abnormal RGC complex function in CHF appears to be associated with the insensitivity of the failing heart to β-adrenergic stimulation.75 This insensitivity to β-

adrenergic stimulation is apparently the result of a decrease in β1-adrenergic receptor density75 and is very important because the heart contains a ratio of 3.3:1.0 β1- to β2adrenergic receptors.75 In CHF, the ratio decreases to approximately 1.5:1.0, producing a 62% decrease in the β1-adrenergic receptors and no significant increase in β2 density.83,84 Although the number of β2 receptors does not appear to change in CHF, the β2 receptor “is partially ‘uncoupled’ from the effector enzyme adenylate cyclase.”82,85 This uncoupling only mildly desensitizes the β2-adrenergic receptors, which initially are able to compensate for the decreased number of β1 receptors by providing substantial inotropic support.86 The duration of inotropic support appears to be short lived, and myocardial failure becomes more pronounced.75

Clinical tip Excessive sympathetic nervous system stimulation occurs in CHF, and because of abnormalities in particular parts of the neurohumoral system, the heart becomes insensitive to β-adrenergic stimulation, which results in a decreased force of myocardial contraction and an inability to attain higher heart rates during physical exertion. This is where the role of β blockers plays a major part in treatment of CHF.

Hepatic Function The fluid overload associated with CHF affects practically all organs and body systems, including liver function. Increased fluid volume eventually leads to hepatic venous congestion, which prevents adequate perfusion of oxygen to hepatic tissues. Subsequent hypoxemia from the hypoperfusion produces cardiac cirrhosis, which is characterized histologically by central lobular necrosis, atrophy, extensive fibrosis, and occasionally sclerosis of the hepatic veins.10

Clinical tip Hepatomegaly, or liver enlargement, is frequently associated with CHF and can be identified readily as tenderness in the right upper quadrant of the abdomen. Patients with long-standing CHF, however, are generally not tender to palpation, although hepatomegaly is frequently present. Laboratory values showing liver involvement include abnormal aspartate aminotransferase (AST), bilirubin, and lactate dehydrogenase (LDH-5).

Hematologic Function The normal morphology of the blood and blood-forming tissues is frequently disrupted

in CHF. The most common abnormality is a secondary polycythemia (excess of red corpuscles in the blood), which is a result of either a reduction in oxygen transport or an increase in erythropoietin production.87 Erythropoietin is an α2-globulin responsible for red blood cell production, and its important role is demonstrated in Fig. 4-16. This figure shows that the hypoxia occasionally observed in patients with CHF may stimulate erythropoietin production, which increases not only red blood cell mass, but also blood volume, in an already compromised cardiopulmonary system (partly because of fluid volume overload). This potentially vicious circle can progress and cause cardiopulmonary function to deteriorate further. Clinically, anemia (low hemoglobin and hematocrit), which may be present in some patients with CHF, is a paradox, for when it is severe it can cause CHF independently, but when it precedes CHF, anemia may actually allow for more efficient and effective cardiac function.87 Improved cardiac output may occur because blood viscosity is reduced in patients with anemia, which subsequently decreases systemic vascular resistance. Consequently, anemia acts as an afterload reducer and may promote an increased cardiac output, but at the cost of lower arterial oxygen and oxygen saturation levels, as well as increased work for the heart.87 Such a condition (and others) is termed “a shift in the oxyhemoglobin curve.” The curve can be shifted to the right or left but normally follows the pattern depicted in Fig. 2-10 which represents a specific percentage of oxygen saturation for a given concentration of arterial oxygen. Oxygen saturation remains relatively stable, with arterial oxygen concentrations greater than 60 mm Hg, but below this level, the oxygen saturation drops dramatically. Table 4-6 shows the oxygen saturation levels when arterial oxygen concentrations are less than 60 mm Hg. Various conditions move this normal curve to the right or left, and these changes subsequently affect the respective oxygen saturation. For example, anemia shifts the curve to the right, representing a lower concentration of arterial oxygen, which moves the critical point of oxygen saturation to 70 mm Hg (therefore to the right). This means that at levels of less than 70 mm Hg, the level of oxygen saturation decreases dramatically compared with the normal level of 60 mm Hg. Thus patients with anemia have less reserve before their oxygen stores desaturate.87

FIGURE 4-16 Mechanisms of hematologic function. Hematologic function is occasionally disrupted in congestive heart failure and can further impair cardiopulmonary function and patient status.

Clinical tip Treatment for severe anemia often involves blood transfusion; however, a blood transfusion may increase the heart’s work because of the increase in volume and subsequently increased preload on a weak heart. The patient with a poor performing heart should be monitored carefully after blood transfusions, including heart rate, dyspnea, SpO2 (oxygen saturation measured by pulse oximetry), blood pressure, and other symptoms. Also of concern for patients with advanced CMD is the state of hemostasis (the mechanical and biochemical aspects of platelet function and coagulation), which is frequently disrupted as a result of accompanying liver disease.5 Inhibition of platelet function to the point at which the platelet count drops below 150,000 cells/µL is termed thrombocytopenia and is caused by hereditary factors or drugs, or often is acquired from systemic disease.88 Inherited thrombocytopenia is uncommon; however, thrombocytopenia caused by drugs is much more common and frequently is an adverse reaction associated with use of aspirin, corticosteroids, antimicrobial agents (penicillins and cephalothins), phosphodiesterase inhibitors (dipyridamole), caffeine, sympathetic blocking agents (β antagonists), and heparin.88 Acquired disorders of platelet function are a common complication of renal failure. This is usually corrected by renal dialysis, but patients with chronic CHF may demonstrate a mild-to-moderate level of platelet dysfunction.88

Clinical tip Hematologic impairments in CHF consist of the following: possible polycythemia, possible anemia (if present, oxygen saturation should be monitored), and possible hemostasis abnormalities such as thrombocytopenia (monitoring laboratory blood values is recommended).

Skeletal Muscle Function Skeletal muscle myopathy has been identified in patients with CHF and in those with CHF and preexisting cardiomyopathy.89,90 Among the causes of heart failure, including coronary artery disease, high blood pressure, and diabetes, skeletal muscle diseases can also cause cardiomyopathy and lead to heart failure. Table 4-6 Relationship of PaO2 to SpO2

Skeletal muscle dysfunction in patients with CHF has been studied far less in patients without cardiomyopathy than in patients with cardiomyopathy. A review by Limongelli et al defines the link between heart and skeletal muscle dysfunction and lists the disease, noncardiac phenotype, and the corresponding cardiomyopathy. Charcot–Marie–Tooth disease; myofibrillar myopathy and degeneration; Friedreich’s ataxia; glycogen storage disease; Danon disease; carnitine deficiency; Barth syndrome; myoadenylate deaminase deficiency; ocular myopathies; neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome; and Kearns–Sayre syndrome all contribute to hypertrophic, dilated cardiomyopathies and will require management of arrhythmias, including pacemaker/automatic implantable cardioverter-defibrillator (AICD) or transplantation. Muscular dystrophies of all types lead to a higher incidence of dilated cardiomyopathies and hypertrophic cardiomyopathies with a risk of sudden cardiac death. To quote Limongelli et al: “Adult and pediatric cardiologists should be aware that skeletal muscle weakness may indicate a primary neuromuscular disorder…, a mitochondrial disease…a [glycogen] storage disorder… or metabolic disorder. In such patients, skeletal muscle weakness usually precedes cardiomyopathies and dominates the clinical picture. On the other hand, skeletal involvement may be subtle, and the first symptom of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy.… Early screening with ECG and

echocardiogram and eventually, a more detailed cardiovascular evaluation should be performed to diagnose early cardiac involvement in patients with skeletal muscle weakness.”91 Skeletal muscle abnormalities caused by dilated and hypertrophic cardiomyopathies have been reported previously and have consistently revealed type I and type II muscle fiber atrophy.92–99 Patients with CHF and cardiomyopathy have been found to have three distinct skeletal muscle abnormalities: selective atrophy of type II fibers, pronounced nonselective myopathy, and hypotrophy of type I fibers.89 Isometric maximal muscle strength of persons with CHF appears to be reduced to nearly 50% of the value for age-, sex-, and weight-matched control subjects. Loss of muscle strength will result in each muscle fiber operating nearer to its maximal capacity for a given absolute power output. Consequently, the changes in skeletal muscle metabolism that are associated with fatigue might be expected to occur at lower absolute workloads and hence to limit maximal exercise capacity in these patients.90

Pancreatic Function Severe CMD can potentially reduce blood flow to the pancreas “as a consequence of splanchnic visceral vasoconstriction, which accompanies severe left ventricular failure.”100 The reduction in blood flow to the pancreas impairs insulin secretion and glucose tolerance, which are further impaired by increased sympathetic nervous system activity and augmented circulatory catecholamines (inhibiting insulin secretion) that stimulate glycogenolysis and elevate blood sugar levels.101 Reduced secretion of insulin is of paramount importance because hypoxic and dysfunctional heart muscle depends a great deal on the energy from the metabolism of glucose, which is reduced significantly if insulin secretion is impaired.100 Ultimately, there is further deterioration of left ventricular function, creating a vicious circle. Normally, the heart obtains 60% to 90% of its energy requirements from the oxidation of free fatty acids.102 The oxidation of free fatty acids increases the production of acetylcoenzyme A (acetyl-CoA) limiting carbohydrate metabolism.102 However, as previously noted, myocardial ischemia (because of the limited supply of oxygen) inhibits the oxidation of free fatty acids, thus preventing the transport of cytosolic acyl-coenzyme A (acyl-CoA) to the mitochondria for oxidation. Increased intracellular concentrations of acyl-CoA produce inhibition of adenine nucleotide translocase, which is important for myocardial energy metabolism because it transports ATP synthesized in the mitochondria to the cytosol.102,103 This final inhibition of adenine nucleotide translocase may be a key factor contributing to myocardial dysfunction.102 Finally, CMD and CHF are common in persons with diabetes and are important risk factors for the development of cardiomyopathy. Such a relationship clearly identifies the important roles nutrition and proper biochemical functions have in cardiovascular disease.

Nutritional and Biochemical Aspects Nutritional concerns are very important when assessing and treating patients with CMD. Stomach and intestinal abnormalities are not uncommon in these patients, who frequently receive many medications with profound side effects.104 In addition, the interrelated disease processes occurring in other organs because of CMD and CHF frequently produce anorexia, which leads ultimately to malnutrition. The primary malnutrition is a protein-calorie deficiency, but vitamin deficiencies have also been observed (folic acid, thiamine, and hypocalcemia-accompanied vitamin D deficiency).104 These deficient states may simply be the result of decreased intake, but “abnormal intestinal absorption and increased rates of excretion may also contribute.”104 Protein-calorie deficiency is common in chronic CHF because of cellular hypoxia and hypermetabolism that frequently produce cachexia (malnutrition and wasting).104 A catabolic state may also develop, yielding an excess of urea or other nitrogenous compounds in the blood (azotemia). This causes a vicious circle, which, because of gastrointestinal hypoxia and decreased appetite (anorexia) and protein intake, produces cardiac atrophy and more pronounced CMD.104 One particular area of concern is thiamine deficiency because of improper nutrition, which can affect this population dramatically. The force of myocardial contraction and cardiac performance in general appears to be dependent on the level of thiamine, and it has been suggested that “the possibility of thiamine deficiency should be considered in many patients with heart failure of obscure origin.”55 In addition, patients undergoing prolonged treatment with furosemide (Lasix)—the first drug of choice in the treatment of CHF—have demonstrated significant thiamine deficiency, which may improve with replacement.105 Two other nutritional concerns include carnitine deficiency and coenzyme Q10. Skeletal muscle carnitine deficiency has been observed in a small population of patients with hypertrophic cardiomyopathy and has been linked with genetic causes.91 When carnitine was replenished, cardiac symptoms and echocardiographic parameters apparently improved.106 In addition, substantial literature supports the supplementation of coenzyme Q10 in persons with CHF deficient in this apparently important biochemical component, which appears to have a role in the essential function of mitochondria, antioxidation of heart muscle, and cardiostimulation.107–111 Individuals with CHF and renal dysfunction may also demonstrate: ▪ Decreased production of erythropoietin (a hormone synthesized in the kidney that is an important precursor of red blood cell production in bone marrow), causing anemia and possibly less free fatty acid oxidation112,113 ▪ Potential for decreased calcium absorption from the gastrointestinal tract,114 as well as the development of hyperparathyroidism115 ▪ Impaired gluconeogenesis and lipid metabolism, as well as degradation of several peptides, proteins, and peptide hormones, including insulin, glucagon, growth hormone, and parathyroid hormone.116 Individuals with CHF may benefit from enteral or parenteral products to improve

nutrition and the biochemical profile.

Clinical tip There are several nutritional and biochemical aspects of CHF, including malnutrition (this may occur), thiamine and carnitine deficiency (this should be considered in patients with CHF of obscure origin), and a deficiency of coenzyme Q10 (supplementation appears to improve myocardial performance and functional status).

Clinical Manifestations of Congestive Heart Failure Heart failure is commonly associated with several characteristic signs and symptoms (Box 4-2).

BO X 4- 2 C ha ra ct e rist ic signs a nd sym pt om s of he a rt fa ilure 1. Dyspnea 2. Tachypnea 3. Paroxysmal nocturnal dyspnea (PND) 4. Orthopnea 5. Peripheral edema 6. Cold, pale, and possibly cyanotic extremities 7. Weight gain 8. Hepatomegaly 9. Jugular venous distension 10. Rales (crackles) 11. Tubular breath sounds and consolidation 12. Presence of an S3 heart sound 13. Sinus tachycardia 14. Decreased exercise tolerance or physical work capacity

Symptoms of Congestive Heart Failure Dyspnea Dyspnea (breathlessness, or air hunger) is probably the most common finding associated with CHF and is frequently the result of poor gas transport between the lungs and the cells of the body. The cause of poor transport at the lungs is often excessive blood and extracellular fluid in the alveoli and interstitium, interfering with diffusion and causing a reduction in vital capacity.5 However, the cause of poor transport at the cellular level may be less apparent. Inadequate oxygen supply either at rest or during muscular activity increases the frequency of breathing (respiratory rate) or the amount of air exchanged (tidal volume) or both.117 For this reason, subjects with CHF characteristically complain of easily provoked dyspnea or, in severe cases of CHF, dyspnea at rest.

Paroxysmal Nocturnal Dyspnea Another common complaint of individuals suffering from CHF is paroxysmal nocturnal dyspnea (PND), in which sudden, unexplained episodes of shortness of breath occur as patients with CHF assume a more supine position to sleep.5 After a period of time in a supine position, excessive fluid fills the lungs. Earlier in the day, this fluid is shunted to the lower extremities and the lower portions of the lungs because upright positions and

activities permit more effective minute ventilation (V) and perfusion (Q) of the lungs (correcting the V/Q mismatch) and the effects of gravity keep the lungs relatively fluid free. Individuals who suffer from PND frequently place the head of the bed on blocks or sleep with more than two pillows. Patients with marked CHF often assume a sitting position to sleep and are sometimes found sleeping in a recliner instead of a bed.5

Orthopnea The term orthopnea describes the development of dyspnea in the recumbent position.5 Sleeping with two or more pillows elevates the upper body to a more upright position and enables gravity to draw excess fluid from the lungs to the more distal parts of the body. The severity of CHF can sometimes be inferred from the number of pillows used to prevent orthopnea. Thus the terms two-, three-, four-, or more pillow orthopnea indirectly allude to the severity of CHF (e.g., four-pillow orthopnea suggests more severe CHF than two-pillow orthopnea).

Signs Associated with Congestive Heart Failure Breathing Patterns A rapid respiratory rate at rest, characterized by quick and shallow breaths, is common in patients with CHF. Such tachypnea is apparently not caused by hypoxemia, but rather by stimulation of stretch receptors in the interstitium stimulated by increased pressure or fluid. The quick, shallow breathing of tachypnea may assist the pumping action of the lymphatic vessels, thus minimizing or delaying the increase in interstitial liquid.71 A clinical finding observed in many patients with CMD is extreme dyspnea after a change in position, most frequently from sitting to standing. This response appears to be occasionally but inconsistently associated with orthostatic hypotension and increased heart rate activity. The orthostatic hypotension and dyspnea (tachypnea) may be the result of (1) lower extremity muscle deconditioning, producing a pooling of blood in the lower extremities when standing, with a subsequent decrease in blood flow to the heart and lungs, which may result in marked dyspnea and increased heart rates; and/or (2) attenuation of the natriuretic peptide factor (ANP/BNP), which may suggest advanced atrial distension and poor left ventricular function.118 It appears that the more pronounced the dyspnea, the more severe the CMD, and vice versa. This pattern of breathing, therefore, is another clinical finding that can be timed (time for the dyspnea to subside) and occasionally measured (blood pressure and heart rate) to document progress or deterioration in patient status. In addition, frequently associated with CHF is a breathing pattern characterized by waxing and waning depths of respiration with recurring periods of apnea. Although the Scottish physician John Cheyne and the Irish physician William Stokes first observed this breathing pattern in asthmatics and thus coined the term Cheyne–Stokes respiration, it has been observed in individuals who are suffering central nervous system damage (particularly those in comas) and in individuals with CMD.5

Clinical tip Patients with CHF often demonstrate breathing impairments, including tachypnea, resting dyspnea, dyspnea with exertion, occasional dyspnea with positional change (with or without orthostatic hypotension), and/or waxing and waning depth of breathing (Cheyne–Stokes respiration).

Rales (Crackles) Pulmonary rales, sometimes referred to as crackles, are abnormal breath sounds that, if associated with CHF, occur during inspiration and represent the movement of fluid in the alveoli and subsequent opening of alveoli that previously were closed because of excessive fluid.5 This sound is produced in the body with the opening of alveoli and airways that previously had no air; after the sound associated with such an opening is transmitted through the tissues overlying the lungs, the characteristic sound of rales is identical to that of hair near the ears being rubbed between two fingers. Rales are frequently heard at both lung bases in individuals with CHF, but may extend upward, depending on the patient’s position, the severity of CHF, or both. Therefore auscultation of all lobes should be performed in a systematic manner, allowing for bilateral comparison. The importance of the presence and magnitude of rales was addressed in 1967 and provided data for the Killip and Kimball classification of patients with acute myocardial infarction.119 Table 4-7 defines classes I through IV, each of which is associated with an approximate mortality rate.120 Individuals with rales extending over more than 50% of the lung fields were observed to have a very poor prognosis.

Heart Sounds Heart sounds can provide a great deal of information regarding cardiopulmonary status but unfortunately are ignored in most physical therapy examinations. The normal heart sounds include a first heart sound (S1), which represents closure of the mitral and tricuspid valves, and a second sound (S2), which represents closure of the aortic and pulmonary valves. The most common abnormal heart sounds are the third (S3) and fourth (S4), which occur at specific times in the cardiac cycle as a result of abnormal cardiac mechanics. An S3 heart sound may be normal in children and young adults and is termed a physiologic normal S3.121 An S4 is presystolic (heard before S1), and S3 occurs during early diastole, after S2. The presence of an S3 indicates a noncompliant LV and occurs as blood passively fills a poorly relaxing LV that appears to make contact with the chest wall during early diastole.121 The presence of an S3 is considered the hallmark of CHF.122 There are several reasons why the left ventricle may be noncompliant, of which fluid overload and myocardial scarring (via myocardial infarction or cardiomyopathy) appear to be the most common.

The presence of an S4 represents “vibrations of the ventricular wall during the rapid influx of blood during atrial contraction” from an exaggerated atrial contraction (atrial “kick”).121 It is commonly heard in patients with hypertension, left ventricular hypertrophy, increased left ventricular end-diastolic pressure, pulmonary hypertension, and pulmonary stenosis.121 Auscultation of the heart (Fig. 4-17) may also reveal adventitious (additional) sounds, most frequently murmurs. Murmurs not only are common in patients with CMD, but also appear to be of great clinical significance. Stevenson and coworkers demonstrated that the systolic murmur of secondary mitral regurgitation was an important marker in the treatment of a subgroup of patients with congestive cardiomyopathy.123 The patients who benefited from afterload (the resistance to ventricular ejection or peripheral vascular resistance) reduction were those with a very large LV (left ventricular end-diastolic dimension >60 cm) and a resultant systolic murmur.123 This study demonstrated the importance of auscultation of the heart at rest and immediately after exercise in persons with CHF to gain insight into the dynamics of myocardial activity. Table 4-7 The Killip and Kimball classification of patients with acute myocardial infarction

Mortality rates of 1906 documented AMI patients admitted to CCU. Killip classification as a significant, sustained, consistent predictor and independent of relevant covariables Data from Gallindo de Mello BH, et al. Validation of the Killip–Kimball Classification and Late Mortality after Acute Myocardial Infarction. Arq Bras Cardiol 103(2):107-117, 2014.

Peripheral Edema Peripheral edema frequently accompanies CHF, but in some clinical situations it may be absent when, in fact, a patient has significant CHF.5 In CHF, fluid is retained and not excreted because the pressoreceptors of the body sense a decreased volume of blood as a result of the heart’s inability to pump an adequate amount of blood. The pressoreceptors subsequently relay a message to the kidneys to retain fluid so that a greater volume of blood can be ejected from the heart to the peripheral tissue.69 Unfortunately, this compounds the problem and makes the heart work even harder, which further decreases its pumping ability. The retained fluid commonly accumulates bilaterally in the dependent extracellular spaces of the periphery.5 Dependent spaces, such as the ankles and pretibial areas, tend to accumulate the majority of fluid and can be measured by applying firm pressure to the pretibial area for 10 to 20 seconds, then measuring the resultant indentation in the skin (pitting edema). This is frequently graded as mild,

moderate, or severe, or it is given a numerical value, depending on the measured scale (Table 4-8). Peripheral edema can also accumulate in the sacral area (the shape of which resembles the popular fanny packs) or in the abdominal area (ascites). By using the pitting edema scale to determine the severity and location of peripheral edema (pretibial or sacral, distal or proximal) and obtaining girth measurements of the lower extremities and the abdomen, important information regarding patient status can be obtained. However, it should be noted that peripheral edema is a sign that is associated with many other pathologies and does not by itself imply CHF.

FIGURE 4-17 Primary auscultatory areas. Auscultation of the heart is performed in a systematic fashion using both the bell and diaphragm of the stethoscope at the indicated sites.

Jugular Venous Distention Jugular venous distension also results from fluid overload. As fluid is retained and the heart’s ability to pump is further compromised, the retained fluid “backs up,” not only into the lungs, but also into the venous system, of which the jugular veins are the simplest to identify and evaluate. The external jugular vein lies medial to the external jugular artery, and with an individual in a 45-degree semirecumbent position, it can be readily measured for signs of distension. Although individuals with marked CHF may demonstrate jugular venous distension in all positions (supine, semisupine, and erect), typically, jugular venous distension is measured when the head of the bed is elevated to

45 degrees.60,121 The degree of elevation should be noted, as well as the magnitude of distension (mild, moderate, severe). Normally, the level is less than 3 to 5 cm above the sternal angle of Louis. Measurements of the internal jugular vein may be more reliable than those of the external jugular vein. Nonetheless, the highest point of visible pulsation is determined as the trunk and head are elevated, and the vertical distance between this level and the level of the sternal angle of Louis is recorded (Fig. 4-18).71,121 Evaluation of the jugular waveforms can also be performed in this position, but catheterization of the pulmonary artery for assessment of pulmonary arterial pressures provides the greatest amount of information. A tremendous amount of information can be projected to a hemodynamic monitor, where the pulmonary artery pressure can be assessed and specific waveforms may be observed. The A wave of venous distension from right atrial systole, occurring just before S1, and the V wave, frequently indicating a regurgitant tricuspid valve, are two such examples and are displayed in Fig. 4-19.71,121 Although the assessment of hemodynamic function via pulmonary artery pressure monitoring is considered an advanced skill, it is relatively simple to interpret the typical intensive care unit monitor and thus obtain important hemodynamic information. Perhaps the most important aspect of such monitoring is identifying the pulmonary artery pressure, which is schematized in Fig. 4-19. A mean pulmonary artery pressure greater than 25 mm Hg is the definition of pulmonary hypertension and appears to be associated with a variety of pathophysiologic phenomena (hypoxia, cardiac arrhythmias, and pulmonary abnormalities).60,121 Table 4-8 Pitting edema scale Edema Characteristics Barely perc eptible depression (pit) Easily identified depression (EID) (skin rebounds to its original c ontour within 15 sec ) EID (skin rebounds to its original c ontour within 15 to 30 sec ) EID (rebound >30 sec )

Score 1+ 2+ 3+ 4+

FIGURE 4-18 Evaluation of venous pressure. Elevated venous pressure frequently represents right-sided and left-sided heart failure, which is characterized by pulmonary congestion and distension of the external jugular vein that is greater than 3 to 5 cm above the sternal angle of Louis.

FIGURE 4-19 The relationship of the jugular venous pulse to the electrocardiogram and heart sounds. The jugular venous pulse (and its various component wave patterns, C, V, and A waves) can be observed in the external jugular vein or via intensive care monitoring (which is often accompanied by an electrocardiogram). The physiologic and mechanical events producing these wave patterns can be better analyzed by assessing the heart sounds and their respective location in the cardiac and venous pulse cycles.

Pulsus Alternans Pulsus alternans (mechanical alteration of the femoral or radial pulse characterized by a regular rhythm and alternating strong and weak pulses) can frequently identify severely depressed myocardial function and CHF in general. This is performed using light pressure at the radial pulse with the patient’s breath held in midexpiration (to avoid the superimposition of respiratory variation on the amplitude of the pulse).121 Sphygmomanometry can more readily recognize this phenomenon, which commonly demonstrates 20 mm Hg or greater alternating systolic blood pressure. Characteristically, if pulsus alternans exists, a 20 mm Hg or greater decrease in systolic blood pressure occurs during breath holding because of increased resistance to left ventricular ejection. It should be noted that a difference exists between pulsus alternans and pulsus paradoxus, which is characterized by a marked reduction of both systolic blood pressure (−20 mm Hg) and strength of the arterial pulse during inspiration. Pulsus paradoxus can also be detected by sphygmomanometry121 and is occasionally seen in CHF. However, it is associated more frequently with cardiac tamponade and constrictive pericarditis primarily because of increased venous return and volume to the right side of the heart, which bulges the interventricular septum into the LV, thus decreasing the amount of blood present in the LV and the amount of blood ejected from it (because of decreased left ventricular volume and opposition to stroke volume from the bulging septum).121

Changes in the Extremities Occasionally, the extremities of persons with CHF will be cold and appear pale and cyanotic. This abnormal sensation and appearance are a result of the increased sympathetic nervous system activation of CHF, which increases peripheral vascular vasoconstriction and decreases peripheral blood flow.124,125

Weight Gain As fluid is retained, total body fluid volume increases, as does total body weight. Fluctuations of a few pounds from day to day are usually considered normal, but increases of several pounds per day (more than 3 lb) are suggestive of CHF in a patient with CMD.5 Body weight should always be measured from the same scale at approximately the same time of day with similar clothing and before exercise is started.

Sinus Tachycardia Sinus tachycardia or other tachyarrhythmias may occur in CHF as the pressoreceptors and chemoreceptors of the body detect decreased fluid volume and decreased oxygen levels, respectively.5 The body attempts (via increased heart rate) to increase the delivery of fluid and oxygen to the peripheral tissues where it is needed. Unfortunately, this only compounds the problem and makes the heart work even harder, which further impairs its ability to pump.

Decreased Exercise Tolerance Decreased exercise tolerance is ultimately the culmination of all of the preceding pathophysiologies that produce the characteristic signs and symptoms just discussed. It is apparent that as individuals at rest become short of breath, gain weight, and develop a faster resting heart rate, their ability to exercise is dramatically decreased. This effect has been observed repeatedly in patients with CHF and is the result of the interrelationships among the pathophysiologies briefly discussed.5 Table 4-9 Weber classification of functional impairment in aerobic capacity and anaerobic threshold as measured during incremental exercise testing

VO2max, peak exercise oxygen consumption. From Mann DL: Heart failure: a companion to Braunwald’s heart disease, Philadelphia, 2004, Saunders.

Individuals with heart failure demonstrate early onset anaerobic metabolism as a result of abnormalities in the skeletal muscle. The other changes in the skeletal muscle include fiber atrophy, loss of oxidative type I fibers, and an increase in glycolytic type IIB fibers.126,127 The methods of measuring exercise tolerance in patients with CHF have improved significantly in the past few years, but many investigators still use the criteria set forth by the New York Heart Association (NYHA) in 1964.128 These criteria categorize patients into one of four classes, depending on the development of symptoms and the amount of effort required to provoke them. In short, patients in class I have no limitations in ordinary physical activity, whereas patients in class IV are unable to carry on any physical activity without discomfort. Patients in classes II and III are characterized by slight limitation and marked limitation in physical activities, respectively (see Table 4-7). A great deal of investigation has been done on measuring exercise tolerance, functional capacity, and survival in persons with CHF.128–140 Peak oxygen consumption measurements have traditionally been used to categorize persons with CHF, and numerous studies have shown that persons with lower levels of peak oxygen consumption have poorer exercise tolerance, functional capacity, and survival than persons with greater levels of peak oxygen consumption (Table 4-9).128–135 A peak oxygen consumption threshold range of 10 to 14 mL/kg/min appears to exist, below which patients have been observed to have

poorer survival.130–135 In fact, a peak oxygen consumption below this range is frequently used to list patients for cardiac transplantation.135 Measurement of the anaerobic threshold (or ventilatory threshold) and the “slope of the rate of CO2 output from aerobic metabolism plus the rate of CO2, generated from buffering of lactic acid, as a function of the VO2,” as well as the change in oxygen consumption to change in work rate above the anaerobic threshold, appear to be useful and relatively reliable in determining exercise tolerance in patients with CHF (Fig. 420).136–140

FIGURE 4-20 Ventilation/carbon dioxide production ( e/ co2) slope in heart failure (HF). Note that the relation between e and co2 remains linear but that the slope increases with worsening heart failure. Thus, for a co2 of 1 l/min, a normal subject has to ventilate at 22 l/min and the patient with moderate heart failure ventilates at 42 l/min. (Data from Clark AL: Origin of symptoms in chronic heart failure, Heart 92(1):12-16, 2006.)

Unfortunately, most physical therapists do not have access to equipment (or training in its use) to measure respiratory gases. However, simple but thorough exercise assessments that evaluate symptoms, heart rate, blood pressure, heart rhythm via electrocardiogram, oxygen saturation via oximetry, and respiratory rate at specific workloads can provide important and useful information to compare patient response from day to day. Examples of such an assessment include treadmill ambulation, bicycle ergometry, hallway ambulation, and gentle callisthenic or strength training. Through this type of assessment, progress or deterioration can be documented and appropriate therapy implemented. The 6-minute walk test (6MWT) is a valuable tool when assessing patients with CHF.141 It provides an insight into the functional status, exercise tolerance, oxygen consumption,

and survival of persons with CHF. Although the exercise performed during the 6MWT is considered submaximal, it nonetheless closely approximates the maximal exercise of persons with CHF and is correlated to peak oxygen consumption.141,142 Information obtained from the 6MWT has been used to predict peak oxygen consumption (unfortunately, with a modest degree of error) and survival in persons with advanced CHF awaiting cardiac transplantation (Table 4-10). Fig. 4-21 demonstrates that patients unable to ambulate greater than 468 m during the 6MWT had poorer short-term survival, but did not find a relationship with long-term survival. However, Bittner and colleagues143 found patients unable to ambulate greater than 300 m had poorer long-term survival. Therefore not only can the cardiopulmonary response and exercise tolerance of a person with CHF be evaluated with the 6MWT, but a distance of 300 m appears to be important in determining short- and long-term survival. Several important responses observed during submaximal and maximal exercise testing in patients with CMD are also important factors of prognosis and are found in Box 4-3.144 Table 4-10 Multivariate equations for the prediction of peak oxygen uptake (VO2)

CI, Cardiac index; LVEF, left ventricular ejection fraction; PAP, pulmonary artery pressure; r= correlation coefficient; r 2 = coefficient of determination; RPP, rate-pressure product; SEE, standard error of the estimate.

FIGURE 4-21 Relationship of 6MWD to long term cardiovascular survival in men with systolic heart failure. (Data from Wegrzynowska-Teodorczyk K, et al: Distance covered during a 6-minute walk test predicts long-term cardiovascular mortality and hospitalization rates in men with systolic heart failure: an observational study, J Physiother 59:177-187, 2013.)

Quality of Life in Congestive Heart Failure Comprehensive instruments have been designed and consist primarily of questionnaires that measure specific attributes of life such as socioeconomic factors, psychological status, and function. One such questionnaire was designed by Rector and associates and is titled the Minnesota Living with Heart Failure Questionnaire.145 This questionnaire (Table 4-11) consists of 21 questions that the patient answers to the best of the patient’s ability. This self-administered questionnaire appears to be more accurate and reliable with a modest degree of supervision. The Minnesota Living with Heart Failure Questionnaire has been used in several recent studies investigating the effects of various pharmacologic agents in persons with CHF, as well as exercise training in CHF, and appears useful for measuring quality of life and changes in the quality of life.146–149 These areas are two very important issues for clinical practice and research, and the information provided by this questionnaire is therefore highly desirable. Other similar questionnaires have been developed, but none have been used as extensively as the Minnesota Living with Heart Failure Questionnaire.

BO X 4- 3 Re sponse s obse rve d during subm a x im a l a nd m a x im a l

e x e rcise t e st ing in pa t ie nt s wit h C MD 1. A more rapid heart rate rise during submaximal workloads 2. A lower peak oxygen consumption and oxygen pulse (an indirect measure of stroke volume obtained by dividing the heart rate into oxygen consumption) during submaximal and maximal work 3. A flat, blunted, and occasionally hypoadaptive (decrease) systolic blood pressure response to exercise 4. A possible increase in diastolic blood pressure 5. Electrocardiographic signs of myocardial ischemia (ST depression and/or T-wave inversion) 6. More easily provoked dyspnea and fatigue, often accompanied by angina 7. Lower maximal workloads compared with those of subjects without heart disease 8. A chronotropic (increased heart rate response) and possibly an inotropic (force of myocardial contraction) incompetence (resulting in an inability to increase the heart rate or force of myocardial contraction) during exercise in patients with severe coronary artery disease and multisystem disease that may be partially caused by an autonomic nervous system dysfunction Data from Deboeck G, Van Muylem A, Vachiéry JL, Naeije R: Physiological response to the 6-minute walk test in chronic heart failure patients versus healthy control subjects, Eur J Prev Cardiol 21(8):997-1003, 2014.

Significant depression is associated with an increased risk of functional decline, as well as increased morbidity and mortality independent of severity of disease.150–153 Significant depression also is associated with more than a double increase in mortality at 3 months and with triple the rate of rehospitalization in 1 year.150 Table 4-11 The minnesota living with heart failure questionnaire These questions c onc ern how your heart failure (heart c ondition) has prevented you from living as you wanted during the past month. The items listed here desc ribe different ways some people are affec ted. If you are sure an item does not apply to you or is not related to your heart failure, then c irc le 0 (No) and go on to the next item. If an item does apply to you, then c irc le the number rating of how muc h it prevented you from living as you wanted. Remember to think about ONLY THE PAS T MONTH. Did your heart failure prevent you from living as you wanted during the last month by

Copyright University of Minnesota, 1986. IN Rector TS, Cohn JN: Assessment of patient outcome with the Minnesota Living with Heart Failure Questionnaire: Reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. Am Heart J 124(4):1017–25, 1992..

Cognition Cognitive impairment is increasingly becoming recognized as an important predictor of poor clinical outcomes, repeat hospitalizations, and higher mortality rates.154 Exercise has been established as preventing and reducing the effects of inactivity in peripheral vasculature; the effects of exercise on cerebral vasculature are starting to be studied. Cognitive impairment is thought to be the cumulative effect of decreased cerebral perfusion and oxygenation, structural changes in the brain (particularly hippocampal damage), atrophy, loss of gray matter, and microemboli. The hippocampus is especially vulnerable to oxygen deprivation. When hippocampal tissue is damaged, the ability to perform essential self-care activities of daily living (ADLs) and routine daily tasks is diminished. Cerebral hypoperfusion has been shown to be predictive of cognitive decline

from mild cognitive impairment to severe dementia.155 In patients with heart failure, a 12week, 3-day-per-week cardiac rehabilitation intervention demonstrated and maintained memory improvements at 12 months.156 Aerobic activity has been demonstrated to improve cognitive function in a number of domains, including spatial and executive functioning. The most noted improvement was in executive function; aerobic exercise was shown to reverse cognitive impairments in individuals with dementia with an overall moderate effect size of 0.57 between the exercise and control groups. Low-to-moderate-intensity aerobic exercise three or more times per week can reduce the risk of dementia by 34%. In longitudinal studies, patients who participated in exercise at age 36 and 43 had the lowest rate of memory decline at age 53.157 Most evidence supports that aerobic exercise benefits cognitive function. The benefits of exercise training seem to be greater for executive functioning than other cognitive processes. Exercise may also have a protective effect against cognitive decline with aging. Further research is needed to better understand the molecular mechanisms of the influence of exercise on cognitive function.

BO X 4- 4 La bora t ory ﬁndings in C HF 1. ↑ Elevated BNP or NT-proBNP 2. ↑ Protein in urine 3. ↑ Urine specific gravity 4. ↑ Elevated BUN 5. ↑ Elevated creatinine 6. ↓ Erythrocyte sedimentation rates 7. ↓ PaO2 8. ↓ SpO2 9. ↑ PaCO2 10. ↑ Elevated AST 11. ↑ Elevated alkaline phosphatase 12. ↑ Bilirubin 13. ↓ Na+ 14. ↑ or ↓ K+

Radiologic Findings in Congestive Heart Failure Identification of several of the signs and symptoms frequently suggests the presence of CHF, but radiologic and occasionally laboratory findings usually confirm the diagnosis and provide a baseline from which to evaluate therapy.5 Radiologic evidence of CHF is dependent on the size and shape of the cardiac silhouette (evaluating left VEDV), as well as the presence of interstitial, perivascular, and alveolar edema (evaluating fluid in the

lungs).5 Interstitial, perivascular, and alveolar edema form the radiologic hallmark of CHF and generally occur when pulmonary capillary pressures (which reflect the left ventricular end-diastolic pressure) exceed 20 to 25 mm Hg.5 Pleural effusions (parenchymal fluid accumulations) and atelectasis (collapsed lung segments) may also be present.

Laboratory Findings in Congestive Heart Failure Proteinuria; elevated urine specific gravity, BUN, and creatinine levels; and decreased erythrocyte sedimentation rates (because of decreased fibrinogen concentrations resulting from impaired fibrinogen synthesis) are associated with CHF.5 Frequently, but not consistently, PaO2 and oxygen saturation levels are reduced and PaCO2 levels elevated.158 Liver enzymes, such as AST and alkaline phosphatase, are often elevated, and hyperbilirubinemia commonly occurs, resulting in subsequent jaundice.5 Serum electrolytes are generally normal, but individuals with chronic CHF may demonstrate hyponatremia (decreased Na+) during rigid sodium restriction and diuretic therapy or hypokalemia (decreased K+), which also may be the result of diuretic therapy.1 Hyperkalemia can occur for several reasons, but most commonly is caused by a marked reduction in the GFR (especially if individuals are receiving a potassium-retaining diuretic) or overzealous potassium supplementation (when a non–potassium-retaining diuretic is used) (Box 4-4).5 Brain natriuretic peptide and its amino-terminal fragment NT-proBNP have an established role in the diagnosis of patients presenting with dyspnea of uncertain etiology and possibly in determining decompensation in CHF.66

Echocardiography Echocardiography (including Doppler flow studies) is the most useful diagnostic test for evaluation of anatomy, possible etiology, and severity of heart failure. The following three major concerns regarding heart failure can be answered with echocardiography: ▪ Is the left ventricular LEVF preserved or reduced? ▪ What is the structure of the LV (hypertrophy, dilated, normal)? ▪ Are other structural abnormalities present (pericardial, valvular functioning, right ventricle) that would affect LV functioning?23 The echocardiography report should include EF, ventricular dimensions, ventricular volume, wall thickness measurement, chamber geometry, and regional wall motion.23

Medical Management The treatment of CHF, in general, is directed at the underlying cause or causes. The fundamental treatment for CHF involves controlling the pathophysiologic mechanisms responsible for its existence. By improving the heart’s ability to pump and reducing the workload and controlling sodium intake and water retention, CHF can be relatively well controlled.159 Table 4-12 outlines these measures. In addition, Box 4-5 defines common predisposing factors causing decompensated heart failure. The specific treatments for CHF include the restriction of sodium intake, use of medications (diuretics, digitalis, and other positive inotropic agents, dopamine, dobutamine, amrinone, vasodilator therapy, venodilators, ACE inhibitors, and βadrenergic blockers), other special measures, and properly prescribed physical activity. Fig. 4-22 outlines these treatments, and a brief discussion of each reveals how the pathophysiology of CHF is affected with each of the following measures.

Dietary Changes and Nutritional Supplementation Because of the associated dietary and nutritional deficiencies, supplementation of vitamins, minerals, and amino acids is often provided to persons with CHF. Vitamins C and E, as well as various minerals, have shown some promise as important supplements to the diet of persons with CHF.160–163 Dietary changes are also important for persons with CHF and include decreasing sodium intake, fluid restrictions, and eating heart-healthy foods that are low in cholesterol and fat. Such changes have been observed to decrease hospital readmissions in persons with CHF. Also, dietary counseling alone has been found to produce similar reductions in hospital readmissions and to improve patient outcomes.164,165

Pharmacologic Treatment See Chapter 14 for detailed description of the following medications.

Table 4-12 Outline of treatment of chronic congestive heart failure Treatment/P rescription Proper presc ription of physic al ac tivity

Dec rease or disc ontinue exhaustive ac tivities Dec rease or disc ontinue full-time work or equivalent ac tivity, introduc ing rest periods during the day Gradual progressive exerc ise training that fluc tuates frequently from day to day Exerc ise intensity determined by level of dyspnea or adverse physiologic effort (i.e., angina or dec rease in systolic blood pressure) Restric tion of sodium intake Institute a low-sodium diet Digitalis glyc oside and other Dopamine inotropic agents Dobutamine Amrinone Diuretic s Moderate diuretic (thiazide) Loop diuretic (furosemide) Loop diuretic plus distal tubular (potassium-sparing) diuretic Loop diuretic plus thiazide and distal tubular diuretic Aldosterone antagonists S pironolac tone Vasodilators or venodilators Captopril, enalapril, or c ombination of hydralazine plus isosorbide dinitrate Intensific ation of oral vasodilator regimen Intravenous nitroprusside Angiotensin-c onverting enzyme β Bloc kers

S pec ial measures

Captopril—may prevent c ardiac dilation Enalapril maleate Lisinopril Metoprolol Buc indolol Xamoterol Dialysis and ultrafiltration Assisted c irc ulation (intraaortic balloon, left ventric ular assist devic e, artific ial heart) Cardiac transplantation

Common Factors in Decompensated Heart Failure Not partic ipating in rehabilitation

Not c hanging diet Toxic ity c an c ause arrhythmia

Not watc hing water intake, weighing daily

Nonc omplianc e with medic ations c an c ause unc ontrolled hypertension Nonc omplianc e with medic ations c an c ause unc ontrolled hypertension

Nonc omplianc e with medic ations c an c ause unc ontrolled hypertension Nonc omplianc e with medic ations c an c ause unc ontrolled arrhythmias

BO X 4- 5 C om m on pre cipit a t ing fa ct ors in de com pe nsa t e d

he a rt fa ilure • Medicine and dietary noncompliance • Cardiac causes • Ischemia • Arrhythmia • Uncontrolled hypertension • Noncardiac causes • Infection (pneumonia with or without hypoxia) • Exacerbation of comorbidity (chronic obstructive pulmonary disease) • Pulmonary embolus • Toxins (nonsteroidal antiinflammatory drugs) • Volume overload The specific medications discussed here are used for the pharmacologic treatment of CHF, including diuretics, digitalis and other positive inotropic agents, dopamine, dobutamine, amrinone, vasodilator therapy, venodilators, ACE inhibitors, and βadrenergic blockers. Three classes of drugs can exacerbate the syndrome of heart failure and should be avoided in most patients, including:

▪ Antiarrhythmic agents, which act as cardiodepressants and often have proarrhythmic effects. Only amiodarone and dofetilide have been shown to not adversely affect survival. ▪ Calcium-channel blockers can lead to worsening heart failure and are associated with increased risk of cardiovascular events. ▪ Nonsteroidal antiinflammatory drugs often increase sodium retention, cause peripheral vasoconstriction,23 and impair the action of diuretics and ACE inhibitors.

Diuretics Diuretics remain the cornerstone of treatment for CHF.159 As outlined in Table 4-12, moderate diuretics and loop diuretics are commonly used to reduce the fluid overload of CHF by increasing urine flow. Most of these diuretics act directly on kidney function by inhibiting solute (substances dissolved in a solution) and water reabsorption. As previously discussed, furosemide (Lasix) is the most commonly used diuretic, inhibiting the cotransport of sodium, potassium, and chloride.159 As a result, individuals on Lasix need to be on K+ supplements.

FIGURE 4-22 Stages in the development of heart failure (HF) and recommended therapy by stage. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; EF, ejection fraction; FHx CM, family history of cardiomyopathy; LV, left ventricular; LVH, left ventricular hypertrophy; MI, myocardial infarction. (From Jessup M, Abraham WT, Casey DE, et al. 2009 Focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119(14):1977–2016, 2009.)

The major principles of diuretic use are as follows: ▪ Higher doses are required to restore than to maintain optimal volume status. ▪ Doses should generally be doubled when an increased effect is desired. ▪ The addition of metolazone or intravenous thiazides frequently resolves apparent “diuretic resistance” but should be reserved for intermittent rather than chronic use. ▪ Adequacy of oral diuretic dosing should be demonstrated before discharge. With these considerations, furosemide (in bolus or continuous infusion) is generally effective to achieve diuresis, sometimes with the addition of intravenous thiazides.129

Aldosterone Antagonists Aldosterone antagonists (e.g., spironolactone) are often added to the medical regimen of individuals with mild-to-moderate symptoms of heart failure in addition to other diuretics.23

Digoxin (Lanoxin) and Other Positive Inotropic Agents Digoxin (digitalis) is one of medicine’s oldest drugs, and most of the digitalis drugs in use today are steroid glycosides derived from the leaves of the flowering plant foxglove, or Digitalis purpurea. Despite its long history, there is still controversy over its use in patients with CHF and normal sinus rhythm.166–168 However, several studies demonstrate favorable hemodynamic and clinical responses in selected patients.169–173 The most significant clinical observations tend to be related to the positive inotropic (increased force of contraction) effect evidenced by an increased LVEF.174 In addition, the electrophysiologic effects of digoxin on the heart help control rapid supraventricular arrhythmias (primarily atrial fibrillation or flutter) by increasing the parasympathetic tone in the sinus and atrioventricular nodes, thereby slowing conduction.174 Current standard treatment recommendations involve the four-drug approach (digoxin, diuretics, ACE inhibitors, and β blockers) for all patients with left ventricular dysfunction and symptomatic heart failure, regardless of cause.129 Results from the Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE) trials indicate that digoxin increases LVEF more in patients with dilated cardiomyopathy than in patients with ischemic heart disease and that withdrawal of digoxin leads to a significantly greater likelihood of clinical deterioration in patients with dilated cardiomyopathy.175

Dopamine Dopamine hydrochloride is a chemical precursor of norepinephrine, which stimulates dopaminergic, β2-adrenergic, and α-adrenergic receptors, as well as the release of norepinephrine. This results in increased cardiac output and, at doses greater than 10 µg/kg/min, markedly increased systemic vascular resistance and preload.20 For this reason, the primary indication for dopamine is hemodynamically significant hypotension in the absence of hypovolemia.20 Dopamine is also useful for patients with refractory CHF, in which case it is carefully titrated until urine flow or hemodynamic parameters improve. In such patients, the hemodynamic and renal effects of dopamine can be profound. Frequently, dopamine is infused together with nitroprusside or nitroglycerin to counteract the vasoconstricting action. In addition, dopamine is frequently administered (as are dobutamine and amrinone) during and after cardiac surgery to improve low cardiac output states.20

Dobutamine

Dobutamine is a sympathomimetic amine that stimulates β1 receptors in the myocardium, with very little effect on α-adrenergic receptors. It provides potent inotropic effects, but is only given via intravenous infusion.176 Like dopamine, dobutamine increases cardiac output and decreases the peripheral resistance; with the use of dopamine, there is a potentially significant increase in peripheral resistance. For this reason, dobutamine in addition to a moderate increase in volume is the treatment of choice in patients with hemodynamically significant right ventricular infarction.20

Amrinone/Milrinone Amrinone and milrinone are phosphodiesterase inhibitors that lead to increased cAMP by preventing its breakdown, thereby producing rapid inotropic and vasodilatory effects. Some of the side effects can include exacerbation of myocardial ischemia if coronary occlusion exists,177 hypotension as a result of intense vasodilation, elevation in heart rate, and increase in atrial and ventricular tachyarrhythmias. Amrinone can also cause thrombocytopenia in 2% to 3% of patients, as well as a variety of other side effects (e.g., gastrointestinal dysfunction, myalgia, fever, hepatic dysfunction, cardiac arrhythmias). Milrinone has a prolonged half-life, and its physiologic half-life may be excessive in individuals with renal dysfunction. More has been learned about the long-term effects of milrinone than about the other intravenous inotropic drugs in current use. Mortality from both heart failure and sudden death was increased with chronically administered milrinone compared with placebo without any significant improvement in symptoms.178 Despite these adverse effects, amrinone is recommended and has proved to be therapeutic for patients with severe CHF that is refractory to diuretics, vasodilators, and other inotropic agents.179 In addition, an increase in exercise tolerance has been observed with the use of milrinone.180

Vasodilators and Venodilators Vasodilators (nesiritide, nitroglycerin, nitroprusside) are given to patients with CHF or CMD to relax smooth muscle in peripheral arterioles and to produce peripheral vasodilation that reduces filling pressures, decreases the afterload, lessens the work of the heart, decreases symptoms, and potentially decreases the degree of CMD. These medications include calcium-channel blockers and α-blockers. The clinical management of patients with CHF and CMD frequently combines vasodilators, venodilators, and ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors and α-Receptor Blockers The combined use of ACE inhibitors, vasodilators, and venodilators has been demonstrated to be very effective in reducing symptoms and improving exercise tolerance.181 The primary mechanism of action of these inhibitors is probably via the reduction of angiotensin II, a hormone that causes vasoconstriction,174 but other less well-defined actions may be responsible for the therapeutic effects of ACE inhibitors in

patients with CHF. Other poorly understood mechanisms of such inhibitors include “nonspecific vasodilation with unloading of the ventricle, inhibition of excessive sympathetic drive and perhaps modulation of tissue receptor systems.”174 A great deal of interest has focused on the “prevention” hypothesis regarding the use of ACE inhibitors and the prevention of progressive CMD (dilation and CHF).182–185 Notably, captopril may prevent such progressive cardiac dilation.182,183 Recent studies have focused on the addition of β blockers to ACE inhibitors (and sometimes α-receptor blockers) and demonstrated a greater improvement in symptoms and reduction in the risk of death than when ACE inhibitors were used alone and the dosage was increased.186

α-Adrenergic Antagonists and Partial Agonists Perhaps one of the most confusing groups of medications used in treating CHF and CMD is the β-adrenergic blockers group. One of the many uses of β blockers is to lower blood pressure, primarily via a reduction in cardiac output.174 This reduction in cardiac output is the result of a decrease in heart rate and stroke volume, which causes an increase in end-diastolic volume and end-diastolic pressure (the slowing of the heart rate allows more time for the ventricles to fill before the next myocardial contraction with more time for the coronary arteries to fill) but somewhat paradoxically reduces the myocardial oxygen requirement.187 This paradoxical reduction in oxygen requirement probably is the result of a decrease in sympathetic nervous system stimulation because of the blocking of the β receptors. Sympathetic (catecholamine-driven) increases in heart rate, force of myocardial contraction, velocity, and extent of myocardial contraction, as well as systolic blood pressure, are prevented by β blockade.188,189 β Blockers interfere with the sustained activation of the nervous system and therefore block the adrenergic effects on the heart. Although there are a number of potential benefits to blocking all three receptors (β1, β2, and α), most of the deleterious effects of sympathetic activation are mediated by the β1-adrenergic receptor. β Blockers are usually prescribed in conjunction with ACE inhibitors and in combination have demonstrated a reversal of the LV remodeling that occurs with injury and long-standing muscle dysfunction, improves symptoms, prevents rehospitalizations, and prolongs life. Consequently, β blockers are indicated for patients with symptomatic or asymptomatic heart failure and a depressed EF of lower than 40%. Three β blockers have been shown to be effective in reducing mortality in patients with chronic heart failure, including metoprolol succinate (Toprol), bisoprolol, and carvedilol.190–192 In the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), a 34% reduction in mortality was reported in individuals with mild-tomoderate heart failure and moderate-to-severe systolic dysfunction who were taking metoprolol CR/XL compared with placebo.193 In addition, metoprolol CR/XL reduced mortality from both sudden death and progressive pump failure.193 In patients with dilated cardiomyopathy who were supported with a left ventricular assist device (LVAD) and given a specific pharmacologic regimen consisting of an ACE

inhibitor, an angiotensin receptor blocker, an aldosterone antagonist, and a β blocker, followed by treatment with a β2-adrenergic receptor agonist (clenbuterol), improvement in the myocardium resulted in explantation of the LVAD, as well as an improvement in quality of life and absence of recurrent heart failure for 1 to 4 years.194 Thus β blockers, in addition to other pharmacologic agents like ACE inhibitors, play a significant role in LV remodeling. Recent studies indicate that β blockers can be started as early as during the hospitalization after an acute injury and should be continued for a minimum of 1 year postinjury date to optimize the ventricular remodeling.190–192

Anticoagulation The patient hospitalized with heart failure is at increased risk for thromboembolic complications and deep venous thrombosis and should receive prophylactic anticoagulation with either intravenous unfractionated heparin or subcutaneous preparations of unfractionated or low-molecular-weight heparin, unless contraindicated.195

Mechanical Management Implantable Cardiac Defibrillator Implantation Implantable cardiac defibrillator implantation is recommended in the 2013 American Heart Association guidelines for the treatment of CHF for patients with an EF less than or equal to 35% and mild-to-moderate symptoms of heart failure and in whom survival with good functional capacity is otherwise anticipated to extend beyond 1 year.196 Implantable cardiac defibrillator implantation should not be considered until medical therapy has been maximized and the patient’s EF is measured under the current medical therapy.196 Implantable cardiac defibrillators are not indicated in patients with refractory symptoms of heart failure (stage D) or in patients with concomitant diseases that would shorten their life expectancy independent of CHF.196

Cardiac Resynchronization Therapy In individuals with heart failure with abnormalities in the chamber size, ventricular dyssynchrony often exists. The consequences of dyssynchrony include suboptimal ventricular filling, a reduction in the rate of rise of ventricular contractile force or pressure, prolonged duration of mitral regurgitation, and paradoxical septal wall motion.176,177,179 These same individuals may demonstrate a prolonged QRS on the electrocardiogram (>0.12 seconds). Ventricular dyssynchrony has also been associated with increased mortality in heart failure patients.197 As a result, electrical stimulation (activation) of the right and left ventricles in a synchronized manner can be provided by a biventricular pacemaker device. This approach, called cardiac resynchronization therapy (CRT), may improve ventricular contraction and reduce the degree of secondary mitral regurgitation.58,59 In addition, the short-term use of CRT is associated with improvements in cardiac function and hemodynamics without an accompanying increase in oxygen use.198 When CRT was added to patients on optimal medical therapy who continued to have symptoms, significant improvement was noted in quality of life, functional class, exercise capacity and 6MWD, and EF.68,69,146 In a meta-analysis of several CRT trials, heart failure hospitalizations were reduced by 32% and all-cause mortality by 25%.69,197

Special Measures Patients who respond unfavorably to the aforementioned methods of treatment for CHF and CMD and who demonstrate signs and symptoms of severe CHF are frequently managed using several rather extreme methods. As noted in Table 4-12, there are three “special measures” categories for treating CHF and CMD: dialysis and ultrafiltration, assisted circulation, and cardiac transplantation.

Dialysis and Ultrafiltration The mechanical removal of fluid from the pleural and abdominal cavities of patients with

CHF is usually unnecessary, but patients unresponsive to diuretic therapy because of severe CHF or insensitivity to diuretics may be in need of peritoneal dialysis or extracorporeal ultrafiltration.23,159 The mechanical removal of fluid in patients with acute respiratory distress because of large pleural effusions or diaphragms elevated by ascites (both of which compress the lungs) frequently brings rapid relief of dyspnea. However, mechanical removal of fluid (primarily peritoneal dialysis) may be associated with risk of pneumothorax, infection, peritonitis, hypernatremia, hyperglycemia, hyperosmolality, and cardiac arrhythmias.159,199 Cardiovascular collapse may also occur if too much fluid is removed or if removal takes place too rapidly. It is recommended that no more than 200 mL of fluid per hour be removed and no more than 1500 mL of pleural fluid be removed during dialysis.159,199

FIGURE 4-23 The intraaortic balloon pump. Inflation and deflation of the intraaortic balloon pump improve diastolic and systolic heart function, respectively.

For these reasons, as well as for simplicity, cost effectiveness, and long-lasting effects, ultrafiltration has become the treatment of choice for patients in need of mechanical fluid removal.199 Extracorporeal ultrafiltration removes plasma water and sodium via an ultrafiltrate (a blend of water, electrolytes, and other small molecules with concentrations identical to those in plasma) from the blood by convective transport through a highly permeable membrane. Ultrafiltration can be performed vein to vein using an extracorporeal pump or with an arteriovenous approach.199 Although hemodynamic side effects (hypotension, organ malperfusion, and hemolysis) are also possible with ultrafiltration, proper monitoring of the rate of blood flow through the filter (rates above 150 mL/min or below 500 mL/hr are tolerated without side effects), as well as right atrial pressure (ultrafiltration should be discontinued when the right atrial pressure falls to 2 or 3 mm Hg)200 and hematocrit levels (should not exceed 50%), should, for the most part, prevent them.199

Assisted Circulation

Several methods of treatment assist the circulation of blood throughout the body. Perhaps the most widely used is intraaortic balloon counterpulsation via the intraaortic balloon pump (IABP). The IABP catheter is positioned in the thoracic aorta just distal to the left subclavian artery via the right or left femoral artery (Fig. 4-23). Inflation of the balloon occurs at the beginning of ventricular diastole, immediately after closure of the aortic valve. This increases intraaortic pressure and diastolic pressure in general and forces blood in the aortic arch to flow in a retrograde direction into the coronary arteries. This mechanism of action is referred to as diastolic augmentation and profoundly improves oxygen delivery to the myocardium.201 In addition to this physiologic assist (greater availability of oxygen for myocardial energy production) to improve cardiac performance, hemodynamic assistance is also obtained as the balloon deflates just before systole, which decreases left ventricular afterload by forcing blood to move from an area of higher pressure to one of lower pressure to fill the space previously occupied by the balloon.201 Consequently, the intraaortic balloon pump causes “a 10% to 20% increase in cardiac output as well as a reduction in systolic and an increase in diastolic arterial pressure with little change in mean pressure. There is also a diminution of heart rate and an increase in urine output.”201 In addition, intraaortic balloon counterpulsation produces a reduction in myocardial oxygen consumption “and decreased myocardial ischemia and anaerobic metabolism,”201 all of which are very important in the management of CHF and CMD. The IABP is occasionally used in conjunction with a slightly different but similar treatment called pulmonary artery balloon counterpulsation (PABC) in the pulmonary artery versus the thoracic aorta, which is helpful in treating right ventricular and biventricular failure unresponsive to inotropic drugs and the IABP alone.201

Ventricular Assist Devices A ventricular assist device (VAD) is a mechanical pump that provides support to a failing ventricle, either the LV, right ventricle, or both (Fig. 4-24). The VAD can act as a bridge to transplant or bridge to recovery for those patients in whom ventricular function is expected to return, as a bridge to decision for patients whose status is declining and a decision on transplant eligibility is pending, or as a destination therapy for patients ineligible for heart transplant. First-generation VADs consisted of a flexible polyurethane blood sac and diaphragm placed within a rigid case outside the body that provided a pulsatile flow of blood. Second-generation VADs, which provide a continuous flow of blood, utilize a rotary pump implanted in the thoracic cavity to divert blood from the LV and propel it directly to the ascending aorta and the rest of the body. A drive line exits the patient’s abdomen and attaches to a system controller that controls pump operations. Third-generation VADs are now employing a bearingless rotary pump implanted directly into the apex of the heart. Therapists working with patients who have a VAD must be aware of special precautions and safety mechanisms related to the VAD, including lowflow alarms, low-pressure alarms, and loss of standard vital signs. See Chapter 12 for more information on VADs.

Surgical Management Reparative, reconstructive, excisional, and ablative surgeries are sometimes performed in the treatment of CHF and CMD. Reparative procedures correct cardiac malfunctions such as ventricular septal defect, atrial septal defect, and mitral stenosis, and frequently improve cardiac hemodynamics, resulting in improved cardiac performance. Coronary artery bypass graft surgery is probably the most common reconstructive surgery because myocardial ischemia and infarction are the primary causes of CMD and CHF.202 Its effects are often profound, improving cardiac muscle function and eliminating CHF. Reconstruction of incompetent heart valves is also common.18 Excisional procedures in patients with atrial myxomas (tumors) and large LVs are employed less often. The excision of a tumor or aneurysm is occasionally performed, and the excised area is replaced with Dacron patches.18 Ablative procedures are also used less frequently, but for patients with persistent and symptomatic Wolff–Parkinson–White syndrome or intractable ventricular tachycardia, ablation (e.g., via laser or cryotherapy) of the reentry pathways appears to be very therapeutic.18 The surgical implantation of automatic implantable defibrillators is increasingly common and appears to be of great therapeutic value for those with ventricular tachycardia that is unresponsive to medications and ablative procedures.18

FIGURE 4-24 Left ventricular assist device (LVAD). The left ventricular assist device provides myocardial assistance until heart transplantation or corrective measures are taken. (From Monahan FD, Sands JK, Neighbors M: Phipps’ Medical-Surgical Nursing, Health and Illness Perspectives, ed 8, St. Louis, 2007, Mosby.)

Abandoned Procedures Although somewhat unusual, the use of muscle flaps (cardiomyoplasty), usually dissected from the latissimus dorsi or trapezius muscle, had been an alternative treatment for a limited number of patients with severe CMD and CHF.203 The muscle flap is wrapped around the LV and attached to a pacemaker, which stimulates the flap to contract, thus contracting the LV. Also, initial investigations appeared to indicate that the removal of dilated, noncontracting myocardium (partial left ventriculectomy or Batista procedure) of persons with CHF and subsequent suturing of remaining viable myocardial tissue decreased the left ventricular chamber size and improved myocardial performance. These procedures have been largely abandoned due to lack of evidence for clinical benefit.204–207

Cardiac Transplantation Cardiac transplantation is the last treatment effort for a patient with CHF and CMD because “potential recipients of cardiac transplants must have end-stage heart disease with severe heart failure and a life expectancy of less than 1 year.”159 Heart transplantation can be heterologous (or xenograft, from a nonhuman primate) or, more commonly, homologous (or allograft, from another human).159 Orthotopic homologous cardiac transplantation is performed by removing the recipient’s heart and leaving the posterior walls of the atria with their venous connections on which the donor ’s atria are sutured. In heterotopic homologous cardiac transplantation, the recipient’s heart is left intact and the donor heart is placed in parallel, with anastomoses between the two right atria, pulmonary arteries, left atria, and aorta. Orthotopic heart transplantation is most commonly performed. Chapter 12 provides a more complete description of cardiac transplantation.

Prognosis As a result of multivariate analysis of clinical variables, the most significant predictors of survival in individuals with CHF have been identified and include decreasing LVEF, worsening NYHA functional status, degree of hyponatremia, decreasing peak exercise oxygen uptake, decreasing hematocrit, widened QRS on 12-lead electrocardiogram, chronic hypotension, resting tachycardia, renal insufficiency, intolerance to conventional therapy, and refractory volume overload.208,209 In addition, elevated circulating levels of neurohormonal factors are associated with high mortality rates, but routine laboratory assessment of norepinephrine or endothelin is neither practical nor helpful in managing the patient’s clinical status. Likewise, elevated BNP (or NT-proBNP) levels predict higher risk of heart failure and other events after myocardial infarction, whereas marked elevation in BNP levels during hospitalization for heart failure may predict rehospitalization and death. However, controversy still exists regarding BNP measurement and its prognostic value.208,209 Currently, a few mathematical models exist to help predict outcome in heart failure patients for clinicians managing treatment. Aaronson and colleagues developed a noninvasive risk stratification model based upon clinical findings and peak VO2 that includes seven variables: presence of ischemia, resting heart rate, LVEF, presence of a QRS duration greater than 200 msec, mean resting blood pressure, peak VO2, and serum sodium.210 A heart failure score was then developed and related to subsequent morbidity and mortality. The model defined low-, medium-, and high-risk groups based upon 1-year event-free survival rates of 93%, 72%, and 43%, respectively. Interestingly, adding invasive data did not improve the prediction. Campana and coworkers developed a model using cause of heart failure, NYHA functional class, presence of an S3 gallop, cardiac output, mean arterial pressure, and either pulmonary artery diastolic pressure or pulmonary capillary wedge pressure.211 Patients were risk stratified into low-, intermediate-, and high-risk groups for 1-year event-free survival rates of 95%, 75%, and 40%, respectively.211 For three other clinical scoring systems for evaluation of heart failure (Framingham, Boston, and National Health and Nutritional Examination Surveys [NHANES]), see Box 4-6 and Table 4-13.

Physical Therapy Assessment Because of the increase in number of patients with CHF, physical therapists in all practice settings are seeing these individuals and are responsible for assessing functional status and providing optimal treatment to improve the quality of their lives and possibly decrease morbidity and mortality. Although Chapter 16 provides cardiopulmonary assessment in detail and Chapter 18 provides detailed interventions, a brief overview of assessment and interventions for individuals with CHF is provided here. A thorough assessment includes an interview that should include a series of questions: ▪ When did your symptoms start? ▪ Are your symptoms stable or are they getting worse? ▪ Are symptoms provoked or do they occur at rest? ▪ Are there accompanying symptoms such as chest pain or calf claudication? ▪ Is orthopnea or PND present? ▪ How far can you walk? ▪ Do you retain fluid? ▪ Do you restrict sodium in your diet? ▪ What sorts of activities can you no longer do? ▪ Are you losing or gaining weight? ▪ How do you sleep? After the interview, a physical examination should involve an assessment of the patient’s cardiopulmonary status, including: ▪ Notation of symptoms of CHF (dyspnea, PND, and orthopnea) ▪ Evaluation of pulse and electrocardiogram to determine heart rate and rhythm ▪ Evaluation of respiratory rate and breathing pattern ▪ Auscultation of the heart and lungs with a stethoscope

BO X 4- 6 C om pa rison of NHANES, Bost on a nd Fra m ingha m

C rit e ria

▪ Evaluation of radiographic findings to determine the existence and magnitude of pulmonary edema ▪ Performance of laboratory blood studies to determine the PaO2 and PaCO2 levels ▪ Evaluation of the oxygen saturation levels via oximetry ▪ Palpation for fremitus and percussion of the lungs to determine the relative amount of air or solid material in the underlying lung ▪ Performance of sit-to-stand test to evaluate heart rate and blood pressure (orthostatic hypotension) and dyspnea ▪ Objective measurement of other characteristic signs produced by fluid overload, such as peripheral edema, weight gain, and jugular venous distension ▪ Assessment of cardiopulmonary response to exercise (e.g., heart rate, blood pressure, electrocardiogram) ▪ Administration of a questionnaire to measure quality of life Upon the collection of data and the determination of a treatment diagnosis and prognosis, a plan of care is developed for the patient with CHF that details the

interventions that are used to achieve the optimal outcome. Table 4-13 Boston and NHANES-1 clinical scoring systems for heart failure

Diagnosis of heart failure Boston criteria: Definite (8–12 points); Possible (5–7 points); Unlikely (≤4 points). Diagnosis of heart failure NHANES-1 criteria: ≥3 points. NHANES, National Health and Nutrition Examination Surveys. Data from Mosterd A, Deckers JW, Hoes AW, et al: Classification of heart failure in population based research: An assessment of six heart failure scores. Eur J Epidemiol 13(5):491–502, 1997.

