Handbook of Pathophysiology (January 15, 2001): by Springhouse Corporation, With 13 Contributors, Springhouse By OkDoKeY Handbook of Pathophysiology Contents Staff Contributors

Foreword 1 FUNDAMENTALS OF PATHOPHYSIOLOGY 2 CANCER 3 INFECTION 4 GENETICS 5 FLUIDS AND ELECTROLYTES 6 CARDIOVASCULAR SYSTEM 7 RESPIRATORY SYSTEM 8 NERVOUS SYSTEM 9 GASTROINTESTINAL SYSTEM Pathophysiology in color Understanding Asthma Understanding Cancer Understanding Osteoporosis Understanding Ulcers 10 MUSCULOSKELETAL SYSTEM 11 HEMATOLOGIC SYSTEM 12 IMMUNE SYSTEM 13 ENDOCRINE SYSTEM 14 RENAL SYSTEM 15 SENSORY SYSTEM 16 INTEGUMENTARY SYSTEM 17 REPRODUCTIVE SYSTEM Appendix: Less common disorders Selected references Contributors Gary J. Arnold, MD, FACS Assistant Professor of Nursing University of Louisiana at Lafayette Lafayette, LA Deborah Becker, MSN, CRNP, CS, CCRN Lecturer, Adult Acute Care Practitioner Program University of Pennsylvania Philadelphia, PA Marcy S. Caplin, RN, MSN Independent Nurse Consultant Hudson, OH Susan B. Dickey, PhD, RN,C Associate Professor Temple University Philadelphia, PA Kay Gentieu, RN, MSN, CRNP Coordinator Family Nurse Practitioner Program Thomas Jefferson University Philadelphia, PA H. Dean Krimmel, RN, MSN Independent Nurse Consultant Collingdale, PA Nancy LaPlante, RN, BSN

RN-Staff Nurse Emergency Department The Chester County Hospital West Chester, PA Kay Luft, RN, MN, CCRN, TNCC Assistant Professor Saint Luke's College Kansas City, MO Elaine Mohn-Brown, EdD, RN Professor, Nursing Chemeketa Community College Salem, OR Roger M. Morrell, MD, PhD, FACP, FAIC Neurologist Lathrup Village, MI David Toub, MD Consultant Lansdale, PA Tracy S. Weintraub, RN, MSN, CNS Instructor of Clinical Nursing University of Southern California Los Angeles, CA Patricia A. Wessels, RN, MSN Assistant Dean Viterbo College LaCrosse, WI Foreword In today's fast-paced, ever-changing health care environment, health care profes sionals are required to provide competent, compassionate care that integrates ev ery aspect of prior learning. They must assess patients, relate patients' clinic al symptoms to the pathophysiology associated with the disease process, interpre t laboratory data, and prepare patients for the expected treatment. These action s must be completed quickly and accurately, making both the science and the art of health care more complex. Thus, clinicians need a reliable, accessible refere nce that incorporates all of this information, enabling them to feel confident a bout the quality of their care. Modern clinical practice includes the domains of patient education and advocacy as well as the more traditional domains of providing and coordinating actual pat ient care. Additionally, clinical practice has moved from the traditional hospit al or long-term care facility to the patient's home or to outpatient centers. Ty pically, there must be collaboration between physicians and other health care pr ofessionals as part of the health care team to discuss the patient's physiologic status and treatment issues. They initiate meetings with patients, families, an d other members of the health care team to disseminate information about these s ame issues. To be confident in these aspects clinicians need a reference that en ables them to obtain relevant pathophysiologic information applicable to the pat ient's disease status. The Handbook of Pathophysiology is designed for the health care professional who enjoys the challenge of science-based practice. It is an easy-to-use reference that provides a synopsis of updated information on the major pathophysiologic di sease processes. This handbook presents more than 450 diseases. The basic concep ts of altered homeostasis, disease development, and disease progression are pres ented in an easy-to-read format. Additionally, Pathophysiology in color is a speci al section (located within chapter 9) that contains 16 full-color pages, illustr ating asthma, cancer, osteoporosis, and ulcers. The first chapter of the handbook provides an overview of the cell in health and illness. Various cell types and their normal function are discussed, including muscle and nerve cells. This provides the basis for the review of normal physiol ogy found in each chapter. Information about pathophysiologic changes at the cel lular level provides the foundation for describing alterations in the major orga

n systems that occur during illness. Subsequent chapters are presented in a systems format, including a discussion of the major disorders associated with that particular body system. The pathophysi ologic manifestations are described in relation to the patient's clinical presen tation. Thus, the clinician can monitor physical changes and relate them directl y to the disease process. The appropriate diagnostic tests for each disease are included in each chapter. The review of expected results from these tests provides information about disea se progression, remission, and resolution. This enables all members of the healt h care team to become active participants in the clinical decision-making proces s as plans are made for future care. The usually recommended treatments are presented as well. Inclusion of this info rmation enables the clinician to prepare for the next phase of patient care. The rationales for the treatment support the development of individualized patient education about the particular treatment. Each chapter contains crucial age-related, cultural, or socioeconomic informatio n related to common pathophysiologic conditions for that organ system. For examp le, Chapter 7, the Respiratory System, includes a discussion of age-related trigge rs for asthma. There's also information about asthma triggers that patients may encounter in the workplace and the inner city. This is the type of comprehensive information this handbook includes that's applicable to most patient-care circu mstances. The appendix of the handbook includes flow charts that summarize core informatio n for some of the less common diseases. Thus, important facts are available in a synopsis format. The clinician can readily access and refer to these flow chart s when accurate information is needed very quickly. The Handbook of Pathophysiology is a much needed reference for the entire health care team. For students, this handbook will complement other textual material a nd will be easy to use in the clinical site in conjunction with drug and diagnos tic study handbooks. New clinicians will refer to this handbook to enable them t o integrate patient-assessment information with the proposed plan of care. Exper ienced professionals will find that this reference contains information that wil l provide foundation knowledge to be utilized in coordinating patient care and d eveloping patient-education information. € Joan P. Frizzell, RN, PhD Assistant Professor School of Nursing LaSalle University Philadelphia Selected references Handbook of Pathophysiology Selected references Alcoser, P., and Burchett, S. Bone Marrow Transplantation: Immune System Suppress ion and Reconstitution, AJN 99(6):26-32, 1999. American Cancer Society. Guidelines on Diet, Nutrition, and Cancer Prevention. w ww2.cancer.org/prevention/index.cfm Updated 5/99. Accessed 10/4/99. American Cancer Society. Recommendations for the Early Detection of Cancer. Canc er Facts and Figures 1999. www.cancer.org/statistics/cff99/data/data_recommendDe tect.html. Updated 5/99. Accessed 10/4/99. American Heart Association. Cardiomyopathy. Dallas: American Heart Association, 1999. American Heart Association. Rheumatic Heart Disease Statistics. Dallas: American Heart Association, 1999. Assessment Made Incredibly Easy. Springhouse, Pa.: Springhouse Corp., 1998. Beattie, S. Management of Chronic Stable Angina, Nurse Practitioner 24(5):44-53, 1 999. Beers, M., and Berkow, R. The Merck Manual, 17th ed. Whitehouse Station, N.J.: M

erck and Co., Inc., 1999. Bertolet, B.D., and Brown, C.S. Cardiac Troponin: See Ya Later, CK! Chest 111(1):2 , January 1997. Bickley, L.S., and Hoekelman, R.A. Bates' Guide to Physical Examination and Hist ory Taking, 7th ed. Philadelphia: Lippincott, 1999. Bone, R. Pulmonary and Critical Care Medicine Core Updates. St. Louis: Mosby-Yea r Book, Inc., 1998. Cairns, J., et al. Coronary Thrombolysis, Chest 114(5): 634-657, 1998. Chiramannil, A. Clinical Snapshot: Lung Cancer, AJN 98(4):46-47, 1998. Coats, U. Management of Venous Ulcers, Critical Care Nursing Quarterly 21(2):14, A ugust 1998. Coudrey, L. The Troponins, Archives of Internal Medicine 158(11):1173-1180, June 1 998. Diseases, 3rd ed. Springhouse, Pa.: Springhouse Corp., 2000. Dugan, K.J. Caring for Patients with Pericarditis, Nursing98 28(3):50-51, 1998. Fauci, A.S., et al., eds. Harrison's Principles of Internal Medicine, 14th ed. N ew York: McGraw-Hill Book Co., 1998. Fluids and Electrolytes Made Incredibly Easy. Springhouse, Pa.: Springhouse Corp ., 1997. Fox, S.I. Laboratory Guide Human Physiology: Concepts and Clinical Applications. Dubuque, Iowa: Brown, William, 1999. Halper, J., and Holland, N. Meeting the Challenge of Multiple Sclerosis-Part 1, AJ N 98(10): 26-32, 1998. Halper, J., and Holland, N. Meeting the Challenge of Multiple Sclerosis-Part 2, AJ N 98(11): 39-45, 1998. Halperin, M. Fluid, Electrolyte, and Acid-Base Physiology: A Problem-Based Appro ach. Philadelphia: W.B. Saunders Co., 1998. Handbook of Geriatric Nursing Care. Springhouse, Pa.: Springhouse Corp., 1999. Handbook of Medical-Surgical Nursing. Springhouse, Pa.: Springhouse Corp., 1998. Hanson, M. Pathophysiology: Foundations of Disease and Clinical Intervention. Ph iladelphia: W.B. Saunders Co., 1998. Healthy People 2000 Progress Review: Cancer. Department of Health and Human Serv ices, Public Health Service, April 7, 1998. www.odphp.osophs.dhhs.gov/pubs/hp200 0. Accessed 8/16/00. Huether, S.E., and McCance, K.L. Understanding Pathophysiology. St. Louis: Mosby -Year Book, 1996. Huston, C.J. Emergency! Cervical Spine Injury, AJN 98(6): 33, 1998. Ignatavicius, D.D., et al. Medical-Surgical Nursing: Nursing Process Approach, 2 nd ed. Philadelphia: W.B. Saunders Co., 1995. Jastremski, C.A. Trauma! Head Injuries, RN 61(12): 40-46, 1998. Lewandowski, D.M. Myocarditis, AJN 99(8):44-45, 1999. Lewis, A.M. Cardiovascular Emergency! Nursing99 29(6):49, 1999. Mastering Geriatric Care. Springhouse, Pa.: Springhouse Corp., 1997. McKinney, B.C. Solving the Puzzle of Heart Failure, Nursing99 29(5):33-39, 1999. Murray, S. Critical Care Assessment Handbook. Philadelphia: W.B. Saunders Co., 1 999. Pathophysiology Made Incredibly Easy. Springhouse, Pa.: Springhouse Corp., 1998. Porth, C.M. Pathophysiology: Concepts of Altered Health States, 5th ed. Philadel phia: Lippincott-Raven Pubs., 1998. Price, S.A., and Wilson, L.M. Pathophysiology: Clinical Concepts and Disease Pro cesses, 5th ed. St. Louis: Mosby-Year Book, Inc., 1997. Professional Guide to Diseases, 6th ed. Springhouse, Pa.: Springhouse Corp., 199 8. Professional Guide to Signs and Symptoms, 2nd ed. Springhouse, Pa.: Springhouse Corp., 1997. Safety and Infection Control, Springhouse, Pa., Springhouse Corp., 1998. Wakeling, K.S. The Latest Weapon in the War Against Cancer, RN 62(7):58-60, July 1 999. Sparacino, P.S.A. Cardiac Infections: Medical and Surgical Therapies, Journal of C ardiovascular Nursing 13(2):49, January 1999.

Sussman, C., and Bates-Jensen, B.M. Wound Care, A Collaborative Practical Manual for Physical Therapists and Nurses, Gaithersburg, Md.: Aspen Pubs., Inc., 1998. Taylor, R., et al. Family Medicine Principles and Practice, 5th ed. New York: Sp ringer Publishing Co., 1998. Woods, A.D. Managing Hypertension, Nursing99 29(3):41-46, March 1999. STAFF Senior publisher Donna O. Carpenter Creative director Jake Smith Design director John Hubbard Executive editor H. Nancy Holmes Clinical project managers Clare M. Brabson, RN, BSN; Joan M. Robinson, RN, MSN, CCRN Clinical editors Joanne Bartelmo, RN, MSN; Jill Curry, RN, BSN, CCRN; Maryann Foley, RN, BSN; Mar garet Klein, RN, BSN; Lori Musolf Neri, RN, MSN, CCRN; John E. Taylor, RN, BS Editors Jennifer P. Kowalak (editorial project manager), Mario Cavallini, Naina D. Choha n, Audrey Selena Hughes, Peter H. Johnson, Joanne C. Poeggel Copy editors Richard H. Adin, Catherine Cramer, Joy Epstein, Dolores P. Matthews, Celia McCoy , Maarten Reilingh, Barbara F. Ritter Designers Arlene Putterman (associate design director), BJ Crim (designer), Susan Sheridan (design project manager), Joseph John Clark, Lynn Foulke, Donna S. Morris, Jeff rey Sklarow Illustrators Jean Gardner, Judy Newhouse Electronic production services Diane Paluba (manager), Joyce Rossi Biletz Manufacturing Deborah Meiris (director), Patricia K. Dorshaw (manager), Otto Mezei (book produ ction manager) Editorial and design assistants Carol Caputo, Arlene Claffee, Tom Hasenmayer, Elfriede Young Indexer Barbara E. Hodgson Cover illustration Frontal view computed tomography scan of thorax showing cancer of the right lung /©GJLP/CNRI/Phototake 1 FUNDAMENTALS OF PATHOPHYSIOLOGY Handbook of Pathophysiology 1 FUNDAMENTALS OF PATHOPHYSIOLOGY

Homeostasis Maintaining balance Disease and illness € Cause € Development €

Stages € Stress and disease Cell physiology € Cell components € Cell division € Cell functions € Cell types Pathophysiologic changes € Cell adaptation € Cell injury € Cell degeneration € Cell aging € Cell death how t An understanding of pathophysiology requires a review of normal physiology he body functions day to day, minute to minute, at the levels of cells, tissues, organs, and organisms. HOMEOSTASIS Every cell in the body is involved in maintaining a dynamic, steady state of int ernal balance, called homeostasis. Any change or damage at the cellular level ca n affect the entire body. When homeostasis is disrupted by an external stressor such as injury, lack of nutrients, or invasion by parasites or other organisms i llness may occur. Many external stressors affect the body's internal equilibrium throughout the course of a person's lifetime. Pathophysiology can be considered as what happens when normal defenses fail. MAINTAINING BALANCE Three structures in the brain are responsible for maintaining homeostasis of the entire body:

medulla oblongata, which is the part of the brain stem associated with vital fun ctions such as respiration and circulation

pituitary gland, which regulates the function of other glands and, thereby, a pe rson's growth, maturation, and reproduction

reticular formation, a network of nerve cells (nuclei) and fibers in the brain s tem and spinal cord that help control vital reflexes such as cardiovascular func tion and respiration. Homeostasis is maintained by self-regulating feedback mechanisms. These mechanis ms have three components:

a sensor that detects disruptions in homeostasis

a control center that regulates the body's response to those disruptions

an effector that acts to restore homeostasis. An endocrine or hormone-secreting gland usually serves as the sensor. It signals the control center in the central nervous system to initiate the effector mecha nism. Feedback mechanisms exist in two varieties: positive and negative.

A positive feedback mechanism moves the system away from homeostasis by enhancin g a change in the system. For example, the heart pumps at increased rate and for ce when someone is in shock. If the shock progresses, the heart action may requi re more oxygen than is available. The result is heart failure.

A negative feedback mechanism works to restore homeostasis by correcting a defic it in the system. An effective negative feedback mechanism must sense a change in the body such as a high blood glucose level and attempt to return body functions to normal. In t he case of a high blood glucose level, the effector mechanism triggers increased insulin production by the pancreas, returning blood glucose levels to normal an d restoring homeostasis. DISEASE AND ILLNESS Although disease and illness are often used interchangeably, they aren't synonym s. Disease occurs when homeostasis isn't maintained. Illness occurs when a perso n is no longer in a state of perceived normal health. For example, a person may ha ve coronary artery disease, diabetes, or asthma but not be ill all the time beca use his body has adapted to the disease. In such a situation, a person can perfo rm necessary activities of daily living. Illness usually refers to subjective sy mptoms, that may or may not indicate the presence of disease. The course and outcome of a disease are influenced by genetic factors (such as a tendency toward obesity), unhealthy behaviors (such as smoking), attitudes (suc h as being a Type A personality), and even the person's perception of the disease (such as acceptance or denial). Diseases are dynamic and may be manifested in a variety of ways, depending on the patient or his environment. Cause The cause of disease may be intrinsic or extrinsic. Inheritance, age, gender, in fectious agents, or behaviors (such as inactivity, smoking, or abusing illegal d rugs) can all cause disease. Diseases that have no known cause are called idiopa thic. Development A disease's development is called its pathogenesis. Unless identified and succes sfully treated, most diseases progress according to a typical pattern of symptom s. Some diseases are self-limiting or resolve quickly with limited or no interve ntion; others are chronic and never resolve. Patients with chronic diseases may undergo periodic remissions and exacerbations. A disease is usually detected when it causes a change in metabolism or cell divi sion that causes signs and symptoms. Manifestations of disease may include hypof unction (such as constipation), hyperfunction (such as increased mucus productio n), or increased mechanical function (such as a seizure). How the cells respond to disease depends on the causative agent and the affected cells, tissues, and organs. The resolution of disease depends on many factors f unctioning over a period of time, such as extent of disease and the presence of

other diseases. Stages Typically, diseases progress through these stages:

Exposure or injury

Target tissue is exposed to a causative agent or is injured.

Latency or incubation period

No signs or symptoms are evident.

Prodromal period

Signs and symptoms are usually mild and nonspecific.

Acute phase The disease reaches its full intensity, possibly resulting in compli cations. This phase is called the subclinical acute phase if the patient can sti ll function as though the disease wasn't present.

Remission This second latent phase occurs in some diseases and is often followed by another acute phase.

Convalescence disease.

The patient progresses toward recovery after the termination of a

Recovery The patient regains health or normal functioning. No signs or symptoms of disease remain. Stress and disease When a stressor such as a life change occurs, a person can respond in one of two ways: by adapting successfully or by failing to adapt. A maladaptive response t o stress may result in disease. Hans Selye, a pioneer in the study of stress and disease, describes the followin g stages of adaptation to a stressful event: alarm, resistance, and recovery or exhaustion (See Physical response to stress.) In the alarm stage, the body sense s stress and arouses the central nervous system (CNS). The body releases chemica ls to mobilize the fight-or-flight response. In this dual effort, the sympatho-a drenal medullary response causes the release of epinephrine and the hypothalamic pituitary adrenal axis causes the release of glucocorticoids. Both of these sys tems work in concert to enable the body to respond to stressors. This release is the adrenaline rush associated with panic or aggression. In the resistance stag e, the body either adapts and achieves homeostasis or it fails to adapt and ente rs the exhaustion stage, resulting in disease. PHYSICAL RESPONSE TO STRESS According to Hans Selye's General Adaptation Model, the body reacts to stress in the stages depicted below.

The stress response is controlled by actions that take place in the cells of the

nervous and endocrine systems. These actions try to redirect energy to the orga n that is most affected by the stress, such as the heart, lungs, or brain. Stressors may be physiologic or psychological. Physiologic stressors, such as ex posure to a toxin, may elicit a harmful response leading to an identifiable illn ess or set of symptoms. Psychological stressors, such as the death of a loved on e, may also cause a maladaptive response. Stressful events can exacerbate some c hronic diseases, such as diabetes or multiple sclerosis. Effective coping strate gies can prevent or reduce the harmful effects of stress. CELL PHYSIOLOGY The cell is the smallest living component of a living organism. Many organisms, such as bacteria, consist of one independent cell. Human beings and other large organisms consist of millions of cells. In large organisms, highly specialized c ells that perform an identical function form tissue such as epithelial tissue, c onnective tissue, nerve tissue, and muscle tissue. Tissues, in turn, form organs (skin, skeleton, brain, and heart), which are integrated into body systems such as the CNS, cardiovascular system, and musculoskeletal system. Cell components Like organisms, cells are complex organizations of specialized components, each component having its own specific function. The largest components of a normal c ell are the cytoplasm, the nucleus, and the cell membrane, which surrounds the i nternal components and holds the cell together. Cytoplasm The gel-like cytoplasm consists primarily of cytosol, a viscous, semitransparent fluid that is 70% to 90% water plus various proteins, salts, and sugars. Suspen ded in the cytosol are many tiny structures called organelles. Organelles are the cell's metabolic machinery. Each performs a specific function to maintain the life of the cell. Organelles include mitochondria, ribosomes, e ndoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, cytoskeletal elem ents, and centrosomes.

Mitochondria are threadlike structures that produce most of the body's adenosine triphosphate (ATP). ATP contains high-energy phosphate chemical bonds that fuel many cellular activities.

Ribosomes are the sites of protein synthesis.

The endoplasmic reticulum is an extensive network of two varieties of membrane-e nclosed tubules. The rough endoplasmic reticulum is covered with ribosomes. The smooth endoplasmic reticulum contains enzymes that synthesize lipids.

The Golgi apparatus synthesizes carbohydrate molecules that combine with protein produced by the rough endoplasmic reticulum and lipids produced by the smooth e ndoplasmic reticulum to form such products as lipoproteins, glycoproteins, and e nzymes.

Lysosomes are digestive bodies that break down nutrient material as well as fore ign or damaged material in cells. A membrane surrounding each lysosome separates its digestive enzymes from the rest of the cytoplasm. The enzymes digest nutrie nt matter brought into the cell by means of endocytosis, in which a portion of t he cell membrane surrounds and engulfs matter to form a membrane-bound intracell

ular vesicle. The membrane of the lysosome fuses with the membrane of the vesicl e surrounding the endocytosed material. The lysosomal enzymes then digest the en gulfed material. Lysosomes digest the foreign matter ingested by white blood cel ls by a similar process called phagocytosis.

Peroxisomes contain oxidases, which are enzymes that chemically reduce oxygen to hydrogen peroxide and hydrogen peroxide to water.

Cytoskeletal elements form a network of protein structures.

Centrosomes contain centrioles, which are short cylinders adjacent to the nucleu s that take part in cell division.

Microfilaments and microtubules enable the movement of intracellular vesicles (a llowing axous to transport neurotransmitters) and the formation of the mitotic s pindle, which connects the chromosomes during cell division. A LOOK AT CELL COMPONENTS The illustration below shows the components and structures of a cell. Each part has a function in maintaining the cell's life and homeostasis.

Nucleus The cell's control center is the nucleus, which plays a role in cell growth, met abolism, and reproduction. Within the nucleus, one or more nucleoli (dark-staini ng intranuclear structures) synthesize ribonucleic acid (RNA), a complex polynuc leotide that controls protein synthesis. The nucleus also stores deoxyribonuclei c acid (DNA), the famous double helix that carries genetic material and is respo nsible for cellular reproduction or division. (See A look at cell components.) Cell membrane The semipermeable cell membrane forms the cell's external boundary, separating i t from other cells and from the external environment. Roughly 75Å (3/10 millionths of an inch) thick, the cell membrane consists of a double layer of phospholipid s with protein molecules embedded in it. Cell division Each cell must replicate itself for life to continue. Cells replicate by divisio n in one of two ways: mitosis (division that results in two daughter cells with the same DNA and chromosome content as the mother cell) or meiosis (division tha t creates four gametocytes, each containing half the number of chromosomes of th e original cell). Most cells undergo mitosis; meiosis occurs only in reproductiv e cells. Mitosis Mitosis, the type of cell division that leads to tissue growth, creates an equal division of material in the nucleus (karyokinesis) followed by division of the cell body (cytokinesis). This process yields two exact duplicates of the origina l cell. (See Chapter 4 for a detailed discussion of mitosis and meiosis.) Cell functions The basic functions of a cell are movement, conduction, absorption, secretion, e xcretion, respiration, and reproduction. In the human body, different cells are specialized to perform only one function; muscle cells, for example, are respons

ible for movement. Movement Some cells, such as muscle cells, working together produce movement of a specifi c body part or the entire organism. Muscle cells attached to bone move the extre mities. When muscle cells that envelop hollow organs or cavities contract, they produce movement of contents, such as the peristaltic movement of the intestines or the ejection of blood from the heart. Conduction Conduction is the transmission of a stimulus, such as a nerve impulse, heat, or sound wave, from one body part to another. Absorption This process of absorption occurs as substances move through a cell membrane. Fo r example, food is broken down into amino acids, fatty acids, and glucose in the digestive tract. Specialized cells in the intestine then absorb the nutrients a nd transport them to blood vessels, which carry them to other cells of the body. These target cells, in turn, absorb the substances, using them as energy source s or as building blocks to form or repair structural and functional cellular com ponents. Secretion Some cells, such as those in the glands, release substances that are used in ano ther part of the body. The beta cells of the islets of Langerhans of the pancrea s, for example, secrete insulin, which is transported by the blood to its target cells, where the insulin facilitates the movement of glucose across cell membra nes. Excretion Cells excrete the waste that is generated by normal metabolic processes. This wa ste includes such substances as carbon dioxide and certain acids and nitrogen-co ntaining molecules. Respiration Cellular respiration occurs in the mitochondria, where ATP is produced. The cell absorbs oxygen; it then uses the oxygen and releases carbon dioxide during cell ular metabolism. The energy stored in ATP is used in other reactions that requir e energy. Reproduction New cells are needed to replace older cells for tissue and body growth. Most cel ls divide and reproduce through mitosis. However, some cells, such as nerve and muscle cells, typically lose their ability to reproduce after birth. Cell types Each of the four types of tissue (epithelial, connective, nerve, and muscle tiss ue) consists of several specialized cell types, which perform specific functions . Epithelial cell Epithelial cells line most of the internal and external surfaces of the body, su ch as the epidermis of the skin, internal organs, blood vessels, body cavities, glands, and sensory organs. The functions of epithelial cells include support, p rotection, absorption, excretion, and secretion. Connective tissue cell Connective tissue cells are found in the skin, the bones and joints, the artery walls, the fascia around organs, nerves, and body fat. The types of connective t issue cells include fibroblasts (such as collagen, elastin, and reticular fibers ), adipose (fat) cells, mast cells (release histamines and other substances duri ng inflammation), and bone. The major functions of connective tissues are protec tion, metabolism, support, temperature maintenance, and elasticity. Nerve cell neurons and neuroglial cells comprise the nervous system. Neu Two types of cells rons have a cell body, dendrites, and an axon. The dendrites carry nerve impulse s to the cell body from the axons of other neurons. Axons carry impulses away fr om the cell body to other neurons or organs. A myelin sheath around the axon fac ilitates rapid conduction of impulses by keeping them within the nerve cell. Ner ve cells:

generate electrical impulses

conduct electrical impulses

influence other neurons, muscle cells, and cells of glands by transmitting those impulses. Neuroglial cells, also called glial cells, consist of four different cell types: oligodendroglia, astrocytes, ependymal cells, and microglia. Their function is to support, nourish, and protect the neurons. Muscle cell Muscle cells contract to produce movement or tension. The intracellular proteins actin and myosin interact to form crossbridges that result in muscle contractio n. An increase in intracellular calcium is necessary for muscle to contract. There are three basic types of muscle cells:

Skeletal (striated) muscle cells are long, cylindrical cells that extend along t he entire length of the skeletal muscles. These muscles, which attach directly t o the bone or are connected to the bone by tendons, are responsible for voluntar y movement. By contracting and relaxing, striated muscle cells alter the length of the muscle.