Physical Therapy Interventions Exercise Training Exercise training is a therapeutic modality that should be considered for all patients with ventricular dysfunction (Table 4-14). Patients who are prescribed exercise training and other interventions need to be without any overt signs of decompensated heart failure, and should be monitored during treatment to observe for abnormal responses and symptoms. Increased levels of physical activity do not appear to have adverse effects on subsequent cardiac mortality or on ventricular function in patients with ventricular dysfunction. In addition, these patients derive psychological benefits from participation in exercise training, and the close medical surveillance available in the content of a supervised exercise program may facilitate better clinical decisions concerning pharmacologic therapy, interpretation of symptoms, or the necessity for and timing of operative procedures.202 Specific benefits of exercise training for individuals with heart failure include improvement in symptoms, clinical status, and exercise duration.212,213 Other studies have reported improved functional capacity and quality of life and reduced hospitalizations for heart failure.214 There also is indication that exercise training may have beneficial effects on ventricular structure and remodeling.215 The most recent Heart Failure Action Study reported that exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.216,217

Guidelines for Exercise Training Studies that have demonstrated improvements in exercise tolerance and patient symptoms were all performed using different methodologies—varying modes, intensities, durations, and frequencies of exercise (see Table 4-15). Specific guidelines for exercise training of patients with CHF are difficult to implement because patient status frequently changes. Despite a lack of specific guidelines for exercising persons with CHF, the U.S. Department of Health and Human Services Agency for Health Care Policy and Research outlined the importance of exercise training in treatment of CHF.216–218 Exercise training was recommended “as an integral component of the symptomatic management” of persons with CHF “to attain functional and symptomatic improvement but with a potentially higher likelihood of adverse events.” This recommendation was based upon significant scientific evidence from previously published investigations that were reviewed by experts in the field of cardiac rehabilitation.218

Table 4-14 Summary of interventions for CHF Intervention Exerc ise training (in general) Exerc ise training with intravenous inotropic agents

Guidelines Low level, low-impac t exerc ise (e.g., walking) for 5 to 10 min/day gradually inc reasing duration to 30 min. Intensity should be monitored via level of dyspnea or perc eived exertion. Frequenc y: 1 to 2×/day for 5 to 7 days/wk. Progressive inc rease in low-impac t exerc ise with monitoring of blood pressure response. If patient has an ICD, monitor for ICD firing, espec ially with exerc ise.

Exerc ise with LVADs

Progressive inc rease in exerc ise; should demonstrate normal responses. May have flow limitations (10 to 12 L/min), or c ardiovasc ular func tion from the mec hanic ally driven c ardiac output, and the effec ts of a 6-lb mass resting below the diaphragm that may alter ventilatory performanc e. CPAP may func tion to reduc e preload and afterload on heart, and dec rease the workload on inspiratory musc les, whic h may also inc rease lung c omplianc e.

Exerc ise with c ontinuous positive airway pressure (CPAP) Breathing exerc ises

Exerc ise program set at a spec ific perc entage of the maximal inspiratory pressure or maximal expiratory pressure (similar to aerobic exerc ise training) with a devic e that resists either inspiration or expiration. Expiratory musc le training Performed in a variety of ways; most c ommonly with weights upon the abdomen and hyperpneic breathing. Results in improved symptoms, func tional status, and pulmonary func tion and reduc ed pulmonary c omplic ations. May also use positive end-expiratory pressure devic es. Inspiratory musc le training One protoc ol: Threshold inspiratory musc le trainer at 20% of maximal inspiratory pressure, 3 times a day, for 5 to 15 min. Instruc tion in energyBalanc ing ac tivity and rest, and performing ac tivities in an energy-effic ient manner; sc heduling ac tivities and rest. c onservation tec hniques S elf-management Inc orporate individuals into the management of the disease by making them responsible for their own health. tec hniques

Patients with decompensated (uncontrolled) CHF are typically very dyspneic and therefore should not begin aerobic exercise training until the CHF is compensated. Table 4-16 lists specific exercise training guidelines, which include the attainment of a cardiac index of 2.0 L/min/m2 or greater (for invasively monitored patients in the hospital) before aerobic exercise training is implemented and the maintenance of an adequate pulse pressure (not less than a 10 mm Hg difference between the systolic and diastolic blood pressure) during exercise. The development of marked dyspnea and fatigue, S3 heart sound, or crackles during exercise requires the modification or termination of exercise.219 Table 4-15 Rehabilitation and exercise in HF Exerc ise training in patients with HF Cardiac rehabilitation programs for patients with rec ently dec ompensated or advanc ed HF Exerc ise presc ription and exerc ise modalities in HF

S upervised, tailored program with experienc ed c linic ian evaluating appropriateness, stability for exerc ise Gradual mobilization and/or small musc le group strength/flexibility should be c onsidered as soon as possible with experienc ed HF team Moderate-intensity c ontinuous aerobic exerc ise training (walking, jogging, c yc ling) at modified Borg rating of perc eived exertion 3 to 5/10 65% to 85% max heart rate or 50% to 75% of peak VO 2 (need experienc ed evaluator for peak or max testing), keep heart rate 20 bpm below ICD firing range

Data from Moe GW, et al: The 2013 Canadian Cardiovascular Society heart failure management guidelines update: focus on rehabilitation and exercise and surgical coronary revascularization, Can J Cardiol 30: 249-263, 2014.

For most patients, ambulation may be the most effective and functional mode of exercise to administer and prescribe, beginning with frequent short walks and progressing to less frequent, longer bouts of exercise. Occasionally, patients may be so deconditioned that gentle strengthening exercises, restorator cycling, or ventilatory muscle training is the preferred mode of exercise conditioning. As strength and endurance improve, patients can be progressed to upright cycle ergometry or ambulating with a rolling walker.

Because dyspnea is the most common complaint of patients with CHF, the level of dyspnea or Borg rating of perceived exertion appears to be an acceptable method to prescribe and evaluate an exercise program.202 This is supported by the observation that these subjective indices correlate well with training heart rate ranges in this patient population.220 Therefore a basic guideline of increasing the exercise intensity to a level that produces a moderate degree of dyspnea (conversing with modest difficulty, ability to count to 5 without taking a breath, or a Borg rating of 3 on a scale of 10) may be the simplest and most effective method to prescribe exercise for patients with CHF. It also appears to be the most effective method to progress a patient’s exercise prescription. The exercise prescription of patients with CHF can be progressed when (1) the cardiopulmonary response to exercise is adaptive (see Table 4-15) and (2) workloads that previously produced moderate dyspnea (e.g., Borg rating of 3/10) produce mild dyspnea (e.g., Borg rating of 2/10 or less). Because an increasing number of patients with CMD and CHF are being prescribed β blockers, which often cause little or no change in resting and exercise heart rates, the Borg rating scale again is a good clinical tool. In addition, instructing patients to increase the respiratory rate to a level that allows one to converse comfortably may be another method for prescribing exercise training in patients with CHF (“talk test”).202 Table 4-16 Exercise training guidelines for patients with CHF

From Cahalin LP: Heart failure, Phys Ther 76(5):516, 1996.

The end result of such exercise assessments and exercise training is an improved quality of life for patients with CHF.

Exercise Training and Quality of Life The quality of life of persons with CHF appears to be related to the ability to exercise.145,147,148,214,221–227 Two recent studies have investigated the effects of exercise training upon the quality of life of persons with CHF. Kavanagh and associates147 and Keteyian and associates224 found significant improvements in exercise capacity, symptoms, and quality of life after 24 and 52 weeks of exercise training, respectively. A recent meta-analysis found that exercise training improved functional capacity and

quality of life in patients with HFpEF.228 An overview of Cochrane systematic reviews also found that quality of life does appear to be improved after exercise training in persons with CHF.229

Exercise Training During Continuous Intravenous Dobutamine Infusion Many patients with severe CHF are hospitalized for prolonged periods, receiving continuous IV dobutamine infusion for inotropic support (to improve cardiac muscle contraction) while awaiting cardiac transplantation.230 Also, it is becoming common practice for patients with severe CHF to be occasionally hospitalized for IV dobutamine infusion (“dobutamine holiday”) to transiently improve myocardial performance.231 Many patients are also being sent home on portable IV dobutamine pumps; their physical activity is less restricted when the large IV pumps are not used.232 However, exercise training during continuous IV dobutamine infusion has received little attention.233 Individuals receiving inotropic support have only recently been prescribed exercise training programs.234 Kataoka and associates233 presented the results of a single case study in which a 53-year-old man with CHF was prescribed an exercise training program while receiving 10 µg/kg/min IV dobutamine (which he had been prescribed for 10 months before exercise training). Positive training adaptations were observed without complication and resulted in the patient being weaned from dobutamine.234 In the ESSENTIAL trial, no adverse effects occurred when exercising patients with heart failure on enoximone, yet clinically significant differences were not reported between the treatment and the placebo groups.235 The 6MWD was increased in the group with the inotrope support, but was not statistically significant, and no improvement in other clinical outcomes were reported.235

Exercise Training with Ventricular Assist Devices Particular adjuncts to exercise conditioning in CHF include mechanical support of severe CMD via IABP and left or right VADs. Although individuals with IABPs are limited to breathing exercises and gentle exercise with upper extremities and the noncatheterized leg, individuals with VADs have enjoyed the freedom to exercise with minimal limitation. Improved technology has enabled patients who otherwise were immobilized because of IABP placement or nonmobile VAD placement to become mobile and ambulate with a cart or electric belt system that provides left ventricular assistance via portable pumping of the heart.236–238 Patients using LVADs underwent 1173.6 hours of exercise conditioning without major complication and with only four minor complications (3.4 incidents per 1000 patient hours). The four minor complications were quickly corrected and resulted from an acute decrease in pump flow from venous pooling, decreased driveline air volume, and hypovolemia. Improvements in exercise tolerance and functional capacity continued until week 6 of conditioning, after which further improvements were minimal. It has been suggested that delay in cardiac transplantation until 6 weeks of exercise conditioning have been performed may improve postoperative recovery and surgical

success.239 The reason for a lack of further improvement in exercise tolerance and functional capacity after week 6 was most likely because of the mechanical constraints of the LVAD. Cardiopulmonary exercise testing has demonstrated that LVAD patients demonstrate a modest training effect from chronic exercise training and appear to be limited at maximal exercise by the mechanics of the LVAD.240 The mechanical constraints of the LVAD appear to prevent maximal levels of exercise from being attained and result in no substantial change in peak oxygen consumption after a mean of 16 weeks of aerobic exercise training. Possible mechanical constraints of the LVAD include flow limitations (10 to 12 L/min), altered cardiovascular function from the mechanically driven cardiac output, and the effects of a 6-lb mass resting below the diaphragm that may alter ventilatory performance. Limited training adaptations may also be a result of the same mechanism, but the reductions in submaximal heart rate and blood pressure, as well as increases in exercise duration, ventilation, and oxygen consumption at the ventilatory threshold, support the benefits that can be attained by exercising patients on LVAD.237,238,240

Exercise Training During Continuous Positive Airway Pressure Ventilation Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) have been observed to improve the exercise performance of patients with obstructive lung disease.241–243 Despite the lack of research on the effect of CPAP or BiPAP upon the exercise performance of patients with CHF, resting myocardial performance has repeatedly been observed to improve with CPAP in patients with CHF244–246 and patients with CHF and coexistent obstructive or central sleep apnea.247–249 The beneficial effect of CPAP upon cardiac performance is postulated to be caused by increased intrathoracic pressure, which reduces cardiac preload (by impeding cardiac filling) and afterload (by reducing left ventricular transmural pressure),244,245,249–251 as well as unloading the inspiratory muscles by providing positive pressure ventilation that may increase lung compliance.246 The effects of CPAP or BiPAP upon exercise performance in patients with CHF are unknown, but several studies cited here have noted an improvement in dyspnea and functional status and exercise tolerance.252

Ventilation Ventilatory Muscle Training Breathing Exercises Persons with CHF appear to benefit from breathing exercises.253,254 Breathing exercises can be simple or complex and should be provided after a measurement of breathing strength is obtained. Such measurements include the maximal inspiratory pressure (MIP) and the maximal expiratory pressure (MEP), which are frequently measured with a manometer in centimeters of water. After strength measurements are obtained, patients are provided a breathing exercise program at a specific percentage of the MIP or MEP (similar to aerobic exercise training) with a device that resists either inspiration or expiration. The methods of measuring MIP and MEP and implementing a ventilatory muscle training program are provided.253,254 Facilitation of diaphragmatic breathing and inhibition of excessive accessory muscle use may decrease the work of breathing for a person with CHF and in conjunction with pursed-lip breathing may improve respiratory performance and, possibly, cardiac performance. Pursed-lip breathing is beneficial for persons with COPD by maintaining airway patency via increased positive end-expiratory pressure (PEEP).255,256 In view of recent research, the same maintenance of airways from increased PEEP may be helpful for persons with CHF.257,258 Furthermore, the increased PEEP and associated increase in intrathoracic pressure from varying degrees of pursed-lip breathing may decrease venous return, which could possibly decrease the left VEDV and pressure and improve myocardial performance for persons with severe CHF.259

Expiratory Muscle Training The majority of studies investigating the effects of expiratory muscle training have involved persons with spinal cord injury or other neurologic disorders. In the majority of these studies, expiratory muscle training (performed in a variety of ways, but most commonly with weights on the abdomen and hyperpneic breathing) improved symptoms, functional status, and pulmonary function and reduced pulmonary complications. There is recent interest in expiratory muscle training of persons with various forms of COPD using PEEP devices, but very little literature exists. Likewise, there is little literature regarding expiratory muscle training alone in CHF. A study by Mancini and associates evaluated the effects of inspiratory and expiratory muscle training in CHF and found significant improvements in ventilatory muscle force and endurance, submaximal and maximal exercise performance, and dyspnea after 3 months of aggressive ventilatory muscle training in eight patients with chronic CHF.254 Despite a lack of research in expiratory muscle training alone in CHF, the observations of Mancini and associates254 and others suggest that expiratory muscle training may be beneficial for persons with CHF by (1) increasing expiratory muscle strength to improve pulmonary function; (2) increasing PEEP to improve airway compliance; and (3) possibly

decreasing venous return and the left VEDV to improve myocardial performance.259 These changes may improve the exercise tolerance and functional status of persons with CHF. However, further investigation is needed in this area.

Inspiratory Muscle Training Inspiratory muscle training has previously been shown to be helpful for patients with pulmonary disease by increasing ventilatory muscle strength and endurance and by decreasing dyspnea, need for medications, emergency room visits, and number of hospitalizations.260,261 Individuals with chronic CHF have been found to have poor ventilatory muscle strength,262–264 yet after inspiratory muscle training demonstrated significant improvements in ventilatory muscle strength and endurance, as well as dyspnea.254,265 Significant improvements in maximal inspiratory and expiratory pressures and degree of dyspnea were recently observed as soon as 2 weeks after ventilatory muscle training was initiated with the threshold inspiratory muscle trainer at 20% of MIP, three times a day, for 5 to 15 minutes (Fig. 4-25).253 The improvement in ventilatory muscle strength was associated with significantly less dyspnea at rest and with exercise. However, the effects of ventilatory muscle training upon ventilatory muscle endurance, which may be the most important effect of ventilatory muscle training in this patient population, were not evaluated. Nonetheless, improvement in ventilatory muscle strength may decrease the dependency, impairment, and possibly even cost associated with chronic CHF. Increased ventilatory muscle strength may also enhance early postoperative recovery in patients undergoing cardiac transplantation or other cardiac surgery.

FIGURE 4-25 Demonstrates the effect size of inspiratory muscle training compared with control groups. These studies worked at a percentage of maximum inspiratory pressure at gradually increasing resistances. It is recommended to start working at 20% to 30% of PImax. (Data from Lin SJ1, McElfresh J, Hall B, et al: Inspiratory muscle training in patients with heart failure: a systematic review. Cardiopulm Phys Ther J 23(3):29-36, 2012.)

Instruction in Energy Conservation Energy conservation techniques should be included in the interventions for individuals with heart failure to decrease the workload on the heart without loss of function. An analysis of all the activities an individual performs helps to develop an inventory to set priorities and organize the individual’s day. Particular attention should be paid to activities that create fatigue or increased dyspnea. Box 4-7 provides suggestions for conserving energy for patients with heart failure.

Self-Management Techniques Chronic disease management programs should identify the patients who are at high risk for morbidity and mortality and incorporate the individual into the management of the disease by making him or her responsible for his or her own health. Disease management programs for heart failure should include components that not only improve the management of the disease, but also demonstrate improved outcomes and reduction of costs. These components include:266

BO X 4- 7 Ene rgy conse rva t ion t e chnique s for individua ls wit h

he a rt fa ilure • Sit while working whenever possible. • Before you get tired, stop and rest. • Spread tedious tasks out throughout the week. • Do the tasks that require the most energy at times that you have the most energy. • Alternate easy tasks with difficult tasks, and plan a rest period. • Devote a portion of your day to an activity you enjoy and find relaxing. • Keep items within easy reach. • Plan ahead so you don’t have to rush or push yourself hard. • Decide activities that are not necessary for you to do, and delegate to other family members or caregivers; share the work. ▪ Individualized, comprehensive patient and family or caregiver education and outpatient counseling ▪ Optimization of medical therapy ▪ Vigilant follow-up ▪ Increased access to health care professionals ▪ Early attention to fluid overload ▪ Coordination with other agencies as appropriate ▪ Physician-directed care (and/or use of nurse coordinators or nurse-managed care) ▪ Specific content for patient and family education and counseling should include: • Discussion of limitation of dietary sodium to 1500 mg/day • Adherence to medication regimen • Regular flu and pneumococcal immunizations • Importance of daily weighing and monitoring of symptoms (shortness of breath, dizziness, or swelling) • Instruction in signs/symptoms of decompensation (excessive shortness of breath, fatigue, peripheral swelling, waking at night with dyspnea or cough, etc.) • Instruction in importance of seeking assistance when necessary • Adherence to regular exercise program • Limitation of alcohol intake • Control of comorbid conditions (diabetes, elevated blood pressure, elevated lipids) This educational content is much better received and remembered if given when the patient is in an outpatient versus an inpatient setting. Inpatient education is usually inadequate as well, as individuals do not retain what they are taught in the hospital. Individuals who are in the hospital are usually ill, anxious, distracted, or in poor condition to listen, learn, and retain any instructions. Instruction in self-management techniques after a critical event resulting in hospitalization results in improved adherence, if the patient is ready and able to learn, and in improved management of the disease.

Summary ▪ Causes of CMD include: • Myocardial infarction or ischemia • Cardiomyopathy • Cardiac arrhythmias • Heart valve abnormalities • Pericardial effusion or myocarditis • Pulmonary embolus • Pulmonary hypertension • Renal insufficiency • Spinal cord injury • Congenital abnormalities • Aging ▪ The term cardiac muscle dysfunction accurately describes the primary cause of pulmonary edema, as well as the underlying pathophysiology, which essentially impairs the heart’s ability to pump blood or the LV’s ability to accept blood. ▪ Cardiomyopathy, congenital abnormalities, renal insufficiency, and aging are associated more commonly with chronic heart failure, whereas the other factors tend to cause acute CHF. ▪ Right-sided or left-sided CHF simply describes which side of the heart is failing, as well as the side initially affected and behind which fluid tends to localize. ▪ Heart failure with reduced EF is the description associated with heart failure and is the result of a low cardiac output at rest or during exertion. Heart failure with preserved EF usually results from a volume overload. ▪ The impaired contraction of the ventricles during systole that produces an inefficient expulsion of blood is termed systolic heart failure. Diastolic heart failure is associated with an inability of the ventricles to accept the blood ejected from the atria. ▪ Hypertension and coronary artery disease are the most common causes of CMD. ▪ Cardiac arrhythmias and renal insufficiency can also cause CMD for reasons similar to those of myocardial infarction. ▪ Cardiomyopathies are classified from a functional standpoint, emphasizing three categories: dilated, hypertrophic, and restrictive. ▪ Heart valve abnormalities can also cause CMD as blocked or incompetent valves, or both, cause heart muscle to contract more forcefully to expel the cardiac output. ▪ Injury to the pericardium can cause acute pericarditis, which may progress to pericardial effusion. ▪ Cardiac muscle dysfunction from a pulmonary embolus is the result of elevated pulmonary artery pressures, which dramatically increase right ventricular work. ▪ Spinal cord injury can also produce CMD because of cervical spinal cord transection, which causes an imbalance between sympathetic and parasympathetic control of the cardiovascular system. ▪ Congestive heart failure is commonly associated with several characteristic signs and

symptoms, including dyspnea, tachypnea, PND, orthopnea, hepatomegaly, peripheral edema, weight gain, jugular venous distension, rales, tubular breath sound and consolidation, presence of an S3 heart sound, sinus tachycardia, and decreased exercise tolerance. ▪ Proteinuria; elevated urine specific gravity, BNP, BUN, and creatinine levels; and decreased erythrocyte sedimentation rates are associated with CHF. ▪ Dyspnea is probably the most common finding associated with CHF. ▪ A rapid respiratory rate at rest, characterized by quick and shallow breaths, is common in patients with CHF. ▪ The presence of an S3 heart sound indicates a noncompliant left ventricle and occurs as blood passively fills a poorly relaxing LV. ▪ The retention of sodium and water is caused by (1) augmented α-adrenergic neural activity; (2) circulating catecholamines; and (3) increased levels of circulating and locally produced angiotensin II, resulting in renal vasoconstriction. ▪ Laboratory findings suggestive of impaired renal function in CHF include increases in BUN, as well as blood creatinine levels and BNP. ▪ Pulmonary edema can be cardiogenic or noncardiogenic in origin. ▪ The most common hematologic abnormality is a secondary polycythemia, which is caused by either a reduction in oxygen transport or an increase in erythropoietin production. ▪ Skeletal muscle abnormalities caused by dilated and hypertrophic cardiomyopathies have been reported previously and consistently reveal type I and type II fiber atrophy. Genetic causes may also contribute to muscle atrophy. ▪ Severe CMD has the potential to reduce blood flow to the pancreas, which impairs insulin secretion and glucose tolerance. ▪ The primary malnutrition in CHF is a protein-calorie deficiency, but vitamin deficiencies have also been observed. ▪ The specific treatments for CHF include restriction of sodium intake, use of medications, and self-management techniques. ▪ Many patients with CHF apparently have lower anaerobic thresholds, and the resultant anaerobic metabolism (because of acidosis) becomes the limiting factor in exercise performance. ▪ Although echocardiography is the most widely used method for the confirmation of the clinical diagnosis of heart failure, BNP is rapidly emerging as a very sensitive and specific adjunctive diagnostic marker.66 It may also be an important prognostic marker and can be used as a rapid screening test in the urgent care setting.65,66 Greater levels of ANP and BNP have also been found to be associated with higher morbidity and mortality rates. ▪ Plasma BNP, although consistently increased in patients with heart failure because of systolic dysfunction, is also increased in some patients with aortic stenosis, chronic mitral regurgitation, diastolic heart failure, and hypertrophic cardiomyopathy. ▪ The most significant predictors of survival in individuals with CHF have been identified

and include decreasing LVEF, worsening NYHA functional status, degree of hyponatremia, decreasing peak exercise oxygen uptake, decreasing hematocrit, widened QRS on 12-lead electrocardiogram, chronic hypotension, resting tachycardia, renal insufficiency, intolerance to conventional therapy, and refractory volume overload.

Case study 4-1 An 85-year-old woman had a medical history of coronary artery bypass graft surgery in 1992 to the right coronary artery and left anterior diagonal artery, cholecystectomy, hiatal hernia, gastritis, and peptic ulcer disease. She was admitted August 9, 2010, with angina (a myocardial infarction was ruled out) and underwent cardiac catheterization on August 16, 2010, which revealed 99% occlusion of the right coronary artery graft, 85% occlusion of the left anterior diagonal artery graft, 95% stenosis of the circumflex artery, moderate mitral regurgitation, dilated left atrium, inferior hypokinesis, and an EF of approximately 30%. Echocardiographic study revealed severe left ventricular hypertrophy with a small left ventricular chamber size, inferior hypokinesis, calcified mitral valve with moderate mitral regurgitation, abnormal left ventricular compliance (left ventricular stiffness), and a dilated left atrium. The referral for cardiac rehabilitation was written on August 11, 2010, at which time the patient was assessed and complained of left scapular pain that increased with deep breathing (different from previous angina and altered with breathing pattern). Physical examination revealed normal sinus rhythm and slightly decreased breath sounds in the left lower lobe. The patient ambulated approximately 250 feet with an adaptive heart rate and blood pressure response, without angina. The patient continued with twice-daily cardiac rehabilitation, increasing the distance ambulated to 800 feet, and underwent a thallium treadmill stress test on August 13, 2010. The patient completed 2 minutes 25 seconds of the modified Bruce protocol (attaining a maximal heart rate of 104 bpm, 67% of the age-predicted maximal heart rate), which was terminated because of leg fatigue. The patient experienced no angina and demonstrated no ECG changes consistent with myocardial ischemia. The thallium scan demonstrated moderately severe stress-induced ischemic change in the inferior and septal areas. Cardiac rehabilitation was performed August 14, 2010, through August 16, 2010, during which the patient walked 5 to 10 minutes (500 to 1000 feet) with adaptive heart rate and blood pressure responses to exercise, without angina. On August 17, 2010, while resting in bed, the patient developed severe angina and dyspnea, which required morphine sulfate, nitroglycerin, and heparin, suggesting impending graft occlusion. In view of these findings, coronary artery bypass graft surgery was repeated on August 20, 2010, after which the patient developed numerous complications, requiring intraaortic balloon pump assistance from which weaning was difficult. In addition, the patient experienced a postoperative anterolateral myocardial infarction as a result of a

third-degree heart block that decreased the blood supply to the myocardium, respiratory failure that required full ventilatory support, congestive heart failure, and severe abdominal distension. The patient’s status further deteriorated as she became anemic and was unable to maintain adequate nutritional requirements. However, a radiograph on August 24, 2010, revealed no evidence of CHF, and ventilatory measurements demonstrated improved pulmonary function. In addition, hemoglobin and hematocrit levels were slightly increased (10.7 and 29.4, respectively). The patient was extubated on August 25, 2010, and began ambulation with nursing on August 26, 2010, during which she complained of severe abdominal pain and a feeling of increased abdominal swelling. Because of persistent abdominal pain and distension, an exploratory laparotomy was performed on August 28, 2010, resulting in resection of the small bowel. The patient remained on bed rest for 3 days, after which she began ambulating with nursing. On September 4, 2010, the patient ambulated 50 feet with physical therapy, during which she complained of severe dyspnea and mild-to-moderate abdominal discomfort. For this reason, physical therapy discontinued ambulation but continued chest physical therapy and bedside exercise to the upper and lower extremities. However, nursing continued to ambulate the patient approximately four times per day despite her complaints of severe shortness of breath and abdominal discomfort. On September 6, 2010, immediately after walking, she developed severe abdominal discomfort associated with nausea and vomiting. Nonetheless, that evening, the patient was ambulated 200 feet, walking approximately 15 minutes, at which time she complained of severe abdominal pain; her respiratory rate was noted to be in the high 50s. On September 7, 2010, the patient was again walked approximately 75 feet with a walker and maximal assist of three, at which time she became unresponsive. Physician examination at this time revealed severe tachypnea and abdominal distension. On September 10, 2010, the patient’s status further deteriorated with effusion and atelectasis of the left lung base, ischemic bowel, possible abdominal infection, anemia, and azotemia. She expired on September 11, 2010.

Discussion This case study is an example of an 85-year-old patient who underwent bypass surgery after the following occurred: 1. She remained asymptomatic during prolonged cardiac rehabilitation exercise assessments with adaptive heart rate and blood pressure responses, but somewhat paradoxically developed angina at rest. 2. A thallium treadmill stress test demonstrated moderately severe ischemic change. 3. A cardiac catheterization revealed occluded grafts to the right coronary artery and left anterior diagonal artery and high-grade occlusion of the circumflex artery, inferior hypokinesis, and depressed EF (approximately 30%). Unfortunately, after bypass surgery was performed, the patient developed numerous complications caused primarily by pump failure and improper exercise training that was not appropriately adjusted to the patient’s needs. At no time should a patient be

ambulated with moderate-to-severe pain (whatever the location or cause), as it most likely represents a pathologic process (in this case, ischemia of the small intestine). In addition, inappropriate responses to exercise training, such as a rapid heart rate or respiratory rate with minimal exercise, must be reassessed and treated before subsequent exercise is performed, or at least changes must be made in the type of exercise performed. Sitting lower extremity exercise would have been much more appropriate for this patient, who demonstrated many interrelated pathophysiologic processes that were exacerbated by improper exercise training and ultimately led to her death.

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Restrictive lung dysfunction Ellen Hillegass, Tamara Klintworth-Kirk, and Karlyn Schiltgen

CHAPTER OUTLINE Etiology 126 Pathogenesis 126 Compliance 126 Lung Volumes 126 Work of Breathing 128 Clinical Manifestation 129 Signs 129 Symptoms 129 Treatment 129 Maturational Causes of Restrictive Lung Dysfunction 129 Abnormalities in Fetal Lung Development 129 Respiratory Distress Syndrome 130 Bronchopulmonary Dysplasia 131 Normal Aging 131 Interstitial Causes 133 Idiopathic Pulmonary Fibrosis 133 Sarcoidosis 134 Bronchiolitis Obliterans 136 Environmental/Occupational Causes 137 Coal Workers’ Pneumoconiosis 137 Silicosis 137 Asbestosis 139 Infectious Causes 140 Pneumonia 140 Neoplastic Causes 145 Bronchogenic Carcinoma 145 Pleural Diseases 147 Pleural Effusion 147

Atelectasis 150 Acute Respiratory Distress Syndrome/Acute Lung Injury 150 Cardiovascular Causes 152 Pulmonary Edema 152 Pulmonary Emboli 154 Neuromuscular Causes 157 Spinal Cord Injury 157 Amyotrophic Lateral Sclerosis 158 Poliomyelitis 159 Guillain–Barré Syndrome 160 Myasthenia Gravis 161 Tetanus 161 Pseudohypertrophic (Duchenne) Muscular Dystrophy 162 Other Muscular Dystrophies 162 Musculoskeletal Causes 163 Diaphragmatic Paralysis or Paresis 163 Kyphoscoliosis 164 Ankylosing Spondylitis 165 Pectus Excavatum 166 Pectus Carinatum 166 Connective Tissue Causes of RLD 166 Rheumatoid Arthritis 166 Systemic Lupus Erythematosus 168 Scleroderma 169 Polymyositis 170 Dermatomyositis 170 Immunologic Causes 170 Goodpasture’s Syndrome 170 Wegener’s Granulomatosis 172 Pregnancy as Cause 172 Nutritional and Metabolic Causes 173 Obesity 173 Diabetes Mellitus 174 Traumatic Causes 174 Crush Injuries 174 Penetrating Wounds 176

Pulmonary Laceration 176 Thermal Trauma 178 Therapeutic Causes 178 Surgical Therapy 178 Lung Transplantation 180 Pharmaceutical Causes 181 Oxygen 181 Antibiotics 181 Anti-inflammatory Drugs 182 Cardiovascular Drugs 182 Chemotherapeutic Drugs 182 Poisons 182 Anesthetics 182 Muscle Relaxants 182 Illicit Drugs 182 Radiologic Causes 183 Radiation Pneumonitis and Fibrosis 183 Summary 184 References 185

Pulmonary pathology can be organized and discussed in a number of ways. Within this text, pulmonary function abnormalities have been divided into two main categories: obstructive dysfunction and restrictive dysfunction. If the flow of air is impeded, the defect is obstructive. If the volume of air or gas is reduced, the defect is restrictive (Fig. 51).1 Although this organization of pulmonary pathology may in some ways clarify the discussion, it must be remembered that a number of diseases and conditions result in both obstructive and restrictive lung impairment (mixed impairment). This chapter discusses those pathologies and interventions that result in restrictive lung dysfunction (Table 5-1).

Etiology Restrictive lung dysfunction (RLD) is an abnormal reduction in pulmonary ventilation due to restriction of expansion by the chest wall or the lungs. Lung expansion is restricted, and therefore the volume of air or gas moving in and out of the lungs is decreased.2 Restrictive lung dysfunction is not a disease. In fact, this dysfunction may result from many different diseases arising from the pulmonary system or almost any other system in the body. Restrictive lung dysfunction differs from obstructive lung dysfunction in several important aspects. These differences are summarized in Table 5-2.

Pathogenesis Three major aspects of pulmonary ventilation must be considered to understand the pathophysiology of RLD. They are (1) compliance of both the lung and the chest wall; (2) lung volumes and capacities; and (3) the work of breathing. In order to classify pulmonary disease into one of the two categories (obstructive vs. restrictive), pulmonary function testing (PFT) needs to be performed. With RLD, PFTs will typically show a decrease in almost all volumes and capacities with fairly normal flow rates, along with a decrease in diffusion capacity (Fig. 5-2).3

Compliance Pulmonary compliance encompasses both lung and chest wall compliance. It is the physiologic link that establishes a relationship between the pressure exerted by the chest wall or the lungs and the volume of air that can be contained within the lungs.2 With RLD, chest wall or lung compliance, or both, is decreased.

FIGURE 5-1 Pathophysiologic aspects of lung disease. (From Kacmarek R, Stoller J, Heuer A: Egan’s Fundamentals of Respiratory Care, ed 10, St. Louis, 2013, Mosby.)

As discussed in Chapter 2, a decrease in compliance of the lungs indicates that they are becoming stiffer and thus more difficult to expand. It takes a greater transpulmonary pressure to expand the lung to a given volume in a person with decreased lung compliance.3 If the amount of pressure used to move air into the lungs is constant, the volume of air would be decreased. A chest wall low in compliance limits thoracic expansion and, therefore lung inflation, even if the lung itself has normal compliance. Because pulmonary compliance is decreased in RLD, resistance to lung expansion is increased. In other words, decreased pulmonary compliance requires an increase in pressure just to maintain adequate lung expansion and ventilation. This means the patient has to work harder just to move air into the lungs.

Lung Volumes Restrictive lung dysfunction eventually causes all the lung volumes and capacities to become decreased. Because the distensibility of the lung is decreased, the inspiratory

reserve volume (IRV) is diminished. Although the body tries to preserve the tidal volume (TV) in RLD, the compliance gradually decreases and the work of breathing increases; thus the TV decreases. The expiratory reserve volume (ERV) is the volume of air or gas that can be exhaled following a normal exhalation. No matter the etiology, RLD effects a reduction in the ERV; this reduction is particularly pronounced if a decrease in lung compliance is the principal etiologic factor. The residual volume (RV) is usually decreased, but with some causes of RLD (spinal cord injury, amyotrophic lateral sclerosis [ALS], and other neuromuscular disorders), it may be increased. This results in decreasing the dynamic lung volumes. The most marked decreases in lung volumes are seen in the IRV and ERV. Table 5-1 Examples of restrictive and obstructive lung disease with general presentation and symptoms.

CO2, carbon dioxide; DLCO, diffusing capacity of lung for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, total amount of air exhaled during the FEV test; IPF, idiopathic pulmonary fibrosis; RV, residual volume; TLC, Total lung capacity. ∗

Six classic signs of RLD.

∗∗

Classic symptoms of RLD.

Table 5-2 Clinical manifestation of respiratory distress syndrome

FRC, functional residual capacity; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RDS, respiratory distress syndrome; RR, respiratory rate; VC, vital capacity; V/Q, ventilation–perfusion.

FIGURE 5-2 Changes in lung volumes and capacities with pulmonary disease. ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; TV, tidal volume; VC, vital capacity. (From Kacmarek R, Stoller J, Heuer A: Egan’s Fundamentals of Respiratory Care, ed 10, St. Louis, 2013, Mosby.)

Because all lung volumes are decreased with RLD, all lung capacities are also decreased. Total lung capacity (TLC) and vital capacity (VC) are the two most common spirometric measurements used in the identification of RLD. Decreases in TLC and functional residual capacity (FRC) are a direct result of a decrease in lung compliance. At TLC, the force of the inspiratory muscles is balanced by the inward elastic recoil of the lung. Because the recoil pressure is increased if lung compliance is decreased, this balance occurs at a lower volume, and thus the TLC is diminished. At FRC, the outward recoil of the chest wall is balanced by the inward elastic recoil of the lung. Because this elastic recoil is increased, the balance is achieved at a lower lung volume and so the FRC is decreased (see Fig. 5-2).3

Work of Breathing With RLD, the work of breathing is increased. The respiratory system normally finetunes the respiratory rate and the VT to minimize the mechanical work of breathing. As previously mentioned, a greater transpulmonary pressure is required to achieve a normal VT. The result is that the patient’s work of breathing is increased and a new equilibrium, with a decreased VT and an increased respiratory rate, is sought in an effort to reduce energy expenditure. However, if the respiratory rate is too high, energy is wasted in overcoming airway resistance and in ventilating the anatomic dead space. Furthermore, if the TV is larger than required, energy is wasted overcoming the natural recoil of the lung and in expanding the chest wall. Anything that increases airway resistance, increases flow rates, or decreases lung or chest wall compliance increases the work of breathing. In RLD, both lung and chest wall compliance and lung volumes may decrease. These

changes can significantly affect the work of breathing.4 To overcome the decrease in pulmonary compliance, the respiratory rate is usually increased; the normal inspiratory muscles, especially the diaphragm, work harder; and the accessory muscles of respiration, the scaleni and the sternocleidomastoid (see Chapters 1 and 2), are recruited to assist in expanding the thorax.5 These additional efforts require additional oxygen (O2) expenditure. In normal persons at rest, the body uses less than 5% of the oxygen consumption per minute (O2), or 3 to 14 mL O2/min, to support the work of breathing.4,6 With RLD, the percentage of O2 needed to support the work of breathing can reach and exceed 25%.4,6 This change is usually very insidious as the RLD progresses and is countered by the concurrent decrease in activity seen in these patients. Although the respiratory muscle pump is very resistant to fatigue, these patients can experience respiratory muscle fatigue, overuse, and failure as RLD progresses.

Clinical Manifestation Signs Six classic signs often indicate and are always consistent with RLD (see Table 5-1). The first is tachypnea, or an increased respiratory rate. Because the inspiratory muscles have to work so hard to overcome the decreased pulmonary compliance, an involuntary adjustment is made to increase the respiratory rate and decrease the volumes so that the minute ventilation is maintained. Early in the course of RLD, there may be overcompensation, with the respiratory rate increasing to the point that minute ventilation is increased and alveolar hyperventilation occurs, resulting in greater exhalation of carbon dioxide (CO2). Ventilation–perfusion mismatching, an invariable finding in RLD, leads to the second classic sign: hypoxemia. This mismatching may be due to changes in the collagenous framework of the lung, scarring of capillary channels, distortion or narrowing of the small airways, compression from tumors within the lung or bony abnormalities of the chest wall, or a variety of other causes. Even if patients are not hypoxemic at rest, they may quickly become hypoxemic with exercise. The third classic sign of RLD is decreased breath sounds with dry inspiratory crackles, which are thought to be caused by atelectatic alveoli opening at end inspiration, and are most often heard at the bases of the lungs. The fourth and fifth classic signs are apparent from PFT. The decrease in lung volumes and capacities, determined by spirometry, is the fourth classic sign of RLD. The fifth classic sign is the decreased diffusing capacity of lung for carbon monoxide (DLCO). This arises as a consequence of a widening of the interstitial spaces as a result of scar tissue, fibrosis of the capillaries, and ventilation–perfusion abnormalities. In RLD, the DLCO has been measured at less than 50% of predicted.7 The sixth classic sign usually apparent with RLD is cor pulmonale. This right-sided heart failure is due to hypoxemia, fibrosis, and compression of the pulmonary capillaries, which leads to pulmonary hypertension. The rise in pressure in the pulmonary circulation increases the work of the right ventricle. Because the pulmonary capillary bed is fibrotic, it is also less able to distend to handle the ordinary increase in cardiac output expected with exercise. Therefore during exercise, hypoxemia may occur earlier or be more pronounced. Other signs include a decrease in chest wall expansion and possible cyanosis or clubbing (see Table 5-1).

Symptoms Three hallmark symptoms are usually experienced with RLD (see Table 5-1). The first is dyspnea, or shortness of breath. This symptom typically manifests itself with exercise, but as RLD progresses, dyspnea at rest may also be experienced. The second symptom, and the one that usually brings the patient into the physician’s office, is an irritating, dry, and nonproductive cough. The third hallmark symptom of RLD is the wasted, emaciated

appearance these patients present as the disease progresses. With the work of breathing increased as much as 12-fold over normal, these individuals are using caloric requirements similar to those necessary for running a marathon 24 hours a day.4 Additionally, because breathing is such hard work and eating makes breathing more difficult, these patients usually are not eager to eat and often report a decrease in appetite. Because their energy expenditure is up and their caloric intake is down, they are very often in a continual weight loss cycle, which becomes more severe as the RLD progresses.

BO X 5- 1 Support ive m e a sure s for t re a t m e nt of re st rict ive lung

dysfunct ion • Supplemental O2 • Antibiotic therapy for secondary infection • Interventions to promote adequate ventilation • Interventions to prevent accumulation of secretions • Good nutritional support

Treatment Treatment interventions for RLD are discussed briefly for each disease. Generally, however, if the etiologic factors that are causing RLD are permanent (spinal cord injury) or progressive (idiopathic pulmonary fibrosis), the treatment consists primarily of supportive measures (Box 5-1). Supportive interventions include supplemental oxygen to support the arterial partial pressure of oxygen (PaO2), antibiotic therapy to fight secondary pulmonary infection, measures to promote adequate ventilation and prevent the accumulation of pulmonary secretions, and good nutritional support. However, if the changes that are causing the RLD are acute and reversible (pneumothorax) or chronic but reversible (Guillain–Barré syndrome), the treatment consists of specific corrective interventions (e.g., chest tube placement) and supportive measures (e.g., temporary mechanical ventilation) to assist the patient to maintain adequate ventilation until he or she is again able to be independent in this activity. Each section discusses the pathology that would apply to each condition.

Maturational Causes of Restrictive Lung Dysfunction Abnormalities in Fetal Lung Development ▪ Agenesis is the total absence of the bronchus and the lung parenchyma. Unilateral agenesis is rare.8 ▪ Aplasia is the development of a rudimentary bronchus without the development of the normal lung parenchyma. This condition is also rare.8 ▪ Hypoplasia is the development of a functioning although not always normal bronchus with the development of reduced amounts of lung parenchyma. This developmental abnormality is much more common and may affect one lung or one lobe of a lung. It is often present in infants born with a large diaphragmatic hernia and displaced abdominal organs.8

Clinical Manifestation Depending on the amount of lung parenchyma lost, these infants can be asymptomatic or can exhibit severe pulmonary insufficiency. The pulmonary impairment is restrictive, in that the volumes are decreased even though the lung compliance may be normal.

Respiratory Distress Syndrome Respiratory distress syndrome (RDS), also known as hyaline membrane disease (HMD), is a disorder of prematurity or lack of complete lung maturation in the human fetus. It usually takes 36 weeks of normal gestation to achieve lung maturity in the fetus. Infants born with a gestational age less than 36 weeks often exhibit respiratory distress and may develop the full complement of signs and symptoms associated with RDS.9

Etiology Insufficient maturation of the lungs is the cause of RDS, and it is usually linked directly to the gestational age of the fetus at birth. The incidence of RDS in infants with a gestational age of 26 to 28 weeks at birth is approximately 75%.8 In contrast, the incidence of RDS in infants with a gestational age of 36 weeks at birth is less than 5%.9 Other factors that seem to contribute to the development of RDS are gender, race, abruptio placentae, and maternal diabetes. Premature male infants are more at risk to develop RDS than are premature female infants. White premature infants have a greater incidence of RDS than black premature infants. Fetal lung maturation is delayed in pregnant women with diabetes, so infants born of diabetic mothers are at increased risk of developing RDS. Worldwide, 1% of infants are affected by RDS.8 In the United States, 60,000 to 70,000 are affected.1,10

Pathophysiology

Respiratory distress syndrome is caused primarily by abnormalities in the surfactant system and inadequate surfactant production. Structural abnormalities within the immature lung, such as alveolar septal thickening, may also contribute to the pathophysiology of this syndrome. The surfactant dysfunction causes the overall retractive forces of the lung to be greater than normal, which decreases lung compliance, increases the work of breathing, and leads to progressive diffuse microatelectasis, alveolar collapse, increased ventilation–perfusion mismatching, and impaired gas exchange (Fig. 5-3). In addition, alveolar epithelial and endothelial permeability are abnormal in the immature lung. Therefore when these premature infants are mechanically ventilated without sufficient normal surfactant, the bronchiolar epithelium is disrupted. This leads to pulmonary edema and the generation of hyaline membranes. Further, because the proximal and distal airways in the infant are very compliant and the alveoli may be less compliant due to atelectasis and the formation of hyaline membrane, the mechanical ventilator pressures used can disrupt, dilate, and deform the airways. Mechanical ventilator pressures can also cause air leaks, tension pneumothorax, and extensive pulmonary interstitial emphysema. Another cause of decreased gas exchange is the often severe pulmonary hypertension evident in infants with RDS. These infants have hypoxemia and are acidotic, both of which cause vasoconstriction. This response is exaggerated in the infant and causes severe pulmonary hypertension, increased ventilation–perfusion mismatching, and decreased gas exchange. Restrictive lung dysfunction may be complicated further by persistent patency of the ductus arteriosus, resulting in a left-to-right shunt within the infant’s heart. The patent ductus arteriosus increases pulmonary pressures and blood flow and could allow plasma proteins to leak into the alveolar space, causing pulmonary edema and further interfering with surfactant function.

FIGURE 5-3 Surfactant abnormalities.

Complications common in infants with RDS include intracranial hemorrhage, sepsis, pneumonia, pneumothorax, pulmonary hemorrhage, and pulmonary interstitial emphysema. This syndrome can also result in the development of bronchopulmonary dysplasia. Recovery in RDS is usually preceded by an abrupt unexplained diuresis.9

Many infants still die or have chronic effects from RDS. However, over the past three decades the death rate has significantly decreased, and most deaths are limited to infants who are 24 to 26 weeks’ gestation weighing 500 to 800 g at birth.1

Diagnostic Tests Definitive diagnosis for RDS usually is made by chest radiograph (Fig. 5-4).

Clinical Manifestation The clinical manifestation of RDS can be found in Table 5-2.

Treatment Traditional treatment for RDS entails continuous positive airway pressure (CPAP) and positive end expiratory pressure (PEEP). Surfactant replacement therapy and highfrequency ventilation (HFV) have also been added as traditional treatment approaches. A trial of CPAP using nasal prongs is indicated. If oxygenation does not improve or the infant’s clinical condition deteriorates, mechanical ventilation with PEEP should be institued.1 Surfactant replacement is currently the standard of care in treating infants with RDS. The artificial surfactant is given as a liquid suspension in saline and delivered to the infant by aerosol via endotracheal intubation. The results of this therapeutic intervention are immediate reduction in oxygen requirements, a major decrease in pulmonary complications such as pneumothoraces or pulmonary interstitial emphysema, and rapid weaning from mechanical ventilation, often within 12 to 24 hours.10

FIGURE 5-4 Radiopaque appearance of severe respiratory distress syndrome. Anteroposterior (A) and lateral (B) radiographs show diffuse hazy appearance with low lung volumes and air bronchograms that extend into the periphery. (From Kacmarek R, Stoller J, Heuer A: Egan’s Fundamentals of Respiratory Care, ed 10, St. Louis, 2013, Mosby.)

If the infant does not adequately respond to surfactant administration, then the infant, if large enough, may be treated with extracorporeal membrane oxygenation (ECMO) or nitric oxide administration delivered in the inspiratory gas to cause pulmonary vasodilation.10 An alternative to treatment is prevention of the disease by maternal/fetal treatment with corticosteroids. Administration of corticosteroids to the mother before delivery can accelerate fetal lung maturation by stimulating surfactant synthesis, inducing changes in the elastic properties of the fetal lung, stimulating alveolarization, and decreasing the permeability of the airway and alveoli epithelium.9,10

Bronchopulmonary Dysplasia Bronchopulmonary dysplasia (BPD) is a chronic pulmonary syndrome in neonates that occurs in some survivors of RDS who have been ventilated mechanically and have received high concentrations of oxygen over a prolonged period. Other names used for this syndrome are pulmonary fibroplasia and ventilator lung.8,9

Etiology The incidence of BPD following RDS varies from 2% to 68% in different studies.9 The incidence increases in neonates who had low birth weights (< 1000 g); required mechanical ventilation, particularly using continuous positive pressure; received inspired

oxygen concentrations (FiO2) at 60% or higher; or received supplemental oxygen for more than 50 hours.8,9 In fact, BPD almost invariably develops in neonates who received oxygen at an FiO2 of 60% or higher for 123 hours or more.8 See Chapter 6 for more details on BPD.

Normal Aging Maturation of the various body systems is a natural process that takes place throughout a lifetime. Normal aging usually refers to physiologic changes that occur with regularity in the majority of the population and can therefore be predicted. Physiologic changes that commonly are considered part of the aging process can begin as early as 20 years of age.11

Etiology The normal aging process in the pulmonary system is very slow and insidious, and because we have great ventilatory reserves, the changes are often not felt functionally until the sixth or seventh decade of life.12 Universally, the normal aging process in the lungs is complicated by the fact that throughout life the lungs have had to cope with the external environment. This includes general pollution, noxious gases, specific occupational exposures, inhaled drug use, and, of course, cigarette smoking.11

Physiology The compliance of the pulmonary system starts to decrease at about age 20 and decreases approximately 20% over the next 40 years.11 Maximum voluntary ventilation decreases by 30% between the ages of 30 and 70.11 Vital capacity also drops by about 25% between 30 and 70 years of age.12 However, functional status often is not affected until the sixth and seventh decades.

FIGURE 5-5 Respiratory changes with aging. MVV, maximum voluntary ventilation; RV, residual volume; VC, vital capacity; , ventilation–perfusion; PaO2, arterial partial pressure of oxygen; DLCO, diffusing capacity of the lungs for carbon monoxide.

The control of ventilation undergoes significant change (Fig. 5-5). The peripheral chemoreceptors are not as responsive to hypoxia, and the central receptors are not as responsive to acute hypercapnia. These changes mean that the ventilatory response mediated by the central nervous system is significantly depressed.4,9 The normal PaO2 in a 70-year-old is 75, a measurement that is not interpreted as hypoxia by the central nervous system.11 The thorax undergoes a number of changes, including decalcification of the ribs, calcification of the costal cartilages, arthritic changes in the joints of the ribs and vertebrae, dorsal thoracic kyphosis, and increased anteroposterior diameter of the chest (barrel chest). The effects of these changes combine to decrease the compliance of the chest wall and increase the work of breathing. Oxygen consumption in the respiratory muscles is increased, causing an increase in the minute ventilation. The strength and endurance of the inspiratory muscles gradually diminishes, which results in a decreased maximal ventilatory effort.3 The forced expiratory volume in 1 second (FEV1) is reduced by about 40 mL per year.11 The lung tissue itself shows enlargement of the air spaces due to enlargement of the alveolar ducts and terminal bronchioles. The alveolar surface area and the alveolar parenchymal volume are decreased. The alveolar walls become thinner, and the capillary

bed incurs considerable loss, with an increase in ventilation–perfusion mismatching. Distribution of inspired air and pulmonary blood flow becomes less homogeneous with age. Diffusing capacity is therefore reduced, and physiologic dead space is increased.11 The static elastic recoil of the alveolar tissue decreases, which means that alveolar compliance is increased and the lungs do not empty well. The lung compliance curve is shifted to the left in the elderly. Thus although TLC may not change with age, RV increases and dynamic volumes therefore decrease.11,12 Closing volumes are increased, which results in early closure of the small airways, particularly in the dependent lung regions. By approximately age 55, small airways are closed at or above FRC in the supine position. In the upright position, with the attendant increase in FRC, this change occurs at approximately age 70.11 Of course, normal concomitant aging changes take place in the cardiovascular system, including a decrease in maximum heart rate and cardiac output. These changes combine with the decreased oxygen exchange capability of the lungs and result in a decrease in the maximum oxygen uptake with exercise and therefore a decrease in the anaerobic threshold. After 50 years of age, the maximum oxygen uptake usually declines at a rate of 0.45 mL/kg/min for each year.4,9 Ventilation during sleep is altered in the elderly. Electroencephalographic (EEG) studies have shown that total nocturnal sleep time is shorter, with more frequent and longer nocturnal awakenings in the elderly. The pattern of ventilation during sleep is irregular more often in the elderly than in young adults. Repetitive periodic apneas occur in 35% to 40% of the elderly, predominantly in males during sleep stages 1 and 2.9

Clinical Manifestation The clinical manifestation of normal aging can be found in Table 5-3.

Treatment Biological aging is a process of change affecting tissues and organs. However, a healthy lifestyle choice, including avoidance of health-damaging behaviors, may slow functional decline. Existing evidence also supports the need to keep aerobically exercising and possibly adding strength training into one’s daily regimen.13–15 The elderly should be encouraged to remain active and fit. Although even with regular activity about 0.45 mL/kg/min of oxygen consumption is lost each year, the fit elderly person has a greater maximum oxygen consumption than the sedentary person. In addition, a sedentary elderly person beginning regular exercise can improve maximum oxygen consumption by 5% to 25% and can regain the exercise capability that was present as much as 5 to 10 years earlier.11

Table 5-3 Comparison of obstructive and restrictive types of pulmonary diseases Characteristic Anatomy affec ted

Obstructive disease Airways

Restrictive disease Lung parenc hyma, thorac ic pump

Breathing phase diffic ulty Expiration Inspiration Pathophysiology Inc reased airway resistanc e Dec reased lung or thorac ic c omplianc e Useful measurements Flow rates Volumes or c apac ities

Pulmonary Causes of Restrictive Lung Dysfunction Interstitial Causes Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, and usually lethal lung disease. It occurs mostly in older adults, and the cause is unknown.16 It is characterized by progressive worsening of dyspnea and lung function.17 It affects all of the components of the alveolar wall, including epithelial and endothelial cells, the cellular and noncellular components of the interstitium, and the capillary network. These components are supported by the connective tissue framework made up of collagen and elastic fibers and contain a milieu of ground substance. Prevalence estimates have varied from 2 to 29 cases per 100,000 in the general population, and more men have been reported with IPF than women.17

Etiology The cause of IPF is unknown; however, it appears to be a disease that likely arises from the interplay between genetic and environmental factors.16 Initially, the disease was thought to be a chronic inflammatory process. Research now is revealing that it likely is due to a fibrotic response driven by abnormally activated alveolar epithelial cells.16 The most important environmental risk factors are cigarette smoking and exposure to metal and wood dust.16 Other potential risk factors include microbial agents and gastroesophageal reflux.17 Genetic transmission occurs in about 0.5% to 3.7% of cases.16

Pathophysiology The pathogenesis remains largely unknown. Over the past decade, research has changed the perspective on IPF. Rather than primarily a proinflammatory disorder, IPF now appears to be the result of an atypical reparative process that occurs after an injury to the lung epithelium. The disease is, therefore, marked by proliferation and accumulation of fibroblasts or myofibroblasts and excessive deposition of extracellular matrix. This results in scarring and destruction of the lung architecture (Fig. 5-6).16,18,19

FIGURE 5-6 Pathogenic alterations in IPF. (From Loomis-King H, Flaherty KR, Moore BB: Pathogenesis, current treatments and future directions for idiopathic pulmonary fibrosis, Curr Opin Pharmacol 13(3):377-385, 2013.)

Along with a steady decline in lung function, the course includes acute exacerbations characterized by rapid deterioration in lung function not due to infections or heart failure. The acute exacerbations include low-grade fever, worsening dyspnea and cough, worsening gas exchange, and appearance of new opacities on radiology.20 Idiopathic pulmonary fibrosis is associated with a median survival rate of 2 to 3 years after initial diagnosis.21

Diagnostic Tests Diagnosis of IPF requires a detailed review of the patient’s clinical history, as well as the exclusion of other known causes of interstitial lung disease (drug toxicity, occupational environmental exposures).17 Testing by high-resolution computerized tomography (HRCT) of the chest is also indicated, and if this is not definitive, surgical lung biopsy

may be needed (Fig. 5-7).22

Clinical Manifestation The clinical manifestation of IPF can be found in Table 5-4.

Treatment At present, there is no effective standard treatment.23 However, based on research over the past 10 years and new understanding of the pathogenesis, the pharmacologic approach to the disease has changed. Trials previously were focused on the efficacy of drugs that would suppress the inflammatory or immune response, such as corticosteroids. Currently, treatment approaches and trials are now geared toward agents with antifibrotic properties. At present, pirfenidone is the only antifibrotic drug approved for treatment of IPF.23

FIGURE 5-7 A, Posteroanterior chest radiograph showing the characteristic features of idiopathic pulmonary fibrosis, a common interstitial lung disease. Notice the bilateral lower zone reticulonodular infiltrates and the loss of lung volume in the lower lobes. B, Chest CT image shows the peripheral nature of the fibrosis. (From Kacmarek R, Stoller J, Heuer A: Egan’s Fundamentals of Respiratory Care, ed 10, St. Louis, 2013, Mosby.)

Other supportive therapies include provision of supplemental oxygen for hypoxemia, pulmonary rehabilitation, and lung transplantation in appropriate candidates.22 The number of lung transplants for IPF is steadily rising, especially in the United States, where IPF now represents the leading indication for lung transplantation. Fiveyear survival rates after lung transplantation in IPF are estimated at 50% to 56%. Additional evidence suggests that patients with pulmonary fibrosis undergoing lung transplantation have favorable long-term survival compared with other disease indications.18 However, this surgical therapeutic intervention is not without risks (see Chapter 12), including restrictive lung dysfunction, namely, bronchiolitis obliterans.

Sarcoidosis Sarcoidosis is an idiopathic granulomatous inflammatory disorder that affects many

organ systems, including the lungs, heart, skin, central nervous system, and eyes, among others.24 Clinically, the lung is the most involved organ (Fig. 5-8).25–27 Table 5-4 Clinical manifestation of idiopathic pulmonary fibrosis

DLCO, diffusing capacity of the lungs for carbon monoxide; FRC, functional residual capacity; HR, heart rate; HRCT, highresolution computed tomography; IPF, idiopathic pulmonary fibrosis; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Etiology Despite extensive research, the etiology of sarcoidosis is unknown. Infectious agents, chemicals or drugs, allergy, autoimmunity, and genetic factors have all been researched as possible causes.30 Sarcoidosis most commonly affects young adults, with 70% of the cases diagnosed in persons 20 to 40 years of age. Sarcoidosis is more common in women than in men. The incidence is increased tenfold in black Americans compared with whites. It is rare in Native Americans.31

FIGURE 5-8 Various manifestations of sarcoidosis. A, Bilateral hilar adenopathy and right paratracheal lymph node enlargement demonstrated on a posterior anterior chest roentgenogram, Scadding stage 1. B, Facial lesion consistent with lupus pernio. C, Hand changes consistent with sarcoidosis in the fingers. D. Noncontrast magnetic resonance image of the pelvis demonstrating bone marrow replacement by granulomatous tissue. E, Cystic changes (arrows) within the bones of the fingers of a patient with sarcoidosis. F, Gadolinium enhancement of lesions of the spine seen on magnetic resonance image of a sarcoidosis patient. (From Firestein G, Budd R, Gabriel SE, et al: Kelley’s Textbook of Rheumatology, ed 9, Saunders, St. Louis, 2013.)

Pathophysiology This disease presents with three distinctive features within the lung: alveolitis, formation of well-defined round or oval granulomas, and pulmonary fibrosis.25 The alveolitis usually appears earliest and is an infiltration of the alveolar walls by inflammatory cells, especially macrophages and T lymphocytes. The core of the sarcoid granuloma contains epithelioid cells and multinucleated giant cells; there is rarely any necrosis in the core. The core is surrounded by monocytes, macrophages, lymphocytes, and fibroblasts. These granulomas may resolve without scarring, but many go on to become obliterative fibrosis, which is characterized by the accumulation of fibroblasts and collagen around the granuloma. Diffuse fibrosis of the alveolar walls is not typical in this disease, although it can occur late in the disease progression. Approximately 25% of patients with pulmonary sarcoidosis experience a permanent decrease in lung function, which over time proves fatal in 5% to 10% of patients.25 This loss of lung function is due to restrictive lung impairment primarily, but this disease also has an obstructive component. Prognosis seems to be better if the onset of pulmonary symptoms is acute. If the onset is insidious, with progressive dyspnea, then the prognosis is worse (patients will have more

impairments, less function, and may have higher mortality rates). Sarcoidosis is a multisystem disease, and although the pulmonary system is the most commonly involved (90%), other systems are affected also. Seventeen percent of patients have ocular involvement, which can lead to blindness.25 The most common ocular presentation is granulomatous uveitis, which causes redness and watering of the eyes, cloudy vision, and photophobia.32 Five percent of patients have neurologic involvement, which can include encephalopathy, granulomatous meningitis, or involvement of the cranial nerves.25 Other organ systems that can be involved are the liver (60% to 80%), the lymphatics (50% to 75%), the heart (30%), the skin (30%), the spleen (15%), the kidney, muscles, joints, and the immune system.3,8,25,26,31,33 The progression of this disease is extremely variable. It can be active and resolve spontaneously, or it can be inactive and stable for long periods. About 30% of patients with sarcoidosis develop chronic progressive disease.2 Mortality in sarcoidosis is less than 5%.2 Neurologic and cardiac involvement may present acutely and portend a poor prognosis. Progressive pulmonary fibrosis is the most common cause of death.32

Clinical Manifestation The clinical manifestation of sarcoidosis can be found in Table 5-5.

Treatment Most patients require no treatment. When treatment is necessary, patients usually improve with moderate doses of corticosteroids. Steroid-sparing agents often are administered to minimize the long-term side effects of systemic corticosteroids.32 In treating the three pulmonary manifestations of this disease, corticosteroids are used early to suppress the alveolitis and granuloma formation, especially if the patient has respiratory symptoms and/or a 20% to 30% reduction in PFT values.10,28 Established granulomas with pulmonary fibrosis are relatively fixed lesions and do not respond to therapy.

Table 5-5 Clinical manifestation of sarcoidosis

CHF, congestive heart failure; DLCO, diffusing capacity of the lungs for carbon monoxide; PaO2, arterial partial pressure of O2; PFT, pulmonary function testing; RR, respiratory rate; RV, residual volume; TLC, total lung capacity.

Bronchiolitis Obliterans Bronchiolitis obliterans is a fibrotic lung disease that affects the smaller airways. It can produce restrictive and obstructive lung dysfunction. This syndrome has been known and discussed under a variety of names, including bronchiolitis, bronchiolitis obliterans with organizing pneumonia (BOOP), bronchiolitis fibrosa obliterans, follicular bronchiolitis, and bronchiolitis obliterans with diffuse interstitial pneumonia.25

Etiology Bronchiolitis obliterans was first recognized in children, usually those under the age of 2 years. Pediatric bronchiolitis obliterans is often caused by a viral infection, most commonly by the respiratory syncytial virus (RSV), parainfluenza virus, influenza virus, or adenovirus.32 An adult form of the disease has now been recognized that can occur in persons from 20 to 80 years of age and has a wider variety of causes. In the adult, bronchiolitis obliterans may be caused by toxic fume inhalation (nitrogen dioxide) or by viral, bacterial, or mycobacterial infectious agents, particularly Mycoplasma pneumoniae. It may be associated with connective tissue diseases, such as rheumatoid arthritis (RA); related to organ transplantation and graft versus host reactions; or allied with other diseases, such as IPF. It also may be idiopathic, with no known cause.25

FIGURE 5-9 Bronchiolitis obliterans. The lumen is obliterated by the fibrosis. The bronchiole is identifiable only by the presence of smooth muscle bundles or discontinuous elastic tissue around a central scar. (From Husain A: Thoracic Pathology, St. Louis, 2013, Saunders.)

Pathophysiology Bronchiolitis obliterans is characterized by necrosis of the respiratory epithelium in the affected bronchioles. This necrosis allows fluid and debris to enter the bronchioles and alveoli, causing alveolar pulmonary edema and partial or complete obstruction of these small airways. With complete obstruction, the trapped air is absorbed gradually and the alveoli then collapse, causing areas of atelectasis. When the destruction of the respiratory epithelium is severe or widespread, it may be followed by a significant inflammatory response. This causes fibrotic changes in the adjacent peribronchial space, the alveolar walls, and the air spaces. The fibrotic changes are patchy and usually occur primarily within the bronchial tree and alveoli rather than in the interstitial lung tissue, as happens in IPF. All these changes combine to increase ventilation–perfusion mismatching; decrease lung compliance; impair gas transport; and, in some patients, cause demonstrable airway obstruction (Fig. 5-9).25

Clinical Manifestation The clinical manifestation of bronchiolitis obliterans can be found in Table 5-6.

Treatment In children, treatment is supportive, usually consisting of hydration and supplemental oxygen. If the child is unable to clear secretions, postural drainage and suctioning are employed. Mechanical ventilation is rarely needed. If RSV is the causative pathogen, then the antiviral agent ribavirin may be administered via aerosol.32 Corticosteroids,

antibiotics, and bronchodilators are not recommended in the treatment of pediatric bronchiolitis obliterans. In adults, supplemental oxygen and proper fluid balance are also very important. Corticosteroids have proved very effective in treating adult bronchiolitis obliterans that is idiopathic, caused by toxic fume inhalation, or associated with connective tissue disease. Table 5-6 Clinical manifestation of bronchiolitis obliterans

BO, bronchiolitis obliterans; DLCO, diffusing capacity of the lungs for carbon monoxide; RR, respiratory rate.

Environmental/Occupational Causes Coal Workers’ Pneumoconiosis Coal workers’ pneumoconiosis (CWP), an interstitial lung disease, is defined as the accumulation of coal dust in the lungs and the subsequent reaction by the surrounding tissue. Coal workers’ pneumoconiosis is classified into two categories based on radiographic findings: simple CWP with small opacities (1 cm).34

Etiology Coal workers’ pneumoconiosis is caused by repeated inhalation of coal dust over a long period; usually, 10 to 12 years of underground work exposure is necessary for the development of simple CWP.35 Complicated CWP usually occurs only after even longer exposure to coal dust. Anthracite coal is more hazardous than bituminous in the development of this disease.32

Pathophysiology The pathologic hallmark of CWP is the coal macule, which is a focal collection of coal dust with little tissue reaction either in terms of cellular infiltration or fibrosis. These coal macules are often located at the division of respiratory bronchioles and are often associated with focal emphysema.35 Lymph nodes are enlarged and homogeneously pigmented and are firm but not fibrotic. The pleural surface appears black due to the deposits of coal dust. Simple CWP is a benign disease if complications do not develop. Less than 5% of cases progress to complicated CWP.31 Complicated CWP results in large confluent zones of dense fibrosis that are usually present in apical segments in one or both lungs. These zones are made up of dense, acellular, collagenous, black-pigmented tissue. The normal lung parenchyma can be completely replaced, and the blood vessels in the area then show an obliterative arteritis. These fibrous zones can completely replace the entire upper lobe.35 Other conditions that may result from complicated CWP include emphysema, chronic bronchitis, tuberculosis, cor pulmonale, and pulmonary thromboembolism. Although CWP is preventable, it continues to occur at a disturbing rate, which leads to significant morbidity and mortality in coal miners.34 The main cause of death is progression of lung disease and then development of respiratory failure.34

Diagnostic Tests The diagnosis of CWP can be made by an adequate history of exposure to coal mine dust and characteristic chest radiograph.34

Clinical Manifestation The clinical manifestation of CWP can be found in Table 5-7.

Treatment Complicated CWP with pulmonary fibrosis is nonreversible; there is no cure for it. Supportive treatment includes cessation of exposure to coal dust, good nutrition, interventions to ensure adequate oxygenation and ventilation, and progressive exercise training to maximize the remaining lung function and tolerance to activity. Lung transplantation may be an option for those with advanced disease (Fig. 5-10).36

Silicosis Silicosis, one of the occupational pneumoconioses, is a fibrotic lung disease caused by the inhalation of free crystalline silicon dioxide or silica.37 Table 5-7 Clinical manifestation of coal workers’ pneumoconiosis (CWP)

DLCO, diffusing capacity of the lungs for carbon monoxide; FRC, functional residual capacity; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; TB, tuberculosis; TLC, total lung capacity; VC, vital capacity.

Etiology Free crystalline silicon dioxide is very common and widely distributed in the earth’s crust in a variety of forms, including quartz, flint, cristobalite, and tridymite.35 Industries in which silicon dioxide exposure can occur include mining, tunneling through rock, quarrying, grinding and polishing rock, sandblasting, ship building, and foundry work.29 More recent exposure hazards now include hydraulic fracturing (fracking) of oil and gas wells.38 The most important factor in developing silicosis is the cumulative dose of silica inhaled.38 Even after the patient is no longer exposed, lung function impairment worsens

as the disease progresses.37

FIGURE 5-10 Coal workers’ pneumoconiosis. The lungs show increased black pigmentation. (From Danjanov I: Pathology: a color atlas, St. Louis, 2000, Mosby.)

Currently, about 2 million U.S. workers are exposed to silica. According to the National Institute for Occupational Safety and Health, there has been a decrease in U.S. death rates due to silicosis, from about 1200 in 1968 to fewer than 100 per year in the early 2000s. Aside from a few states having their own, there is no national surveillance system.38

Pathophysiology Inhaled silica causes macrophages to enter the area to ingest these particles. But the macrophages are destroyed by the cytotoxic effects of the silica. This process releases lysosomal enzymes that then induce progressive formation of collagen, which eventually becomes fibrotic. Another characteristic of silicosis is the formation of acellular nodules composed of connective tissue called silicotic nodules. Initially, these nodules are small

and discrete, but as the disease progresses, they become larger and coalesce. Silicosis normally affects the upper lobes of the lung more than the lower lobes. Silicosis also seems to predispose the patient to secondary infections by mycobacteria, including Mycobacterium tuberculosis. Complicated silicosis follows a steadily deteriorating course that leads to respiratory failure.3,33

FIGURE 5-11 Axial high-resolution computed tomography sections of two patients with silicosis. Early silicosis with sparse and small silicotic nodules (A) and silicosis with many nodules of varying sizes (B). (From Leung CC, Tak Sun Yu I, Chen W: Silicosis, Lancet 379(9830):2008 - 2018, 2012.)

Diagnostic Tests Diagnosis is made based on a history of substantial exposure to silica, exclusion of other competing diagnoses, and chest radiography (Fig. 5-11).37

Clinical Manifestation

The clinical manifestation of silicosis can be found in Table 5-8.

Treatment No curative treatment exists, but comprehensive management strategies help to improve quality of life and slow deterioration. Supportive therapy includes avoidance of further exposure, provision of adequate oxygenation, ventilation, and nutrition. It has been shown that physical training can improve functional exercise capacity, shortness of breath, and quality of life in patients with interstitial lung disease. Another therapeutic option for those with advanced lung disease is lung transplantation, especially for young patients with acute silicosis.37 Table 5-8 Clinical manifestation of silicosis

FEV1, forced expiratory volume in 1 second; PaO2, arterial partial pressure of O2; TLC, total lung capacity; VC, vital capacity.

Asbestosis Asbestosis is a pneumoconiosis caused by the inhalation of asbestos.32,39 Occupational asbestos exposure is also associated with an increased incidence of primary cancer of the larynx, oropharynx, esophagus, stomach, and colon.35

Etiology There are six naturally occurring fibrous silicate minerals that are referred to as asbestos fibers.39 They include chrysotile, which accounts for more than 70% of the asbestos used in the United States; crocidolite; amosite; tremolite; anthophyllite; and actinolite (amphiboles). There is another naturally occurring silicate called vermiculite, which may be contaminated with asbestos fibers, therefore also posing a health risk.39 Asbestos was initially used due to its exceptional fireproof and insulation properties. The most common trades known for asbestos exposure include aircraft mechanics and manufacturers, aerospace/missile production, electrical workers, power plant employees, telephone linemen, shipyard workers (e.g., insulators, laggers, painters, pipefitters), building supply manufacturers, railroad and sheet metal workers, operational navy and coast guard personnel, and asbestos mining and transport.39

Pathophysiology How asbestos causes a fibrotic reaction is not understood. It is hypothesized that the asbestos fiber causes an alveolitis in the area of the respiratory bronchioles, which then progresses to peribronchiolar fibrosis due to the release of chemical mediators. Plaques, which are localized fibrous thickenings of the parietal pleura, are common and are usually seen posteriorly, laterally, or on the pleural surface of the diaphragm. Pleural effusions may also occur with asbestosis. Also, “asbestos bodies,” or ferruginous bodies, appear in the lungs and sputum of these patients. These rod-shaped bodies with clubbed ends seem to be an asbestos fiber coated by macrophages with an iron–protein complex.3,8,32,35 There is often a dormancy period of 20 to 30 years for asbestos-related lung disease to reveal itself. Prevalence in the United States is unknown.39 Studies have shown conclusively that cigarette smoking has a multiplicative effect in the development of primary lung cancer in persons who have been exposed to asbestos.35 Complications of asbestosis include bronchiectasis, pleural mesothelioma, and bronchogenic carcinoma.8

Diagnostic Tests Diagnosis can be made based on a history of respiratory symptoms and occupational exposure, including type of work and duration of exposure. A complete history on smoking is also important. The posteroanterior chest radiograph remains the standard

for evaluation and classification of asbestosis.39

Clinical Manifestation The clinical manifestation of asbestosis can be found in Table 5-9.

Treatment There is no curative treatment for asbestosis and the disease progresses even though exposure to asbestos has ceased. Symptomatic support includes cessation of smoking, good nutrition, exercise conditioning to maximize lung function, and prompt treatment of recurrent pulmonary infections. For those with advanced diseases, lung transplant may be an option.36

Infectious Causes Pneumonia Pneumonia is an inflammatory process of the lung parenchyma that usually begins with an infection in the lower respiratory tract. Causative agents include bacteria, viruses, fungi, or mycoplasmas. There are four categories of pneumonias: community-acquired pneumonias, hospitalacquired pneumonias (HAPs), health care–associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP). The latter three were known as nosocomial.1 The World Health Organization estimates that lower respiratory tract infection is the most common infectious cause of death in the world (the third most common cause overall), with almost 3.5 million deaths yearly.2 Together, pneumonia and influenza constitute the ninth leading cause of death in the United States, resulting in 50,000 estimated deaths in 2010.40

Etiology Community-acquired pneumonias can be divided into two types: acute and chronic. The group depends on the clinical presentation. Acute pneumonia generally appears with sudden onset over a few hours to several days.1 Chronic is more insidious, often with gradually worsening of symptoms over days, weeks, or even months.1 Streptococcus pneumonia, also called pneumococcus, has been found to be the most common cause of community-acquired pneumonia, accounting for 20% to 70% of cases. Other causative organisms include Haemophilus influenzae, Staphylococcus aureus, and gram-negative bacilli, each accounting for 3% to 10% of cases. Legionella spp., Chlamydophila pneumonia, and M. pneumonia together account for 10% to 20% of cases and are considered atypical.1 Although there are many infectious agents in the environment, few pneumonias develop because of the efficient defense mechanisms in the lung. Those who develop communityacquired pneumonias usually have been infected with an exceedingly virulent organism or a particularly large inoculum or have impaired or damaged lung defense mechanisms.32

Table 5-9 Clinical manifestation of asbestosis

DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; RV, residual volume; TLC, total lung capacity; VC, vital capacity.

Health care–associated pneumonia, HAP, and VAP are often caused by different microorganisms than community-acquired pneumonia (Table 5-10). Hospital-acquired pneumonia is a common clinical problem and represents the second most common nosocomial infection in the United States and accounts for 15% to 18% of all such infections.9 The patients most likely to develop a nosocomial pneumonia have one or more of the following risk factors: nasogastric tube placement; intubation; dysphagia; tracheostomy; mechanical ventilation; thoracoabdominal surgery; lung injury; diabetes; chronic cardiopulmonary disease; intraabdominal infection; uremia; shock; history of smoking; advanced age; poor nutritional status; or certain therapeutic interventions, such as the administration of broad-spectrum antibiotics, corticosteroids, antacids, or high oxygen concentrations. Table 5-10 Pneumonia transmission and treatment

AIDS, acquired immunodeficiency syndrome; ARDS, adult respiratory distress syndrome; COPD, chronic obstructive pulmonary disease. From Cottrell GP, Surkin HB: Pharmacology for Respiratory Care Practitioners. Philadelphia, 1995, FA Davis.

Pathophysiology Bacteria and other microbes commonly enter the lower respiratory tract. It has been estimated that during sleep, 45% of healthy people aspirate oropharyngeal secretions into the lower respiratory tract.9 However, because of the elaborate defense mechanisms within the pulmonary system, pneumonia usually does not develop. The mechanical defenses include cough, bronchoconstriction, angulation of the airways favoring impaction and subsequent transport upward, and action of the mucociliary escalator. The immune defenses include bronchus-associated lymphoid tissue; phagocytosis by polymorphonuclear cells and macrophages; immunoglobulins A and G; and complement, surfactant, and cell-mediated immunity by T lymphocytes.32 The most common routes for infection leading to pneumonia are inhalation and aspiration (see Table 5-10). When the causative agent is bacterial, the first response to infection is an outpouring of edema fluid. This is followed rapidly by the appearance of polymorphonuclear leukocytes that are involved in active phagocytosis of the bacteria,

and then fibrin is deposited in the inflamed area. Usually by day 5, specific antibodies are in the area fighting the bacterial infection. Clinically, bacterial pneumonia usually has an abrupt onset and is characterized by lobar consolidation, high fever, chills, dyspnea, tachypnea, productive cough, pleuritic pain, and leukocytosis.2,35,41 When the causative agent is viral, the virus first localizes in respiratory epithelial cells and causes destruction of the cilia and mucosal surface, leading to the loss of mucociliary function. This impairment may then predispose the patient to bacterial pneumonia. If viral infection reaches the level of the alveoli, there may be edema, hemorrhage, hyaline membrane formation, and possibly the development of adult RDS. Primary viral pneumonia is a serious disease with diffuse infiltrates, extensive parenchymal injury, and severe hypoxemia. Clinically, viral pneumonia usually has an insidious onset and is characterized by patchy diffuse bronchopulmonary infiltrates, moderate fever, dyspnea, tachypnea, nonproductive cough, myalgia, and a normal white blood cell count.32

Diagnostic Tests Radiographic appearances of new or progressive pulmonary infiltrates, as well as clinical symptoms, are seen in Table 5-9.

Clinical Manifestation The clinical manifestation of pneumonia can be found in Table 5-11.

Treatment Drug therapy is the primary focus in the treatment of pneumonia, particularly antibiotics for treating bacterial pneumonia. Antibiotic therapy should be pathogen specific if the pathogen can be determined; if not, an empiric regimen of multiple antibiotics may be needed. Oxygen and temporary mechanical ventilation or noninvasive ventilation may be necessary in patients with refractory hypoxemia (PaO2 < 60 mm Hg). Other supportive therapy includes postural drainage, percussion, vibration, and assisted coughing techniques for patients who are producing more than 30 mL per day of mucus or have an impaired cough mechanism.32 Adequate hydration and nutrition are also important. These infections can also be prevented by rigorous environmental controls in hospitals, such as strict guideline adherence for the prevention of contamination of ventilators and other respiratory equipment, careful aseptic patient care practices, and surveillance of infections and antibiotic susceptibility patterns in high-risk areas.

Table 5-11 Clinical manifestation of pneumonia

HR, heart rate; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate.

Pneumonia is simply an inflammatory process of some part of the lung where gas exchange occurs that progresses beyond inflammation and develops into infection. The key to treatment of pneumonia is to first identify the microbe (virus vs. gram-positive or gram-negative bacteria). Specific medical treatment (specific antibiotic) is based on identification of the microbe, although broad-spectrum medications may be initiated before identification has been made.

Clinical tip The problem with treating pneumonia in recent years is the identification of microbes that are resistant to many forms of antibiotics. These microbes can be spread via aerosol or physical contact and can cause severe disability and even death in immunosuppressed individuals. Some of the common ones are methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (C-diff).

Specific Pneumonias Bacterial Pneumonias Streptococcus pneumoniae S. pneumoniae is more common in the elderly; in alcoholics; and in those with asplenia,

multiple myeloma, congestive heart failure (CHF), or chronic obstructive lung disease. Seventy percent of patients report a preceding viral illness.32 This type of pneumonia occurs more frequently during the winter and early spring. Specific signs and symptoms include rusty-colored sputum, hemoptysis, bronchial breath sounds, egophony, increased tactile fremitus, pleural friction rub, severe pleuritic chest pain, pleural effusion in 25% of patients, and slight liver dysfunction.30,32 Complications can include lung abscess, atelectasis, delayed resolution in the elderly, pericarditis, endocarditis, meningitis, jaundice, and arthritis.35 Streptococcal pneumonia is treated with penicillin G, ampicillin, or tetracyclines.42 There is also a pneumococcal vaccine; this injection provides lifetime protection against serotypes of the pneumococcus that account for 85% of all cases of pneumococcal pneumonia.32,42 Legionella pneumophila Legionella pneumophila can occur in epidemic proportions because the organism is water borne and can emanate from air-conditioning equipment, drinking water, lakes, river banks, water faucets, and shower heads. L. pneumophila accounts for 7% to 15% of all community-acquired pneumonias.32 It is found commonly in patients who are on dialysis; in persons who have a malignancy, a chronic obstructive pulmonary disease (COPD), a smoking history, or are older than 50 years; and in persons who are alcoholics or diabetics. Transplant recipients of any organ are at the highest risk.30 Signs and symptoms in addition to those characteristic of bacterial pneumonias include headache, myalgias, preceding diarrhea, mental confusion, hyponatremia, bradycardia, and liver function abnormalities. Productive coughs with purulent sputum and hemoptysis can develop in 50% to 75% of patients.30 However, most patients (90%) begin with a nonproductive cough.30 The chest radiograph may show lobar consolidation or unilateral or bilateral bronchopneumonia; rounded densities with cavitation may also be seen. Fifteen percent of these patients have pleural effusions. The antibiotic of choice is erythromycin. Rifampin may also be used in addition to erythromycin.32 Haemophilus influenzae H. influenzae causes pneumonia, particularly in children who have had their spleen removed, in patients with COPD, in alcoholics, in AIDS patients, in those with lung cancer, in patients with hypogammaglobulinemia, and in the elderly.10 In addition to the expected signs and symptoms of bacterial pneumonia, H. influenzae often causes a sore throat. The chest radiograph may show focal lobar, lobular, multilobar, or patchy bronchopneumonia or segmental pneumonia that usually involves the lower lobes. Complications can include empyema, lung abscess, epiglottitis, otitis media, pericarditis, meningitis, and arthritis. The preferred antibiotic is ampicillin; however, 20% of patients have been shown to be resistant to ampicillin. In these cases, cephalosporins, trimethoprim–sulfamethoxazole, and chloramphenicol are used.32,35 Klebsiella pneumoniae

Klebsiella pneumoniae may cause either a community-acquired pneumonia or nosocomial pneumonia. The community-acquired Klebsiella pneumonia is seen most commonly in men over the age of 40 who are alcoholic or diabetic or who have underlying pulmonary disease. These patients may show purulent blood-streaked sputum, hemoptysis, cyanosis, and hypotension. Chest radiographic findings most frequently show right-sided involvement of the posterior segment of the upper lobe or the lower lobe segments. There may be outward bulging of a lobar fissure as a result of edema, and 25% to 50% of these patients have lung abscesses.35 Complications include empyema, lung abscess, pneumothorax, chronic pneumonia, pericarditis, meningitis, and anemia. Treatment includes a two-drug therapy: an aminoglycoside and a cephalosporin. Oxygen is also used to maintain an oxygen saturation level of 80% to 85%. The mortality rate for this gram-negative pneumonia is 20%.35 Nosocomial Klebsiella pneumonia is a fulminant infection that causes severe lung damage and has a 50% mortality rate.32 It affects debilitated patients in hospitals and nursing homes, middle-aged or older, who suffer from concomitant alcoholism, diabetes, malignancy, or chronic renal or cardiopulmonary disease. Their sputum is thick, purulent, and bloody or is thin and has a “currant jelly” texture. Tachycardia is common. The chest radiograph can show lobar consolidation, usually in the upper lobes, with lung abscesses, cavities, scarring, and fibrosis. A bronchopneumonia appearance may also occur. Complications are the same as those in community-acquired Klebsiella pneumonia. Drug therapy includes the use of aminoglycosides, cephalosporin, and antipseudomonal penicillin.32,35 Pseudomonas aeruginosa Pseudomonas aeruginosa is a gram-negative bacillus and is the most common cause of nosocomial pneumonias. It causes 15% of all HAPs and affects 40% of all mechanically ventilated patients.32 Those at most risk for this infection are patients with cystic fibrosis, bronchiectasis, tracheostomy, or neutropenia or those who are on mechanical ventilation or corticosteroid therapy. This necrotizing pneumonia causes alveolar septal necrosis, microabscesses, and vascular thrombosis and has a mortality rate of 70% in postoperative patients.32 Signs and symptoms include confusion, bradycardia, and hemorrhagic pleural effusion. The chest radiograph shows bilateral patchy alveolar infiltrates, usually in the lower lobes, with nodular infiltrates and cavitation.32 Treatment always involves two drugs. Aminoglycosides, carbenicillin, and aztreonam are used to overcome this bacterium.42 Staphylococcus aureus S. aureus causes approximately 5% of community-acquired pneumonias.32 This type of pneumonia is usually seen in infants and children under the age of 2 years, in patients with cystic fibrosis or COPD, or in patients who are recovering from influenza. The hallmark lesion seen in this pneumonia is ulcerative bronchiolitis with necrosis of the bronchiolar wall.42 Signs and symptoms include cough with dirty salmon-pink purulent

sputum, high fever, dyspnea, and pleuritic chest pain.42 Other manifestations commonly seen in children are cyanosis, labored breathing, grunting, flaring of the nostrils, and chest wall retractions. The chest radiograph shows a diffuse bronchopneumonia, with bilateral infiltrates, cavitary lung abscesses, pneumatoceles, and pleural effusions. Complications include pneumothorax, lung abscess, endocarditis, and meningitis. Treatment is with antistaphylococcal penicillin, cephalosporin, vancomycin, clindamycin, and gentamicin.32,35,42 Mycoplasma pneumonias Mycoplasmas are the smallest free-living organisms that have yet been identified. This class of organisms is intermediate between bacteria and viruses. Unlike bacteria, they have no rigid cell wall, and unlike viruses, they do not require the intracellular machinery of a host cell to replicate. Mycoplasma pneumoniae M. pneumoniae is seen in all age groups but is more common in persons less than 20 years old. Mycoplasma pneumonias account for 20% of all community-acquired pneumonias.32 This infection is common year round, but usually the incidence increases in the fall and winter. Mycoplasma pneumonia has also been termed walking pneumonia because the respiratory symptoms are often not severe enough for people to seek medical attention. The course of the disease is approximately 4 weeks, and it is very infectious; whole families may become ill once a child brings it into the home. The signs and symptoms often include many extrapulmonary manifestations that are not common in bacterial or viral pneumonias. Patients may have fever, shaking chills, dry cough, headache, malaise, sore throat, earache, arthralgias, arthritis, immune dysfunction with an autoantibody response, meningoencephalitis, meningitis, transverse myelitis, cranial nerve palsies, Guillain–Barré syndrome, myocarditis, pericarditis, gastroenteritis, pancreatitis, glomerulonephritis, hepatitis, generalized lymphadenopathy, and erythema multiforme, including Stevens–Johnson syndrome.30 The chest radiograph shows interstitial infiltrates, usually unilateral in the lower lobe; 20% of patients have a pleural effusion. Treatment is with erythromycin, tetracycline, or streptomycin.32,42

Viral Pneumonias Cytomegalovirus, varicella zoster, and herpes simplex cause viral pneumonias most commonly in immunocompromised hosts, such as patients who have had major organ transplants or who have AIDS or malignancy. The respiratory syncytial virus and the parainfluenza virus cause viral pneumonias in children. The adenovirus is a source of viral pneumonias in children and in military recruits. Viral pneumonias in the debilitated elderly are most commonly caused by the influenza virus. Persons most at risk for a viral pneumonia are those who have an underlying cardiopulmonary disease or who are immunosuppressed or pregnant. Complications of viral pneumonias include secondary bacterial infections, bronchial hyperreactivity and possibly asthma, chronic air flow

obstruction, tracheitis, bronchitis, bronchiolitis, and acellular hyaline membrane formation. Some antiviral agents are now available. Acyclovir is used against herpes simplex and varicella-zoster. Amantadine is the drug of choice for influenza A. Ribavirin is used in children to treat the respiratory syncytial virus. Cytomegalovirus is treated with the acyclovir analog dihydroxyphenylglycol (DHPG). No drug therapy is available for all the varieties of viral agents, so treatment is often limited to supportive measures.32,35

Fungal Pneumonias Pneumocystis jiroveci Previously called Pneumocystis carinii and originally described as a protozoan, this is now thought to be a fungal organism.30 Pneumocystis carinii pneumonia (PCP) is closely associated with AIDS because nearly 75% of AIDS patients have at least one episode of PCP during their lifetime.30 Patients with AIDS have impairment of T-cell function, as well as humoral immune dysfunction, and thus are susceptible to infection from bacteria, viruses, fungi, and parasites. Pneumocystis carinii pneumonia is also seen in transplant patients, especially those on cyclosporine, and in patients with lymphoreticular hematologic malignancies.10 The chest radiograph most commonly shows bilateral diffuse interstitial or alveolar infiltrates, more prominent in the perihilar regions, and a solitary pulmonary nodule.10 Pneumocystis carinii pneumonia damages the parenchymal cells within the lung and alters the alveolar–capillary permeability. This type of pneumonia usually has a subacute course of fever, dyspnea, cough, chest pain, malaise, fatigue, weight loss, and night sweats, but the symptoms can progress to include tachypnea, reduced PaO2, and cyanosis.10 Treatment is with trimethoprimsulfamethoxazole. If this drug is not tolerated, then pentamidine is prescribed.10,12,32

Chlamydial Pneumonias Chlamydia psittaci C. psittaci causes approximately 12% of the community-acquired pneumonias in the student population and about 6% of the community-acquired pneumonias in the elderly.32 The onset is usually insidious, with cough, sputum, hemoptysis, dyspnea, headache, myalgia, and hepatosplenomegaly.10,30 Complications include laryngitis, pharyngitis, encephalitis, hemolytic anemia, bradycardia, hepatitis, renal failure, and macular rash. Treatment is with tetracycline or chloramphenicol.10,30

Neoplastic Causes Bronchogenic Carcinoma Lung cancer, collectively called bronchogenic carcinoma, is a growth of abnormal epithelial cells in the tracheobronchial tree.32,43 As the tumor enlarges, irritation occurs in the airways and alveoli, causing swelling, fluid buildup in adjacent alveoli, mucus production, and eventual obstruction.43 This growth or tumor may spread by infiltrating surrounding tissues, such as the mediastinum, chest wall, ribs, or diaphragm, or by metastasizing to other body organs, or both (Fig. 5-12).7 Currently, the International Association for the Study of Lung Cancer (IASLC) has defined two main types of lung cancer: small cell cancer and non–small cell lung cancer, which includes squamous cell, adenocarcinoma, and large cell, undifferentiated.44 With more than 221,000 new cases annually (as estimated for 2015), lung cancer is the leading cause of cancer deaths, accounting for 27% (Fig. 5-13).43-45

FIGURE 5-12 Primary lung cancer metastasizes to pleura, lymph, bone, brain, kidney, and liver. (From Damjanov I: Pathology for the Health Professions, ed 3, St. Louis, 2006, Saunders.)

Etiology The causes of lung cancer are numerous. It has now been well established through numerous studies that the primary causative factor is tobacco use. Approximately 80% to 90% of lung cancers are caused by tobacco, and heavy smokers are 25% more likely to develop a neoplasm compared with nonsmokers.30,43,44 The average cigarette smoker has ten times the risk of developing lung cancer as the nonsmoker, as there are 4000 different carcinogenic chemicals in tobacco smoke. Most disturbing is the finding that lung cancer risk is closely related to initiating smoking at an early age. When children start smoking at 15 years of age or younger and continue smoking, after 50 years, they have a 100-fold increased risk of lung cancer over that of a nonsmoker.30 Passive smoking, or secondhand smoking—exposure to cigarette smoke exhaled by a smoker—as well as side-stream smoke have also been shown to increase the incidence of lung cancer by approximately 30%. Like active smoking at an early age, passive smoking during childhood and adolescence may pose a significantly increased risk.30,43

Occupational agents have also been implicated in the development of bronchogenic carcinoma. The known carcinogens present in the workplace include radioactive material, asbestos, chromates, nickel, mustard gas, isopropyl oil, hydrocarbons, arsenic, hematite, vinyl chloride, diesel exhaust, and bis(chloromethyl) ether.32,43 Increased exposure to radon or significant air pollution also increases the incidence of lung cancer, although the relationship is very difficult to quantify. It is interesting that diets containing beta carotene (found in many green, yellow, and orange fruits and vegetables) have been shown to modestly decrease the risk for lung and other cancers.28 In some individuals and families, a genetic predisposition for the development of lung cancer seems to be present. Globally, it is estimated that one death occurs each minute as a result of lung cancer.30 Currently, lung cancer accounts for 33% of all cancer deaths in men and 23% of all cancer deaths in women and is the second most common cancer. Over the past 20 years, the male–female ratio of lung cancer deaths has dropped from 5.7:1 to 1.4:1 as a result of the striking increase in lung cancer among women, which began about 1965.10 It is now the leading cause of death from cancer in both men and women, surpassing breast cancer. In 2008 approximately 159,400 Americans died of lung cancer: 88,900 men and 70,500 women.29 In the same year, almost 219,000 new cases of lung cancer were diagnosed.32

FIGURE 5-13 Age-adjusted mortality rates for asbestosis in US residents aged 15 or older by state (1990-1999). Delaware and West Virginia had the highest asbestosis mortality rates during 19901999. States in the second highest mortality rate category were predominantly coastal states. All states in these 2 groups had asbestosis mortality rates above the US average rate of 5.4 per million. (From NIOSH 2002 IN Lazarus AA, Philip A: Asbestosis. Disease-a-Month. 2011; 57(1):14-26.)

Pathophysiology Each of the four major types of bronchogenic carcinoma is discussed separately (Table 5-

12).43,45 Small cell carcinoma, also called oat cell carcinoma, accounts for 10% to 15% of all lung cancer.3,45 It may arise in any part of the bronchial tree; however, 75% of the time it presents as a centrally located proximal lesion.32 It often has hilar or mediastinal lymph node involvement. This tumor usually does not extend into the bronchial lumen, but spreads through the submucosa and can cause obstructive and restrictive dysfunction through compression of the surrounding lung tissue. This type of lung cancer rapidly involves the vascular channels, lymph nodes, and soft tissue. It is known to metastasize widely and early, and in most patients has metastasized by the time the diagnosis is made. This tumor rarely cavitates, but commonly produces hormones that can lead to a wide variety of symptoms in many different body systems not involved in direct metastasis. A number of body organs, however, are involved in direct metastasis. Seventy-five percent of small cell carcinoma metastasizes to the central nervous system, 65% to the liver, 58% to the adrenal gland, 30% to the pancreas, 28% to bone, 20% to the genitourinary system, 10% to the thyroid, and 10% to the spleen.32 The metastases to the central nervous system and the bone often produce clinical symptoms such as hemiplegia, epilepsy, personality changes, confusion, speech deficits, headache, bone pain, and pathologic fractures. Metastases to the liver and the adrenal glands are often clinically silent.9 Other clinical symptoms caused by tumor hormone production that are of particular interest to the physical therapist include abnormalities in the neurologic or musculoskeletal systems. These complications of small cell carcinoma can include progressive dementia, ataxia, vertigo, sensory neuropathy with numbness and loss of reflexes, motor neuropathy with progressive muscle weakness and wasting, atrophic paresis of the proximal limb-girdle musculature, marked fatigability, osteoarthropathy, arthralgia, and peripheral edema.32 Squamous cell carcinoma accounts for 25% to 30% of all lung cancer.45 It arises from the bronchial mucosa after repeated inflammation or irritation caused by cancer stimuli. Squamous cell carcinoma often arises in the segmental or subsegmental bronchi, but can also cause a hilar tumor. It is considered a centrally located tumor and occurs in the peripheral lung only about 30% of the time. Squamous cell tumors are bulky. They cause obstructive dysfunction because they extend into the bronchial lumen, which can prevent airflow and lead to atelectasis and pneumonia. They cause restrictive dysfunction because the tumor can compress the surrounding lung tissue and cause atelectasis and pneumonia, both of which decrease the ventilation–perfusion matching and impair gas exchange. These tumors often cavitate but do not metastasize early. When squamous cell cancer does metastasize, it most often involves the liver, adrenal gland, central nervous system, and pancreas.32

Table 5-12 Descriptions of types of Bronchogenic Carcinoma

Adenocarcinoma includes acinar adenocarcinoma, papillary adenocarcinoma, and bronchoalveolar carcinoma and accounts for 40% to 50% of all lung cancer.10 This is now the most common type of lung cancer in the United States.30,45 The majority of these tumors are located in the periphery of the lung and may not be spatially related to the bronchial tree. These tumors may arise as a solitary nodule and may involve the pleura, causing a carcinogenic pleural effusion. Adenocarcinomas metastasize widely and often involve the central nervous system, which produces neurologic symptoms already listed under small cell carcinoma. Approximately half of these tumors involve the hilar and mediastinal lymph nodes.32 Large cell carcinoma includes all tumors not categorized in the first three groups and accounts for 10% to 15% of all lung cancer.3 These tumors are most frequently subpleural in location. Peripheral tumors are often large, lobulated, and bulky, causing compression of the normal lung tissue. They are usually sharply defined lesions, which may be necrotic or cavitate. This type of tumor spreads locally by invasion and also metastasizes widely, with more than 50% metastasizing to the brain.32 The prognosis for lung cancer is usually discussed in terms of 5-year survival rates according to the stage of the disease. The assigned stage number is determined by the International Cancer Staging System and is determined using a TNM classification (primary tumor, nodal involvement, and metastatic presence and extent). The 5-year survival rate for stage I is 50%, for stage II is 30%, for stage IIIa is 17%, and for stage IIIb and stage IV is less than 5%.43 Lung cancer prognosis is bleak. About 41% of patients die within 1 year of the diagnosis. However, from 2001 to 2011, the mortality rates for men decreased by 2.5% per year and 0.9% for women.44 Despite the decrease in mortality rates, the majority of these people could have been spared this diagnosis, with its pain, health care costs, morbidity, and unrelenting fatal conclusion, if they had given up smoking.

Diagnostic Tests Routine chest x-ray can be used to identify nodules or tumors if they are large enough. Positron emission tomography (PET) scans or CT scans can show smaller lesions and presence of metastatic lesions. Bronchoscopy, mediastinoscopy, transbronchial needle biopsy, thoracentesis, video-assisted thorascopy, or open lung biopsy can allow for tissue

sampling and confirmation of diagnosis (Fig. 5-14).46,47

Clinical Manifestation The clinical manifestation of bronchogenic carcinoma can be found in Table 5-13.

Treatment The three most widely accepted forms of therapy are still surgery, radiation, and chemotherapy. Newer treatment interventions being applied to patients with lung cancer include immunotherapy (also called targeted therapy), laser, brachytherapy, stent placement, and nutritional therapy.45 Targeted therapies include drugs that target tumor blood vessel growth and drugs that target the epidermal growth factor. These targeted therapies are still being assessed for impact on survival rate, but some initial studies are showing prolonged survival of patients with non–small cell lung cancer when added to chemotherapy.45 Surgical removal of the tumor remains the treatment of choice for all non–small cell lung carcinoma when the location of the tumor makes resection possible.32 The more defined and smaller the lesion, the better the surgical success rate. Radiation can be either external beam radiation therapy or internal radiation therapy (brachytherapy) where a radioactive substance is inserted into the tumor by needles.45 However, small cell lung carcinoma is the most radiosensitive, followed by squamous cell carcinoma and adenocarcinoma. Large cell carcinoma is the least responsive to radiation.32 The response to radiation therapy depends on the size of the tumor and the intrathoracic spread of the cancer. Chemotherapy does not significantly benefit non– small cell lung carcinoma. The response rates are low, and the toxicity rates for the drugs used are high. Chemotherapy is the treatment of choice for small cell lung carcinoma.32 Due to the early spread of small cell carcinoma, surgery has little to offer patients with this type of cancer. Chemotherapy and radiation in combination with chemotherapy are often used to treat small cell carcinoma. See Chapter 7 for the effects of chemotherapy and radiation on the cardiopulmonary system.

Pleural Diseases Pleural Effusion The pleural space is the cavity between the visceral and parietal pleura; this cavity normally contains between 10 and 25 mL of fluid. This fluid, which is a filtrate created in the pleural capillaries and lymphatics, is mostly reabsorbed by the lymphatics of the parietal pleura. Whenever there is an abnormal amount of pleural fluid in the pleural space, it is called pleural effusion. In disease states, greater than 3 L of fluid can accumulate48 (Fig. 5-15). The fluid is a transudate if it has a low protein content and accumulates due to changes in the hydrostatic pressure within the pleural capillaries. The fluid is an exudate if it has a high protein content and accumulates because of changes in the permeability of the pleural surfaces.33

FIGURE 5-14 Bronchogenic carcinoma presenting as a solitary mass in the right lower lung field (arrow). Courtesy Steven P. Brownstein, MD (From Marchiori DM: Clinical Imaging with Skeletal, Chest, and Ab dominal Pattern Differentials, ed 3, St. Louis, 2014, Elsevier.)

Table 5-13 Clinical manifestation of bronchogenic carcinoma

JVD, jugular venous distention; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2.

Etiology There are 60 different causes of pleural effusions, with the most common conditions being cardiac failure, pneumonia, and malignant neoplasm.46,48

Pathophysiology The capillaries in the parietal pleura receive blood via the high-pressure systemic arterial circulation. The capillaries in the visceral pleura receive blood via the low-pressure pulmonary circulation. Because of this pressure gradient, fluid is constantly moving from the parietal pleural capillaries into the pleural space and is then reabsorbed into the visceral pleural capillaries. Normally, pleural fluid formation and pleural fluid resorption are balanced so fluid does not accumulate in the pleural space. When this balance is disrupted by any cause and a significant amount of fluid is allowed to accumulate in the pleural space, this limits the lungs’ ability to expand, which results in a restrictive

pulmonary impairment.3

Clinical tip The diagnosis of pleural effusion is not an indication for bronchopulmonary hygiene techniques. Instead, prevention of further pulmonary complications can be achieved with change of position, breathing exercises in different positions, and increasing activity. However, until the fluid is removed or reabsorbed, compression of the alveoli will occur, and atelectasis will be present. Transudative pleural effusions are associated with an elevation in the hydrostatic pressure in the pleural capillaries. This is most commonly due to left-sided heart failure, right-sided heart failure, or both. Because of the increased pressure, more fluid is moved out of the pleural capillaries and less fluid is reabsorbed. There is therefore excess fluid in the pleural space, causing a bilateral pleural effusion. Congestive heart failure is the single most common cause of transudative pleural effusions.3 Exudative pleural effusions are associated with an increase in the permeability of the pleural surfaces that allows protein and excess fluid to move into the pleural space. Therefore in exudative pleural effusions, the pleurae are in some way involved in the pathologic process. Most commonly, the pleurae may be involved in an inflammatory process or with neoplastic disease. Inflammatory processes such as pneumonia, tuberculosis, or pulmonary emboli with infarction can begin in the lung but extend into the visceral pleura, causing disruption of the normal pleural permeability. Cancer can also cause disruption of the normal pleural permeability, either by direct extension of a lung tumor to the pleural surface or by hematogenous dissemination of tumor cells to the pleural surface from a distant source. Tumor cells are also spread via the lymphatic system and therefore can alter the normal lymphatic clearance of the pleural space or are brought into the pleural space by the pleural lymphatics (Fig. 5-16).3

FIGURE 5-15 Pleural effusion, a collection of fluid in the pleural space between the membrane encasing the lung and the membrane lining the thoracic cavity, as seen on upright x-ray examination. Pleurisy (pleuritis) is an inflammation of the visceral and parietal pleurae. When there is an abnormal increase in the lubricating fluid between these two layers, it is called pleurisy with effusion. (From Goodman CC: Pathology: Implications for the Physical Therapist, ed 3, St. Louis, 2009, Saunders.)

FIGURE 5-16 Pleural diseases. Pleuritis is usually associated with pleural effusion. Fibrothorax is an encasement of the lungs with fibrous tissue that obliterates the pleural cavity. Pneumothorax denotes the entry of air into the pleural cavity. Empyema involves pockets of pus enclosed in fibrous adhesions. (From Damjanov I: Pathology for the Health Professions, ed 3, St. Louis, 2006, Saunders.)

Diagnostic Tests Diagnosis begins with obtaining a clinical history and doing a physical examination, followed by chest radiography and analysis of pleural fluid in appropriate instances. Further investigative studies include CT of the thorax, pleural biopsy, thoracentesis, thoracoscopy, and occasionally bronchoscopy.1,48

Table 5-14 Clinical manifestation of pleural effusions

Clinical Manifestation The clinical manifestation of pleural effusions can be found in Table 5-14.

Treatment The underlying cause of the pleural effusion must be identified and treated. In many cases, this treatment causes the pleural effusion to resolve secondarily.10 Diagnostic thoracentesis, a procedure during which a needle is inserted into the chest wall to extract fluid, and tissue samples can be used to determine whether the fluid is a transudate or exudate.10 Thoracentesis can also be used therapeutically to remove excess pleural fluid via a large-bore needle. However, there is little evidence that patients benefit from this intervention, and it is being used less frequently.28 A new procedure, thoracoscopy, uses a rigid scope with a light source to explore the entire hemithorax. Thoracoscopy can be used to biopsy the pleura, biopsy the lung, obtain pleural fluid samples, remove pleural fluid, and perform a pleurodesis, and, if necessary, lysis of adhesions can be accomplished (Fig. 5-17).10 Another treatment option that is used if a large infected pleural effusion (empyema) is present is the placement of a pleural space chest tube for drainage of this fluid.28 For additional therapeutic management, see practice pattern 6B (Impaired Aerobic Capacity/Endurance Associated with Deconditioning).49

Atelectasis The term atelectasis, meaning “incomplete expansion,” describes a state where a region of the lung parenchyma is collapsed and nonaerated. There are several pulmonary and chest disorders for which this pathologic condition is associated. Atelectasis represents a manifestation of these disorders rather than it being a disease itself.47

Etiology Atelectasis can be classified into five types. (1) Resorptive, also known as obstructive atelectasis, is the most common type. It is often due to an obstruction such as a tumor, foreign body, or mucus plug. There is resorption of the alveolar air distal to the obstruction. Resorptive atelectasis can be divided into two groups depending on whether bronchial obstruction involves a large airway such as segmental, lobar, or main bronchus or smaller peripheral bronchi or bronchioles.50 (2) Passive atelectasis refers to loss of volume in the lung and is caused by simple pneumothorax or diaphragmatic dysfunction. It also occurs with persistent use of small TVs by the patient. This may occur with use of sedatives, bed rest, lack of deep breathing, and when a patient has been under general anesthesia.1 Both resorptive and passive atelectasis are associated with postoperative or bedridden patients. (3) Adhesive atelectasis may occur when there is a surfactant deficiency. When this occurs, there is a greater tendency for the alveoli to collapse. When this happens, the alveoli walls adhere, therefore making reexpansion difficult. Conditions that would cause this include HMD, smoke inhalation, adult RDS, pulmonary embolus, cardiac bypass surgery, uremia, acute radiation pneumonitis, and pneumonia.50 (4) Compressive atelectasis results from compression of the lung from a space-occupying lesion. This compresses the lung and squeezes air out of the alveoli.50 This may occur with a pleural effusion, pleural tumor, or empyema.50 (5) Cicatrization atelectasis indicates volume loss, which is due to decreased pulmonary compliance due to fibrosis.50

Diagnostic Tests Atelectasis is seen by chest radiograph using anteroposterior and lateral projections (Fig. 5-18).47

FIGURE 5-17 The technique of thoracentesis involves passage of a needle just superior to the rib. If the needle is placed too low on the chest, the diaphragm or organs below the diaphragm can be punctured. Diagnostic thoracentesis can be performed with small amounts of pleural fluid. (From Kacmarek R, Stoller J, Heuer A: Egan’s Fundamentals of Respiratory Care, ed 10, St. Louis, 2013, Mosby.)

Clinical Manifestation Chest radiograph may show opacification of the atelectatic segment or lobe, or with significant lung collapse, the radiograph will show elevation of the hemidiaphragm on the affected side, shift of the mediastinum toward the affected side, and a decrease in size of the rib interspaces over the affected hemithorax. The symptoms the patient experiences with atelectasis are more likely from the cause of the atelectasis, such as postoperative pain and low-grade fever; however, if obstruction is the cause, the patient may be extremely dyspneic and demonstrate increased work of breathing.

Treatment Treatment includes management of the underlying cause. Atelectasis, occurring postoperatively or in bedridden patients, such as with resorptive or passive atelectasis, can respond to deep breathing or incentive spirometry exercises, as well as coughing. Other airway clearance techniques may help as well. If simple measures do not improve the lung collapse, fiber-optic bronchoscopy can be performed to suction secretions that may be causing the atelectasis. Prevention of atelectasis should be the goal for all hospitalized patients who are unconscious or who may have poor airway clearance techniques, have postoperative pain preventing adequate inspiration and cough, or who demonstrate respiratory muscle weakness.

See Also

OCR | Washington and Lee University

Acute Respiratory Distress Syndrome/Acute Lung Injury Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) occur as the result of a disease that causes inflammation, leading to increased pulmonary vascular

permeability, increased lung weight, and loss of aerated tissue.51 It was previously named “adult” respiratory distress syndrome to distinguish it from neonatal acute respiratory failure, which was due to immature lungs with inadequate surfactant production. It was later changed to “acute” respiratory distress syndrome as it became known that diffuse lung injury from a variety of causes could affect both adult and pediatric populations.52 Also recently updated was the term ALI. Previously, the term was used to describe the milder end of the spectrum; however, now the term used is mild ARDS.51

FIGURE 5-18 Mechanism of atelectasis. A, Collapse of the lung in pneumothorax. B, Compression of the lung by pleural fluid. C, Resorption of the air from alveoli distal to an obstructed bronchus. Obstructive atelectasis is usually focal. Atelectasis of premature infants, which is caused by a deficiency of pulmonary surfactant, is not shown. (From Damjanov I: Pathology for the Health Professions, ed 3, St. Louis, 2006, Saunders.)

Etiology Approximately 150,000 cases of ARDS are diagnosed annually in the United States.32 Table 5-15 presents the most common pulmonary and extrapulmonary triggers of ARDS.

Table 5-15 Triggers of ARDS

Pathophysiology Acute respiratory distress syndrome is a widespread inflammatory condition affecting the pulmonary tissue. It includes a three-stage process: exudative, proliferative, and fibrotic. In the exudative phase, a capillary leak causes the alveoli to fill with a neutrophilic infiltrate and protein-rich edema. This cycle of leakage and inflammation is worsened by the release of inflammatory mediators from the activated neutrophils. If the syndrome develops into the proliferative and fibrotic phases, chronic inflammation will subsequently lead to scar formation. Inflammatory debris in the early phase will cause diffusion abnormalities, ventilation–perfusion mismatch, and reduced compliance. Thrombus formation within the pulmonary capillaries increases dead space ventilation, and hypoxic pulmonary vasoconstriction may contribute to right-sided heart failure. This will ultimately lead to respiratory failure (Fig. 5-19).51

Diagnostic Tests Arterial blood gas analysis, as well as chest radiograph and/or CT scan, are required. Bilateral opacities consistent with pulmonary edema are the defining criteria (Fig. 5-20).51

FIGURE 5-19 Pathogenesis of adult respiratory distress syndrome. A, Alveolar cell injury. B, Endothelial cell injury. Regardless of the initial injury, the established lesions appear identical and comprise hyaline membranes, ruptured alveolar walls, and intraalveolar edema fluid. PMN, polymorphonuclear neutrophil. (From Damjanov I: Pathology for the Health Professions, ed 3, St. Louis, 2006, Saunders.)

FIGURE 5-20 Pulmonary edema (From Mettler F: Essentials of radiology, ed 2, St. Louis, 2014, Saunders.)

Clinical Manifestation The clinical manifestation of ARDS can be found in Table 5-16.

Treatment The first area is treatment of the precipitating cause of the ARDS. A wide range of treatment protocols are used to address the many underlying causes. The second area of treatment is mechanical ventilation. A treatment strategy called lung protective ventilation is utilized where the goal is to achieve adequate gas exchange with the lowest possible TVs (4 to 8 mL/kg of ideal body weight), airway pressures (goal plateau pressures 30 cm H2O or less), and oxygen concentrations.52 This has been shown to reduce further damage due to mechanical ventilation.52 Positive end expiratory pressure of approximately 5 to 15 cm H2O is often utilized. Positive end expiratory pressure will increase oxygenation by inflating collapsed alveoli.51 Also, because the dependent areas of the lung are often more severely affected, positioning the patient in a prone position is recommended. This will improve oxygenation by altering the dependent area of lung to areas less severely affected.51 Thus oxygenation will improve. The next area of treatment is supportive: managing the patient’s nutritional status and fluid balance. Fluid and electrolyte balance is very important in these patients. Management may mean monitoring input and output and using diuretics. Or, because ARDS can be associated with multiorgan failure, it may mean the use of highly technical interventions such as continuous arteriovenous

hemofiltration (CAVH) or dialysis in patients with chronic renal insufficiency.9 The final focus of treatment is to prevent and treat complications of the patient’s condition, along with intensive care measures. The prognosis in ARDS is always guarded; mortality can be as high as 50% to 70%, especially if this syndrome is associated with failure in other organ systems or is complicated by serious or repeated infections.9,32 Table 5-16 Clinical manifestation of adult respiratory distress syndrome

COPD, chronic obstructive pulmonary disease; DLCO, diffusing capacity of the lungs for carbon monoxide; FRC, functional residual capacity; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; VC, vital capacity; VT, tidal volume.

All patients with ARDS suffer some degree of muscle wasting and weakness, which continues past 1-year postdischarge. For this reason, when appropriate to initiate, early mobility is crucial.

Cardiovascular Causes Pulmonary Edema Pulmonary edema is an increase in the amount of fluid within the lung resulting from excessive fluid movement from the pulmonary vascular system to the extravascular system. Usually, the pulmonary interstitium is affected first and then the alveolar spaces.32,43,53

Etiology Pulmonary edema has two main categories: cardiogenic pulmonary edema and noncardiogenic pulmonary edema. Cardiogenic pulmonary edema, which is discussed in this section, is an increase in the pulmonary capillary hydrostatic pressure, often secondary to left ventricular failure (see Fig. 4-8). Cardiogenic pulmonary edema is also known as high-pressure pulmonary edema, hydrostatic pulmonary edema, or hemodynamic pulmonary edema. Common causes of cardiogenic pulmonary edema include arrhythmias producing low cardiac output, congenital heart defects, excessive fluid administration, left ventricular failure, mitral or aortic disease, myocardial infarction, pulmonary embolus, renal failure, rheumatic heart disease or myocarditis, and systemic hypertension. Noncardiogenic pulmonary edema has a multitude of causes, including increased capillary permeability, lymphatic insufficiency, decreased intrapleural pressure, or decreased oncotic pressure. Pulmonary edema can also be caused by increased alveolar capillary membrane permeability secondary to various causes. This type of pulmonary edema is also named ARDS and was discussed under the section “Pulmonary Causes of Restrictive Lung Dysfunction.”9,32,43

Pathophysiology As the left ventricle fails, its ability to contract and pump blood into the systemic circulation efficiently is diminished. This results in an increase in left atrial pressure, which is transmitted back to the pulmonary circulation. Because of this impedance to blood flow, the pressure in the microcirculation of the lung is increased, which increases the transvascular flow of fluid into the interstitium of the lung. When the pulmonary vascular hydrostatic pressure rises above 25 to 30 mm Hg, the oncotic pressure loses its holding force and fluid is allowed to spill into the interstitial space. The interstitial space can accommodate a small amount of excess fluid, approximately 500 mL.32 The lymphatic drainage can be enhanced to move some excess fluid out of the thorax. However, when the left atrial pressure rises above 30 mm Hg, these protective mechanisms are overcome.32 The interstitial edema fluid disrupts the tight alveolar epithelium, floods the alveolar spaces, and moves through the visceral pleura, causing pleural effusions. The pulmonary edema fluid in cardiogenic pulmonary edema is characterized by low protein concentrations. This finding is in contrast to that in ARDS in which the pulmonary edema fluid has elevated protein concentrations. With fluid in the alveoli and the

interstitium, lung compliance is decreased, ventilation–perfusion mismatching is increased, gas exchange is disrupted, the work of breathing is increased, and there is restrictive lung dysfunction.9,32,53 As a result of gravity, as well as the pulmonary perfusion pressure and pulmonary venous pressure from the apex to the base, excess fluid gathers in the dependent areas of the lung.54 Prognosis for patients with pulmonary edema does not directly correlate with the edema itself, but rather the impact of the edema. Adequate treatment of the fluid buildup is critical for treatment. Correct diagnosis of cardiogenic pulmonary edema and therefore adequate treatment can aid in improving prognosis.53,54

Diagnostic Tests Pulmonary edema is usually seen as basilar infiltrates with pulmonary vascular redistribution and with increased upper lobe appearance. In the context of patients with CHF, the cardiac silhouette is often visualized as large. Brain natriuretic peptide (BNP) levels can increase in relation to factors beyond pressure, and volume overload may be elevated.54 Table 5-17 Clinical manifestation of pulmonary edema

DLCO, diffusing capacity of the lungs for carbon monoxide; PaO2, arterial partial pressure of O2; PFT, pulmonary function test; RR, respiratory rate.

Clinical Manifestation The clinical manifestation of pulmonary edema can be found in Table 5-17 and Fig. 5-21.

Treatment Treatment is aimed at decreasing the cardiac preload and maintaining oxygenation of the tissues. To decrease cardiac preload, venous return to the heart is decreased, which decreases the left ventricular filling pressure. Venodilators, such as morphine sulfate or sodium nitroprusside, and diuretics, such as furosemide, are used to decrease the venous return and decreased afterload. Angiotensin-converting enzyme (ACE) inhibitors may also be used to decrease afterload in more chronic cases. Positive inotropes, such as dopamine, dobutamine, amiodarone, and digitalis, may be given to improve cardiac contractility and increase cardiac output. To maintain oxygenation, supplemental oxygen is provided. Intubation with mechanical ventilation may also be necessary.28 Bronchial hygiene treatments may be used to assist with clearance of secretions. Furthermore, albumin or mannitol may be used to increase osmotic pressure to combat the increased hydrostatic forces.

FIGURE 5-21 Cardiogenic pulmonary edema following myocardial infarction in a 52-year-old man, illustrating widespread fissural thickening and lack of clarity of the intrapulmonary vessels. There is frank alveolar edema in the right lower zone. The fissural thickening caused by subpleural edema is particularly striking. A, Frontal view. B, Lateral view. (From Armstrong P, Wilson AG, Dee P, et al: Imaging of diseases of the chest, ed 3, St. Louis, 2000, Mosby.)

Pulmonary Emboli Pulmonary emboli are a complication of venous thrombosis in which blood clots or thrombi travel from a systemic vein through the right side of the heart and into the pulmonary circulation, where they lodge in branches of the pulmonary artery (Fig. 522).3,26,43

Etiology Pulmonary embolism is the most common acute pulmonary problem among hospitalized patients in the United States. Each year it is estimated that 300,000 to 600,000 Americans have a pulmonary embolic event.32,43,55 Many of these events may go unnoticed because they are clinically silent, with only 20% presenting with the classic

triad of symptoms: dyspnea, hemoptysis, and pleuritic chest pain. However, approximately 10% to 30% of pulmonary embolisms result in the patient’s death within 1 month of diagnosis.32 About one-third of the deaths occur within 1 hour of the acute event, and more than half of these fatalities occur in patients in whom the diagnosis was not clinically suspect.32,43 In more than 95% of the cases, the thrombi that caused the pulmonary emboli were formed in the lower extremities.3,43 In the remaining 5% of the cases, the thrombi may be formed in the pelvis, the arms, or the right side of the heart. Numerous risk factors increase the likelihood of thrombus formation in the lower extremities (Box 5-2). The highest risk group for thrombophlebitis is orthopedic patients. Studies have shown that the frequency of deep vein thrombosis (DVT) perioperative is 80% in patients after hip or knee surgery.28,43

Pathophysiology The pathophysiologic changes that occur following pulmonary embolism affect the pulmonary system and the cardiovascular system. First, the occlusion of one or more pulmonary arterial branches causes edema and hemorrhage into the surrounding lung parenchyma. This is known as congestive atelectasis. Second, the lack of blood flow causes coagulative necrosis of the alveolar walls; the alveoli fill with erythrocytes, and there is an inflammatory response. Third, there is an increase in the alveolar dead space because a portion of the lung is being ventilated but no longer perfused. Pneumoconstriction of the affected area occurs, with a marked decrease in alveolar carbon dioxide due to the lack of gas exchange and the patient’s respiratory pattern of hyperventilation. In addition, the alveolar surfactant decreases over a period of approximately 24 hours, which results in alveolar collapse and regional atelectasis. These changes combine to cause an acute increase in ventilation–perfusion mismatching, a decrease in lung compliance, and impaired gas exchange. If the oxygen supply is completely cut off to a portion of the lung, then frank necrosis and infarction of lung tissue results. This happens in less than 10% of all pulmonary embolisms because lung tissue has three sources of oxygen: the pulmonary vascular system, the bronchial vascular system, and the alveolar gas.32 However, infarction of lung tissue is followed by contraction of the affected tissue and scar formation.

FIGURE 5-22 Pathophysiology of pulmonary embolism. Pulmonary embolism usually originates in the deep veins of the legs, most commonly the calf veins. These venous thrombi originate predominantly in venous valve pockets and at other sites of presumed venous stasis (inset). If a clot propagates to the knee vein or above or if it originates above the knee, the risk of embolism increases. Thromboemboli travel through the right side of the heart to reach the lungs. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. (From Tapson VF: Acute pulmonary embolism. N Engl J Med 358(10):1037-1052, 2008.)

The first cardiovascular change that occurs because of a pulmonary embolism is an increase in the pulmonary arterial resistance due to a decrease in the cross-sectional area of the pulmonary arterial bed. If this cross-sectional area is decreased by more than 50%, then the pressure needed to maintain pulmonary blood flow rises and pulmonary hypertension results.32 This also increases the work of the right ventricle and can lead to right ventricular failure. If the pulmonary embolus is massive, right ventricular failure

and cardiac arrest can occur within minutes.9,32,53 Prognosis for pulmonary embolism is largely dependent on identification and adequate treatment and anticoagulation therapy. The ultimate prognosis is extremely variable. In patients who experience no shock and are treated medically, the mortality rate is 10% to 20%.28 Patients who have pulmonary embolism and a simultaneous cardiac arrest have a 45% mortality rate. Patients who have a pulmonary embolism with extreme increases in right ventricular pressures have a 90% mortality rate.32 Pulmonary embolism is the cause of as many as 100,000 deaths per year and a contributory factor in 100,000 more.21 However, prognosis is generally favorable due to the fact that small emboli resolve without serious complication.21

BO X 5- 2 Risk fa ct ors for lowe r e x t re m it y t hrom bus form a t ion • Immobilization: • Bed rest • Long periods of travel • Fracture stabilization • Injuries to leg (blow to leg, athletic injury, surgery, radiation therapy) • Increased age • Inherited clotting disorders • Factor 5V Leiden • Prothrombin gene mutation • Infections and inflammatory diseases • Systemic lupus erythematosus • Rheumatoid arthritis • Crohn disease • Glomerulonephritis • Pregnancy and individuals taking oral contraceptives • Cancer (ovaries, pancreas, lymphatic, liver, stomach, and colon) • Smoking • Obesity • Burns • Thrombocytosis • Sickle cell anemia • Orthopedic patients: after hip or knee surgery (highest risk)

Diagnostic Tests An embolism often cannot be found on chest x-ray, but x-rays can assist with differential diagnosis of a pulmonary embolism and can show the extent of infiltrate and atelectasis, which occurs in 50% of cases. In addition, the chest x-ray may show an elevated hemidiaphragm in 40% of cases. An ECG can be helpful to identify associated

arrhythmias with ST-T wave abnormalities, tachycardia, atrial flutter, or fibrillation occurring more commonly. V/Q scans do assist with confirming embolisms, and often the patient with a pulmonary embolism will present with a normal V/Q scan. Computed tomography scans are becoming the primary test for pulmonary embolism secondary to the noninvasive nature and quick turn-around time. Blood tests such as the fibrinogen test can be helpful in checking for protein fibrinogen, which is an important part of the clotting cascade. Pulmonary angiogram, extremity venography, and magnetic resonance imaging (MRI) may also be used but are less likely due to invasive nature or cost or time factors. The Wells score is a clinical prediction rule that health care professionals may use to assist with differential diagnosis. A numerical score of 3 points is given for clinically suspected DVT and alternative diagnosis is less likely than pulmonary embolism.56 A point value of 1.5 is given for tachycardia (pulse >100), immobilization (≥3d/surgery in previous 4 weeks), or a history of a pulmonary embolism or DVT. One point is given for hemoptysis or malignancy with treatment in the past 6 months. A score above 6 is a high probability, 2 to 6 is a moderate probability, and below 2 is low.56 Table 5-18 Clinical manifestation of pulmonary emboli

ECG, electrocardiograph; PE, pulmonary emboli; RR, respiratory rate.

Clinical Manifestation The clinical manifestation of a pulmonary embolus can be found in Table 5-18.

Treatment Treatment begins with prevention of DVT. Two methods are used in preventing or minimizing DVT. The mechanical approach includes ankle pumping exercises in bed, early ambulation, use of gradient compression stockings, pneumatic calf compression, and electrical stimulation of calf muscles. The pharmacologic approach includes the use

of agents that decrease the hypercoagulability of the blood, such as warfarin, dextran, low-molecular-weight heparin, heparinoids, and heparin.28 Newer medications have more recently appeared on the market that do not require frequent international normalized ratio (INR) checks for coagulation, with examples being dabigatran etexilate, apixaban, and rivaroxaban. The risks and benefits of these newer medications are still being evaluated for long-term side effects, but they are approved for the treatment of DVT/PE after the patient has been treated with parenteral anticoagulant for 5 to 10 days. With repeated thrombus formation and embolic events, surgical placement of a transvenous device (e.g., Greenfield filter) to prevent migration of thrombi may be utilized.54 Heparin therapy is most commonly used to treat pulmonary embolism. Heparin does not lyse existing clots, but it prevents formation and propagation of further clots.28 To maintain adequate tissue oxygenation, mechanical ventilation with supplemental oxygen may be required. In addition, if the patient is hypotensive or in shock, fluid therapy and vasopressors may be needed. Mild sedation and analgesia may be used to decrease anxiety and pain. Thromboembolic lysing agents (e.g., streptokinase) can be used to lyse the emboli, but this therapeutic intervention is no more effective than heparin therapy in terms of the patient’s morbidity or mortality.28 Pulmonary embolectomy is being performed less frequently due to the increased mortality rate (50% to 94%) compared with the mortality rate (10% to 20%) for conventional medical treatment.28 However, this emergent surgical intervention may be indicated in patients who have large emboli and cannot receive heparin therapy or have overt right ventricular heart failure leading to cardiac arrest.

Neuromuscular Causes Spinal Cord Injury Spinal cord injury (SCI) is damage to or interruption of the neurologic pathways contained within the spinal cord.53,57

Etiology An SCI can result from an acute traumatic event, often a motor vehicle accident or a diving accident, or from a pathologic process that invades the spinal cord and damages it or in some way interrupts the neurologic transmissions.

Pathophysiology For this discussion, SCIs include cervical injuries only. An SCI in the cervical region produces paralysis or paresis in the arms, legs, and trunk, therefore resulting in tetraplegia. With this type of injury, the expiratory muscles are paralyzed or very weak, leading to an inability to cough. This ineffective cough may cause an increase in the incidence of pulmonary infections. The external intercostals are inactive, and the patient may have a functional, weak, or absent diaphragm, depending on the level of the injury (see Table 5-16).9,57 Weakness in the inspiratory muscles results in alveolar hypoventilation, hypoxemia, and hypercapnia. Because the alveoli are not well ventilated, the patient is prone to atelectasis, particularly in the dependent lung regions, which could lead to recurrent pulmonary infections. With parts of the lung underventilated, the ventilation–perfusion matching is impaired and the diffusing capacity is reduced. A cervical injury also results in the loss of the sigh reflex, which increases the incidence of atelectasis and contributes to alveolar collapse. If the patient retains use of the diaphragm, breathing dynamics are altered markedly, resulting in paradoxical breathing (Fig. 5-23). In paradoxical breathing, the diaphragm descends on inspiration, causing the abdomen to rise and the paralyzed thoracic wall to be pulled inward. The diaphragm relaxes on exhalation, causing the abdomen to fall and the chest wall to move outward. Immediately after a cervical injury, the VC and the maximum voluntary ventilation are markedly reduced.

FIGURE 5-23 Paradoxical breathing. Note the position of the rib cage and abdomen. Top, Paradoxical breathing when the diaphragm is strong, but the accessory muscles are absent. Bottom, Paradoxical breathing during paralysis of the diaphragm.

Approximately 6 months after injury, the VC has improved significantly if the patient has an intact diaphragm. And although it may not be normal, the VC may have doubled since the acute postinjury period. Paradoxical breathing is also diminished or eliminated because of the developing spasticity in the thorax and abdomen.9,12,57 Over time, pulmonary compliance is decreased due to the shallow breathing and atelectasis within the lung, and chest wall compliance is decreased as a result of paralysis of the thoracic musculature and the developing thoracic spasticity. This increases the work of breathing and can lead to diaphragmatic fatigue. All these pathophysiologic alterations lead to RLD and a chronic state of hypoxemia. The patient may therefore need mechanical ventilation part-time or full-time or an enriched FiO2.3,9,35 Over the years, advances in urologic management have improved. Now pneumonia and septic infections have the greatest impact on mortality rates.44 Paralysis of the respiratory muscles is highly correlated with morbidity and mortality during the first 4 weeks, with the highest mortality rates occurring in the first year. Other causes related to the cardiovascular system include pulmonary embolism, myocardial infarction, cardiac arrest, and myocarditis; however, due to improved pharmacologic treatments, the

mortality in the SCI population does not differ greatly from the general population.43,44

Diagnostic Tests Diagnosis of SCI is often a result of medical history and physical examination. Spine xrays, myelogram, CT scan, or MRI may be used to visualize areas of the spinal cord affected. Somatosensory-evoked potential testing or magnetic stimulation may also be used to assist in diagnostics as well as prognostics.54

Clinical Manifestation The clinical manifestation of SCI can be found in Tables 5-19 and 5-20.

Treatment Patients with SCIs must be taught ways to strengthen and increase the endurance of any remaining ventilatory muscles via use of an inspiratory muscle trainer, resistance exercises to the diaphragm, or an incentive spirometer. Patients must learn how to perform active and passive chest wall stretching, using rolling, positioning, side leaning, and air shift maneuvers. Patients, family members, or caregivers need to know how to assist the patient in clearing excess secretions with postural drainage, percussion, assisted coughing, and possibly suctioning. Learning how to perform glossopharyngeal breathing or how to operate a portable ventilator may also be necessary for selected patients.57

Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis is a progressive degenerative disease of the nervous system that involves both upper and lower motor neurons, causing both flaccid and spastic paralysis.2,3

Etiology The cause of the disease is unknown.54 Recently, the genetic component has become clearer in families with a history of ALS. Although this is only 5% to 10% of cases, it is thought to be an autosomal-dominant trait with a characteristic early onset. It occurs worldwide, but the onset is usually after the age of 40. Men are affected 1.7 times as often as women.44,53 It is estimated that 20,000 to 30,000 Americans have ALS, with approximately 5600 people diagnosed each year.44,54

Table 5-19 Innervation levels of the respiratory muscles

Pathophysiology Amyotrophic means the muscle is void or has limited nourishment; demyelination and death of the upper and lower motor neurons occurs, and defects in protein degradation also play a role. The anterior horn cells of the cervical, lower thoracic, and lumbosacral spinal segments usually are the most involved, which means that the respiratory muscles may be affected severely. Muscles innervated by the cranial nerves and the spinal nerves frequently are involved, causing problems with dysarthria and dysphagia. Muscle weakness and wasting are profound. The course is aggressively progressive following the onset of neurologic symptoms. The average life expectancy is 2 to 5 years from time of diagnosis.55 Ten percent survive more than 10 years, and 5% live to 20 years.44 Death is often the result of acute respiratory failure.35

Diagnostic Tests Diagnosis is based on the combination of electromyogram (EMG) and clinical presentation. Time of diagnosis is largely dependent on the first presenting symptom. Electrodiagnosis of rapidly developing ALS and slowly developing ALS is very different, and therefore multiple sites in the head, upper extremity, and lower extremity are recommended.54

Table 5-20 Clinical manifestation of spinal cord injury

CNS, central nervous system; FRC, functional residual capacity; IC, inspiratory capacity; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Clinical Manifestation The clinical manifestation of ALS can be found in Table 5-21.

Treatment There is no treatment for this disease except supportive therapy to make the patient more comfortable. Physical exertion is not recommended because it tires the patient so rapidly. However, the patient should be encouraged to get out of bed and be as mobile as possible. Patients eventually develop weakness of respiratory muscles that follows with need for mechanical ventilation to maintain adequate gas exchange. Diaphragm pacing has recently been used in the ALS and SCI population to facilitate diaphragm function.58 In a recent multicenter study, laparoscopic diaphragm motor pacing was shown to be safe and effective in both SCI and ALS patients. Mechanical ventilation can be delayed in patients with ALS, which in turn increases survival. In patients with SCI, it allows freedom from the ventilator.58

Poliomyelitis Poliomyelitis (polio) is a viral disease that attacks the motor nerve cells of the spinal cord and brainstem and can result in muscular paralysis.3

Table 5-21 Clinical manifestation of amyotrophic lateral sclerosis

ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MVV, maximum voluntary ventilation; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Etiology Polio is caused by an acute viral infection, which can reach epidemic proportions in atrisk populations. It is reported most commonly in children. This infection can now be prevented by vaccine.