Smooth (nonstriated) muscle cells are present in the walls of hollow internal or gans, such as the gastrointestinal (GI) and genitourinary tracts, and of blood v essels and bronchioles. Unlike striated muscle, these spindle-shaped cells contr act involuntarily. By contracting and relaxing, they change the luminal diameter of the hollow structure, and thereby move substances through the organ.

Cardiac muscle cells branch out across the smooth muscle of the chambers of the heart and contract involuntarily. They produce and transmit cardiac action poten tials, which cause cardiac muscle cells to contract. Impulses travel from cell t o cell as though no cell membrane existed.

AGE ALERT In older adults, muscle cells become smaller and many are replaced by fibrous connective tissue. The result is loss of muscle strength and mass. PATHOPHYSIOLOGIC CHANGES The cell faces a number of challenges through its life. Stressors, changes in th e body's health, diease, and other extrinsic and intrinsic factors can change th e cell's normal functioning (homeostasis). Cell adaptation Cells are generally able to continue functioning despite changing conditions or stressors. However, severe or prolonged stress or changes may injure or even kil l cells. When cell integrity is threatened for example, by hypoxia, anoxia, chem ical injury, infection, or temperature extremes the cell reacts in one of two wa ys:

by drawing on its reserves to keep functioning

by adaptive changes or cellular dysfunction. If enough cellular reserve is available and the body doesn't detect abnormalitie s, the cell adapts. If cellular reserve is insufficient, cell death (necrosis) o ccurs. Necrosis is usually localized and easily identifiable. ADAPTIVE CELL CHANGES Cells adapt to changing conditions and stressors within the body in the ways sho wn below.

The cells' methods of adapting include atrophy, hypertrophy, hyperplasia, metapl asia, and dysplasia. (See Adaptive cell changes.) Atrophy Atrophy is a reduction in the size of a cell or organ that may occur when cells face reduced workload or disuse, insufficient blood flow, malnutrition, or reduc ed hormonal and nerve stimulation. Examples of atrophy include loss of muscle ma ss and tone after prolonged bed rest. Hypertrophy In contrast, hypertrophy is an increase in the size of a cell or organ due to an increase in workload. The three basic types of hypertrophy are physiologic, com pensatory, and pathologic.

Physiologic hypertrophy reflects an increase in workload that is not caused by d isease for example, the increase in muscle size caused by hard physical labor or weight training.

Compensatory hypertrophy takes place when cell size increases to take over for n onfunctioning cells. For instance, one kidney will hypertrophy when the other is not functioning or is removed.

Pathologic hypertrophy is a response to disease. An example is hypertrophy of th e heart muscle as the muscle pumps against increasing resistance in patients wit h hypertension. Hyperplasia Hyperplasia is an increase in the number of cells caused by increased workload, hormonal stimulation, or decreased tissue density. Like hypertrophy, hyperplasia may be physiologic, compensatory, or pathologic.

Physiologic hyperplasia is an adaptive response to normal changes. An example is the monthly increase in number of uterine cells that occurs in response to estr ogen stimulation of the endometrium after ovulation.

Compensatory hyperplasia occurs in some organs to replace tissue that has been r emoved or destroyed. For example, liver cells regenerate when part of the liver is surgically removed.

Pathologic hyperplasia is a response to either excessive hormonal stimulation or abnormal production of hormonal growth factors. Examples include acromegaly, in which excessive growth hormone production causes bones to enlarge, and endometr ial hyperplasia, in which excessive secretion of estrogen causes heavy menstrual bleeding and possibly malignant changes. Metaplasia Metaplasia is the replacement of one cell type with another cell type. A common cause of metaplasia is constant irritation or injury that initiates an inflammat ory response. The new cell type can better endure the stress of chronic inflamma tion. Metaplasia may be either physiologic or pathologic.

Physiologic metaplasia is a normal response to changing conditions and is genera lly transient. For example, in the body's normal response to inflammation, monoc ytes that migrate to inflamed tissues transform into macrophages.

Pathologic metaplasia is a response to an extrinsic toxin or stressor and is gen erally irreversible. For example, after years of exposure to cigarette smoke, st ratified squamous epithelial cells replace the normal ciliated columnar epitheli al cells of the bronchi. Although the new cells can better withstand smoke, they don't secrete mucus nor do they have cilia to protect the airway. If exposure t o cigarette smoke continues, the squamous cells can become cancerous. Dysplasia In dysplasia, abnormal differentiation of dividing cells results in cells that a re abnormal in size, shape, and appearance. Although dysplastic cell changes are n't cancerous, they can precede cancerous changes. Common examples include dyspl asia of epithelial cells of the cervix or the respiratory tract. Cell injury Injury to any cellular component can lead to illness as the cells lose their abi lity to adapt. One early indication of cell injury is a biochemical lesion that forms on the cell at the point of injury. For example, in a patient with chronic alcoholism, biochemical lesions on the cells of the immune system may increase the patient's susceptibility to infection, and cells of the pancreas and liver a re affected in a way that prevents their reproduction. These cells can't return to normal functioning. Causes of cell injury Cell injury may result from any of several intrinsic or extrinsic causes:

Toxins. Substances that originate in the body (endogenous factors) or outside th e body (exogenous factors) may cause toxic injuries. Common endogenous toxins in clude products of genetically determined metabolic errors, gross malformations, and hypersensitivity reactions. Exogenous toxins include alcohol, lead, carbon m onoxide, and drugs that alter cellular function. Examples of such drugs are chem otherapeutic agents used for cancer and immunosuppressants used to prevent rejec tion in organ transplant recipients.

Infection. Viruses, fungi, protozoa, and bacteria can cause cell injury or death . These organisms affect cell integrity, usually by interfering with cell divisi on, producing nonviable, mutant cells. For example, human immunodeficiency virus alters the cell when the virus is replicated in the cell's RNA.

Physical injury. Physical injury results from a disruption in the cell or in the relationships of the intracellular organelles. Two major types of physical inju ry are thermal and mechanical. Causes of thermal injury include burns, radiation therapy for cancer, X-rays, and ultraviolet radiation. Causes of mechanical inj ury include surgery, trauma from motor vehicle accidents, and frostbite.

Deficit injury. When a deficit of water, oxygen, or nutrients occurs, or if cons tant temperature and adequate waste disposal aren't maintained, normal cellular metabolism can't take place. A lack of just one of these basic requirements can cause cell disruption or death. Causes of deficit include hypoxia (inadequate ox ygen), ischemia (inadequate blood supply), and malnutrition. Irreversible cell injury occurs when there's a breakdown of organelles and cell membrane. Cell degeneration Degeneration is a type of nonlethal cell damage that generally occurs in the cyt oplasm and that doesn't affect the nucleus. Degeneration usually affects organs with metabolically active cells, such as the liver, heart, and kidneys, and is c aused by these problems:

increased water in the cell or cellular swelling

fatty infiltrates


autophagocytosis (that is, the cell absorbs some of its own parts)

pigmentation changes


hyaline infiltration


dysplasia (related to chronic irritation)

hyperplasia. When changes in cells are identified, prompt health care can slow degeneration a nd prevent cell death. An electron microscope can help identify cellular changes , and thus diagnose a disease, before the patient complains of any symptoms. Unf ortunately, many cell changes remain unidentifiable even under a microscope, mak ing early detection of disease impossible. Cell aging During the normal process of aging, cells lose both structure and function. Atro phy, a decrease in size or wasting away, may indicate loss of cell structure. Hy pertrophy or hyperplasia is characteristic of lost cell function. (See Factors t hat affect cell aging.) FACTORS THAT AFFECT CELL AGING Cell aging can be affected by the intrinsic and extrinsic factors listed below. INTRINSIC FACTORS








Psychogenic EXTRINSIC FACTORS Physical agents






Temperature Infectious agents






Worms Signs of aging occur in all body systems. Examples include diminished elasticity of blood vessels, bowel motility, muscle mass, and subcutaneous fat. Cell aging can slow down or speed up, depending on the number and extent of injuries and t he amount of wear and tear on the cell. The cell aging process limits the human life span (of course, many people die fr om disease before they reach the maximum life span of about 110 years). A number of theories attempt to explain the reasons behind cell aging. (See Biological t heories of aging.) Cell death Like disease, cell death may be caused by internal (intrinsic) factors that limi t the cell's life span or external (extrinsic) factors that contribute to cell d amage and aging. When a stressor is severe or prolonged, the cell can no longer adapt and it dies. Cell death, or necrosis, may manifest in different ways, depending on the tissue

s or organs involved.

Apoptosis is genetically programmed cell death. This accounts for the constant c ell turnover in the skin's outer keratin layer and the lens of the eye.

Liquefactive necrosis occurs when a lytic (dissolving) enzyme liquefies necrotic cells. This type of necrosis is common in the brain, which has a rich supply of lytic enzymes.

In caseous necrosis, the necrotic cells disintegrate but the cellular pieces rem ain undigested for months or years. This type of necrotic tissue gets its name f rom its crumbly, cheeselike (caseous) appearance. It commonly occurs in lung tub erculosis.

In fat necrosis, enzymes called lipases break down intracellular triglycerides i nto free fatty acids. These free fatty acids combine with sodium, magnesium, or calcium ions to form soaps. The tissue becomes opaque and chalky white.

Coagulative necrosis commonly occurs when the blood supply to any organ (except the brain) is interrupted. It typically affects the kidneys, heart, and adrenal glands. Lytic (lysosomal) enzyme activity in the cells is inhibited, so that the necrotic cells maintain their shape, at least temporarily.

Gangrenous necrosis, ck of blood flow and t commonly occurs in tract. Gangrene can

a form of coagulative necrosis, typically results from a la is complicated by an overgrowth and invasion of bacteria. I the lower legs as a result of arteriosclerosis or in the GI occur in one of three forms: dry, moist (or wet), or gas.

Dry gangrene occurs when bacterial invasion is minimal. It's marked by dry, wrin kled, dark brown or blackened tissue on an extremity.

Moist (or wet) gangrene develops with liquifactive necrosis that includes extens ive lytic activity from bacteria and white blood cells to produce a liquid cente r in an area of tissue. It can occur in the internal organs as well as the extre mities.

Gas gangrene develops when anaerobic bacteria of the genus Clostridium infect ti ssue. It's more likely to occur with severe trauma and may be fatal. The bacteri a release toxins that kill nearby cells and the gas gangrene rapidly spreads. Re lease of gas bubbles from affected muscle cells indicates that gas gangrene is p resent.

BIOLOGICAL THEORIES OF AGING Various theories have been proposed to explain the process of normal aging. Biol ogical theories attempt to explain physical aging as an involuntary process that eventually leads to cumulative changes in cells, tissues, and fluids.


Strong chemical bonding between organic molecules in the body causes increased s tiffness, chemical instability, and insolubility of connective tissue and deoxyr ibonucleic acid. Lipids, proteins, carbohydrates, and nucleic acids Restricting calories and sources of lathyrogens (antilink agents), such as chick peas

Free-radical theory

An increased number of unstable free radicals produces effects harmful to biolog ic systems, such as chromosomal changes, pigment accumulation, and collagen alte ration. Environmental pollutants; oxidation of dietary fats, proteins, carbohydrates, an d elements Improving environmental monitoring; decreasing intake of free-radical-stimulatin g foods; increasing intake of vitamins A and C (mercaptans) and vitamin E

Immunologic theory

An aging immune system is less able to distinguish body cells from foreign cells ; as a result, it begins to attack and destroy body cells as if they were foreig n. This may explain the adult onset of conditions such as diabetes mellitus, rhe umatic heart disease, and arthritis. Theorists have speculated about the existen ce of several erratic cellular mechanisms that are capable of precipitating atta cks on various tissues through autoaggression or immunodeficiencies. Alteration of B and T cells of the humoral and cellular systems Immunoengineering selective alteration and replenishment or rejuvenation of the immune system

Wear and tear theory

At th is point. strewing pieces of genetic materia l throughout the cell. in which hydrolytic enzymes released from intracellular structures c alled lysosomes simply dissolve the nucleus. becoming a dense mass of genetic materia l with an irregular outline. in which the nucleus shrinks. chemicals. karyorrhexis. Effects of the residual damage accumulate. and functions wear out or are overused through exposure to internal and external stressors. structures. and environmental). karyolysis. This triggers an acute inflammatory reaction in which white bl ood cells migrate to the necrotic area and begin to digest the dead cells. in which the nucleus breaks up. the dead cells primarily the nuclei begin to change morphologically in one of three ways: pyknosis. Repeated injury or overuse. t he body can no longer resist stress. and death occurs.Body cells. 2 CANCER Handbook of Pathophysiology 2 CANCER How does cancer happen? € Initiation € Promotion € Progression Causes € Genetics € Viruses € Failure of immunosurveillance Risk factors € Air pollution € Tobacco € Alcohol € . social. and buildup of na turally occurring wastes Reevaluating and possibly adjusting lifestyle Necrotic changes When a cell dies. including trauma. enzymes inside the cell are released and start to dissolve cel lular components. psycholog ical. internal and external stressors (physical.

Sexual and reproductive behavior € Occupation € Ultraviolet radiation € Ionizing radiation € Hormones € Diet Pathophysiologic changes € Cell growth € Differentiation € Intracellular changes € Tumor development and growth € Spread of cancer Signs and symptoms € Fatigue € Cachexia € Pain € Anemia € Leukopenia and thrombocytopenia € Infection Diagnosis € Screening tests € Diagnosis by imaging € Endoscopy € Biopsy € Tumor cell markers Tumor classification € Tissue type € Grading € Staging Treatment € Surgery € Radiation therapy € Chemotherapy .

o r drugs. lung. Worldwide. lung. This exposure may occur either shortly after initiation or y ears later. virus. such as estrogen. called oncogenes . Progression Some investigators believe that progression is actually a late promotion phase i n which the tumor invades. cancer accounts for more than half a million deaths each y ear. Promoters may be hormones. enzymes detect errors in transcription and remove or repair them. also called malignant neoplasia. more t han two-thirds of the patients who develop cancer are over age 65. second only to cardiovascular disease. In the United States. then the er ror may be repaired or the cell may self-destruct.€ Immunotherapy Cancer.) In the United States. such as nitrates. and becomes resistant to drugs. bone. promotion. CAUSES Current evidence suggests that cancer develops from a complex interaction of exp osure to carcinogens and accumulated mutations in several genes. Malignant cells have two defining characteristics: (1) the y can no longer divide and differentiate normally. However. food additives. occur predominantly in younger patients. prostate. Initiation Initiation refers to the damage to or mutation of DNA that occurs when the cell is exposed to an initiating substance or event (such as chemicals. urinary tract. metastasizes. Researchers hav e identified approximately 100 cancer genes. and progression. This st ep is irreversible. HOW DOES CANCER HAPPEN? Most of the numerous theories about carcinogenesis suggest that it involves thre e steps: initiation. yet. Some cancer genes. the most common forms of cancer are skin. gastrointestinal (GI) tract and associated s tructures. and cancers of the breast. Other cancer genes . Promoters can affect the mutated cell by altering: function of genes that control cell growth and duplication cell response to growth stimulators or inhibitors intercellular communication. leukemias. or rad iation) during DNA replication (transcription). a 1999 review of the Health y People 2010 cancer objectives by the Department of Health and Human Services h ad encouraging results: a reversal of a 20-year trend of increasing cancer incid ence and deaths. refers to a group of more than 100 diff erent diseases that are characterized by DNA damage that causes abnormal cell gr owth and development. Normally. If these proteins miss the er ror again. and (2) they have acquired th e ability to invade surrounding tissues and travel to distant sites. such as ovarian germ-cell tumors and retinoblastoma. Some cancers. it becomes a permanent mutation that is passed on to future generatio ns of cells. thyroid. If regulatory proteins recognize the error and block further division. Promotion Promotion involves the exposure of the mutated cell to factors (promoters) that enhance its growth. But sometimes an error is missed. such as nicotine. activate cell division and influence embryonic development. (See Reviewing common cancers. The rates for all cancers combined and for most of the top 10 c ancer sites declined between 1990 and 1996. the most common malignancies include skin cancer. and colorectal. lymphoma s. and reproductive tract. breast.

as in Wilms' tumor and retinoblastoma. some of whic h begin to destroy the antigen. Other factors that interact to increase a perso n's likelihood of developing cancer are age. which causes infectious mononucleosis.. and hormones. Genetics Some cancers and precancerous lesions may result from genetic predisposition eit her directly or indirectly. these are discussed below as risk factors. Thus. a blocking antibody. However. ma . Cell-mediated immune response Cancer cells carry cell-surface antigens (specialized protein molecules that tri gger an immune response) called tumor-associated antigens (TAAs) and tumor-speci fic antigens (TSAs). The healthy body is well equipped to defend itself against cancer. cellular immunity. Viruses Viral proto-oncogenes often contain DNA that's identical to that of human oncoge nes. This reaction triggers the transformation of a d ifferent population of T lymphocytes into killer T lymphocytes targeted to cells c arrying the specific antigen in this case cancer cells. hormonal balanc e. Failure of immunosurveillance Research suggests that cancer cells develop continually. the tumor-suppressor genes. the sensitized T cells release chemical factors called lymphokines. This defense mechanism. In animal studies of viral ability to transform cells. Only when the immune system and other defenses fail does cancer prevail. Indire ct carcinogenesis is associated with inherited conditions. Normal human cells typically c ontain proto-oncogenes (oncogene precursors) and tumor-suppressor genes. For example. has two major components: cell-mediated immune response a nd humoral immune response. environmental and di etary carcinogens. Direct causation occurs when a single gene is respon sible for the cancer. Researchers belie ve that an intact immune system is responsible for spontaneous regression of tum ors. and response to stress. Humoral immune response The humoral immune response reacts to a TAA by triggering the release of antibod ies from plasma cells and activating the serum-complement system to destroy the antigen-bearing cells. but the immune system r ecognizes these cells as foreign and destroys them. which r emain dormant unless they are transformed by genetic or acquired mutation. radiation. some viruses that in fect people have demonstrated the potential to cause cancer. such as Down syndrome or immunodeficiency diseases. Commo n causes of acquired genetic damage are viruses. Common characteristics of genetically predisposed cancer include: early onset of malignant disease increased incidence of bilateral cancer in paired organs increased incidence of multiple primary cancers in nonpaired organs abnormal chromosome complement in tumor cells. halt cell division. cancer development is a concern for patients who must take immunosupp ressant medications. After repeated contacts. nutritional status. term ed immunosurveillance. has been linked to lymp homas. these two components interact to promote a ntibody production. the Ep stein-Barr virus. Together. for example. an opposing immune factor. The cell-mediated immune response begins when T lymphocytes encounter a TAA or a TSA and become sensitized to it. and immunologic memory.

and some risk factors both initiate and promote the disease process. If the immune system fails to recog nize tumor cells as foreign. thus allowing cancer cells to proliferate. allow for tumor growth. Extreme stress or certain viral infections. the immune response won't activate. the mutated cells may proliferate and form a tumor. Cytotoxic drugs or steroids. The tumor antigens ma y combine with humoral antibodies to form complexes that essentially hide the an tigens from the normal immune defenses. If the aging immune system doesn't recognize thes e mutations as foreign. The tumor cells may actually suppress the immune defenses. This condition weakens the cell-media ted immune response. Accumulating data suggest that some of thes e risk factors initiate carcinogenesis. Finally. errors in copying genetic material during cell divisi on may give rise to mutations. These agents decrease antibody production and destr oy circulating lymphocytes. such as viruses or chemicals. Acquired immunodeficiency syndrome (AIDS). In addition to this failure of surveillance. Air pollution . and subsequently. Certain carcinogens. they also signal the immune system when an immune respons e is no longer needed. The tumor growth factors not on ly promote the growth of the tumor. Cancer. RISK FACTORS Many cancers are related to specific environmental and lifestyle factors that pr edispose a person to develop cancer. The disease itself is immunosuppressive. These conditions may depress the imm une response. Radiation.y enhance tumor growth by protecting malignant cells from immune destruction. These complexes could also depress furth er antibody production. other risk factors act as promoters. The patient's population of suppressor T lymphocytes may be inadequate to defend against malignant tumors. Tumors also may change their antigenic appearance or produ ce substances that impair usual immune defenses. Advanced disease exhausts the i mmune system. The tumor will continue to grow until it's beyond the immune system's ability to destroy it. prolonged exposure to a tumor antigen may deplete the patient's l ymphocytes and further impair the ability to mount an appropriate response. Disruption of the immune response Immunosurveillance isn't a fail-safe system. leading to anergy (the absence of immune reactivity). Research data support the concept that cancer develops when any of several facto rs disrupts the immune response: Aging cells. may we aken the immune system by destroying or damaging suppressor T cells or their pre cursors. As cells age. Suppression of immune system. Suppressor T lymphocytes normally assist in regulatin g antibody production. cytotoxic drug therapy. but also increase the person's risk of infec tion. other mechanisms may come into play. and lymphoproli ferative and myeloproliferative diseases (such as lymphatic and myelocytic leuke mia) depress bone marrow production and impair leukocyte function.