Pathophysiology The virus is neurotropic and has a predilection for the motor cells of the anterior horn and the brainstem. The lesions are patchy and asymmetric, and microscopically healthy and diseased cells can be seen side by side. This results in a patchy flaccid paralysis or paresis of the lower motor neuron type. Both the diaphragm and intercostal muscles may be affected, resulting in a respiratory muscle weakness that can progress to respiratory failure. One form of polio, bulbar polio, affects the brainstem and can result in the loss of the swallowing reflexes, thus leading to aspiration problems. There are two stages in polio. The preparalytic stage is characterized by fever, headache, malaise, and symptoms in the gastrointestinal (GI) and upper respiratory tracts. For some patients, this stage is followed by the paralytic stage, which includes tremulousness of the limbs, tenderness in the muscles, and swollen painful joints, as well as flaccid paralysis of from one to two muscles to all four limbs and the trunk.2,3,35 Of those infected with polio, 72% have no symptoms, 24% have minor symptoms, and 1% have permanent paralysis.44 Postpolio syndrome (PPS) is a slowly progressive disorder. Stable periods can last up to 3 to 10 years with a decline in functional status correlating to a poorer quality of life. Postpolio syndrome affects survivors of polio years (21 plus) after recovery from the initial illness. The clinical manifestation of PPS includes new weakening of muscles that were previously affected, as well as muscles that were not affected. The onset is slow, with progressive muscle weakness, general fatigue, and possibly muscle atrophy and joint pain. Problems occur if respiratory muscle weakness develops and the patient develops hypoxemia and low ventilation or weakness of swallowing muscles, making him

or her at increased risk of aspiration pneumonia. It is estimated that PPS affects 25% to 50% of the polio survivors (approximately 440,000 individuals).59

Diagnostic Tests Electromyogram can be used to confirm denervation. Orthopedic, neurologic, and psychiatric disorders must be ruled out; therefore polio is largely a diagnosis of exclusion.54

Clinical Manifestation The clinical manifestation of polio with respiratory involvement can be found in Table 522.

Treatment There is no specific treatment for poliomyelitis. Prevention through the use of oral or parenteral vaccine is very effective. Supportive therapy consisting of rest during the acute phase, with proper positioning, pain relief, good nutrition, and ventilatory support, as needed, appropriate. Later, active range-of-motion exercises, strengthening exercises, bracing, and other equipment evaluation are required for patients with paralysis. Electrical stimulation may be used to improve and maintain muscle strength, and use of progressive isometric resistance training has been shown to improve overall strength and cardiovascular and pulmonary status.54 Table 5-22 Clinical manifestation of poliomyelitis

DLCO, diffusing capacity of the lungs for carbon monoxide; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MVV, maximum voluntary ventilation; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; VT, tidal volume.

Guillain–Barré Syndrome Guillain–Barré syndrome is a demyelinating disease of the motor neurons of the peripheral nerves.35

Etiology This idiopathic polyneuritis is a disorder that is linked to the immune system, presenting with ascending paralysis. The history of most patients with Guillain–Barré syndrome includes a viral illness (hemophilic influenza, Epstein–Barr virus, and cytomegalovirus), bacterial infections, surgical intervention, or vaccinations (specifically the Menactra meningococcal vaccine).43 Two-thirds report acute infection within 2 months, and 90% had an illness within the past 30 days.3,54

Pathophysiology Guillain–Barré syndrome is characterized by a rapid bilateral flaccid motor paralysis and areflexia. The loss of muscular strength is usually fully realized within 30 days, often within 10 to 15 days, and may leave the patient so involved that mechanical ventilation is required. Approximately 10% to 20% of all patients with Guillain–Barré syndrome develop acute respiratory failure and must be placed on a ventilator.9 The duration of mechanical ventilation is variable but is usually between 2 weeks and 2 months.2,3,9,35 If severe pulmonary dysfunction is noted, outside the context of muscle weakness, differential diagnosis is warranted. Controlling responses to this autoimmune disease have improved mortality rates, which now exceed 5%. Poorer outcome is associated with diagnosis at an older age, a longer time before recovery begins, and the need for mechanical ventilation. Most patients recover, but up to 20% have remaining deficits, with 20% of patients sustaining significant debility up to 1 year postincident. Length of time to the maximal level of impairment has not been shown to correlate with outcomes; however, the quicker recovery begins to occur, the less likely long-term disability will occur.53 Table 5-23 Clinical manifestation of Guillain–Barré syndrome

ERV, expiratory reserve volume; IRV, inspiratory reserve volume; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Diagnostic Tests Cerebrospinal fluid (CSF) analysis is often started 1 week after the presentation of symptoms. If albumin levels are elevated in the CSF with 10 or fewer mononuclear leukocytes, Guillain–Barré is suspected. Electromyogram can be used to show decreased

nerve conduction velocity and/or fibrillation potentials. Differential diagnosis includes hysteria, stroke in the brainstem, acute neuropathies, and porphyria.54

Clinical Manifestation The clinical manifestation of Guillain–Barré syndrome can be found in Table 5-23.

Treatment Patients diagnosed with Guillain–Barré often undergo plasmapheresis and high-dose immunoglobulin therapy, both of which have been shown to be effective and safe. Steroids have been shown to reduce the severity.60 Because there is no cure, patients are supported throughout the syndrome’s progression. Heat may be used to decrease muscular pain. Passive range-of-motion exercise is begun immediately. Active exercises, including breathing exercises to assist the patient in weaning from the ventilator, should be started as soon as the patient’s condition has stabilized. Although exercise is important, patients with syndrome fatigue easily and should not be overly stressed. This polyneuropathy usually leads to complete recovery with minimal permanent sequelae. Recurrence of Guillain–Barré syndrome in the same patient is possible; in fact, patients with this syndrome are at slightly higher risk than the general public. However, even a second bout of the syndrome usually resolves.3,53

Myasthenia Gravis Myasthenia gravis is a chronic neuromuscular disease characterized by progressive muscular weakness on exertion.2

Etiology Myasthenia gravis is caused by an autoimmune attack on the acetylcholine receptors at the postsynaptic neuromuscular junction. What causes the production of this antibody is unknown. This disease predominantly affects women, and its onset is usually between 20 and 40 years of age.53

Pathophysiology The antibody immunoglobulin G (IgG) binds to the acetylcholine receptor sites, which impairs the normal transmission of impulses from the nerves to the muscles. The muscles most characteristically involved are those innervated by the cranial nerves. This causes ptosis, diplopia, dysarthria, dysphagia, and proximal limb weakness. The signs and symptoms of this disease may fluctuate over a period of hours or days. Severe generalized quadriparesis may develop. Approximately 10% of patients develop respiratory muscle involvement that can be life threatening.53,61 The relapses and exacerbations associated with myasthenia gravis are more frequent in the first year, and remissions are rarely complete or permanent. This disease follows a slow progressive course, with the onset of systemic disorders and infections causing

most of the common crises. A crisis is when the respiratory muscles are affected, requiring mechanical ventilation with treatment in the intensive care unit (ICU). Fifty percent of patients who undergo a thymectomy have stable and long-lasting complete resolution of symptoms.60

Diagnostic Tests History and clinical manifestations are primarily used for diagnosis. Monitoring symptoms of weakness and improvement of symptoms with rest is an important aspect of differential diagnosis, as many other diseases need to be ruled out. Immunologic testing detects antiacetylcholine receptor antibodies in the serum. Treatment and improvement with edrophonium (Tensilon), which inhibits acetylcholinesterase (required for acetylcholine uptake), may indicate myasthenia gravis. Electromyography may also be used with normal results at rest and rapidly decreasing amplitude in the motor action potential with repetitive stimulation. Measurements of ventilatory function should also be performed for analysis of the respiratory impairment.54

Clinical Manifestation The clinical manifestation of myasthenia gravis can be found in Table 5-24. Table 5-24 Clinical manifestation of myasthenia gravis

DLCO, diffusing capacity of the lungs for carbon monoxide; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; SOB, shortness of breath; VT, tidal volume.

Treatment Treatment of the disease’s symptoms is with an anticholinesterase (pyridostigmine or neostigmine helps to improve neuromuscular transmission and increase muscle strength) and immunosuppressive drugs (to suppress the production of abnormal antibodies). Plasmapheresis can be used to remove abnormal antibodies, and high-dose intravenous immunoglobulin can modify the abnormal antibodies by infusing them with

antibodies from donated blood. Thymectomy is recommended for thymoma and is used in an effort to alter the disease’s progression by reducing symptoms and possibly rebalancing the immune system.35,53,60

Tetanus Tetanus is a disease of the neuromuscular system caused by the neurotoxin produced by C. tetani.2 This anaerobic bacillus is found in the soil and the excreta of humans and animals and usually enters via a contaminated wound. The neurotoxin binds to the ganglioside membranes of the nerve synapses and blocks release of the inhibitory transmitter. This action causes severe muscle spasticity with superimposed tonic convulsions. This muscle rigidity can become so severe that the chest wall is immobilized, resulting in asphyxia and death. Tetanus can produce the most severe example of decreased chest wall compliance, leading to a restrictive impairment incompatible with life. The best treatment for tetanus is prevention via immunization. Prompt and careful wound debridement is also important. Once a patient has developed the disease, the tetanus antitoxin can be used to neutralize non-fixed toxin in the system. Once fixed or bound, the toxin cannot be neutralized. Supportive therapy is primarily focused on maintaining an airway and ensuring adequate ventilation.2,53

Pseudohypertrophic (Duchenne) Muscular Dystrophy Pseudohypertrophic muscular dystrophy is a genetically determined, progressive degenerative myopathy.53,61

Etiology Pseudohypertrophic muscular dystrophy is a sex-linked (X chromosome) recessive disorder that occurs only in boys and is transmitted by female carriers. It is the most common of the muscular dystrophies, with a prevalence rate of 15 per 100,000 males in the United States.44,53,61

Pathophysiology Pseudohypertrophic muscular dystrophy typically appears when boys who have this recessive gene are 3 to 5 years of age.53,60 Muscle biopsy at this time shows both muscle fiber hypertrophy and necrosis with regeneration. There is also excessive infiltration of the muscle with fibrous tissue and fat. Muscle innervation is not normal in this disease, but the abnormality is due to loss of motor end plates when muscle fibers degenerate and not to neurogenic disease. The pelvic girdle is affected first, and then the shoulder girdle muscles become involved. Although the calf often shows pseudohypertrophy, the quadriceps usually appear atrophied. The progression of the disease is steady, and most patients are confined to wheelchairs by 10 to 12 years of age. Involvement of the diaphragm occurs late in the course of this disease. However, respiratory failure and

infection are the causes of death in 75% of these patients, which occurs usually by age 20.9,53,61 Prognosis varies depending on the type of muscular dystrophy. In general, the earlier the signs and symptoms appear, the poorer the prognosis. The source of morbidity and mortality is often pulmonary complications from respiratory muscle dysfunction and cardiac myopathy. Life into the third decade for pseudohypertrophic muscular dystrophy is uncommon.54,60 In a recent study conducted by the Centers for Disease Control and Prevention in four states in the United States, survival rates were 100% for males aged 5 to 9 years old, 99% for ages 10 to 14, 85% for ages 15 to 19, and 58% for ages 20 to 24.44

Diagnostic Tests Electromyography, muscle biopsy, and serum enzymes are used for diagnosis of muscular dystrophy.54 Specific to pseudohypertrophic muscular dystrophy, chorionic villi sampling and amniocentesis prenatal diagnostics may be used to analyze DNA. Serum enzyme creatine kinase MM (CK-MM) and creatine kinase MB (CK-MB) may both be elevated, with CK-MM levels elevated two to ten times normal, reflecting protein wasting.54

Clinical Manifestation The clinical manifestation of pseudohypertrophic muscular dystrophy can be found in Table 5-25.

Treatment There is no curative treatment. Supportive treatment is aimed at preserving the patient’s mobility as long as possible and making the patient comfortable. Respiratory treatment involves prevention of infection with maintenance of good inspiratory effort and good airway clearance to mobilize any secretions.

Other Muscular Dystrophies Facioscapulohumeral Muscular Dystrophy Facioscapulohumeral muscular dystrophy is an autosomal-dominant disorder characterized by weakness of the facial and shoulder girdle muscles. Respiratory involvement or failure is uncommon in this type of muscular dystrophy.9,53

Limb-Girdle Muscular Dystrophy Limb-girdle muscular dystrophy is a disorder in which adults exhibit weakness of the pelvic and shoulder girdle musculature. There can be severe involvement of the diaphragm early in the course of this disease.9,53

Myotonic Muscular Dystrophy Myotonic muscular dystrophy is an autosomal-dominant disorder that combines

myotonia with progressive peripheral muscle weakness. Respiratory involvement and failure are common as this disease progresses.9,53 Table 5-25 Clinical manifestation of pseudohypertrophic muscular dystrophy

MVV, maximum voluntary ventilation; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Musculoskeletal Causes Diaphragmatic Paralysis or Paresis Diaphragmatic paralysis or paresis is the loss or impairment of motor function of the diaphragm because of a lesion in the neurologic or muscular system. The paralysis or paresis may be temporary or permanent.32,35

Etiology Unilateral paralysis or paresis of the diaphragm is most commonly caused by invasion of the phrenic nerve by bronchogenic carcinoma.32 Another very common cause is thoracic surgery. An estimated 20% of patients who undergo thoracic surgery suffer injury to the phrenic nerve due to either cold or stretching of the nerve.28,32 In hemiplegic patients, it is not uncommon to find paralysis of the corresponding hemidiaphragm. The left hemidiaphragm is involved in left hemiplegia more frequently than the right hemidiaphragm is involved in right hemiplegia.35 Other causes of unilateral diaphragmatic dysfunction include poliomyelitis; Huntington chorea; herpes zoster; or peripheral neuritis associated with measles, tetanus, typhoid, or diphtheria. Bilateral paralysis or paresis of the diaphragm may result from high SCI, thoracic trauma, Guillain–Barré syndrome, multiple sclerosis, muscular dystrophy, or anterior horn cell disease.28,32,35

Pathophysiology Normally, as the crural portion of the diaphragm contracts, the pleural space pressure decreases; the central tendon moves caudally; the lungs inflate; and the abdominal pressure increases, which moves the abdominal wall outward. Contraction of the costal portion of the diaphragm accomplishes these same effects and causes the anterior lower ribs to expand and move in a cephalad direction.9 In diaphragmatic paralysis or significant weakness, the negative pleural space pressure moves the diaphragm in a cephalad direction so that the diaphragm’s resting position is elevated Fig. 5-24. During inspiration, as the pleural space pressure becomes more negative, the paralyzed diaphragm is pulled farther upward and the anterior lower ribs are pulled inward rather than being expanded.32 These changes in ventilatory mechanics cause alveolar hypoventilation with secondary changes that are seen in the lung parenchyma. The decreased inspiratory capacity leads to microatelectasis, ventilation–perfusion mismatching, alveolar collapse, and hypoxemia. The atelectasis leads to a decrease in lung compliance and an increase in the work of breathing. These pathologic changes are heightened in the supine position. The rib cage is elevated in the supine position, putting the rib cage musculature at a mechanical disadvantage, thereby decreasing its ability to generate an inspiratory volume.10 Therefore in the supine position, diaphragmatic dysfunction produces a more significant decrease in alveolar ventilation than that produced in the upright position. The changes in the ventilatory mechanics and within

the lung parenchyma combine to increase the risk of pulmonary infection or pneumonia in patients with diaphragmatic dysfunction.9,32,35

Diagnostic Tests The diaphragm can be evaluated in multiple ways. Indirect measures include functional respiratory tests to assess flow rate and pressure.54,62 Fluoroscopy, CT scan, or ultrasound can provide direct monitoring through indirect visualization. Finally, electromyography can be used to directly assess the muscle electrical activity. The diaphragm contractile force measurement is a direct way of measuring transdiaphragmatic pressure by using a probe with a double balloon (esophageal and gastric). This allows for calculation of the difference between gastric pressure and esophageal pressure, which is the transdiaphragmatic pressure. The degree of weakness of the diaphragm is best measured by transdiaphragmatic pressure.54,62 The normal transdiaphragmatic pressure is higher than 98 cm H2O.26,35 When the transdiaphragmatic pressure is lower than 20 cm H2O, the patient exhibits significant respiratory distress.35 The maximum transdiaphragmatic pressure is decreased 50% and the maximum inspiratory pressure is decreased 40% with unilateral paralysis.28,32 The reduction is even more profound with bilateral involvement.

FIGURE 5-24 A and B, congenital eventration of the right hemidiaphragm (arrows). (From Marchiori DM: Clinical Imaging with Skeletal, Chest, and Ab dominal Pattern Differentials, ed 3, St. Louis, 2014, Mosby.)

Clinical Manifestation The clinical manifestation of diaphragmatic paralysis or paresis can be found in Table 526.

Treatment Patients with unilateral diaphragmatic involvement usually do not require treatment because of the large pulmonary reserve and the other respiratory muscles that are still functional. With bilateral involvement, either full-time or part-time mechanical

ventilation is often required. Diaphragmatic pacing via an intact phrenic nerve is also a possibility for some of these patients; however, the success rate with this treatment intervention is estimated at only 50%.28,35 Table 5-26 Clinical manifestation of diaphragmatic paralysis or paresis

Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; TLC, total lung capacity; VC, vital capacity; VT, tidal volume

Kyphoscoliosis Kyphoscoliosis is a combination of excessive anteroposterior and lateral curvature of the thoracic spine (Fig. 5-25, A).3,9 This bony abnormality occurs in 3% of the population. However, lung dysfunction occurs in only 3% of the population with kyphoscoliosis (see Fig. 5-25, B).28,32 In severe kyphoscoliosis, the lungs are compressed and the alveoli are restricted from full expansion; this causes hypoventilation and atelectasis.43

FIGURE 5-25 Kyphoscoliosis. A, Schema showing the rotation of the spine and rib cage in kyphoscoliosis. B, This chest radiograph of a patient with kyphoscoliosis reveals a markedly abnormal, reverse-S-shaped curve of the thoracic spine that is deforming the mediastinal structures and the ribs. This patient is breathing primarily with the diaphragm. (A From Bergofsky EH, Turino GM, Fishman AP: Cardiorespiratory failure in kyphoscoliosis. Medicine (Baltimore) 38:263-317, 1959.) (B From Frownfelter D, Dean E: Cardiovascular and Pulmonary Physical Therapy: Evidence and Practice, ed 4, St. Louis, 2006, Mosby.)

Etiology The cause of kyphoscoliosis is unknown or idiopathic in 85% of the cases. Idiopathic kyphoscoliosis is usually divided into three groups by age at onset: infantile, juvenile, and adolescent (10 to 14 years of age), with most cases appearing in the adolescent group. There is a 4:1 ratio of females to males in this group. The other 15% of the cases are due to known congenital causes (e.g., hemivertebrae) or develop in response to a neuromuscular disease (e.g., poliomyelitis, syringomyelia, muscular dystrophy).28,32

Pathophysiology In addition to the excessive anteroposterior and lateral curvature, the lateral displacement causes two more structural changes. A second lateral curve develops to

counterbalance the primary curve. In addition, the spine rotates on its longitudinal axis so that the ribs on the side of the convexity are displaced posteriorly and splayed, creating a gibbous hump, whereas the ribs on the side of the concavity are compressed. Significant spinal curvature must be present before pulmonary symptoms develop. Usually angles less than 70 degrees do not produce pulmonary symptoms. Angles between 70 and 120 degrees cause some respiratory dysfunction, and respiratory symptoms may increase with age as the angle increases and as the changes associated with aging affect the lung. Angles greater than 120 degrees are commonly associated with severe RLD and respiratory failure.9 These skeletal abnormalities decrease the chest wall compliance, which may be as low as 25% of predicted.9 Lung compliance is also decreased and dead space increased. The distribution of ventilation is disturbed, with more air going to the apices. Ventilation–perfusion matching is markedly impaired. These changes lead to a state of alveolar hypoventilation and a profound increase in the work of breathing—as high as 500% over normal.9 The hypoventilation causes pulmonary hypertension, which over time causes structural changes in the vessels and thickening of the pulmonary arteriolar walls, leading to cor pulmonale. Although the respiratory muscles need to work harder to overcome the decreased pulmonary compliance, they are impaired because of the mechanical disadvantages from the thoracoabdominal deformity. When the VC is decreased to less than 40% of the predicted value, cardiorespiratory failure is likely to occur.35 This usually occurs in the fourth or fifth decade of life. Sixty percent of deaths are due to respiratory failure or cor pulmonale.35

Diagnostic Tests Posture analysis and clinical examinations are primarily used, with confirmation from radiographic findings. Radiographic findings may include Schmorl’s nodes, end-plate narrowing, or irregular end plates.54

Clinical Manifestation The clinical manifestation of kyphoscoliosis can be found in Table 5-27 and Fig. 5-25.

Treatment Kyphoscoliosis is treated conservatively with orthotic devices and an exercise program. Surgical intervention includes placement of Harrington distraction strut bars. Pulmonary compromise is treated with preventive and supportive measures, including immunizations, good hydration, aggressive treatment of pulmonary infections, avoidance of sedatives, supplemental oxygen, and respiratory muscle training.10 Serious pulmonary involvement, including recurrent episodes of respiratory failure, seems to benefit from long-term nocturnal mechanical ventilation either through a chest cuirass or a positive pressure ventilator.32,35 Studies have shown that nasal CPAP is also beneficial, and it is now the preferred therapy.28 Unless surgical intervention is completed, kyphoscoliosis is a permanent condition, and symptom management is the primary method of treatment.

Ankylosing Spondylitis Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine characterized by immobility of the sacroiliac and vertebral joints and by ossification of the paravertebral ligaments.2,12 Table 5-27 Clinical manifestation of kyphoscoliosis

DLCO, diffusing capacity of the lungs for carbon monoxide; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; RV, residual volume; VC, vital capacity; VT, tidal volume; HR, heart rate; CO, cardiac output; BP, blood pressure.

Etiology Ankylosing spondylitis is an inherited arthritic condition that ultimately immobilizes the spine and results in a fixed thoracic cage.32 It occurs predominantly in men aged 20 to 40 years.10

Pathophysiology The pulmonary impairment caused by this disease results from the markedly decreased compliance of the chest wall. With thoracic expansion so markedly decreased, ventilation becomes dependent almost entirely on diaphragmatic movement. Displacement of the abdomen during inspiration may be increased to compensate for the lack of rib expansion. Because the diaphragm is the major muscle of inspiration, the restrictive impairment involving the chest wall may result in only minimal respiratory symptoms.9,32 However, approximately 6% of patients with AS develop specific fibrosing lesions in the upper lobes as part of this disease process.8 Why these lesions occur in some patients is unknown, but the immune system may be involved.31 The pulmonary lesions may be unilateral or bilateral; they begin as small irregular opacities in the upper lobes. These lesions then increase in size, coalesce, and contract the lung parenchyma. Cavitation is frequent. The lung architecture becomes distorted, showing dense fibrosis that can lead to bronchiectasis and repeated pulmonary infections and an obstructive pulmonary deficit superimposed on the RLD.8,31 Apical pleural thickening is invariably present.10 Less than 1% of patients affected by AS have complete remission, and 80% of patients that are ill for 20 years face daily pain. Patients undergo periods of exacerbation and remission throughout the course of AS, with the severity of symptoms occurring in the

first decade of diagnosis. The severity during this period has been shown to correlate with long-term severity and disabling nature. A more severe course affects the peripheral joints, and hip involvement is a prognostic marker for long-term severity of the disease.21,54

Clinical Manifestation The clinical manifestation of AS can be found in Table 5-28.

Treatment There is no curative treatment for AS. It is important to maintain good body alignment and as much thoracic mobility as possible. If there is direct lung involvement, then treatment of repeated pulmonary infections is required. Tumor necrosis factor (TNF) blocker slows the TNF by targeting the protein that causes inflammation in RA and therefore can reduce pain, stiffness, and swelling in joints in AS as well. A joint replacement is an option with severely compromised joints.54

Pectus Excavatum Pectus excavatum (funnel chest) is a congenital abnormality characterized by sternal depression and decreased anteroposterior diameter (Fig. 5-26, A). The lower portion of the sternum is displaced posteriorly, and the anterior ribs are bowed markedly. Pulmonary function values are normal or near normal, and respiratory symptoms are uncommon. If the deformity is very severe, the patient may have decreased TLC, VC, and maximum voluntary ventilation and may complain of dyspnea on exertion, precordial pain, palpitation, and dizziness. Usually, no treatment is indicated because the deformity is only cosmetic, with no functional deficits.2,32,35 Table 5-28 Clinical manifestation of ankylosing spondylitis

FRC, functional residual capacity; IC, inspiratory capacity; RV, residual volume; VC, vital capacity.

Pectus Carinatum Pectus carinatum (pigeon breast) is a structural abnormality characterized by the sternum protruding anteriorly (Fig. 5-26, B). Fifty percent of patients with atrial or

ventricular septal defects have pectus carinatum. It also has been associated with severe prolonged childhood asthma. There is no pulmonary compromise associated with this structural abnormality, and no treatment is indicated.32

Connective Tissue Causes of RLD Rheumatoid Arthritis Rheumatoid arthritis is a chronic process characterized by inflammation of the peripheral joints that results in progressive destruction of articular and periarticular structures.2,32

Etiology The etiology is unknown. There is a high prevalence of RA in the United States; in 2005 about 1.5 million adults were estimated to have a diagnosis with this chronic condition.25,44 There have been varied estimates (5% to 58%) of the incidence of pulmonary involvement as part of the RA disease.31,44 Lung involvement with RA usually occurs between 50 and 60 years of age and is very rare in children who have RA.25 Rheumatoid arthritis is more prevalent in women (two to three times higher), which may be attributed to use of oral contraceptives, hormone replacement therapy, and history of breastfeeding and live birth, as well as menstrual history.44 The onset for men and women is usually highest among those that are in their 60s.44 Pulmonary involvement, particularly pulmonary fibrosis, is more common in men.33 There is also a strong correlation between smoking and RA, with a 1.3 to 2.4 increased risk.44

FIGURE 5-26 A, Twelve-year-old boy with the most frequent form of pectus excavatum: the thorax is symmetric, with a depression in the inferior portion of the sternum.Pictures courtesy of Dr. Dickens St-Vil. (From Gilbert-Barness E, Kapur R, Oligny LL, et al, editors: Potter’s Pathology of the Fetus, Infant and Child, ed 2, St. Louis, 2007, Mosby.) B, Thirteen-year-old boy with pectus carinatum. Bilateral depressions are seen laterally to the cartilage of the costochondral junction, which is bilaterally hypertrophic; the sternum projects anteriorly. Pictures courtesy of Dr. Dickens St-Vil. (From Gilbert-Barness E, Kapur R, Oligny LL, et al, editors: Potter’s pathology of the fetus, infant and child, ed 2, St. Louis, 2007, Mosby.)

Pathophysiology Pulmonary involvement in RA was first recognized and reported by Ellman and Ball in 1948.33 Rheumatoid arthritis can affect the lungs in seven different ways: pleural involvement, pneumonitis, interstitial fibrosis, development of pulmonary nodules, pulmonary vasculitis, obliterative bronchiolitis (OB), and an increased incidence of bronchogenic cancer.10 These different pulmonary manifestations of RA may occur individually or in combination within the lungs.33 Pleural involvement may include pleuritis, pleural friction rub, repeated small exudative pleural effusions, and pleural thickening and fibrosis.25,31,63 These pulmonary abnormalities can result in pain and some RLD. Pneumonitis causes an inflammatory reaction in the lung, including patchy infiltrates, which can resolve spontaneously or can progress to fibrotic changes. The cause of interstitial fibrosis in the patient with RA is unknown, but seems to correlate with increased manifestations of autoimmunity.33 Patients with a high titer of rheumatoid factor are more likely to develop interstitial fibrosis.16 There seems to be a temporal relationship between joint involvement and development of fibrosing alveolitis, with the joint involvement usually coming first.25 Interstitial fibrosis can be diffuse but predominates in the lower lobes. Rheumatoid (necrobiotic) nodules usually occur subpleurally in the upper lung fields or in the interlobular septa. They may be single, multiple, unilateral, or bilateral. Spontaneous

resolution of these nodules can occur. Cavitation is common.33,35 If a patient with RA is exposed to coal dust, pulmonary nodules known as Caplan syndrome can develop. These multiple peripheral pulmonary nodules have a pigmented ring of coal dust surrounding the lesion. Rheumatoid nodules and Caplan syndrome rarely produce significant RLD.27,31 Pulmonary vasculitis often occurs adjacent to pulmonary nodules. There is intimal fibrosis in the pulmonary arterioles.8,33 Obliterative bronchiolitis is rare; however, the onset is usually acute and progresses within 2 years to a fatal outcome. The bronchioles become inflamed and edematous and are then replaced with granulation tissue. The bronchial lumen is severely narrowed or obliterated.8,35 The increased incidence of bronchogenic cancer in RA is related to coexisting interstitial fibrosis in both smokers and nonsmokers.10 In addition to lung involvement with RA, chest wall compliance may be decreased significantly due to increased rigidity of the thorax because of RA, decreased inspiratory muscle power because of rheumatoid myopathy, or decreased mobility because of pain caused by pleurisy. Therefore the RLD that can result in RA patients may be due to a decrease in both lung and chest wall compliance.25

Diagnostic Tests Diagnostic criteria for RA have been set by the American College of Rheumatology. Four or more of the following must be present to establish a diagnosis: (1) 1 hour of morning stiffness present for at least 6 weeks; (2) inflammatory arthritic manifestations in three or more joints for at least 6 weeks; (3) swelling of the wrist, metacarpophalangeal, or proximal interphalangeal joints for 6 or more weeks; (4) symmetric joint swelling; (5) radiographic evidence of changes in hand or wrist joints that must include erosions or unequivocal bony calcification; (6) rheumatoid nodules; and (7) presence of serum rheumatoid factor. Use of radiography, ultrasound, and MRI are often used to visualize the joints.54

Clinical Manifestation The clinical manifestation of RA can be found in Table 5-29.

Treatment Corticosteroids and immunosuppressant drugs are commonly used to treat pulmonary involvement in RA.33,35,54 Rheumatoid arthritis is often treated with medications that can slow the progression and relieve symptoms. These medications include TNF blockers, medications that block the rate of bone loss, immunosuppressants, and nonsteroidal anti-inflammatory drugs (NSAIDs). Synovectomy, tenosynovectomy, or total joint replacements are surgical techniques that may be used if conservative management does not allow for adequate symptom mangement.54

Table 5-29 Clinical manifestation of rheumatoid arthritis

DLCO, diffusing capacity of the lungs for carbon monoxide; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; VC, vital capacity.

There is no cure for RA at this time, and joint changes are irreversible; however, those who receive intervention at an early stage tend to have less joint inflammation and reduced joint pain with preservation of function. Common complications include subluxation of the upper cervical spine, infection, and GI hemorrhage and perforation, along with renal, lung, and heart disease. Quality-of-life issues are often related to when the expected level of function is severely compromised.21

Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) is a chronic inflammatory connective tissue disorder.2,35,53

Etiology The etiology is unknown, although the immune system seems to be involved.2,23 Ninety percent of cases occur in women, and SLE is more common in black women.9 It usually occurs between the ages of 15 and 45, most frequently in the second and third decades of life.8 It is interesting that certain drugs (procainamide hydrochloride, phenytoin, hydralazine hydrochloride, penicillamine, isoniazid) can evoke a clinical syndrome indistinguishable from spontaneous SLE.25

Pathophysiology This disorder involves the autoimmune system and is characterized by a variety of antigen–antibody reactions.2 Systemic lupus erythematosus can involve the skin, joints, kidneys, lung, nervous tissue, and heart. In 50% to 90% of the cases, it does involve the lungs or pleura; this incidence of pulmonary involvement is higher than that of any other connective tissue disorder.27,60 The most common lung involvement is pleurisy, often with the development of small bilateral exudative pleural effusions that may be recurrent, may be associated with pericarditis, and may lead to fibrous pleuritis.9,63 Acute lupus pneumonitis is another manifestation of lung involvement. It usually causes hypoxemia, severe shortness of breath, cyanosis, tachypnea, and tachycardia.9,35,63 There may be an

accompanying pleuritis, with or without pleural effusion. Acute lupus pneumonitis may resolve or may lead to chronic interstitial pneumonitis and fibrosis. Alveolar hemorrhage is a rare but life-threatening pulmonary manifestation of SLE. It can occur suddenly with no prior hemoptysis and can carry a mortality rate as high as 70%.9 The reasons some patients develop recurrent pulmonary hemorrhages or have a massive intraalveolar hemorrhage are not known. Recurrent hemorrhages can lead to interstitial fibrosis. It has been found that diaphragmatic weakness is relatively common in SLE patients. It is now appreciated that the “shrinkage” of the lower lobes, elevated diaphragms, and bibasilar atelectasis can be attributed largely to diaphragmatic weakness. The diaphragm may show muscle atrophy and fibrosis with minimal inflammation.9 Other ventilatory muscles may also be weak, even with no noticeable weakness in the muscles of the extremities. This muscle involvement may cause a marked restrictive ventilatory impairment in 25% of SLE patients.10 Nephritis occurs in more than 50% of patients and is the major cause of mortality in SLE.9 Prognosis improves with early detection and intervention, as well as compliance with treatment regimens.44,54 Prevention of organ damage can improve life expectancy. A reduction in large-dose corticosteroids in recent years had improved morbidity and mortality.54 The annual number of deaths from SLE has increased from 879 in 1979 to 1406 in 1998 with no further data released by the Centers for Disease Control and Prevention.44

Drug-Induced Systemic Lupus Erythematosus Nearly 50 drugs have been reported to induce SLE, but only 6 regularly induce antinuclear antibodies and therefore symptomatic SLE. They are procainamide hydrochloride, hydralazine hydrochloride, practolol, penicillamine, isoniazid, and hydantoins. Patients who take one of these drugs for months or years may develop clinical SLE, and of these, 50% develop pleuropulmonary involvement, including interstitial lung disease. In the majority of patients, these changes are reversible by discontinuing the drug. Use of corticosteroids may accelerate the resolution.25

Diagnostic Tests Much like RA, SLE has a set of 11 criteria that the American College of Rheumatology has set forth for diagnosis. Four or more of the following, serially or simultaneously, during any interval of observation must be present for diagnosis of SLE: (1) abnormal titer of antinuclear antibodies (ANAs); (2) butterfly (malar) rash; (3) discoid rash; (4) hemolytic anemia, leucopenia, or thrombocytopenia; (5) neurologic disorder, seizures, or effusion; (6) nonerosive arthritis of two or more peripheral joints characterized by tenderness, swelling, or effusion; (7) oral or nasopharyngeal ulcerations; (8) photosensitivity; (9) pleuritis or pericarditis; (10) positive lupus erthematosus cell preparation, anti-DNA, or anti-Sm test or chronic false-positive serologic test for syphilis; and (11) renal disorder with profuse proteinuria (>0.5 g/day) or excessive cellular casts in urine. History and physical examination are important, as SLE can mimic many other

diseases and symptoms are often vague. Antinuclear antibodies are present in all cases, but this is not indicative of SLE for definitive diagnosis. Magnetic resonance imaging is used to rule out other causes of neurologic symptoms.54

Clinical Manifestation The clinical manifestation of SLE can be found in Table 5-30.

Treatment The objective of treatment is to reverse autoimmune and inflammatory changes, as well as prevent complications.54 Nonsteroidal anti-inflammatory drugs, corticosteroids, antimalarial agents, and immunosuppressants are among the top treatments. Corticosteroids cause rapid improvement of acute lupus pneumonitis and, together with plasmapheresis, are also used to treat alveolar hemorrhage.9,63 Fibrotic changes in the lungs are irreversible, so only supportive therapy is indicated.54

Scleroderma Scleroderma (progressive systemic sclerosis) is a progressive fibrosing disorder that causes degenerative changes in the skin, small blood vessels, esophagus, intestinal tract, lung, heart, kidney, and articular structures.2,35

Etiology The etiology is unknown, and the pattern of involvement, progression, and severity of the disease varies widely. It is four times more common in women than in men and is rare in children. The majority of patients are diagnosed between 30 and 50 years of age.63

Pathophysiology Within the lung, scleroderma appears as progressive diffuse interstitial fibrosis, in which collagen replaces the normal connective tissue framework of the lung. There is fibrotic replacement of the connective tissue within the alveolar walls. The pulmonary arterioles undergo obliterative changes; however, necrotizing vasculitis is rare.35 These changes may be accompanied by parenchymal cystic sclerosis, thus increasing the restrictive impairment in the lung. Scleroderma is often classified as limited or diffuse. Limited cutaneous systemic scleroderma, also known as CREST syndrome, has close correlation with pulmonary hypertension. The CREST term reflects calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia with limited internal organ involvement. Diffuse scleroderma is more widespread and has more rapid and symmetric skin thickening.

Table 5-30 Clinical manifestation of systemic lupus erythematosus

DLCO, diffusing capacity of the lungs for carbon monoxide; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2.

At autopsy, 75% to 80% of scleroderma victims show evidence of interstitial pulmonary fibrosis.31 Pleuritis and pleural effusions are unusual, unlike in the other collagen diseases that have pulmonary involvement.23 Carcinoma of the lung also has been reported in association with scleroderma.35 Prognosis is largely dependent on early diagnosis, as well as the type of scleroderma, secondary to the different rates of involvement of visceral organs. Mortality is often calculated with 80% accuracy by using a combination of proteinuria, elevated erythrocyte sedimentation rate (ESR), and low carbon monoxide–diffusing capacity. In the absence of these factors there is a 93% survival rate.54 Esophageal dysfunction is the most frequent visceral disturbance and occurs in most patients.63 Lung dysfunction is the second most common visceral disturbance, occurring in approximately 90% of scleroderma patients.10,30 The disease is often slowly progressive. However, if cardiac, pulmonary, or renal involvement is early, the prognosis is poor. Death is usually due to cardiac or renal failure.31

Diagnostic Tests Diagnosis is often delayed due to the lack of specific tests for systemic scleroderma. Physical examination and history are important, and the extent of involvement may be identified using laboratory tests such as skin biopsy, urinalysis, and blood studies. Pulmonary function tests, electroencephalogram, radiology, and GI series may also be used to determine extent.54

Table 5-31 Clinical manifestation of scleroderma

DLCO, diffusing capacity of the lungs for carbon monoxide; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; TLC, total lung capacity; VC, vital capacity.

Clinical Manifestation The clinical manifestation of scleroderma can be found in Table 5-31.

Treatment There is no effective drug treatment for sclerodermatous pleuropulmonary disease. The interstitial fibrosis is progressive and nonreversible. There is also no drug therapy that has been shown to be effective in altering the course of scleroderma. A number of agents are used to treat specific symptoms in affected organs.63 Lung transplantation may be an option, particularly if the scleroderma has not affected any other organ system.10 Otherwise, only supportive treatment of pulmonary symptoms is available.

Polymyositis Polymyositis is a systemic connective tissue disease characterized by symmetric proximal muscle weakness and pain.35,53,63

Etiology The etiology is unknown but may involve an autoimmune reaction. The disease can occur throughout life, but most commonly appears before age 15 or between 40 and 60 years of age. The disease is twice as common in women.53,63

Pathophysiology Approximately 5% to 20% of patients exhibit involvement of the lung parenchyma.30 Aspiration pneumonia is the most common pulmonary abnormality and is seen in 15% to 20% of patients.30 Other changes can include interstitial pneumonitis and fibrosis, bronchiolitis obliterans, or diffuse pulmonary infiltrates. The pleura is usually not involved. In addition to these changes, which result in a restrictive pulmonary impairment, the respiratory muscles may be weak, which increases the restrictive

dysfunction. Striated muscle involvement includes inflammation, degeneration, atrophy, and necrosis. This results in profound weakness of the limb-girdle muscles, the respiratory muscles, the laryngeal muscles, and the pharyngeal muscles. When the disease occurs in children, diffuse soft tissue calcification may occur also, which could decrease chest wall compliance further. Dysphagia and aspiration problems are common. Although characteristics of the disease are similar in children and adults, the onset is often more acute in children and more insidious in adults. The disease may enter long periods of remission. However, it seems to be more severe and unrelenting in patients with pulmonary or cardiac involvement.33,35,63

Diagnostic Tests Internal malignancy must first be ruled out, as diagnosis is difficult and can present like several other diseases. Laboratory studies such as muscle enzymes, muscle fiber biopsy, and electromyography to measure electrical activity must be conducted to diagnose myositis. Magnetic resonance imaging can be used to identify muscle inflammation and site for biopsy.54

Clinical Manifestation The clinical manifestation of polymyositis can be found in Table 5-32.

Treatment Pulmonary involvement is treated with corticosteroids, with good results if started early during the inflammatory phase.35

Dermatomyositis Dermatomyositis is a systemic connective tissue disease characterized primarily by inflammatory and degenerative changes in the skin. The pulmonary involvement that occurs with this disease mirrors the involvement that occurs with polymyositis described earlier. The incidence of lung involvement in dermatomyositis patients is also 5% to 20%.12,25,33

Immunologic Causes Goodpasture’s Syndrome Goodpasture’s syndrome is a disease of the immune complex that is characterized by interstitial or intraalveolar hemorrhage, glomerulonephritis, and anemia.33 Table 5-32 Clinical manifestation of polymyositis

DLCO, diffusing capacity of the lungs for carbon monoxide; PaO2, arterial partial pressure of O2.

Etiology This rather rare disease is most often brought on by the presence of antiglomerular basement membrane (anti-GBM) antibodies that react with the vascular basement membranes of the alveolus and the glomerulus, causing pulmonary hemorrhage and glomerulonephritis. How these antibodies come to be formed is still unknown. Prodromal viral infections or exposure to chemical substances such as hydrocarbon solvents may be involved. Why these anti-GBM antibodies cannot be demonstrated in all patients with Goodpasture’s syndrome is another mystery. This syndrome is approximately four times more prevalent in men than in women. The onset of the disease occurs between the ages of 17 and 27 in 75% of the cases.32

Pathophysiology Whatever the cause of these autoantibodies, it has been shown that when they are present in the circulating blood, they cross-react with the basement membrane of the alveolar wall and deposit along the GBM. This results in the release of cytotoxic substances that damage the pulmonary and glomerular capillaries. Blood leaks from the damaged pulmonary capillaries into the interstitium and the alveolar spaces, which over time can lead to significant and widespread pulmonary fibrosis. The pulmonary hemorrhages are episodic and seem to be precipitated by nonimmunologic factors such as fluid overload, smoking, toxic exposure, or infection. Within the kidney, the damaged glomerular capillaries lead to a rapidly progressive, often necrotizing type of glomerulonephritis and renal failure.9,32,33 The overall prognosis for Goodpasture’s syndrome is poor. Until recently,

approximately 50% of the patients died within 1 year of diagnosis. One-half of the deaths were due to pulmonary hemorrhage and the other half to renal failure.9,32,33 Currently, however, it has been recognized that there can be milder forms of the disease and that the disease’s responsiveness to treatment can be variable. Therefore early aggressive therapy encompassing plasmapheresis, drugs, ventilator support, acute hemodialysis, treatment of infection, and careful avoidance of cardiogenic edema has been used to increase survival rates to 70% to 80%.10 Table 5-33 Clinical manifestation of Goodpasture’s syndrome

ECG, electrocardiograph; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2.

Diagnostic Tests Because Goodpasture’s is a rare disorder, diagnosis is difficult. Biopsy of the suspected tissue looking for evidence of the anti-GBM antibodies is the most direct form of diagnosis.54

Clinical Manifestation The clinical manifestation of Goodpasture’s syndrome can be found in Table 5-33.

Treatment Treatment usually combines plasmapheresis and immunosuppressive therapy to lower the levels of anti-GBM antibodies circulating in the blood. Cyclophosphamide with prednisone is the regimen of choice. Methylprednisolone may be used to treat pulmonary hemorrhage. Dialysis is used to counteract renal failure.

Wegener’s Granulomatosis Wegener ’s granulomatosis is a multisystem disease characterized by granulomatous vasculitis of the upper and lower respiratory tracts, glomerulonephritis, and widespread small vessel vasculitis.32

Etiology

The etiology is unknown. Some studies seem to indicate that the disease may be due to a hypersensitivity reaction to an undetermined antigen. During the active disease process, circulating immune complexes have been identified. Immune reactants and complexlike deposits have also been identified in renal biopsies of patients with Wegener ’s granulomatosis. Although histologically the immune system and hypersensitivity reactions seem to be involved, the disease appears clinically as an infectious process due to some unknown pathogen. This disease can occur at any age, but the average age at onset is 40 years. The disease is twice as common in males as in females.32

Pathophysiology The disease often seems to start in the upper respiratory tract with necrotizing granulomas and ulceration in the nasopharynx and paranasal areas. Inflammation with perivascular exudative infiltration and fibrin deposition in the pulmonary arteries and veins causes focal destruction. Multiple nodular cavitary infiltrates develop in one or both lungs. These lesions often consist of a necrotic core surrounded by granulation tissue. Early in the disease, the kidney shows acute focal or segmental glomerulitis with hematuria. As the disease progresses, necrotizing glomerulonephritis leading to kidney failure often occurs.26,32

Diagnostic Tests Blood tests, chest x-ray, and urine analysis may be used to identify Wegener ’s granulomatosis, in addition to tissue biopsy.54

Clinical Manifestation The clinical manifestation of Wegener ’s granulomatosis can be found in Table 5-34.

Treatment The treatment of choice is with cyclophosphamide. This drug can produce marked improvement or partial remissions in 91% of patients and complete remissions in 75% of patients.10 Without drug therapy, this disease progresses rapidly and is fatal. The mean duration between diagnosis and death is 5 months when not treated.32 Death is most often due to renal disease progressing to kidney failure. Kidney transplantation has been used successfully in cases of renal failure.

Pregnancy as Cause During the third trimester of pregnancy, ventilation to the dependent regions of the lungs is impaired by the growth and position of the developing fetus. This restrictive change in ventilation is due to a decrease in chest wall compliance caused primarily by the decreased downward excursion of the diaphragm (Fig. 5-27). The decreased ventilation in the bases of the lungs results in early small airway closure and increased ventilation–perfusion mismatching. The voluntary lung volumes are decreased, particularly the ERV (8% to 40%).10 The work of breathing is increased, and the woman may feel that she is unable to take a deep breath, particularly in the supine position. To counteract some of these changes and to keep the PaO2 within the normal range, the body increases the progesterone level during this trimester. The increased level of progesterone increases the woman’s ventilatory drive, which in turn increases the TV and respiratory rate, thereby increasing the minute ventilation. This increase results in a decrease in Paco2 and a rise in PaO2, which ensures that the mother and the fetus do not become hypoxemic.10,12 Table 5-34 Clinical manifestation of Wegener’s granulomatosis

PaO2, arterial partial pressure of O2.

FIGURE 5-27 Lung volumes and capacities during pregnancy. ERV, expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; VT, tidal volume; VC, vital capacity. (From Chestnut DH: Ob stetric Anesthesia, ed 4, St. Louis, 2009, Mosby.)

Nutritional and Metabolic Causes Obesity Obesity is defined as a condition in which the body weight is 20% or more over the ideal body weight.53

Etiology Obesity is the result of an imbalance between the calories ingested and the calories expended. This imbalance may be due to overeating, inadequate exercise, a pathologic process that alters metabolism, or a psychological need or coping mechanism.

Pathophysiology The increase in body weight represents a significant increase in body mass, and this extra tissue requires additional oxygen from the lungs and produces additional carbon dioxide, which must be eliminated by the lungs. The excess soft tissue on the chest wall decreases the compliance of the thorax and therefore increases the work of breathing. The excess soft tissue in the abdominal wall exerts pressure on the abdominal contents, forcing the diaphragm up to a higher resting position. This shift results in decreased lung expansion and early closure of the small airways and alveoli, especially at the bases or the dependent regions of the lung. These areas are hypoventilated relative to their perfusion, which can markedly increase the ventilation–perfusion mismatching and result in hypoxemia.3,9 In addition, some overweight individuals have demonstrated an obesityhypoventilation syndrome, which results when there is an imbalance between the ventilatory drive and the ventilatory load.10

Diagnostic Tests Physical examination is often sufficient for detection of excess body fat. Calculation of body mass index and use of calipers to estimate body fat percentage may also be considered.54

Clinical Manifestation The clinical manifestation of obesity can be found in Table 5-35.

Treatment It is becoming better recognized that obesity is a very complex disorder. It involves virtually all the body’s systems via the patient’s metabolism, the psychological and mental processes within the patient, and the patient’s behaviors and habits. Treatment consisting of dieting and will power is usually not effective over an extended period. Patients who have been markedly obese over a long period usually can demonstrate expertise in dieting and remarkably significant will power. It is not unusual for these patients to have lost three or four times their body weight over their lifetime, only to

regain the lost weight and more. Current treatment strategies for the obese patient combine interventions. Weight loss programs now often include extensive medical evaluation and a variety of therapeutic interventions, including diet, increased activity, behavior modification, psychological support, nutritional counseling, and family involvement. Weight loss will decrease the work of breathing, increase the VC, and increase the ventilatory drive in these patients.10 Sleep apnea is most commonly treated with weight loss, avoidance of ethanol, position therapy, dental devices, nasal CPAP, increased FiO2, and tracheostomy.10,30 Table 5-35 Clinical manifestation of obesity

CHF, congestive heart failure; ERV, expiratory reserve volume; MVV, maximum voluntary ventilation; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; VT, tidal volume.

A great deal is still to be learned and understood about the body’s metabolism: how food is broken down, stored, and eliminated and how obesity can be reversed so that recurrence is not the norm. Currently, two surgical procedures are being utilized for morbid obesity, which shows promising results: gastric bypass surgery and the lap band procedure. Both procedures help with weight loss: the former by bypassing the stomach and effectively decreasing the amount of food that can be absorbed, and the latter by decreasing the actual size of the stomach, again decreasing the amount of food that can be absorbed. See Chapter 7 for more details on obesity.

Diabetes Mellitus Diabetes mellitus is a syndrome that results from abnormal carbohydrate metabolism and is characterized by inadequate insulin secretion and hyperglycemia.53

Etiology Diabetes mellitus has no distinct etiology, but seems to result from a variable interaction of hereditary and environmental factors.53

Pathophysiology The most common pathologic changes seen in diabetes mellitus result from hyperglycemia, large vessel disease, microvascular disease (particularly involving the

retina and kidney), and neuropathy.53 The effects of this metabolic disorder on the lungs have been reported, and although the incidence of pulmonary involvement does not seem to be high, it can be significant in some patients. Hyperglycemic patients have an increased incidence of pulmonary infections and tuberculosis, which is manifested more frequently in the lower lobes.28 Diffuse alveolar hemorrhage has also been reported in diabetics and may be due to inflammation and necrosis of the pulmonary capillary endothelium. This could then be followed by fibrotic changes.16 In a study of more than 31,000 patients with diabetes mellitus, pulmonary fibrosis was found in 0.8% of the diabetic population, which is a moderately greater incidence than that reported for the general population.35 Juvenile diabetics have shown a decrease in elastic recoil of the lungs and in lung compliance, causing a decrease in TLC.33,35 These abnormalities in ventilatory mechanics are thought to be due to changes in the elastin and collagen within the lung. Another mechanism that can cause a restrictive impairment in the lung is diabetic ketoacidosis, which can produce a noncardiogenic pulmonary edema. The physiologic cause for this change is unclear, but may be an alteration in the pulmonary capillary permeability.35 See Chapter 7 for more details on diabetes.

Traumatic Causes Crush Injuries Crush injuries to the thorax are usually caused by blunt trauma that results in pathologic damage, particularly rib fractures, flail chest, or lung contusion.2

Etiology The leading cause of blunt trauma to the thorax is motor vehicle accidents. The second most common cause of thoracic crush injuries is falls, which usually occur in the home.32

Pathophysiology Rib Fractures Rib fractures most commonly involve the fifth through the ninth ribs because they are anchored anteriorly and posteriorly and are less protected than ribs 1 through 4 from the kinetic energy of a traumatic blow.32 Even nondisplaced rib fractures can be very painful, and it is the pain on any movement of the chest wall that causes the restrictive impairment. Patients with rib fractures breathe very shallowly in an effort to keep the thoracic wall still. The muscular splinting around the fracture site also decreases chest wall excursion and lung expansion. In addition, fractured ribs may be accompanied by a hemothorax (blood in the pleural cavity), which can progress to a large sanguineous effusion and empyema. This fluid in the pleural space compresses the underlying lung parenchyma and can cause fibrosis and scarring of the pleura, leading to permanent restrictive dysfunction.9 More frequently, the pain of the rib fractures decreases significantly during the first 2 weeks after the injury, atelectasis improves, and normal lung function is restored, although coughing may cause pain for up to 6 months. Patients who have multiple rib fractures, are older than 50 years, or have underlying pulmonary or cardiovascular disease are at greater risk of developing a pneumonia following rib fracture.5,32

Flail Chest Flail chest refers to a free-floating segment of ribs due to multiple rib fractures both anteriorly and posteriorly that leave this part of the thoracic wall disconnected to the rest of the thoracic cage (Fig. 5-28).32 This segment can usually be identified by its paradoxical movement during the respiratory cycle. It moves inward during inspiration, drawn by the increase in the negative pleural space pressure. It moves outward during expiration, as the pleural space pressure approaches atmospheric pressure. Both the pain and the paradoxical movement of a part of the thoracic cage during the respiratory cycle contribute to the restrictive dysfunction. Lung volumes are decreased, and the distribution of ventilation is altered, causing an increase in ventilation–perfusion mismatching. The force of the blunt trauma that causes a flail chest is usually greater

than that causing a simple rib fracture. Because the force is greater, flail chest is often associated with lung contusion.5,28,32 Long-term pulmonary disability following flail chest is common; 60% of these patients have chest wall pain, chest wall deformity, dyspnea on exertion, and mild restrictive pulmonary dysfunction for months to years following the injury.28

FIGURE 5-28 Forces producing disordered chest wall motion in flail chest. A, During inspiration, the lowering of pleural pressure produces inward motion of the flail segment. B, During expiration, the increase in pleural pressure produces an outward displacement of the flail segment. (From Mason RJ, Broaddus VC, Murray JF, et al: Murray & Nadel’s Textb ook of Respiratory Medicine, ed 4, St. Louis, 2005, Saunders.)

Lung Contusion Lung contusion occurs when the lung strikes directly against the chest wall. The local pulmonary microvasculature is damaged, causing red blood cells and plasma to move into the alveoli.32 This immediately decreases the compliance of the lung, changes the distribution of inspired gases, and increases ventilation–perfusion mismatching. Although the injury due to the lung contusion may resolve in approximately 3 days, patients are at high risk for serious pulmonary complications. Approximately 50% to 70% develop pneumonia in the contused segment, 35% develop an empyema, and some patients develop ARDS, with complete “white out” of the injured lung on chest radiograph.4,28,32

Diagnostic Tests Chest radiographs are often used in an attempt to visualize rib fractures; however, rib fractures are not always seen on the image if they are not displaced. Computed tomography scan and MRI may be indicated if there is suspicion of respiratory failure. Lung contusions will show as localized infiltrates on the chest radiograph (Fig. 5-29).

Clinical Manifestation The clinical manifestation of lung contusion, fracture, and flail chest can be found in Table 5-36.

FIGURE 5-29 A, A 53-year-old male patient with a fracture of the left sixth rib (arrow). The elevated left hemidiaphragm suggests volume loss of the left lung. Also, blunting of the lateral costophrenic angle denotes pleural effusion (crossed arrow). B, Pneumothorax with displaced visceral pleura in the fourth posterior rib interspace (arrows). Courtesy John A.M. Taylor (A, Courtesy John A.M. Taylor, from Marchiori DM: Clinical imaging with skeletal, chest, and ab dominal pattern differentials, ed 3, St. Louis, 2014, Mosby; B, From Marchiori DM: Clinical imaging with skeletal, chest, and ab dominal pattern differentials, ed 3, St. Louis, 2014, Mosby.)

Table 5-36 Clinical manifestation of lung contusion/fracture/flail chest

ARDS, acute respiratory distress syndrome; FRC, functional residual capacity; PaO2, arterial partial pressure of O2; RR, respiratory rate; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.

Treatment Rib Fractures Pain control is the primary treatment and can be accomplished by oral analgesics, intercostal nerve block, or epidural anesthesia, depending on the extent of the injury.32 The goal is to allow the patient to reestablish a normal breathing pattern. In patients at high risk for developing pneumonia, hospital admission may be indicated for close observation and for aggressive pulmonary hygiene in addition to pain relief.28

Flail Chest Flail chest may have to be managed by mechanical ventilation when the patient’s respiratory rate exceeds 40 breaths per minute, the VC progressively decreases to less than 10 to 15 mL/kg of body weight, the arterial oxygenation falls to less than 60 mm Hg with an FiO2 of 40%, and hypercapnia develops with the PaCO2 higher than 50 mm Hg, or other injuries sustained in the trauma necessitate its use.32 Mechanical ventilatory support may be needed for 2 to 4 weeks. With severe chest wall injuries or marked displacement of the fracture fragments, surgical stabilization may be required. Surgery usually shortens the time the patient needs to be on mechanical ventilation, decreases the pain, and increases anatomic alignment during the healing process.32 When the injuries are less severe, it might be possible to treat the flail chest with excellent pain control and aggressive breathing exercises, use of an incentive spirometer, positioning, and coughing.

Lung Contusion Treatment is supportive and preventive. Mechanical ventilation and supplemental oxygen may be required. Fluid monitoring to ensure against volume overload, which could lead to pulmonary edema, is important. Although corticosteroids have been used, there are no current data that show corticosteroids improve the morbidity or mortality rates in these patients.28 Deep breathing exercises, positioning, and coughing are also used to assist in clearing infiltrates and to decrease the incidence of pneumonia.32

Penetrating Wounds Penetrating wounds to the thorax are usually caused by shooting or stabbing and result in pathologic damage, particularly pneumothorax, hemothorax, pulmonary laceration, tracheal or bronchial disruption, diaphragmatic injury, esophageal perforation, or cardiac laceration. Only the first three are discussed within the scope of this chapter.2,5

Etiology The leading cause of penetrating wounds to the thorax is gunshot wounds and stab wounds. Penetrating wounds to the chest are usually more specific and defined and are less likely to have the multisystem involvement more commonly seen with thoracic crush injuries.5,32

Pathophysiology Pneumothorax Traumatic pneumothorax is defined as the entry of free air into the pleural space. This often occurs after a penetrating wound to the thorax. A traumatic pneumothorax can be further classified as an open pneumothorax or a tension pneumothorax.2

An open pneumothorax means the air in the pleural space communicates freely with the outside environment. When air can move freely through the chest wall, into and out of the pleural space, the patient is unable to maintain a negative pleural space pressure. Because an effective negative pleural space pressure cannot be maintained in both the affected and unaffected hemithorax, the patient’s ability to move air into the lungs is severely diminished. Lung volumes are decreased, lung compliance is decreased, ventilation–perfusion mismatching is increased, and gas exchange is impaired.2 A tension pneumothorax means air can enter the pleural space but cannot escape into the external environment. This is an acute life-threatening situation.33 As air continues to enter and become trapped in the pleural space, the intrapleural pressure rapidly increases. This causes the lung on the involved side to collapse. The mediastinal structures are pushed away from the affected side. The increased thoracic pressure causes a decrease in venous return, cardiac output falls, and systemic hypotension and shock are the result. Lung volumes are significantly reduced, lung compliance is decreased, and the alveolar–capillary surface area available for gas exchange is cut by more than 50%.2,5,32

Hemothorax Hemothorax is the presence of blood in the pleural space. It can occur with both penetrating wounds and crush injuries to the thorax. Approximately 70% of patients with chest trauma develop a hemothorax.28 Collection of blood in the pleural space causes compression of the underlying lung tissue and prevents lung expansion. This process usually affects the lower lobes because the blood in the pleural space is pulled by gravity to the most dependent area. Compression of the lung tissue causes an increase in ventilation–perfusion mismatching, decreases lung compliance, and promotes atelectasis. Occasionally, trauma to the thorax results in a massive hemothorax, which almost always means that the heart or great vessels were injured directly. Hemothorax can have serious sequelae if all the blood is not evacuated from the pleural space. The residual blood becomes organized into nonelastic fibrous tissue, which can form a restrictive pleural rind. This condition is known as fibrothorax and can limit lung expansion markedly, causing a restrictive lung dysfunction and predisposing the patient to atelectasis and pneumonic complications.28 In addition, approximately 5% of patients with hemothorax develop an infection within the pleural space called an empyema, which can lead to further scarring of the pleural surfaces.2,5,32

Pulmonary Laceration A laceration directly into the lung parenchyma is usually caused by a penetrating wound. It results in air and blood escaping from the lung into the pleural space and often into the environment. Therefore a pulmonary laceration most commonly appears in combination with a pneumothorax and hemothorax. The hemothorax is usually not massive because the lung is perfused at low pressures, so the bleeding is not profuse.

The restrictive impairments caused by pneumothorax and hemothorax described earlier are present, and in addition the damaged lung tissue is not participating in gas exchange.32

Diagnostic Tests Pneumothorax is often visualized on the chest radiograph, and blood gas analysis can be used to assist in indicating the level of pulmonary involvement. Transthoracic aspiration biopsy of the fluids in the pleural space may be used to confirm hemothorax. Analysis of fluids assists with differential diagnosis and often includes pH analysis, specific gravity protein, eosinophilia count, glucose concentrations, and stains and cultures for bacteria, tuberculosis and fungi (Fig. 5-30).54

Clinical Manifestation The clinical manifestation of pneumo- or hemothorax can be found in Table 5-37.

Treatment Pneumothorax The definitive treatment of an open pneumothorax is the application of an airtight, sterile dressing over the sucking chest wound and the placement of a chest tube into the pleural space of the affected hemithorax. The chest tube is connected to suction so that the air and any fluid or blood within the pleural space can be evacuated. These measures will reexpand the collapsed lung. Mechanical ventilation and supplemental oxygen may be required until the patient can maintain tissue oxygenation independently.28,32 A tension pneumothorax is treated as an emergency by inserting a needle into the pleural space to allow air to escape. This is immediately followed by placement of a chest tube connected to suction so that air can be continuously evacuated from the pleural space along with any blood or fluid.5,28,32

FIGURE 5-30 Advanced collapse of the left lung appearing as an airless radiodense mass adjacent the left heart border with corresponding absence of normal bronchovascular markings in the space lateral. Courtesy Steven P. Brownstein, MD. (From Marchiori DM: Clinical Imaging with Skeletal, Chest, and Ab dominal Pattern Differentials, ed 3, St. Louis, 2014, Mosby.)

Hemothorax The definitive treatment for hemothorax is to evacuate the blood from the pleural space by placement of a dependent chest tube. This chest tube is connected to suction. Autotransfusion devices are becoming more common so that the patient’s own blood can be returned to the cardiovascular system to replace lost blood volume.28 If the wound involves the lung parenchyma, the bleeding often stops because of clotting and internal repair mechanisms. Only 4% of these patients require thoracotomy and surgical intervention to control the bleeding.63 If the wound involves the heart or great vessels, then emergency surgery may be required to stop massive bleeding; this surgery takes precedence over all other treatment other than respiratory and cardiac resuscitation. Following placement of the chest tube, the patient should be monitored carefully by chest radiograph to be sure all the blood is evacuated from the pleural space. An additional chest tube may be required to accomplish this goal. If a fibrothorax does develop and impairs lung expansion, a surgical procedure known as a decortication may be required. A decortication removes the restrictive pleural rind, which is usually done

through a minithoracotomy.32,33 An empyema may also develop if the hemothorax is not completely resolved. The empyema would be treated with placement of a chest tube and antibiotics.32 Table 5-37 Clinical manifestation of pneumo- or hemothorax

Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RR, respiratory rate; SOB, shortness of breath.

Thermal Trauma Thermal trauma involving the pulmonary system is usually due to inhalation injuries, direct burn injuries to the thorax, or a combination of both.12

Etiology Thermal trauma is usually caused by exposure to fire and smoke, particularly in an enclosed space. The effects of this exposure are dependent on what is burning, the intensity of or the temperatures generated by the fire, the length of the exposure, and the amount of body surface involved.64

Pathophysiology Smoke inhalation causes pulmonary dysfunction in three different ways. First is a direct injury from inhaling hot, dry air containing heated particulate matter. This injury is localized in the upper airway because most of the heat is dissipated in the nasopharynx. Nasal hairs may be scorched. There is usually edema of the laryngeal and tracheal mucosa, with laryngospasm and bronchospasm almost always present. Mucus production is increased, and commonly there is damage to the mucociliary clearance mechanism. This can lead to bronchopneumonia.12,64 The second cause of pulmonary dysfunction is the inhalation of carbon monoxide, a gas present in smoke. Carbon monoxide is a colorless, odorless, tasteless, nonirritating gas. Exposure to carbon monoxide can be life threatening: many suicides are committed by overexposure to carbon monoxide. This gas has more than 200 times the affinity for hemoglobin compared with oxygen.12 This means that when carbon monoxide is taken into the lungs, it diffuses quickly into the pulmonary capillaries, enters the red blood cells, and binds with hemoglobin to form carboxyhemoglobin. This abnormal process

decreases the available hemoglobin-binding sites for oxygen and significantly decreases the oxygen-carrying capacity of the blood.10 The third cause of pulmonary dysfunction is the inhalation of noxious and toxic gases, the effects from which are dependent on the materials being burned. The specific pulmonary abnormalities depend on the specific gas inhaled and the length of time exposed to the gas. However, exposure to noxious gases often results in surfactant inactivation and chemical pneumonitis.12,64,65 Later in the clinical course, the lungs may develop an OB (see Figure 5-30). Although this complication is uncommon, when it occurs, it causes significant RLD.10 Direct burn injuries to the thorax cause pulmonary dysfunction in five ways: ▪ The pain of the burn decreases chest wall mobility. ▪ If the depth of the burn is third degree, involving chest wall musculature, then the effectiveness of the respiratory pump is diminished. ▪ Major burns involving 25% of the body surface area or more result in a massive shift of fluid from the intravascular to the interstitial spaces, causing pulmonary edema and possibly acute pulmonary insufficiency. ▪ With circumferential burns of the thorax, eschar formation may severely restrict chest wall expansion. ▪ Because these patients may have to be on bed rest for protracted periods, the pulmonary system is at risk for atelectasis and bronchopneumonia.12,64

Diagnostic Tests Chest radiographs may be helpful in identifying interstitial, intraalveolar infiltrates, and other pulmonary complications.54

Clinical Manifestation The clinical manifestation of thermal injuries can be found in Table 5-38.

Treatment Treatment of the seriously burned patient is usually divided into emergency, acute, and rehabilitative care and involves monitoring and providing support and care for every body system. Treatment of the pulmonary system includes humidification, supplemental oxygen, bronchodilators, appropriate positioning, and pulmonary hygiene techniques.64 Bronchoscopy, intubation, ventilatory support using high-frequency ventilation (HFV) and PEEP, suctioning, and perhaps hyperbaric oxygen may be necessary in some patients.10

Therapeutic Causes Surgical Therapy Surgery can be defined as a planned entry into the human body by a trained practitioner under well-controlled conditions.2 Table 5-38 Clinical manifestation of thermal injuries

PaO2, arterial partial pressure of O2; RR, respiratory rate.