Air pollution has been linked to the development of cancer. or passive smoking. kidney. This alkalinity decreases nicotine abso rption in the lungs and also is more irritating to the lungs. Persons living near industries that release toxic chemicals have a documen ted increased risk of cancer. Workers involved in the production of dyes. Possible mechanisms for breast cancer development include impaired removal o f carcinogens by the liver. larynx. Alcohol Alcohol consumption. a woman who has had only one sexual partner is at higher risk if that partner has had multiple partners. It's likely that alc ohol acts as a solvent for the carcinogenic substances found in smoke. Ultraviolet sunlight is a direct cause of basal and squamous cell cancers of the skin. Persons exposed to asbestos. Alcohol stimulates rectal cell prol iferation in rats. Heavy use of alcohol and cigarette smoking synergistically increases the inciden ce of cancers of the mouth. benze ne. and cervix. so that the smoker doesn't inhale as readily. causes genetic mutation in the P 53 control gene. Research also shows that a person who stops smoking decreases his or her risk of lung cancer. rubbe r. enhancing their absorption. some evidence suggests that the effects are less severe. Asbestos also may act as a p romoter for other carcinogens. Indoor air pollution. Ultraviolet radiation Exposure to ultraviolet radiation. HPV types 6 and 11 are associated with genital warts. an observation that may help explain the increased incidence of colorectal cancer in humans. The age of first sexual intercourse and the number of sexual partners are positively correlated w ith a woman's risk of cervical cancer. is common ly associated with cirrhosis of the liver. increase the ri sk of cancer. HPV is the most common cause of abnormal Papanicolaou (Pap) smears. are at risk of a specific type of lung cancer. also poses an incr eased risk of cancer. and cervica l dysplasia is a direct precursor to squamous cell carcinoma of the cervix. in which the o ral tissue directly absorbs nicotine and other carcinogens. Sunlight also releases tumor necrosis factor alpha in exposed s kin. Sexual and reproductive behavior Sexual practices have been linked to specific types of cancer. Smoke from cigars and pipes is more alkaline. a precursor to hepatocellular cancer. The risk o f lung cancer from cigarette smoking correlates directly with the duration of sm oking and the number of cigarettes smoked per day. pharynx. and interference with cell membrane permeability of the breast tissue. The suspected underlying mechanism here involves virus transmission. polyvinyl chlorides. indoor air pollution is considered to be more car cinogenic than outdoor air pollution. Many outdoor air pollutants such as arsenic. because of exposure to specific substances. especially in conjunction with cigarette smoking. hydrocarbons. Plus use of smokeless tobacco. two carcinogens that are known to cause mutations. The amount of exposure to . such as from cigarette smoke and radon. by nonsmokers also increases t he risk of lung and other cancers. and other industrial emissions as well as vehicle exhaust have been studied for their carcinogenic properties. both of which have been linked to HPV (especially types 16 and 31). Tobacco smoke contains nitrosamines and polycy clic hydrocarbons. Tobacco Cigarette smoking increases the risk of lung cancer more than tenfold over that of nonsmokers by late middle age. particularly lung ca ncer. In fact. Inhalation of secondhand smoke. possibly diminishing the immune response. The risk of breast and colorectal cancers also increases with alcohol consumpti on. most likely hu man papilloma virus (HPV). Occupation Certain occupations. Tobacco smoke is also associa ted with laryngeal cancer and is considered a contributing factor in cancer of t he bladder. impaired immune response. paint. is linked to an incr ease in oral cancers that seldom occur in persons who don't use the product. and esophagus. Furthermore. and beta-naphthylamine are at increased risk of bladder cancer. pancreas. Although the risk associated with pipe and cigar smoking is similar to that of c igarette smoking. or sunlight. such as insulation installers and min ers.

and testo sterone have been implicated as promoters of breast. Prolonged exposure to estrogen. Progesterone may play a protective role. the person's age. or pr ostate cancer. hormonal balance. Low doses can cause DNA mutations and chromosomal abnormalities. counteracting estrogen 's stimulatory effects. prescribed drugs and preexisting or concurrent conditions. prostatic. lipid. is considered a promoter for breast and endometrial cancers. which are linked to stom ach cancer . which may be linked to gastric cancer naturally occurring carcinogens (such as hydrazines and aflatoxin) in foods. stomach. Ionizing radiation Ionizing radiation (such as X-rays) is associated with acute leukemia. colon. possibly related to production of estrogen by fatty tiss ue). Likewise. ovarian. Other compounding variables include the part an d percentage of the body exposed. and rectal cancers high consumption of smoked foods and salted fish or meats and foods containing n itrites. which stimulates the proliferation of breast and endometrial cells. Hormones Hormones specifically the sex steroid hormones estrogen. and severe episodes of burning and blistering at a young age are associated with melanoma. cumulative exposure to ultraviolet sunlight is associated with basal a nd squamous cell skin cancer. and nucleic acids (macromolecules).ultraviolet radiation also correlates with the type of cancer that develops. ovarian. and large doses can inhibit cell division. The male sex hormones stimulate the growth of prostatic tissue. researc h fails to show an increased risk of prostatic cancer in men who take exogenous androgens. or it can act on intracellula r water to produce free radicals that damage the macromolecules. Ionizing radiation also can enhance the effects of genetic abnormalities. For example. including: obesity (in women only. This damage can directly affect carbohydrate. breast. which is linked to endometrial. For ex ample. increases the ris k of breast cancer. However. thyroid. Diet Numerous aspects of diet are linked to an increase in cancer. progesterone. it increases the risk of cancer in persons with a genetic abnormality tha t affects DNA repair mechanisms. and urinary tract cancers as well as multiple myel oma. endometrial. lung. breast. Estrogen. which is linked to a suspected increased risk of endometrial cancer high consumption of dietary fat (due to an increase in free radical formation). long-term use of estrogen replacement without prog esterone supplementation for menopausal symptoms increases a woman's risk of end ometrial cancer. as in women with early menarche and late menopause. whi ch are linked to liver cancer carcinogens produced by microorganisms stored in foods. p rotein.

Be at least moderately active for 30 minutes or more on most days of the week. cancer cel ls differ from normal cells in terms of cell size. Limit consumption of meats. Thus. Limit your consumption of alcoholic beverages. and cancer preventi on. ACS GUIDELINES: DIET. differentiatio n. cereals. AND CANCER PREVENTION Because of the numerous aspects of diet and nutrition that may contribute to the development of cancer. The P53 and c-myc genes are two examples of control genes: P53 can stop DNA replication if the cell's DNA has been damaged. These genes produce proteins that act as on and off switches. This spread occurs through circulation in the blood or lymphatic fluid. Be physically active and achieve and maintain a healthy weight. (See Cancer cell characteristics. which is linked to co lorectal cancer. and purpose or function. and cell production exceed s cell loss. Eat 5 or more servings of fruits and vegetables each day. uncontrollable proliferation of cells and independent spread from a primary site (site of origin) to other tiss ues where it establishes secondary foci (metastases). Choose most of the foods you eat from plant sources. especially high-fat meats. Choose foods low in fat. number.diet low in fiber (which slows transport through the gut). These controls are absent in cancer cells. c-myc helps initiate DNA replication and if it senses an error in DNA replication. Plus cancer cells can travel to distant tissues and organ systems. (See ACS guidelines: Diet. Mitotic reproduction occurs i n a sequence called the cell cycle. different cells respond to specific control genes. Eat other foods from plant sources such as breads. There is no gener alized control gene. each of the billions of cells in the human body has an internal clock that tells the cell when it is time to reproduce. NUTRITION. Limit your intake of high-fat foods. nutrition. Stay within your healthy weight range. pasta. or beans several times each day. it can cause the cell to self-destruct. if you drink at all. and they spend very little time in the resting phase. the American Cancer Society (ACS) has developed a list o f guidelines to reduce cancer risk in persons ages 2 years and older. The American Cancer Society (ACS) has developed specific nutritional guidelines for cancer prevention. grain products. rice . particularly from animal sources.) Cell growth Typically. cancer cells enter the cell cycle more frequently and at different rates. Consequently. thus providing a mechanism for controlling growth and differ entiation. and by local extension. Normal cells reproduce at a rate controlled through the activity of specific con trol or regulator genes (called proto-oncogenes when they are functioning normal ly). They're most commonly found in the synthesis and mitosis ph ases of the cell cycle.) PATHOPHYSIOLOGIC CHANGES The characteristic features of cancer are rapid. Normal cell division occurs in direct propor tion to cells lost. shape. . by unintentional transplantation f rom one site to another during surgery.

the nearby cells will signal the same type of cells to s low or cease reproduction.Hormones. released from virus-infecte d and immune cells. Examples of hormones and growth factors that affect control genes include: erythropoietin. which undergo uncontrolled cellular growth and development. may affect the cell's rate of reproduction. which stimulates connective tissue cell prolifer ation. CANCER CELL CHARACTERISTICS Cancer cells. the control genes fail to function normally. Interferon. Any of these mechanisms may lead to uncontrolled cellular reproduction. and chemicals released by neighboring cells or by immu ne or inflammatory cells can influence control gene activity. An imbalance of growth factors may occur. or the cells may fail to respond to the suppressive action of the growth factors. thus allowing the formation of only a single layer of cells. growth factors. exhibi t these typical characteristics: Vary in size and shape Undergo abnormal mitosis Function abnormally Don't resemble the cell of origin . Injured or infected nearby cells or those of the immune system also affect cellu lar reproduction. The nearby cells send out ph ysical and chemical signals that control the rate of reproduction. interleukin. In cancer cells. For example. cells that are close to one another appear to communicate with eac h other through gap junctions (channels through which ions and other small molec ules pass). This feature is called density-dependent growth inhibition. For example. which stimulates fat and connective tissue prolifera tion platelet-derived growth factor. These substances b ind to specific receptors on the cell membranes and send out signals causing the control genes to stimulate or suppress cell reproduction. stimulates cell proliferation and differentiation. which stimulates epidermal cell proliferation insulin-like growth factor. This communication provides information to the cell about the neighb oring cell types and the amount of space available. which stimulates red blood cell proliferation epidermal growth factor. released by immune cells. if the area is crowded. The actual control may be lost or the gene may become damaged. Additionally.

cells of the same type in the same site exhibit many diff erent shapes and sizes. they lose the typical characteristics of the original cell. These changes affect the cel l membrane. oat-cell lung cancer cells often produce antidiuretic hormone (ADH). cells become specialized. and nucleus. possibly becomi ng a site for hormone production. wh ite blood cells (WBCs). the cells devel op highly individualized characteristics that reflect their specific structure a nd functions in their corresponding tissue. cytoskeleton. That is. This independence is further evidenced by the ability of cancer cells to break off and travel to othe r sites. and other lipid s. Cancer cells lose the ability to differentiate. all blood cells are der ived from a single stem cell that differentiates into red blood cells (RBCs). The bilayer is composed of phospholipids. For example. Differentiation Normally. a common characteristic of canc er cells. Some anaplastic cells begin functioning as another type of cell. cal led anaplasia. and lymphocytes. As the cells beco me more specialized. platelets. (See Understanding anaplasia. The less the cells resemble the cell of ori gin. Instead of forming only a single layer. that is. Intracellular changes The abnormal and uncontrolled cell proliferation of cancer cells is associated w ith numerous changes within the cancer cell itself. The loss of control over normal growth is termed autonomy. monocytes. during development. are programmed to die and be replaced. The protein molecules help stabilize the structure of the membrane and participa . their reproduction and development slow down. h ighly differentiated cells become unable to reproduce and some. they enter a state. which is produced by the hypothalamus but st ored in and secreted by the posterior pituitary gland.Produce substances not usually associated with the original cell or tissue Aren't encapsulated Are able to spread to other sites One striking characteristic of cancer cells is that they fail to recognize the s ignals emitted by nearby cells about available tissue space. When anaplasia occurs. As differentiation is lost. UNDERSTANDING ANAPLASIA Anaplasia refers to the loss of differentiation. For example. skin cells for e xample. It consists of two layers of lipid molecules (called the lipid bilayer) with protein molecules attached to or embedded in ea ch layer. such as cholesterol. Eventually. the cancer cells no longer demonstrate the appearance and function of the original cell. the more anaplastic they are said to be. in which they no longer appear or function like the original cell . cancer cells continue to accumulate in a disorderly array. Mitosis is abnormal and chromosome defects are common.) Anaplasia occurs in varying degrees. As the anaplastic cells continue t o reproduce. dynamic semipermeable structure separates the cell's internal environ ment from its external environment. glycolipids. Cell membrane This thin.

the tu mor continues to grow only if available nutrients. Some of the other proteins and glycolipids are also absent or altered. structure. rapid proliferation. thus affecting the organization. called fibronectin. In ca ncer cells. Tumors need an available blood supply to provide nutrients and oxygen for contin ued growth. actin filaments exert a pull on the extracellular organic molecules that bind cells together. and recognition of other cells is diminished. The appearance of the mitotic cancer cell under light microsco py is often described as atypical and bizarre. anchoring junctions need not be present. epithelial cells have a shorter cell cycle than connective tissue cells. the cancer cell has a much greater metabolic demand for nutrients to sustain its growth. meaning enlarged and of various shapes and sizes. cytoplasmic components are fewer in number and abnormally shaped. are responsible for holding the cell s in place and maintaining the specific arrangement of the receptors to allow fo r the exchange of material. Disruption or blockage of gap junctions interferes with intercellular communicat ion. and repli cate. Chromatin (uncoiled chromosomes) may clump along the outer areas of the nucleus. each time undergoing successive changes and further mutations. and migration of the cel ls. adhesion. oxygen. Some tumors secrete tumor angioge . a nd division. Cytoskeleton The cytoskeleton is composed of protein filament networks including actin and mi crotubules. Add itionally. The result is uncontrolled growth. Communication between the cells becomes impaired. nuclei are pleomorphic. During this time. Microtubules control cell shape. and blood supply are adequate and the immune system fails to recognize or respond to the tumor. Thus. tumors of epithelial c ells grow more rapidly than do tumors of connective tissue cells. even in a crowded enviro nment. How fast a tumor grows depends on specific characteristics of the tumor itself a nd the host. They also are highly pigmented and have larger and more numerous nucl eoli than normal. For example. These changes affect the density of the receptors on the cell membrane and the shape of the cell. the cancer cells continue to grow. in turn. cell division can occur only when the cells are ancho red to nearby cells or to extracellular molecules via anchoring junctions. but a tumor larger than 1 to 2 mm in size has typically outgrown its available blood supply. response to growt h factors is enhanced. develop. This may be the underlying mechanism by which cancer cells continue to grow and migrate. Thus. The nuclear membrane is often irregular and commonly has proje ctions. and to remove wastes. and fewer pores. Breaks. and abnormal karyotypes (chromosome shape and number) are common changes in the chromosomes. determines the cell cycle time. fibronectin is defective or is broken down as it is produced . Permeability of the cancer cell membrane also is altered. movement. forming layers of undifferentiated cells. The chromosome defects seem to stem from the increased mitotic rate in cancer cells. or blebs. After the initial event. Les s cellular work occurs because of a decrease in endoplasmic reticulum and mitoch ondria. The location determines the originating cell type. Large glycoproteins. During its uncontrolle d. deletions. pouches. In the cancer cell. wh ich. an initiating event or events must cause a mutation that wi ll transform the normal cell into a cancer cell. Nucleus In cancer cells. Tumor development and growth Typically. they continue to divi de and can metastasize. During normal development. the functions of these components are altered. a long time passes between the initiating event and the onset of the disease. translocations.te in the transport and exchange of material between the cell and its environmen t. Effect of tumor characteristics Two important tumor characteristics affecting growth are location of the tumor a nd available blood supply. Normally. Tumor growth needs For a tumor to grow. In cancer cells.

These charact eristics include age. cervical. to meet the d emand. further enhances cancer cell proliferation. This process is called metastasis. are associated with the development of skin cancer. they can alter normal body processes and cause c achexia. tumor growth may s low. actinic keratoses. Thi s increase in receptors. precancerous or dysplast ic lesions can progress and give rise to cancer. the cells continue to grow and enlarge forming a mass or clumps of cells. the less differentiated the cells and the more rapi dly they divide. Effect of host characteristics Several important characteristics of the host affect tumor growth. and immune system function. b . or chronic inflammation causes dyspla stic changes that may be reversed by removing the initiating stimulus or treatin g its effects. the tumor can gain access to the circulation. sex h ormones influence tumor growth in breast. And the number of cancerous cells soon begins to exceed the number of normal cells. spreadin g into local tissues and invading the surrounding tissues. Localized tumor Initially. radiation. The survivors. such as during wound healing. if the person is nutritionally depleted. For example. shape. the tumor mass extends. Certain cancers are more prevalent in one sex than the other. As a result. AGE ALERT Age is an important factor affecting tumor growth. and organization of the cells leads to a condition called dysplasia. viruses. Once access is gained. This suggests that numerous or cumulative events are necessary f or the initial mutation to continue. which stimulate the formation of new blood vessels. various body tissues experience periods of benign rapid growt h. When the local tissue is blood or lymph. eventually forming a tumor. However. Numerous growth factor receptors are present on the cell membranes of rapidly growing cancer cells. Eventually. overall health status. a tumor remains localized. Yet the incidence of cancer correlates directly with increasing age. Exposure to chemicals. New blood vessels form to support continued gr owth and proliferation. Knowledge about precancerous lesions and promoter events provide the rationale for early detection and screening as important preventative measures. Many cancer cells also produce their own growth factors. and prostate ca ncers. changes in the size. For example. the y become more undifferentiated. the great er the likelihood of mutations. if the stimulus is not removed. tumor cells that detach or break off travel to distant sites in the bod y. Chronic tissue trauma also has been linked with tumor growth because healin g involves increased cell division. The mass exerts pressure on the neighboring cells. Spread of cancer Between the initiating event and the emergence of a detectable tumor. The degree of anaplasia also affects tumor growth. reproduce until the tumor reaches a diameter of 1 to 2 mm. Dysplasia Not all cells that proliferate rapidly go on to become cancerous. And the more rapidly cells divide. As tumors obtain nutr ients for growth from the host. thus promoting carcinogenesis. Remember that the more anapla stic the cells of the tumor. Relatively few canc ers are found in children. Recall that cancer cells communicate poorl y with nearby cells. sex. Conversely. Researchers believe that the hormone sensitizes the cell to the initial p recipitating factor. As the cells further mutate and divide more rapidly.nesis factors. if any. in conjunction with the changes in the cell membranes. Throughout a p erson's life span. In some cases. Removal of the lesions and use of sun block helps minimize the risk that the lesions will progress to s kin cancer. some or al l of the mutated cells may die. where tumor cells can survive and form a new tumor in the new secondary site. thickened patches on the skin of the face and hands of persons exposed to sunli ght. endometrial. Overall health status also is an important characteristic.

Reduced cell adhesion also is seen with cancer cells. travels downstream and commonly lodges in the first capi llary bed it encounters. the surviving tumor mass of cells. which eventually die because the ir blood supply has been cut off or blocked. Finally. Hematogenous spread. but a few escape the host defenses and the turbulent env ironment of the bloodstream. Then they become atta ched to the epithelium. Invasive tumor cells break down the basement membrane and w alls of blood vessels. mechanical pressure. as s hown here. and the circulation. which are the most common site of metastasis. enabling the cancer cells to enter. Experimental data indicate that the interaction of all five me chanisms is necessary for invasion. Once lodged. th e new tumor develops its own vascular network and may ultimately spread again. and the tumor sheds malignant cells into the circulation. and subsequently causing their death. blood from most organs next enters the cap illaries of the lungs. Some cancer cells produce and excrete powerful proteolytic enz ymes. Cancer cells also secrete a chemotactic factor that stimulates motility. enabling the cancer cells to ente r. HOW CANCER METASTASIZES Cancer usually spreads through the bloodstream to other organs and tissues. It's actually the firs t step in metastasis. forming a bridge -like connection. the tumor cells develop a protective coat of fibrin. These recept ors permit the cancer cells to attach to the basement membrane. For example. metastasi s occurs through the blood vessels and lymphatic system. such as collagenases and proteases destroy the normal cells and break through their basement membrane. Five mechanisms are linked to invasion: cellular multiplic ation. ultimately invading the vessel wall. they e xert pressure on surrounding cells and tissues. a thin sheet of noncellular connective tissue upon which cells rest. other cancer cells induce normal host cells to produce them. These enzymes . and in creased motility. Invasive tumor Invasion is growth of the tumor into surrounding tissues. may be due to the increased tumor growth w . As discussed in the sectio n on intracellular changes. (See How cancer metastasizes. The consequent enlargement. and clotting factors to evade detection by the immune system. lysis of nearby cells. By their very nature. and t he parenchyma of the target organ. reduced cell adhesion likely results when the cell-s tabilizing glycoprotein fibronectin is deficient or defective. possi bly the first evidence of metastasis. reduced cell adhesion. Loss of mechanical resistance leads the way for the cancer cells to spread along the lines of least resistance and occupy the space once filled by the dead cells. Lymphatic spread. In this case. interstitium. such as carria ge on instruments or gloves during surgery. As they grow. Vesicles on the cancer cell surface contain a rich supply of receptors for lamin in. platelets. The lymphatic system is the most common route for distant meta stasis. Thus.) To survive. the tumor becomes trapped in the first lymph node it encounters. Tumor cells also can be transported from one body location to another by external means. cancer cells develop fingerlike projections cal led pseudopodia that facilitate cell movement. Metastatic tumor Metastatic tumors are those in which the cancer cells have traveled from the ori ginal or primary site to a second or more distant site. Most commonly. Most of the cells die.locking their blood supply. From here. calle d a tumor cell embolus. the cancer cells a re able to move independently into adjacent tissues. These projections injure and kill neighboring cells and attach to vessel walls. and th en to a secondary site. a complex glycoprotein that is a major component of the basement membrane. cancer cells are multiplying rapidly. Tumor cells enter the lymphatic vessels through damaged basement membran es and are transported to regional lymph nodes.

anemia. a generalized wasting of fat and protein. and lac king energy or the ability to concentrate. The lymph node may f ilter out or contain some of the tumor cells. these signs and symptoms are nonspecific and can be attr ibuted to many other disorders. (See Common sites of meta stasis. The exact underlying mechanism for fa tigue is not known. weig ht loss. marked weakness. CANCER TYPE SITES FOR METASTASIS .ithin the node or a localized immune reaction to the tumor. the axillary lymp h nodes. being tired. and in fection. (See Cancer's seven warning signs . Some cancers may be diagnosed on a routine physical examination. Cachexia is characterized by a norexia (loss of appetite). they are a frequent site for metastasis. Pain can be physically and emotionall y draining. In breast cancer. malnutrition. The ACS developed a mne monic device to identify cancer-warning signs. For example. Lung cancer can interfere w ith gas exchange and oxygen supply to the heart and peripheral tissues.) Unfortunately. Stress. pain. Accumula ting waste products and muscle loss from the release of toxic products of metabo lism or other substances from the tumor further add to the fatigue. and anemia can contribute to complaints of f atigue. The very existence of the tumor may contribute to fatigue.) SIGNS AND SYMPTOMS In most patients. Other factors also play a role in fatigue. but it is believed to be the combined result of several path ophysiologic mechanisms. These patients may present with some of the commoner signs and symptoms of advancing disease. cachexia. consequent lack of energy reserves. limiting the further spread. COMMON SITES OF METASTASIS The chart below lists some of the more common sites of metastasis for selected c ancers. such as fatigue. A malignant tumor nee ds oxygen and nutrients to grow. anxiety. This organ tropism may be a result of growth factor or hormones secreted by the targe t organ or chemotactic factors that attract the tumor. which are in close proximity to the breast. whether lymphatic or vascu lar. Other types of cancer seem most likely to spread to specific organs. and other emotional factors further compound the pr oblem. even before the person develops any signs or symptoms. because the lungs receive all of the systemic venous retu rn. Fatigue Patients commonly describe fatigue as feelings of weakness. thrombocytopenia and leukopenia. The c ells that escape can enter the blood from the lymphatic circulation through plen tiful connections between the venous and lymphatic systems. Others may display some early warning signals. is common in persons with ca ncer. a vascular tumor can cause lethargy secondary to inadequate oxygen supply to the brain. it depletes the surrounding tissues of ad equate blood and oxygen supply. and altered metabolism of proteins. and lipids. encountered by the circulating tumor mass determines the location of the me tastasis. Typically. the more effective the treatm ent is likely to be and the better the prognosis. alterations in taste perception. A person with cachexia typically appears emaciated and wasted. Cachexia Cachexia. Thus. Unfortunately. For example. And if the person lacks the energy required for self-care. the first capillary bed. carbohydra tes. a person may not notice or heed the warning signs. and experie nces an overall deterioration in physical status. early satiety. anemia. are a common site of metast asis. the earlier the cancer is found. Metastatic sites.

and wasting begins. lung. liver Anorexia may accompany pain or adverse reactions to chemotherapy or radiation th erapy. relying on carbohydrates and fats for energy production. muscle wasting. liver. This feeling is believed to be the result of metabolites released from the tumor . As cancer cells appropri ate nutrients to fuel their growth. the body spares protein. bone Ovarian Peritoneum. which normally keep fluid in the blood vessels. brain Colorectal Liver. or salty sensations also contribute to anorexia. normal tissue becomes starved and depleted. sour. peritoneum Lung Liver. cancer cells metabolize both protein and fatty acids to produce energy. Diminished perception of sweet. enables fluid to esca pe into the tissues). lungs Prostate Bone Testicular Lungs. . brain. Under normal circumstances. Food that once seemed seasoned and palatable now tastes bland. Also. Protein-calorie malnutrition may cause hypoalbuminemia. tumor necrosis factor produced by the body in response to cancer contrib utes to cachexia. edema (the lack of serum proteins. lung. when starvation occurs. bone. Each letter in the word CAUTION represents a possible warni ng sign that should spur an individual to see a doctor.Breast Axillary lymph nodes. CANCER'S SEVEN WARNING SIGNS The American Cancer Society has developed an easy way to remember the seven warn ing signs of cancer. liver. C hange in bowel or bladder habits A sore that doesn't heal U nusual bleeding or discharge T hickening or lump in the breast or elsewhere I ndigestion or difficulty swallowing O bvious change in a wart or mole N agging cough or hoarseness Patients with cancer commonly feel sated after eating only a few bites of food. The high metabolic activity of malignant tumor cells carries with it the need fo r nutrients above those required for normal metabolism. and immunodeficiency. diaphragm. Howeve r.

blood vessels. direct invasion of the bone marrow. development o f fistulas. the severity of the pain usually increases. Leukopenia greatly increases the patient's risk of infection. pain occurs when the v iscera. Additionally. as cancer progresses . Leukopenia and thrombocytopenia Typically. In areas where space for the tumor to grow is limited. obstructions. or chemotherapy or radiation. Anem ia in patients with metastatic cancer is commonly the result of chronic bleeding . Malnutrition and anemia further increase the patient's risk of infection. Diagnostic tests serve several purposes. platelet function may be impaired in certain hematologic cancers. leukopenia and thrombocytopenia occur when cancer invades the bone ma rrow. or other tissues and organs leads to tissue hypoxia. accumulation of lactic acid. particularly those with my elosuppression from treatment. however. Generally. and possibly cell death. creating a favorable environment for microbial growth. which is normally hollow. pain is the re sult of one or more of the following: pressure obstruction invasion of sensitive tissue visceral surface stretching tissue destruction inflammation. is stretched by a tumor. pain is typically absent or mild. as in GI cancer. WBCs. Also.Pain In cancer's early stages. severe malnutrition. DIAGNOSIS A thorough history and physical examination should precede sophisticated diagnos tic tests. This injury sets up a painful inflammatory response. compression is a common cause of pain. Even when the platelet count is normal . Anemia Cancer of the blood-forming cells. Chemotherapy and radiation therapy to the bones also can cause leukopenia. Cancer cells also release proteolytic enzymes that directly injure or destroy ne ighboring cells. Infection Infection is common in patients with advanced cancer. or immunosuppression from hormonal release in response to chronic st ress. The choice of diagnostic tests is determined by the patient's present ing signs and symptoms and the suspected body system involved. or RBCs may directly cause anemia. effusions. The patient with t hrombocytopenia is at risk of hemorrhage. such as in the brain or b one. including: . and ulcerations may develop. Pressure on or obstruction of nerves.

organs. ultrasonography. The radiologist evaluates their distribution (uptake) thr oughout tissues. Useful tests for early detection and staging of tumors include screening tests. brain. and bone. the exception is the bo ne scan. The area of uptake is termed either a hotspot or a coldspot (an area of decrea sed uptake). and abdomen to evaluate for neu rologic. They may provide valuable information about the possibility of cancer even before the patient develops signs and symptoms. and magnetic resonance imaging ( MRI). CT and MRI scans have largely replaced it. Typically tumors are revealed as coldspots. This specialized X-ray technique is helpful in evaluating tumors of the lymph nodes and metastasis. . Examples of organs commonly evaluated with radioactive isotope scanning include thyroid. For example. The single most important diagnostic tool is the biopsy for direct histolo gic study of the tumor tissue. CT scans ar e commonly obtained of the brain and head. Because lymphangiography is invasive a nd may be difficult to interpret. abdominal. body. in which hotspots indicate the presence of disease. and their flow can be monitored by lymphangiography. a chest X-ray may be indicated to identify lung cancer if the patient is an old er smoker or to rule out lung metastasis in a patient with colorectal cancer. X-rays. endoscopy. It also c an reveal different characteristics of tissues within a solid organ. This type of scanning provides a vie w of organs and regions within the organ that cannot be seen with a simple X-ray . Screening tests Screening tests are perhaps the most important diagnostic tools in the preventio n and early detection of cancer. radioactive isotope scanning (nuclear medicine imaging). Computed tomography Computed tomography (CT) scanning evaluates successive layers of tissue by using narrow beam X-ray to provide a cross-sectional view of the structure. pelvic. The type and location of the X-ray is determined by the patient's signs and symptoms and the suspected location of the tumor or metastases.establishing tumor presence and extent of disease determining possible sites of metastasis evaluating affected and unaffected body systems identifying the stage and grade of tumor. and thoracic cancers. The ACS has recommended specific screening tests to aid in the early detection of ca ncer. liver. computed tomogr aphy (CT) scanning. spl een. and organ systems. X-rays are ordered to identify and evaluate changes in tissue den sities.) Diagnosis by imaging X-rays Most commonly. Radioactive isotope scanning A specialized camera detects radioactive isotopes that are injected into the blo od stream or ingested. ACS GUIDELINES: EARLY CANCER DETECTION The following recommendations from the American Cancer Society focus on five com mon cancers whose survival rates can be improved if detected early. (See ACS guidelines: Early cancer detection. Some X-rays such as those of the GI tract (barium enema) and the urinary tract ( intravenous pyelogram) involve the use of contrast agents. Radiopaque substances also can be injected into the lymphatic system.

SCREENING AREA RECOMMENDATIONS Generalized cancer-related checkup (including health counseling and specific exa minations for malignant and nonmalignant disorders) Every three years for ages 20 to 40 Every year for ages 40 and older Breast € Mammogram Clinical breast exam Self breast exam Every year for ages 40 and older Every year for ages 40 and older Every 3 years for ages 20 to 39 Monthly for ages 20 and older Colon and rectum (one of the examinations below) Men and women age 50 and older: Fecal occult blood and flexible sigmoidoscopy Colonoscopy .

Double-contrast barium enema Digital rectal examination Every year Every 10 years Every 5 to 10 years At the same time as sigmoidoscopy. colonoscopy. until 3 or more consecutive satisfactory examinations with normal find . or double-contrast barium enema Prostate Men age 50 and older with life expectancy of at least 10 years and younger men a t high risk: Prostate specific antigen (PSA) Digital rectal examination Annually Annually Cervix Sexually active females or females age 18 and older: Pap smear Pelvic examination Annually.

aspirate fluid.) Tumor cell markers have many clinical uses. abdominal. endoscopy (rectal polyps and esophageal lesions). Like CT scanning. called tumor markers or biologic markers. the removal of a portion of suspicious tissue. Ultrasound helps to differentiate cysts from solid tumors and is commonly use d to provide information about abdominal and pelvic cancer. Biopsy A biopsy. During endoscopy. Endoscopy Endoscopy provides a direct view of a body cavity or passageway to detect abnorm alities. Common endoscopic sites include the upper and lower gastrointestinal tr act. Tumor cell markers include hormones. or obtain tissue samples for histologic examinati on. for example: screening people who are at high risk of cancer diagnosing a specific type of cancer in conjunction with clinical manifestations . dermal punch ( skin or mouth). and bronchial tree of the lungs.ings. the physician can excise small tumors. The specimen then undergoes laboratory anal ysis for cell type and characteristics to provide information about the grade an d stage of the cancer. is the only definitive method to diagnose cancer. are produced either by the cancer cell's genetic material dur ing growth and development or by other cells in response to the presence of canc er. it's commonly used to evaluat e neurologic. or urine. and surgical e xcision (visceral tissue and nodes). Biopsy tissue samples can be taken by curettage. These substances. fine-needle aspiration (breast). flui d aspiration (pleural effusion). (See Common tumor cell markers. and thoracic cancers. then may be performed less frequently Annually Endometrium € Tissue sampling At the onset of menopause Ultrasonography Ultrasonography uses high frequency sound waves to detect changes in the density of tissues that are difficult or impossible to observe by radiology or endoscop y. Magnetic resonance imaging MRI uses magnetic fields and radio frequencies to show a cross-sectional view of the body organs and structures. Tumor cell markers Some cancer cells release substances that normally aren't present in the body or are present only in small quantities. pelvic. enzymes. Markers may be found on the cell membrane of the tumor or in the blood. antigens. and antibodies. genes. cere brospinal fluid.

They ar e seldom encapsulated and are often poorly delineated. Commonl y encapsulated with well-defined borders. Tumor cell markers provide a method for detecting and monitoring the progression of certain types of cancer. COMMON TUMOR CELL MARKERS Tumors cell markers may be used to detect. the disease may be too far advanced to treat. havin g cells that may differ considerably from those of the tissue of origin. and therefore causing only sligh t damage. benign tumors are well differentiat ed. also are associated with tumor cell markers. mucinous ovarian cancer tumors typically do not express the ovarian cancer marker CA-125. such as pancreatitis or ulcerative colitis. Typically. For example. MARKER MALIGNANT CONDITIONS NONMALIGNANT CONDITIONS Alpha-fetoprotein (AFP) . M ost malignant tumors metastasize through the blood or lymph to secondary sites. They rapidly expand in al l directions. Some nonmalignant diseases. how ever. Tumor cell markers may also be ass ociated with other benign (nonmalignant) conditions. their cells closely resemble those of the tissue of origin. By the time the tumor cell marker level is elevated. benign tumors grow slowly. Conversely. Unfortunately.monitoring the effectiveness of therapy detecting recurrence. The chart below highlights some of the more commonly used tumor cell markers and their associated malignant and nonmalignant conditions. causing extensive damage as they infiltrate surrounding tissues. diagnose. Benign tumors do not metastasize. Perhaps the worst drawback is that the absence of a tumor cell marker does not m ean that a person is free of cancer. TUMOR CLASSIFICATION Tumors are initially classified as benign or malignant depending on the specific features exhibited by the tumor. several disadvantages of tumor marke rs may preclude their use alone. Alone. so that a negative t est doesn't eliminate the possibility of ovarian malignancy. or treat cancer. For example. most malignant tumors are undifferentiated to varying degrees. they aren't sufficient for a diagnosis. often displ acing but not infiltrating surrounding tissues. Most tumor cell markers are not specific enough to identify one certain type of cancer. that is.

Endodermal sinus tumor Liver cancer Ovarian germ cell cancer Testicular germ cell cancer (specifically embryonal cell carcinoma) Ataxia-telangiectasia Cirrhosis Hepatitis Pregnancy Wiskott-Aldrich syndrome Carcinoembryonic antigen (CEA) Bladder cancer Breast cancer Cervical cancer Colorectal cancer Kidney cancer Liver cancer .

Lymphoma Lung cancer Melanoma Ovarian cancer Pancreatic cancer Stomach cancer Thyroid cancer Inflammatory bowel disease Liver disease Pancreatitis Tobacco use CA 15-3 Breast cancer (usually advanced) Lung cancer Ovarian cancer .

Prostate cancer Benign breast disease Benign ovarian disease Endometriosis Hepatitis Lactation Pelvic inflammatory disease Pregnancy CA 19-9 Bile duct cancer Colorectal cancer Pancreatic cancer Stomach cancer Cholecystitis Cirrhosis Gallstones .

Pancreatitis MARKER MALIGNANT CONDITIONS NONMALIGNANT CONDITIONS CA 27-29 Breast cancer Colon cancer Kidney cancer Liver cancer Lung cancer Ovarian cancer Pancreatic cancer Stomach cancer Uterine cancer Benign breast disease Endometriosis .

Kidney disease Liver disease Ovarian cysts Pregnancy (first trimester) CA 125 Ovarian cancer Pancreatic cancer Endometriosis Liver disease Menstruation Pancreatitis Pelvic inflammatory disease Peritonitis Pregnancy Human chorionic gonadotropin (HCG) Choriocarcinoma .

Embryonal cell carcinoma Gestational trophoblastic disease Liver cancer Lung cancer Pancreatic cancer Specific dysgerminomas of the ovary Stomach cancer Testicular cancer Marijuana use Pregnancy Lactate dehydrogenase Almost all cancers Ewing's sarcoma Leukemia Non-Hodgkin's lymphoma Testicular cancer .

Anemia Heart failure Hypothyroidism Lung disease Liver disease MARKER MALIGNANT CONDITIONS NONMALIGNANT CONDITIONS Neuron-specific enolase (NSE) Kidney cancer Melanoma Neuroblastoma Pancreatic cancer Small cell lung cancer Testicular cancer Thyroid cancer Wilms' tumor .

Tissue type Histologically. or in ectodermal tissues. and most of t he urinary and reproductive system. Tumors arising from glandular epithelial tissue are commonly called aden ocarcinomas. which develop into supporting stru . Carcinomas are tumors of epithelial tissue. degree of differentiatio n (grading). They may originate in the endodermal tissues. Three cell layers form during the early stages of embryonic devel opment: Ectoderm primarily forms the external embryonic covering and the structures that will come into contact with the environment. which develop into external structures such as th e skin. Endoderm gives rise to the internal linings of the embryo. such as the epithelia l lining of the pharynx and respiratory and gastrointestinal tracts. and extent of the disease (staging). High-grade tumors are poorly d ifferentiated and are more aggressive than low-grade tumors. muscles. supporting tissue. Mesoderm forms the circulatory system. the type of tissue in which the growth originates classifies mal ignant tumors. such as the stomach and intest ine. which develop into internal structures.Unknown Prostatic acid phosphatase (PAP) Prostate cancer Benign prostatic conditions Prostate-specific antigen (PSA) Prostate cancer Benign prostatic hypertrophy Prostatitis Malignant tumors are further classified by tissue type. Sarcomas originate in the mesodermal tissues. Early-stage cancers carry a more favorable prognosis than later-stage cancers that have spread to n earby or distant sites.

T FOR PRIMARY TUMOR The anatomic extent of the primary tumor depends on its size. cells exhibit no similarity to tissue of origin. muscle. malignant tumors are classified by their degree of differentiati on. N2. TNM staging enables reliable comparison of treatments and survi val rates among large population groups. which e valuates Tumor size. the greater the tumor cells' similarity t o the tissue of origin. from plasma cells. Levels range from MX to M4 as follows: MX distant metastasis can't be assessed M 0 no evidence of distant metastasis . such as the bone. N3 increasing involvement of regional lymph nodes M FOR DISTANT METASTASIS Metastasis denotes the extent (or spread) of disease. Nodal involvement. Sarcomas may be further classif ied based on the specific cells involved. Typically. in order of increasing clinical severity.) UNDERSTANDING TNM STAGING The TNM (tumor. This classifica tion system provides an accurate tumor description that is adjustable as the dis ease progresses. fat. For example. lymphomas. T2. Some differences in classification m ay occur. Tumor stages progress from TX to T4 as follows: TX primary tumor can't be assessed T 0 no evidence of primary tumor Tis carcinoma in situ T1. cells vary somewhat in size and shape w ith increased mitosis.ctures. depending on the primary cancer site. The most commonly used method for staging is the TNM staging system. node. Grade 1: Well differentiated. myelomas. Grading Histologically. depth of invasion. T4 increasing size or local extent (or both) of primary tumor N FOR NODAL INVOLVEMENT Nodal involvement reflects the tumor's spread to the lymph nodes as follows: NX regional lymph nodes can't be assessed N 0 no evidence of regional lymph node metastasis N1. It also offers a convenient structure to stan dardize diagnostic and treatment protocols. and Metastatic progress. cells closely resemble the tissue of origin and ma intain some specialized function. or blood. (See Understanding TNM staging. Grade 2: Moderately well differentiated. malignant tumors arising from pigmented cells are called melanomas. and from lymphatic tissue. and surface spread. mitosis is greatly increased. cells vary widely in size and shape with little resemblance to the tissue of origin. Grade 4: Undifferentiated. Grade 3: Poorly differentiated. T3. a malignant tumor is graded on a scale of 1 t o 4. The greater their differentiation. and metastasis) system developed by the American Joint Com mittee on Cancer provides a consistent method for classifying malignant tumors b ased on the extent of the disease. Staging Malignant tumors are staged (classified anatomically) by the extent of the disea se.

a nd infection. and neutropenia. localizatio n. Hypercalcemia is the most common metabolic abnormality experienced by cancer patients. Indeed. M3. Cancer treatment has four goals: cure. immunotherap y (also called biotherapy). thrombocytopenia. to alleviate symptoms when the disease is beyond control prophylaxis. such as fluid and electrolyte imbalances secondary to anorexia. leukopenia. As with any treatment regimen. COMMON CANCER EMERGENCIES The following chart shows what can cause certain oncologic emergencies and the u nderlying malignancy.M1 single. Each may be used alone or in co mbination (called multimodal therapy). in addition to primary. Cancer treatment is further categorized by type according to when it is used. to arrest tumor growth palliation. to eliminate microscopic disease and promote c ure or improve the patient's response salvage. complications may arise. M4 multiple foci or multiple organ metastasis TREATMENT Cancer treatments include surgery. to manage recurrent disease. but the patient i s known to be at high risk of tumor development or recurrence. many complicatio ns of cancer are related to the adverse effects of treatment. can reach intolerable levels. to provide treatment when no tumor is detectable. Pain. including anemia. which accompanies all progressing cancers. stage. bone marrow suppression. and responsiveness of the tumor and on limitations imposed by the patient's c linical status. depending on the type. radiation therapy. as follows: primary. solitary distant metastasis M2. and hormone therapy. or diarrhea. to eradicate the cancer and promote long-term patient survival control. chemotherapy. to eradicate the disease adjuvant. vomiting. EMERGENCIES AND CAUSE ASSOCIATED MALIGNANCY .

osteoclast-activating factor. or prostaglandin levels Breast cancer Lung cancer Multiple myeloma Renal cancer Disseminated intravascular coagulation € Widespread clotting in arterioles and capillaries and simultaneous hemorrhage .Cardiac tamponade € Fluid accumulation around pericardial space or pericardial thickening secondary to radiation therapy Breast cancer Leukemia Lymphoma Melanoma Hypercalcemia € Increased bone resorption due to bone destruction or tumor-related elevation of parathyroid hormone.

tumor obstruction of lymphatic channels or pulmonary veins.Hematologic malignancies Mucin-producing adenocarcinomas Malignant peritoneal effusion € Seeding of tumor into the peritoneum. excess intraperitoneal fluid production or release of humoral factors by the tumor Ovarian cancer Malignant pleural effusion € Implantation of cancer cells on pleural surface. shed of necrotic tumor cells into the pleural space or thoracic duct perforation Breast cancer GI tract cancer Leukemia Lung cancer (most common) Lymphoma Testicular cancer Spinal cord compression € .

or cervix Melanoma Superior vena cava syndrome € Impaired venous return secondary to occlusion of vena cava Breast cancer Lymphoma Lung cancer EMERGENCIES AND CAUSE ASSOCIATED MALIGNANCY Syndrome of inappropriate antidiuretic hormone (SIADH) € Ectopic production by tumor. gastrointestinal tract. mimicking or enhanced effects on kidney. may be induced by chemotherapy Bladder cancer GI tract cancer Hodgkin's disease . breast. abnormal stimulation of hypothalamus-pituitary axis . prostate.Encroachment on spinal cord or cauda equina due to metastasis or vertebral colla pse and displacement of bony elements Cancer of lung. kidney.

ulceration. Ultimately the choice belongs t o the patient. . and surrounding structures that may be at high risk of disease spread.Prostate cancer Sarcomas Small-cell lung cancer Tumor lysis syndrome € Rapid cell destruction and turnover caused by chemotherapy or rapid tumor growth Leukemias Lymphomas Certain complications are life threatening and require prompt intervention.) Surgery Surgery. Here. such as pain. It may be performed to diagnose the disease. Palliative surgery is used to relieve complications. and is occasionally done for prophylaxis. including lymph nodes. A common method of surgical removal of a small tumor mass is called wide and loc al excision. hemorrhage. nearby involved st ructures. Much controversy exists over this type of surgery because of the possible long-term physiologic and psychological effects. (See Common cancer emergencies. or achieve palliation. along with surrounding tissues. nonvital tissues or organs with a hig h potential for developing cancer are removed. A radical or modified radic al excision removes the primary tumor along with lymph nodes. When used as a primary treatment method. Prophylactic surgery may be done if a patient has personal or familial risk fact ors for a particular type of cancer. The su rgical biopsy procedure is diagnostic surgery. The tumor mass is removed along with a small or moderate amount of easily accessible surrounding tissue that is normal. or adverse eff ects of treatment. One example is prophylactic maste ctomy. The health care professional and the patient should discuss the type of surgery. although potential benefits ma y significantly outweigh the downside. once the mainstay of cancer treatment. Examples include a cordotomy to relieve int ractable pain and bowel resection or ostomy to remove a bowel obstruction. surgery may be performed to remove hormone-producing glands and thereby limit the growth of a hormone-sensitive tumor. Often a radical excision results in some degree of disfigurement and altered fu nctioning. Today's less-radical surgical procedures such as a lumpectomy instead of mastectomy are more acceptable to patients. is now typically combined with o ther therapies. or pressure. o bstruction. Addit ionally. secondary involvement of other organs due to disease spread. and continuing surgery then remov es the bulk of the tumor. surgery is an attempt to remove the entire tumor (or as much as possible. initiate primary tr eatment. Thes e oncologic emergencies may result from the effects of the tumor or its by-produ cts. by a procedure call ed debulking).

Patients receiving radiation therapy must have frequent blood counts. e ither immediately or when they attempt to divide. For example. it aims to destroy dividing canc er cells while damaging normal cells as little as possible. a protracted schedule allows t ime for normal tissue to recover between doses. dyspnea. such as weakness. GI epithelium. fatigue. cells of th e bone marrow. Two types of radiati on are used to treat cancer: ionizing radiation and particle bean radiation. ulcerations. cells most vulnerable to radiation therapy are those that undergo frequent cell division. Generally. steroids. the cells die. RADIATION'S ADVERSE EFFECTS Radiation therapy can cause local adverse effects depending on the area irradiat ed. Thus. n ormal cells recover from radiation faster than malignant cells. and gonads. colognes. nausea. and hemorrhage. They are seldom severe enough to require discontinuing radiation but they may mandate a dosage adjustment. anorexia. It can also promote healing o f pathologic fractures after surgical stabilization and delay metastasis. Combining radiation and surgery can minimize the need for radical surgery. Normal cells are also affected but can recover. frequent small meals. obstruction. which also damage the DNA. single dose of radiation has greater cellular effects than fra ctions of the same amount delivered sequentially. previous irradiation. postoperative doses preven t residual cancer cells from multiplying or metastasizing. Therapeutic radiation may be delivered by external beam radiation or by intracav itary or interstitial implants. Use d alone or in conjunction with other therapies. particular ly of WBCs and platelets if the target site involves areas of bone marrow produc tion. and immune status. Use of implants requires that anyone who comes i n contact with the patient while the internal radiation implants are in place mu st wear radiation protection. and preserve anatomic function. Bot h target the cellular DNA. How well the treatment meets this goal is k nown as the therapeutic ratio. lymph.) Systemic a dverse effects. The guiding principle for radiation therapy is that the dose administered be lar ge enough to eradicate the tumor. cough. for example. and other topical agents during treatment. preoperative doses of radiation shrink a large tumor to operable size while preventing further spread of the disease during surgery.Radiation therapy Radiation therapy involves the use of high-energy radiation to treat cancer. but small enough to minimize the adverse effec ts to the surrounding normal tissue. The particles can cause more cell damage than ionizing ra diation does. Radiation therapy has both local and systemic adverse effects. depending on blood supply. such as covering the i rradiated area with loose cotton clothing to protect it from light and avoiding deodorants. After the wound heals. vomiting. because it affect s both normal and malignant cells. and anemi a may respond to antiemetics. fluid maintenance. (See Radiation's adverse effects. If this damage isn't repaired. Radiation interacts with oxygen in the nucleus to break strands of DNA and inter acts with water in body fluids (including intracellular fluid) to form free radi cals. Success of treat ment and damage to normal tissue also vary with the intensity of the radiation. The chart below highlights some of the more commonly seen local effects and the measures to manage them. prolo ng survival. oxygen saturation. Ionizing radiation deposits energy that damages the g enetic material inside the cancer cells. Radiation also may render tumo r cells unable to enter the cell cycle. Particle bean radiation uses a special machine and fast-moving particle s to treat the cancer. . and rest. malignant effus ions. Although a large. Adverse effects Radiation may be used palliatively to relieve pain. Normal and malignant cells respond to radiation differently. Radiation also requires special skin care measures.

AREA IRRADIATED ADVERSE EFFECT MANAGEMENT Head Alopecia Gentle combing and grooming Soft head cover Mucositis Cool carbonated drinks Ice Soft. nonirritating diet Viscous lidocaine mouthwash Monilia Medicated mouthwash Dental caries Gingival care .

Prophylactic fluoride to teeth Chest Lung tissue irritation Avoidance of persons with upper respiratory infections Humidifier. if necessary Smoking cessation Steroid therapy Pericarditis Myocarditis Antiarrhythmic drugs Esophagitis Analgesia Fluid maintenance Total parenteral nutrition Kidneys .

which may induce reg ression of a tumor and its metastasis.Anemia Azotemia Edema Headache Hypertensive nephropathy Lassitude Nephritis Fluid and electrolyte maintenance Monitoring for signs of renal failure Abdomen/pelvis Cramps Diarrhea Fluid and electrolyte maintenance Loperamide and diphenoxylate with atropine Low-residue diet Chemotherapy Chemotherapy includes a wide range of antineoplastic drugs. It's particularly useful in controlling r .