Etiology The pulmonary dysfunction that results from surgical therapy is due to three primary factors: (1) the anesthetic agent; (2) the surgical incision or procedure itself; and (3) the pain caused by the incision or procedure.2,32

Pathophysiology The anesthetic agent causes a decrease in the pulmonary arterial vasoconstrictive response to hypoxia. This increases ventilation–perfusion mismatching and decreases pulmonary gas exchange. Anesthesia also depresses the respiratory control centers so that ventilatory response to hypercapnia and hypoxia is decreased.28 Placement of an endotracheal tube increases airway resistance.32 Placing the patient in a supine position reduces the functional residual capacity by 20%.28 During surgery, the shape and configuration of the thorax change. The anteroposterior diameter decreases, and the lateral diameter increases. The vertical diameter of the thorax also decreases, with the diaphragm moving in a cephalad direction due to the effect of general anesthesia on central nervous system innervation of diaphragmatic tone.28 These changes in configuration result in a further decrease in thoracic volumes; the FRC is decreased an additional 15%.28 If the site of surgery is in the upper abdomen or the thorax, the surgical incision causes a significant, although temporary, restrictive impairment. Following upper abdominal surgery, the VC is decreased by 55% and the FRC by 30%.32 These decreases in lung volumes reach their greatest values 24 to 48 hours after surgery. Lung volumes then

return to relatively normal values in 5 days, although full recovery may take 2 weeks.32 Postoperative lung volume changes after upper abdominal surgery resemble changes seen in patients with unilateral diaphragmatic paralysis. In fact, diaphragmatic dysfunction has been demonstrated in some abdominal surgery patients. Diaphragmatic dysfunction also can occur after thoracic surgery, particularly if the phrenic nerve experiences hypothermic damage because of external cardiac cooling. Some studies have shown that a transverse abdominal incision results in better postoperative lung volumes and fewer postoperative pulmonary complications than the vertical midline abdominal incision. This is not a universal finding.32 However, it is well accepted that the median sternotomy incision is better tolerated and results in fewer pulmonary complications than the posterolateral thoracotomy.32 The surgical procedure itself can result in a permanent restrictive impairment when lung tissue is excised. Because pulmonary reserves are significant, a pneumonectomy or possibly a lobectomy has to be performed before any measurable restrictive dysfunction results. Thoracoplasty is another surgical procedure that results in restrictive dysfunction. This procedure removes portions of several ribs so that the soft tissue of the chest wall can be used to collapse underlying lung parenchyma. Thoracoplasty was used to treat tuberculosis and was designed to close cavities caused by tuberculosis in the upper lobes. Currently, this procedure is rarely performed, although it has been used to treat bronchopulmonary fistulas.2 Another surgical procedure that can result in significant RLD is lung transplantation. This therapeutic cause of RLD is discussed later in this section. Surgical incisions invariably cause pain, particularly abdominal incisions and posterolateral thoracotomies. Because of the pain, the tone in the muscles of the thorax and the abdominal wall increases, thereby decreasing chest wall compliance. This change contributes to decreased lung volumes and increased work of breathing during the postoperative period. The phenomenon of increased muscle tone in and around the incision is known as muscular splinting of the incision (Fig. 5-31).

Clinical Manifestation The clinical manifestation of surgery on the lungs can be found in Table 5-39.

Treatment The pulmonary status of surgical patients should be evaluated before surgery. Many patients require preoperative treatment, including deep breathing and coughing exercises and practice with an incentive spirometer. In addition, patients should abstain from smoking for a minimum of 6 weeks before surgery. To prevent aspiration pneumonia, patients usually fast for 12 hours or longer before surgery. Drugs such as cimetidine or ranitidine can be used preoperatively to increase gastric pH and decrease gastric volume.66 Postoperatively, hypoxia can be treated with inflation-hold breathing techniques, PEEP, CPAP, and occasionally with increased oxygen concentrations. Common techniques used to treat postoperative atelectasis include deep breathing

exercises, early mobilization of the patient out of bed, incentive spirometry, and CPAP.28 Nosocomial pneumonias are not uncommon after upper abdominal surgery, and 12% to 20% of patients experience this complication.29 Nosocomial pneumonias are treated with an appropriate antibiotic and possibly with postural drainage, percussion, and vibration if the patient’s secretion clearance mechanisms are impaired. Postoperative pulmonary embolism is usually treated with low-dose heparin. Prevention of venous thromboembolism may include simple leg exercises (ankle dorsi and plantar flexion), low-dose subcutaneous or adjusted-dose heparin, external pneumatic compression devices, and gradient compression stockings.28

FIGURE 5-31 Increased muscle tone in and around the incision is known as muscular splinting of the incision.

Table 5-39 Clinical manifestation of effect of surgeries on lungs

FRC, functional residual capacity; PaO2, arterial partial pressure of O2; RR, respiratory rate; SpO2, saturation of peripheral oxygen; VC, vital capacity; V/Q, ventilation–perfusion; VT, tidal volume.

Lung Transplantation Lung transplantation can be defined as the replacement of poorly functioning lung tissue in the recipient with better-functioning lung tissue (the lung tissue is never normal; there is always some preservation injury) from the donor.67 The many aspects of this surgical therapeutic intervention are discussed in Chapter 12. Only the possible development of OB after lung transplantation will be discussed in this section.

Etiology Obliterative bronchiolitis, sometimes referred to as bronchiolitis obliterans syndrome (BOS), is primarily a restrictive lung impairment and the major long-term complication of lung transplantation. Acute cellular rejection, development of donor-specific antihuman leukocyte antigen (HLA) antibodies, aspiration, respiratory viral infections, and gastroesophageal reflux disease may all be associated with development of OB after lung transplant.63,67

Pathophysiology Obliterative bronchiolitis clinically shows both restrictive and obstructive pulmonary function deficits and histologically shows obliteration of the terminal bronchioles.28 In OB there is fibrotic narrowing of the bronchiolar lumen that may be irregular, regular, or totally obliterative. The smooth muscle is often destroyed, and there is extension of the fibrosis into the interstitium. In addition, after lung transplant the regenerative capacity is diminished due to microvascular insufficiencies in the small airways from interrupted blood supply during the surgery and increased susceptibility to alloimmune immunologic insults.63 Early in OB there is mononuclear cell infiltration, epithelial damage, and ulceration. Later, as this complication develops and becomes more chronic, the fibrosis is more acellular, and the terminal bronchioles are completely obliterated.67 This decreases the surface area for gas exchange. Although the patchy fibrosis seen in OB may not involve the entire transplanted lung, it does decrease lung compliance, decrease

lung volumes, and increase ventilation–perfusion mismatching, all hallmarks of a restrictive lung impairment. Obliterative bronchiolitis is often accompanied by bronchiectasis and recurrent respiratory infections. Death is usually due to pneumonia from gram-negative bacteria or Aspergillus.68 Infection and OB are currently the most frequent causes of post–lung transplantation death.10 The 10-year probability of remaining free of the disease in long-term survivors of lung transplant is 30%.63

Diagnostic Tests It occurs most commonly between 8 and 12 months after transplant and is often preceded by an upper respiratory infection.28 A transbronchial biopsy (TBB) is used to confirm the diagnosis (sensitivity ranging from 5% to 99%).28,67

Clinical Manifestation The clinical manifestation of OB can be found in Table 5-40.

Treatment Immunosuppressive regimens used after transplant often include calcineurin inhibitors (tacrolimus or cyclosporine), glucocorticoids, and purine synthesis inhibitors (azathioprine or mycophenolate mofetil).63 A recent study showed patients treated with tacrolimus rather than cyclosporine had no difference in survival rate but did show a lower incidence of OB.63 Optimal maintenance of the immunosuppressive drug regimen, prompt diagnosis and treatment of infections and episodes of acute rejection, and careful cytomegalovirus matching may all contribute to the prevention of OB.67 Once diagnosed, OB was treated with high-dose methylprednisolone followed by a tapering course of oral corticosteroids. However, a recent metaanalysis of treatment of OB found that treatment with azithromycin was shown to reverse or halt FEV1.69 The mean percentage increase in FEV1 was 8.8% after an average follow-up period of 2.9 years.69 Immunosuppressants, immune-modulating medications, low-dose macrolide antibiotics, leukotriene-receptor antagonists, and combinations of inhaled bronchodilators and glucocorticoids are other options for treatment. For select end-stage OB patients, retransplantation has been used as an acceptable therapeutic option.63

Table 5-40 Clinical manifestation of bronchiolitis obliterans after transplant

ERV, expiratory reserve volume; FEV1, forced expiratory volume in 1 second; IRV, inspiratory reserve volume; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RV, residual volume.

Pharmaceutical Causes More than 100 drugs are capable of causing RLD. Approximately 80 of these drugs adversely affect the lung parenchyma directly, causing drug-induced interstitial lung disease.25 Other drugs affect the ventilatory pump, ventilatory drive, or chest wall compliance.1 Most drug-induced interstitial lung disease is reversible if it is recognized early and the drug is discontinued. Drug-induced RLD contributes to the morbidity of an estimated several hundred thousand patients in the United States annually. Approximately 50% of patients treated with chemotherapeutic drugs develop some degree of interstitial pneumonitis.25 Some patients who take chemotherapeutic drugs demonstrate pathologic alterations with no radiologic, symptomatic, or physiologic abnormalities. Therefore probably less than 5% of all adverse drug-induced interstitial lung disease is reported or recognized.25 It is very difficult to predict which drugs may affect a particular person’s lung adversely. The basic reason for this difficulty is insufficient knowledge. First, knowledge of the metabolites of different drugs and their effects on the lung is lacking. Second, some patients seem to have a genetic predisposition to react adversely to certain drugs, but this is not well understood. Third, many patients are on multiple drugs, and the interaction of the various metabolites has not been well studied.25 Drug-induced interstitial lung disease probably results from a combination of mechanisms, including: ▪ Toxic effects of the drug or its metabolites ▪ Interference with the oxidant–antioxidant system30 ▪ An indirect inflammatory reaction ▪ Altered immunologic processes25

BO X 5- 3 Drugs ca pa ble of inducing int e rst it ia l lung dise a se • Oxygen • Antibiotics • Nitrofurantoin • Sulfasalazine • Anti-inflammatory drugs • Cardiovascular drugs • Chemotherapeutic drugs • Poisons • Anesthetics • Muscle relaxants • Illicit drugs Drugs capable of causing drug-induced interstitial lung disease are discussed here by drug category and found in Box 5-3.

Oxygen High concentrations of oxygen for more than 24 hours can produce interstitial lung disease. The lung damage occurs in two phases. First is the exudative phase, which begins after using high oxygen concentrations for 24 to 72 hours. During this phase, perivascular, interstitial, and alveolar edema and alveolar hemorrhage and atelectasis occur. The second, or proliferative, phase is marked by hyperplasia of the type II pneumocytes and deposition of collagen and elastin in the interstitium, and is irreversible. Oxygen toxicity can result in significant RLD. Treatment is primarily preventive. Oxygen toxicity can be minimized by keeping the FiO2 less than 40% and the PaO2 less than 120 mm Hg.25

Antibiotics Some antibiotics used to fight infections can be neurotoxic. Drugs such as polymyxin, gentamicin, and kanamycin, when given intravenously, can cause neuromuscular blockade. This neuromuscular blockade can result in respiratory muscle paralysis, failure of the ventilatory pump, and such significant restrictive lung impairment that assisted ventilatory support may be necessary. The significance of the respiratory impairment is even greater when these drugs are used with anesthetic agents or muscle relaxants.66

Nitrofurantoin This drug is an antiseptic agent used to fight specific urinary tract infections. It can cause acute or chronic interstitial pneumonitis and is responsible for more reported cases of drug-induced pulmonary disease than any other drug.30 There seems to be no relation between the acute and chronic reactions. The acute pneumonitis is characterized by fever, dyspnea, cough, and rales; approximately 35% of patients experience pleuritic pain. The acute pneumonitis (90% of reported cases) is completely reversible if the drug is discontinued.30 Chronic pneumonitis (10% of reported cases) mimics IPF and usually begins 6 to 12 months after initiation of the drug. Patients complain of dyspnea and a mild, nonproductive cough. There can be diffuse fibrosis with lower zone predominance. Treatment includes discontinuation of the drug, lung biopsy, and possibly corticosteroids. Therapeutic results are inconsistent, and the mortality rate is 10%.25,30,66

Sulfasalazine This drug is used to treat inflammatory bowel disease (chronic ulcerative colitis) and more recently to treat rheumatologic disorders.30 Patients who develop lung complications complain of dyspnea and cough approximately 1 to 8 months after the initiation of the drug. Approximately half the patients also complain of fever. This can develop into interstitial pulmonary fibrosis. Treatment is to discontinue the drug. Pulmonary involvement and symptoms are reversible in most patients. Corticosteroids hasten improvement in some patients.30 Three fatalities have been recorded as caused by

sulfasalazine-induced diffuse pulmonary fibrosis.25,30

Anti-inflammatory Drugs Gold Gold is used in the treatment of rheumatoid arthritis and is also being used to treat osteoarthritis and asthma, but in some patients it causes diffuse interstitial pneumonitis and fibrosis.30 These patients develop dyspnea and a nonproductive cough approximately 6 weeks to many months after initiation of gold therapy. Treatment is discontinuation of the drug, which allows the reaction to regress spontaneously. Some patients with respiratory distress are given corticosteroids to speed up this process.8,25

Penicillamine This drug is used to treat Wilson disease, cystinuria, primary biliary cirrhosis, scleroderma, and severe RA in patients who have failed to respond to conventional therapy.30 However, it can cause bronchiolitis obliterans, which contributes to both obstructive and restrictive lung dysfunction, Goodpasture’s syndrome, or penicillamineinduced SLE. The drug is discontinued in patients who develop any of these pulmonary complications. Patients who have developed Goodpasture’s syndrome are also treated with hemodialysis, immunosuppression, and plasmapheresis. Patients who have penicillamine-induced SLE may also receive corticosteroids to accelerate the resolution of this pulmonary complication.25,66

Cardiovascular Drugs Amiodarone This antiarrhythmic drug is given for ventricular dysrhythmias that are refractory to other antiarrhythmic drugs. The pulmonary complications seem to be dose related and rarely occur if the dose is under 400 mg/day. The incidence of pulmonary complications is approximately 6%, and the pulmonary complications may be fatal in 10% to 20% of patients.30 Patients with pulmonary involvement experience an insidious onset of dyspnea and a nonproductive cough with occasional fever and chills. Rales are heard on auscultation, and the chest radiograph shows asymmetric lesions in the lung, which appear mostly in the upper lung fields. Treatment is to discontinue the drug; the value of corticosteroids is uncertain.25,30

Chemotherapeutic Drugs These cytotoxic drugs used in cancer chemotherapy are a major cause of morbidity and mortality in the immunocompromised individual. It has been reported that the majority of these drugs can cause pulmonary fibrosis.8 They are also responsible for causing pulmonary infiltrates, secondary neoplasms, and non-Hodgkin lymphoma, all of which

compromise lung function. The precise mechanism that incites the inflammatory and fibrotic response in the lung is unknown. Dyspnea appears gradually, usually within a few weeks of the drug therapy, followed by fever and a nonproductive cough. With some drugs, symptoms may be delayed for months or years (e.g., cyclophosphamide). Early chest radiographs show asymmetric parenchymal changes in one lobe or lung; eventually, these changes progress and become diffuse and uniform in distribution. Pulmonary function tests show a classic restrictive impairment. The DLCO usually falls before the patient experiences the onset of any overt symptoms (except with methotrexate). Rales are heard on auscultation. Treatment consists of discontinuation of the drug and in some cases the use of corticosteroids.25

Poisons Paraquat Paraquat is used as a weed killer. If it is ingested, it causes acute pulmonary fibrosis. There are usually no symptoms for 24 hours after ingestion, and then the person experiences progressive respiratory distress leading to death in 1 to 38 days.8 Other drugs can cause RLD via a variety of pathophysiologic mechanisms other than that of producing alveolar pneumonitis and fibrosis. A few of these drug categories or specific drugs are discussed.

Anesthetics Anesthetic agents such as halothane (Fluothane), methoxyflurane (Penthrane), or thiopental sodium (Pentothal) are used to provide anesthesia during surgical procedures. These agents also inhibit the respiratory centers in the medulla and therefore depress ventilation so that lung volumes are significantly reduced. Assisted mechanical ventilation is usually required with the use of these drugs. The effects of these drugs and the effects of the assisted mechanical ventilation usually result in significant but brief RLD.2,66

Muscle Relaxants Muscle relaxants such as pancuronium bromide (Pavulon), dantrolene sodium (Dantrium), diazepam (Valium), and cyclobenzaprine hydrochloride (Flexeril) are used to enhance surgical relaxation, overcome muscle spasm, and control shivering (with systemic hypothermia). However, because these drugs act on skeletal muscle, they also decrease thoracic expansion, decrease chest wall compliance, and decrease pulmonary ventilation. As soon as the drug effects have worn off, the transient RLD also disappears.2,66

Illicit Drugs

Cocaine It is estimated that there are more than 5 million regular cocaine users in the United States.30 Cocaine became affordable and very popular in the 1980s with the introduction of the alkaloidal form of cocaine hydrochloride, known as free-base or crack. Crack is smoked, is usually 30% to 90% pure, and produces a rapid and intense euphoria that is extremely addictive. Lung disease is much more common among crack smokers than other cocaine users.30 Pulmonary pathologic conditions caused by crack use include acute pulmonary hemorrhage (58%), interstitial pneumonia with or without fibrosis (38%), vascular congestion (88%), and intraalveolar edema (77%).30 The major symptoms of lung involvement are dyspnea (63%), cough (58%), cough with blood-stained or black sputum (34%), and chest pain (25%).30 Fever, bronchospasm, perihilar infiltrates, hypoxemia, and respiratory failure also occur. In fact, the term crack lung is used to describe acute pulmonary eosinophilia or acute respiratory failure, both of which can occur after smoking free-base cocaine. These different pulmonary disorders cause acute or chronic RLD with decreased lung compliance, increased ventilation–perfusion mismatching, decreased DLCO, hypoxemia, and hypercapnia. Treatment of acute pulmonary diseases with corticosteroids (prednisone) can result in rapid improvement. When lung tissue is repeatedly involved in hemorrhage, edema, and pneumonia, then fibrosis may result. Chronic fibrosis of the lung does not seem to respond to corticosteroids. A number of deaths have been attributed to pulmonary involvement after crack cocaine use.30

Heroin An overdose of methadone hydrochloride, propoxyphene hydrochloride, or heroin can lead to a noncardiac pulmonary edema with interstitial pneumonitis. This reaction can begin within minutes of an intravenous injection or within an hour of oral ingestion. Respiration is depressed, lung compliance is decreased, and hypoxemia and hypercapnia result. Treatment includes mechanically assisted ventilation and usually antibiotics to deal with the invariable aspiration pneumonia.25 It is estimated that there are 800,000 heroin users in the United States.30

Talc Talc (magnesium silicate) is used as a filler in oral medications such as amphetamines, tripelennamine hydrochloride, methadone hydrochloride, meperidine, and propoxyphene hydrochloride (Darvon). When addicts inject these drugs intravenously, talc granulomatosis results. Talc granulomatosis is characterized by granulomas in the arterioles and the pulmonary interstitium. The clinical picture includes dyspnea, pulmonary hypertension, and restrictive lung impairment with a decreased DLCO. Treatment is abstinence from further intravenous talc exposure. Use of corticosteroids has afforded variable results.25

Radiologic Causes Radiation Pneumonitis and Fibrosis Radiation pneumonitis or fibrosis is a primary complication of irradiation to the thorax. It usually occurs 2 to 6 months after this treatment intervention.30,32

Etiology Irradiation of the thorax is a treatment option for lymphoma (Hodgkin disease), breast cancer, lung cancer, and esophageal cancer. Not all patients who receive irradiation to the thorax develop radiation pneumonitis or fibrosis. This serious pulmonary complication of irradiation seems to depend on the rate of delivery of the irradiation, the volume of lung being irradiated, the total dose, the quality of the radiation, and the concomitant chemotherapy.3,9,25 Time–dose relationships are extremely important in predicting the occurrence of radiation pneumonitis or fibrosis. The number of fractions into which a dose is divided seems to be the most important factor.9 Also important is the total dose and the span of time over which the radiation is delivered. Approximately 50% of patients undergoing irradiation of the thorax show radiologic abnormalities in the lung.30 Only 5% to 15% of patients who receive radiation to the thorax actually develop signs and symptoms of radiation pneumonitis.3,30 Currently one group of patients seems to be at higher risk for developing radiation pneumonitis or fibrosis. Bone marrow transplant patients receive whole-lung irradiation. They are also on cytotoxic chemotherapeutic agents that can intensify the pneumonitis, and these patients often have a graft versus host reaction that can add to radiation damage.9

Pathophysiology The pathogenesis of radiation pneumonitis or fibrosis is uncertain.30 It is known that irradiation causes breaks in the DNA strands. When these breaks are double stranded, the cell cannot correctly repair the damage, and so the integrity of the chromosome is disrupted.30 Chromosomal aberrations do not affect the survival or function of the cell until it tries to replicate itself. Cell death usually occurs with cell mitosis during the first or subsequent mitotic divisions. Radiation responses are seen first in cells with rapid rates of cell replication. In the lung, this would include the capillary endothelial cells, the type I alveolar epithelial cells, and the type II pneumocytes. In addition to cellular death caused by molecular changes, irradiation causes an inflammatory syndrome. This inflammation may be initiated by the release of free radicals.30 Pulmonary injury after radiation of the thorax is usually divided into two clinical syndromes: acute radiation pneumonitis and chronic radiation fibrosis.10 The onset of acute radiation pneumonitis is insidious, beginning 2 to 3 months after radiation. It is characterized by swelling of endothelial cells, capillary engorgement and disruption, intimal proliferation, subintimal accumulation of macrophages, and capillary occlusion

and thrombosis.10 Endothelial injury may lead to increased vascular permeability, which may have a profound effect on gas exchange and ventilation–perfusion matching. Chronic radiation fibrosis occurs 6 to 9 months after radiation and is characterized by basement membrane damage, fibroblastic proliferation, collagen deposition, capillary endothelium hyalinization and sclerosis, obliteration of alveoli, dense fibrosis, and contraction of lung volume.9,10,25 There is evidence that the pneumonitis and fibrosis are two separate phases and that radiation fibrosis may not always be preceded by radiation pneumonitis.30 It seems that the earlier the onset, the more serious and protracted the complications.10,33 Usually one-third to one-half of the volume of one lung must be irradiated for pneumonitis to develop and show any clinical symptoms.9 Some patients have a complete resolution of the pneumonitis, but many go on to develop permanent fibrosis. Occasionally pleural effusion, spontaneous pneumothorax, bronchial obstruction, rib fractures, pericardial effusion, or tracheoesophageal fistula may further complicate the clinical picture.10 With whole-lung irradiation, the involved fibrotic lung may contract to a remarkable degree, even causing shifts in the mediastinal structures, overexpansion of the other lung, and death. It has been reported that a late complication of radiation fibrosis may be the rapid development of adenocarcinoma of the lung. Bilateral adenocarcinoma of the lung has been described 2 years after radiation therapy for Hodgkin disease (the patient had also received chemotherapy). Malignant fibrous histiocytoma may also complicate radiation fibrosis.30 Table 5-41 Clinical manifestation of radiation pneumonitis and fibrosis

DLCO, diffusing capacity of the lungs for carbon monoxide; ERV, expiratory reserve volume; HR, heart rate; IC, inspiratory capacity; Paco2, arterial partial pressure of CO2; PaO2, arterial partial pressure of O2; RV, residual volume; SOB, shortness of breath; TLC, total lung capacity; VC, vital capacity.

Clinical Manifestation The clinical manifestation of radiation pneumonitis and fibrosis can be found in Table 541.

Treatment Asymptomatic patients with radiologic abnormalities do not require treatment.10

Corticosteroids are used to treat acute radiation pneumonitis and may produce dramatic results. However, there are reports of a lack of response to corticosteroids, even during the acute radiation pneumonitis phase.10 Corticosteroids offer no help in treating chronic radiation fibrosis and should not be used prophylactically because terminating corticosteroid therapy may actually precipitate radiation pneumonitis. Pneumonectomy has been reported to treat severe unilateral radiation fibrosis. Otherwise, treatment is supportive and consists of oxygen therapy, cough suppression medications, analgesics, and antibiotics to treat any superimposed infection.3,9,10,35 Prophylactic antibiotics should not be used because they could predispose patients to aggressive antibiotic-resistant organisms.10 Prevention is the ultimate treatment, and the occurrence of radiation injury to the lung is decreasing with the refinement of radiotherapy techniques, particularly the careful tailoring of radiation fields.8,9

Summary ▪ Restrictive lung dysfunction is not a disease: It is an abnormal reduction in pulmonary ventilation. ▪ Restrictive lung dysfunction can be caused by a variety of disease processes occurring in different body systems, trauma, or therapeutic measures. ▪ In RLD, one or more of the following is abnormal: lung compliance, chest wall compliance, lung volumes, or the work of breathing. ▪ The classic signs of RLD include tachypnea, hypoxemia, decreased breath sounds, dry inspiratory rales, decreased lung volumes, decreased diffusing capacity, and cor pulmonale. ▪ The hallmark symptoms of RLD include shortness of breath; cough; and a wasted, emaciated appearance. ▪ Treatment interventions for RLD vary and are dependent on the cause of the restrictive impairment. Sometimes corrective measures are possible. However, once the lung has undergone fibrotic changes, the pathologic alterations are irreversible and only supportive interventions are used. ▪ Idiopathic pulmonary fibrosis is the pulmonary disease entity most commonly associated with RLD. ▪ Pneumonia is an inflammatory process within the lung that can be caused by bacteria, mycoplasmas, viruses, fungi, or chlamydial agents. ▪ There are four major types of lung cancer: squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and large cell carcinoma. All types can cause a restrictive impairment within the lung. This restrictive impairment may be due to direct pressure from the tumor, may result from susceptibility to other disease processes in the weakened cancer patient, may be related to changes that occur as the tumor metastasizes to other body systems, or may be produced by hormones arising from the tumor, which can cause a variety of symptoms in different body systems. ▪ Cigarette smoking has been linked to a variety of pathologic conditions, including bronchogenic carcinoma, cancer of the mouth and larynx, esophageal cancer, kidney and urinary bladder cancer, pancreatic cancer, chronic bronchitis, emphysema, increased incidence of respiratory infection, increased frequency and severity of asthmatic attacks, coronary artery disease, myocardial infarction, peripheral vascular disease, hypertension, stroke, low birth weights in infants, increased incidence of stillbirths, impotence, burn injuries, and reduced exercise capacity. ▪ Neuromuscular causes of RLD include SCI, ALS, polio, Guillain–Barré syndrome, muscular dystrophy, and myasthenia gravis, and any of these disease entities can cause such a significant decrease in alveolar ventilation that a mechanical ventilator is required to maintain life. ▪ Crush injuries and penetrating wounds to the thorax can cause significant RLD but are almost always reversible with corrective interventions. ▪ More than 100 drugs have the side effect of causing restrictive lung impairment, including oxygen and the majority of drugs used in the treatment of cancer.

▪ Radiation fibrosis of the lung is a complication of radiation therapy and is dependent on the number of fractions into which the radiation dose is divided, the total dose of radiation, the volume of lung being irradiated, and the quality of the radiation.

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Chronic obstructive pulmonary diseases Ellen Hillegass, Natalie Goldberg, and Susan Garritan

CHAPTER OUTLINE Overall Etiology, Pathology, and Pathophysiology of COPD 187 Lung Function in Obstructive Lung Diseases 189 Symptoms Associated with Obstructive Lung Diseases 189 Physical and Psychological Impairments Associated with Obstructive Lung Diseases 189 Quantification of Impairment in Obstructive Lung Diseases 191 Pulmonary Function Testing 191 Lung Volumes 191 Disease-Specific Obstructive Lung Conditions 191 Adult Obstructive Lung Conditions 192 Pediatric Obstructive Lung Conditions 201 Cystic Fibrosis 201 Asthma 206 Case study 210 References 211

Chronic obstructive pulmonary disease (COPD) is a term given to a cluster of problems that affect the airways and the lung parenchyma that produce obstruction to expiratory airflow. Airflow obstruction can be related to any or all of the following problems: ▪ Retained secretions ▪ Inflammation of the mucosal lining of airway walls ▪ Bronchial constriction related to increased tone or spasm of bronchial smooth muscle ▪ Weakening of the support structure of airway walls ▪ Air sac destruction and air sac overinflation with destruction of surfactant Chronic obstructive pulmonary disease is a major public health problem and has a significant effect on the elderly. It is often associated with multiple comorbidities. As such, COPD often is a term given to individuals who have a combination of diseases identified as emphysema, chronic bronchitis, and bronchoconstriction or asthma. Additional diseases are defined as obstructive diseases, which include cystic fibrosis, bronchiectasis, and bronchopulmonary dysplasia. All of the conditions that are

defined as obstructive diseases have the potential to decrease the size of the bronchial lumen and/or increase the size of the alveolar sac and increase the resistance to expiratory airflow. Therefore regardless of the mechanism, obstructive lung diseases generally result in incomplete emptying of the lung, which produces the classic signs of lung hyperinflation seen in chest radiographs (chest x-rays [CXRs]) and reduced lung function as seen on pulmonary function studies. Chronic obstructive pulmonary disease is currently the third most deadly disease, with cardiovascular disease and all-cause cancer taking first and second place, respectively. The symptoms of obstructive pulmonary disease are similar to restrictive disease in that many individuals complain of dyspnea or shortness of breath. However, other symptoms occur with chronic obstructive disease that will be discussed in this chapter. In addition, due to improved knowledge and research, the etiology and pathophysiology of obstructive pulmonary disease is increasingly understood by health care providers. With our increased understanding of mechanisms leading to various pulmonary diseases, more effective medical and physical therapy interventions are available to improve the quality of life for affected individuals. Our enhanced understanding of obstructive pulmonary diseases has resulted in recommendations for preventive strategies, which are expected to reduce incidences of this disease in future generations. In the future, our knowledge and understanding of a variety of medical conditions will result in necessary changes to current treatment approaches. Therefore it is critical that physical therapists treating patients with cardiovascular and pulmonary disorders keep current with medical research, review metaanalysis articles, and practice evidence-based physical therapy to provide the best possible care to clients with obstructive pulmonary disease.

Overall Etiology, Pathology, and Pathophysiology of COPD Chronic obstructive pulmonary disease has two primary causes: inhalation factors and genetics. Inhalation of cigarette smoke is the primary cause of the majority of the insult to the lung and can occur actively or passively (secondhand inhalation). An inhalation of 40 pack-years is more predictive of developing the disease than less smoking.1 Inhalation of other factors, including chemicals, air pollution, and occupational dusts, has less of an impact but can play a role in the development of COPD. The other cause of COPD is genetic and involves inheriting an α1-antitrypsin deficiency. This genetic disorder primarily affects the surfactant production and integrity of the alveolar sac, leading to early-onset emphysema. Chronic obstructive pulmonary disease presents with multiple pathologic features that restrict airflow. Because COPD is a combination of diseases, it presents as a combination of pathologic features, including hyperplasia of the mucus-secreting cells, reactive airways and destruction of terminal bronchioles, and actual alveolar sac destruction (Fig. 6-1). All these features will reduce airflow out of the air sacs and the airways and result in hyperinflation and poor gas exchange. Inhalation exposure is often the initiating factor to an inflammatory response in the airways and the alveoli that leads to disease, especially if the individual is genetically susceptible. An increase in protease activity and a decrease in antiprotease activity initiate the inflammatory response, which ultimately breaks down elastin and connective tissue, and hyperplasia of mucus-secreting cells results. This inflammatory response will continue as long as the inhalation exposure occurs, and if long-term exposure has occurred, the inflammatory damage may not be reversible despite smoking cessation or removal of the inhalation exposure. In addition to the inflammatory response, infection may occur, which increases the progression of lung destruction. Impairment in cilia in the airways to assist in secretion removal occurs due to cigarette smoke, and alveolar macrophages within the lung parenchyma can be permanently destroyed, increasing the risk of infection. As a result, airway obstruction occurs due to hypersecretion of mucus, mucus plugging, edema of mucosal lining, increased reactivity of airways, and eventual bronchial fibrosis and destruction of terminal airways. The elastic recoil of the airways and the air sacs can be destroyed, which leads to hyperinflation, ventilation/perfusion mismatch, hypoxemia, and oftentimes hypercapnea.1

FIGURE 6-1 Disorders commonly observed in chronic obstructive pulmonary disease (COPD). (From Patton K, Thibodeau G: Human Body in Health and Disease, ed 6, St. Louis, 2016, Mosby.)

Lung Function in Obstructive Lung Diseases Lung hyperinflation affects both the mechanical function of the respiratory muscles and the gas exchange capabilities of the lung. The CXRs shown in Fig. 6-2 illustrate the most common signs of lung hyperinflation associated with obstructive lung diseases. These signs include the following: ▪ Elevation of the shoulder girdle ▪ Horizontal ribs ▪ Barrel-shaped thorax (increased anteroposterior diameter) ▪ Low, flattened diaphragms

Clinical tip Chest x-ray findings such as those shown in Fig. 6-2 are present only in severe obstructive lung disease; therefore a CXR is of limited value in diagnosing obstructive lung disease. Results of spirometry testing are more important in identifying the presence of most obstructive lung diseases. One type of obstructive pulmonary disease, bronchiectasis, is best diagnosed by computed tomography (CT). More information about bronchiectasis can be found later in this chapter. Abnormalities in gas exchange are seen by examining the arterial blood gas (ABG) values. Oxygenation levels (PaO2) become decreased as disease severity progresses, and CO2 levels vary according to either the type or stage of disease. CO2 levels can be decreased (in emphysema), normal in early obstructive pulmonary disease, or elevated (in chronic bronchitis or impending respiratory failure). Disease-specific abnormalities in lung function will be discussed in detail in the section for each of the obstructive diseases.

Symptoms Associated with Obstructive Lung Diseases In general, individuals with obstructive lung diseases frequently complain of dyspnea on exertion (DOE), especially during functional activities such as stair climbing or longdistance or fast walking. The sensation of DOE can be so uncomfortable and occasionally frightening for individuals with obstructive lung disease that the onset can lead to an increased anxiety level. In some obstructive diseases, secretion production and cough are prominent features. Disease-specific symptoms will be discussed in the relevant sections for each disease.

Physical and Psychological Impairments Associated with Obstructive Lung Diseases As physical therapists, identification of patients’ impairments is a crucial part of our evaluation and assessment, as it leads to the development of an appropriate treatment plan. These impairments can be few or many and, in the case of patients with COPD, include not just the physical impairments but the psychological as well. Chronic obstructive pulmonary disease is “a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.”2 The physical changes associated with COPD occur not just within the lungs themselves, but within the entire musculoskeletal system. These physical changes can significantly affect the individual’s activity tolerance not just with exercise but also with his or her daily life. There is also a psychological component to the disease process that can significantly affect an individual’s ability to participate in activities of daily living and his or her ability to participate in physical therapy intervention.

FIGURE 6-2 Radiographic signs of lung hyperinflation. (From Hess D, MacIntyre NR, Mishoe SC, et al: Respiratory Care Principles and Practice, St. Louis, 2002, Saunders.)

The physical impairments begin with the changes that occur within the lung tissue itself. Chronic inflammation starts the process by causing structural changes and narrowing of the small airways within an individual’s lungs. The same inflammation causes destruction of the lung parenchyma and leads to loss of alveolar attachments to the small airways, decreasing the lungs’ ability for elastic recoil. As the lungs’ ability for elastic recoil diminishes, the small airways are unable to remain open during expiration,2 which is a detriment to the lungs’ ability to perform gas exchange necessary for oxygen to perfuse to the body’s tissues. This loss of elastic recoil leads to chronic lung

hyperinflation, which in turn leads to changes within the thorax. The rib cage takes on a barrel shape, affecting the ribs’ ability to move in the normal bucket and pump handle motions. As the rib cage changes shape, the diaphragm begins to flatten, there is a loss of sarcomeres, and there is a change in the length–tension relationship of the muscle. A normal length–tension relationship within the diaphragm is the key to achieving the pressure changes needed for ventilation. As the diaphragm flattens, its ability to contract and relax affects the individual’s ability to perform a normal passive exhalation. As the disease progresses, exhalation can become forced instead of passive, increasing intraabdominal pressure and putting more stress on the pelvic floor. This can lead to pelvic floor dysfunction that can manifest as urinary incontinence in both males and females. The individual’s ability to inspire is also affected, leading to the recruitment of accessory muscles of inspiration, including the sternocleidomastoid; the upper trapezius, the scalenes, and the pectoralis muscle group can also be recruited. With prolonged use, these muscles can become hypertrophied and shortened, causing postural deviations including forward head, rounded shoulders, and thoracic kyphosis, as well as causing the posterior thoracic musculature to weaken and lengthen. Patients may also take on a forward-leaning posture to improve exhalation (Fig. 6-3). Muscle composition is also affected in individuals with COPD. There is a shift from type I to type II skeletal muscle fibers, a reduction in mitochondrial density per fiber bundle, and a reduction in capillary density—all of which correlate to a reduction in aerobic metabolism and poor muscle endurance.3 These individuals also show higher levels of C-reactive protein and proinflammatory cytokines (interleukin-6 and -8, tumor necrosis factor [TNF])—inhibiting muscle contractility and mitochondrial biogenesis, as well as promoting muscle wasting.3 The decreases in strength of both the skeletal and respiratory musculature are “independently associated with poorer exercise capacity and lower extremity functioning across the spectrum of chronic obstructive pulmonary disease severity. Furthermore, the effect of concurrent leg and respiratory muscle weakness on exercise capacity suggests a negative combined effect leading to far worse impairment.”3 It is also important to take note that individuals with chronic obstructive lung disease rate lower extremity weakness as a specific cause of exercise impairment.3 The estimated overall prevalence of skeletal muscle weakness in patients with COPD was shown to be 32%.4 In addition, a trend toward a higher prevalence of skeletal muscle weakness with disease severity (Global initiative for chronic Obstructive Lung Disease or GOLD stages) has been reported.4 Multiple factors affect muscle weakness, as noted earlier, but it is also important to remember that multiple exacerbations, nutritional status, and inactivity also contribute to muscle strength impairments in individuals with COPD.5

FIGURE 6-3 Forward-leaning posture of patient with COPD.

Psychological impairments also play a significant role in activity tolerance, exercise capacity, and individuals’ ability to perform activities of daily living. The most common psychological impairments seen in patients with pulmonary diseases, including COPD, are depression and anxiety.6–9 Prevalence of depression and anxiety in the pulmonary population are estimated to range from 10% to 80%.6 The wide variation in prevalence of depression and anxiety are due to differing instruments and methods used to screen and detect these conditions in individuals’ with COPD. The wide variation could also have been affected by the type of population included in each study. The prevalence of depression and anxiety were shown to be higher in patients with more severe COPD and in those requiring supplemental oxygen.9 Some estimates suggest that individuals with COPD are two and a half times more likely to have anxiety and depression than are healthy persons.10 Cognitive impairment is also prevalent in patients with COPD and can be complicated by chronic hypoxemia.11–13 Cognitive impairment worsens as the disease progresses.14–17 These impairments include recent memory loss, construction, visual processing, number sequencing, attention, language and orientation, cognition flexibility, and shifting

capacity. Cognitive impairment can contribute to a person’s inability to self-manage his or her medications, finances, or basic activities of life. Impaired performance in tests that require a drawing task, such as producing a clock, or other complex goal-directed cognitive tasks, indicates problems with judgment and complexity18 and has been proposed to be prognostic in patients with hypoxemic COPD.19 A few other psychological concerns that should also be taken into consideration are coping, stress, motivation, and chemical dependency issues such as smoking. Although their prevalence is not as well characterized as anxiety, depression, and cognitive impairment, they nevertheless can impair an individual’s ability to participate in physical therapy intervention.

Quantification of Impairment in Obstructive Lung Diseases Pulmonary Function Testing Spirometry tracings measure time–volume relationships in the lung (see Chapter 10). Typically, obstructive diseases are characterized by delayed and incomplete emptying of the lung during exhalation. To assess the progression of COPD, two forced spirometry measures that can be followed over time are the forced expiratory volume in 1 second (FEV1) (Fig. 6-4) and the forced vital capacity (FVC) (see Chapter 10 for further information). Another way of expressing airflow limitation is to measure the amount of air that can be exhaled in 1 second as a percentage of the total amount of air that can be forcefully exhaled, or the FEV1/FVC ratio × 100%. A normal FEV1/FVC ratio is considered to be greater than 75%,19 and the ratio’s value reflects the increased time it takes to expel air as an obstructive disease becomes more severe. The FEV1/FVC ratio decreases as the severity of lung obstruction increases. Forced flow rates measured during exhalation are used to: ▪ Quantify the degree of airway obstruction present ▪ Document improvements in lung function after the administration of medications ▪ Follow the progression, or worsening, of an obstructive lung disease

Clinical tip Individuals with obstructive pulmonary disease require increased time to expel air from their lungs. As the severity of lung obstruction increases, less and less air can be exhaled in 1 second.

Lung Volumes Pulmonary function tests (PFTs) provide information regarding the volume of air the lung contains after different levels of inhalation or exhalation, as well as information regarding the lung capacities (the sums of different lung volumes). In general, individuals with COPD show larger-than-normal total lung capacities (TLCs) and larger residual volumes (RVs) compared with individuals of the same age, height, gender, and race (Fig. 6-5).20 See Chapter 10 for more detailed information on PFTs.

Clinical tip Individuals with obstructive lung disease demonstrate an increased total lung capacity and an increased RV as a result of air trapping and lung hyperinflation.

FIGURE 6-4 The progression of COPD over time. Natural history of COPD as measured by FEV1 as a percentage of the baseline value at age 25. Normal nonsmoking individuals have a progressive loss of FEV1 but never become symptomatic with airway obstruction. Patients with COPD who quit smoking experience an FEV1 decline that parallels a nonsmoking, age-matched person. Patients with progressive COPD can develop a loss of FEV1, which may eventually produce symptoms, disability, and death. Some COPD patients have steep declines in lung function during discreet clinical episodes. (Modified from Fletcher C, Peto R: The natural history of chronic airflow obstruction, Br Med J 1:1645–1648, 1977.)

FIGURE 6-5 Lung volumes in chronic obstructive pulmonary disease compared with normal values. In the presence of obstructive lung disease, the vital capacity (VC) is normal to decreased, the residual volume (RV) and functional residual capacity (FRC) are increased, the TLC (total lung capacity) is normal to increased, and the RV/TLC ratio is increased. ERV, expiratory reserve volume; IC, inspiratory capacity; VT, tidal volume. (From Hines Rl, Marschall K: Stoelting’s Anesthesia and Co-existing Disease, ed 5, Philadelphia, 2008, Churchill Livingstone.)

Disease-Specific Obstructive Lung Conditions In the sections that follow, the obstructive lung diseases will be considered separately to highlight the unique features, such as etiology; pathophysiology; and variations in clinical presentation, medical management, and prognosis. Knowledge of diseasespecific differences is important to help determine appropriate physical therapy interventions and the best sequence of intervention application to help individuals attain their maximal functional potential and reduce their symptoms of shortness of breath.

Adult Obstructive Lung Conditions Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease is currently the third leading cause of death in the world. It continues to increase in the adult population, and additional increases in prevalence and mortality are predicted in the coming decades.21 “Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles and gases.”22 The chronic airflow limitation that characterizes COPD is caused by a mixture of parenchymal alveolar disease (emphysema) and small-airway disease (obstructive bronchiolitis). Most commonly, these conditions occur in combination, with proportions varying from individual to individual.22 However, in some cases, either emphysema or chronic bronchitis is clearly dominant. These two disorders are discussed separately next.

Emphysema “In emphysema of the lungs, the size of the vesicles (alveoli) is much increased, and is less uniform. The greater number equal or exceed the size of a millet seed, while some attain the magnitude of hemp-seed or cherry-stones, or even french beans (haricot vert). These latter are probably produced by the reunion of several of the air cells through rupture of the intermediate partitions; sometimes, however they appear to arise from the simple enlargement of a single vesicle.”23 Today, emphysema is defined similarly. In anatomic terms, emphysema is defined as a condition of the lung characterized by destruction of alveolar walls and enlargement of the air spaces distal to the terminal bronchioles, including the respiratory bronchioles, alveolar ducts, and alveoli.24 The key role inflammatory cells play in activating potentially destructive mechanisms within the lung has been clearly recognized (see the section on the pathophysiology of COPD). The concept that the lung has some ability to repair itself has recently emerged, with emphysema representing an imbalance between destruction and repair.24 This is especially true in α1-antitrypsin deficiency, a genetic condition that predisposes affected individuals to the early development of emphysema.

There are three subtypes of emphysema: centriacinar (centrilobular), panacinar (panlobular), and paraseptal (distal acinal or subpleural) (Fig. 6-6): ▪ Centrilobular emphysema describes proximal dilation of the respiratory bronchioles, with alveolar ducts and sacs remaining normal. It is most common in the upper lobes and posterior portions of the lung. ▪ Panlobular emphysema describes dilation of all the respiratory airspaces in the acinus and occurs most frequently in the lung bases. Panlobular emphysema is seen in emphysema associated with α1-antitrypsin deficiency. ▪ Distal acinar (subpleural) emphysema describes dilation of airspaces underneath the apical pleura, associated with apical bullae (large air collection contained within a thin outer wall), which can lead to spontaneous pneumothorax.

FIGURE 6-6 Subtypes of emphysema. (From Black JM, Hawks SJ: Medical-surgical nursing: clinical management for positive outcomes, ed 8, Philadelphia, 2008, Saunders.)

Pathology Cigarette smoking, which is a major cause of emphysema, leads to inflammatory cell recruitment, proteolytic injury (the hydrolysis of proteins by enzymes) to the extracellular matrix, and cell death. In addition, airway walls become perforated, and in the absence of repair, the walls become obliterated and small distinct airspaces appear, changing into larger abnormal airspaces.24 Three types of emphysema are named for the location of airspace enlargement within the acinus. The acinus includes all the lung tissue distal to the terminal bronchiole and is composed of respiratory bronchioles, alveolar ducts, and alveolar sacs, all of which participate in gas exchange.24

Chronic Bronchitis Bronchitis “Pulmonary catarrh is inflammation of the mucous membranes of the bronchia. … This inflammation is attended, from the commencement, with a secretion of mucus more abundant than natural … it obstructs, more or less completely, the bronchial tubes, especially those of small calibre … and the impeded transmission of air … produces the sound usually denominated the rattles.”23 Today, chronic bronchitis is defined in clinical terms, as the presence of a chronic productive cough for 3 months in each of 2 successive years, provided that other causes of chronic mucus production (cystic fibrosis [CF], bronchiectasis, and tuberculosis [TB]) have been ruled out.25 Hypersecretion of mucus begins in the large airways and is not associated with airway obstruction (simple bronchitis). Later, hypersecretion progresses to smaller airways, where airway obstruction begins as chronic bronchitis. Obstruction of the small airways in COPD is associated with thickening of the airway wall. This remodeling, which involves tissue repair and malfunction of the mucociliary clearance system, results in the accumulation of inflammatory mucous exudates in the airway lumen.26 The progression of COPD is strongly associated with this increase in the volume of tissue in the walls of small airways and the accumulation of inflammatory mucous exudates.26

Pathology In chronic bronchitis, there is hypertrophy of the submucosal glands, and the gland-tobronchial wall thickness ratio, or Reid index, is used as an indicator of mucous gland hypertrophy. In individuals with chronic bronchitis, this ratio may be as high as 8 to 10, whereas it normally is less than 3 to 10.27 Surface epithelial secretory cells are increased,

and patchy areas of squamous metaplasia may replace normally ciliated epithelium. The degree of small-airway involvement (bronchioles) determines the degree of disability (Fig. 6-7).27

FIGURE 6-7 Chronic bronchitis may lead to the formation of misshapen or large alveolar sacs with reduced space for oxygen and carbon dioxide exchange. The client may develop cyanosis and pulmonary edema. (From Goodman CC, Snyder TE: Differential Diagnosis for Physical Therapists: Screening for Referral, ed 4, St. Louis, 2006, Saunders.)

Chronic Obstructive Pulmonary Disease: The Combination Disease Etiology Cigarette smoking is the most common risk factor worldwide contributing to the development of COPD, although in many countries, air pollution from the burning of wood and other biomass fuels has also been identified as a risk factor.22 Chronic obstructive pulmonary disease is a term that describes obstructive airway disease caused by a combination of emphysema and chronic bronchitis (including small-airway disease).

Clinical presentation and symptoms can vary from individual to individual (Fig. 6-8).

Clinical tip Spirometry is considered the gold standard for diagnosing COPD and monitoring its progression. Decreases in expiratory flow rates result in decreased FEV1 and FEV1/FVC values. Spirometry is the best standardized, reproducible, and objective measure of airflow limitation available.22 Smokers lose lung function in a dose-dependent manner, with heaviest smokers sustaining greater loss of lung function. However, many other factors, both genetic and environmental, affect individual susceptibility to develop COPD.24 The onset of COPD usually begins in midlife.22 When the onset occurs at a young age (30 mm Hg or dec rease in DBP of >10 mm Hg DBP response to sustained S NS After establishing maximum forc e by performing a maximal c ontrac tion on a handgrip dynamometer, the grip is squeezed isometric exerc ise at 30% maximum for 5 min and toward the end a BP is obtained in the other arm Normal response: Inc rease in DBP of >16 mm Hg Abnormal response: Dec rease in DBP of >10 mm Hg Test

BP, blood pressure; bpm, beats per minute; DBP, diastolic blood pressure; ECG, electrocardiogram; HR, heart rate; PNS, parasympathetic nervous system; SBP, systolic blood pressure; SNS, sympathetic nervous system. a b

All indexes of HR variability are age dependent.

Lowest normal value of R-R expiration/inspiration ratio is 1.17 for ages 25 to 29 years, 1.15 for ages 30 to 34, 1.13 for ages 35 to 39, 1.10 for ages 40 to 44, 1.08 for ages 45 to 49, 1.07 for ages 50 to 54, 1.06 for ages 55 to 59, 1.04 for ages 60 to 64, 1.03 for ages 65 to 69, and 1.02 for ages 70 to 74.

Table 7-12 Signs and symptoms of hypoglycemia Hypoglycemic reactions Adrenergica Mild Tremor or shakiness (BG ≤60 to 70 mg/dL) Anxiety and nervousness Tac hyc ardia Palpitations Inc reased sweating Exc essive hunger Moderate Irritability and abrupt mood c hanges (BG ∼40 to 50 mg/dL) Weakness Dizziness Numbness or tingling of lips and tongue Nausea or vomiting (rare)

S evere c

Neuroglycopenicb

Headac he Lethargy, drowsiness Impaired c onc entration and attentiveness Blurred vision Mental c onfusion Nightmares Nighttime restlessness or inability to go bac k to sleep Night sweats Loss of c onsc iousness S eizures Coma Death

Caused by increased activity of the autonomic nervous system.

Caused by decreased activity of the central nervous system.

Definitions of severe hypoglycemia vary and include hypoglycemia, resulting in a seizure or a coma, reactions that require the intervention of another person, or a reaction that requires the administration of intravenous glucose, intramuscular glucagon, or hospitalization.

Table 7-13 Signs and symptoms of hyperglycemia and ketoacidosis Adrenergica Mild-to-moderate hyperglyc emiac Frequent urination Dry mouth, inc reased thirst More marked hyperglyc emia Inc reased hunger Flulike ac hiness S erious ketoac idosis Fac ial flushing Dry skin Nausea or vomiting Abdominal pain Deep, rapid breathing Fruity-smelling breath

Neuroglycopenicb Weakness or fatigue Headac he Blurred vision Coma Death

Caused by increased activity of the autonomic nervous system.

Caused by decreased activity of the central nervous system.

Perceptions of hyperglycemia vary among individuals: some persons notice symptoms only when blood glucose is very high, whereas others notice symptoms with more mild degrees of hyperglycemia.

To reduce risk of hypoglycemia related to the injection site, diabetics should avoid injecting insulin into tissue near the exercising muscles, particularly if the patient will be exercising within 40 minutes after regular insulin or within 90 minutes after intermediate insulin. Injection in the abdomen or arm is preferable to the leg, and rotation within the same site is recommended over using different sites.163 Interestingly, exercise does not appear to affect the absorption rate of the long-acting insulin analog glargine.161 In individuals with type 2 DM who take oral antihyperglycemic agents, the risk of hypoglycemia is generally very low. Only the insulin secretagogues (sulfonylureas and glinides) are associated with a higher risk of hypoglycemia, and typically a 50% dose

reduction is recommended on the days of exercise (unless the patient exercises on a daily basis and dosages have already been adjusted accordingly).137 Patients with type 2 DM should avoid exercise if BG is more than 400 mg/dL, which is usually related to overeating. Table 7-14 General strategies for limiting blood glucose excursions associated with exercise

BG = blood glucose concentration; CHO = carbohydrate; CSII = Continuous Subcutaneous Insulin Infusion. a

Adjustment of insulin dose varies according to individual responses to exercise and dose adjustment. It is a trial-and-error process that requires experience, such that dosages are adjusted on subsequent exercise days based on the measured response.

Dietary adjustments are important for diabetics to prevent hypo- and hyperglycemic reactions, as well as to meet their increased caloric and fluid requirements. To maximize endogenous energy stores, a meal containing 200 to 350 g of carbohydrates along with fats and protein should be ingested about 3 to 6 hours before a sports competition. In addition, in the absence of hyperglycemia, excessive heat and humidity, or competition stress, the performance of moderate-to-high intensity exercise is enhanced by a carbohydrate beverage containing 6% to 8% simple sugar, which optimizes absorption, or a low-fat carbohydrate snack (e.g., crackers, fruit, yogurt) that provides 1 g CHO/kg body weight ingested approximately 1 hour before exercise; alternatively, for exercise lasting less than 45 minutes, a preexercise carbohydrate snack of about 15 to 30 g consumed 15 to 30 minutes before exercise is usually adequate.137,161,194 Resistance training is most effective at improving glycemic control when high-intensity exercise targeting all major muscle groups is performed in three sets of eight to ten repetitions at a weight that induces near fatigue three times a week.171,195 Greater CVD risk reduction is achieved with at least 4 hours per week of moderate-to-vigorous aerobic, resistance, or combined exercise,177 but larger volumes of exercise (7 hours per week) are

more successful in achieving and maintaining major weight loss.110 A few other factors should be emphasized in the care of diabetics. First, diabetics should practice good foot care by wearing proper shoes and cotton socks, inspecting feet after exercise, and maintaining good hygiene. Patients with severe peripheral neuropathy should engage in non–weight-bearing exercise to reduce the risk of skin breakdown, infection, and the development of Charcot joint destruction. Second, diabetics should never exercise alone and should always carry medical identification and supplemental carbohydrates. Lastly, patients should be alerted to the possibility of delayed exerciseinduced hypoglycemia, which may occur up to 24 or more hours after exercise. In patients with type 2 DM, medications used to treat comorbidities can affect exercise responses. Diuretics can decrease or increase potassium levels, leading to various arrhythmias. Diuretics and β-blockers may impair thermoregulation during exercise, particularly when it is hot and humid. β-Blockers attenuate the HR response to exercise and may reduce exercise capacity and exercise performance. Aspirin and angiotensinconverting enzyme (ACE) inhibitors may increase the patient’s susceptibility to hypoglycemia.

Chronic Kidney Disease and Failure The kidneys are complex organs whose major functions include the control of extracellular fluid volume; the regulation of serum osmolality, electrolyte, and acid–base balances; and the secretion of hormones such as renin and erythropoietin. Thus when renal function becomes impaired, the resultant metabolic disturbances affect virtually every other body system. Impairment of glomerular filtration results in renal insufficiency or failure, which can be staged according to severity (Table 7-15). Chronic kidney disease is usually an insidious process that is generally asymptomatic initially (stages 1 and 2), being manifested only as microalbuminuria and increasing glomerular filtration rate (GFR), and later presents with symptoms of only vague general malaise and ill health (stages 3 and 4) until late in its progression. Only when renal failure becomes marked (stage 5), with the accumulation of water, crystalloid solutes, and waste products, are the symptoms of uremia manifested: altered electrolyte homeostasis and acid–base imbalance, GI distress, severe anemia, and multiple other abnormalities involving the skin, respiratory, CV, neurologic, musculoskeletal, endocrine, genitourinary, and immune systems. Risk factors for CKD include DM, HTN, CVD, and obesity.196 Other less common but important etiologies include primary glomerulonephritis, lupus, and polycystic kidney disease. On rare occasions, CKD can develop as a complication of overuse of some common drugs, such as aspirin, ibuprofen, acetaminophen, and cocaine. The major sequelae of CKD include development and progression of CVD (the most common cause of morbidity and mortality), anemia, bone disease, and continued progression of the disease toward chronic renal failure (CRF). Renal failure sometimes results from acute kidney injury (AKI), such as poor renal blood flow while on cardiopulmonary bypass or drug overdose, and is characterized by rapidly progressive loss of renal function, which is potentially reversible with proper treatment, including dialysis, until the kidneys recover sufficient function. More commonly, it results from a progressive and irreversible chronic disease that affects the kidneys, such as DM (∼40% of cases), HTN (∼25% of cases), and CHF (∼50% of cases).197–200 On occasion, AKI can occur on top of CKD, which is referred to as acute-onchronic renal failure (AoCRF). Chronic renal failure is associated with a number of major health problems: HTN, pericarditis with pericardial effusion and sometimes cardiac tamponade, accelerated atherosclerosis, anemia, bleeding disorders, renal osteodystrophy (bone changes resembling osteomalacia and rickets occurring in patients with chronic renal failure), proximal myopathy (wasting and weakness of the proximal skeletal muscles), peripheral neuropathy, peptic ulceration, and immunosuppression leading to intercurrent infections.201 Although most of these complications are reversible with frequent dialysis, patients maintained on dialysis can develop other problems, as will be described later.

Table 7-15 Stages of chronic kidney disease and corresponding cardiovascular risk

CKD, chronic kidney disease; CV, cardiovascular; ESRD, end-stage renal disease (indicating the need for renal replacement therapy); GFR, glomerular filtration rate a

The increase in CV risk in comparison with people free of CKD depends on the age of the population studied: the younger the person, the higher the relative risk. Microalbuminemia increases the CV risk two- to fourfold. b

Stage 1 CKD is mostly recognized by either albuminuria or structural renal abnormality (usually identified using ultrasound).

Data from Schiffrin EL, Lipman ML, Mann JFE. Chronic kidney disease: Effects on the cardiovascular system. Circulation 116:85–97, 2007.

Cardiovascular and Pulmonary Complications of Chronic Kidney Disease Chronic kidney disease and renal failure are associated with a number of CV and pulmonary complications.

Cardiovascular Complications Chronic kidney disease increases the risk of major CV events, which appears even with relatively minor renal abnormalities, such as slightly reduced GFR or microalbuminuria occurring within the normal range, and intensifies in proportion to the severity of the disease, as shown in Table 7-15. Decreasing renal function results in a number of abnormalities involving changes in coagulation, fibrinolysis, endothelial dysfunction, anemia, calcium–phosphorous balance, RAAS, lipid abnormalities, and arrhythmia.197,198,202 By the time patients require dialysis, 40% have evidence of CAD and 85% of these patients have abnormal LV structure and mass.198 The annual mortality rate for patients with end-stage renal disease (ESRD) is above 20%, and approximately 50% of deaths are related to CVD, particularly MI, CHF, and stroke.197,198,202 In fact, death due to CVD complications is more common in patients with CKD than progression to CRF. Hypertension is almost invariably present, as it is both a cause and a consequence of renal disease and greatly aggravates renal dysfunction in CKD, particularly in blacks. About 50% to 75% of individuals with stage 3 or greater CKD have HTN and LVH, which accelerates CV morbidity and mortality due to CAD, stroke, and PAD.203 Additionally, LVH increases the incidence of myocardial ischemia, leading to further impairment of LV

function. Left ventricular hypertrophy is also aggravated by anemia, and there is some evidence that treatment of anemia with erythropoietin ameliorates LVH and improves survival.204 Treatment is usually initiated when BP is 130/80 mm Hg or higher and almost always consists of ACE inhibitors or angiotensin II receptor blockers (ARBs), which are known to delay progression of CKD and reduce CV mortality; most patients require multiple antihypertensive medications, often three to four, to achieve adequate BP control. Also, HTN commonly develops in kidney transplant recipients, often as a complication of the antirejection medication cyclosporine, and contributes to graft loss and premature death; newer immunosuppressive regimens are associated with lower rates of HTN. Accelerated atherosclerosis is related to numerous CV risk factors commonly seen in patients with CKD: DM and insulin resistance, HTN, dyslipidemia, and obesity. Endothelial dysfunction, low-grade inflammation, enhanced coagulability, and hyperhomocysteinuria observed in CKD contribute to higher prevalences of CAD, cerebrovascular accident (CVA) and transient ischemic stroke (TIA), and PAD.197,198 Morbidity and mortality rates are elevated following acute MI and coronary revascularization procedures and are directly related to the degree of renal dysfunction.198,202 Heart failure is also prevalent in CKD, occurring in about 40% of those more than 65 years of age, and 65% to 70% of patients with ESRD have CHF.199 Not only is it likely that CKD itself is a major contributor to severe cardiac damage, but it also appears that CHF is a major cause of progressive CKD, as about half of patients with CHF have some degree of CKD. The codependence between the kidneys and heart also leads to the cardiorenal syndrome, which includes the presence of renal insufficiency, diuretic resistance, anemia, tendency to hyperkalemia, and low SBP and is related to anemia, microalbuminuria, and calcium–phosphorous imbalance.205 Treatment with ACE inhibitors and ARBs reduces mortality rates for both CHF and CKD. Other causes of CHF in individuals with CKD include HTN, CAD, DM and increased insulin resistance, anemia, and hypervolemia between renal replacement treatments. Other CV abnormalities that occur as complications of CKD and CRF include coronary microvascular dysfunction (producing myocardial ischemia), cardiac autonomic neuropathy (CAN) (∼75% of patients show reduced HR variability),193 and uremiainduced pericarditis and pericardial effusion (which occasionally leads to cardiac tamponade).

Pulmonary Complications Acute or chronic renal failure is also associated with a number of pulmonary complications. Pulmonary edema is the most serious problem and may be due to fluid overload, hypoalbuminemia, and possibly increased pulmonary microvascular permeability (in addition to CHF). Fibrinous pleuritis is found in 20% to 40% of patients who die of CRF and is manifested as pleuritic chest pain with pleural rubs, pleural effusion, or fibrothorax.206 Other pulmonary complications that occur in patients with

CRF include pulmonary calcification that may be induced by secondary hyperparathyroidism, pleural effusion due to uremia, and an increased risk of respiratory tract infection, especially TB and pneumonia, probably caused by pathologic changes in the respiratory tract and impaired immune function. There is evidence of respiratory muscle weakness contributing to restrictive lung dysfunction in patients with ESRD, which improves following renal transplantation. The treatment of ESRD is often associated with pulmonary complications. The majority of patients treated with hemodialysis show a decrease in arterial oxygen concentration (PaO2) during treatment, which results from hypoventilation induced by loss of CO2 or metabolic alkalosis, depending on the type of dialysate used.207 Other forms of treatment are also associated with pulmonary abnormalities. Peritoneal dialysis is commonly associated with pleural effusions and an elevated diaphragm. Renal transplantation is complicated by pulmonary problems in an estimated 18% to 24% of patients, which include opportunistic pulmonary infections (pneumonia and TB) due to immunosuppression, pulmonary edema, pulmonary thromboembolism, and pulmonary calcification.208,209 In addition, immunosuppression with sirolimus following transplantation is sometimes complicated by pleural effusion and interstitial pneumonitis.

Treatment of Chronic Renal Failure The primary goals of treatment for CKD are to retard the rate of progressive deterioration in renal function and to minimize the complications of CRF. Preventive measures to limit disease progression include ACE inhibitors or ARBs to thwart RAAS and control BP, statins for dyslipidemia, early treatment of anemia to achieve hemoglobin levels of 11 to 12 g/dL, intensive hyperglycemia management, and smoking cessation.141,197,203 Primary and secondary prevention strategies to reduce the risk of CVD and associated mortality are also essential, and patients are usually prescribed a number of medications: β-blockers, calcium channel blockers, and ACE inhibitors or ARBs to control BP and HF and to provide secondary prevention following MI, and statins to improve lipid abnormalities and inhibit inflammatory processes involved in plaque formation. When the symptoms or complications of CKD become unacceptable, renal replacement therapy (RRT) is indicated and is most commonly accomplished using hemodialysis or peritoneal dialysis. Dialysis is a process that replaces the excretory functions of the kidney through the use of a semipermeable membrane and a rinsing solution (dialysate) to filter out toxic waste substances from the blood. Dialysis also allows for control of fluid and electrolyte balances. However, RRT fails to adequately provide the regulatory and endocrine functions normally afforded by the kidneys and is associated with renal osteodystrophy, anemia, vascular access infections and thromboses, pericarditis, and ascites. In standard hemodialysis, patients go to an outpatient dialysis center, typically 3 days per week, to be connected to a dialysis machine (dialyzer) through an arteriovenous

fistula or venous graft; the treatment typically takes 3 to 4 hours, but can take longer in very large individuals. The same treatment is used for inpatients when they are hospitalized for some reason. Many patients undergo peritoneal dialysis, whereby a dialysis fluid is introduced into the peritoneal cavity via a permanent catheter placed in the abdominal wall and remains for several hours while waste products and extra fluid are filtered out from the vascular system through the peritoneal membrane into the dialysate solution. In continuous ambulatory peritoneal dialysis (CAPD), the used fluid from the previous treatment is drained from the abdomen after a few hours of “dwell time” and new fluid is introduced; this is a manual procedure that requires no machine, and the fluid exchanges are performed four times per day. Although many patients do well for more than 10 years on dialysis, success is limited by the impaired clearance of waste products and other substances and the marked impairment of the regulatory and endocrine functions normally provided by the kidneys. Therefore the treatment of choice for ESRD, particularly in younger patients, is kidney transplantation. It offers the best opportunity for normalization of renal function and lifestyle, but its application is dependent on organ availability. Furthermore, transplantation can be complicated by a number of early and late immunologic, surgical, and medical events, as well as problematic side effects of the immunosuppressive medications that are required.

Exercise and Chronic Kidney Disease and Failure Patients with CKD exhibit impaired exercise tolerance and reduced muscle strength and endurance, which become more limiting as kidney disease progresses. Contributory factors include anemia, CVD, chronic physical inactivity, skeletal muscle dysfunction, and metabolic acidosis. In most patients with ESRD, exercise capacity is reduced to approximately 50% to 60% of normal.193,210,211 However, it is important to keep in mind that these values were determined from studies that included only the highest functioning patients, with exclusion of patients with DM and/or CVD comorbidities; therefore they are not representative of the larger percentage of patients who are more physically limited.211 In addition, many dialysis patients suffer from mild-to-severe neuropathy, which is compounded by diabetic neuropathy in a large percentage of patients and is a major cause of disability.212 Lastly, patients are frequently limited by reduced flexibility and impaired coordination.213 Thus many ADLs and lower levels of employment are challenging for the majority of individuals, especially those with DM. Typically, the limiting symptom is skeletal muscle fatigue, and patients with CKD have notable skeletal muscle atrophy and weakness. Biopsy studies indicate that skeletal muscles frequently have abnormal structure and function, referred to as uremic myopathy. Contributory factors include malnutrition because of inadequate protein and/or energy intake and increased protein catabolism (protein-restricted diets are recommended for patients with CKD, as they have been shown to delay the progression of the disease and alleviate uremic symptoms), impaired protein synthesis and amino acid metabolism, chronic deconditioning, and side effects of excess parathyroid hormone and other uremic

toxins, among others.214–217 This skeletal muscle wasting results in multiple functional, metabolic, and psychological deficits, as illustrated in Fig. 7-6. For patients with ESRD, compliance is highest when exercise sessions are performed during dialysis, which is well tolerated when performed within the first 1 to 2 hours of a dialysis session. However, because the intensity is lower with intradialytic exercise, the effects are less pronounced.210,218,219 In patients with chronic renal insufficiency, resistance training has been reported to improve muscle strength and mass, functional performance (6-minute walk test, normal and maximal gait speed, sit-to-stand test), peak exercise capacity, and possibly GFR; it also reduces inflammation, maintains body weight, and increases protein utilization and nitrogen retention to counteract the catabolic effects of protein restriction, low energy intake, and uremia.215,220 In dialysis patients, resistance exercise produces additional benefits as well, including enhanced cardiac vagal tone at rest, leading to lower resting HR and reduction in the incidence of cardiac arrhythmias, increased body weight, and improved quality of life.205,214,221–223 Combined aerobic exercise and resistance training appear to provide augmented benefits, increasing VO2max by 41% to 48% (more accurately referred to as VO2peak because most patients cannot exercise intensely enough to reach their true maximum), augmenting HR variability, and reducing risk of arrhythmia.224,225 More randomized clinical trials are needed to identify optimal training regimens according to patient characteristics and the effects on specific outcomes in patients with CKD.