They prevent cell replication by breaki ng and cross-linking DNA. Acting in any phase of the cell cycle. repeated cycles of chem otherapy are used to destroy nondividing cells as they enter the cell cycle to b egin active proliferation. or they may inhibit the growth of hormone-susceptible tumors by changing their chemical environment.esidual disease and as an adjunct to surgery or radiation therapy. substituting themselves for purines and pyrimidines which a re essential for DNA and ribonucleic acid (RNA) synthesis. Act ing primarily in the M phase of the cell cycle. Therefore. regression of the tumor requires repeated doses of drugs. Tumor cells that are in the active phase of cell division (called the growth fra ction) are the most sensitive to chemotherapeutic agents. Other chemotherapeutic agents include podophyllotoxins and taxanes which. They exert their effe ct during the S phase of the cell cycle. Therefore. Nondividing cells are the least sensitive and thus are the most potentially dangerous. they bind t o DNA and generate toxic oxygen free radicals that break one or both strands of DNA. The may alter the cell environment. These agents include adrenocorticosteroi ds. Antimetabolites prevent cell growth by competing with metabolites in the product ion of nucleic acid. and aromatase inhibitors. As a palli ative treatment. It can induce long remissions and sometimes effect cure. Hodgkin's disease. The goal is to eradicate enough of the tumor so that the immune system can destroy the re maining malignant cells. such as hydroxyurea and L-asparaginase. or testicular cancer. Antitumor antibiotics block cell growth by binding with DNA and interfering with DNA-dependent RNA synthesis. they interfere with the formatio n of the mitotic spindle by binding to microtubular proteins. They must be de stroyed to eradicate a malignancy completely. interfere with formation of the mitotic spindle. Combination therapy typically includes drugs with different toxici ties and also synergistic actions. thereby affecting the permeability of the cell membrane. Hormones and hormone antagonists impair cell growth by one or both of two mechan isms. and miscellaneo us agents. like p lant alkaloids. androgens. gonadotropin inhibitors. which seem to be cell-cycle s pecific agents but whose mode of action is unclear. especially in patients with childhoo d leukemia. Plant (Vinca) alkaloids prevent cellular reproduction by disrupting mitosis.) A combination of drugs from different categories may be used to maximize the tum or cell kill. Depending on the type of cancer. (See Chemotherapy's action i n the cell cycle. choriocarcinoma. chemotherapy aims to improve the patient's quality of life by t emporarily relieving pain and other symptoms. one or more different categories of chemotherap eutic agents may be used. The most commonly used types of chemotherapeutic agent s are: Alkylating agents and nitrosoureas inhibit cell growth and division by reacting with DNA at any phase of the cell cycle. Every dose of a chemotherapeutic agent destroys only a percentage of tumor cells . Use of combination therapy also helps prevent .

with adjustments for general condition and degree of myelos uppression. and they can cause v enous sclerosis and pain when administered. Biologic agents are usually combined with chemothe rapy or radiation therapy. To minimize the ri sk of extravasation. whereas other biologic agents activate or influence the immune system. Many patients approach chemotherapy apprehensively. intracavitarily. leukopenia. Immunotherapy Immunotherapy. Expl anations about what to expect. Dosages are calculated according to the patient' s body surface area. subcutaneously. BMT restores hematologic and immunologi c function. their availability may be r estricted and their adverse effects generally unpredictable. they may cause deep cutaneous necrosis. including possible adverse effects. Many antineoplastic agents are given intravenously. several ap proaches appear promising. and melanoma. Tamoxifen. They need to be allowed to e xpress their concerns and be provided with simple and truthful information. impairing cellular growth by causing changes in the cell during specific phases of the cell cycle. If extravasated. intravenously. The pharmacologic action of a given drug determines whether it is administered o rally. Hormonal therapy Hormonal therapy is based on studies showing that certain hormones can inhibit t he growth of certain cancers. Two useful immunologic techniques that are not used to treat cancer directly are the use of monoclonal antibodies and colony stimulating factors (CSF). Adrenocortical steroids are effective in treating leuk emias and lymphomas because they suppress lymphocytes. Antineoplastic agents can cause transient changes in normal tissues. vomiting because they irritate the gastrointestinal epithelial cells. can help mini mize the fear and anxiety. Some biologic agents such as interferons have a direct antitumor effect. Many types of immunotherapy are still experimental. and alopecia and dermatitis because they destroy hair follicles and skin cells. affecting the cell at any phase during the cel l cycle. this hormone inhibits testosterone release and tumor growth. With long-term use. Monoclon al antibodies labeled with radioisotopes may be injected into the body to help l ocalize tumors. Biologic agents are useful in treating hairy cell leukemia. blocks estrogen receptors in breast tumor cells that re quire estrogen to thrive. requiring debridement and skin grafting. The illustration below shows where the cell-cycle-specific agents work to disrupt cancer cell growth. or by arterial infusion. The most widely used are the interferons and interleukin-2. and thrombocytopenia because they suppress bone marrow function. Adverse effects Chemotherapy causes numerous adverse effects that reflect the drugs' mechanism o f action. where . is treatment with agents known as biologic response modifiers. CHEMOTHERAPY'S ACTION IN THE CELL CYCLE Some chemotherapeutic agents are cell-cycle specific. lymphoma. leuprolide. an anti estrogen hormonal agent. The antibodies attach to surface antigens on tumor cells. For example. intramuscularly. For example. most drugs with the potential for direct tissue injury are now given through a central venous catheter. However. renal cell carcinoma. antineoplastic agents typ ically cause anemia. is used to treat prostate cancer. and some breast cancers. now commonly called biotherapy. and are most effective in the early stages of cancer. Other a gents are cell-cycle nonspecific. intrathe cally.the development of drug-resistant mechanisms by the tumor cells. the luteinizing hormone-releasing hor mone analogue. Bone marrow transplantation (BMT) is the therapy of choice for curing many malig nancies that otherwise require high-dose chemotherapy or radiation. such as leuk emia. e specially those with proliferating cells.

CSFs. REVIEWING COMMON CANCERS The chart below highlights the important signs and symptoms and diagnostic test results for some of the most common cancers. papilledema. may be used to support the patient who has low blood counts caused by chemothera py. blurred vision and meningeal irritation secondary to leukemic infiltration or cerebral bleeding Liver. which are naturally produced by many cells in the immune system. facial palsy.they are identified by radiologic techniques. One day soon these antibodies may be linked with toxins to destroy specific cancer cells without disturbing health y cells. and lymph node enlargement related to leukemic cell infiltration . lassitude related to anemia from bone marrow invasion Pallor and weakness related to anemia Chills and recurrent infections related to proliferation of immature nonfunction ing white blood cells Bone pain from leukemic infiltration of bone Neurologic manifestations including headache. spleen. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Acute leukemia € Sudden onset of high fever resulting from bone marrow invasion and cellular prol iferation within bone marrow Thrombocytopenia and abnormal bleeding secondary to bone marrow suppression Weakness.

Differential WBC count reveals cell type. appearing as ov al or irregularly shaped. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Bladder cancer € Early stages: Commonly asymptomatic Later: . and nasolabi al folds) appearing as small. lightly pigmented scaly plaques with sharply defined. depressed centers wi th firm elevated borders with enlargement resulting from basal cell proliferatio n in the deepest layer of epidermis with local extension Superficial basal cell epitheliomas. Lumbar puncture reveals leukemic infiltration to cerebrospinal fluid (CSF).Bone marrow aspiration reveals proliferation of immature white blood cells (WBCs ). sclerotic yellow to white plaques without distinct borders resulting fr om basal cell proliferation Incisional or excisional biopsy and cytology confirm the cell type. eyelid regions. Complete blood count (CBC) shows thrombocytopenia and neutropenia. threadlike elevated borders resembling psoriasis or eczema resulting from basal cell proliferation Sclerosing basal cell epitheliomas occurring on the head and neck and appearing as waxy. Basal cell carcinoma € Noduloulcerative lesions usually on face (forehead. occasionally pigmented. pinkish and translucent papules with telan gietactic vessels crossing surface. commonly on chest and back. smooth.

possibly palpable mass resulting from tumor growth . differentiates presence of tu mor from cyst. Computed tomography (CT) scan reveals thickened bladder wall and enlarged retrop eritoneal lymph nodes. Excretory urography identifies large early stage tumor or infiltrating tumor.Gross painless intermittent hematuria secondary to tumor invasion Suprapubic pain after voiding from pressure exerted by the tumor or obstruction Bladder irritability and frequency related to tumor compression and invasion Cystoscopy and biopsy confirm cell type. Pelvic arteriography confirms tumor invasion into bladder wall. Retrograde cystography reveals changes in structure and bladder wall integrity. Urinalysis reveals hematuria and malignant cytology. Ultrasonography detects metastasis beyond bladder. swollen. Bone cancer € Possibly asymptomatic Bone pain especially at night from tumor disruption of normal structural integri ty and pressure on surrounding tissues Tender.

TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Breast cancer € Hard stony mass in the breast related to cellular growth Change in symmetry of breast secondary to growth of tumor on one side Skin thickening or dimpling. scaly skin around nipple or changes in nipple. edem a or ulceration related to tumor cell infiltration to surrounding tissues Warm.Pathologic fractures secondary to tumor invasion and destruction of bone causing weakening Hypercalcemia from ectopic parathyroid hormone production by the tumor or increa sed bone resorption Limited mobility (late in the disease) from continued tumor growth and disruptio n of bone strength Incisional or aspiration biopsy confirms cell type. and CT scan reveal tumor size. Bone scan reveals increased uptake of isotope in area of tumor. bone scan. hot. pink area from inflammation and infiltration of surrounding tissues Unusual discharge or drainage indicating tumor invasion and infiltration into th . Serum alkaline phosphatase is elevated. Bone X-rays.

Hormonal receptor assay identifies tumor as hormonal dependent.e ductal system Pain related to advancement of tumor and subsequent pressure Hypercalcemia or pathologic fractures secondary to metastasis to bone Breast examination reveals lump or mass in breast. Ultrasonography reveals solid tumor differentiating it from a fluid filled cyst. Mammography reveals presence of mass and location. Cervical cancer € Abnormal vaginal bleeding with persistent vaginal discharge and postcoital pain and bleeding related to cellular invasion and erosion of the cervical epithelium Pelvic pain secondary to pressure on surrounding tissues and nerves from cellula r proliferation Vaginal leakage of urine and feces from fistulas due to erosion and necrosis of cervix . Needle or surgical biopsy confirms the cell type. Bone scan and CT scan reveal metastasis. and liver function studies r eveal liver metastasis. liver biopsy. Elevated alkaline phosphatase levels.

Serum globulin levels are decreased. and lymphangiography identify metastasis. . nuclear imaging scan. and anemia related to the hypermetabolic activity of cell ular proliferation and increased tumor growth needs Pap smear reveals malignant cellular changes. weight loss. CT scan.Anorexia. Chronic lymphocytic leukemia € Slow onset of fatigue related to anemia Splenomegaly secondary to increase numbers of lysed red blood cells being filter ed Hepatomegaly and lymph node enlargement from infiltration by leukemic cells Bleeding tendencies secondary to thrombocytopenia Infections related to deficient humoral immunity CBC count reveals: numerous abnormal lymphocytes with mild but persistently elevated WBC count granulocytopenia common but WBC count increasing as disease progresses hemoglobin levels below 11 g/dL neutropenia lymphocytosis thrombocytopenia. Colposcopy identifies the presence and extent of early lesions. Biopsy confirms cell type.

a nd rectal pressure related to increasing tumor size and ulceration of mucosa Dark red or bright red blood in stools secondary to erosion and ulceration of mu cosa Digital rectal examination (DRE) reveals mass. fatigue. Stools for guaiac test positive. Tumor on left colon: Intestinal obstruction including abdominal distention. vomiting. cramps. pain. pressure. anorexia. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Colorectal cancer € Tumor on right colon: Black tarry stools secondary to tumor erosion and necrosis of the intestinal lin ing Anemia secondary to increased tumor growth needs and bleeding resulting from nec rosis and ulceration of mucosa Abdominal aching. Proctosigmoidoscopy or sigmoidoscopy reveals tumor mass. or cramps secondary to pressure from tumor Weakness. weight loss secondary to increased tumor growth nee ds Vomiting as disease progresses related to possible obstruction. .Bone marrow aspiration and biopsy show lymphocytic invasion.

CT scan reveals areas of possible metastasis. tumor growth and increasing obstruction. Carcinoembryonic antigen (tumor marker) may be elevated. Esophageal cancer € No early symptoms Dysphagia secondary to tumor interfering with passageway Weight loss resulting from dysphasia. Endoscopic examination with punch and brush biopsies confirms cancer cell type.Colonoscopy visualizes tumor location up to the ileocecal valve. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Hodgkin's disease € . Barium X-ray shows location and size of lesions not manually or visually detecta ble. a nd anorexia related to tumor growth needs Ulceration and subsequent hemorrhage from erosive effects (fungating and infiltr ative) of the tumor Fistula formation and possible aspiration secondary to continued erosive tumor e ffects Esophageal X-ray with barium swallow and motility studies reveals structural and filling defects and reduced peristalsis.

lymphocytopenia. Hematologic tests show: mild to severe normocytic anemia normochromic anemia elevated.Painless swelling in one of lymph nodes (usually the cervical region) with a his tory of upper respiratory infection Persistent fever. and spleen biopsies reveal histolog ic presence of cells. lymph node. nerve irritation. or reduced WBC count differential with any combination of neutrophilia. Bone marrow. monocytosis. and lymphangiography detec t lymph and organ involvement. weight loss. and eosinophilia. nodular fibrosis. and neck vein engorgement second ary to direct invasion from mediastinal lymph nodes Enlargement of retroperitoneal nodes. bone scan. pericardial effusion. fatigue. liver. abdominal CT scan. or absence of pulse due to obstruction of pres sure of tumor in surrounding lymph nodes Pericardial friction rub. and liver related to progression o f disease and cellular infiltration Lymph node biopsy confirms presence of Reed-Sternberg cells. lung scan. mediastinal. Chest X-ray. a nd necrosis. night sweats. and malaise related to hyp ermetabolic state of cellular proliferation and defective immune function Back and neck pain with hyperreflexia related to epidural infiltration Extremity pain. Laryngeal cancer . spleen. normal. Elevated serum alkaline phosphatase indicates bone or liver involvement.

weakness. or laryngography identif ies borders of the lesion. Liver cancer € Mass in right upper quadrant with a tender nodular liver on palpation secondary to tumor cell growth Severe pain in epigastrium or right upper quadrant related to tumor size and inc reased pressure on surrounding tissue Weight loss. Chest X-ray reveals metastasis. biopsy. laryngeal tomography. anorexia related to increased tumor growth needs Dependent edema secondary to tumor invasion and obstruction of portal veins . CT scan.€ Hoarseness persisting longer than 3 weeks related to encroachment on the true vo cal cord Lump in the throat or pain or burning when drinking citrus juice or hot liquids related to tumor growth Dysphagia secondary to increasing pressure and obstruction with tumor growth Dyspnea and cough related to progressive tumor growth and metastasis Enlargement of cervical lymph nodes and pain radiating to ear related to invasio n of lymphatic and subsequent pressure Laryngoscopy shows presence of tumor. Xeroradiography.

Alpha-fetoprotein levels are elevated. Serum aspartate aminotransferase. or hypocholesterolemia. and bilirubin are elevated indicating abnormal liver fun ction. leukocytosis. hemoptysis. serum laborato ry studies reveal hypoglycemia. dyspnea. hoarseness. Liver scan may show filling defects. lactic dehydrogenase. weakness. Chest X-ray reveals possible metastasis. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Lung cancer € Cough. weight loss. anorexia related to increased tumor growth needs f rom hypermetabolic state of cellular proliferation Bone and joint pain from cartilage erosion due to abnormal production of growth hormone Cushing's syndrome related to abnormal production of adrenocorticopic hormone Hypercalcemia related to abnormal production of parathyroid hormone or bone meta . alanine aminotransferase. wheezing.Liver biopsy confirms cell type. alkaline phosphatase . Serum electrolyte studies reveal hypernatremia and hypercalcemia. and chest pain related to loca l infiltration of pulmonary membranes and vasculature Fever.

and dyspnea from bronchial obstruction rel ated to increasing growth Shoulder pain and unilateral paralysis of diaphragm due to phrenic nerve involve ment Dysphagia related to esophageal compression Venous distention. Bone scan. atelectasis. severe arm pain secondary to invasion o f the chest wall Chest X-ray shows an advanced lesion. bone marrow biopsy. . increasing dyspnea. Bronchoscopy locates tumor. washings reveal malignant cell type. Sputum cytology reveals possible cell type. pneumonitis. Thoracentesis shows malignant cells in pleural fluid. and CT scan of brain and abdomen reveal metastasi s. neck and chest edema secondary to obstruction of vena cava Piercing chest pain. Needle lung biopsy confirms cell type. including size and location.stasis Hemoptysis. Mediastinal and supraclavicular node biopsies reveal possible metastasis. CT scan of the chest delineates tumor size and relationship to surrounding struc tures. facial.

Lumbar puncture shows increased pressure and protein levels. Skull X-ray. tumor cells in CSF.Malignant brain tumors € Headache. learning and mem ory Local: Dementia. sensory disturbances (anesthesia. hemianopia. paresthesia. gait disturbances. Brain scan reveals area of increased uptake in location of tumor. or gait disorders) . hemiparesis. ataxia. personality or behavioral changes. and autonomic dysfunction depending on location of tumor. Stereotactic tissue biopsy confirms cell type. vertigo. nystagmus. and papilledema secondary to increased intracranial pressure from tumor invasion and compression of surroundi ng tissues Cranial nerve dysfunction secondary to tumor invasion or compression of cranial nerves Focal deficits including motor deficits (weakness. and. and cerebral angiography identify location of mass. cranial nerve dysfunction. Neurologic assessment reveals manifestations of lesion affecting specific lobe. decreased glucose l evels. CT scan. paralysis. . or disturbances of vision or he aring) secondary to tumor invasion or compression of motor or sensory control ar eas of the brain Disturbances of higher function including defects in cognition. Sensory loss. dizziness. langua ge disorders. nausea and vomiting. MRI. occasionally. seizures. pupillary abnormali ties.

n otched margin typically on areas of chronic irritation Nodular melanoma: Polypoidal nodule with uniformly dark discoloration appearing as a blackberry bu t possibly flesh colored with flecks of pigment around base Lentigo maligna mela noma: Large flat freckle of tan. Multiple myeloma € Severe constant back pain that increases with exercise secondary to invasion of bone Arthritic symptoms including achiness. joint swelling. Chest X-ray. or textural changes secondary to m alignant transformation of melanocytes in the basal layer of the epidermis or wi thin the aggregated melanocytes of an existing nevus Superficial spreading melanoma: Red. whitish. inflammatio n or soreness. or slate color with irregularl y scattered black nodules on surface Skin biopsy with histologic examination confirms cell type and tumor thickness. and blue color over a brown or black background with an irregular. bleeding. or CT of brain reveals metastasis. brown. white.TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Melanoma € Enlargement of skin lesion or nevus accompanied by changes in color. itching. Bone scan reveals bone metastasis. and tenderness possibly f rom vertebral compression . black. ulceration. CT scan of chest and abdomen.

particularly in the skull. Bone X-rays early reveal diffuse osteoporosis. and spine. in later stages. Serum electrophoresis shows elevated globulin spike that is electrophoretically and immunologically abnormal. and infections secondary to tumor effects on bone marrow cell production Thoracic deformities and increasing vertebral complaints secondary to extension of tumor and continued vertebral compression Loss of 5 inches or more of body height due to vertebral collapse CBC shows moderate to severe anemia. pelvis. differential may show 40% to 50% lymphocyte s but seldom more than 3% plasma cells.Pathologic fractures resulting from invasion of bone causing loss of structural integrity and strength Azotemia secondary to tumor proliferation to the kidney and pyelonephritis due t o subsequent tubular damage from large amounts of Bence Jones protein. hypercalc emia. bleeding. and hyperuricemia Anemia. Differential smear reveals Rouleaux formation from elevated erythrocyte sediment ation rate. Bone marrow aspiration detects myelomatous cells (abnormal number of immature pl asma cells). they show multip le sharply circumscribed osteolytic lesions. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS . Urine studies reveal Bence Jones protein and hypercalciuria.

bone marrow. Serum protein levels are normal.Non-Hodgkin's lymphoma € Lymph node swelling from cellular proliferation Dyspnea and coughing related to lymphocytic infiltration of oropharynx Enlarged tonsils and adenoids from mechanical obstruction by the tumor Abdominal pain and constipation secondary to mechanical obstruction of surroundi ng tissues Lymph node biopsy reveals cell type. CBC may show anemia. Bone and chest X-rays. Ovarian cancer € Vague abdominal discomfort. dyspepsia and other mild gastrointestinal complaints from increasing size of tumor exerting pressure on nearby tissues . bowel. and excretory urography show evidence of metastasis. Uric acid level may be elevated or normal. or skin reveals malignant cells. lymphangiography. Serum calcium levels are elevated if bone lesions are present. liver and spleen scans. abdominal CT sc an. liver. Biopsy of tonsils.

CT. Mammography is normal to rule out breast cancer as the primary site. Lymphangiography reveals lymph node involvement. CBC may show anemia. constipation from obstruction resulting from increased tumor size Pain from tumor rupture. Abdominal ultrasound. or infection Feminizing or masculinizing effects secondary to cellular type Ascites related to invasion and infiltration of the peritoneum Pleural effusions related to pulmonary metastasis Pap smear may be normal. Excretory urography reveals abnormal renal function and urinary tract abnormalit ies or obstruction. . torsion. Liver functions studies are abnormal with ascites. Barium enema shows obstruction and size of tumor. Chest X-ray reveals pleural effusion with distant metastasis. or X-ray delineates tumor presence and size.Urinary frequency.

Paracentesis fluid aspiration reveals malignant cells. Angiography reveals vascular supply of the tumor. secondary to effects of increased tumor grow th needs Abdominal or back pain secondary to tumor pressure Blood in the stools from ulceration of gastrointestinal tract or ampulla of Vate r Laparotomy with biopsy confirms cell type. and malaise. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Pancreatic cancer € Jaundice with clay-colored stools and dark urine secondary to obstruction of bil e flow from tumor in head of pancreas Recurrent thrombophlebitis from tumor cytokines acting as platelet aggregating f actors Nausea and vomiting secondary to duodenal obstruction Weight loss. Ultrasound identifies location of mass. Tumor markers such as carcinoembryonic antigen and human chorionic gonadotropin are positive. anorexia. . Endoscopic retrograde cholangiopancreatography visualizes tumor area.

.MRI identifies tumor location and size. Prostatic surface antigen is elevated. Serum laboratory tests reveal increased serum bilirubin. serum amylase and serum lipase. urine retention secondary to obstruction of urinary tract from tumor growth Hematuria (rare) from infiltration of bladder DRE reveals a small hard nodule. Plasma insulin immunoassay shows measurable serum insulin in the presence of isl et cell tumors. Prothrombin time (PT) is prolonged. dribbling. Marked elevation of alkaline phosphatase indicates biliary obstruction.or hyperglycemia. Fasting blood glucose may reveal hypo. Prostate cancer € Symptoms appearing only in late stages Difficulty initiating a urinary stream. Hemoglobin and hematocrit may show mild anemia. Elevations of aspartate aminotransferase and alanine aminotransferase indicate n ecrosis of liver cells.

MRI.Serum acid phosphatase levels are elevated. Renal cancer € Pain resulting from tumor pressure and invasion Hematuria secondary to tumor spreading to renal pelvis Possible fever from hemorrhage or necrosis Hypertension from compression of renal artery with renal parenchymal ischemia an d renin excess Polycythemia secondary to erythropoietin excess Hypercalcemia from ectopic parathyroid hormone production by the tumor or bone m etastasis Urinary retention secondary to obstruction of urinary flow Pulmonary embolism secondary to renal venous obstruction CT scan. . cystoscopy and nephrotomog raphy. and excretory urography identify tumor mass. and retrograde pyelography. ultrasound. CT scan.V. Elevated alkaline phosphatase levels and positive bone scan indicate bone metast asis. I. and renal angiography identify presence of tumor and help differentiate i t from a cyst.

polycythemia. dorsa of hands and forearms from cell prolife ration in sun-damaged areas Induration and inflammation as cell changes from nonmalignant to malignant cell Ulceration from continued cell proliferation Excisional biopsy confirms cell type. TYPE AND FINDINGS DIAGNOSTIC TEST RESULTS Stomach cancer € Chronic dyspepsia and epigastric discomfort related to tumor growth in gastric c ells and destruction of mucosal barrier Weight loss. CBC shows anemia. aspartate aminotransferase. anemia. anorexia. feelings of fullness after eating. Serum calcium levels are elevated. bilirubin. Squamous cell carcinoma € Lesions on skin of the face. and fatigue se condary to increased tumor growth needs Blood in stools from erosion of gastric mucosa by tumor . ears.Liver function tests show increased levels of alkaline phosphatase. a lanine aminotransferase. and prolonged PT. and increased erythrocyte sedimentation rate. Urinalysis reveals gross or microscopic hematuria.

hemoptysis. ultrasound. and abnormal mucosa with or without ulceration. and abdominal CT scan reveal mass and possible met astasis. loss of flexibility and distensibility. liver and bone scans. CT scans. Excretory urography detects ureteral deviation from para-aortic node involvement . Serum alpha-fetoprotein and beta human chorionic gonadotropin levels as tumor ma rkers are elevated.Barium X-ray with fluoroscopy shows tumor or filling defects in outline of stoma ch. and liver biopsy reveal metastasis. . Surgical excision and biopsy reveals cell type. Gastroscopy with fiberoptic endoscopy visualizes gastric mucosa including presen ce of gastric lesions for biopsy. Lymphangiography. Testicular cancer € Firm painless smooth testicular mass and occasional complaints of heaviness seco ndary to tumor growth Gynecomastia and nipple tenderness related to tumor production of chorionic gona dotropin or estrogen Urinary complaints related to ureteral obstruction Cough. X-rays. and shortness of breath from invasion of the pulmonary system Transillumination of testicles reveals tumor that does not transilluminate.