Clinical Implications for Physical Therapy As discussed, patients with CRF are often debilitated and have poor tolerance for activity. A major contributing factor appears to be physical inactivity. Approximately 60% of patients with ESRD participate in no physical activity beyond basic ADLs, and their sedentary behavior may contribute to a number of adverse effects, as illustrated in Fig. 76. Sedentary patients show a 62% greater risk of mortality over 1 year compared with nonsedentary patients, given adjustments for other variables associated with survival.223,226 Fortunately, there is evidence that dialysis patients will increase their physical activity if given specific information and encouragement to do so, generating the improvements in physical functioning and exercise capacity already described.223

FIGURE 7-6 Causes and consequences of muscle wasting in end-stage renal disease. (From Cheema BSB: Review article: Tackling the survival issue in end-stage renal disease: time to get physical on haemodialysis, Nephrology 13(7):560–569, 2008.)

Laboratory values should be reviewed before each treatment, especially in dialysis patients. Particular attention should be directed to hemoglobin, hematocrit, glucose, potassium, calcium, creatinine and blood urea nitrogen (BUN), white blood cells (WBC), and platelets (see Chapter 8), and appropriate treatment modifications should be made if values are abnormal. Treatment of anemia with erythropoietin improves exercise tolerance, quality of life, and possibly survival.197 Fluid status should also be assessed, as hypervolemia may reduce exercise tolerance. In patients with CKD, maximal exercise capacity and muscle strength decrease as renal disease progresses long before they develop ESRD. Exercise training, using both aerobic and resistance exercise, is beneficial for the prevention of physical deterioration as the disease progresses.213,227 As with the general population, exercise prescription

incorporates four parameters: mode, intensity, duration, and frequency. Yet, in dialysis patients, a fifth exercise parameter should also be considered: the timing of exercise relative to the patient’s dialysis treatment. Patients who perform exercise during dialysis benefit from improved dialysis efficacy (by 10% to 15%), with greater removal of waste products produced by augmented flux between the blood and the dialyzer because of increased cardiac output, as well as expanded capillary blood flow as a result of exerciseinduced vasodilation in the exercise muscle bed.218 Because of the prevalence of DM in patients with CKD, the clinical implications previously discussed for diabetics should be noted when appropriate. Furthermore, given that patients with CKD often have CVD and DM, they are often taking multiple medications that may have adverse effects on exercise responses and tolerance, which are also described at the end of the section on diabetes.

Other Specific Diseases and Disorders A wide variety of other specific diseases may be associated with cardiopulmonary complications. The presence of CV or pulmonary complications may affect patient tolerance for physical activity and many PT interventions. Tables 7-16 to 7-20 summarize the CV and pulmonary manifestations of a number of specific diseases and disorders that are commonly encountered by physical therapists, as well as those associated with various cancer treatments.

Connective Tissue Diseases The connective tissue diseases (CTDs) are a diverse group of diseases in which connective tissue (CT) cells or extracellular matrix proteins, particularly collagens, proteoglycans, and elastins, are damaged by various genetic mutations, inflammatory mechanisms, or degenerative processes. Because of the wide distribution of connective tissues throughout the body, CTDs often have diffuse systemic effects, and all have the potential for CV and pulmonary involvement. Cardiopulmonary effects are often subclinical or found only at autopsy, although this may be due, at least in part, to limitations imposed by the musculoskeletal features that mask their presence. Table 7-16 Most common cardiovascular and pulmonary manifestations of the connective tissue diseases

AI, aortic incompetence; Art, abnormalities affecting the arterial system; CA, coronary arteries; CHF, congestive heart failure; E/V, endocardial/valvular; ECG, ECG changes, arrhythmias and conduction disturbances; F, fibrosis; HTN, hypertension; I, interstitial; M, myocardial; Mm., respiratory muscle weakness; MR, mitral regurgitation; MVP, mitral valve prolapse; P, pericardial; Pl., pleural; Pn., pneumonitis; pulm., pulmonary; Vasc., vascular. +, convincing association; ++, very common; +/−, possible association; −, no association reported for specific disease/disorder.

Table 7-17 Pulmonary and cardiac complications of the common infiltrative diseases

CHF, congestive heart failure; CM, cardiomyopathy.

Table 7-18 Cardiac and pulmonary manifestations of some neurologic and neuromuscular diseases

AV, atrioventricular; Bulb, bulbar muscle involvement; CA, coronary arteries; CHF, chronic heart failure; Cond, conduction system; ECG, electrocardiogram; Mm, respiratory muscle weakness or paralysis; RLD, restrictive lung dysfunction; Sleep, sleep-disordered breathing. +, convincing association, ++, very common, +/−, possible association, −, no association reported for specific disease/disorder.

Table 7-19 Cardiac and pulmonary manifestations of some other specific diseases

CA, coronary arteries; E/V, endocardial/valvular; H, hypertension; I, interstitial; M, myocardial; P, pericardial; Pl., pleural; Pn., pneumonitis; Vasc., vascular. +, convincing association; ++, very common; +/−, possible association; −, no association reported for specific disease/disorder.

Table 7-20 Pulmonary toxicity associated with cancer treatments

Autoimmune Rheumatic Diseases The autoimmune rheumatic diseases are systemic diseases that are characterized by immune-mediated inflammatory abnormalities that affect the joints, muscles, and connective tissues. The autoimmune rheumatic diseases can affect all pulmonary structures (the respiratory muscles, the pleura, the small airways, the interstitium, and the pulmonary vessels), either separately or in combination, and all cardiac structures (endocardium, myocardium, conduction system, pericardium, and coronary arteries), as shown in Table 7-16, and this involvement is often responsible for increased morbidity and mortality.228–230 Not infrequently, pulmonary involvement precedes the musculoskeletal manifestations by several months to several years and appears as pleuritis, infection, pneumonitis, interstitial disease, and pulmonary vascular disease. Pulmonary disease can also develop from a toxic reaction to drugs used to treat autoimmune rheumatic diseases (e.g., d-penicillamine, methotrexate, gold, cyclophosphamide, sulfasalazine, nonsteroidal anti-inflammatory drugs). Pericarditis is the most common cardiac manifestation, appearing as pericardial effusion or pericardial thickening. In addition, involvement of the endocardium can induce arrhythmias and valvular dysfunction, myocardial involvement can lead to cardiomyopathy, and involvement of the coronary arteries can result in myocardial ischemia and, on rare occasions, infarction. Of note, as improved therapies and preventive measures have reduced the incidence and severity of cardiopulmonary complications of these diseases and extended the longevity of these patients, atherosclerotic CVD has become an even

greater cause of death and disability.231 Inflammatory mechanisms, along with physical inactivity, are important contributory factors, as well as acceleration of atherosclerosis by corticosteroid treatment.232

Rheumatoid Arthritis The chronic inflammation of rheumatoid arthritis (RA) frequently affects other organ systems, including the CV and respiratory systems, particularly when the disease is severe and long-standing. The most prevalent pulmonary manifestations are pleural effusions (40% to 70% of patients), which are usually small but occasionally can be massive, causing shortness of breath and/or pleural chest pain; interstitial lung disease (80% of cases by lung biopsy), which is typically mild but sometimes evolves into progressive pulmonary fibrosis; bronchiectasis (20% to 35% of cases); and rheumatoid lung nodules (20% to 30% of patients).228 Although evidence of CV involvement is commonly seen during echocardiography and at autopsy, it is seldom clinically evident. Pericarditis can be detected in 30% to 50% of patients, valvular disease is found in 30% to 80% of patients, and cardiomyopathy is noted in 3% to 30% of RA patients on postmortem studies.233 Dyspnea is the most common symptom, followed by cough, and digital clubbing is found in many patients. Increased CV mortality results from CHF and ischemic heart disease and associated arrhythmias.

Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) results in diffuse and widespread inflammation involving the skin, joints, brain, kidney, heart, and virtually all serous membranes. Cardiovascular disease is the most common cause of death in patients with SLE.234 Pericarditis can be found in 62% of patients, becoming symptomatic with chest pain and sometimes a rub mainly at the onset of SLE or during flares; constriction or tamponade is rare. More than 50% of patients have valvular disease (usually regurgitation or rarely stenosis), which is clinically apparent in about 20% of patients.229 Another common problem is premature atherosclerotic CAD, which sometimes produces myocardial ischemia or infarction. More uncommon cardiac manifestations include myocarditis, which can lead to dilated cardiomyopathy, and endocarditis (both infective and pseudoinfective), which can result in valvular disease. Cardioembolism from valvular vegetations or left heart thrombi causes ischemic stroke in 10% to 20% of patients. Pleurisy is the most prevalent pulmonary complication, occurring in at least 45% to 60% of patients at some time during the disease228; it is often asymptomatic but sometimes causes recurrent or intractable pleuritic chest pain, pleural rub, and effusion. Inflammation of the lung parenchyma sometimes causes diffuse lung disease, with cough, hemoptysis, and pulmonary infiltrates. Restrictive lung dysfunction due to “shrinking lung syndrome” is a well-recognized complication of SLE that is thought to result from limited thoracic compliance. Uncommon but potentially lethal complications of SLE include pulmonary HTN due to either vasoconstriction or recurrent thromboembolism, diffuse alveolar hemorrhage, and chronic lupus pneumonitis.

Scleroderma Systemic sclerosis (SSc, or scleroderma) produces slowly progressive fibrosis and vascular obliteration of the skin, subcutaneous tissues, and often the visceral organs. It is known most for its pulmonary complications, which are the leading cause of morbidity and mortality, but CV involvement also occurs. Accumulation of CT matrix cells and proteins in the lungs leads to interstitial lung disease with progressive fibrosis, affecting 75% of patients at autopsy, and subsequent pulmonary HTN in up to 50% of cases.228 The incidence of lung cancer is increased 4- to 16-fold in patients with SSc and pulmonary fibrosis. Overt heart disease occurs in less than 25% of patients but is found in up to 80% at autopsy and results from either primary involvement of the heart or secondary involvement by SSc affecting the kidneys or lungs.229 Myocardial fibrosis (resulting from vasospasm and small vessel disease producing ischemia/reperfusion damage, as well as occlusive arterial disease) leads to cardiomyopathy.235 Other cardiac manifestations of SSc include myocarditis, pericarditis, and occasionally conduction disturbances and arrhythmias and valvular abnormalities. Dyspnea is the most frequent symptom, occurring in more than 60% of patients, particularly those with vascular disease. However, a sedentary lifestyle due to skin and joint restrictions often masks the symptoms of dyspnea on exertion until late in the disease process. Exercise testing frequently reveals subclinical pulmonary abnormalities not detected during routine PFTs.236

Ankylosing Spondylitis Ankylosing spondylitis mainly affects the spine and sacroiliac joints and is only occasionally associated with significant pulmonary or cardiac manifestations. Thoracic restriction due to severe rib cage immobility and kyphosis leads to restrictive lung dysfunction, which is usually surprisingly mild; symptoms of shortness of breath or chest wall pain are uncommon. On rare occasions, patients develop upper lobe fibrobullous lung disease or nonapical interstitial lung disease237; progressive dyspnea and cough are the usual symptoms, though cyst formation and subsequent infection may cause hemoptysis. Lastly, ankylosing hyperostosis of the cervical spine can cause dysphagia, foreign-body sensation, and aspiration. Cardiac involvement typically takes the form of sclerosing inflammatory lesions involving the aortic cusps, proximal aortic root, and adjacent atrioventricular nodal tissue, which can be identified in up to 100% of patients and induces aortic regurgitation in 10% of cases and varying degrees of atrioventricular conduction disturbances in about 5% of patients.229 Left ventricular dilatation and diastolic dysfunction are very common. Mitral regurgitation may also develop.

Mixed Connective Tissue Disease Mixed CTD is an overlap syndrome with clinical features of SLE, SSc, and myositis. Pulmonary involvement occurs in 20% to 85% of patients, according to the most dominant clinical pattern, and most often consists of interstitial lung disease and

pulmonary fibrosis, pleural effusion, and pulmonary HTN, which is a major cause of morbidity and mortality.228 The most common cardiac manifestations are pericarditis and mitral valve prolapse.

Inflammatory Myopathies The inflammatory myopathies are often included in the CTDs. Two types, polymyositis and dermatomyositis, are particularly likely to be associated with cardiopulmonary complications. Pulmonary involvement, which bears a poor prognosis, includes respiratory muscle dysfunction, interstitial lung disease (one form of which evolves quickly into acute respiratory failure, whereas others lead to progressive fibrosis), aspiration pneumonia (due to pharyngolaryngeal muscle weakness), and lung cancer. Death due to respiratory insufficiency occurs in 30% to 66% of patients.228 The muscle inflammation that is characteristic of the myositis also affects the heart, resulting in myocarditis and cardiomyopathy. The most common clinical manifestations seen in polymyositis and dermatomyositis are those of CHF and CAD (because of vasculitis, small vessel disease, and vasospasm, as well as atherosclerosis), which are major causes of mortality.238

Inherited Connective Tissue Diseases The inherited CTDs are characterized by abnormalities of the CTs that affect the great arteries, cardiac valves, skeletal system, and skin. The most common of these include Marfan syndrome, Ehlers–Danlos syndrome, and osteogenesis imperfecta. These diseases may cause minimal CV dysfunction, such as mitral valve prolapse or mild aortic root dilatation, or severe problems, such as severe aortic or mitral insufficiency or aortic aneurysm and dissection, depending on the degree of CT abnormalities and their response to prolonged hemodynamic stress. Some patients develop serious ventricular or supraventricular arrhythmias. Pulmonary problems may also develop as a result of bullous emphysema, chest wall deformities, kyphoscoliosis, and obstructive sleep apnea due to increased upper airway collapsibility.

Infiltrative Diseases Some diseases affect the heart and/or lungs through the infiltration or deposition of various substances within these organs (as well as other organs of the body). Amyloidosis, sarcoidosis, and hemochromatosis are the most recognized of these diseases, and their effects on the CV and pulmonary system are presented in Table 7-17.

Amyloidosis Amyloidosis results from the overproduction of certain proteins leading to the deposition of amyloid fibrils in various organs. It can occur as a primary process and also as a complication of some inflammatory processes, as in rheumatoid arthritis, inflammatory bowel disease, and bronchiectasis. Pulmonary amyloidosis can occur along

with systemic disease or as a localized entity, resulting in progressive diffuse parenchymal infiltrates, restrictive lung disease (RLD), and impaired gas exchange versus localized tracheobronchial plaques or diffuse parenchymal nodules and possible pulmonary HTN, obstructive sleep apnea caused by massive infiltration of the tongue, and respiratory failure induced by infiltration of the diaphragm. Cardiac involvement is commonly manifested as diastolic dysfunction due to infiltration of rigid amyloid fibrils and sometimes systolic dysfunction. Cardiomyopathy may occur as a result of restrictive dysfunction or dilation. Other CV problems include atrial arrhythmias, particularly atrial fibrillation, which has a high risk of thromboembolism; syncope caused by orthostatic hypotension, bradyarrhythmias, or tachyarrhythmias; and MI and sudden death provoked by involvement of the coronary arteries.

Sarcoidosis Sarcoidosis is a chronic inflammatory disease characterized by the presence of noncaseating granulomas in multiple organ systems with resultant combinations of inflammation and scarring, which can vary from mild and asymptomatic with spontaneous resolution to severe progressive disease leading to organ failure and death. Pulmonary manifestations consist of granulomas within the lung parenchyma (more often in the upper rather than the lower lobes) and within the bronchi, which can lead to bronchostenosis. Typical symptoms are dyspnea and nonproductive cough. Cardiac involvement is noted in up to 50% of patients at autopsy, but clinical manifestations are found in less than 10% of patients and include ventricular tachyarrhythmias and cardiomyopathy appearing as impaired LV function or CHF.

Hemochromatosis Hemochromatosis is a common inherited disorder of iron metabolism that leads to iron deposition in various organs, including the liver, heart, pancreas, joints, skin, and endocrine organs. Excess deposition of iron in the liver can be fatal but can be prevented by regular therapeutic phlebotomy to reduce circulating iron levels. Involvement of the heart can lead to secondary myocardial fibrosis, cardiomyopathy (either restrictive or dilated), and conduction disturbances or arrhythmias.

Neuromuscular Diseases and Neurologic Disorders A number of diseases and disorders affecting the neurologic or neuromuscular systems are associated with CV and pulmonary dysfunction (see Table 7-18). Among the most notable are spinal cord injury (SCI), stroke, Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Guillain–Barré syndrome (GBS), myasthenia gravis, the muscular dystrophies, and Friedreich ataxia. The incidence and severity of dysfunction in all the disorders vary widely. Pulmonary compromise is a common complication of many neuromuscular and neurologic disorders and is the major cause of morbidity and mortality.239–242 Respiratory

muscle weakness or paralysis, or abnormal tone, restricts chest expansion and ventilation and reduces cough force and effectiveness, leading to retained secretions, atelectasis, and high risk of pneumonia. Abnormally low pulmonary compliance, which may result from chronically impaired chest wall mobility and low lung volumes, makes the chest wall stiffer and adds to the difficulty in expanding the lungs. Hypoventilation, which is particularly common at night, and microatelectasis give rise to CO2 retention and hypoxemia, which may be exacerbated by different positions (e.g., lying flat in high cervical SCI, sitting in lower cervical SCI). Bulbar muscle weakness with dysfunction of the pharyngeal and laryngeal muscles, which is common in such diseases as ALS, myasthenia gravis, and multiple sclerosis (MS), increases the risk of recurrent aspiration and resultant pneumonia and interferes with cough effectiveness (due to poor glottic closure). Sleep-disordered breathing, including central apneas and hypopneas and obstructive sleep apnea, is seen in many patients, including those with quadriplegia, postpolio syndrome (PPS), ALS, and the muscular dystrophies. Nocturnal hypoventilation is often an indication of chronic respiratory muscle fatigue and increased risk of ventilatory failure, which can be ameliorated with the use of nocturnal ventilatory assistance, usually via nocturnal noninvasive positive pressure ventilation in most cases. Pulmonary embolism is a constant threat to patients with SCI, stroke, and other neurologic and neuromuscular diseases because of reduced peripheral blood flow and limited activity level.

Clinical tip It is important to realize that respiratory symptoms often do not correlate well with the degree of respiratory dysfunction in slowly progressive disorders. Measures of maximal inspiratory and expiratory pressures can be used to detect and monitor respiratory muscle weakness and are more sensitive than spirometric measures of lung volume. There are several recent studies regarding inspiratory muscle training and its benefits in the neuromuscular population.243,244 Patients with neuromuscular and myopathic disorders involving the respiratory muscles are particularly prone to hypoventilation and oxygen desaturation during sleep. Therefore clinicians should be attentive to the development of symptoms such as sleep disturbances, morning headache, excessive daytime somnolence, impaired concentration, and loss of appetite and alert the patient’s physician if they are noted. Cardiovascular dysfunction also occurs in many patients with neuromuscular and neurologic disorders, although the typical symptoms of dyspnea and reduced exercise tolerance are difficult to appreciate in nonambulatory patients. Instead, these patients may exhibit increased fatigue, difficulty sleeping, impaired concentration, and more subtle variants of poor performance.245 Cardiac abnormalities found in this population include cardiomyopathy associated with neuromuscular diseases, arrhythmias, and conduction disturbances. Disruption of autonomic nerve fibers in SCI with lesions above

T1 or nerve involvement by other neurologic pathologies, such as MA, ALS, PD, and GBS, can result in orthostatic hypotension and impaired thermoregulation. In older individuals, the presence of HTN and CAD often adds to CV dysfunction. In addition, abnormal movement patterns due to muscle weakness or abnormal neural input increase the energy cost of mobility and daily activities; impaired mobility induces a more sedentary lifestyle, which leads to CV and muscular deconditioning and diminished efficiency. Both of these factors contribute to exaggerated physiologic demands of mobility and ADLs and increase the risk of activity intolerance, as well as that of CVD morbidity and mortality. Appropriate exercise training provides many benefits for these patients.246–253 Hemiplegia can result from a number of events, including CVA due to thrombosis, embolism, or hemorrhage; surgical excision of a brain tumor; and trauma. Regardless of cause, weakness or spastic paralysis of the affected side of the body can include the diaphragm and intercostal muscles, leading to altered respiratory mechanics and reduced respiratory muscle efficiency. Left diaphragmatic dysfunction is more common than right. Pulmonary function tests reveal decreased volumes and flows to about 60% to 70% predicted normal values239–242,254; these abnormalities take on additional clinical significance in the presence of preexisting pulmonary disease. Respiratory failure can develop in patients whose vital capacity decreases to 25% or less of predicted normal values, and mechanical ventilation will be required. The major pulmonary complications associated with stroke occur when the facial and pharyngeal muscles are affected, causing impairments in secretion management, proper swallowing, airway protection, and cough effectiveness. The vast majority of patients with ischemic stroke also have CVD, particularly HTN and CAD, although most patients are asymptomatic and not diagnosed; CVD is responsible for the majority of deaths following TIAs, stroke, and carotid endarterectomy.255–258 There is also some evidence that both hemorrhagic and ischemic strokes are associated with nonischemic cardiac damage, most likely related to stress-induced release of catecholamines and possibly corticosteroids.259,260 The usual lack of clinical symptoms in hemiplegic patients is probably due to their low level of physical exertion; however, strenuous exertion or PT activities may elicit dyspnea and other signs of exercise intolerance, especially when lying flat. Spinal cord injury is associated with significant pulmonary dysfunction, according to the severity and level of injury.239,242,261 Spinal cord injury at or above C3 to C5 interferes with phrenic nerve function, causing partial or complete bilateral hemidiaphragmatic paralysis, and diminishes intercostal muscle forces, leading to marked reductions in ventilation and cough force; ventilatory assistance is almost always required for lesions above C4. Abnormal respiratory mechanics result in a paradoxical breathing pattern characterized by inward movement of the abdomen as the upper chest rises on inspiration. Lesions below C5 will have corresponding intercostal muscle involvement and therefore some restrictive lung dysfunction (VC may be reduced to 60% of predicted normal in high thoracic lesions and to 78% of predicted normal in low thoracic lesions),242 but because diaphragmatic and accessory muscle function is preserved, hypoventilation usually does not occur. In this case strong contraction of the diaphragm produces a

paradoxical breathing pattern marked by inward movement of the upper chest on inspiration. The work done by the diaphragm is up to nine times normal in lower cervical and high thoracic injuries, which is due in large part to the work required to displace the abdominal viscera, and dyspnea on exertion is common.239,242 The major problems with weakness of the expiratory muscles (internal intercostals and abdominals) are poor cough and impaired clearance of airway secretions. Cardiovascular abnormalities, mostly related to interruption of autonomic nervous system signals, also occur in patients with SCI. Acute injury to the cervical spine is frequently accompanied by cardiac arrhythmias and occasionally by sudden death. Patients with SCI at or above the T6 level often experience serious disturbances of BP. Orthostatic hypotension is common in the early phase of recovery but usually resolves over time. Autonomic dysreflexia (hyperreflexia) can produce marked elevation of BP when noxious visceral or cutaneous stimuli, such as a full bladder, are sensed below the level of the lesion. Furthermore, autonomic denervation interferes with temperature regulation so that body temperature tends to fluctuate according to the ambient temperature, especially in higher lesions; therefore hypo- and hyperthermia can develop. In addition, SCI above the T1 level is associated with reductions in both preload and afterload, which leads to atrophy of the LV and reduced systolic efficiency.250 Moreover, limited physical activity promoting a sedentary lifestyle and exercise intolerance increases the risk of CV morbidity and mortality.

Parkinson Disease Parkinson disease is a common dyskinetic disorder of the extrapyramidal system, which is characterized by resting muscle tremors, rigidity, slowness and poverty of motion, gait impairment, and postural instability. Secondary parkinsonism may develop following some cases of encephalitis and as a result of drug abuse and repeated brain trauma. Although rarely recognized clinically, impaired ventilatory function occurs in 50% to 87% of patients and tends to be proportional to the severity of the skeletal muscle disease and improves with effective treatment.262–265 Erratic or chaotic breathing due to the rigidity and weakness of the respiratory muscles, as well as abnormal control of ventilation, is common and results in restrictive lung dysfunction, decreased maximal inspiratory and expiratory forces and peak expiratory flow rate, and reduced maximum voluntary ventilation on PFTs. Upper airway obstruction is found in 5% to 62% of patients, most likely due to involvement of the upper airway musculature.263,266 In addition, an obstructive pulmonary disease may be associated with PD. Furthermore, medications used to treat PD are also associated with pulmonary dysfunction: overtreatment with levodopa causes dyskinetic breathing and abnormal central control of ventilation, and the ergot derivatives can cause pleuropulmonary fibrosis.262,265 Lastly, pneumonia resulting from pulmonary complications is a significant cause of morbidity and mortality in PD.265 There are no specific cardiac complications associated with PD; however, patients often have the same CV problems (HTN, atherosclerotic heart disease, etc.) that commonly occur in their same-aged peers. Exercise testing has shown that individuals

with mild-to-moderate PD who regularly exercise can maintain normal exercise tolerance; more involved patients exhibit significantly lower exercise capacity.267 Moreover, it is possible to improve exercise capacity in patients with mild-to-moderate PD with exercise training.

Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis (or Lou Gehrig disease) is the most common motor neuron disease in the United States and is characterized by progressive neurologic deterioration without remission due to loss and degeneration of both upper and lower motor neurons. Patients experience a combination of spasticity and hyperreflexia and muscle wasting, weakness, and fasciculations. Irreversible hypoventilation results from weakness of the intercostal muscles and diaphragm, but the insidious onset of gradually developing dyspnea may delay the diagnosis.241,242 Nocturnal hypoventilation can occur despite only mild respiratory muscle dysfunction and normal gas exchange. With bulbar involvement, which occurs eventually in 80% of patients, swallowing becomes impaired, leading to aspiration pneumonia. Mechanical ventilator dependence and fatal respiratory failure are common in the later stages of the disease, producing an average life expectancy of 4 years after diagnosis.268

Guillain–Barré Syndrome Guillain–Barré syndrome, or acute inflammatory polyneuropathy, is an autoimmune demyelinating disease of motor neurons that is usually triggered by an infectious process and is the most common cause of acute neuromuscular paralysis. Clinical manifestations include progressive symmetric ascending weakness and dyspnea, difficulty in coughing, and, later on, dysphagia and difficulty with speech. However, many patients do not notice respiratory dysfunction even in the presence of significant respiratory insufficiency because of the gradual onset and slow progression of the respiratory muscle weakness. Respiratory complications develop in approximately half of patients as a result of hypoventilation, impaired coughing, airway secretion retention, and atelectasis, and 30% of all patients progress to ventilatory failure and require mechanical ventilatory support during the course of their disease.242,269,270 There is a poor correlation between peripheral muscle strength and the presence or absence of respiratory muscle weakness. In addition, bulbar dysfunction causes upper airway obstruction and aspiration and increases the risk of ventilatory failure.

Multiple Sclerosis Multiple sclerosis is an autoimmune disease that causes demyelination of the CNS and is characterized clinically by periods of remissions and relapses of symptoms, although on occasion its course can be chronic and progressive. Multiple sclerosis is the most common neurologic disease affecting young adults. Its classic clinical symptoms include paresthesias, motor weakness, blurred and double vision, dysarthria, bladder incontinence, and ataxia. Because MS can cause focal lesions anywhere in the CNS,

different patterns of respiratory impairment can occur but are relatively rare. The three most common pulmonary manifestations are respiratory muscle weakness, bulbar dysfunction, and abnormalities of respiratory control.242,271–273 Pulmonary dysfunction correlates with the severity of the disease, so that quadriplegic patients with bulbar involvement are at highest risk for developing respiratory failure. Even with severe disability and impaired respiratory muscle strength, patients with MS seldom complain of dyspnea, most likely due to their low activity level and greater expiratory than inspiratory muscle dysfunction. Clinical signs that may be helpful in predicting respiratory muscle impairment are weak cough and inability to clear secretions, limited ability to count to 10 on a single breath, and upper extremity involvement. There are no specific CV abnormalities associated with MS.

Myasthenia Gravis Myasthenia gravis is an acquired autoimmune disorder with specific autoantibodies that attack the nicotinic acetylcholine receptors in the neuromuscular junction, producing muscle weakness that is aggravated by repetitive muscle contractions. The disease may affect only the ocular or bulbar muscles, but the limb and respiratory muscles are often involved. Respiratory muscle weakness occurs in about 10% of patients, and ventilatory failure may necessitate prolonged ventilatory assistance.239 The risk of ventilatory insufficiency is increased by surgery, acute infection, and the administration of corticosteroids or antimicrobial drugs. Of note, patients may have severe respiratory muscle involvement even with mild peripheral muscle weakness; however, most patients with moderate, generalized myasthenia gravis exhibit mild-to-moderate reductions in FVC and maximal inspiratory and expiratory forces.239,242 Cardiac involvement occurs in 10% to 40% of patients, especially those with thymoma, and appears to be caused by heart-reactive autoantibodies.274,275 Focal inflammation and necrosis are found on autopsy. Clinical symptoms include tachycardia and other arrhythmias and dyspnea. Notably, drugs used to treat CV problems, such as quinidine, procainamide, lidocaine, and morphine, may adversely affect myasthenia gravis. Treatment with acetylcholine esterase inhibitors (e.g., neostigmine and pyridostigmine) results in improvements in cardiac function and respiratory muscle strength and pulmonary function, but may have relatively little effect on respiratory muscle endurance. Plasmapheresis to remove the immunoglobulin G (IgG) antibody is sometimes used.

Duchenne Muscular Dystrophy Progressive (Duchenne) muscular dystrophy (DMD) is the most common inherited progressive myopathy and is caused by a lack of dystrophin. It is characterized by delayed motor development or early onset of progressive, generalized muscle weakness and pseudohypertrophy of certain muscle groups, especially the calves, resulting in increasing orthopedic, pulmonary, and cardiac complications and the inability to ambulate by the age of 10 or 11. Respiratory impairment becomes clinically manifest as chronic alveolar ventilation and poor cough caused by respiratory muscle weakness in

the advanced stages of the disease, usually in the late teens.241,242,276 Sleep-disordered breathing occurs in up to two-thirds of patients during the early teenage years and is associated with transient hypoxemic dips. Progressive kyphoscoliosis resulting from severe muscle weakness contributes to the respiratory decline. Finally, loss of the diaphragm late in the disease leads to hypercapnia and rapid deterioration. The most common cause of death is respiratory failure, which is usually precipitated by respiratory infection and occurs by the age of 20 unless ventilatory support is provided. Virtually all patients with DMD develop a dilated cardiomyopathy by age 10, but clinical recognition may be masked by severe skeletal muscle weakness.245,277–280 Dystrophic myocardial changes occur most prominently in the posterobasal and adjacent lateral LV and consist of vacuolar degeneration and fibrous replacement of the muscle fibers, as well as fatty infiltration of the heart muscle and peripheral circulatory system. Arrhythmias and conduction disturbances are common findings. Involvement of the posteromedial papillary muscle sometimes causes mitral valve prolapse and mitral regurgitation. Congestive heart failure usually develops in the preterminal stage of the disease. Becker ’s muscular dystrophy is a milder variant of DMD with more variable clinical manifestations. It presents later in life and is slower in progression, so that 50% of patients survive to age 40 and some have a near-normal life expectancy. Cardiac involvement, which is also more variable and unrelated to the extent of the musculoskeletal disease, is often more severe than in DMD.245,277,280 Dilated cardiomyopathy, bundle branch block, complete heart block, or tachyarrhythmias may develop.280,281 About 30% of patients develop dilated cardiomyopathy and CHF, and some patients have received heart transplants.281,282 Respiratory impairment develops similar to DMD, although its onset is later and its course is more slowly progressive.

Myotonic Dystrophy Myotonic dystrophy (Steinert disease), an autosomal-dominant multisystem disease, is the most common adult form of muscular dystrophy. Symptoms usually present during adolescence or early adulthood, with premature death usually resulting from cardiopulmonary complications. Respiratory muscle weakness is common in patients with myotonic dystrophy and can be severe, despite mild limb weakness. Myotonia of the respiratory muscles produces a chaotic breathing pattern, increased work of breathing, and often hypercapnia.241–245,276,283 Bulbar dysfunction and sleep-related breathing disturbances also occur. These patients are particularly susceptible to respiratory failure with general anesthesia and sedatives. Respiratory failure can also result from chronic respiratory muscle weakness, altered central control of breathing, and pneumonia. Myotonic dystrophy is associated with cardiac involvement, especially electrocardiogram (ECG) abnormalities and arrhythmias, in at least two-thirds of patients; high-grade heart block or ventricular tachycardia may cause sudden death.281,284,285 Occasionally, there is acute LV failure or CHF.

Additional Types of Muscular Dystrophy

Other types of muscular dystrophy are also associated with cardiopulmonary dysfunction.241,242,276,281 Cardiomyopathy may occur in fascioscapulohumeral (FSH) dystrophy and the limb-girdle syndromes, but they are usually less prominent and CHF is unusual. There may be cardiac gallop sounds, cardiac enlargement, and ECG abnormalities. Atrial abnormalities are present in all patients with X-linked scapuloperoneal myopathy (Emery–Dreifuss dystrophy) and result in sinus arrest, atrial arrhythmias, varying atrioventricular block, and permanent atrial paralysis with junctional bradycardia. Because sudden death is common in young adults, permanent pacing is recommended for ventricular rates below 50, regardless of atrial activity. Fascioscapulohumeral dystrophy and the scapuloperoneal syndromes have also been associated with atrial paralysis. Pulmonary function has not been studied in much detail in most of the other muscular dystrophies. Fascioscapulohumeral dystrophy affects the pelvic girdle and trunk muscles in approximately 20% of patients, and this involvement may be associated with impairment of pulmonary function, which tends to be mild and complicated by an increased incidence of obstructive sleep apneas related to upper airway muscle weakness. Facial muscle weakness makes spirometric measures unreliable. Limb girdle dystrophy may be accompanied by chronic hypoventilation, but rarely requires assisted ventilation. Finally, oculopharyngeal muscular dystrophy is associated with swallowing dysfunction, complicated by repeated aspiration, which may improve after cricopharyngeal myotomy.

Postpolio Syndrome Postpolio syndrome is a late sequela of poliomyelitis, which afflicts from 15% to 80% of polio survivors and develops 30 to 40 years after the acute enterovirus infection.286,287 Factors known to precipitate PPS include overuse syndromes, recent weight gain, acute illnesses, trauma, exposure to toxic agents, and hormonal changes. The most common symptoms reported by PPS patients include fatigue and weakness, joint and muscle pain, respiratory difficulties, cold intolerance, and dysphagia. In general, PPS affects the same muscle groups that were originally involved with the disease; however, because patients with mild-to-moderate respiratory muscle involvement often went undetected, there is a higher incidence of late-onset respiratory symptoms, which occur in up to 40% of PPS patients288 and range from mildly reduced pulmonary function, dyspnea, morning headaches, and daytime hypersomnolence to frank respiratory failure requiring ventilatory assistance. Individuals who required ventilatory assistance in the acute phase or had an onset of polio after 10 years of age and those with chest deformities are at highest risk of respiratory impairment, which often occurs without shortness of breath.286,289 Sleep-disordered breathing, including obstructive sleep apnea and nocturnal hypoventilation, is common. Weakening of bulbar muscles leads to dysphagia in at least 15% of patients. Patients with PPS benefit from supervised muscular training that avoids muscular overuse, as well as recognition of respiratory impairment, use of respiratory muscle training, and early introduction of noninvasive ventilatory aids.286 No specific CV complications are associated with PPS.

Friedreich Ataxia Friedreich ataxia is a hereditary disease characterized by progressive spinocerebellar degeneration beginning during adolescence. Progressive weakness and ataxia of the upper and lower extremities gradually develop, resulting in difficulty walking, unsteadiness of the arms and hands, and problems with writing and using eating utensils. Cardiac involvement occurs in 50% to 100% of patients and is characterized by cardiomyopathy with decreased ventricular compliance and varying degrees of hypertrophy and occasionally obstruction to ventricular outflow.277,278,290,291 Cardiac problems often present as the initial manifestation of the disease, although most patients are asymptomatic, except for dyspnea, which could be explained on the basis of their neurologic disability. When other symptoms are noted, they usually consist of palpitations and angina. Arrhythmias are common, especially premature atrial contractions, atrial flutter or fibrillation, and premature ventricular contractions. Progression of the neuromuscular disease usually results in the development of ventilatory failure. Death is usually caused by CHF or intercurrent infections and usually occurs within 20 to 30 years after onset of symptoms.242,277

Hematologic Disorders Many hematologic disorders are associated with CV and pulmonary dysfunction because of reduced oxygen-carrying capacity, reduced immune function, or coagulopathy or other forms of vascular obstruction.

Anemia Anemia is defined as a reduced circulating red blood cell (RBC) mass relative to an individual’s gender and age and can result from impaired RBC production, excessive destruction of RBCs (hemolysis), loss by hemorrhage, or a combination of these factors. Causes include dietary deficiency; acute or chronic blood loss; genetic defects of hemoglobin; exposure to toxins or certain drugs; diseases of the bone marrow; and a variety of chronic inflammatory, infectious, or neoplastic diseases.

Sickle Cell Disease Sickle cell disease (SCD) is a genetic disease found most commonly in individuals of equatorial African ancestry, which is characterized by structurally abnormal hemoglobin that causes the RBCs to become less pliable and some become crescent or sickle shaped with deoxygenation.292–295 Hemolytic anemia develops because of shortened circulatory survival of damaged RBCs (10 to 12 days rather than 120 days), which are destroyed intravascularly by macrophages and extravascularly in the spleen. Acute painful episodes resulting from occlusion of small capillaries and venules by the adherence of sickled RBCs to the vascular endothelium, termed vasoocclusive crises, are the most common complication of SCD, which typically occur one to six times a year and last for a few days up to several weeks. These episodes may be precipitated by cold, dehydration, infection,

stress, menses, or alcohol consumption, although the cause is frequently unknown. They result in tissue ischemia–reperfusion injury and infarction that affect nearly all organs, particularly the spleen, kidneys, CNS, bones, liver, lungs, and heart, leading to progressive systemic vasculopathy and chronic organ failure. Most patients are anemic but asymptomatic except during painful episodes. Cardiopulmonary dysfunction is common in SCD, as shown in Table 7-19. As with anemia, cardiac output and tissue oxygen extraction increase, but in SCD the reduction in oxygen content of the RBCs induces further sickling and compounds the cardiopulmonary complications. The leading cause of death in SCD is the acute chest syndrome, which occurs in approximately 30% of patients and is induced by vasoocclusion, infection, and pulmonary fat embolism from infarcted bone marrow. It typically presents with dyspnea, chest pain, fever, tachypnea, hypoxemia, leukocytosis, pulmonary infiltrates on chest radiography, and airflow limitation on PFTs, but sometimes it is insidious, with nonspecific signs and symptoms.296–298 It progresses to acute respiratory failure in 13% of patients and has a mortality rate of 4.3% to 23%. The heart is also affected by SCD. Biventricular hypertrophy and dilatation are induced by chronic anemia and the compensatory volume overload that increases cardiac output.299,300 Clinical manifestations include diminished exercise tolerance, dyspnea on exertion, and progressive loss of cardiac reserve. Diastolic dysfunction, most likely due to relative systemic HTN, has been noted in 18% of patients and increases the mortality risk, especially when combined with pulmonary HTN.301 Congestive heart failure is a late occurrence. Systolic cardiac murmurs are common. Venoocclusion can cause MI. Arrhythmias and second-degree AV block may occur during painful episodes and increase the risk of sudden death. Exercise capacity is reduced, most likely because of ongoing lung injury and diminished oxygen-carrying capacity of the blood, and may be associated with an exercise-induced drop in cardiac output or myocardial ischemia.301,302

Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome Patients with human immunodeficiency virus (HIV) are living much longer and suffering less disability than in the 1990s as a result of highly active antiretroviral therapy (HAART), which aims to preserve immune function and minimize viral replication in order to delay the progression to acquired immune deficiency syndrome (AIDS). Thus HIV has become a chronic illness with episodes of exacerbations and remissions, which often affects the neurologic, cardiopulmonary, integumentary, and musculoskeletal systems. Although the success of HAART has sharply reduced the incidence of opportunistic infections, pulmonary complications continue to be a major cause of morbidity and mortality in individuals with HIV/AIDS.303 Noninfectious pulmonary complications are common in HIV and include malignancies (lung, Kaposi sarcoma, and non-Hodgkin lymphoma), pulmonary HTN (possibly through increased production of inflammatory cytokines and chemokines by infected lymphocytes and alveolar macrophages, as well as

due to endothelial dysfunction), and lymphoproliferative disorders (lymphocytic interstitial pneumonitis and alveolitis).304 Human immunodeficiency virus also increases the risk of developing active TB and TB recurrence, which are associated with accelerated progression and mortality of HIV, partially due to a number of drug–drug interactions between the various medications used to treat the two diseases.303 Fungal (e.g., Pneumocystis pneumonia [PCP]) and bacterial infection (e.g., Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas, and Mycobacterium avium) also occur more frequently and are a major problem where HAART is not available. In addition, reactivation of cytomegalovirus (CMV) may occur in conjunction with PCP and is a marker of poor prognosis. Cardiovascular complications also occur in many patients with HIV and are fatal in some patients.305 The most common CV problem seen in HIV, particularly in children with AIDS, is pericardial effusion, which may be induced by opportunistic infection or malignancy, but more often, no definitive cause can be identified.

Hepatic Diseases Several diseases of the liver, including cirrhosis and hepatitis, produce or are associated with multiple cardiac and pulmonary abnormalities, as shown in Table 7-19. Patients with cirrhosis have a hyperdynamic systemic circulation, particularly in the supine position, which is characterized by increased HR and cardiac output, expanded plasma volume, and reduced systemic vascular resistance and low-normal BP. These alterations contribute to cardiopulmonary dysfunction. As many as 70% of patients with chronic liver diseases suffer from pulmonary problems.306 Certain liver diseases have known associations with specific pulmonary pathologies: primary biliary cirrhosis is associated with fibrosing alveolitis, diffuse interstitial pneumonitis, airflow limitation and emphysema, and bronchiectasis; chronic active hepatitis and possibly chronic hepatitis C are associated with fibrosing alveolitis; sclerosing cholangitis is associated with bronchiectasis and fibrosing alveolitis; and α1proteinase deficiency is associated with chronic airflow limitation and emphysema.307 Patients with cirrhosis, the most prevalent type of chronic liver disease in the United States, may experience the pulmonary effects of pleural effusions and ascites, as well as two unique disorders: hepatopulmonary syndrome (HPS) and portopulmonary HTN (POPH).207,306 Between 5% and 10% of patients with cirrhosis develop pleural effusions, most commonly on the right side, which are usually mild to moderate in size and asymptomatic, but occasionally they can be massive and provoke shortness of breath. Hepatopulmonary syndrome consists of the clinical triad of advanced chronic liver disease, intrapulmonary vascular dilation (in the absence of intrinsic cardiopulmonary disease), and hypoxemia, which occurs in 8% to 29% of patients with cirrhosis, and it may also be found in some patients with noncirrhotic portal HTN and occasionally in acute hepatic conditions, such as viral hepatitis and ischemic hepatitis. The symptoms of HPS are not specific, consisting of insidious onset of dyspnea on exertion and often on standing (platypnea), which may progress to dyspnea at rest in more severely affected

patients. Arterial hypoxemia, which is found in 30% to 70% of patients with cirrhosis, is usually mild to moderate, but oxygen desaturation may occur during exercise. Digital clubbing and cyanosis are seen in many patients. The presence of ascites further compromises pulmonary function due to diaphragmatic elevation and reduced lung volumes, resulting in tachypnea and dyspnea. Additionally, 2% to 10% of patients with cirrhosis may develop POPH (the coexistence of pulmonary HTN and portal HTN), which is characterized by pulmonary HTN induced by increased pulmonary blood flow, which results from splanchnic vasodilatation and a hyperdynamic high-flow circulatory state that are provoked by portal HTN. Both HPS and POPH can become fatal as hepatic damage progresses. Chronic alcohol consumption is associated with pulmonary and cardiac abnormalities. It increases the risk of developing pulmonary tuberculosis, chronic bronchitis, aspiration pneumonitis, lung abscess, and the pulmonary complications of alcoholic cirrhosis and alcoholic cardiomyopathy.308 Acute respiratory distress syndrome (ARDS) also occurs more frequently in patients with a history of alcohol abuse. Furthermore, chronic alcohol consumption is associated with higher prevalences of HTN, cerebrovascular accident, cardiac arrhythmias, sudden death, and CHF. The major cardiac abnormality specific to hepatic disease is alcoholic cardiomyopathy (or alcoholic heart muscle disease), which is the leading cause of dilated cardiomyopathy in the United States, accounting for approximately one-third of cases.309 In addition, up to 50% of asymptomatic alcoholics demonstrate subclinical systolic and diastolic dysfunction, with LVH and dilation and impaired contractility.310 Autonomic dysfunction is also common. Abstaining from alcohol consumption early in the course of alcoholic CM may halt the progression of or even reverse LV systolic dysfunction. A distinct cirrhotic cardiomyopathy that differs from alcoholic cardiomyopathy has been identified in patients with nonalcoholic cirrhosis, which is associated with hyperdynamic circulatory function, patchy myocardial fibrosis, subclinical diastolic and systolic dysfunction, an impaired myocardial response to an erect posture, and eventually high cardiac output failure.311 These individuals also exhibit autonomic dysfunction with enhanced SNS tone and vagal dysfunction, which is directly related to the severity of cirrhosis. Patients with both alcoholic and nonalcoholic cirrhosis exhibit significantly impaired cardiovascular responses to exercise, marked by blunted HR response, reduced myocardial contractility, subnormal increases in LV ejection fraction and cardiac output, and abnormally elevated cardiac pressures.311,312 Furthermore, profound wasting of skeletal muscle impairs oxygen extraction and utilization.

Eating Disorders The two most common eating disorders are anorexia nervosa and bulimia. Both disorders occur predominantly in young, previously healthy females and have specific behavioral and psychological features, as well as physiologic abnormalities, including those involving the heart and lungs, as summarized in Table 7-19. The medical complications

caused by eating disorders occur as a result of starvation, purging behaviors, and binge eating and involve almost all organ systems. Cardiac complications occur in 80% of patients with an eating disorder and include bradycardia and other cardiac arrhythmias, hypotension, decreased cardiac mass, and mitral valve prolapse. Arrhythmias are the leading cause of death.313

Anorexia Nervosa Anorexia nervosa is characterized behaviorally by severe self-induced weight loss (at least 15% below ideal body weight) through extreme restriction of food intake and sometimes ritualized exercise and purging. The major psychological manifestations are a distorted body image and an unreasonable concern about being “too fat,” as well as denial of hunger, fatigue, and emaciation. A number of medical problems besides the characteristic amenorrhea have been reported in anorexia nervosa: salivary gland enlargement, pancreatitis, pancreatic insufficiency, liver dysfunction, thiamine deficiency, coagulopathies, electrolyte imbalance, decreased gastric emptying and intestinal mobility, hypophosphatemia, bilateral peroneal nerve palsies, hypoglycemia, osteoporosis, hypothalamic dysfunction, and cardiac abnormalities.314 Furthermore, anorexia nervosa has a significant mortality rate, which is approximately 6% over a 5-year period and 15% to 20% at 15 years, and these deaths are often sudden due to cardiac arrhythmias.315 Cardiac complications account for most of these deaths. Nutritional depletion due to starvation can result in wasted cardiac muscle and reduced LV mass, diminished glycogen stores, and evidence of myofibrillar atrophy and destruction.313,316 Both systolic and diastolic ventricular dysfunction may occur.313,317–319 Mitral valve prolapse is found in one-third of patients, resulting from wasted cardiac muscle disproportionate to mitral valve size. Clinically, bradycardia, hypotension, and impaired exercise tolerance (approximately 50% of predicted normal) with blunted HR and BP responses are common.314,319,320

Bulimia Nervosa Bulimia nervosa is a much more common disorder, which is characterized behaviorally by binge eating counterposed with purging by self-induced vomiting, laxative abuse, or diuretic abuse. In addition, many patients participate in fasting and extreme exercise. Psychologically, there is an awareness that the eating pattern is abnormal, a fear that eating cannot be controlled, and feelings of depression following binge eating. Because severe weight loss is not a problem for the majority of patients, many of the physiologic abnormalities seen in anorexia nervosa do not occur in most bulimic patients. However, there are major complications associated with bulimia, including electrolyte disorders resulting from the abuse of diuretics and laxatives, tooth decay, aspiration pneumonia, esophageal or gastric rupture, pneumomediastinum, pancreatitis, and neurologic abnormalities. Hypokalemia occurs in approximately 14% of patients with bulimia and sometimes leads to arrhythmias, which can be fatal, and the degeneration of cardiac and

skeletal muscle.313 In addition, the chronic use of ipecac to induce vomiting can cause cardiomyopathy, arrhythmias, and death.321

Cardiopulmonary Toxicity of Cancer Treatment The development of more aggressive treatments for a number of malignancies using chemotherapy, irradiation, and biologic agents, as well as hematopoietic stem cell or bone marrow transplantation and other medications to support patients during cancer treatments, has yielded higher survival rates and longer survival periods but has also increased the incidence of cardiac and pulmonary toxicity causing acute and late complications. There is hope that the development of cardioprotective agents, such as the free-radical scavenger dexrazoxane currently under investigation, and medications that can reduce the incidence of radiation pneumonitis will reduce treatment-related toxicity that affects the lungs and heart. A number of chemotherapeutic agents are associated with cardiac and pulmonary toxicity, which can occur acutely or may become apparent months to years following the completion of treatment. As with other situations involving cardiopulmonary complications, damage is found on autopsy much more frequently than is clinically apparent. The most notable complications are presented here. Chemotherapy is often complicated by pulmonary toxicity, as indicated in Table 720.322–327 Despite a variety of mechanisms by which chemotherapeutic agents can injure the lungs, the clinical presentations are often similar, with dyspnea, nonproductive cough, and frequently fever, which develop weeks to years after treatment. Bleomycin has the highest incidence of pulmonary toxicity (up to 20% of patients), which is sometimes severe and can be fatal.325 Acute bleomycin-induced hypersensitivity pneumonitis occurs in a small number of patients even with very low doses. More commonly pneumonitis develops that mainly appears as chronic pulmonary fibrosis; risk factors include higher cumulative dose (especially if >450 to 500 mg), patient age, smoking, renal dysfunction, prior or concomitant thoracic irradiation, and administration of oxygen. Bleomycin can also produce a number of other patterns of interstitial lung disease. Other chemotherapeutic agents that can induce interstitial pneumonitis include: ▪ Busulfan ▪ Chlorambucil ▪ Cyclophosphamide ▪ Methotrexate ▪ Mitomycin C ▪ The nitrosoureas (particularly carmustine and lomustine) ▪ Sometimes fludarabine, irinotecan (Camptosar), paclitaxel (Taxol), and procarbazine (Matulane, Natulan) A number of other agents are also associated with other types of lung injury: busulfan (Myleran) can cause pulmonary fibrosis and sometimes an alveolar–interstitial process with alveolar proteinosis, which is often fatal. Noncardiac pulmonary edema develops in 13% to 28% of patients during the administration of cytosine arabinoside (Cytarabine) and in a few patients months after treatment with mitomycin C. Pneumothorax occurs in some patients treated with the nitrosoureas. Acute hypersensitivity reactions have occurred with docetaxel (Taxotere) and procarbazine. Gemcitabine (Gemzar) causes

dyspnea, which can be severe, in up to 10% of patients, and there have been reports of acute hypersensitivity reaction with bronchospasm, diffuse alveolar damage, and ARDS, and a rare severe idiosyncratic reaction with pulmonary infiltrates and marked dyspnea that may progress to life-threatening respiratory insufficiency. Procarbazine and vincristine (and theoretically cytarabine and chlorambucil) can cause neuropathies that may affect the respiratory muscles, inducing weakness. Zinostatin can produce a unique drug reaction involving hypertrophy of the pulmonary vasculature. In addition, sometimes pulmonary toxicity develops when specific chemotherapeutic agents are used in combination (e.g., vinblastine [Velban, Velsar] combined with mitomycin C induces bronchospasm, interstitial pneumonitis, and noncardiac pulmonary edema). A number of chemotherapeutic agents are also known to cause CV dysfunction, as listed in Table 7-21.323,328,329 The most well-recognized agents linked with cardiotoxicity are the anthracycline antibiotics: ▪ Doxorubicin (Adriamycin) ▪ Daunorubicin (Cerubidine) ▪ Epirubicin (Ellence, Pharmorubicin) ▪ Idarubicin (Idamycin) ▪ Mitoxantrone (Novantrone) Radiation therapy (XRT) to the chest, as for the treatment of Hodgkin disease (HD), lymphoma, lung, breast, esophageal, and head and neck cancers, necessarily exposes the heart and lungs to varying degrees and dosages of radiation, depending on the extent of disease. Fortunately, modern treatment techniques instituted in 1985, particularly for HD, have drastically reduced cardiac and pulmonary complications. Radiation-induced pulmonary toxicity is usually related to the volume of lung tissue radiated, total dose of radiation, and the dose per treatment fraction (see Table 7-20).327,330 The advent of threedimensional treatment planning has permitted higher radiation doses to be delivered to the tumor while sparing surrounding normal tissue and is associated with a marked reduction in pulmonary toxicity. Acute radiation pneumonitis, which usually develops 4 to 6 weeks after XRT and is manifested clinically as a nonproductive cough, dyspnea (often at rest), and fever, occurs in 5% to 15% of patients who receive high-dose externalbeam radiation for lung cancer, 3% of those treated for HD with radiation alone and 11% of those who received combined modality treatment with XRT and chemotherapy, and less than 1% of women treated for breast cancer using breast XRT as part of a breastconserving approach.323,330 Most patients with acute radiation pneumonitis require no treatment and show complete resolution within 6 to 8 weeks, but a few patients develop severe pneumonitis requiring hospitalization and aggressive supportive care. Radiation therapy to the chest can damage all structures of the heart (see Table 7-21), with the highest risk occurring in survivors of pediatric HD.323,328 Late sequelae, which may not become clinically apparent for up to 25 or more years after treatment, often involve more than one cardiac structure in affected individuals, so that a number of conditions occur together. An estimate of the aggregate incidence of radiation-induced cardiac dysfunction is between 10% and 30% by 5 to 10 years posttreatment, although asymptomatic abnormalities of the heart muscle, valves, pericardium, conduction

system, and the vascular system are detected in up to 88% of patients.323 Factors that increase the risk of cardiac sequelae after mediastinal irradiation include cotreatment with anthracycline chemotherapy, location of tumor close to the heart border, age less than 18 years at the time of treatment, presence of CV risk factors or preexisting cardiac disease, treatment occurring more than 10 years earlier, and a number of radiation factors (use of orthovoltage radiation [mostly before 1970s], increased volume of irradiated heart, total dose to heart >30 Gy or daily dose fraction >2 Gy/day, or absence of subcarinal blocking). Cardiotoxicity typically manifests as pericarditis with pericardial effusion in 2% to 5% of patients receiving modern XRT for HD, which usually has a delayed onset (4 months to years after treatment). Approximately 10% to 20% of patients with pericardial effusion develop tamponade and require pericardiocentesis.328 Interferons (IFNs: -α, -β, -γ) are used in a wide variety of malignant, idiopathic, infectious, and inflammatory conditions, and their administration is associated with a variety of pulmonary reactions: severe exacerbation of bronchospasm in patients with preexisting asthma and a granulomatous reaction similar to sarcoidosis occur with IFN-α therapy; interstitial lung disease, possibly cryptogenic organizing pneumonia, develops weeks to months after initiation of IFN therapy; and severe radiation pneumonitis can develop with multimodality therapy when IFN-γ is used.322,324,325 Adverse CV effects are sometimes noted with IFNs: acute toxicity may be manifested as hypotension with compensatory tachycardia or, more rarely, as HTN, and in severe cases, as angina and MI, and there are rare reports of cardiomyopathy.328,329 Table 7-21 Cardiotoxicity associated with cancer treatments

CAD, coronary artery disease; CHF, congestive heart failure; DVT, deep vein thrombosis; HSCT, hematopoietic stem cell transplantation; LV, left ventricular; MI, myocardial infarction.

Cardiotoxicity after hematopoietic stem cell transplantation and bone marrow transplantation is usually related to previous chemotherapy or that used as part of the conditioning regimen.331,332 Acute toxicity is usually manifested by ECG abnormalities, such as arrhythmias and conduction disturbances, and pericardial effusion, which are usually asymptomatic but occasionally cause more serious problems. Some patients develop chemotherapy-induced cardiomyopathies, which may not become clinically apparent for many years to decades after treatment. A study involving the longitudinal evaluation of cardiopulmonary performance during exercise after bone marrow transplantation in children has revealed a number of functional defects, including significantly reduced maximal cardiac index, oxygen consumption, work performed, and ventilatory threshold, compared with age-matched, healthy control subjects.331 Whereas the percentage of predicted VO2max, maximum work performed, and ventilatory threshold increased over time for most patients, maximal cardiac index did not, providing evidence of subclinical myocardial dysfunction. Finally, some treatments used to support cancer patients during treatment also have the possibility of inducing pulmonary complications. The hematopoietic growth factors, granulocyte and granulocyte-macrophage colony stimulating factors (G/GM-CSF; e.g., filgrastim), used to facilitate neutropenia recovery and prevent infection after high-dose chemotherapy and stem cell transplantation, are associated with an increased risk of

respiratory deterioration as a result of acute lung injury or ARDS (when used in patients with pulmonary infiltrates), as well as arterial thrombosis and vascular leak syndrome. Platelet and blood transfusions sometimes cause pulmonary edema.

Clinical Implications for Physical Therapy The most obvious implication of all the information presented in this chapter is that many patients with many different primary diagnoses may exhibit cardiopulmonary dysfunction. Yet the symptoms of dysfunction are often nonspecific, such as shortness of breath, lightheadedness, and fatigue, or there may not be any symptoms at all, as in HTN. Furthermore, many patients will not complain of symptoms despite significant exercise intolerance because they have gradually limited their physical activity in order to avoid discomfort. Worthy of particular mention based on prevalence are the benefits of exercise for patients with cancer. Increased levels of physical activity during and after cancer treatment has been shown to reduce fatigue, enhance physical performance, and improve quality of life.333–335 Exercise therapy may also mitigate the adverse effects of treatment for cancer on the CV system.336 Resistance training likely helps to improve muscle function, lean tissue mass, and bone mineral density. Furthermore, there is evidence that regular physical activity improves survival in patients with breast and colorectal cancers.337–339 To summarize and reduce to the basics for practical application, recommendations are offered in Box 7-3.

Case study 7-1 JF is a 76-year-old woman admitted 2 days ago because of confusion, incoherent speech, and lethargy. Computed tomography scan revealed a large parietal lobe infarct on the left. Her past medical history is significant for HTN for 30 years, treated with hydrochlorothiazide 75 mg once a day and captopril 50 mg once a day. She has had type 2 diabetes for 15 years, treated with glyburide 5 mg every morning. Positive smoking history: 90 pack/years. The PT assessment reveals a lethargic-appearing 76year-old woman with obvious right facial paresis, severe dysarthria, flaccid right upper extremity, decreasing tone right lower extremity through positive clonus of right ankle. She requires moderate assistance to roll supine, right side; maximal assistance to roll to left; and maximal assistance of one to come to sitting at edge of bed. Sitting balance is poor, with trunk lean to right.

Discussion Admitting diagnosis of CVA indicates carotid or cerebrovascular disease. Comorbidities: diabetes (treated with an oral insulin secretagogue), HTN (treated with a diuretic and ACE inhibitor). Other risk factors for CAD and CVA: Smoking history (90 pack/years; may also have underlying COPD).

Current medical problem of CVA with hemiparesis and functional limitations implies increased work required to perform activities and possible ventilatory limitation due to restrictive lung dysfunction, which increases the risk of atelectasis and pneumonia. The risk of atelectasis and pneumonia is compounded by the patient’s marked limitation of physical activity. Probable speech and swallowing dysfunction increase the risk for aspiration pneumonia and may impair cough effectiveness.

BO X 7- 3 Guide line s for physica l t he ra py int e rve nt ion a nd

e ndura nce t ra ining

BP, blood pressure; HR, heart rate; PT, physical therapy.

This patient, who presents with CVA and also has multiple risk factors for CAD, should be monitored closely for signs and symptoms of CAD and cardiac pump dysfunction, as well as abnormal responses to exercise. She may also benefit from diabetic education. Patients with long-standing smoking history may have underlying COPD and may need to have oxygen saturation monitored, arterial blood gases, and CXR.

Summary A great number of medical problems are associated with CV and pulmonary complications, many of which are not recognized by either the individual or his or her primary medical provider. The symptoms of cardiopulmonary dysfunction are often nonspecific, such as shortness of breath, fatigue and weakness, and lightheadedness, and many patients are unaware of symptoms of activity intolerance despite significant dysfunction because they are unwittingly avoiding activities that cause discomfort. Yet it is important for physical therapists to recognize the presence of cardiopulmonary dysfunction when prescribing PT interventions in order to optimize safety and effectiveness. A summary of the most important points provided in this chapter includes the following: ▪ Several factors are known to affect energy balance and contribute to the development of overweight and obesity, the most important of which are environmental factors, particularly excessive caloric intake and reduced physical activity, and genetic, hormonal, and metabolic factors also play a role. In addition, calcium intake, particularly in dairy products, is inversely related to body fat levels, and sleep deprivation is associated with higher body fat levels. ▪ Overweight and obesity represent major health problems in this country because of their association with increased prevalences of HTN, CAD, stroke, osteoarthritis and other orthopedic problems, GI problems, glucose intolerance, insulin resistance, type 2 DM, dyslipidemia, gallbladder disease, sleep-related breathing disorders, gynecologic problems, pulmonary dysfunction, and certain forms of cancer. ▪ Increased body fat, particularly intraabdominal or visceral adiposity, is directly related to CVD risk and type 2 DM. The measurement of WC provides a simple index of disease risk, with commonly accepted cutoff points of 40 inches (102 cm) for men and 35 inches (88 cm) for women to define central obesity. Risk of future CVD increases by 2% per 1 cm increase in WC. ▪ Treatments for obesity include caloric restriction and other diet modifications, increased physical activity, behavioral modification, pharmacotherapy, and bariatric surgery, depending on the degree of obesity. With the exception of bariatric surgery, the goal is usually set at a 10% reduction in body weight, which is associated with significant health benefits; however, this goal is hard to achieve and even more difficult to maintain. ▪ Obesity is associated with both pulmonary and CV dysfunction, and obese individuals usually exhibit abnormal physiologic responses to exercise and reduced exercise tolerance. Thus obese individuals require clinical monitoring and often treatment modifications when referred to PT. ▪ Aerobic and resistance exercise are important interventions for all individuals who are obese as a means of increasing energy expenditure, improving cardiorespiratory fitness, ameliorating CV risk factors, protecting against loss of lean body mass during caloric restriction, and increasing muscular efficiency, even if no weight loss is achieved.