Dilatation and curettage identifies malignancy in patients whose biopsies were n . dysphagia. and endocervical biopsies are positive for malignant cell s. cervical. ultrasound. Needle biopsy confirms cell type.Thyroid cancer € Painless nodule or hard nodule in an enlarged thyroid gland or palpable lymph no des with thyroid enlargement reflecting tumor growth Hoarseness. Uterine (endometrial) cancer € Uterine enlargement secondary to tumor growth Persistent and unusual premenopausal bleeding or postmenopausal bleeding from er osive effects of tumor growth Pain and weight loss related to progressive infiltration and invasion of tumor c ells and continued cellular proliferation Endometrial. and dyspnea from increased tumor growth and pressure on s urrounding structures Hyperthyroidism from excess thyroid hormone production from tumor Hypothyroidism secondary to tumor destruction of the gland Thyroid scan reveals hypofunctional nodes or cold spots. CT scan. and chest X-ray reveal medullary cancer. revealing cell type.

Chest X-ray and CT scan reveal metastasis.egative. Schiller's test reveals cervix resistant to staining. Barium enema identifies possible bladder or rectal involvement. 3 INFECTION Handbook of Pathophysiology 3 INFECTION What is infection? Risk factors € Weakened defense mechanisms € Environmental factors € Developmental factors Pathogen characteristics Stages of infection Infection-causing microbes € Bacteria € Viruses € Fungi € Parasites € Mycoplasmas € Chlamydia Pathophysiologic changes € Inflammation Signs and symptoms € Fever € Leukocytosis € Chronic inflammation Diagnosis Treatments € Infections .

malnutrition. yet infection remains the most common cause of human disease. and cirrhosis can suppress the i mmune response. Even in coun tries with advanced medical care. a weakened immune system makes it easier for these pathogens t o invade the body and launch an infectious disease. Infe ctious diseases range from relatively mild illnesses to debilitating and lethal conditions: from the common cold through chronic hepatitis to acquired immunodef iciency syndrome (AIDS). Impaired function of white blood cells (WBCs). Diabetes. This weakened state is refer red to immunodeficiency or immunocompromise. env ironmental and developmental factors. The severity of the infection varies with the pathogeni city and number of the invading microorganisms and the strength of host defenses . n asal passages.The twentieth century encompassed astonishing advances in treating and preventin g infection such as potent antibiotics. For infection to be transmitted. infectious reservoir with a portal of exit. as well as low levels of T and B cells. (See Chain of infection. Risk f actors for the development of infection include weakened defense mechanisms. and genitourinary organs defensive structures such as the cilia that sweep foreign matter from the airway s (See How microbes interact with the body. and a susceptible host. However. chronic stress. Weakened defense mechanisms The body has many defense mechanisms for resisting entry and multiplication of m icrobes. However. infectious disease remains a major cause of de ath. An immunodeficiency may be congenital ( caused by a genetic defect and present at birth) or acquired (developed after bi rth). the potential for infection increases.) RISK FACTORS A healthy person can usually ward off infections with the body's own built-in de fense mechanisms: intact skin normal flora that inhabit the skin and various organs lysozymes (enzymes that can kill microorganisms or microbes) secreted by eyes.) a healthy immune system. Such reproduc tion injures the host by causing cell damage from microorganism-produced toxins or from intracellular multiplication. CHAIN OF INFECTION . characterizes immunodeficiencies. or pregnancy. and pathogen characteristics. or by competing with host metabolism. the following must be present: causative agent. complex immunizations. Acquired immunodeficiency may result from infection. The very young and the very old are especially susceptible. mode of transmission. as can drugs such as corticosteroids and chemotherapy. renal failure. if an imbalance develops. WHAT IS INFECTION? Infection is the invasion and multiplication of microorganisms in or on body tis sue that produce signs and symptoms as well as an immune response. and modern sanita tion. glands. stomach. a portal of e ntry into the host.

airborne. The vehicle is not harmful in itsel f but may harbor pathogenic microbes and thus serve as an agent of disease trans mission. MODE OF TRANSMISSION The mode of transmission is the means by which the infectious agent passes from the portal of exit in the reservoir to the susceptible host. As with portals of exit. plasma. Vector-borne transmission occurs when an intermediate carrier. CAUSATIVE AGENT A causative agent for infection is any microbe capable of producing disease. PORTAL OF ENTRY Portal of entry refers to the path by which an infectious agent invades a suscep tible host. urine. the result of immunodeficiency is the same. Indirect contact occurs when a susceptible person comes in contact with a contam inated object. this portal is the site where the organism grows. genitourinary. sputum. Direct contact refers to person-to-person spread of organisms through actual phy sical contact. and then are spread widely b y air currents and inhaled. Usually. multiply. Some organisms use more than one transmission mode to get from the reservoir to a new host. the transmission mode varies with the s pecific microbe. Usually. The human body has many defense mechanisms for resisting the entry and multiplic ation of pathogens. providing the essential requirements for a microbe to survive at specific stages in its life cycle. SUSCEPTIBLE HOST A susceptible host is also required for the transmission of infection to occur. and genital secretions also serve as portals o f exit. Infections can be t ransmitted through one of four modes: contact. this path is the same as the portal of exit.An infection can occur only if the six components depicted here are present. Examples of vehicles are water. PORTAL OF EXIT The portal of exit is the path by which an infectious agent leaves its reservoir . in some cases. Droplet transmission results from contact with contaminated respiratory secretio ns. Blood. When these mechanisms function normally. and dr oplet spread (contact with droplets that enter the environment). Airborne transmission occurs when fine microbial particles containing pathogens remain suspended in the air for a prolonged period. where insects commonly t ransmit disease. emes is. stool. and gastrointestinal (GI) tracts. and the placenta ( in transplacental disease transmission from other to fetus). indirect contact. food . The portal of exit varies from one infectious agent to the next. serum. and vector-bor ne. A vehicle is a substance that maintains the life of the microbe until it's inges ted or inoculated into the susceptible host. Regardless of cause. Common portals of e xit associated with human reservoirs include the respiratory. and other animals can all serve as reservoirs. wound drainage. People who are immunodeficient . human beings. Vector-b orne transmission is of most concern in tropical areas. transfers a microbe to another living organism. and feces. Inanimate objects. RESERVOIR The reservoir is the environment or object in or on which a microbe can survive and. The body's abil ity to recognize and fight pathogens is impaired. vehicle. Contact transmission is subdivided into direct contact. medications. Rem oving one link in the chain prevents infection. in a weakened host. an infectious agent is more likely to invade the body and launch an infectious disease. However. blood. or vector. such a s a flea or a mosquito. It differs from airborne transmission in that the droplets don't remain susp ended in the air but settle to surfaces. the skin and mucous membranes. infection does not occur.

Alon g with a balanced diet. DOUBLE BENEFIT Some of the microorganisms of the normal human flora interact with the body in w ays that mutually benefits both parties. Advancing age. HOW MICROBES INTERACT WITH THE BODY Microbes may interact with their host in various ways. PATHOGEN CHARACTERISTICS A microbe must be present in sufficient quantities to cause a disease in a healt hy human. and untended skin is more likely to allow invasion. The most common type of infection in tod dlers affects the respiratory tract. they're notoriously difficult to expel. Frequent washing rem oves surface microbes and maintains an intact barrier to infection. obtain nutrients from the human host. are more acutely ill when they become i nfected. inadequate physical barriers. Escherichia coli organisms. malnutrition. Lack of immunization also contributes to incidence of childho od diseases. w hich is usually dangerous only in the presence of severe immunosuppression. can weaken defenses by impairing blood flow and nutrie nt delivery to body systems. witho ut which the body can't mount an effective attack against microbe invasion. medical and surgical treatments. Environmental factors Other conditions that may weaken a person's immune defenses include poor hygiene . on the other hand. including the microbe's patho . poor hygiene increases the risk of i nfection. For example. lubricants and emollients may be use d to prevent cracks and breaks. Unclean skin harbors microbes and offers an environment for them to co lonize. and require a much longer time to heal. in return. Dust can facilitate transportation of pathogens. which the human body needs for blood clotting. Accidents are common in childhood as well.are more susceptible to all infections. When young children put toys and other obje cts in their mouths. and broken or abraded skin opens the way for b acterial invasion. but it may d amage the skin. per sons with intact immune systems can usually resist infection with aspergillus. SINGLE BENEFIT Other microbes of the normal flora have a commensal interaction with the human b an interaction that benefits one party (in this case. Good hygiene promotes normal host defenses. To maintain skin integrity. they increase their exposure to a variety of pathogens. Chronic diseases. such as diab etes and atherosclerosis. This means tha t they harm the host while they benefit from their interaction with the host. the microbes) without ody affecting the other. Fortunately. partly as a result of decreasing thymus function. part of the normal intestinal flora. as children pr ogress from daycare facilities to schools. and lice infestation commonly pass from one child to the next at this age. Developmental factors The very young and very old are at higher risk for infection. Protein malnutrition inhibits the production of antibodies. chronic diseases. is associated with a declining immune system. An infant exposed to an infectio us agent usually develops an infection. The body needs a balanced diet to provide the nutrients that an effective immune system needs. The se verity of an infection depends on several factors. The number needed to cause a disease varies from one microbe to the ne xt and from host to host and may be affected by the mode of transmission. the body needs adequate vitamins and minerals to use ing ested nutrients. emotional and physical stressors. dustborne spores o f the fungus aspergillus transmit the infection. If the inhaled spores become es tablished in the lungs. and inadequate immunization. Skin diseases. The immune system doesn't fully develop until about age 6 months. they secrete vitamin K. such as impetigo. Exposure to communicable diseases continues throughout childhood. PARASITIC INTERACTION Some pathogenic microbes such as helminths (worms) are parasites.

Specificity is the range of hosts to which a microbe is attracted. others can enter only if the skin or mucous membrane is broken. Antigenicity is the degree to which a pathogen can induce a specific immune resp onse. as discussed under the topic Chain of infection. Most microbe s can't live and multiply outside a reservoir. incubation. and the still-contagious host makes vague complaints of feeling unwell. acute illness. Infection with a pathogen known to be particularly viru lent requires early diagnosis and treatment. may be almost instantaneous or last for years. and viabil ity. Adhesiveness is the ability of the pathogen to attach to host tissue. Invasiveness (sometimes called infectivity) is the ability of a microbe to invad e tissues. microbes are activ ely destroying host cells and affecting specific host systems. The prodromal stage (stage two) follows incubation. It describes a pathogen's potential to dam age host tissues by producing and releasing toxins. Some microbes produce enzymes that enhan ce their invasiveness. the likelihood that it will cause pathogenic changes or disea se. any infection can be life-threatening in an immunodeficient patient. Virulence is the severity of the disease a pathogen can produce. Toxigenicity is related to virulence. those that disseminate quickly throughout the host's body generate an antibody response. STAGES OF INFECTION Development of an infection usually proceeds through four stages. Some patho gens secrete a sticky substance that helps them adhere to tissue while protectin g them from the host's defense mechanisms. In stage three. Microbes that invade and localize in tissue initially stimulate a cellular response. The patient recog . virulence. Some microbes may be attracted to a wide range of both humans and animals. antigenicity. while others selec t only human or only animal hosts. Some microbes can enter through intact skin. that is. The first stag e. Virulence can v ary depending on the host defenses. Viability is the ability of a pathogen to survive outside its host. invasiv eness. adhesiveness.genicity. Quantity refers to the number of microbes that succeed in invading and reproduci ng in the body. toxigenicity. the pathogen is replicating and the infected person is contagious. quantity. During this time. Factors that affect pathogenicity include the microbe's specificity.

) Viruses lack the genes nece ssary for energy production. the convalescent stage (stage four) begins when the body's defen se mechanisms have confined the microbes and healing of damaged tissue is progre ssing. and fever. Bacteria Bacteria are simple one-celled microorganisms with a cell wall that protects the m from many of the defense mechanisms of the human body. spheres (cocci). parasites. such as inflammation. fungi. and their tendency to form protective capsules (encapsulated or nonencapsulated) or spores (sporulating or nonsporulating). altering its function or killing it.) Viruses Viruses are subcellular organisms made up only of a ribonucleic acid (RNA) nucle us or a deoxyribonucleic acid (DNA) nucleus covered with proteins. mycoplasma. They depend on the ribosomes and nutrients of infec ted host cells for protein production. Endotoxins are contained in the cell walls of gram-negative bacteria . Rather. clotting. the specific virus. chicken pox. and mucous membranes. rod-shaped bacill i. (See Viral infection of a host cell. (See How bacteria dam age tissue. b roken skin. INFECTION-CAUSING MICROBES Microorganisms that are responsible for infectious diseases include bacteria. and whether the intracellular environment provides good living conditions for the virus. and means of transmission (re spiratory. Viruses can produce a wide variety of illnesse s. herpes simplex. they invade a host cell and stimulate it to participate in f orming additional virus particles. are transmitted through blood. GI. sexual). such as the intestinal bacteria that produce vitamins. Exotoxins also ca n cause diffuse reactions in the host. bleeding. rickettsia. Finally. are beneficial. HOW BACTERIA DAMAGE TISSUE Bacteria and other infectious organisms constantly infect the human body. cholera. COMPARING BACTERIAL SHAPES Bacteria exist in three basic shapes: rods (bacilli). so tiny that only an electron microscope can make them visible. and chlamydiae.nizes which area of the body is affected and voices complaints that are more spe cific. (See Comparing bacterial shapes. and spira ls (spirilla). thei r mobility (motile or nonmotile). and they are released during lysis of the bacteria. (See How viruses size up. Examples of bacterial infection include staphylococcal wound infection. herpes zoster. and genital tracts. such as human immunodeficiency virus (HIV). they affe ct the vomiting center of the brain and cause gastroenteritis. hepatitis B and C. (See Gram-positive and gram-negative bacteria. the cells release exotoxins. They're the s mallest known organisms. Most viruses enter the body through the respiratory. infect ious mononucleosis. including the common cold. and rubella. Others ar . vi ruses. which cause cell damage. A f ew. shape. Bacteria can be classified according to shape spherical cocci. bacteria possess all the other mechanisms they need to survive and rapidl y reproduce. oral.) During bacterial growth. Bacteria damage body tissues by interfering with essential cell function or by r eleasing exotoxins or endotoxins. Some. fecal. Although they lack a nu cleus. enzymes that damage the host cell. and streptococcal pneumonia. Signs and symptoms depend on the status of the host cell.) Independent of the host cells. Some viruses destroy surrounding tissue and r elease toxins. The estimated 400 viruses that infect hum ans are classified according to their size. and spiral-shaped spirilla. viruses can't replicate. Enterotoxins are a sp ecific type of exotoxin secreted by bacteria that infect the GI tract.) Bacteria can al so be classified according to their need for oxygen (aerobic or anaerobic).

Parasites Parasites are unnicellular or multicellular organisms that live on or within ano ther organism and obtain nourishment from the host. fungi live on organic matter. skin. which invade host cells. which. antibiotic treatment or a change in the pH of the su sceptible tissues (because of a disease. on animals and plants. The most notorious retrovirus t oday is HIV. oval-shaped organisms) or molds (organisms with hyp hae. the smallest of the cellular microbes th at can live outside a host cell. such as mites. causing leakage. such as diabetes. To infect a host. Found almost everywhere on earth. which changes viral RNA into DNA. Superficial fungal infe ctions cause athlete's foot and vaginal infections. For example. fleas. bacteria must first enter it. For exa mple. . They take only the nutrients they need and usually don't kill their hosts. Lacking cell wa lls. Depending on the environment. Helminths can infect the human gut. some fungi may occur in both forms. Fungi Fungi have rigid walls and nuclei that are enveloped by nuclear membranes. and GI tract. The result is a di sruption of normal cell function or cell death (see illustration below). vagina. They occur as yeast (single-cell. impairs the heart's ability to pump enough blood to vital organs (see illustration below). although some may be parasitic.e harmful. Mycoplasmas Mycoplasmas are bacterialike organisms. and on a wide variety of unlikely mate rials. it can cause yeast infe ctions of virtually any part of the body but especially the mouth. They can live both inside and outside their host. in turn. Retroviruses are a unique type of virus that carry their genetic code in RNA rat her than the more common carrier DNA. as some organisms multiply. The tissues supplied by these vessels may be deprived of blood and damaged (see illustration below). Other toxins can damage the cell walls of small blood vessels. or branching filaments). they extend into deeper tissue and eve ntually gain access to the bloodstream. such as oral contraceptives) can wipe out the normal bacteria that normally keep the yeast population in check. they can assume many different shapes ranging from coccoid to filamentous. in water and soil. causing illnesses ranging from the common cold to life-threatening se ptic shock. or use of certain dru gs. and ticks. This fluid loss results in decreased blood pressure. and arthropods. such as pinworms and tapeworms. In addition. GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA This flowchart highlights the different types of gram positive and gram-negative bacteria. Candida albicans is part of the body's normal flora but under certain circumstances. They do this either by adhering to the mucosal surface and directly invading the host cell or by attaching to ep ithelial cells and producing toxins. The host cell then incorpora tes the alien DNA into its own genetic material. Examples of parasites that can pr oduce an infection if they cause cellular damage to the host include helminths. the diphtheria toxin damages heart muscle by inhibiting protein synthesis. These RNA viruses contain the enzyme rever se transcriptase. Some toxins cause blood to clot in small blood vessels. arthropods commonly cause skin and systemic disease.

The y depend on host cells for replication and are susceptible to antibiotics. which may be similar or very different from host to host.The lack of a cell wall makes them resistant to penicillin and other antibiotics that work by inhibiting cell wall synthesis. a person will complain of some common. arterioles at or near the site of the injury briefly constrict and then dilate. which fu rther increase capillary permeability. Escherichia coli (E. Inflammation The inflammatory response is a major reactive defense mechanism in the battle ag ainst infective agents. The consequent movement of plasma into the interstitial space causes edema. contributing to edema. bacteria-like organisms that can cause life -threatening illness. Rickettsial infections that occur in the United States include Rocky Mountain spotted fever. signs and symptoms that are more specific provide evidence of the microbe's target. T hey are a common cause of infections of the urethra. Most of the signs and symptoms result from ho st responses. typhus. bladder. replicates (D). appearance. causing an increase in fluid pressure in the capillar ies. depending on the pathogen invol ved and the organ system affected. However. Mycoplasmas can cause primary atyp ical pneumonia and many secondary infections. VIRAL INFECTION OF A HOST CELL The virion (A) attaches to receptors on the host-cell membrane and releases enzy mes (called absorption) (B) that weaken the membrane and enable the virion to pe netrate the cell. inflammatory cells release histamine and bradykinin. Rickettsia Rickettsia are small. they must live ins ide another. HOW VIRUSES SIZE UP Viruses vary in size. and behavior. They may be coccoid. and Q fever. rickettsia require a host cell for replication. This illustration compares the s izes of selected viruses with the size of a typical bacterium. nonspecific signs and symptoms. In the vascular stage. such as fever. Be cause they're live viruses. coli). Chlam ydiae are transmitted by direct contact such as occurs during sexual activity. rod-shaped. fallopian tubes. white blood cells (WBCs) and platelet . and matures. Acute inflammation has two stages: vascular and cellul ar. and through exposure to their waste products. The virion removes the protein coat that protects its genetic material (C). Rickettsia are transmitted by the bites of a rthropod carriers. In the acute sta ge. gram-negative. Chlamydia Chlamydiae are smaller than rickettsia and bacteria but larger than viruses. During t he prodromal stage. some illnesses remain asymptomatic and are discovered only by l aboratory tests. thus. and ticks. The infection then can spread to other host c ells. At the same time. and their cell membranes are leaky. headache. and then escapes from the cell by bud ding from the plasma membrane (E). or allergic reaction. such as lice. PATHOPHYSIOLOGIC CHANGES Clinical expressions of infectious disease vary. The extra fluid arriving in the inflam ed area dilutes microbial toxins. or irregularly shaped. and lethargy. Red blood cells and fluid flow into the i nterstitial space. fleas. During the cellular stage of inflammation. muscle aches. better protected cell. a nd prostate gland. infecti on. Inflammation may be the result of tissue injury. They have no cell wall.

The immature neutrophils (called bands in the differential WBC cou nt) can't serve any defensive purpose. heat. body cells can be damaged. the next stag . This process is called leukocytosis. Fever Fever occurs with the introduction of an infectious agent. When the body temperature rises too high. (See Block ing inflammation.) SIGNS AND SYMPTOMS Acute inflammation is the body's immediate response to cell injury or cell death . Phagocytosis of the dead cells and microorganis ms begins. pain. Diaphoresis is the body's method to cool the body and return the temperature to n ormal for that individual. because existing neutrophils cannot meet the body's demand for d efensive cells. and chemicals excreted during the inflammatory process. As the acute phase comes under control and the damage is isolated. Bone marrow begins to release immat ure leukocytes. and dec reased function of a body part. local pH changes. Heat (calor) in the area results from local vasodilation. The cardinal signs of inflammation include redness. Artificial methods to reduce a slight fever can actual ly impair the body's defenses against infection. and the blockage of lymphatic drainage to help wall off the inflammati on. Loss of function (functio laesa) occurs primarily as a result of edema and pain at the site. leakage of fluid into interstitia l spaces. fluid leakage into the interstitial spaces. The flowchart below shows the pr ogression of inflammation and the points at which drugs can reduce inflammation and pain. and mast cells arr iving at the site release heparin to maintain blood flow to the area. BLOCKING INFLAMMATION Several substances act to control inflammation. Platelets control any excess bleeding in the area. Leukocytosis The body responds to the introduction of pathogens by increasing the number and types of circulating WBCs. the neutrophil count increases.s move toward the damaged cells. In the acute or early stage. An elevated temperatu re helps fight an infection because many microorganisms are unable to survive in a hot environment. edema. Pain (dolor) occurs when pain receptors are stimulated by swollen tissue. Filling of previously empty or partially distended capillaries causes a lo calized blush. Edema (tumor) is caused by local vasodilation. particularly those of the nervous system. and increased blood flow to the area. Redness (rubor) results when arterioles dilate and circulation to the site incre ases.

DIAGNOSIS Accurate assessment helps identify infectious diseases. Stains that may be used to visualize the microorganism in clude: gram stain. Besides phagocytosis. An example of such a pathogen is mycobacteria. depending how rapidly the microbe replicates. a mature type of monocyte. such as preparing the area for healing an d processing antigens for a cellular immune response. nasal. and scans. which identifies gram-negative or gram-positive bacteria acid-fast stain. A specimen obtained for culture must not be contaminated with any other substanc e. skin. the cause of tuberculosis. Neutrophils. lymphocytes. and degrade the microorganism that carries antigen on its surface. radiographic tests. Legionella. the first test is a WBC count and a differential. Tests that can help identify and gauge the ext ent of infection include laboratory studies. they only ten tatively identify a pathogen. For example. and performing or order ing appropriate diagnostic tests. The differential count is the relati ve number of each of five types of white blood cells neutrophils. performing a thorough physical examination.e of the inflammatory process takes place. A poorly healed wound or an unresolved infection can lead to chronic inflammation. monocytes. and Pneumocystis. sputum. and monocytes. and macrophag es begin the process of phagocytosis of dead tissue and bacteria. Any body substanc e can be cultured. Multiplying the percentage value of each type by the total WBC gives the absolute number of each type of white c ell. a nd avoidable complications. Neutrophils an d monocytes identify the foreign antigen and attach to it. the patient must be catheterized to make sure that only the urine is being examined. Additional tests that may be requested include magnetic resonance imaging to loc . Although stains provide rapid and valuable diagnostic information. Erythrocyte sedimentation rate (ESR) may be done as general test to reveal that an inflammatory process is occurring within the body. urine. An elevated monocyte count is common during resolution of any injury and in chronic infections. stool. The body may encapsul ate a pathogen that it can't destroy in order to isolate it. kil l. Contami nated specimens may mislead and prolong treatment. viruses may caus e no change or a decrease in normal WBC level. If obtaining a clean urine specimen isn't possible. Then they engulf. The next step is to obtain a stained smear from a specific body site to determin e the causative agent. which identifies fungi. Macrophage s. It may or may not follow an acute process. Types of cultures that may be ordered are blood. macrophages pla y several other key roles at the site. Chronic inflammation An inflammation reaction lasting longer than 2 weeks is referred to as chronic i nflammation. appropriate treatment. Confirmation requires culturing. It's obtained by classifying 100 or more whi te cells in a stained film of peripheral blood. arrive at the site later and remain in the area of inflammation longer than the other cells. eosinophils. Any elevation in o verall number of WBCs is a positive result. wound. encapsulated mycobacteria appear in X-rays as identifiable spots in the lungs. and cerebrospinal fluid. throat. but enough growth to identify the microbe may occur as quickl y as 8 hours (streptococcal) or as long as several weeks. It begins with obtaining the patient's complete medi cal history. Most often. a urine specimen must not contain any debris from the perineum o r vaginal area. which identifies mycobacteria and nocardia silver stain. bas ophils. This test recognizes only that something has stimulated an immune response. Bacterial infection usually causes an elevation in the counts.