▪ To achieve and maintain long-term weight loss, at least 45 to 60 minutes per day of at least moderate-intensity exercise may be required, such that a total of 250 to 300 minutes of exercise is performed each week. ▪ Metabolic syndrome refers to a cluster of interrelated risk factors, including abdominal obesity, atherogenic dyslipidemia, HTN, insulin resistance, and impaired glucose tolerance, that is associated with increased risk of CVD events and death, type 2 DM, and chronic kidney disease. Lifestyle interventions to lose weight and increase physical activity can markedly reduce the risk of developing DM. ▪ Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and caused by inadequate insulin production or ineffective insulin action. Abnormalities in the metabolism of carbohydrates, fats, and proteins result. In addition, chronically elevated BG levels and other associated abnormalities result in damage to the arteries, heart, kidneys, eyes, and peripheral and autonomic nerves. ▪ Cardiovascular disorders are the most common cause of morbidity and mortality in people with both type 1 and type 2 DM. Microvascular disease results in retinopathy, renal damage, and neuropathy, and macrovascular disease due to accelerated atherosclerosis causes CAD, stroke, and PAD. Strict glycemic control can reduce the risk of developing vascular complications related to DM. ▪ Glycosylated hemoglobin (Hb A1c , or simply A1c ) provides a reliable indication of the degree of glycemic control achieved by an individual over the preceding 2- to 3-month period. For individuals with DM, the goal is to achieve levels of below 7% (normal levels are 2.5% to 6%) through intensive glycemic control in order to reduce the risk of diabetic complications. ▪ Type 1 DM requires insulin therapy, whereas other antihyperglycemic medications are used for the treatment of type 2 DM, at least until there is significant β-cell dysfunction, when insulin will also be needed. ▪ The major problem associated with insulin therapy is hypoglycemia, which occurs when the level of circulating insulin exceeds need, such as during the hour or so immediately before mealtime or when there is persistent increased insulin sensitivity and mandatory repletion of muscle and liver glycogen stores after exercise. Risk factors for exercise-related hypoglycemia include intensive insulin therapy and tight glycemic control (so smaller safety margin), inadequate food intake preceding exercise (e.g., when a meal is delayed or skipped), rapid absorption of depot insulin from an injection site near exercising muscle, exercising at the time of peak insulin effect, and prolonged moderate-intensity exercise. ▪ The glucoregulatory responses to exercise are abnormal in DM. A number of important variables affect these responses in individuals with type 1 diabetes: the preexercise levels of circulating insulin and the counterregulatory hormones, as indicated by the BG level, both at the onset of exercise (which are determined by the type and dose of insulin administered before exercise and the timing of previous insulin injection and carbohydrate intake relative to the onset of exercise) and during exercise (which are affected by the injection site and the intensity, type, and duration of exercise). ▪ To allow safe participation in physical activity and high-level athletic performance,

persons with type 1 DM must carefully match insulin dose, carbohydrate intake, and exercise in order to avoid either hypoglycemia or hyperglycemia. Thus it is important to monitor BG level 60 and 30 minutes before exercise in order to identify the individual’s glucoregulatory status. If BG levels are low, supplemental carbohydrates may be required to prevent exercise-induced hypoglycemia. If BG levels are high, there is a risk of further aggravation of hyperglycemia during exercise, particularly with higher-intensity or longer-duration exercise. Both situations require BG monitoring during exercise to clarify the individual’s glucoregulatory responses and need for treatment modifications. If BG levels are excessively low (300 mg/dL) or if ketones are present, exercise is contraindicated, at least until corrective measures have taken effect. ▪ Adjustments in insulin dose before and sometimes after exercise may be required to prevent exercise-associated hypoglycemia or, less commonly, hyperglycemia. ▪ The concerns for patients with type 2 DM differ from those for type 1 DM. They should avoid exercise if BG is more than 400 mg/dL because of the risk of hyperosmolar hyperglycemic nonketonic syndrome. In addition, only the insulin secretagogues (sulfonylureas and glinides) are associated with a higher risk of hypoglycemia and may require dose reduction on the day of exercise. ▪ Cardiac autonomic neuropathy should be suspected in all individuals with type 2 DM and in those with type 1 DM for more than 5 years. Clinical manifestations include higher resting HR and reduced HR variability, orthostatic hypotension, impaired exercise tolerance, and painless myocardial ischemia and infarction (due to cardiac denervation). Simple tests are available to determine the presence of CAN and should be included in the PT evaluation of susceptible individuals. ▪ The kidneys are complex organs whose major functions include the control of extracellular fluid volume; the regulation of serum osmolality, electrolyte, and acid– base balances; and the secretion of hormones, such as renin and erythropoietin. Thus when renal function becomes impaired, the resultant metabolic disturbances affect virtually every other body system. ▪ Chronic renal failure is associated with a number of major complications: HTN, pericarditis with pericardial effusion and sometimes cardiac tamponade, accelerated atherosclerosis, anemia, bleeding disorders, renal osteodystrophy, proximal myopathy, peripheral neuropathy, peptic ulceration, and immunosuppression leading to intercurrent infections. Pulmonary edema can also occur as a result of fluid overload as well as increased capillary permeability. ▪ Although many patients do well for more than 10 years on dialysis, success is limited by the impaired clearance of waste products and other substances and the marked impairment of the regulatory and endocrine functions normally provided by the kidneys. ▪ Most patients with CRF have very limited exercise tolerance, and many have difficulty doing more than self-care activities. Contributory factors include anemia, CVD, chronic physical inactivity, skeletal muscle dysfunction, and metabolic acidosis. The limiting symptom is usually skeletal muscle fatigue, and patients have notable skeletal muscle

atrophy and weakness. ▪ Connective tissue diseases affect all pulmonary and CV structures, either separately or in combination. Not infrequently, pulmonary involvement precedes the musculoskeletal manifestations by several months to several years. Cardiovascular abnormalities most often involve the pericardium, arterial vasculature, and cardiac valves and usually cause minimal CV dysfunction (e.g., asymptomatic mitral valve prolapse or mild aortic root dilatation) but occasionally results in significant problems (e.g., cardiomyopathy producing CHF, MI, severe aortic or mitral insufficiency, or dissecting aortic aneurysm). ▪ Many neurologic and neuromuscular diseases and disorders are associated with pulmonary and cardiac complications, and symptoms often do not correlate well with the degree of dysfunction in slowly progressive disorders. Sleep-disordered breathing is often an indication of chronic respiratory muscle fatigue and increased risk of ventilatory failure, which can be ameliorated with the use of nocturnal ventilatory assistance. Therefore physical therapists should be attentive to relevant symptoms, such as sleep disturbances, morning headache, excessive daytime somnolence, impaired concentration, and loss of appetite, and alert the patient’s physician if they are noted. The therapist should be aware of the benefits of inspiratory muscle training in this population and implement as indicated. ▪ The clinical manifestations of anemia depend on the cause of anemia, its extent, the rapidity of onset, and the presence of any other medical problems that compromise the individual’s health. Most cases of chronic anemia are asymptomatic other than vague fatigue until the hemoglobin concentration falls below 50% of normal, whereupon more notable symptoms appear, including fatigue and weakness, exertional dyspnea and diminished exercise tolerance, palpitations, pallor, and sometimes tachycardia. Patients with CAD may develop myocardial ischemia with mild anemia. ▪ Sickle cell disease is characterized by hemolytic anemia and periodic acute painful crises resulting from occlusion of small capillaries and venules, which result in progressive systemic vasculopathy and chronic organ failure. ▪ Pulmonary complications are the leading cause of morbidity and mortality in patients with HIV and AIDS; CV complications also occur in many patients and are sometimes fatal. ▪ The vast majority of patients with chronic liver disease exhibit pulmonary abnormalities, particularly arterial hypoxemia, which is usually mild, although oxygen desaturation may occur during exercise. Pleural effusions and ascites will compound pulmonary dysfunction as a result of restriction of ventilation, resulting in tachypnea and dyspnea. Chronic alcohol consumption is associated with numerous pulmonary and CV complications, some of which cause serious dysfunction and death; alcoholic cardiomyopathy (or alcoholic heart muscle disease) is the leading cause of dilated cardiomyopathy in the Western world. ▪ Eating disorders are associated with numerous medical complications. Cardiac complications are responsible for most of the deaths, which may be sudden due to arrhythmias induced by electrolyte imbalances. In addition, the chronic use of ipecac

to induce vomiting can cause cardiomyopathy, arrhythmias, and death. ▪ Nearly all therapies used to treat cancer are associated with cardiac and pulmonary toxicity, which can cause acute or late complications that may be serious and/or fatal. There is often a synergistic effect of radiation therapy and some chemotherapeutic agents, and also of some of the drugs when used in combination, which can increase the extent of cardiac or pulmonary injury. Regular exercise provides a number of benefits for individuals during and after cancer treatment, possibly including increased survival. ▪ The only way to determine whether a patient is responding to exercise appropriately is to assess his or her physiologic responses. This is achieved by monitoring HR, BP, and other signs and symptoms of exercise intolerance during every PT evaluation. Abnormal responses indicate the need for treatment modifications. ▪ Endurance and resistance training should be included as components of the PT program for every patient who is not already performing regular aerobic exercise, except those who have cardiopulmonary instability or debilitating neuromuscular diseases that are adversely affected by exercise.

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340. Borg G. Borg’s RPE Scale. Copyright Gunnar Borg. 1994. 341. Borg G. Borg CR10 Scale. Copyright Gunnar Borg. 1982 1998, 2003.

SECT ION 3

Diagnostic Tests and Procedures OUT LINE 8. Cardiovascular diagnostic tests and procedures 9. Electrocardiography 10. Pulmonary diagnostic tests and procedures

Cardiovascular diagnostic tests and procedures Ellen Hillegass, Kelley Crawford, and Susan Butler McNamara

CHAPTER OUTLINE Diagnostic Test Interpretation and Probability of Disease 267 Sensitivity/Specificity of Testing 267 Clinical Laboratory Studies 267 Serum Enzymes and Cardiac Biomarkers 267 Blood Lipids 270 Other Potential Clinical Laboratory Risk Factors for CAD 271 Complete Blood Cell Count 272 Coagulation Profiles 272 Electrolytes 273 Blood Urea Nitrogen and Creatinine and B-type Natriuretic Peptide 273 Serum Glucose 274 Other Laboratory Values 274 Other Noninvasive Diagnostic Tests 274 Holter Monitoring 274 Echocardiography 275 Contrast Echocardiography 276 Other Imaging Modalities 277 Positron Emission Tomography 277 Computed Tomography 277 Multigated Acquisition Imaging 278 Magnetic Resonance Imaging 278 Exercise Testing 279 Maximal versus Submaximal Stress Testing 279 Low-Level Exercise Testing 280 Safety in Exercise Testing 281 Contraindications to Testing 282

Exercise Testing Equipment 282 Protocols for Exercise Testing 283 Terminating the Testing Session 284 Interpretation of Results 284 Prognostic Value of Maximal Exercise Testing 284 Heart Rate Recovery 285 Exercise Testing with Ventilatory Gas Analysis 286 Exercise Testing with Imaging Modalities 286 Radioactive Nuclide Perfusion Imaging 287 Pharmacologic Stress Testing 288 Adenosine or Dipyridamole–Walk Protocol 288 Ergonovine Stimulation 289 Heart Rate Variability 289 Cardiac Catheterization: Coronary Angiography and Ventriculography 289 Indications for Cardiac Catheterization 290 Procedure for Cardiac Catheterization 291 Interpreting the Test Results 291 Digital Subtraction Angiography 291 Intravascular Ultrasonography 292 Diagnostic Tests for Women 293 Endocardial Biopsy 294 Vascular Diagnostic Testing for Aortic, Peripheral, and Carotid Disease 294 Aortic Disease and Dysfunction and Diagnosis 294 Peripheral Arterial Disease and Dysfunction and Diagnosis 295 Ankle–Brachial Index 295 Segmental Limb Pressures 295 Pulse Volume Recordings 295 Arterial Duplex Ultrasonography 295 Exercise Studies 295 Other Clinical Tests 295 Carotid Artery Disease and Diagnosis 298 Case study 8-1 298 Summary 299 References 300

Objective information on the patient’s cardiovascular system is derived from data obtained from laboratory studies and from diagnostic tests and procedures. Physical therapists must be able to identify and interpret the results of these medical tests and procedures in order to assess the status of their patients’ cardiovascular systems. This chapter provides the basis for an understanding of the importance and impact of medical tests that may be ordered to determine key disease states and impairments. In addition, these tests facilitate the achievement of a correct diagnosis, aid in the prevention of complications, develop information to determine a prognosis, identify subclinical disease states, and assist in the monitoring of the progress of treatments. The tests and procedures that are discussed in this chapter include clinical laboratory studies (e.g., for cardiac enzymes and markers, cholesterol and triglycerides, and complete blood cell count), Holter monitoring, echocardiography, contrast echocardiography, positron emission tomography (PET), computed tomography (CT), single-photon emission computed tomography (SPECT), electron beam computed tomography (EBCT), multigated acquisition or angiogram (MUGA) imaging, magnetic resonance imaging (MRI), perfusion imaging, exercise testing, coronary angiography and ventriculography, digital subtraction angiography (DSA), ergonovine stimulation, heart rate variability, and endocardial biopsy. Table 8-1 provides an overview of all tests and their indications found in this chapter. Electrocardiography is a separate diagnostic evaluation that is covered in Chapter 9. Table 8-1 Cardiovascular diagnostic tests and procedures and their indications Tests Rhythm abnormalities

Indications Holter monitor 12-Lead ECG Exerc ise ECG Elec trophysiologic studies (EPS mapping) Isc hemia Resting ECG (if isc hemia or c omplaints of angina are oc c urring at time of ECG being taken) Exerc ise ECG (with or without dye or stress ec ho) Pharmac ologic stress testing S ingle-photon emission c omputed tomography (S PECT) Positron emission tomography (PET) Ergonovine c hallenges Contrast ec hoc ardiography Cardiac c atheterization Cardiac magnetic resonanc e imaging (MRI) Digital subtrac tion angiography Valve integrity Ec hoc ardiography Contrast ec hoc ardiography Cardiac c atheterization Ventric ular size and ejec tion frac tion Chest x-ray Multigated ac quisition or angiogram (MUGA) imaging Ec hoc ardiography Cardiac musc le pump func tioning MUGA Ec hoc ardiography Ventric ulography Digital subtrac tion angiography Ac ute myoc ardial infarc tion Cardiac enzymes and markers Resting ECG Vasc ular diagnostic testing Ankle–brac hial index S egmental limb pressures Pulse volume rec ordings Arterial duplex ultrasonography Exerc ise studies

Diagnostic Test Interpretation and Probability of Disease Because all diagnostic tests are not 100% accurate, a brief description of terminology used to define accuracy of testing is included. Usually the literature will report on the sensitivity/specificity of the test or the predictive value of the test.

Sensitivity/Specificity of Testing Sensitivity is defined as the proportion of those individuals with the disease who have a true positive test. For example, a high sensitivity means the test will have low falsenegative rates. Specificity is defined as the proportion of those individuals without the disease with a true negative test. A test with a high specificity will have a low falsepositive rate. Predictive values are used because they are more clinically informative than sensitivity and specificity, and translate into the likelihood individuals have the disease. These values are highly dependent on the prevalence of the disease. ▪ A positive predictive value is defined as the proportion of individuals who had a positive test and actually have the disease. ▪ A negative predictive value is defined as the proportion of individuals who had a negative test and truly do not have the disease.

Clinical Laboratory Studies Laboratory studies provide important information regarding the clinical status of the patient. The laboratory tests that are specific to the patient with cardiac dysfunction measure the serum enzymes/cardiac biomarkers, blood lipids (triglycerides and cholesterol), complete blood cell count, coagulation profile (prothrombin time), electrolyte levels, blood urea nitrogen (BUN), creatinine levels, B type natriuretic peptide (BNP) testing, and serum glucose levels. Table 8-2 provides the laboratory studies and the normative values.

Serum Enzymes and Cardiac Biomarkers Evaluation of specific serum enzyme levels and cardiac protein markers contributes to a definitive diagnosis of myocardial necrosis and in some cases to an assessment of the degree of myocardial damage or the effectiveness of reperfusion. When damage has occurred to the myocardial tissue, cellular integrity is lost and intracellular cardiac enzymes are released into the circulation. These enzymes are released at a variable rate and are cleared by the kidney and other organs. Their presence can be measured by serum blood tests. However, due to their variable release and clearing rate, their absence does not rule out the possibility of injury. The markers that are diagnostic of cardiac injury include: ▪ Creatine phosphokinase (CPK-MB isoenzyme) ▪ Troponin ▪ Myoglobin ▪ Carbonic anhydrase III ▪ Cardiac myosin light chains More specifically, isoenzymes, which are different chemical forms of the same enzyme, have been found to be most conclusive of specific muscle cell necrosis. Creatine phosphokinase (CPK; also CK) has three isoenzymes (MB, MM, BB), which are differentiated by their tissue distribution. The CPK-MB fraction is most conclusive of all three isoenzymes for myocardial injury. MM is most conclusive for skeletal muscle damage, and BB for brain tissue injury. CPK-MB is considered abnormal if its serum level is greater than 3%; MB is found in healthy skeletal muscle up to 3%. CPK-MB has been used as a cardiac marker for more than 35 years; however, it has been shown to be elevated after cardiac surgery and cardiopulmonary resuscitation (especially if the person was defibrillated) and has been shown to be abnormally elevated in patients undergoing thrombolysis with streptokinase or tissue plasminogen activator.1 Chapter 14 discusses specific cardiac medications. Falsely elevated CPK-MB index of more than 6% without myocardial infarction (MI) was evidenced in 43.3% of elective hip surgery patients.2 Troponin I levels were elevated higher than 3.1 ng/mL only in the patients who suffered MI postoperatively. All the patients who suffered MI had both CPK-MB index and troponin I levels elevated. Also, there was a high correlation between maximum CPK-MB levels and size of implants, which means that reaming of the bone for the implant and its

heating effect may be responsible for false-elevated CPK-MB levels, aside from the direct muscle damage caused by the surgical incision.2 Table 8-2 Clinical laboratory studies with normative values

∗

Myo/CAIII = myoglobin value/carbonic anhydrase III.

More recently, blood levels of the troponins have been assessed to determine myocardial damage and are now considered the gold standard. Elevated levels of troponin occur earlier3 and may last for up to 5 to 7 days in plasma (normal range = 0 to 3.0 mg/mL).4 The troponins are a group of structurally related proteins found in striated muscle cells and are bound to the actin filament. The troponins include TnC, which binds calcium; TnI, which inhibits the interaction between actin and myosin; and TnT, which links the troponin complex to tropomyosin. With cell necrosis, there is a release of the troponins into the circulation. The cardiac isoforms of cTnI and cTnT are expressed only in cardiac muscle and therefore are the two troponins tested during severe ischemia and infarction. The cTnI and cTnT are the most sensitive and specific biochemical markers of myocardial cell damage and have replaced CPK-MB as the preferred marker for diagnosis of myocardial injury.5,6 Troponin, a three-protein complex consisting of troponins I, T, and C, is found in cardiac and skeletal muscle. Most of these proteins stored in myofibrils (the area actually bound to the myofibril) are key for calcium-regulated cardiac and skeletal contraction.7 Some troponin is also found in the cytosol (unbound). Troponins I (cTnI) and T (cTnT) are cardiac tissue specific, but troponin C (cTnC) is not.8 Injured cardiac muscle releases troponin into the bloodstream. Thus increased levels of cardiac troponin may suggest myocardial injury.7 Troponin released after cardiac injury usually remains elevated (its half-life is about 2 hours), leading to better identification of cardiac injury.7 Monoclonal antibodies can now detect cardiac troponins, resulting in immunoassays for blood measurement.

Although acute coronary syndrome (ACS) can cause elevated troponin levels, so can other conditions. Cardiac surgery can cause myocardial damage from procedures such as cross-clamping to using cardiopulmonary bypass. Therefore elevations in troponin are not specific to the cause of the injury; however, the more elevated the level is postoperatively, the greater the damage and the more grave the prognosis.7 Because troponin levels are being tested more frequently, cardiac injury has been identified more often, but the causative factors are not always known. Direct damage to the heart, such as from blunt cardiac trauma, is another cause of elevated troponin levels. Also, therapies such as electrical cardioversion or defibrillation may injure the heart. Elective cardioversion usually does not raise troponin levels, but levels are more likely to be elevated after defibrillation or prolonged resuscitation. Elevated cardiac troponin has been found in critically ill patients without a cardiac diagnosis.9 Critically ill patients with sepsis often have increased troponin levels, although the reason is unclear. The elevated troponin could be related to underlying coronary artery disease (CAD) or the release of toxins in sepsis (such as tumor necrosis factor) that can injure the heart and cause increased troponin levels.10 Other patient groups that show elevated troponin include patients with renal failure. The elevation may be due to musculoskeletal injury, but these patients are at high risk for cardiovascular disease as well, so a baseline troponin value that can be used as comparison in future acute cardiac events should be obtained.7 Patients with heart failure also have increased levels of cardiac troponins, both in acute and chronic phases, with and without CAD. In patients with ventricular hypertrophy (left or right), the ventricular wall stress or oxygen imbalances could cause troponin elevations.7 Similarly, right ventricular strain and increased pulmonary vascular resistance may explain increased troponin levels in patients with acute pulmonary embolism (PE). The troponin elevation in PE resolves in 40 hours or less.7 The amount of cardiac troponin in the blood initially rises in about 4 to 6 hours. Peak concentrations appear at 18 to 24 hours after symptoms begin.7 Usually troponin is collected on admission and then testing is repeated 6 to 9 hours later. Troponin can remain elevated for 10 days after the injury.8 Prolonged elevation makes diagnosing cardiac injury in a patient who does not seek treatment for more than 24 hours easier because other cardiac biomarkers, such as CPK-MB, may be normal in these patients. Elevated troponin levels have also been found to be prognostic in the ACS patient. The risk of short-term mortality is increased in patients with ST-segment elevation MI (STEMI), although the risk of death and repeat MI is higher in patients with non-STsegment elevation MI (NSTEMI) when troponin levels are elevated, compared with those patients without elevations. Troponin elevations have also helped clinicians detect reinfarctions and estimate infarct size.7 Levels of troponin are not elevated in unstable angina.9,11 The assay used to measure cTnT levels has cardiac specificity equivalent to that of assays for cTnI. That is, troponin I: 0 to 0.1 ng/mL (onset: 4 to 6 hours, peak: 12 to 24 hours, return to normal: 4 to 7 days); troponin T: 0 to 0.2 ng/mL (onset: 3 to 4 hours, peak:

10 to 24 hours, return to normal: 10 to 14 days).11 Current research has demonstrated an increase in the cardiac troponins with heart failure and renal insufficiency; therefore the troponins alone may not indicate specificity of MI.12 Several studies have shown an increased short-term mortality rate (30 to 40 days) in individuals with elevations in cTnI and cTnT.13–17 Myoglobin is a heme protein found in all muscle tissue and has recently come under study as a potentially powerful diagnostic tool for acute MI. Myoglobin can be detected as early as 2 hours after injury and peaks approximately 3 to 15 hours after injury.18 The presence of myoglobin requires ruling out possible skeletal muscle injury versus cardiac muscle injury. Carbonic anhydrase III is a cytoplasmic protein that is present in skeletal muscle but not in cardiac muscle. In situations of skeletal muscle injury, both the myoglobin and the carbonic anhydrase III are elevated, but the ratio is constant, whereas in acute MI the ratio is not constant and changes within 2 to 15 hours after injury. This finding, although only recent, may prove to be more beneficial to emergency room monitoring of patients in the future than CPK and the troponins. Skeletal and cardiac muscle contain two heavy chains and two light chains in the myosin molecule. Cardiac myosin light chains (CMLCs) have been shown to be released after MI 19 and may have a role in identification of cardiac injury in unstable angina pectoris.20,21 Cardiac myosin light chains are currently difficult to separate from skeletal muscle chains and difficult to detect because of the lack of a reliable immunoassay; however, once a means of detection becomes available, this diagnostic test might prove to be the most sensitive and specific for cardiac injury. Aspartate aminotransferase (AST) or aspartate transaminase has two isoenzymes (GOT1/cAST in red blood cells and heart and GOT2/mAST in liver). Elevations in AST indicate pathology in liver, heart, kidneys, brain, skeletal muscle, or red blood cells. Aspartate aminotransferase is an important enzyme in amino acid metabolism. It was a common biochemical marker for acute MI in 1954. Use of AST has been replaced by more specific tests like cardiac troponins.22 Enzyme and isoenzyme levels increase within the first 36 hours after myocardial injury, reaching their individual peaks at different rates (Table 8-3).23 Marked elevation in CPK enzyme levels occurs whenever thrombolytic medications (streptokinase and tPA) are used to lyse clots. Clinically, an early or secondary peak in CPK levels followed by a more rapid decline in the CPK-MB levels is strongly suggestive of reperfusion after thrombolytic therapy.24

Clinical tip Troponin assessment is considered the gold standard for cardiac injury. In the absence of troponin information, the therapist should depend on CPK-MB information, electrocardiographic (ECG) changes, and symptoms. In any case where the CPK-MB is elevated, especially after hip surgery, confirmation of lack of troponin rise should be

made before increasing the patient’s activity.

Blood Lipids Elevation in blood lipid levels (hyperlipidemia) is considered a major risk factor contributing to CAD.25 The concentrations of serum cholesterol and triglycerides are the blood lipids of concern. The American Heart Association (AHA) defines elevated blood cholesterol levels as being higher than 200 mg/100 mL; however, the more stringent recommendations suggested by Castelli define 180 mg/100 mL as the upper end of normal (Table 8-4).26 Elevated cholesterol levels are associated with ingestion of excess amounts of saturated fat and cholesterol, as well as with hereditary influences. Elevated triglyceride levels are defined as being higher than 150 mg/100 mL. Elevated triglyceride levels are associated with increased carbohydrate ingestion and often preclude diabetes mellitus. Caution should be taken if measurements of cholesterol and triglyceride levels are taken at the time of acute injury, as research has shown these values to be inaccurate.27 Such measurements are most accurate when obtained before a myocardial injury or a minimum of 6 weeks after an acute injury.27 Table 8-3 Cardiac enzymes

CPK, creatine phosphokinase; LDH, lactic dehydrogenase; SGOT, serum glutamic oxaloacetic transaminase. a

1 IU is the amount of enzyme that will catalyze the formation of 1 μmol of substrate per minute under the conditions of the test. b

CPK-MB, 0% to 3%

LDH-1, 14% to 26%

From Smith AM, Theirer JA, Huang SH: Serum enzymes in myocardial infarction, Am J Nurs 73(2):277, 1973. Used with permission. All rights reserved. Copyright © 1973 The American Journal of Nursing Company.

Table 8-4 Normal lipid values

LDL, low-density lipoprotein; HDL, high-density lipoprotein; VLDL, very-low-density lipoprotein. Data from NCEP Expert Panel. Detection, Evaluation and treatment of high cholesterol in adults. Adult Treatment Panel III. NIH publication#01-3670 May 2001. Downloaded from http://circ.ahajournals.org/ on August 11, 2015

The usefulness of clinical laboratory reports is improved by giving a breakdown of the component parts of the total cholesterol. Current information now lists the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, as well as the ratio of total cholesterol to HDL cholesterol. High plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of CAD. High-density lipoprotein has been further subdivided into apolipoproteins and apo A-I (A-1), which is the main protein constituent of the HDL particle and has identical results in relation to risk for coronary disease. As a result, medications to raise apo A-1 are currently in clinical trials for the primary purpose of decreasing the risk of CAD.

Table 8-5 Total cholesterol to high-density lipoprotein (HDL) ratio as a predictor of heart disease

From Gordon T, Castelli WP, Hjortland MC, et al: Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women, Ann Intern Med 87:393, 1977.

Research has shown that the absolute values of total cholesterol or HDL cholesterol are of less importance than the ratio of total cholesterol to HDL cholesterol in establishing an individual’s relative risk for developing CAD (Table 8-5). An increased ratio of total cholesterol to HDL cholesterol identifies a person at an increased risk for development of CAD.28 High levels of LDL (higher than 130 mg/100 mL) also increase a person’s relative risk for developing CAD. Lowering total cholesterol, and especially LDL cholesterol, has shown to result in a 25% to 35% reduction in cardiovascular events.29 Recently several new markers have been identified that are considered to be probable risk factors, including lipoprotein a (Lpa), LDL subclasses, oxidized LDL, homocysteine, hematologic factors (primarily fibrinogen, factor VII, and tPA), inflammatory markers such as C-reactive protein (CRP), and infective agents such as Chlamydia pneumoniae (CPN). Elevated serum levels of a lipid particle called Lpa have been strongly associated with atherosclerosis and also identified as an independent risk factor for CAD.29 Lipoprotein a appears to have an atherogenic and prothrombotic effect that interferes with plasminogen and tPA binding to fibrin. Lipoprotein a levels are thought to be genetic in origin and were found in 50% of the offspring of patients with CAD in the Framingham study.29 Increased Lpa levels are associated with a threefold increase in the risk of a primary CAD event.28 Response to standard treatment for lowering LDL in individuals with elevated Lpa was not successful except with LDL apheresis.29 In addition to Lpa, the presence of an elevated amount of small, dense LDL particle subtype (phenotype B) is also associated with an elevated risk for CAD (threefold increased risk).29 Small, dense LDL is also associated with elevated triglyceride levels. Apparently small LDL particles can be moved into the vessel wall 50% faster than the

large LDL particles. Treatment for the presence of elevated small, dense LDL particle subtype consists of low-fat diet; exercise; and pharmacologic therapy with statins, bile acid sequestrants, nicotinic acid, and fibrates.30 Individuals with diabetes often have abnormal lipid levels. The most common pattern of lipid abnormalities in type 2 diabetes patients is elevated triglycerides and decreased LDL levels.31 However, type 2 diabetes patients have a preponderance of smaller, denser LDL particles, although their LDL cholesterol concentration is usually not significantly different from that of individuals without diabetes. Therefore elevated triglyceride levels may be a better predictor of coronary heart disease in type 2 diabetes patients than elevated LDL levels because of the correlation with insulin resistance and small, dense LDL.

Other Potential Clinical Laboratory Risk Factors for CAD Homocysteine, which is a type of amino acid found in the blood, has been linked to increased risk of development of cardiovascular diseases when the levels in the blood are elevated. Elevated levels of homocysteine have been reported to be greater than 13 µmol/L. In addition, elevated plasma homocysteine has been associated with increased risk of death in individuals with many cardiovascular diseases, including CAD, congestive heart failure,32 first major cardiovascular event,33,34 recurrent stroke,35 and persistent atrial fibrillation.36 Low levels of folate and vitamin B6 are related to elevated circulating homocysteine blood levels, and therefore sufficient folate intake may be an important factor in the prevention of coronary heart disease.37,38 The odds ratio for CAD of a 5-µmol/L homocysteine increase was discovered to be 1.6 for males and 1.9 for females.38 Hematologic factors, such as fibrinogen and elevated white blood cell (WBC) counts have been associated with increased risk of CAD. Individuals with elevated fibrinogen levels in the highest quartile demonstrated a double risk of CAD, whereas the Multiple Risk Factor Intervention Trial found that an elevated WBC count is associated with increased risk.39 Inflammatory markers and infection markers have shown some relationship to CAD. Inflammatory markers such as CRP, an acute-phase reactant to inflammation, have recently been related to increased risk for CAD. Testing CRP levels in the blood may be an additional way to assess cardiovascular disease risk. A more sensitive CRP test, called a highly sensitive C-reactive protein (hs-CRP) assay, is available to determine heart disease risk. Higher hs-CRP levels also are associated with lower survival rates in patients with CAD and therefore may be a useful risk predictor.40 Elevated levels of hs-CRP may increase the risk that an artery will reclose after it has been opened by balloon angioplasty. In addition, elevated levels of hs-CRP in the blood seem to predict prognosis and recurrent events in patients with stroke or peripheral arterial disease. One study looked at hs-CRP levels in individuals who took aspirin regularly versus those who did not take aspirin and found that hs-CRP levels were predictive of MI in those who did not take aspirin.40

Normative values for hs-CRP are less than 1.0 mg/L, indicating a person has a low risk of developing cardiovascular disease. If hs-CRP is between 1.0 and 3.0 mg/L, a person has an average risk, and if hs-CRP is higher than 3.0 mg/L, a person is at high risk of developing cardiovascular disease.41 If, after repeated testing, patients have persistently unexplained, markedly elevated hs-CRP (>10.0 mg/L), they should be evaluated to exclude non-cardiovascular causes. Patients with autoimmune diseases or cancer, as well as other infectious diseases, often have elevated CRP levels. Males with CRP levels in the highest quartile may have a fivefold increase in risk of developing an MI. Infection markers, including C. pneumoniae, have shown a twofold increase in risk of CAD. Systemic infection may act directly on the arterial wall, or may work by local or systemic inflammation. Because these are new risk factors with insufficient evidence to support regular screening for them, they should be measured only in families with unexplained CAD or premature CAD. Future studies documenting their efficacy in identifying CAD will be necessary before routine screening is recommended. In recent years B-type natriuretic peptide (BNP), a protein produced by the ventricles of the heart, has become an important tool to diagnose heart failure and may have implications for CAD. One of four known natriuretic peptides (atrial NP [ANP], BNP, Ctype NP [CNP], and DNP), BNP is released from the cardiac ventricles, especially the left ventricle, during pressure or volume overload. B-type natriuretic peptide functions to dilate arteries and veins and acts as a neurohormonal modulator in decreasing vasoconstricting and sodium-retaining neurohormones. It also functions with ANP to promote diuresis. B-type natriuretic peptide and N-terminal (NT) pro-BNP are peptide fragments derived from a common precursor molecule, proBNP. Recently BNP and NT-proBNP concentrations have been shown to be strongly predictive of short- and long-term survival in patients with ACSs.42 B-type natriuretic peptide has now been associated with increased risk of heart failure, whereas NT-proBNP appears to be associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incidents of heart failure, and NT-proBNP also improved the model for cardiovascular death.42

Complete Blood Cell Count The physical therapist should evaluate the complete blood cell count for three components: hemoglobin, hematocrit values, and WBC count. Hemoglobin plays a major role in the transport of oxygen throughout the body, and the hematocrit (the amount of the blood that is cells) is a significant indicator of the viscosity of the blood. Hemoglobin values are reported as a concentration in the blood (in grams per 100 mL of blood). The normal range of hemoglobin for females is 12 to 16 g/100 mL, and for males it is 14 to 18 g/100 mL.22 Low levels of hemoglobin or a diagnosis of anemia will increase the work on the

myocardium because of a lack of oxygen-carrying capacity and subsequently low levels of oxygen available to the tissues. In order to transport adequate oxygen to the tissues (even when the body is at rest), the heart rate is elevated and subsequently the cardiac output increases, thereby increasing the work on the myocardium. In addition, the mean corpuscular volume (MCV) test measures red blood cells (RBCs) in terms of individual volume. This test is used to classify anemias as microcytic (RBC size smaller than normal), normocytic, or macrocytic (larger than normal). Microcytic anemias are found in iron deficiency, chronic infections, chronic renal disease, and malignancies. Normocytic anemia (hypochromic) is found in chronic infections, lead poisoning, chronic renal disease, and malignancies, whereas normochromic anemia is found in hemorrhage, hemolytic anemia, bone marrow hypoplasia, and splenomegaly. Macrocytic anemia is found in pernicious anemia, folic acid deficiency, hypothyroidism, and hepatocellular disease. Defining the MCV therefore assists in treatment of the cause of the anemia.43–45

Clinical tip Many facilities use a cutoff value for Hb of less than 8 g/100 mL as a red flag for out-ofbed activities. An Hb value below 8 g/100 mL would cause the individual to have an extremely low oxygen-carrying capacity and therefore be performing a lot of work even with bed rest and activities of daily living (ADLs). Heart rates are elevated with low Hb, and the patient would also be performing a lot of work with breathing. The lower-limit value for hematocrit is 37 g/100 mL for females and 42 g/100 mL for males.22 Decreased levels of hemoglobin and hematocrit are often found in post– coronary artery bypass graft surgery patients. Elevated hematocrit levels suggest that the flow of blood to the tissues may be impeded because of an increase in the viscosity of the blood. Elevated hematocrit levels are often seen in individuals with chronic obstructive pulmonary disease (a response to chronic low PO2).

Clinical tip After surgery, particularly after coronary artery bypass graft surgery, patients will demonstrate decreased hematocrit and hemoglobin values (and usually normocytic and normochromic MCV) and may be more symptomatic with activity because of low oxygen-carrying capacity. White blood cells are monitored for the body’s response to infectious diseases. Elevated levels of WBCs (leukocytosis) are found in response to leukemia, bacterial infection, or polycythemia (secondary to bone marrow stimulation). Some studies have identified a possible association between elevated WBC counts and increased risk of CAD.39 Decreased WBC count (leukopenia) is found with bone marrow depression, acute

viral infection, alcohol ingestion, and agranulocytosis. Disease processes may result in a change within individual leukocyte groups by altering morphology, function, or total numbers. Therefore the differential WBC count is important to assess in order to determine possible causes of the abnormal WBC count.

Coagulation Profiles Coagulation profiles have become an important component of the patient’s medical record because of the use of thrombolytic agents to dissolve clots in the early stages of MI. Prothrombin time and partial thromboplastin time measure the coagulation of the blood. Streptokinase or tissue plasminogen activator (tPA) infusion is a means of dissolving critical clots that are blocking a coronary artery and creating a potential infarction and subsequent necrosis. These thrombolytic agents are most commonly administered intravenously but can also be injected directly into the coronary arteries. After the initial infusion of thrombolytics is begun, an intravenous infusion of heparin is started. As a result, prothrombin time and partial thromboplastin time must be monitored closely to determine the therapeutic ranges of anticoagulation.22 Partial thromboplastin time will often be elevated following any thrombolytic or heparin infusion. An elevated partial thromboplastin time indicates an increased time to form a clot; therefore the chance of bleeding when bruised or cut is increased and caution should be taken. Another oral anticoagulant commonly used to treat and prevent venous thrombosis and PE is warfarin (Coumadin). Warfarin interferes with the vitamin K–dependent activation of clotting factors II, VII, IX, and X. When the amount of anticoagulation is within narrow limits, warfarin therapy is both safe and effective; however, too little anticoagulation can lead to treatment failure or recurrence of thrombosis, and too much anticoagulation can lead to serious or fatal bleeding. The amount of anticoagulation cannot be accurately predicted from the dose of warfarin because patient response is affected by several factors. Laboratory monitoring is critical to maintain warfarin anticoagulation within a therapeutic range. Prothrombin time is the most accurate way to monitor warfarin therapy; however prothrombin time values do not agree well between laboratories, making prothrombin time unsuitable for defining therapeutic ranges for warfarin therapy. The international normalized ratio, or INR, was developed to standardize prothrombin time values so that test results from different thromboplastins and coagulation analyzers become equivalent. Under the INR system, a thromboplastin is assigned an international sensitivity index (ISI) value.46 Post-MI and mechanical valve patients have a target INR of 3 (2.5 to 3.5), and all other clotting problems have a target INR of 2.5 (2.0 to 3.0) (see Table 8-2). Non-valvular atrial fibrillation (AF) increases the risk of ischemic stroke by as much as a factor of 5, and the intensity of anticoagulation therapy reduces not only the frequency of ischemic stroke, but also its severity and risk of death from stroke. Although warfarin is highly effective in preventing stroke in patients with AF by minimizing the formation

of atrial thrombi, an INR of 2.0 or above decreases the risk of ischemic stroke to a higher degree than just the treatment with warfarin, emphasizing the need to follow a patient’s INR regularly.47 However, any anticoagulant therapy has the risk of hemorrhage associated with it, yet research has shown that if the INR is less than 2.0 because of the fear of bleeding, the patient is at an increased risk of having a more severe stroke and of having higher mortality poststroke.47

Clinical tip If a patient has been on thrombolytics or heparin (including low-dose heparin), the therapist should take extreme care to prevent falls, as well as bumping extremities with all movement, as the individual will be at a greater risk of bruising and bleeding.

Electrolytes All electrolyte levels should be observed when evaluating the laboratory results because disturbances in the electrolytes may affect the patient’s performance. The electrolytes involved in maintaining cell membrane potential—Na+, K+, and CO2—are the most important electrolytes to monitor. Hydration state, medications, and disease can affect these values. Patients receiving diuretics (e.g., for hypertension or heart failure) should have their sodium and potassium levels monitored carefully, because some diuretics act on the kidney. The action of these medications on the kidney is on the renal tubules and collecting ducts, where these electrolytes are allowed to diffuse out or are reabsorbed from the bloodstream. Hyponatremia, where serum sodium (NA+) levels are below 136 mmol/L, and hypernatremia (NA+ levels are greater than 145 mmol/L) will usually manifest as nausea, vomiting, headaches, seizures, or other neurologic disturbances and can lead to death if not treated. Dangerously low levels of potassium (lower than 3.5 mEq/L) can cause serious, life-threatening arrhythmias. Dangerously high levels of potassium (greater than 5.0 mEq/L) can affect the contractility of the myocardium. Low levels of CO2 can cause an alkalotic state, muscle weakness, and dizziness.22

Blood Urea Nitrogen and Creatinine and B-type Natriuretic Peptide The BUN and creatinine values can be found on the same laboratory form as that reporting the electrolytes and cholesterol. The normal range for the BUN is 8 to 23 mg/dL; an elevated BUN can be an indication of heart failure or renal failure. Elevated BUN values also indicate uremia or retention of urea in the blood. Decreased BUN values may indicate starvation, dehydration, or even other organ dysfunction such as liver disease.

Clinical tip Abnormal laboratory values found in heart failure include increased BUN, increased LDH, increased BNP, normal CPK-MB, and possibly increased creatinine levels due to renal dysfunction. The BUN value is unsuitable as a single measure of renal function, and therefore the creatinine value should also be noted. Normal serum creatinine levels are lower than 1.5 mg/dL. Endogenous creatinine is fully filtered in the glomerulus and is not reabsorbed in the tubules in the presence of normal renal function. Therefore the clearance of creatinine is a measure of renal efficiency. As the glomerular filtration rate declines, the creatinine level rises and the renal function is assessed as inefficient. Severely elevated creatinine levels greater than 4.0 mg/dL indicate severe renal insufficiency or failure. The interpretation of the BUN and creatinine concentrations is an indication of the severity of the uremia. B type natriuretic peptide is the gold standard for measurement of heart failure, both compensated and uncompensated. This peptide is released by the ventricles of the heart in response to excessive stretch on the heart muscle. It may also be elevated with renal failure. The normal value for BNP is less than 100 pg/mL.48 Values greater than 700 pg/mL indicate acute cardiac decompensation, and between 100 and 700 indicate chronic compensation.

Serum Glucose Serum glucose level is measured when a typical laboratory sample of blood is collected. The normal value for serum glucose is 80 to 110 mg/100 mL of blood, measured in the fasting state. The concentration is maintained within a reasonably narrow range. An elevated blood glucose level (mild hyperglycemia is 120 to 130 mg/100 mL) indicates a surplus of glucose in the blood. An elevated serum glucose value is suggestive of a prediabetic state and warrants testing for diabetes, such as administration of a glucose tolerance test (performed in the fasting individual following the ingestion of 100 g of glucose). Severe hyperglycemia (above 300 mg/100 mL) denotes a crisis situation that requires immediate insulin because cells lack the energy source to function, resulting in severe fatigue and subsequently inadequate metabolic activity. Patients should not exercise when blood glucose measures in the severe range. An elevated serum glucose value may also be found in a patient with diabetes who is not well controlled on oral or injectable insulin. Testing the hemoglobin A1C (Hb A1c is normally 4.8% to 6.0%) measures a diabetic’s insulin control during the past 90 days, which is the life of the RBCs that carry the hemoglobin.22 See Chapter 7 for more information on diabetes.

Other Laboratory Values

Other laboratory values may be abnormal but not usually indicative of cardiac dysfunction and instead may be related to other comorbidities. Abnormal laboratory values should be investigated to assess for comorbidity and any effect on the cardiac system. For example, albumin, a small blood protein, is the first protein detected in the urine when there is renal damage (e.g., burns, shock, low cardiac output). Elevations in albumin are rare, but low levels of albumin may be found in chronic liver disease, protein malnutrition, chronic infection, and acute stress. Elevated bilirubin may be present when there is hemorrhage or hepatic dysfunction, whereas elevations in lipase indicate pancreatic dysfunction or pancreatitis.

Other Noninvasive Diagnostic Tests Holter Monitoring Holter monitoring consists of continuous 24-hour electrocardiographic monitoring of a patient’s heart rhythm, providing information that is essential to the diagnosis and management of episodes of cardiac arrhythmias and corresponding symptoms. Holter monitoring tracings must be reliable to capture, recognize, and reproduce any abnormality in heart rhythm, particularly those that threaten life or cardiac hemodynamics. Indications for use of the Holter monitor include identifying symptoms possibly caused by arrhythmias (e.g., dizziness, syncope, palpitations, or shortness of breath at rest as well as with activity), describing the arrhythmias noted with activity (frequency and severity), and evaluating antiarrhythmic therapy and pacemaker functioning. A common practice is to perform Holter monitoring routinely before discharging any patient who has had an MI, because arrhythmias are commonly associated with coronary disease, ischemia, and injury.

FIGURE 8-1 Holter monitoring is transcutaneous, with multiple leads to record heart rhythm for 24 hours. (From Malarkey L, McMorrow ME: Saunders Nursing Guide to Laboratory and Diagnostic Tests, ed 2, St. Louis, 2012, Saunders.)

The patient’s heart rhythm is monitored by means of a transcutaneous recorder applied to the patient’s chest wall via multiple leads and electrodes and then recorded onto digital flash memory devices (Fig. 8-1). The patient wears the Holter monitor for 24 hours (there are 30-day monitors available as well) while performing normal activities (except bathing). All of the patient’s activities, as well as any symptoms that may be felt during the 24 hours, are documented by the patient. Once the recorder is removed from the patient, the flash memory device is processed by reproducing the recording on computer or paper for visual inspection. The physician then interprets the results and plans the treatment accordingly. Repeat Holter monitoring may be necessary once treatment has been initiated to evaluate the effectiveness of the treatment. It is the responsibility of the physical therapist working with a patient who is wearing or has worn a Holter monitor to obtain the interpretation of the results to determine whether modifications are needed in the patient’s activities. For example, patients with life-threatening arrhythmias recorded by the Holter monitor should not begin physical therapy activity until treatment for the arrhythmia is initiated or modified. Increasing frequency of arrhythmias or more serious (life-threatening) arrhythmias developing with activity also require further evaluation by the physician.49 Patients with abnormal Holter monitor results may be referred for treadmill exercise testing to assess arrhythmias during an assessment of increased work on the heart or may be referred for echocardiography to assess valve functioning. Patients demonstrating life-threatening arrhythmias on the Holter monitor may be referred to electrophysiologic mapping studies (EPS), particularly if they demonstrated sustained or nonsustained ventricular tachycardia. These individuals have a high risk of sudden death. Electrophysiologic mapping studies are performed to identify the specific area that may be initiating the arrhythmia by inducing the arrhythmia and then subsequently attempting to restore normal rhythm with one or more antiarrhythmic medications. If the arrhythmia is induced and unable to be treated successfully by the antiarrhythmic medication, the patient may be referred for an ablation procedure (cauterization of the area inducing the arrhythmia) or pacing techniques, or the patient may be provided an implantable cardiac defibrillator (ICD) for rhythm control. According to the AHA guidelines, indications for ICD therapy include individuals who have ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) lower than 30% or individuals with ischemic or nonischemic heart failure and New York Heart

Association (NYHA) Classes II to III and LVEF less than 35%.50,51 Clinical trials have confirmed that ICDs save lives over current antiarrhythmic treatment in certain populations.52,53 In the MUSTT trial, arrhythmic deaths or cardiac arrests were highest in inducible (able to induce sustained ventricular tachycardia under EPS study) patients randomized to no antiarrhythmic therapy; next were inducible patients receiving an ICD; and lowest were in patients who were noninducible.54 Individuals with recurrent uncontrolled AF may be referred for similar procedures, including an implantable atrial defibrillator or an ablation procedure.

Echocardiography Echocardiography is a noninvasive procedure that uses pulses of reflected ultrasound to evaluate the functioning heart. A transducer that houses a special crystal emits highfrequency sound waves and receives their echoes when placed on the chest wall of the patient (transthoracic echocardiography [TTE]). The returning echoes, reflected from a variety of intracardiac surfaces, are displayed on the ultrasonography equipment. Echocardiography has an advantage over other cardiac diagnostic tests because the technique is completely noninvasive and gives real-time images of the beating heart. The transducer is placed on the chest wall in the third to fifth intercostal space near the left sternal border. The transducer is then tilted at various angles so that the sound waves can scan the segments of the heart. M-mode echo and two-dimensional echo (Fig. 8-2) are common techniques of echocardiography, whereas Doppler echocardiography is a newer procedure. Doppler echocardiography gives information about the blood flow velocities within the heart. Important information can be obtained from the echocardiogram, including the size of the ventricular cavity, the thickness and integrity of the interatrial and intraventricular septa, the functioning of the valves, and the motions of individual segments of the ventricular wall. Assessment of the performance of the heart muscle itself, especially the regional functioning of the left ventricle, is a valuable application of echocardiography. The degree of normal thickening of a portion of the myocardium can be assessed and is an indirect assessment of ischemia because ischemic cardiac muscle does not thicken. Echocardiography can quantify volumes of the left ventricle, estimate stroke volume and therefore ejection fraction, and analyze motion of the valves and the heart muscle. Numerous specific problems can be evaluated with the echocardiogram: ▪ Pericardial effusion ▪ Cardiac tamponade

FIGURE 8-2 M-mode and two-dimensional echocardiography. The tracing on the bottom shows the result of an M-mode echocardiogram (i.e., transducer in single position) during one cardiac cycle. The waves represent motion (“M”) of heart boundaries transected by stationary ultrasonic beam. In two-dimensional echocardiography (upper panel), the probe rapidly rotates between the two extremes (broken lines), producing an image of a slice through the heart at one instant in time. (From Boron WF and Boulpaep: Medical Physiology: A Cellular and Molecular Approach, updated edition, Philadelphia, 2005, Saunders.)

▪ Idiopathic congestive cardiomyopathy ▪ Hypertrophic cardiomyopathy ▪ Mitral valve regurgitation ▪ Mitral valve prolapse ▪ Aortic regurgitation ▪ Aortic stenosis ▪ Vegetation on the valves ▪ Intracardiac masses ▪ Ischemic heart muscle ▪ Left ventricular aneurysm ▪ Ventricular thrombi ▪ Proximal coronary disease

▪ Congenital heart disease ▪ Interventricular thickness ▪ Pericarditis ▪ Aortic dissection ▪ Patency of internal mammary coronary artery bypass graft (determined with Doppler technique) Problems exist with the image quality of standard echocardiograms due to such confounding factors as pulmonary disease, obesity, and chest deformities. Transesophageal echocardiography (TEE) has solved these problems and allows an improved view of the heart and mediastinum (Fig. 8-3). The procedure begins when the patient begins to swallow the specialized probe. The use of anesthesia and a sedative minimizes discomfort, and there is usually no pain. The probe travels down the esophagus the same way as swallowed food. Therefore it is important that the patient swallow the probe rather than gag on it.

FIGURE 8-3 A, Diagram of common scan planes during a transesophageal echocardiogram (TEE) with a two-dimensional view. Transverse plane: cross-sectional view at Level 1a depicts the proximal ascending aorta (Ao), main pulmonary artery (MPA), and left and right pulmonary arteries (LPA and RPA, respectively). A rightward tilt of the transducer shows the RPA as it passes behind the superior vena cava (SVC) and ascending aorta (Asc Ao). B, To obtain a four-chamber view (Level 3), the transducer is advanced in the esophagus with slight retroflexion of the scope. (Part A adapted from Geva T; Echocardiography and Doppler ultrasound. In Garson, A, Bricker JT, Fisher DJ, Neish SR, editors: The science and practice of pediatric cardiology, Baltimore, 1997, Williams & Wilkins, p 789, with permission.)

The transducer at the end of the probe is positioned in the esophagus directly behind the heart. By rotating and moving the tip of the transducer, the physician can examine the heart from several different angles. The heart rate, blood pressure, and breathing are monitored during the procedure. Oxygen is given as a preventive measure, and suction is used as needed.

Further, TEE allows for improved visualization of cardiac structures and function and is valuable in the intraoperative and perioperative monitoring of left ventricular performance, as well as the evaluation of surgical results.55–58 In addition, TEE has become established as the imaging modality of choice for the evaluation of known or suspected cardioembolic stroke.59 Transesophageal echocardiography may also be useful in detection of those at risk for an embolic stroke because of its ability to detect blood clots, masses, and tumors that are located inside the heart and those individuals with nonvalvular AF.60 A TEE can also gauge the severity of certain valve problems and help detect infection of heart valves, certain congenital heart diseases such as atrial septal defect (ASD) (or a hole between the atria), and a tear (dissection) of the aorta.60 Two-dimensional echocardiographic studies during exercise, immediately after exercise, or at both times (also known as stress echocardiography) are currently used to evaluate ischemia-induced wall motion abnormalities noninvasively. In addition to treadmill or bicycle exercise, atrial pacing or the use of pharmacologic agents provides an “artificial exercise” situation from which two-dimensional echocardiographic studies can identify the presence and location of ischemia-induced abnormalities in the ventricular wall.61 Stress echocardiography is especially useful for the evaluation of atypical symptoms such as dyspnea and fatigue,62 as well as for the evaluation of patients with nondiagnostic ECGs with exercise or who have atypical chest pain syndromes.63 The development and use of three-dimensional echocardiography, the newest form of echocardiography, provides enhanced images displaying intracardiac anatomy.64 Threedimensional echocardiography provides accurate quantified data previously assessed by computer analysis.64,65

Contrast Echocardiography Using an intravenously injected contrast agent with the echocardiogram has improved the diagnostic accuracy of echocardiography in assessing myocardial perfusion and ventricular chambers.66 The contrast agent used consists of a suspension of air-filled microspheres that act as an ultrasound tracer. Contrast echocardiography enhances the visualization of intracardiac and intrapulmonary shunts, endocardial wall motion, and ventricular wall thickness and improves the calculation of ejection fraction. In addition, contrast echocardiography appears to have potential for quantifying coronary flow and assessing myocardial viability.67 It is a method for noninvasively assessing areas of the myocardium at risk for damage, presence or absence of coronary collateral flow, and revascularization of occluded arteries after coronary angioplasty. The use of contrast material also improves the visualization of endocardial borders, allowing discrimination between the myocardial tissue and the blood pool.68–70 The Food and Drug Administration (FDA) currently has approved octafluoropropane (Optison) and perflutren lipid microsphere (Definity) as contrast agents for echo imaging, as they increase endocardial border identification. Contrast echocardiography has also been used with transesophageal or epicardial echocardiography (only in the operating room or in the cardiac catheterization

laboratory) to assess the distribution of cardioplegia and the degree of valvular regurgitation, as well as the vascular supply of bypass grafts and bypass graft patency.67 The future of contrast agents with echocardiography may be in the performance of clot lysis and for targeted gene therapy.71 Studies comparing contrast echocardiography with thallium-201 SPECT imaging have demonstrated similar conclusions regarding the presence and amount of jeopardized myocardium, yet it may involve one half the cost of the SPECT and therefore be more cost effective than the SPECT imaging.66,72

Other Imaging Modalities In addition to contrast perfusion echocardiography, other imaging techniques are used in the diagnosis of cardiac dysfunction that may or may not utilize radioactive isotopes. Positron emission tomography, CT, SPECT, EBCT, MUGA, and MRI are all imaging techniques used for evaluation of CAD and cardiac dysfunction. Some of these modalities use high-speed scintillation cameras that can follow the transit of isotopes injected into the peripheral vein through the right side of the heart, much as the dye flow that occurs with cardiac catheterization. Other methods use a camera that times the acquisition of images according to the cardiac cycle. All these tests play an important role in the diagnostic evaluation of coronary artery status, each with their advantages and disadvantages, which will be discussed in the following paragraphs.

Positron Emission Tomography Positron emission tomography is a nuclear technique that provides visualization and direct measurement of metabolic functioning, including glucose metabolism and fatty acid metabolism, as well as blood flow of the heart. It is considered to be the gold standard for blood flow measurement and metabolic assessment of the heart, but it requires specialized technologic equipment and highly trained personnel and therefore is extremely expensive and not available at many hospitals.73 Positron emission tomography has the highest resolution gain, yet given the high cost associated with PET imaging, it is unlikely it will become used routinely for cardiac imaging because there are comparable tests that are more widely available and cost less.74 Positron emission tomography is a test that uses a special type of camera and a tracer (radioactive chemical) to examine organs in the body. It requires administration of dipyridamole to cause vasodilation of the coronary arteries while the patient is at rest, and often FD6 (18F-fluorodeoxyglucose, a tracer liquid) is administered to allow for myocardial metabolism and blood flow to be assessed in three dimensions.75 The tracer moves through the body, where much of it collects in the specific organ or tissue. The tracer gives off tiny positively charged particles (positrons). The camera records the positrons and turns the recording into pictures on a computer. Further, FD6 PET imaging allows for quantification and qualification of regional myocardial tracer distribution. Positron emission tomography imaging demonstrates tissue viability using the metabolic tracers to detect CAD and is especially helpful in identifying the individual with severe left ventricular dysfunction who would be a candidate for revascularization or transplant.75 Therefore PET imaging has advantages over thallium imaging with exercise because it can detect jeopardized but viable myocardium76,77 without requiring the individual to perform an active exercise test. Patients can safely undergo PET imaging from 2 to 10 days after infarction, or when any question of impedance of flow is involved. Since the invention of thrombolytic medications to decrease infarct size, this technique has demonstrated great advantages in evaluating the effectiveness of the thrombolytic

technique because the procedure can be performed so early after infarction.78 Because of the inaccessibility and cost of the procedure, other procedures have been studied and compared with the results of PET to determine equally effective diagnostic tests for myocardial blood flow. Williams determined that the viable myocardium results obtained from dobutamine echocardiography were similar to the results obtained from PET imaging, and it could therefore be performed when PET imaging was not an option.79 In addition, PET imaging has been used as a diagnostic tool to assess brain metabolism and ischemia/injury in cerebrovascular accident and acute trauma patients.80

Computed Tomography Computed tomography is used predominantly to identify masses in the cardiovascular system or to detect aortic aneurysms or pericardial thickening associated with pericarditis. Images are taken of anatomic structures; in this case, cardiac structures are viewed in slices and analyzed, and the slices are approximately 1 to 3 mm apart. Recently CT scanning has been used to assess graft patency in coronary artery bypass graft surgery patients with injection of an intravenous dye. One recent study looked at evaluating low-risk patients admitted to the emergency department with chest pain to see if cardiac CT scans could rule out coronary ischemia and reduce the length of stay and hospital charges.81 Individuals who were admitted with chest pain who were identified as low risk and who had negative cardiac CT scans were discharged earlier and with reduced hospital charges, indicating that CT scans might prove beneficial for some patients admitted with chest pain.81

Single-Photon Emission Computed Tomography Single-photon emission computed tomography is a method to detect and quantify myocardial perfusion defects and contractility defects and is used in conjunction with radioactive isotopes.82 It uses newer gated tomographic techniques and can be performed with the use of sestamibi (a radioactive perfusion agent) to improve the view of a myocardial perfusion study. Images are acquired with either a gamma camera or a camera that times, or “gates,” the acquisition according to the cardiac cycle (via ECG). Single-photon emission computed tomography can determine contractility defects at rest by assessing both left and right ventricular ejection fraction, regional function, and ventricular volumes.82 In addition, SPECT imaging, although less accurate than PET imaging, is more often the diagnostic tool of choice because of the availability of these gated imaging machines and the ease of performance. Further information on SPECT is detailed in perfusion imaging with sestamibi later in this chapter.

Electron Beam Computed Tomography Electron beam computed tomography is used to detect calcium in the coronary arteries and is a noninvasive method to detect and quantify coronary atherosclerosis.83–86 Calcium

in the coronary arteries may be an early sign of CAD. Rumberger used EBCT on older populations; however, recently O’Malley used the procedure for screening for CAD in asymptomatic active-duty U.S. Army personnel.83,87 A typical EBCT scanning protocol involves a 10-minute scan of 40 slices through the heart every 3 to 6 mm.88 Intravenous contrast medium is not used, so radiation exposure is minimal (approximately one half the radiation exposure to the average person living in the United States in 1 year).83 Electron beam computed tomography detects the presence of calcium in the coronary arteries, as well as the location, extent, and density of the deposits, and provides a calcium-scoring system. Results are given in the form of a composite score for the entire epicardial coronary system. Further, EBCT has been studied in individuals undergoing cardiac catheterization and has shown a sensitivity of 81% to 94% for any angiographic evidence of coronary disease and a specificity of 72% to 86%.86,89 It currently appears to have moderate discriminating power in young, symptomatic patients with a high prevalence of obstructive disease, but its reliability with asymptomatic subjects is yet to be determined. Several studies have shown the association of future cardiovascular events with an elevated amount of coronary calcifications and reported that coronary calcium predicts cardiovascular events more accurately than does risk stratification using conventional risk factors.90–93 The determination of coronary calcifications allows the identification of patients with a high risk for future MI and CAD within an asymptomatic population. Becker looked at the ability of EBCT to predict MI compared with adenosine-tri-phosphate (ATP) III risk score and found that there was higher diagnostic accuracy with the EBCT.94 In addition, future MI or CAD during the observation period was excluded in patients without coronary calcifications independent of concomitant cardiovascular risk factors.94–96 Because accuracy of predicting CAD is still not proved with EBCT, further studies are needed in this area.

Clinical tip The use of EBCT to identify individuals at risk for future MI or stroke is still very controversial, and the evidence is not conclusive regarding the sensitivity of this test for identifying CAD in any population. Individuals undergoing this procedure need to know that this is not 100% reliable for all populations (those at risk versus those not at risk for CAD).

Multigated Acquisition Imaging Multigated acquisition imaging, or gated pool imaging, is a technique to calculate LVEF. A radioactive tracer is injected intravenously, and a gamma camera acquires images from the tracer. The information gathered in this study is obtained from the electrical activity of the heart using an electrocardiograph. Multigated acquisition imaging obtains multiple individual ejection fractions knowing the heart rate and RR intervals on the

electrocardiogram and then measures the emptying curves of the heart via computer. This technique has advantages over others in that it is minimally invasive and can therefore be used on critically ill cardiac patients (e.g., those with acute cardiac failure) when other more invasive tests such as catheterization would be dangerous.97–100

Magnetic Resonance Imaging Magnetic resonance imaging is used to evaluate morphology, cardiac blood flow, and myocardial contractility.101 However, use of cardiovascular MRI has been limited because of the existence of echocardiography and nuclear scintigraphy and the familiarity with these two techniques over MRI. Further, MRI has similar diagnostic accuracy as PET imaging and is similarly used as a noninvasive test to assess regional blood flow problems, but it is more widely available and often less expensive.75 Nuclear magnetic resonance can produce high-resolution tomographic pictures of the heart without using any radiation. Originally MRI was used for assessing cardiac anatomy and congenital malformations and to identify masses and thrombi. Currently MRI is being used for assessment of valvular disease, cardiac shunts, quantification of cardiac flow, and coronary artery anatomy.102 Fayad demonstrated that the human coronary vessel wall could be noninvasively imaged in vivo with MRI, thereby providing a technique to show atherosclerotic plaque without the use of coronary angiography.103 Future work with MRI indicates it may be the choice for detection of vulnerable plaque before an acute clinical event.103,104 Yang et al assessed the new cardiac MRI (CMRI) system, comparing it with echocardiography.105 The new CMRI system allows for continuous real-time dynamic acquisition and display. It was completed in less than 15 minutes and showed improved visualization of wall segments and left ventricular function compared with the echocardiography results.105,106 Magnetic resonance imaging is also being used in conjunction with pharmacologic stress testing to determine significant coronary atherosclerotic plaques.107 If an individual has a pacemaker, artificial joint, stent, surgical clips, heart valve, or any other metallic device, he or she might not be a candidate for an MRI.

Magnetic Resonance Angiogram A magnetic resonance angiogram (MRA) is a type of MRI that uses magnetic and radio wave energy to obtain images of the blood vessels inside the body. Intravenous contrast is often utilized to examine the status of blood vessels. An MRA can assess for aneurysms, dissection, or stenosis of blood vessels. An MRA can find the location of a blocked blood vessel and show how severe the blockage is. If an individual has a pacemaker, artificial joint, stent, surgical clips, heart valve, or any other metallic device, he or she might not be a candidate for an MRA.

Exercise Testing Exercise testing continues to be the single most important noninvasive procedure used in the diagnosis and management of patients with CAD, although exercise testing alone is less sensitive and specific for women versus men. Originally exercise testing was used to measure functional capacity or to evaluate abnormalities of coronary circulation. Currently exercise testing is used for a variety of patient management problems that are listed in Box 8-1. Exercise testing involves systematically and progressively increasing the oxygen demand and evaluating the responses to the increased demand. The technique varies with different modes of exercise chosen and different protocols used by the examiner. Formal exercise testing involves the following modes of exercise: ▪ Walking up and down steps ▪ Exercising on a stationary bicycle ▪ Using arm or wheelchair ergometry

BO X 8- 1 Indica t ions for e x e rcise st re ss t e st ing • Evaluation of chest pain suggestive of coronary disease • Evaluation of atypical chest pain • Determination of prognosis and severity of coronary artery disease • Evaluation of the effects of medical or surgical therapy or intervention • Evaluation of arrhythmias • Evaluation of hypertension with activity • Assessment of functional capacity • Screening to provide an exercise prescription • Providing motivation for a lifestyle change to reduce the risk of developing coronary artery disease ▪ Walking or jogging on a treadmill at variable speeds and inclines ▪ Walking a specified distance, as in the 6-minute walk test Informal testing is performed to screen for exercise programs, sometimes on a group basis, and includes such tests as the 12-minute walk, Cooper ’s 12-minute run, the pulse recovery test, or the 1.5-mile run (Table 8-6).108–110

Maximal versus Submaximal Stress Testing The protocols that are used are described as either maximal or submaximal; the distinction between them is the termination point of the test. Submaximal tests are terminated on achievement of a predetermined end point (unless symptoms otherwise limit completion of the test). The predetermined end point may be either the achievement of a certain percentage of the patient’s predicted maximal heart rate

(PMHR) (e.g., 75% of PMHR) or the attainment of a certain workload (e.g., 2.5 mph, 12% grade). A special subset of submaximal testing is low-level testing, performed on patients during the recuperative phase after myocardial injury or coronary bypass surgery. Maximal stress tests usually use the end point of the PMHR or terminate when a patient is limited by symptoms. Maximal stress testing is used to measure functional capacity and to diagnose CAD. The protocol for testing involves performing a progressive workload until the patient perceives an inability to continue because of some limiting symptom such as shortness of breath, leg fatigue, or chest discomfort. Exercise tests also may be described as intermittent or continuous. Intermittent testing intersperses progressive workloads with short rest periods to give the subject time to recover and decrease the effect of peripheral fatigue. Continuous tests utilize incrementally progressive workloads until the test is terminated because of patient symptoms or a defined end point. Table 8-6 The 12-minute walk/run test, which identifies fitness category for the distance covered in 12 minutes

M = Male; F = Female. From Cooper K: The Aerobic Ways, New York, 1981, Bantam Books.

Low-Level Exercise Testing

Low-level exercise testing is usually performed when patients have experienced an MI recently or have undergone coronary artery bypass graft surgery. Such tests have been performed as early as 5 days after MI or surgery,111 but are more likely to be performed just before or immediately after discharge from the hospital following an acute event. Some physicians prefer to wait up to 2 weeks after the cardiac event before administering the low-level exercise test. Low-level exercise testing may be useful in predicting the subsequent course of an MI or bypass surgery, as well as for identifying the high-risk patient. A test that has been gaining use is the 5-meter walk or gait speed test. It has been put forth as a possible predictor of risk in the cardiac surgical patient population.112,113 The 5-meter walk speed test has been used successfully in the geriatric population.. High-risk patients exhibit an increased risk of complications or death as a result of myocardial ischemia or poor ventricular function. High-risk patients need more immediate intervention and should not be treated as typical patients in a cardiac rehabilitation program. After a high-risk patient is identified, the decision for optimal medical management or surgical intervention is more easily made. Many factors have been studied from the results of the low-level exercise test to determine the most outstanding variable for identifying high-risk patients. Exerciseinduced ST-segment depression of 2.0 mm or greater on low-level exercise tests has been identified as the single most valuable indicator of prognosis after MI according to the regression analysis by Davidson and DeBusk.114 In addition, early onset of ST-segment depression is related to increased incidence of coronary events. Starling and colleagues115 demonstrated a significantly increased risk of death after MI when both ST-segment depression and angina were produced during low-level exercise testing in the early period after an MI. Exercise-induced angina alone was associated with subsequent coronary artery bypass surgery.116,117 Other variables of minor prognostic significance after MI include inappropriate blood pressure response, maximum heart rate achieved, and maximum systolic blood pressure achieved.118,119 Low-level exercise testing can also provide information useful for optimal medical management after myocardial injury or surgery, including treatment for angina, arrhythmias, or hypertension. Exercise-induced arrhythmias on a low-level exercise test may be an indication for therapeutic management before hospital discharge. The incidence of sudden death has been reported to be 2.5 times higher in patients manifesting ventricular arrhythmias during low-level exercise testing.120 Poor performance, such as limited exercise duration, has been highly correlated with increased incidence of heart failure and is associated with increased mortality.121 Because of its great prognostic and therapeutic value, low-level testing is often used for screening patients who wish to participate in cardiac rehabilitation programs.122 Activity levels for patients during rehabilitation in the home or hospital setting can be prescribed on the basis of the results of the low-level exercise test. However, not all patients are appropriate candidates for low-level exercise testing. Safety of exercise testing early after MI has been a topic of debate because of the traditional medical belief that a recently damaged myocardium is prone to further injury,

including rupture, aneurysm, extension of infarction, or susceptibility to serious arrhythmias.123 However, the safety of properly conducted exercise testing was documented as early as 1973.124 Knowledge of and adherence to contraindications for testing optimize the safety of exercise testing (Box 8-2).125 See Box 8-3 for indications/contraindications for exercise testing in the emergency department.81

BO X 8- 2 C ont ra indica t ions t o low- le ve l t e st ing • Unstable angina or angina pectoris at rest • Severe heart failure (overt left ventricular failure on examination with pulmonary rales and S3 heart sound) • Serious arrhythmias at rest • Second- or third-degree heart block • Disabling musculoskeletal abnormalities • Valvular heart disease • Blood pressure >180/105 mm Hg • Patient refuses to sign consent form From Starling MR, Crawford MH, et al: Predictive value of early postmyocardial infarction modified treadmill exercise testing in multivessel coronary artery disease detection, Am Heart J 102(2):169, 1981.

BO X 8- 3 Indica t ions a nd cont ra indica t ions for e x e rcise EC G in

t he e m e rge ncy de pa rt m e nt se ing Requirements before exercise ECG testing in the ED Two sets of c ardiac enzymes at 4-hour intervals should be normal ECG at the time of presentation, and pre-exerc ise 12-lead ECG show no signific ant c hange Absenc e of rest ECG abnormalities that would prec lude ac c urate assessment of the exerc ise ECG From admission to the time results are available from the sec ond set of c ardiac enzymes: patient asymptomatic , lessening c hest pain symptoms, or persistent atypic al symptoms Absenc e of isc hemic c hest pain at the time of exerc ise testing

Contraindications New or evolving ECG abnormalities on the rest trac ing Abnormal c ardiac enzymes Inability to perform exerc ise Worsening or persistent isc hemic c hest pain symptoms from admission to the time of exerc ise testing Clinic al risk profiling indic ating imminent c oronary angiography is likely

Institutions vary in the choice of an exercise testing protocol for low-level testing. However, a progressively increasing workload from 2 to approximately 6 METs (Metabolic Equivalent Tables—a multiple of the resting metabolic rate) is often used. Among the protocols for low-level exercise testing, the modified Naughton (Table 8-7) and modified Sheffield–Bruce (Table 8-8) protocols appear to be most widely chosen. The 5-meter walk speed test requires little equipment and can be performed in hospital hallway, for example. Low-level exercise testing soon after MI is a safe, noninvasive method for evaluating the functional capacity for physical activity; for detecting arrhythmias, angina, and hypertensive responses with exercise; for determining optimal medical management; and for predicting the risk of subsequent cardiac events.

Table 8-7 Modified Naughton treadmill protocol

MET, resting metabolic rate.

Table 8-8 Modified Sheffield–Bruce submaximal protocol

Safety in Exercise Testing The physical therapist must have a clear understanding of the rationale for terminating any exercise test. The specific criteria for termination vary from one institution to another, but the general criteria for termination of a maximal stress or low-level stress test are found in Box 8-4. Both the patient and the discharging physician benefit when a predischarge exercise test is conducted.122 The test can facilitate the distinction between chest wall and angina pain. In addition, improvement in exercise performance following an MI has been related to improvement in the patient’s self-confidence following a successful, uneventful predischarge exercise test. Maximal exercise testing and testing of high-risk patients or post–myocardial injury patients should be done in a setting in which emergencies can be managed expertly and efficiently. Appropriate equipment, which includes intravenous and emergency medications, intubation, and suctioning materials, should be present and updated when necessary. A direct current defibrillator should be available and functioning properly. Persons performing the testing should be certified in Advanced Cardiac Life Support,

taught by the AHA, and well trained in emergency cardiac response techniques such as defibrillation. Written protocols describing emergency procedures to be followed should be available to all testing personnel. These can be adopted from the AHA’s guidelines for advanced cardiac life support.126 Safety is a major consideration in exercise testing, and among the most important determinants of safety are the knowledge and experience of the examiner conducting the test. The American College of Sports Medicine has published guidelines that document the knowledge and skills required for exercise testing, including a description of situations in which the involvement or presence of a physician during testing may be necessary.127 Stuart and Ellestad published a survey of more than 500,000 exercise tests, which suggested an overall mortality rate of 0.5 per 10,000 tests and a morbidity rate of 9 per 10,000.128

BO X 8- 4 C rit e ria for t e rm ina t ion of m a x im a l a nd low-

le ve l/subm a x im a l t e st ing Criteria for termination of low level/submaximal testing Inc reasing frequenc y or pairing of premature ventric ular c omplexes An oxygen c onsumption level of 17.5 mL of Development of ventric ular tac hyc ardia oxygen per kg (6 METs) ac hieved Rapid atrial arrhythmias, inc luding atrial fibrillation or atrial flutter, with unc ontrolled ventric ular response 70% to 75% of age-predic ted maximal heart rate rates ac hieved Development of sec ond- or third-degree heart bloc k Fatigue or dyspnea Inc reased angina pain (Level 2 on a sc ale of 4) Maximal heart rate of 120 to 130 beats per minute Hypotensive blood pressure response (20 mm Hg or greater dec rease) Frequent (nine or more per minute) unifoc al or Extreme shortness of breath multifoc al premature ventric ular c ontrac tions, Dizziness, mental c onfusion, or lac k of c oordination paired premature ventric ular c ontrac tions, or S evere S T-segment depression. The Americ an College of S ports Medic ine rec ommends termination ventric ular tac hyc ardia when the S T segment is depressed 2.0 mm or more, although some testing personnel may proc eed S T-segment depression of 1.0 to 2.0 mm when c hanges of greater magnitude are demonstrated as long as there is no evidenc e of other abnormal Claudic ation pain Dizziness responses.102 Dec rease in systolic blood pressure of 10–15 mm Observation of the patient reveals pale and c lammy skin (pallor and diaphoresis) Hg below peak value Extremely elevated systolic or diastolic blood pressure, or both, whic h may or may not be assoc iated Hypertensive blood pressure (systolic >200 mm with symptoms Hg, diastolic >110 mm Hg) On ac hievement of predic ted maximal heart rate; it is usually safe to proc eed with the test beyond the Level 1 (out of 4) angina predic ted maximal heart rate if the patient is able and willing to c ontinue and if other indic ations to terminate the test are absent.108 Presenc e of leg fatigue or leg c ramps or c laudic ation pain Patient request for termination of test Criteria for termination of maximal testing

Exercise testing by nonphysician health care professionals has been performed for more than 30 years, although the AHA Committee on Stress Testing did not endorse the idea of “experienced paramedical personnel” as able to perform the tests until 1979.129 In 1987, Cahalin et al published a report on the safety of testing as performed by physical therapists with advanced clinical competence.130 In 10,577 tests performed, the mortality rate was 0.9 per 10,000 and the morbidity rate was 3.8 per 10,000. In addition, Squires et al reported on the safety of exercise testing of 289 cardiac outpatients with left ventricular dysfunction (ejection fraction over 35%) by paramedical personnel with physician available on call.131 Only one serious event occurred in 289 tests, and the outcome was a successful resuscitation. In addition, Olivotto et al demonstrated that exercise testing was safe in a community-based population of patients with hypertrophic cardiomyopathy

and provides useful information on functional capacity, blood pressure responses to exercise, and presence or absence of inducible ischemia.132 In 2000, the American College of Cardiology/AHA and American College of Physicians published a joint statement on the clinical competence required for stress testing, including skills required for paramedical professionals to perform graded exercise testing, that is found in Box 8-5.133 Factors that enhance the safety of exercise testing include the use of an informed consent form to be signed by the patient, the knowledge of when to exclude a patient from proceeding with an exercise test, the knowledge of when to terminate an exercise test, the knowledge and skills to react to an abnormal response or situation, and the availability of appropriate equipment and supplies to manage an emergency (e.g., defibrillator, emergency medications, intubation, suctioning equipment). Physical therapists wishing to conduct exercise tests on individuals older than 40 years or on persons who are at moderate to high risk of developing CAD should expect to obtain the required knowledge and skills in advanced training or in clinically supervised postprofessional education. However, all physical therapists should understand the procedures involved in exercise testing and interpretation of the test results because one of the major purposes of these tests is the development of exercise prescriptions. Exercise prescriptions are based on the results of the exercise test and other pertinent information (Box 8-6).

Contraindications to Testing Essential to safe testing is recognizing who should not be tested. Performing a thorough evaluation before testing will reveal any contraindications to testing. See Box 8-7 for absolute contraindications to maximal stress testing. In addition to absolute contraindications, the general clinical status of the patient must be considered before determining whether the stress test is contraindicated. See Box 8-4 for contraindications to testing and low-level testing.

Exercise Testing Equipment Clinical monitoring tools used during exercise testing traditionally include continuous ECG monitoring and periodic measurement of blood pressure and heart rate (this can be extracted from the ECG recording; see Chapter 9), patient reported or demonstrated symptoms, and heart and lung sounds. In some testing laboratories, expired gas analysis permits the assessment of oxygen uptake during the test (Fig. 8-4). Multiple-lead ECG monitoring is used to depict the electrical activity of the heart. Detection of both arrhythmias and ischemia can be made from the ECG. A detailed discussion of the interpretation of ECG data and a description of arrhythmias are presented in Chapter 9.

BO X 8- 5 Gra de d e x e rcise t e st ing skills for pa ra m e dica l

profe ssiona ls • Knowledge of absolute and relative contraindications for exercise testing • Ability to communicate properly with the client to complete a medical history and informed consent • Ability to explain to the client the purpose of completing the graded exercise test (GXT), procedures of the test, and the responsibilities of the client during the test • Competence in cardiopulmonary resuscitation certified by American Heart Association Basic Cardiac Life Support and preferably Advanced Cardiac Life Support • Knowledge of specificity, sensitivity, and predictive value of a positive and negative test and diagnostic accuracy of exercise testing in different patient populations • Understanding of causes that produce false-positive and false-negative test results • Knowledge of most appropriate activity and exercise protocol (e.g., Bruce, Naughton, Balke–Ware) for each individual, based on his or her medical history • Knowledge of normal and abnormal hemodynamic responses to graded exercise (blood pressure and heart rate response) in different age groups and with various cardiovascular conditions • Knowledge of metabolic data collected during a GXT and knowledge of how to interpret the data (e.g., maximal oxygen uptake, metabolic equivalent) for different medical conditions • Knowledge of 12-lead electrocardiography and changes in the electrocardiogram that may result from exercise, especially ischemia, arrhythmias, and conduction abnormalities • Knowledge of proper lead placement and skin preparation for a 12-lead electrocardiogram • Knowledge and skills for accurately taking blood pressure under resting and exercise conditions • Knowledge of how to run and troubleshoot the medical equipment used for graded exercise testing (treadmill, electrocardiogram, bicycle ergometer, metabolic cart) • Ability to communicate with the client to assess signs and symptoms of cardiovascular disease before, during, and after the GXT • Knowledge of how to assess signs and symptoms by using appropriate scales (e.g., chest pain, shortness of breath, rating of perceived exertion) • Knowledge of the appropriate time to end the GXT and absolute and relative indications for test termination • Knowledge of when to ask for physician support when the physician is not directly involved in the GXT • Ability to communicate results of the GXT to the supervising physician Data from Rodgers GP, Ayanian JZ, Balady G, et al: American College of Cardiology/American Heart Association clinical competence statement on stress testing: a report of the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine Task Force on clinical competence, Circulation 102(14):1726–38, 2000. In Ehrman JK, Gordon P, Visich PS, et al: Clinical exercise physiology, ed 2, Champaign, 2009, Human Kinetics.

BO X 8- 6 Int e rpre t a t ion of e x e rcise t e st ing • Exercise time completed (and protocol used) • Limiting factors (reason for termination) • Presence or absence of chest pain at peak exercise: Usually defined as positive, negative, or atypical for angina or extreme shortness of breath • Maximal heart rate achieved • Blood pressure response • Arrhythmias: Description of which type developed and when they occurred • ST-segment changes: Usually described as positive, negative, equivocal, or indeterminate for ischemia • Positive: 1.0 mm or greater horizontal or down-sloping ST-segment depression (Fig. 810) • Equivocal: More than 0.5 but less than 1.0 mm horizontal or downsloping ST-segment depression or more than 1.5 mm upsloping depression • Negative: Less than 0.5 mm horizontal or downsloping ST-segment depression108 • Indeterminate: Unable to measure the ST segment accurately because of the presence of any of the following: bundle branch block, medication (if patient is taking digoxin [Lanoxin]), resting ST-segment changes on the ECG, or cardiac hypertrophy • Heart sounds: Notation of pretest and posttest sounds and description of any change • Functional aerobic impairment: Can be determined from a nomogram if the Bruce treadmill protocol is used. This value is compared with normal values to determine impairment in functional capacity (physical work capacity). • R wave changes: Amplitude changes are considered to give additional diagnostic information in interpreting exercise test results. The normal response to exercise is a decrease in R wave amplitude. If no change or an increase in R wave amplitude occurs with exercise, the patient with CAD is considered to be at an increased risk for developing a cardiac problem in the future (Fig. 8-11).124 • Maximal oxygen consumption (VO2max) can be calculated using formulas if not directly measured during the test; however, this method is not very accurate.

BO X 8- 7 Absolut e a nd re la t ive cont ra indica t ions t o e x e rcise

t e st ing Absolute contraindications Rec ent myoc ardial infarc tion (MI; less than 4 to 6 weeks after the MI for a maximal, symptom-limited test) in most c linic al settings Ac ute peric arditis or myoc arditis Resting or unstable angina S erious ventric ular or rapid atrial arrhythmias (e.g., ventric ular tac hyc ardia, c ouplets, atrial fibrillation, or atrial flutter) Untreated sec ond- or third-degree heart bloc k Overt c ongestive heart failure (pulmonary c rac kles, third heart sound, or both) Any ac ute illness

Relative contraindications Aortic stenosis Known left main c oronary artery disease (CAD or its equivalent) S evere hypertension (defined as systolic blood pressure >165 mm Hg at rest, diastolic blood pressure >110 mm Hg at rest, or both) Idiopathic hypertrophic subaortic stenosis S evere depression of the S T segment on the resting elec troc ardiograph Compensated heart failure

Protocols for Exercise Testing Most institutions adopt a standard protocol to facilitate comparisons of the test subject’s responses from test session to test session, as well as for comparisons among other subjects. Standard testing procedures require a 12-lead ECG to be obtained before any test to rule out any acute ischemia or injury before testing. The patient’s ECG is continuously monitored during the test. Standard procedure is to monitor a minimum of three leads during the test. Other pretest procedures include assessment of the patient’s risk factor history for CAD (see Chapter 3; Box 3-2); assessment of the patient’s symptom history; and assessment of the patient’s resting blood pressure, heart rate, and heart and lung auscultation. When the exercise test is initiated, the workload is increased in accordance with a specific protocol. The patient’s heart rate and blood pressure (and in some tests, the expired gases) are periodically monitored throughout the test and during the recovery period. Most tests are symptom limited and, as such, are terminated at the request of the patient or on the identification of an abnormality in one or more of the parameters being measured. The patient is monitored continuously during the recovery period until the pretest values are achieved. Documentation in writing or electronic form, including interpretation of the results, is completed after the test. The most commonly used protocols in testing involve the use of either the stationary bicycle or the treadmill.134 Blood pressure is easier to auscultate on the stationary bicycle than on the treadmill. The bicycle also takes up less room, requires less coordination to operate, and is less expensive than the treadmill. The greatest disadvantage of the stationary bicycle, however, is that bicycling is not a daily functional activity for most persons. Therefore patients develop muscular fatigue faster because they are using muscle groups that are not as “trained” as the muscles used for walking. Such patients do not achieve their best results because the maximal heart rate may be well below what is considered diagnostic (85% of PMHR).125 The treadmill is relatively large, requires a patient to have balance and coordination, and is extremely noisy, making the auscultation of blood pressure very difficult. However, because walking is a functional activity, the muscles do not fatigue as rapidly as they do with cycling, and therefore the treadmill is considered to have greater diagnostic benefits. The two most common treadmill protocols are the Bruce exercise test protocol and the Balke exercise protocol. The Bruce protocol (Table 8-9) is probably most widely used in the clinical setting of hospitals because it provides normative data in the form of a nomogram to calculate functional aerobic impairment (Fig. 8-5). Previous studies have reported limitations in the ability of the functional aerobic impairment nomogram to predict functional capacity. The preferred method of predicting functional capacity is via the maximal workload performed on the treadmill test. According to Froelicher, a true test of aerobic capacity is best limited to a total exercise time of 10 minutes because of the endurance factor, which becomes significant after 10 minutes of exercise.135 The starting speed of the Bruce protocol is 1.7 miles per hour, which is a fairly

comfortable speed for all. However, because of the rapid increases in speed and the fact that the subject starts on a 10% grade, the average time a nontrained subject actually exercises during the test is between 6 and 12 minutes. In comparison, the Balke protocol (Fig. 8-6) starts at a speed of 3.3 miles per hour—this is often too fast for a deconditioned patient or an older individual. In the Balke protocol the subject starts on a level surface and only gradually is an incline added during the test. The gradual workload increments allow closer attainment of a steady state at each stage and facilitate the measurement of true maximal oxygen consumption. However, the Balke protocol requires a longer time to perform due to the gradual addition of the incline. The Balke protocol is used more widely with athletes, especially with runners, because runners typically do not train on steep inclines. Also, this protocol allows the athlete to attain a steady state in a shorter period.

FIGURE 8-4 Patient performing an exercise stress test. (From Baker T, Nikolic G, O’Connor S: Practical cardiology, ed 2, St. Louis, 2009, Churchill Livingstone.)

Table 8-9 Bruce treadmill protocol

1 MET, resting metabolic rate = 3.5 mL of oxygen per kg of body weight per minute.

From Ellestad MH: Stress testing principles and practice, ed 4, New York, 1996, Oxford University Press.

Terminating the Testing Session The person administering the exercise test must continuously observe the patient and the ECG monitor during the test to decide when the test should be terminated. See Box 84 for criteria for termination and for termination criteria for low-level exercise testing.

Interpretation of Results Once the test is concluded, the results are recorded on a worksheet or electronically to provide data for the interpretation (Fig. 8-7). Box 8-6 provides the parameters that are necessary for a thorough interpretation. The final summary of the exercise test should define whether the outcome of the test is normal or abnormal; if the outcome is abnormal, the summary should provide the reasons. Although the physical therapist may not actually perform the stress test, obtaining the interpretation of the results provides valuable data for developing an exercise prescription. The interpretation also provides valuable information regarding safety during exercise for the patient.

Prognostic Value of Maximal Exercise Testing Maximal exercise testing is used as a noninvasive screening method for the detection of coronary disease. Its diagnostic accuracy in determining coronary disease is limited by the fact that it is a noninvasive test and therefore only reflects gross metabolic and electrical changes in the heart. Nonetheless, studies evaluating the specificity and sensitivity of stress testing have suggested that in appropriately chosen populations, it can be very helpful in identifying coronary disease and defining its severity.125 Sensitivity

is the measure of the reliability of stress testing in identifying the presence of disease. Specificity is the measure of the reliability of stress testing in identifying the population without disease. In general, testing demonstrates greater sensitivity and specificity in males over the age of 40 than in females. Females generally demonstrate a greater percentage of false-negative results. It is beyond the scope of this chapter to describe the predictive values for every potential population. The value of diagnostic stress testing is tempered by the amount of variability among examiners conducting the test. Problems with testing include amount of encouragement given to the patient, a lack of strict adherence to protocols, use of handrail support, and interpretation of ST-segment deviation and symptoms.135

FIGURE 8-5 Nomograms for evaluating functional aerobic impairment (FAI) of men, women, and men with cardiac diagnosis, according to age and by duration of exercise on the Bruce protocol for sedentary and active groups. To find the FAI, identify age (in years) in the left column and identify duration of time on the Bruce treadmill protocol in the right column. With a straight edge, line up the two points and read where the straight edge intercepts the FAI nomogram for either active or sedentary. (From Bruce RL, Kusumi F, Hosmer D: Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease, Am Heart J 85:545–562, 1973.)

FIGURE 8-6 The Balke treadmill protocol.

Despite its acknowledged potential limitations, several studies have attempted to identify specific single parameters or combinations of variables that might identify a group of patients with more severe disease.125 Ischemia, reflected by ST-segment depression, which occurs during the early stages of an exercise test, has been correlated with more severe disease than ischemia that occurs at peak exercise. Goldschlager and colleagues reported an increased incidence of subsequent MI in a group of patients who exhibited ST-segment depression at light workloads.136 The severity of coronary disease has also been correlated with the length of recovery time (postexercise rest) for ST segment to return to normal. Other subsets of patients have been identified who demonstrate certain signs and symptoms that suggest a greater risk for the subsequent development of a cardiac event. The signs and symptoms that have increased prognostic value include ST-segment depression, bradycardic heart rate responses, presence of angina, and maximal systolic blood pressure attained. Ellestad identified a population with more serious prognosis of disease when the magnitude of ST-segment depression was considered.125 In addition, a subset of persons at high risk for progression of angina, MI, or death was identified by Ellestad. Persons with normal ST segments at peak effort who achieved maximal heart rates considerably below their predicted pulses (bradycardic heart rate response or chronotropic incompetence) demonstrated high risk of progression of angina, MI, or death. The tendency was to describe the test results as normal because the patients in Ellestad’s study did not demonstrate ischemic ST-segment changes. The presence of angina pain gives added significance when the patient demonstrates ST-segment depression during exercise. Ellestad described a subset of patients at double the risk of a subsequent coronary event when angina and ST-segment depression occurred together, compared with patients without angina but with ST-segment depression (silent ischemia).125 The incidence of sudden death is increased in the following subsets of patients: ▪ Those unable to exceed a maximal systolic blood pressure of 130 mm Hg

▪ Those with increased frequency and severity of arrhythmias during testing137 Calculating a probability score from the combination and weighing of clinical variables from the exercise test identifies the subsets of individuals at greater risk for coronary events. Many institutions are in the process of developing multiple variable analyses to increase the predictive value of exercise testing.138 However, the use of thallium injection at peak performance also increases the information gained from the test, as well as increasing the sensitivity of the test. An exercise time of more than 6 minutes, a maximum heart rate of more than 150 beats/min, and an ST recovery time of less than 1 minute were the variables that best identified women at low risk for developing CAD.139

Heart Rate Recovery Heart rate recovery (HRR) has been defined as the difference in heart rate at peak exercise and at 1 minute recovery. The literature supports that this is predictive of mortality. Studies by Cole et al and Jolly et al have shown this.140–142 Heart rate recovery may be used with both low-level and maximal exercise testing. It may also be employed to assess age-appropriate levels of fitness.

FIGURE 8-7 Worksheet for interpretation of exercise test results. (From Scully R, Barnes ML: Physical therapy, Philadelphia, 1989, JB Lippincott.)

Exercise Testing with Ventilatory Gas Analysis Although exercise testing alone is diagnostic for coronary disease, exercise testing with ventilatory gas analysis using a metabolic cart can provide greater information regarding ventilatory, cardiac, or metabolic limitations of the patient (see Fig. 8-4). A computer is used in conjunction with a system that automatically samples expired air continuously, a system that measures the volume of expired air, a system with oxygen provided electronically, and CO2 analyzers that measure the concentration of gases that are expired. The computer is programmed to compute the oxygen consumption, caloric expenditure, and CO2 production during rest and during any activity. The computer can provide a printout of the gas exchange and other variables every second of the activity and provide information for exercise prescription and for diagnosis of limitation of activity. One disadvantage of using the automatic computer-generated information is that the output data are accurate only if the electronic equipment and analyzers are accurate and calibrated against previously established standards. Cardiopulmonary exercise testing with ventilatory gas analysis provides information

on cardiac performance, functional limitation, and exercise limitations, particularly when the symptom limiting the individual is breathlessness or dyspnea. In assessing dyspnea, the ventilatory reserve and the dyspnea index are the most important variables. Normally 60% of an individual’s maximal ventilatory reserve is utilized during activity. Measurement of maximal voluntary ventilation (MVV) provides the information. Dyspnea occurs when the minute ventilation (VE) divided by the MVV is greater than 50% (otherwise known as the dyspnea index). When the VE/MVV is greater than 70%, respiratory muscle fatigue will occur within minutes. When the ratio is greater than 90%, an individual cannot continue exercising more than a few seconds.143 Dyspnea that occurs in the presence of pulmonary disease will demonstrate early rapid and shallow breathing, with a reduction in peak ventilation and a reduction in tidal volume (VT). Both VO2max and maximal volume of CO2 production are reduced, and the peak exercise dyspnea index is 1.0.144 Dyspnea that occurs in the presence of heart failure produces a different outcome with exercise testing. Individuals with heart failure achieve their anaerobic threshold much earlier than healthy individuals of similar age, with a lower-than-normal maximal ventilation and maximal CO2 production. The dyspnea index, however, is normal.144 Many advantages exist in using ventilatory gas analysis with exercise testing; however, several disadvantages also exist, including the fact that the equipment (a metabolic cart) is not widely available in the clinical setting. This equipment may be in hospital settings for use with resting nutritional studies and may be loaned for exercise testing. Another disadvantage is that many patients feel claustrophobic with the mouthpiece or headpiece and may actually hyperventilate with the mouthpiece.

Exercise Testing with Imaging Modalities Individuals may perform an exercise test to assess the myocardial oxygen supply and demand relationship (to determine whether ischemia occurs during physiologic stress) and undergo additional noninvasive imaging immediately following the performance of the exercise. The use of imaging techniques such as thallium-201 or sestamibi scanning and SPECT allows for greater diagnostic accuracy and sensitivity, particularly in individuals with atypical chest pain syndromes, or in females who demonstrate low sensitivity to exercise testing alone.143,145,146 Two-dimensional echocardiography is often used immediately after exercise testing as well. (See earlier sections on imaging and echocardiography for information.)

FIGURE 8-8 Stress-redistribution thallium scintigram. The patient was studied several days after acute ST-segment elevation MI and medical stabilization. Besides the fixed defect representing the MI in the anterior wall and apex (arrowheads), there is extensive inducible ischemia both within and remote from the infarct territory (septum and inferior walls, arrows), involving 25% of the ventricle. Gated single-photon emission computed tomography EF was 38%. On the basis of the data in A, there is an approximately 25% risk of post-MI adverse event. SA, short axis; VLA, vertical long axis; HLA, horizontal long axis. (From Libby P, Bonow RO, Mann DL, et al: Braunwald’s heart disease: a textb ook of cardiovascular medicine, ed 8, Philadelphia, 2008, Saunders.)

Radioactive Nuclide Perfusion Imaging As advances in cardiac medicine have evolved, assessment of coronary perfusion has been improved with the use of perfusion imaging using radioactively labeled agents. The commonly used agents include thallium-201 and technetium-99m (sestamibi). These agents are taken up by the myocardium based on coronary blood flow. These agents can be injected following exercise, or if the individual is not able to perform exercise, following a pharmacologic stress test (described later in this chapter).

Thallium-201 Perfusion Imaging Thallium-201 is an excellent perfusion tracer that is injected intravenously and used to assess acute cardiac ischemia as a result of induced physiologic stress from an exercise treadmill test, a pharmacologic-induced exercise test, or when ischemia occurs spontaneously. Thallium imaging assesses blood flow and cell membrane integrity as a result of the thallium being taken up by the myocardium in proportion to the coronary blood flow in the region.147 Cells must be both perfused and metabolically intact in order to accumulate thallium-201. Nonperfused, or dead, myocardium appears as “cold spots” on the scan. When exercise thallium imaging is performed, a patient is exercised to maximal exercise potential and injected with the thallium-201 1 minute before the end of the exercise. Immediately after the exercise test, the patient is scanned using a gamma camera to assess thallium-201 uptake and scanned again 4 hours later after the thallium has been redistributed. An area without thallium uptake (cold spot) immediately after exercise as well as 4 hours afterward is considered irreversibly damaged (scarred). An area that is “cold” following exercise but reperfused 4 hours later is considered “ischemic” or “reversible,” and intervention usually is indicated in such cases (Fig. 8-8). Thallium scanning is used to predict the risk of recurrent acute MI or death after the first acute MI.148-150 The use of thallium can also identify viable myocardium that could

functionally improve with revascularization.151 As cost effectiveness of diagnostic tests is scrutinized in the current health care environment, the sensitivity and specificity of the use of thallium has been studied. Van der Wieken et al reported a high sensitivity (97%) and relatively high specificity (77%) for determining future events when used in individuals with acute chest pain and nondiagnostic ECGs.152 The cost of thallium scanning increases the costs of evaluation of these patients significantly.18 In addition, imaging equipment is available in most institutions. The disadvantages of the use of thallium are related to the fact that it is not an ideal isotope; its low-energy photons are easily scattered and have a half-life of 73 hours. Because of the radiation exposure, the dose injected must be low (approximately 2 to 4 mCi).18 In addition, image scanning must commence within 15 to 20 minutes of the actual thallium injection, and experts in nuclear medicine must be available to perform the test and interpret the results.18

Sestamibi Technetium-99m, or sestamibi (99mTc-sestamibi), sometimes abbreviated as MIBI, has become an alternative perfusion agent to thallium-201.148,149,153,154 Like thallium-201, sestamibi is used to assess acute cardiac ischemia or infarction, and, like thallium, it is taken up by the myocardium in proportion to regional blood flow.18 The tracer can then be imaged under the gamma camera. Whereas thallium washes out of the myocardium in proportion to blood flow, 99mTcsestamibi remains stable, and therefore images of blood flow can be scanned immediately after administration or up to several hours later.149 Sestamibi accumulates in irreversibly damaged myocardial cells and might not demonstrate uptake in an infarction that is only a few hours old. Sestamibi is a marker of cell membrane and mitochondrial integrity, as it requires active processes to occur at the level of the sarcolemma and mitochondrial membrane.155,156 Therefore sestamibi is not retained in acute or chronic MIs. Sestamibi has been demonstrated to be a more practical radioactive isotope because of its stability and has shown sensitivity and specificity for predicting any event to be 94% and 83%, respectively.143 The sensitivity and specificity are 100% and 83%, respectively, in prediction of an acute MI.143 One of the problems with sestamibi is that its accuracy is dependent on the skill of the operator and the knowledge and experience of the interpreter. The use of the isotope is slightly more expensive than the use of thallium-201, but it has demonstrated cost effectiveness in use with patients with nondiagnostic ECGs presenting to the emergency room.145,146 Pharmacologic vasodilation with intravenous dipyridamole has been used in conjunction with sestamibi for diagnostic purposes.82 This procedure can be done either while the patient is resting or in conjunction with exercise. Sestamibi is often used in nonacute cardiac ischemic patients to assess myocardial

contractility by assessing both left and right ventricular ejection fraction, regional function, and ventricular volumes.82 Single-photon emission computed tomography, using newer gated tomographic techniques, can be performed with sestamibi to improve the perfusion study.

Pharmacologic Stress Testing When an individual is unable to perform upright exercise on a treadmill or stationary bicycle due to severity of disease or heart failure, a neuromuscular insult (such as following a cerebrovascular accident), a musculoskeletal disability (e.g., following recent hip or knee surgery, back pain), being of increased age with decreased functional capacity, or an individual who is unable to achieve at least 85% of his or her PMHR on an exercise test (as might occur in individuals taking β-blockers or other negative chronotropic agents that would inhibit the ability to achieve an adequate heart rate response), physiologic stress can be induced while the patient remains in a resting position by injection of a pharmacologic agent. Some centers prefer to use pharmacologic stress testing in conjunction with echocardiogram, MRI, or CT scanning because it avoids repositioning the patient, which may be necessary during nuclear imaging. Repositioning the patient may give a false-positive pharmacologic stress test result because of different degrees of attenuation of myocardial tissue imaging with changes in the breast positions as seen in women. The most common agents that are used in pharmacologic stress testing are adenosine, dipyridamole (Persantine), dobutamine, and, most recently, regadenoson (Lexiscan).82 Both dipyridamole and adenosine induce coronary vasodilation, a physiologic phenomenon that is difficult to produce in diseased coronary arteries, thereby affecting the perfusion image. With adenosine testing, approximately 80% of patients experience minor adverse effects from the adenosine infusion. However, absence of these effects does not imply a lack of efficacy of the adenosine with respect to coronary vasodilation. The chest pain experienced during adenosine infusion is very nonspecific and does not indicate the presence of CAD. However, approximately one third of patients with ischemia after perfusion imaging have ST-segment depression during the infusion of adenosine. Adverse effects with adenosine (and similarly dipyridamole) include dizziness, headache, symptomatic hypotension, dyspnea, and cardiac effects (chest pain or ST changes).82 Dobutamine acts as a stimulant (adrenergic), similar to exercise, and results in an increase in myocardial oxygen demand with the purpose of assessing myocardial oxygen supply. A dose-related increase in both heart rate and systolic blood pressure occurs with dobutamine. However, diastolic pressure falls as the dose of dobutamine increases. These hemodynamic changes are similar to those of exercise stress. Adverse effects occur in approximately 75% of patients undergoing dobutamine stress testing. These adverse side effects include ST changes (50%), chest pain (31%), palpitations (29%), and significant supraventricular or ventricular arrhythmias (8% to 10%). Typically, adverse effects requiring early termination subside within 5 to 10 minutes of discontinuation of the infusion (the half-life of dobutamine is 2 minutes). The effect of dobutamine can be reversed with β-blockers. Typically, an intravenous agent with an ultrashort half-life, such as esmolol, is used. Because most patients who undergo dobutamine stress testing have bronchospastic lung disease, β-blockers should be used with caution. See Box 8-8 for absolute and relative contraindications to pharmacologic stress testing.157

Regadenoson (Lexiscan) is a new pharmacologic stress agent approved by the FDA in 2008 as an additional agent for use in stress testing for patients unable to perform the standard exercise stress test.157 Regadenoson produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for radionuclide myocardial perfusion imaging. Regadenoson requires a simple rapid bolus administration and has a short duration of hyperemic effect, which is advantageous for a pharmacologic test.

Adenosine or Dipyridamole–Walk Protocol For patients who are able, combined low-level treadmill exercise during adenosine infusion has been demonstrated in several reports to be associated with a significant decrease in the frequency of adverse effects (e.g., flushing, nausea, headache). In addition, less symptomatic hypotension and bradycardia occur. An additional advantage is that simultaneous low-level exercise allows for immediate imaging, as would be performed with exercise stress testing. This is due to the peripheral vasodilation and splanchnic vasoconstriction induced by exercise. Safety of stress testing with pharmacologic agents is equivalent to the safety found in exercise testing. Safety in testing has been demonstrated in all populations, including those patients with diabetes, as long as similar pretest and monitoring procedures are followed as in exercise testing.158 In addition, pharmacologic stress testing has been shown to be safe in patients who have undergone thrombolysis following acute MI as soon as 2 to 5 days after initiation of thrombolysis.157,159 The sensitivity of dipyridamole SPECT imaging, 89% (95% CI = 84% to 93%), was higher than that of dipyridamole echocardiography, but the specificity of dipyridamole SPECT imaging, 65% (95% CI = 54% to 74%), was lower than that of dipyridamole echocardiography. Dipyridamole and adenosine tests had similar sensitivities and specificities. The sensitivity of dobutamine echocardiography, 80% (95% CI = 77% to 83%), was similar to that of dobutamine SPECT imaging, but dobutamine echocardiography had a higher specificity, 84% (95% CI = 80% to 86%), than dobutamine SPECT imaging did.157

BO X 8- 8 Absolut e a nd re la t ive cont ra indica t ions t o

pha rm a cologic st re ss t e st ing

Absolute Relative Patients with ac tive bronc hospasm or patients being treated for reac tive airway disease Patients with a remote history of reac tive airway disease should not be administered adenosine bec ause this c an lead to prolonged bronc hospasm, (COPD/asthma) that has been quiesc ent for a long time whic h c an be diffic ult to treat or c an remain refrac tory. (approximately 1 year) may be c andidates for adenosine. Patients with more than first-degree heart bloc k (without a ventric ular-demand pac emaker) However, if a question exists c onc erning the status of the should not undergo adenosine infusion bec ause this may lead to worsening of the heart patient’s airway disease, a dobutamine stress test may be the bloc k. Although this is usually transient, bec ause of the extremely short half-life of safer c hoic e. adenosine (approximately 6 sec onds), c ases of prolonged heart bloc k (and asystole) have Patients with a history of sic k sinus syndrome (without a been reported. ventric ular-demand pac emaker) should undergo adenosine Patients with an S BP 1.10 0.5 to 1.0 0.2 to 0.5

P ossible symptoms None Claudic ation Critic al limb isc hemia

Clinical presentation Normal Pain in c alf with ambulation Atrophic c hanges Rest pain Wounds

0.5 second). The name relates to its presentation by twisting around the isoelectric line. This arrhythmia characteristically occurs at a rapid rate and terminates spontaneously.

Signs, Symptoms, and Causes This type of ventricular tachycardia has been identified only in individuals receiving antiarrhythmic therapy and for whom the medication is toxic. Because cardiac output is severely diminished and this arrhythmia often converts to ventricular fibrillation, this condition is considered a medical emergency.1 The individual who remains conscious with this arrhythmia may be extremely lightheaded or near syncope.

Treatment Treatment is usually cardioversion.

Ventricular Fibrillation Ventricular fibrillation is defined as an erratic quivering of the ventricular muscle resulting in no cardiac output. As in atrial fibrillation, multiple ectopic foci fire, creating asynchrony. The ECG results in a picture of grossly irregular up and down fluctuations of the baseline in an irregular zigzag pattern (Fig. 9-42).

Signs, Symptoms, and Causes The causes of ventricular fibrillation are the same as those of ventricular tachycardia because ventricular fibrillation is usually the sequel to ventricular tachycardia.

Treatment Treatment is defibrillation as quickly as possible followed by cardiopulmonary resuscitation, supplemental oxygen, and injection of medications. An example of defibrillation during firing of an implantable cardiac defibrillator (ICD) is shown in Fig. 9-43. However, if the tracing appears to be ventricular fibrillation, the patient does not have a long-term history of recurrent ventricular tachycardia or ventricular fibrillation, and the patient is able to carry on a conversation, the therapist should assume this is probably only lead displacement creating an artifact.

FIGURE 9-43 Tiered arrhythmia therapy and implanted cardioverter defibrillators (ICDs). These devices are capable of automatically delivering staged therapy in treating ventricular tachycardia (VT) or ventricular fibrillation (VF), including antitachycardia pacing (A) and cardioversion shocks (B) for VT, and defibrillation shocks (C) for VF. (From Goldberger AL. Clinical Electrocardiography: A Simplified Approach, ed 7, St. Louis, 2006, Mosby.)

Other Findings on a 12-Lead Electrocardiogram Hypertrophy Hypertrophy refers to an increase in thickness of cardiac muscle or chamber size. Signs of atrial hypertrophy can be noted by examining the P waves of the ECG for a diphasic P wave in the chest lead V1, or a voltage in excess of 3 mV. Signs of right ventricular hypertrophy are noted by changes found in lead V1 that include a large R wave and an S wave smaller than the R wave. The R wave becomes progressively smaller in the successive chest leads (V2, V3, V4, V5). Hypertrophy of the left ventricle creates enlarged QRS complexes in the chest leads in both height of the QRS (R wave) and depth of the QRS (S wave). In left ventricular hypertrophy a deep S wave occurs in V1 and a large R wave in V5. If, when the depth of the S wave in V1 (in mm) is added to the height of the R wave in V5 (in mm) the resulting number is greater than 35, then left ventricular hypertrophy is present (Fig. 9-44).

Ischemia, Infarction, or Injury A review of a 12-lead ECG to detect ischemia, infarction, or injury is performed in a variety of situations, including after any episode of chest pain that brings a patient to the physician’s office or to the hospital, during hospitalization, during a follow-up examination after a cardiac event, or before conducting an exercise test. The difference between ischemia and infarction is covered in detail in Chapter 3. In simplistic terms, ischemia literally means reduced blood and refers to a diminished blood supply to the myocardium. This can occur because of occlusion of the coronary arteries from vasospasm, atherosclerotic occlusion, thrombus, or a combination of the three. Infarction means cell death and results from a complete occlusion of a coronary artery. Injury indicates the acuteness of the infarction. As a result of ischemia, injury, or infarction, conduction of electrical impulses is altered, and therefore depolarization of the muscle changes. As the ECG records the depolarization of the cardiac muscle, changes occur on the ECG in the presence of ischemia, infarction, or injury. The location of the ischemia, infarction, or injury is determined according to the specific leads of the ECG that demonstrate an alteration in depolarization. Ischemia is classically demonstrated on the 12-lead ECG with T-wave inversion or STsegment depression. The T wave may vary from a flat configuration to a depressed inverted wave (Fig. 9-45). The T wave is an extremely sensitive indication of changes in repolarization activity within the ventricles.8 Transient fluctuations in the T wave can be observed in numerous situations and must be associated with the activity and symptoms to determine whether the abnormality is ischemic. For an individual who comes to a physician’s office because of an episode of chest pain, T-wave inversion may be the only noticeable abnormality. If the individual took nitroglycerin while at the office and the pain disappeared before the ECG was administered, abnormalities may be absent due to the resolution of the ischemic event.

The location of the ST segment (that portion of the ECG tracing beginning with the end of the S wave and ending with the beginning of the T wave) is another indication of ischemia or injury. Elevation of the ST segment above the baseline when following part of an R wave indicates acute injury (Fig. 9-46). In the presence of acute infarction, the ST segment elevates and then later returns to the level of the baseline (within 24 to 48 hours).8 ST-segment elevation may also occur in the presence of a ventricular aneurysm (a ballooning out of the ventricular wall, usually following a large amount of damage to the ventricular wall). The ST-segment elevation with ventricular aneurysm never returns to the isoelectric line, and the configuration differs somewhat. The ST-segment elevation in ventricular aneurysm usually follows a large Q wave and not an R wave of the QRS complex (see Fig. 9-46). If the ECG records the presence of ST-segment elevation in the presence of acute onset of chest pain (within hours), a cardiac emergency exists and immediate treatment is indicated.

FIGURE 9-44 Hypertrophy is determined by looking at voltage in V1 and V5. Right ventricular hypertrophy is defined as a large R wave in V1, which gets progressively smaller in V2, V3, and V4; normally there is a very small R wave and a large S wave in V1. Left ventricular hypertrophy is defined as a large S wave in V1 and a large R wave in V5 that have a combined voltage of greater than 35 mV.

FIGURE 9-45 Electrocardiogram tracing showing an inverted T wave, often indicating ischemia (arrows).

The ECG may demonstrate ST-segment depression while the patient is at rest in the presence of chest pain or of suspected coronary ischemia. The ST-segment depression in this situation represents subendocardial infarction and also requires immediate treatment. A subendocardial infarct (also called a nontransmural, non–Q-wave infarct, or non–ST-segment elevation myocardial infarction [STEMI] infarct) is an acute injury to the myocardial wall, but it does not extend through the full thickness of the ventricular wall. Instead, the injury is only to the subendocardium (Fig. 9-47). This ECG sign is extremely significant, because it indicates that a transmural (also called STEMI or Q-wave) infarction could be pending. Research shows that an individual diagnosed with a subendocardial infarction is at extremely high risk for another infarction (this time transmural) within 6 weeks.9 Other situations may precipitate ST-segment depression. ST-segment depression in the absence of suspected ischemia or angina may be caused by digitalis toxicity (see Chapter 14 for discussion of digitalis toxicity). ST-segment depression that develops during exercise, as seen during exercise testing, is defined as an ischemic response to exercise, and following rest it should return to the isoelectric line. This is an abnormal response to exercise that indicates an impaired coronary arterial supply during the exercise. This type of ischemic response should be further evaluated to determine the extent of the coronary artery involvement (see Chapter 8). During myocardial injury, the affected area of muscle loses its ability to generate electrical impulses, and therefore alterations in the initial portion of the QRS complex occur. The cells are dead and cannot depolarize normally, which results in an inability to conduct impulses. Therefore because ST-segment elevation or depression is diagnostic for acute infarction, the presence of a significant Q wave (Fig. 9-48) is also diagnostic for infarction, but the date of the infarction is not able to be determined simply by studying the ECG. The date of the infarction is determined by the patient’s report of symptoms. The Q wave is the first downward part of the QRS complex (not preceded by anything else), and small Q waves may be present normally in some leads. When the Q wave is 0.06 second in duration wide (one small square on the ECG tracing) or is one-third the size (height and depth included) of the QRS complex, the Q wave is considered significant and indicative of a pathologic condition (it persists as a permanent electrocardiographic “scar ” from infarction [see Fig. 9-48]). Therefore any scan of the ECG should include a check for the presence of significant Q waves to identify previous infarction.

FIGURE 9-46 Acute inferior myocardial infarction with ST elevation in the inferior leads. (From Rakel RE: Textb ook of Family Medicine, ed 7, Philadelphia, 2007, Saunders.)

FIGURE 9-47 An ST segment on a resting 12-lead ECG often is indicative of subendocardial injury. A, Normal tracing and normal ventricular wall. B, Subendocardial ischemia with an ECG tracing of Twave inversion. C, Subendocardial injury with ST-segment depression on the ECG.

The leads that demonstrate the presence of T-wave inversion, ST-segment changes, or Q waves identify the location of the ischemia, injury, or infarction. The presence of significant Q waves in the chest leads, particularly in V1, V2, V3, and V4, indicates an infarction in the anterior portion of the left ventricle. When only V1 and V2 are involved, these infarctions are often called septal infarctions because they primarily affect the interventricular septum. Anterior infarctions are easy to recognize if one remembers that the chest leads are placed on the anterior aspect of the left ventricle (Fig. 9-49). Referring back to Chapter 1, remember that because the left anterior descending artery primarily supplies the anterior aspect of the heart, an anterior infarction implies an occlusion somewhere in the left anterior descending artery. An inferior infarction is identified by significant Q waves in leads II, III, and aVF (Fig. 9-50, A). Inferior infarctions are also referred to as diaphragmatic infarctions because the inferior wall of the heart rests on the diaphragm. Given that the right coronary artery primarily supplies the inferior aspect of the myocardium, an inferior infarction implies an occlusion somewhere in the right coronary artery. A lateral infarction demonstrates Q waves in leads I and aVL (Fig. 9-50, B). Because the circumflex artery supplies primarily the lateral and posterior aspects of the myocardium, an occlusion of the circumflex artery is suspected in a lateral infarction.

FIGURE 9-48 A significant Q wave is defined as a minimum of one small square wide and one-third the height of the QRS. In this electrocardiogram tracing, notice the Q waves in leads II, III, and aVF and in V1, V2, V3, and V4.

FIGURE 9-49 A 12-lead electrocardiogram tracing demonstrating an anterior infarction. Note the significant Q waves in V1, V2, and V3 and the inverted T waves throughout many other leads.

Probably the most difficult infarction to detect is the posterior infarction because none of the 12 leads is directly measuring the posterior aspect of the heart. Only two leads detect posterior infarcts—V1 and V2—as they measure the direct opposite wall (anterior). Therefore the direct opposite ECG tracing of an anterior infarction in V1 and V2 should be the ECG tracing of the posterior infarction. An anterior infarction demonstrates a significant Q wave in V1 and V2 with ST-segment elevation. The mirror image of this is

seen in Fig. 9-51, which demonstrates a large R wave in V1 or V2 and ST-segment depression. Given that the posterior aspect of the myocardium may be supplied by either the right coronary artery or the circumflex artery, a posterior infarction may indicate a problem in either one of these arteries. If changes in the lateral leads (e.g., I, aVL) also exist, then the circumflex artery is probably involved. However, if changes in the inferior leads exist (e.g., II, III, aVR) as well as posterior changes, then the right coronary artery is probably involved.8

FIGURE 9-50 A, A 12-lead electrocardiogram tracing demonstrating an inferior infarction. Notice the significant Q waves in leads II, III, and aVF. B, A 12-lead electrocardiogram tracing demonstrating a lateral infarction. Notice the significant Q waves in I and V5 with inverted T waves in aVL as well.

Caution should be taken when evaluation of an ECG for an infarction is performed in the presence of left bundle branch block.8 Identification of significant Q waves can be difficult if the conduction is delayed throughout the myocardium on the left side. Conduction may be delayed through the myocardium due to a dysfunction in the conduction system that is secondary to genetic defect, injury, or infarction. An example of

conduction delay with bundle branch block occurs when a block of the impulse occurs in the right or left bundle branch. A bundle branch block creates a delay of the electrical impulse to the side that is blocked, creating a delay in the depolarization of the myocardium that would have received the blocked impulse. When the left and right sides do not depolarize simultaneously, a widened QRS appearance is seen on the ECG tracing and sometimes two R waves. In the case of left bundle branch block, the left side of the myocardium demonstrates delayed depolarization, thereby allowing the right side of the myocardium to depolarize first and hiding any possible significant Q waves coming from the left ventricle (Fig. 9-52).

FIGURE 9-51 A 12-lead electrocardiogram tracing demonstrating a posterior infarction. Notice the large R waves in V1 and V2 and the inverted T waves in the same leads.

FIGURE 9-52 A, A rhythm strip demonstrating a left bundle branch block. Note the widened QRS interval. B, A left bundle branch block.

A systematic review of the 12-lead ECG will improve one’s ability to interpret the 12lead ECG correctly. A systematic approach includes the following: ▪ Identify and separate the 12 leads by applying vertical lines between leads I and avR, avR and V1, and V1 and V4. ▪ Scan all leads to identify if there are any significant Q waves. If so, note which leads demonstrate a significant Q wave. ▪ Scan all leads to identify if there is any ST elevation or ST depression. If so, note which leads demonstrate ST changes.

FIGURE 9-53 Acute pericarditis. In the first few days, the ECG shows ST elevation, concave upward, with upright T waves in most leads. Classically it is more obvious in lead II than in leads I or III. There are no pathologic Q waves, and the widespread distribution of ST–T changes without reciprocal depression distinguishes acute pericarditis from early myocardial infarction. In the later stages of pericarditis, the T waves become inverted in most leads. The ECG changes in pericarditis are caused by the superficial myocarditis that accompanies it.

FIGURE 9-54 AV sequential pacing. A, Atrial pacing; V, ventricular pacing; AV, AV interval. (From Aehlert BJ: ACLS study guide, ed 3, St Louis, 2007, Mosby.)

FIGURE 9-55 Dual-chamber (DDD) pacemakers sense and pace in both atria and ventricles. The pacemaker emits a stimulus (spike) whenever a native P wave or QRS complex is not sensed within some programmed time interval. (From Goldberger AL: Clinical electrocardiography: a simplified approach, ed 7, Philadelphia, 2007, Mosby.)

▪ Scan leads V1, V5, and V6 to look for ventricular hypertrophy. A large R in V1 indicates R ventricular hypertrophy, and a deep S in V1 with a large R in V5 indicates left ventricular hypertrophy. Acute pericarditis is a condition that causes ECG changes that differ from those caused by ischemia and infarction. These ECG changes are important to mention because they assist in the diagnosis of the condition. Acute pericarditis, defined as an inflammation of the pericardial sac, is often a complication following myocardial infarction and open heart surgery. Pericardial pain is usually intense but can closely mimic angina in location. The pain is usually aggravated or relieved by respiration and change of position. The ECG findings include ST-segment elevation, PR interval depression, late T-wave inversion, and atrial arrhythmias (often supraventricular tachycardia) (Fig. 9-53). The symptoms and the ECG changes are often all that is needed for diagnosis. In addition, a pericardial rub may be present during auscultation of the heart sounds. Other abnormalities may exist on the ECG, including pacemaker functioning (Figs. 9-

54 and 9-55), which is discussed in Chapter 11, and axis deviation. These abnormalities are beyond the scope of this chapter.

Case study 9-1 A 68-year-old man has a history of an acute myocardial infarction that occurred 7 months ago. He subsequently underwent coronary artery bypass graft surgery exactly 1 month after the myocardial infarction. It is now 6 months since his surgery, and he is symptom free. His goal is to return to his previously active lifestyle, so he was referred for an evaluation and exercise program. On evaluation, his heart rate is 70 beats per minute, blood pressure is 124/84 mm Hg, and ECG is NSR. During the exercise treadmill test, he exercised at 2.5 miles per hour with 12% grade but complained of dizziness at 4.5 minutes of the exercise test. His heart rate was 110 beats per minute and blood pressure was 130/78 mm Hg. The ECG rhythm showed a sudden onset of PVCs and a run of ventricular tachycardia. After the exercise was terminated, his rhythm slowed down to frequent PVCs and then NSR.

Discussion This case demonstrates changes in the heart rhythm with increased activity. Premature ventricular complexes and then ventricular tachycardia occurred with increased activity, corresponding to increased irritability of the myocardium (i.e., probably secondary to ischemia). The individual was symptomatic when the arrhythmias were frequent. This patient should not be exercising to a heart rate of 110 beats per minute and may need further evaluation for the abnormal response with exercise.

Summary ▪ Four cell types exist in the myocardium: working or mechanical cells, nodal cells, transitional cells, and Purkinje cells. ▪ Depolarization of the cell membrane allows the influx of sodium ions into the cell and the efflux of potassium ions. ▪ As the cell becomes positive on the interior, the myocardial cells are stimulated to contract (called excitation coupling). ▪ On the ECG, the wave of depolarization is recorded as an upward deflection when moving toward a positive electrode located on the skin. ▪ The cardiac muscle has three properties: automaticity, rhythmicity, and conductivity. ▪ The autonomic nervous system has a major influence on the cardiac system. Stimulation of the sympathetic division increases the heart rate, conduction velocity, and contractile force, and stimulation of the parasympathetic division (acting primarily via the vagal nerve) slows the heart rate and the conduction through the AV node. ▪ The conduction system involves the spread of a stimulus via the SA node (primary pacemaker), internodal pathways, AV node, His bundle, bundle branches, and Purkinje fibers. ▪ The ECG records the electrical activity of the heart on ruled graph paper. Time is represented on the horizontal axis, and each small square is 0.04 second. Voltage is recorded on the vertical axis, and each small square is 1 mm. ▪ A standard 12-lead ECG consists of 6 limb leads and 6 chest leads, each recording the electrical activity from a different angle and providing a different view of the same activity in the heart. ▪ The ECG is reviewed to identify four areas that require interpretation: heart rate, heart rhythm, hypertrophy, and infarction. ▪ Numerous methods can be employed to measure heart rate from the ECG tracing, but often the 6-second strip method is the easiest if the rhythm is regular. ▪ Hypertrophy is detected on a 12-lead ECG by looking at the waveforms, particularly at the P wave and QRS complex for the voltage (greater than 3 mV) or configuration. ▪ Left ventricular hypertrophy is present if the depth of the S wave in V1 plus the height of the R wave in V5 is greater than 35 mm. ▪ In the presence of acute injury, the ST segment is elevated above the isoelectric line and gradually returns to the level of the isoelectric line over a period of 24 to 48 hours. ▪ In ventricular aneurysm, the ST segment remains elevated and does not return to the isoelectric line over time. ▪ ST-segment depression at rest associated with chest pain may indicate acute injury to the subendocardial wall. ▪ ST-segment depression that develops during exercise is an ischemic response to activity and following rest should return to the baseline. ▪ The presence of a significant Q wave is diagnostic for an infarction, but the date of the infarction cannot be determined from the ECG. ▪ A significant Q wave is 1 mm wide or one-third the size of the QRS complex.

▪ A 12-lead ECG is used primarily for determining ischemia or infarction. Single-lead monitoring is employed for evaluating heart rate or rhythm. ▪ The location of the infarction is determined by the leads on the 12-lead ECG that demonstrate changes. ▪ The presence of significant Q waves in V1 through V4 indicates an anterior infarction and probable involvement of the left anterior descending coronary artery. ▪ The presence of significant Q waves in II, III, and aVF indicates an inferior infarction and probable involvement of the right coronary artery. ▪ A systematic approach should be taken when evaluating the rhythm strip. All the waveform configurations should be evaluated, as well as the PR intervals, the QRS intervals, the RR intervals, and the rate to assess the rhythm disturbance. ▪ Following identification of the rhythm disturbance, an assessment of signs and symptoms should be undertaken, after which a clinical decision can be made regarding the amount of monitoring the individual will need with activity, as well as the safety of activity.

References 1. Cohen M, Fuster V. Insights into the pathogenetic mechanisms of unstable angina. Haemostasis. 1990;20(Suppl 1):102–112. 2. Schaper J, Schaper W. Time course of myocardial necrosis. Cardiovasc Drugs Ther. 1988;2(1):17–25. 3. Bekn Haim S.A, Becker B, Edoute Y, et al. Beat to beat electrocardiographic morphology variation in healed myocardial infarction. Am J Cardiol. 1991;68(8):725–728. 4. Phillips R.E, Feeney M.K. The Cardiac Rhythms: A Systematic Approach to Interpretation. ed 3. Philadelphia: Saunders; 1990. 5. Scheidt S. Basic Electrocardiography: Leads, Axes, Arrhythmias. Summit, NJ: CIBA Clinical Symposia; 1983. 6. Berne R.M, Levy M.N. Cardiovascular Physiology. ed 6. St. Louis: Mosby-Year Book; 1992. 7. Grauer K, Curry R.W. Clinical Electrocardiography: A Primary Care Approach. ed 2. Boston: Blackwell Scientific Publishers; 1992. 8. Abedin Z, Conner R.P. 12-Lead ECG Interpretation: The Self-Assessment Approach. Philadelphia: Saunders; 1989. 9. Valle B.K, Lemberg L. Non-Q wave versus nontransmural infarction. Heart Lung. 1990;19(2):208–211.

Pulmonary diagnostic tests and procedures Ana Lotshaw, Traci Tiemann Betts, and Ellen Hillegass

CHAPTER OUTLINE Chest Imaging 338 Chest Radiographs 338 Computed Tomography 344 Magnetic Resonance Imaging 345 Ventilation and Perfusion Scans 345 Bronchoscopy 346 Pulmonary Function Testing 346 Tests of Lung Volume and Capacity 347 Tests of Gas Flow Rates 350 Tests of Diffusion 351 Additional Tests of Gas Exchange 351 Flow-Volume Loop 352 Interpretation of Basic Pulmonary Function Test Results 352 Blood Gas Analysis 352 Normal Values 352 Adequacy of Alveolar Ventilation 354 Acid–Base Balance 355 Henderson–Hasselbalch Equation 355 Acid–Base Terminology 355 Interpreting Arterial Blood Gases 355 Assessing Oxygenation and Hypoxemic Status 356 Oximetry 357 Cytologic and Hematologic Tests 357 Case study 10-1 360 Summary 361 References 362

This chapter introduces the reader to several of the diagnostic tests and procedures commonly used in the assessment of patients with pulmonary disease. Although the tests and procedures described in this chapter may not necessarily be performed by physical therapists, they nonetheless provide physical therapists with invaluable information. To apply this information to the planning, implementation, and monitoring of patient treatments, physical therapists must have a fundamental understanding of chest imaging, pulmonary function testing, bronchoscopy, arterial blood gas analysis, oximetry, and bacteriologic and cytologic tests. Chapter 17 discusses the incorporation of this information in the evaluative process.

Chest Imaging Largely as a result of new technologies, but also because of refinements in older techniques, there are now several imaging options in addition to the standard “plain film” radiograph. It is certainly beyond the scope of this text to present all the abnormal chest findings identifiable by these imaging techniques. Rather, this information is intended to assist in the development of a framework on which to build an understanding of these imaging techniques. A basic knowledge of how these images are produced and what they display can facilitate physician–therapist dialogue and enhance physical therapy treatment planning.

Chest Radiographs Despite the availability of newer methods, in most clinical settings the standard radiograph (chest x-ray [CXR]) remains the predominant diagnostic test to determine anatomic abnormalities and pathologic processes within the chest. The newer, more technologically advanced imaging techniques are discussed in this chapter in their role to confirm or provide differential diagnostic information that can contribute to information obtained from a chest radiograph. The standard upright views of the chest are made when a patient is typically placed between an x-ray source and a cassette (Fig. 10-1). When the x-rays penetrate the tissues of the patient, they stimulate the fluorescent screen to emit light that exposes the film. The radiograph thus produced is referred to as a roentgenogram, named after Wilhelm Konrad Roentgen, who received the first Nobel Prize for Physics in 1901 for his work in defining the major properties of x-rays and the conditions necessary for their production. It was Roentgen who coined the term “x-ray.”1–4

FIGURE 10-1 For a standard posteroanterior radiograph, the patient stands between the film cassette and x-ray source.

Chest radiographs provide a static view of the anatomy of the chest, and as such, they may be used to screen for abnormalities, to provide a baseline from which subsequent assessments can be made, or to monitor the progress of a disease process or treatment intervention. The principal objects shown on a chest radiograph are air, fat, water, tissue, and bone. Air in the lungs has a very low density and thus allows greater x-ray penetration, resulting in a dark image on the radiograph (radiolucency). At the opposite extreme is bone, which, because it is denser, allows fewer x-rays to penetrate and results in a white image on a radiograph (radiopacity). Depending on the densities and thicknesses of the numerous structures in the chest, the x-rays penetrating a patient are variably absorbed and create “shadows” on the radiographic film. Several other factors also affect the image depicted on a radiographic film, but are beyond the scope of this chapter. The reader is referred to standard radiology texts for more detailed information. The standard chest radiograph is routinely taken in two views at near total lung capacity: (1) a posteroanterior (PA) view with the patient in the standing position with the front of the chest facing the film cassette (Fig. 10-2) and (2) a left lateral view (Fig. 10-

3), unless the pathologic process is known to be present on the right side of the chest (in which case, a right lateral view would be obtained). The lateral view is extremely helpful in localizing the position of an abnormality, because in the PA view, the upper and middle lobes of the lung override portions of the lower lobes. Other views that can be obtained include the following: ▪ Decubitus views are taken to confirm the presence of an air–fluid level in the lungs or a small pleural effusion. Depending on the location of the suspected disease, the patient is placed in the supine, prone, or right or left side-lying position. ▪ The lordotic view is used to visualize the apical or middle (right middle lobe or left lingular segments) region of the lungs, or specifically to screen for pulmonary tuberculosis, which typically manifests itself in the apical regions. The x-ray source is lowered and angled upward, and the patient may or may not be tipped slightly backward. ▪ Oblique views are taken to detect pleural thickening, to evaluate the carina, or to visualize the heart and great vessels. The patient is positioned standing diagonally (at an angle of 45 to 60 degrees to the film) with either the left or right anterior, or the left or right posterior, chest against the film cassette (anterior or posterior oblique views, respectively). ▪ The anteroposterior (AP) view is taken at the patient’s bedside when the patient is unable to travel to the radiology department. AP radiographs are obtained with the patient either supine, semirecumbent, or sitting upright against the film cassette and facing the x-ray machine. When the film is taken in the supine position, the abdominal contents tend to elevate the hemidiaphragms, the pulmonary blood flow is redistributed, and the mediastinal structures appear larger (Fig. 10-4).

Clinical tip Positioning for AP views (supine or semirecumbent) often result in a poor inspiratory effort, especially when the patient is critically ill. Clinicians observing AP films must keep this in mind when assessing the film. The potential interpreter of radiographs is presented with several challenges, among these are the two-dimensional representation of three-dimensional objects and the limited gray-scale “shadow” depiction of the various organs, tissues, and pathologic processes. Although it may be more likely that the clinician will have access to a radiologist’s report rather than the actual radiograph, many clinical settings offer the therapist direct access to a patient’s chest radiographs and with electronic medical records CXRs are now readily accessible in the chart. Consequently, therapists should be familiar with the manner in which chest radiographs are assessed.

Examining Chest Radiographs Although there is no single “best” method for examining chest radiographs, a systematic

approach should be used. One approach entails starting at the center of the film and working outward toward the soft tissues. Another method involves starting with an examination of the bones and soft tissues, including the abdomen; the mediastinum from the larynx to the abdomen; the cardiovascular system; the hila; and finally the lung fields themselves. Independent of the method of examination, the mediastinum and hila are typically assessed for abnormal vasculature or mass lesions, the heart for changes in shape or position, and the lungs for abnormal increased density or lucency. By convention, frontal chest radiographs should be viewed as if the patient’s right side was on your left side, as if you were facing each other. The left lateral chest radiograph should be viewed as if the patient’s left side was facing you; the reverse is true for the right lateral view. Box 10-1 provides a systematic approach to assessment of a portable chest radiograph.

FIGURE 10-2 A, Normal chest radiograph, posteroanterior view. B, Same radiograph as in (A), with the normal anatomic structures labeled or numbered: 1, trachea; 2, right mainstem bronchus; 3, left mainstem bronchus; 4, left pulmonary artery; 5, pulmonary vein to the right upper lobe; 6, right interlobular artery; 7, vein to right middle and lower lobes; 8, aortic knob; 9, superior vena cava. (From Fraser RG, Paré JAP: Diagnosis of Diseases of the Chest, vol 1, ed 2, Philadelphia, 1977, Saunders, pp 172-173.)

FIGURE 10-3 A, Normal chest radiograph, lateral view. B, Same radiograph as in (A), with the normal anatomic structures labeled or numbered: 1, trachea; 2, right intermediate bronchus; 3, left upper lobe bronchus; 4, right upper lobe bronchus; 5, left interlobar artery; 6, right interlobar artery; 7, junction of the pulmonary veins; 8, aortic arch; 9, brachiocephalic vessels. (From Fraser RG, Paré JAP: Diagnosis of Diseases of the Chest, vol 1, ed 2, Philadelphia, 1977, Saunders, pp 174-175.)

In the body systems approach to examining chest radiographs, the overall adequacy of the image should first be addressed. The optimal radiograph should be taken with the patient holding a deep inspiration. Furthermore, the entire chest should be visible on the radiograph (see Fig. 10-2). Then, the following should be considered in turn.

Bones and Soft Tissues The size, shape, and symmetry of the bony thorax should be considered; the vertebral

bodies should be faintly visible through the mediastinal shadow, and all of the other bones of the thorax should be included on the radiograph. To determine whether or not the patient is rotated to either side, the medial ends of each clavicle should be checked to see that they are equally distant from the spinous processes of the vertebral bodies (if the patient is rotated, the distances between the medial ends of the clavicles and the spinous processes will be unequal). In a PA film the clavicles often appear to be lower than in an AP film. Because of the position of the shoulders, the medial aspect of the scapulas is typically lateral to and outside the lung fields in a PA film; whereas, in an AP film, the medial borders may appear as vertical or oblique lines within the lung fields. The various densities of the soft tissues (skin, subcutaneous fat, and muscle) normally blend together—called the summation effect. The width of the intercostal spaces should be considered because widened intercostal spaces may be indicative of increased thoracic volume (the best way to gain an appreciation of the normal intercostal space width is to review normal chest radiographs). The two hemidiaphragms should appear as rounded, smooth, sharply defined shadows; the dome of the right hemidiaphragm is normally 1 to 2 cm higher than the left. The diaphragm is said to be elevated if, during a deep inhalation, fewer than nine ribs are visible above the level of the domes; depressed if more than 10 ribs are visible. Where the hemidiaphragms meet the chest wall at their lateral aspects, the costophrenic angles are formed. The costophrenic angles are moderately deep, and they are approximately equal in size on the two sides. Opacification of the costophrenic angle is indicative of either pleural thickening (if the change has occurred over many months or years) or a pleural effusion (if the change has occurred recently). Medially, the hemidiaphragms normally form a cardiophrenic angle where they meet the borders of the heart.

FIGURE 10-4 Summation of the effect of position, projection, and respiration. A normal posteroanterior upright chest radiograph with full inspiration (A). Another radiograph was taken of this perfectly healthy college student 1 minute later; it was done in an anteroposterior projection while he was lying supine and during expiration (B). The wide cardiac shadow and prominent pulmonary vascularity could easily trick you into thinking that this individual was in congestive heart failure. (From Mettler FA: Essentials of Radiology, ed 2, Philadelphia, 2005, Saunders.)

BO X 10- 1 A systematic approach is essential for interpreting the portable chest radiograph. The steps are as follows: • Assess the technical quality of the study. • Evaluate the location of all catheters, tubes, and hemodynamic support devices. • Assess the cardiovascular status of the patient. • Check for abnormal parenchymal opacities. • Search for evidence of barotrauma. • Look for pleural effusions. • Compare with the prior studies; does the patient look the same, better, or worse?

Mediastinum, Trachea, and Cardiovascular System The size of the mediastinum varies with body size, ranging from long and narrow in tall, thin persons to short and wide in short, stocky persons. The borders of the mediastinum include the sternum, spine, clavicles and diaphragm muscle. The trachea normally appears as a vertical translucent shadow superimposed on the mediastinal shadow in the midline, overlying the cervical vertebrae. In most cases, tracheal deviation from the midline position suggests that the patient is rotated. However, pathologic conditions can also result in tracheal deviation. For example, a large pneumothorax can push the trachea toward the contralateral side of the chest, or a massive atelectasis can pull the trachea toward t

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