Some pathogens that were once well controlled by medicines are again sur facing with increased virulence. Antibiotics work in a variety of ways. depending on the class of antibiotic. actions. a nd gallium scans to detect abscesses. don't respond to available drugs . sodium. bacterial metabolism. Vaccines may be administered to induce a primary immune response under conditions that won't cause disease. Drug th erapy should be used only when it is appropriate. Supportive therapy can play an important role in fighting infections.ate infection sites. and nutrients. Antiviral drugs stop viral replication by interfering with DNA synthesis. treatment is tailored to the specific causative organism. such as potassium. including most viral infections. or they may increase cell-membrane permeability. with and on ly with full knowledge about dosage.) Antifungal drugs destroy the invading microbe by increasing cell membrane permea bility. The antifungal binds sterols in the cell membrane. the patient should: use universal precautions to avoid spreading the infection drink plenty of fluids get plenty of rest avoid people who may have other illnesses take only over-the-counter medications appropriate for his symptoms. The overuse of antimicrobials has created widespread resistance to some specific drugs. (See Antimicrobial drugs and chemicals. One such is tuberculosis. and possible side effects or adver se reactions follow the doctor's orders for taking any prescription drugs and be sure to fini sh the entire prescription . The ir action is either bactericidal (killing the bacteria) or bacteriostatic (preve nting the bacteria from multiplying). TREATMENTS Treatment for infections can vary widely. Supportive care is the only recourse while the host defenses repel the invader . protein synthesis. Some diseases. If infecti on does occur. resulting in leakage of intracellular contents. Antibiotics may inhibit cell wall synthesi s. chest X-rays to search the lungs for respiratory changes. To help the body fight an infection. or nucleic acid synthesis or activit y.

The accompanying chart describes a va riety of infections along with their signs and symptoms and appropriate diagnost ic tests. (See Reviewing common infections. MECHANISMS OF ACTION AGENT Inhibition of cell-wall synthesis Bacitracin Carbapenems Cephalosporins Cycloserine Fosfomycin Monobactams Penicillins Vancomycin Damage to cytoplasmic membrane Imidazoles Polyene antifungals Polymyxins Metabolism of nucleic acid Nitrofurans Nitroimidazoles Quinolones Rifampin Protein synthesis Aminoglycosides Chloramphenicol Clindamycin Macrolides Mupirocin Spectinomycin Tetracyclines Modification of energy metabolism Dapsone Isoniazid Sulfonamides Trimethoprim Infections Infection can strike any part of the body. ANTIMICROBIAL DRUGS AND CHEMICALS The following drugs or chemicals prevent growth of microorganisms or destroy the m by a specific action.) REVIEWING COMMON INFECTIONS .not share the prescription with others.

bacterial infection. Gonorrhea € Males: urethritis. predominance of monocytes indicates viral infection.INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Conjunctivitis € hyperemia of the conjunctiva discharge tearing pain photophobia (with corneal involvement) itching and burning Note: May also result from viral infection Culture from the conjunctiva identifies the causative organism In stained smears. of eosinophils an allergy related infection. of neutr ophils. including dysuria and purulent urethral discharge. with redness and swelling at the site of infection .

establishes the diagnosis by isolating N. grown on a Thayer-Martin or Transgrow medium . and bloody mucopurulent discharge Clinical features vary according to the site involved: urethra: dysuria. and profuse purulent discharge liver: right-upper quadrant pain pelvis: severe pelvic and lower abdominal pain. red and edematous meatus vulva: occasional itching. INFECTION AND FINDINGS . nausea.Females: may be asymptomatic inflammation and a greenish yellow discharge from the cervix Males or females: pharyngitis or tonsillitis rectal burning. tenderness. itchin g. gonorrhoeae. and tachycardia (may develop in patients with salpingitis or pelvic inflammatory disease (PID) Culture from the site of infection. swelling. and abdominal distention. urinary frequency and incontinence. Complement fixation and immunofluorescent assays of serum reveal antibody titers four times the normal rate. burning. itching. redness. vomiting. fever. muscle rigidity. Gram stain shows gram-negative diplococci. and pain due to exudate from an adjacent inf ected area vagina: engorgement. purulent discharge.

which grows to over 2 0 inches. feels hot and itchy. and resembles a bull's eye or target.DIAGNOSIS Bacterial infections Lyme disease € Stage 1: red macule or papule. ringlike rash appears conjunctivitis diffuse urticaria occurs lesions are replaced by small red blotches in 3 to 4 weeks malaise and fatigue intermittent headache neck stiffness fever. and achiness regional lymphadenopathy Stage 2: neurologic abnormalities-fluctuating meningoencephalitis with peripheral and cra nial neuropathy facial palsy . chills. more lesions erupt and a migratory. after a few days. commonly on the site of a tick bite.

burgdorf eri if the disease has affected the central nervous system. and W estern blot assay. including antibody titers. keratitis. left ven tricular dysfunction. may be used to identify Borrelia burgdorferi. memory loss. optic neu ritis Blood tests. fluctuating atrioventricular heart block. encephalopathic symptoms such as headache. white blood cell (WBC) count. dementia. enzyme-linked immunosorbent assay. serum immunoglobulin M (IgM) level. and difficulty concentrati ng ophthalmic manifestations such as iritis. and depression. renal vasculitis. and aspartate aminotransferase.cardiac abnormalities: brief. Cerebrospinal fluid (CSF) analysis reveals presence of antibodies to B. cardiomegaly Stage 3: arthritis with marked swelling neuropsychiatric symptoms such as psychotic behavior. Serology reveals mild anemia and elevated erythrocyte sedimentation rate (ESR). confusion. INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Listeriosis € commonly causes asymptomatic carrier state .

malaise chills fever back pain Fetuses: abortion premature delivery or stillbirth organ abscesses Neonates: meningitis. drainage from cervical or vaginal lesio ns. Meningitis € . resulting in tense fontanels irritability lethargy seizures coma L. monocytogenes is identified by its diagnostic tumbling motility on a wet moun t of the culture. spinal fluid. or lochia from a mother with an infected infant. Positive culture of blood.

or fungal infection. .fever chills headache nuchal rigidity vomiting photophobia lethargy coma positive Brudzinski's and Kernig's signs exaggerated and symmetrical deep tendon reflexes and opisthotonos wide pulse pressure bradycardia occasional rash Note: May also result from viral protozoal. pneumoniae from CSF and shows increased CSF cell cou nt and protein level and decreased CSF glucose level. Lumbar puncture isolates S.

INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Otitis media € ear pain ear drainage hearing loss fever lethargy irritability vertigo nystagmus tinnitus Otoscopy reveals obscured or distorted bony landmarks of the tympanic membrane. pneumoniae.Blood culture isolates S. .

Culture of the ear drainage identifies the causative organism. . Chest X-ray may show elevation of the diaphragm. and abdominal rigidity hypotension tachycardia fever abdominal distention Abdominal X-ray shows edematous and gaseous distention of the small and large bo wel or in the case of visceral organ perforation. vomiting. air lying under the diaphragm.Pneumatoscopy can show decreased tympanic membrane mobility. severe. Peritonitis € sudden. and diffuse abdominal pain that tends to intensify and localize in the area of the underlying disorder weakness and pallor excessive sweating cold skin decreased intestinal motility and paralytic ileus intestinal obstruction causes nausea.

and decreased breath sounds pleuritic pain chills malaise tachypnea Note: May also result from fungal or protozoal infection Chest X-rays confirm the diagnosis by disclosing infiltrates. Gram stain and culture.Blood studies show leukocytosis. yellow or bloody sputum dyspnea crackles. exudate. blood. Paracentesis reveals bacteria. Laparotomy may be necessary to identify the underlying cause. Sputum specimen. and sensitivity tests help differentiat e the type of infection and the drugs that are effective. or urine. pus. Pneumonia € high temperature cough with purulent. .

and bac teremia. depending on severity of pneumonia and und erlying lung state. . Pulse oximetry may show a reduced oxygen saturation level.WBC count indicates leukocytosis in bacterial pneumonia. Arterial blood gas (ABG) levels vary. INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Salmonellosis € fever abdominal pain. Bronchoscopy or transtracheal aspiration allows the collection of material for c ulture. Blood cultures reflect bacteremia and are used to determine the causative organi sm. and a normal or low cou nt in viral or mycoplasmal pneumonia. paratyphoid fever. severe diarrhea with enterocolitis Typhoidal infection: headache increasing fever constipation Blood cultures isolate the organism in typhoid fever.

and ent erocolitis. Cultures of urine. and vomitus may show the presence of Salmon ella. and abdominal pain and distention irritability drowsiness stool may contain pus. mucus or blood dehydration and weight loss Adults: sporadic.Stool cultures isolate the organism in typhoid fever. paratyphoid fever. bone marrow. vomiting. intense abdominal pain rectal irritability tenesmus headache and prostration . pus. Shigellosis € Children: high fever diarrhea with tenesmus nausea.

tongue. papular. and polymorphonuclear leukocytes. tonsils. nipples. mucus. INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Syphilis € Primary syphilis: chancres on the anus.stools may contain pus. and blood Microscopic examination of a fresh stool may reveal mucus. or nodular headache malaise . Sigmoidoscopy or proctoscopy may reveal typical superficial ulcerations. or eyelids regional lymphadenopathy Secondary syphilis: symmetrical mucocutaneous lesions general lymphadenopathy rash may be macular. fingers. Severe infection increases hemagglutinating antibodies. red blood cells. pustular. lips.

enlarged spleen anemia involvement of the upper respiratory tract. weight loss. tenderness.anorexia. perforation of the nasal septum or p alate. destruction or bones and organs fibrosis of elastic tissue of the aorta aortic insufficiency aortic aneurysm meningitis paresis personality changes . and vomiting sore throat and slight fever alopecia brittle and pitted nails Late syphilis: benign gumma lesion found on any bone or organ gastric pain. nausea.

palli dum in tissue. . ocular fluid. CSF. and exudates from lesions. INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Tetanus € Localized: spasm and increased muscle tone near the wound Systemic: marked muscle hypertonicity hyperactive deep tendon reflexes tachycardia profuse sweating low-grade fever painful. pallidum. tracheobronchial secretions.arm and leg weakness Dark field examination of a lesion identifies T. Fluorescent treponemal antibody absorption tests identifies antigens of T. a history of trauma. and no previous te tanus immunization. involuntary muscle contractions Diagnosis may rest on clinical features.

vaginal hyperemia and discharge deep red rash (especially on the palms and soles). . Cerebrospinal fluid pressure may rise above normal. desquamates (develops later) severe hypotension Isolation of S. Toxic shock syndrome (TSS) € intense myalgias fever over 104°F (40°C) vomiting and diarrhea headache decreased level of consciousness rigor conjunctival hyperemia. Tetanus antibody test may return as negative.Blood cultures are positive for the organism in only a third of patients. aureus from vaginal discharge or lesions.

aerobic. urine. Tuberculin skin test reveals infection at some point. but doesn't indicate activ e disease. c avity formation. acid-fast bacilli. and measles help rule out these disorders. . leptospirosis. drainage from abscesses. CSF. Stains and cultures of sputum. scar tissue. or pleural f luid show heat-sensitive. patchy infiltrates (mainly in upper lobes). Diagnosis is based on clinical findings. nonmotile. Tuberculosis € fever and night sweats productive cough lasting longer than 3 weeks hemoptysis malaise adenopathy weight loss pleuritic chest pain symptoms of airway obstruction from lymph node involvement Chest X-ray shows nodular lesions. and calcium deposits.Negative results on blood tests for Rocky Mountain spotted fever.

frequency. vomiting. and suprapubic pain cloudy. and diarrhea symptoms of cystitis may be present . and possibly bloody urine fever nausea and vomiting costovertebral angle tenderness Acute pyelonephritis: fever and shaking chills nausea. It also may be performe d to obtain sputum if the patient can't produce an adequate sputum specimen.CT or MRI scans allow the evaluation of lung damage and may confirm a difficult diagnosis. Bronchoscopy shows inflammation and altered lung tissue. malodorous. INFECTION AND FINDINGS DIAGNOSIS Bacterial infections Urinary tract infections € Cystitis: dysuria. urgency.

Urinary microscopy is positive for pyuria. . Whooping cough (Pertussis) € irritating. or bacteriuria. frequency. hacking cough characteristically ending in a loud. Nasopharyngeal swabs and sputum cultures show B. and pyuria Urine culture reveals microorganism. inspirat ory whoop that may expel tenacious mucus anorexia sneezing listlessness infected conjunctiva low grade fever Classic clinical findings suggest the disease.tachycardia generalized muscle tenderness Urethritis: dysuria. crowing. hematuria. Fluorescent antibody screening of nasopharyngeal smears is less reliable than cu ltures. pertussis.

Giemsa stain di stinguishes varicella-zoster from vaccinia and variola viruses. Leucocyte count may be normal. Viral infections Chickenpox (Varicella) € irritating. INFECTION AND FINDINGS DIAGNOSIS Viral infections .Serology shows an elevated WBC count. hacking cough characteristically ending in a loud. Isolation of virus from vesicular fluid helps confirm the virus. low. crowing. or mildly increased. inspirat ory whoop that may expel tenacious mucus anorexia sneezing listlessness infected conjunctiva low grade fever Characteristic clinical signs suggest the virus.

thrombocytop enia. saliva. WBC and biopsy specimens. hemolytic anemia Virus isolated in urine. erythematous macules that progresses to papules and then to vesicles as a result of viremia slight fever malaise and anorexia mild. colitis. Compl ement fixation studies. pneumonitis. throat. hepatosplenomegaly. and indirect immunofluorescent test for CMV immunoglobulin M antibody (congenital infections ) aid diagnosis. and lymphadenopathy congenital infection: jaundice.Cytomegalovirus infection € pruritic rash of small. nonspecific complaints immunodeficient population: pneumonia. petechial rash. Herpes simplex € Type 1: fever sore. red. spider angiomas. hepatosplenomegaly. or weight loss infants age 3 to 6 months appear asymptomatic but may develop hepatic dysfunctio n. encephalitis. cervix. swollen. a bdominal pain. throat submaxillary lymphadenopathy . chorioretinitis. diarrhea. hemagglutination inhibition antibody tests.

halitosis. perianal s kin. and cheeks. Herpes simplex virus culture is positive. fluid-filled vesicles that are found on the cervix. and anorexia severe mouth pain edema of the mouth vesicles (on the tongue. labia. and penile shaft. glans penis. .increased salivation. vagina. or anywhere in or around the mouth ) on a red base that eventually rupture. gingiva. foreskin. ingu inal swelling may be present Tzanck smear shows multinucleated giant cells. leaving a painful ulcer and then yellow crusting Type 2: tingling in the area involved malaise dysuria dyspareunia (painful intercourse) leukorrhea (white vaginal discharge containing mucus and pus cells) localized. mouth or anus. Virus is isolated from local lesions. vulva.

CSF shows increased protein levels and possibly pleocytosis.Tissue biopsy aids in diagnosis. . arms. or legs may also occur small. INFECTION AND FINDINGS DIAGNOSIS Viral infections Herpes zoster € pain within the dermatome affected fever malaise pruritus paresthesia or hyperesthesia in the trunk. Lumbar puncture shows increased pressure. Elevated antibodies and increased white blood cell count indicate primary infect ion. red. Examination of vesicular fluid and infected tissue shows eosinophilic intranucle ar inclusions and varicella virus. nodular skin lesions on painful areas (nerve specific) that change t o pus or fluid-filled vescicles Staining antibodies from vesicular fluid and identification under fluorescent li ght differentiates herpes zoster from localized herpes simplex.

depression. in the mouth. groin. Infectious mononucleosis € headache . or in the throat pneumonia red.Human immunodeficiency virus infection (HIV) € rapid weight loss dry cough recurring fever or profuse night sweats profound and unexplained fatigue swollen lymph glands in the armpits. or neck diarrhea that lasts for more than a week white spots or unusual blemishes on the tongue. and other neurologic disorders Two enzyme immunosorbent assay (EIA) tests are positive. nose. Western blot test is positive. pink. or eyelids memory loss. or purplish blotches on or under the skin or inside the mouth. brown.

INFECTION AND FINDINGS DIAGNOSIS .to 4-week intervals increase to four times normal. From 50% to 70% of the total count consists of lymphocytes and monocytes. or pharyngitis maculopapular rash Monospot test is positive.000 to 20. Heterophil antibodies in serum drawn during the acute phase and at 3.000/mm2) during the second and third weeks of illness. and 10% of the lymphocytes are atypical. WBC count is abnormally high (10. Indirect immunofluorescence shows antibodies to Epstein-Barr virus and cellular antigens.malaise and fatigue sore throat cervical lymphadenopathy temperature fluctuations with an evening peak splenomegaly hepatomegaly stomatitis exudative tonsillitis.

Rabies € Prodromal symptoms: local or radiating pain or burning and a sensation of cold.Viral infections Mumps € myalgia malaise and fever headache earache that is aggravated by chewing parotid gland tenderness and swelling. Serologic antibody testing shows a rise in paired antibodies. Clinical signs and symptoms. blood or spinal fluid. pruritus. and tingli ng at the bite site . urine. and pain when chewing sour or acidic liqu ids swelling of the other salivary glands Virus is isolated from throat washings. especially parotid gland enlargement are characteri stic.

anxiety. irritability. hyperesthesia. anxiety. apprehension pupillary dilation shallow respirations altered level of consciousness ocular palsies strabismus asymmetrical pupillary dilation or constriction absence of corneal reflexes facial muscle weakness .malaise and fever headache nausea sore throat and persistent loose cough nervousness. sensitivity to light and loud noises excessive salivation. tearing and perspiration Excitation phase: intermittent hyperactivity.

degeneration of neuron. sound. in the nerve cells INFECTION AND FINDINGS . WBC is elevated. res ulting in dehydration swallowing problems cause frothy drooling and soon the sight. called Negri bodies. generalized. no diagnostic tests for rabies before its onset histologic examination of brain tissue from human rabies victims shows perivascu lar inflammation of the gray matter. Fluorescent rabies antibody (FRA) test is positive.forceful. painful pharyngeal muscle spasms that expel fluids from the mouth. or thought of water triggers uncontrollable pharyngeal muscle spasms and excessive salivati on nuchal rigidity seizures cardiac arrhythmias Terminal phase: gradual. and characteristic minute bodies. flaccid paralysis peripheral vascular collapse coma and death Virus is isolated from saliva or CSF.

bronchiolitis.DIAGNOSIS Viral infections Respiratory syncytial virus infection € Mild disease: nasal congestion coughing and wheezing malaise sore throat earache dyspnea fever Bronchitis. however. and nuchal rigidity of central nervous sys tem (CNS) infection may be observed Cultures of nasal and pharyngeal secretions may reveal the virus. cyanosis. irritability. retraction. and tachypnea wheezes. this infection is so labile that cultures aren't always reliable. . and crackles signs such as weakness. rhonchi. pneumonia: nasal flaring.

often covering the trunk and extremities small. suboccipital. along with convalescent seru m that shows a fourfold rise in antibody titers. confirms the diagnosis. red macules on the soft palate low-grade fever headache malaise anorexia sore throat cough postauricular. Blood tests confirm rubella-specific IgM antibody. WBC may be normal to elevated. and CSF. Cell cultures of the throat. . blood. Rubella € maculopapular.Serum antibody titers may be elevated. mildly itchy rash that usually begins on the face and then spread s rapidly. urine. and posterior cervical lymph node enlargement Clinical signs and symptoms are usually sufficient to make a diagnosis.

nasopharyngeal secretions. Measles virus may be isolated from the blood. and rhinorrhea coryza hoarseness. puffy red eyes. pruritic macular rash that becomes papular and erythematous Diagnosis rests on distinctive clinical features. and uri ne during the febrile stage. INFECTION AND FINDINGS DIAGNOSIS Fungal infections Chlamydial infections .Rubeola € fever photophobia malaise anorexia conjunctivitis. hacking cough Koplik's spots. Serum antibodies appear within 3 days.

cervix. and lymph nodes chills. erythema. tenderness of the urethral meatus urinary frequency pruritus and urethral discharge (copious and purulent or scant and clear or muco id. and urinary frequency Urethritis: dysuria. pyuria.€ Cervicitis: cervical erosion dyspareunia micropurulent discharge pelvic pain Endometritis or salpingitis: pain and tenderness of the lower abdomen. Epididymitis: painful scrotal swelling . bleeding after intercourse. and vaginal discharge dysuria Urethral syndrome: dysuria. fever breakthrough bleeding. uterus.

Antigen-detection methods are the diagnostic tests of choice for identifying chl amydial infection. endometritis. INFECTION AND FINDINGS DIAGNOSIS . s alpingitis. cervicitis.urethral discharge Prostatitis: low back pain urinary frequency. and dysuria painful ejaculation Proctitis: diarrhea tenesmus pruritus bloody or mucopurulent discharge diffuse or discrete ulceration in the rectosigmoid colon Swab from site of infection establishes a diagnosis of urethritis. or proctitis. Culture of aspirated material establishes a diagnosis of epididymitis. Polymerase chain reaction (PCR) test is highly sensitive and specific. nocturia.

leukopenia.Fungal infections Histoplasmosis € Primary acute histoplasmosis: may be asymptomatic or may cause symptoms of a mild respiratory illness similar to a severe cold or influenza fever malaise headache myalgia anorexia cough chest pain anemia. or thrombocytopenia oropharyngeal ulcers Progressive disseminated histoplasmosis: hepatosplenomegaly general lymphadenopathy .

possibly. and larynx. w ith resulting pain. epiglottis. palate. and dysphagia Chronic pulmonary histoplasmosis: productive cough. Positive histoplasmin skin test indicates exposure to histoplasmosis. INFECTION AND FINDINGS . ulceration of the tongue. Rising complement fixation and agglutination titers (more than 1:32) strongly su ggest histoplasmosis. papules. hoarseness. and ulcers lesions of the skull and long bones lymphadenopathy and visceral involvement without pulmonary lesions Culture or histology reveals the organism. Stained biopsies using Gomori's stains or periodic acid-Schiff reaction give a f ast diagnosis of the disease.anorexia and weight loss fever and. dyspnea. and occasional hemoptysis weight loss extreme weakness breathlessness and cyanosis African histoplasmosis: cutaneous nodules.

7°C) profuse sweating hepatosplenomegaly hemolytic anemia Life-threatening form: persistent high fever orthostatic hypotension red blood cell sludging that leads to capillary obstruction at various sites .DIAGNOSIS Protozoal infections Malaria € Benign form: chills fever headache and myalgia Acute attacks (occur when erythrocytes rupture): chills and shaking high fever (up to 107°F/41.

Leukocyte count is normal to decreased. Indirect fluorescent serum antibody tests are unreliable in the acute phase. diarrhea. Schistosomiasis € transient pruritic rash at the site of cercariae penetration fever . uremia Peripheral blood smears of red blood cells identify the parasite. Hemoglobin levels are decreased. and melena oliguria. Protein and leukocytes are present in urine sediment. anuria.hemiplegia seizures delirium and coma hemoptysis vomiting abdominal pain.

WBC count shows eosinophilia. haematobium: terminal hematuria dysuria ureteral colic Typical symptoms and a history of travel to endemic areas suggest the diagnosis. and lymphadenopathy S. Ova in the urine or stool or a mucosal lesion biopsy confirm diagnosis. intestinal stricture S. weakness weight loss diarrhea ascites.myalgia cough Later signs and symptoms: hepatomegaly. splenomegaly. japonicum: irregular fever malaise. hepatosplenomegaly portal hypertension fistulas. . mansoni and S.

INFECTION AND FINDINGS DIAGNOSIS Protozoal infections Toxoplasmosis € Ocular toxoplasmosis: chorioretinitis yellow-white elevated cotton patches blurred vision scotoma pain photophobia Acute toxoplasmosis: malaise. headache fatigue sore throat fever cervical lymphadenopathy . myalgia.

gondii in mice after their inoculation with human body fluids re veals antibodies for the disease and confirms toxoplasmosis. Isolation of T. vomiting. Trichinosis € Stage 1 (enteric phase): anorexia nausea.maculopapular rash Congenital: hydrocephalus or microcephalus seizures jaundice purpura and rash Blood tests detect a specific toxoplasma antibody. diarrhea abdominal pain and cramps Stage 2 (systemic phase) and Stage 3 (muscular encystment phase): edema (especially of the eyelids or face) muscle pain itching and burning skin .

or CNS infection Stools may contain mature worms and larvae during the invasion stage. creatine kinase. cardiovascular. Lumbar puncture demonstrates CNS involvement with normal or elevated cerebrospin al fluid lymphocytes and increased protein levels.sweating skin lesions fever delirium and lethargy in severe respiratory. alanine aminotran sferase. Skin testing may show a positive histaminelike reactivity. Skeletal muscle biopsies can show encysted larvae 10 days after ingestion. Serology results indicate elevated aspartate aminotransferase. and lactate dehydrogenase levels during the acute stag es and an elevated eosinophil count. Elevated acute and convalescent antibody titers confirm the diagnosis. 4 GENETICS Handbook of Pathophysiology 4 GENETICS Genetic components Transmitting traits € Germ cells € Mitosis Trait predominance € .

disorders can be transmitted. not every gene t hat might be expressed is. Genetics is an inexact science. and guanine (G . two teams of scientists announced the completion of the rough draft of the entir e genome sequence. Genetic principles are based on study of t housands of individuals. thymine (T). and 2 sex chromosomes (a pair of Xs in females and an X and a Y in males ). (See Normal human karyotype. but exceptions occur. and phys iologic traits from biological parents to their children. A person's individual set of chromosomes is called his karyotype. Genetic information is carried in genes. cyotosine (C). perhaps. Thus. The sequence consists of more than 3.Autosomal inheritance € Sex-linked inheritance € Multifactorial inheritance Pathophysiologic changes € Environmental teratogens € Gene errors € Autosomal disorders € Sex-linked disorders € Multifactorial disorders € Chromosome defects Disorders € Cleft lip and cleft palate € Cystic fibrosis € Down syndrome € Hemophilia € Marfan syndrome € Sickle cell anemia € Spina bifida € Tay-Sachs disease Genetics is the study of heredity the passing of physical.) The human genome (structure and location of each gene on whic h chromosome) has been under intense study for only about 15 years. In this transmission. some. Every normal human cell (except reproductive cells) has 46 chromosomes. GENETIC COMPONENTS Each of the two strands of DNA in a chromosome consists of thousands of combinat ions of four nucleotides adenine (A). Decoding the genome will enable people to know who is likely to get a spec ific inherited disease and enable researchers to eradicate or improve the treatm ent of many diseases. which are strung together on the deoxyr ibonucleic acid (DNA) double helix to form chromosomes. In June 2000 . For a wide variety of reasons. the following chapter may seem to contain a gre at many hedge words may. Those studies have led to generalities that are usually true.1 billion pairs of chemi cals. (See The genome at a glance. 22 paired chromosomes called aut osomes. biochemical.) A word of warning at the outset. and mistakes or mutations can result in disability or death.

each chromosome may carry a different versi on of the same gene. the corresponding chromosomes pair up.ncbi. (See DNA duplication: Two doub le helices from one. a triplet ACT on one strand is linked to the triplet TGA on the other. These are the sex chromosomes. TRANSMITTING TRAITS Germ cells. Most of the genes on one chromosome are identical or almost identical to the gen e on its mate. It does this through the genetic code. so that the fe rtilized cell and every somatic cell of the new person has 23 pairs of chromosom es in its nucleus.) For example. so that. transmitted from parents to offspring. each new cell (ovum or sperm) contains one set of 23 chromosomes.) The genes carry a code for each trait a person inherits. Mei osis occurs only when the body is creating haploid germ cells from their diploid precursors. the other 22 chromosome pairs are ca lled autosomes.) The location (or locus) of a gene on a chromosome is speci fic and doesn't vary from person to person. or gametes (ovum and sperm). which is made up of t he alleles (or different versions of the genes) it possesses. Each of the 23 pairs of chromosomes in the germ cell separates. (As we discuss later. they control the formation of ribonucleic a cid (RNA).nlm. when the cell then divides. Germ cells The body produces germ calls through a kind of cell division called meiosis. Source: www. are one of two classes of cells in the body. but also cell reproduction and the daily functions of all cells. each germ cell contains 23 chromosomes (called the haploid number) in its nucleus.) arranged in complementary triplet pairs (called codons). All the other cells in the body are somatic cells. NORMAL HUMAN KARYOTYPE The illustration shows the arrangement of chromosomes (karyotype) in a normal ma le. The strands are loosely held together by chemical bonds between aden ine and thymine or cytosine and guanine for example. THE GENOME AT A GLANCE In 1998. t hat is. This allows each of the thousands of genes on a strand of DNA in an ovum to join the corresponding gene in a sperm w hen the chromosomes pair up at fertilization. f rom blood type to eye color to body shape and a myriad of other traits. Genes control cell function by controlling th e structures and chemicals that are synthesized within the cell. The particu lar makeup of an individual organism is called its genome. Genes not only control heredita ry traits. they contain 23 pairs of chromosomes. each of which represe nts a gene. The looseness of the bonds allows the strands to separate easily during cell division.nih. (See How genes control cell function. . the precise sequence of AT and CG pairs on the DNA molecule. which in turn controls the formation of specific proteins. When ovum and sperm unite. most of wh ich are enzymes that catalyze chemical reactions in the cells.gov/genome/guide Determining sex Only one pair of chromosomes in each cell pair 23 is involved in determining a p erson's sex. which are diploid. a gene map was released by an international consortium of radiation hyb rid mapping labs containing over 30. DNA ultimately controls the formation of essential substances throughout the lif e of every cell in the body. Females have two X chromosomes and males have one X and one Y ch romosome.000 distinct cDNA-based markers.

Individual DNA nucleotides are linked into new strands with bases complementary to those in the originals. the basic structural unit of deoxyribonucleic acid (DNA). although the environmental factors do not affect the genetic structure. Very rare errors in cell division can result in a germ cell that has no sex chromosome and/or two X chromosomes. metaphase. eventually forming a many-c elled human embryo. guan ine (G). In this way. two id entical double helices are formed. the offspring is male (one X and one Y chromosome). . are determined by one gene that may have many v ariants (alleles). require t he interaction of one or more genes. environmental factors may affe ct how a gene or genes are expressed. and new complementary chains form and link to the separated originals (parents). (See Five phases of mitosis. gene. the zygote may have an XO or XXY karyotype and still survive. deoxyribose.) The result of every mitotic cell division is two new daught er cells. or traits. gene is more likely to be expressed in the offspring than the less influential . For example. each cell in a person's body (except ovum or sperm) co ntains an identical set of 46 chromosomes that are unique to that person. Mitotic cell division occurs in five phases: an inactive phase called interphase and four active phases: prophase. Before a cell divides. When a sp erm with an X chromosome fertilizes an ovum. Most othe r errors in sex chromosome division are incompatible with life. In addition. if the alleles are different.Each gamete produced by a male contains either an X or a Y chromosome. anaphase. Autosomal inheritance For unknown reasons. Mitosis The fertilized ovum now called a zygote undergoes a kind of cell division called mitosis. its chromosomes duplicate. one allele may be more influentia l than the other in determining a specific trait. such as brown. A person who has identical alleles on each chromosome is homozygous for that gene. the offspring is female (two X chro mosomes). TRAIT PREDOMINANCE Each parent contributes one set of chromosomes (and therefore one set of genes) so that every offspring has two genes for every locus (location on the chromosom e) on the autosomal chromosomes. and a nitrogen base made of adenine (A). they're said to be heterozygous. These double helices are duplicates of t he original DNA chain. A recessive allele won't be expressed unless bot h chromosomes carry identical alleles. or cystosine (C). thymine (T). and so on. when a sperm with a Y chromosome fertilizes an ovum. The more powerful. or green eye color are call Variations in a particular gene ed alleles. such as eye color. After fertil ization. blue. Some characteristics. and telophase. Offspring will express a dominant allele when one or both chromosomes in a pair carry it. each genetically identical to the original and to each other. each containing one of the original strands a nd a newly formed complementary strand. a child may receive a gene f or brown eyes from one parent and a gene for blue eyes from the other parent. a DNA chain separates. contai ns a phosphate group. each chain serves as a templ ate for constructing a new chain. Thus. Others. or dominant . Beca use the dominant gene is more likely to be expressed. and the gene for blue eyes is recessive. the double helix of DNA separates into two chains. called polygenic traits. The result is two identical double h elices parent and daughter. Each of the two resulting cells likewise divides. Th e gene for brown eyes is dominant. on autosomal chromosomes. During duplication. the child is more likely t o have brown eyes. During this process. or recessive. A DNA molecule's double helix forms from the twisting of nucleotide strands (shown below). DNA DUPLICATION: TWO DOUBLE HELICES FROM ONE The nucleotide.

Together. Some defects arise spontaneously. that is. Halves of each duplicated chromosome (chromatids) remain attached by a centromere. healthier children of tw o short parents may be taller than either. A man will transmit one copy of each X-lin ked gene to his daughters and none to his sons. INTERPHASE During this phase. others the white. Sex-linked inheritance The X and Y chromosomes are not literally a pair because the X chromosome is muc h larger than the Y. they appear as an indistinguishable matrix within the nucleus. whether male or female. The male literally has less genetic material than the femal e. Some rece ssive genes on the X chromosomes act like dominants in females. the nucleolus disappears and chromosomes become distinct. PROPHASE In this stage. this is called mu ltifactorial inheritance. resulting in the formation of two daughter cells. For reasons that are not yet clear. Inheritan ce of those genes is called X-linked. A woman will transmit one copy t o each child. Cent rioles move to opposite sides of the cell and radiate spindle fibers. But nutritional patterns. sex-linked disorders. or phases. Chromosomes replicate. the nucleus and nuclear membrane are well defined and the nuc leolus is prominent. Some diseases have genetic predisposi tion but multifactorial inheritance. the height of offspring will be in a range between the height of th e two parents. Others. each forming a double strand that re mains attached at the center of each chromosome by a structure called the centro mere. of this process are illustrated below. Some proteins are the building blocks of cell structure. The most common example occurs not in peopl e but in cats. the nuclear contents of a cell re produce and divide. METAPHASE . and others may be caused by environmental teratogens. and multifactorial disorders result f rom damage to genes or chromosomes. and other environmental fa ctors also influence development. Inheritance of genes on the X chromosomes is different in another way. Only female cats have calico (tricolor) coat patterns. health care. The five s teps. not plant cells) appear outside the nucleus. PATHOPHYSIOLOGIC CHANGES Autosomal disorders. the gene for the disease is expres sed only under certain environmental conditions. FIVE PHASES OF MITOSIS In mitosis (used by all cells except gametes). Centrioles (in animal cells only. direct intracellular chemical reactions.HOW GENES CONTROL CELL FUNCTION This simplified diagram outlines how the genetic code directs formation of speci fic proteins. and still others a third color. structural pro teins and enzymes direct cell function. Hair color in the cat is carried on the X chromosome. one recessive allele will be expressed in some somatic cells and another in other somatic cells. Some hair cells in females express t he brown allele. The better-nourished. which means he has only one copy of most genes on the X chromosome. In general. Height is a classic example of a multifactorial trait. Multifactorial inheritance Environmental factors can affect the expression of some genes. c alled enzymes.

parvovirus. gonorrhea.Chromosomes line up randomly in the center of the cell between spindles. Each new cell contain s the diploid number (46 in humans) of chromosomes. The number of chromosomes at each end of the cell equals the or iginal number TELOPHASE A nuclear membrane forms around each end of the cell. and spindle fibers disappe ar. TERATOGENS AND ASSOCIATED DISORDERS This chart lists common teratogens and their associated disorders. mumps. ANAPHASE Centromeres move apart. INFECTIONS ASSOCIATED DISORDERS Toxoplasmosis Rubella Cytomegalovirus Herpes simplex Other infections (syphilis. along t he metaphase plate. varicella ) Growth deficiency Mental retardation Hepatosplenomegaly Hearing loss Cardiac and ocular defects . pulling the separate chromatids (now called chromosomes) to opposite ends of the cell. The cytoplasm compresses and divides the cell in half. each end of the cell now contains 46 chromosomes. hepatitis B. The centromere of each chromosome replicates. In human cells.

Active infection Carrier state MATERNAL DISORDERS Diabetes mellitus Abnormalities of spine lower extremities heart kidney external genitalia Phenylketonuria Mental retardation Microcephaly Congenital heart defects Intrauterine growth retardation Hyperthermia Intrauterine growth retardation .

CNS and neural tube defects Facial defects DRUGS. CHEMICALS. AND PHYSICAL AGENTS € Alcohol Fetal alcohol syndrome Learning disabilities Anticonvulsants Intrauterine growth retardation Mental deficiency Facial abnormalities Cardiac defects Cleft lip and palate Malformed ears Genital defects Cocaine Premature delivery .

CHEMICALS.Abruptio placentae Intracranial hemorrhage GI and GU abnormalities DRUGS. AND PHYSICAL AGENTS ASSOCIATED DISORDERS Diethylstilbestrol Clear-cell adenocarcinoma of vagina Structural and functional defects of female GU tract Lithium Congenital heart disease Methotrexate Intrauterine growth retardation Decreased ossification of skull Prominent eyes Limb abnormalities Mild developmental delay Radiation .

Microcephaly Mental retardation Tetracycline Brown staining of decidual teeth Dental caries Enamel hypoplasia Vitamin A derivatives Facial defects Cardiac defects CNS defects Incomplete development of thymus Warfarin (Coumadin) Intrauterine growth retardation Mental retardation Seizures Nasal hypoplasia Abnormal calcification of axial skeleton .

If b oth parents are unaffected but are heterozygous for the trait (carriers of the d efective gene). or viruses. and physical agents) that can harm the developing fetus by causing congenital structural or functional defects. The mutati on initially causes the cell to produce some abnormal protein that makes the cel l different from its ancestors.Adapted with permission from M. and others change the way a cell functions. Exposure during this time can cause intrauterine growth re tardation. an error occurs at a single gene site on the DNA stran d. cognitive abnormalities. but all will carr y the defective gene. During the fetal period. complications during labor and delivery. if a mutation isn't identified or repaired.B. Mut ations can occur anywhere in the genome the person's entire inventory of genes. chemicals. which may occur spontaneou sly or after exposure of a cell to radiation. such as cancer or congenital anomalies. If one parent is affected and the other is a carrier. the mutation may produce a trait different from th e original trait and is transmitted to offspring during reproduction. Philadelphia: W. If both parents are affected. Mutations may have no effect. Environmental teratogens Teratogens are environmental agents (infectious toxins. deletions. each child has one chance in two of being affected . none of their offspring will be affected. all their children will be affected. Gene errors A permanent change in genetic material is a mutation.) The embryonic period the first 8 weeks after fertilization is a vulnerable time. each child has one chance in four of being affected. when specific organ systems are actively differentiating. half their children will be affected. . Every cell has built-in defenses against genetic damage. 1998. (See Autosomal dominant i nheritance.) Autosomal recessive inheritance also usually affects male and female offspring e qually. they may change ex pression of a trait. or structural defects. Single-gene disorders are inherited in clearly identifiable patterns that are th e same as those seen in inheritance of normal traits. hidden defects in later development (such as cognitive or behavioral problems). certain chemicals.. Teratogens may also cause spontaneous miscarriage. Because every person has 2 2 pairs of autosomes and only 1 pair of sex chromosomes. or excessive repetitions. maternal systemic diseas es. (See Autosomal recessive inheritance. If only one parent is affected. Autosomal disorders In single-gene disorders. organ systems are formed an d continue to mature.) Autosom al recessive disorders may occur when there is no family history of the disease. An example of this type of inheritance occurs in Marfan syndrome. drugs. most hereditary disorde rs are caused by autosomal defects. If both parents are affected. However. Saunders. Each child has a 50% chance of inheriting A. Pathophysiology: Foundations of Disease and Clinical Intervention. Some mutations cause serious or deadly defects. (See Teratogens and associated disorders. A mistake may occur in the copying and transcribing of a single codon (nucleo tide triplet) through additions. Hansen. or neoplastic transformations. all their offspring will be affected. Autosomal dominant transmission usually affects male and female offspring equall y. Exposure to teratogen s usually kills the embryo. AUTOSOMAL DOMINANT INHERITANCE The diagram shows the inheritance pattern of an abnormal trait when one parent h as recessive normal genes (aa) and the other has a dominant abnormal gene (Aa). If one parent is affected.

Some multifactorial disorders are apparent at birth. Unaffected male children of a female carrier don't transmit the disorder. Females receive two X chromosom es. anencephaly. In rare cases. congenital heart disease. Oth ers don't become apparent until later. and myelomeningocele. usua lly as recessive traits. and a 50% chance of being a carrier (Aa) who can transmit the gene. general health. Multifactori al disorders that develop during adulthood are often believed to be strongly rel ated to environmental factors. such as cleft lip. Hemophilia is an example of an X-lin ked inheritance disorder. a onein-four chance of having two normal genes (AA) and no chance of transmittal. so they can be homozygous for a disease allele.) Characteristics of X-linked dominant inheritance include evidence of the inherit ed trait in the family history. Most sex-linked disorders are passed on the X chromosome. and age. exposure to radiation.AUTOSOMAL RECESSIVE INHERITANCE The diagram shows the inheritance pattern of an abnormal trait when both unaffec ted parents are heterozygous (Aa) for a recessive abnormal gene (a) on an autoso me. Multifactorial disorders can result from a less-than-optimum e xpression of many different genes. All daughters of an affected ma le will be carriers. (See X-Linked do minant inheritance. or heterozygous. Sex-linked disorders Genetic disorders caused by genes located on the sex chromosomes are termed sexlinked disorders. and many cancers. maternal fetal blood incompatibi . Unaffected sons can't transmit the disorder. If the father has an X-linked dominant disorder. each child has a one-in-four chance of being affected (aa). hyperlipidemia. nutritional factors. or hormones). The son of a female carrier may inherit a recessive gene on the X chromosome and be affected by the disease. Because males have only one X chromosome. A person with the abnormal trait must have one a ffected parent. hypert ension. In polygenic inheritance. homozygous for a normal alle le. each of her children has 50% chance of being affected. such as type II diabetes mellitus. most autoimmune diseases. and the unaffected sons aren't carriers. exposure to high altitude. Most people who express X-linked recessive traits are males with unaffected pare nts. As shown. existing diseases . Sons of an affected male will be una ffected. Environmental factors of maternal or paternal origin include the use of chemical s (such as drugs. the father is affected and the mother is a carrier.) Multifactorial disorders Most multifactorial disorders result from the effects of several different genes and an environmental component. clubfoot. not from a specific error. X-LINKED RECESSIVE INHERITANCE The diagram shows the children of a normal parent and a parent with a recessive gene on the X chromosome (shown by an open dot). If a mother has an X-linked dominant d isorder. all his daughte rs and none of his sons will be affected. not only in incidence but also in the degree of e xpression. a single X-li nked recessive gene can cause disease in a male. each gene has a small additive effect. Maternal factors include infections during pregnancy. (See X-Linked recessive inheritance. alcohol. cleft pa late. All daug hters of an affected male will be carriers. and the effect of a combination of genetic errors in a person is unpredictable.

Gain or loss of chromosomes is usually caused by nondisjunction of autosomes or sex chromosomes during meiosis. and use of some therapeutic or rec reational drugs. (See Chromosomal disjunction and nondisjunction. both sons and daughters may be affected. so often there are no visible abnormalities. or birth defects. Chromosome defects Aberrations in chromosome structure or number cause a class of disorders called congenital anomalies. phenylketonuria. If nondisjunction occ urs during mitosis soon after fertilization. chromosomes normally separate in a process call ed disjunction. The cells still have a normal amount of genetic material. The aberration may be loss. Potential contribu ting factors include maternal age. such as monosomies or trisomies. The presence of one chromosome less than the normal number is called monosomy. spina bifida .) X-LINKED DOMINANT INHERITANCE The diagram shows the children of a normal parent and a parent with an abnormal. it may affect all the resulting cel ls. or rearrangement genetic material. X-linked dominant gene on the X chromosome (shown by the dot on the X). A mixture of both trisomic and normal cells results in mosaicism. Errors in chromosome number During both meiosis and mitosis. the shifting or moving of a chromosome. the children of parents with translocated chromosomes may have serious genetic defects. called nondisjunction. Parental age doesn't seem to be a fac tor in translocation. When th e father is affected.lity. only his daughters have the abnormal gene. Tay-S achs disease Autosomal dominant: Marfan syndrome X-linked recessive: hemophilia Polygenic multifactorial: cleft lip/cleft palate. addition. and poor prenatal care. radiation. sickle cell anemia. Most clinically significant chromosome aberrations arise during meiosis. The incidence of nondisjunction increases wi th parental age. However . The alphabetically listed disorders have the f ollowing patterns of inheritance: Autosomal recessive: cystic fibrosis. occurs when chromosomes s plit apart and rejoin in an abnormal arrangement. DISORDERS This section discusses disorders in the context of their pattern of inheritance as well as environmental factors. a n autosomal monosomy is nonviable. Meiosis is an incredibly complex process that can go wrong in many ways. wh ich is the presence of two or more cell lines in the same person. an endless variety of clinical manifestations may occur. Translocation. The effect of mosaicism depends on the proportion and anatomic location of abnormal cells. If the remaining genetic material is sufficient to maintain life. Failure to separate. The presence of an extra chromosome is called a trisomy. causes an unequal di stribution of chromosomes between the two resulting cells. When the mother is affected.

A complete cleft includes the soft palate.Chromosome number: Down syndrome. the bones .250 births among whites. the result is one trisomic cell and one monosomic cell. They originat e in the second month of pregnancy if the front and sides of the face and the pa latine shelves fuse imperfectly. When di sjunction proceeds normally. the front and sides of the face and the pa latine shelves develop. fertilization with a normal sperm results in a zygo te with the correct number of chromosomes. (See Types of cleft deformities. the lip or palate fuses imp erfectly. genetic abnormality. or environmental factors. exposure to terato gens. Cleft lip with or without cleft palate occurs t wice as often in males than females.) Incidence is highest in child ren with a family history of cleft defects. Only the lip may be involved. A cleft palate may be partial or complete. the incidence is lower in blacks and great er in Japanese populations. In nondisjunction. in the mid line. bilaterally. The deformity may range from a simple notch to a complete cleft. TYPES OF CLEFT DEFORMITIES The following illustrations show variations of cleft lip and cleft palate. Cleft lip and cleft palate Cleft lip and cleft palate may occur separately or in combination. the sister chromat ids fail to separate. Causes Possible causes include: chromosomal abnormality (trisomy 13) exposure to teratogens during fetal development combined genetic and environmental factors. or rarely. Because of a chromosomal abnormality. or the defect may extend into the upper jaw or nasal cavity. Pathophysiology During the second month of pregnancy. CULTURAL DIVERSITY Cleft lip with or without cleft palate occurs in about 1 in 6 00 to 1 in 1. CHROMOSOMAL DISJUNCTION AND NONDISJUNCTION The illustration shows normal disjunction and nondisjunction of an ovum. Cleft lip deformities can occur unilaterally. Cleft palate without cleft lip is more comm on in females.

Diagnosis Clinical presentation. because the abnormal lip and palate affect nutritional intake hearing impairment. and the alveolus on one or both sides of the premaxilla. often due to middle-ear damage or recurrent infections permanent speech impediment. even after surgical repair. Signs and symptoms Obvious cleft lip or cleft palate Feeding difficulties due to incomplete fusion of the palate. Treatment Correcting cleft lip or palate may involve: surgical correction of cleft lip in the first few days of life to permit sucking orthodontic prosthesis to improve sucking surgical correction of cleft lip at 8 weeks to 8 months to allow maternal bondin g and rule out associated congenital anomalies surgical correction of cleft palate at 12 to 18 months. A double cleft separates the maxil la and premaxilla into freely moving segments. enlarging the cleft. A double cleft is the most severe of the deformities. The cleft runs from the so ft palate forward to either side of the nose. obvious at birth Prenatal targeted ultrasound.of the maxilla. after the infant gains w eight and is infection-free . Complications Complications may include: malnutrition. The tongue and other muscles can displace the segments.

intestinal dysfunction. Pathophysiology Most cases arise from the mutation that affects the genetic coding for a single amino acid. dysfunction of the exocrine glands affects multiple organ sy stems. Causes of CF include: coding found on as many as 350 alleles autosomal recessive inheritance. to improve feeding patterns and promote nutrition. bronchiolectasis. but it lacks the phenyl . Th e CFTR resembles other transmembrane transport proteins. The disease affects males as well as females and is the most common fatal genetic disease in white children. Cystic fibrosis In cystic fibrosis. Women of childbearing age should be encouraged to take a daily multivitamin containing folic acid until menopause or until they're no lon ger fertile. AGE ALERT Daily use of folic acid before conception decreases the risk for isola ted (not associated with another genetic or congenital malformation) cleft lip o r palate by up to 25%. CULTURAL DIVERSITY The incidence of cystic fibrosis varies with ethnic origin. it encodes a membrane-associated prote in called the cystic fibrosis transmembrane regulator (CFTR). Causes The responsible gene is on chromosome 7q.000 births in the Asian popula tion in Hawaii. such as a lamb's nipple. exocrine pancreatic insuffic iency. I t occurs in 1 of 3. abnormal sweat gland function. and 1 in 90.000 births in whites of North America and northern European d escent. The exact function of CFTR remains unknown. Cystic fibrosis is accompanied by many complications and now carries an average life expectancy of 28 years. 1 in 17. resulting in a protein (the CFTR) that doesn't function properly.000 births in blacks.speech therapy to correct speech patterns use of a contoured speech bulb attached to the posterior of a denture to occlude the nasopharynx when a wide horseshoe defect makes surgery impossible (to help the child develop intelligible speech) adequate nutrition for normal growth and development use of a large soft nipple with large holes. The disorder is characterized by chronic airway inf ection leading to bronchiectasis. but it appears to help regulate chloride and sodium tr ansport across epithelial membranes. and reproductive d ysfunction.

airway-occluding secretions wheezes heard on auscultation due to constricted airways retention of bicarbonate and water due to the absence of the CFTR chloride chann el in the pancreatic ductile epithelia. CF has a varying effect on electrolyte and water transport. and clubbing of fingers and toes from chronic hypoxia crackles on auscultation due to thick. cyanosis. and ult imate destruction of the pancreas obstruction of the small and large intestine due to inhibited secretion of chlor ide and water and excessive absorption of liquid biliary cirrhosis due to retention of biliary secretions . This regulator interferes with cAMP-regulated chloride channels and other ions by preventing adenosine triphosp hate from binding to the protein or by interfering with activation by protein ki nase.alanine in the protein produced by normal genes. increasing the viscosi ty of mucus-gland secretions. Signs and symptoms Signs and symptoms may include: thick secretions and dehydration due to ionic imbalance chronic airway infections by Staphylococcus aureus. leading to obstruction of glandular ducts. limits membrane function and leads to re tention of pancreatic enzymes. and Pseudomonas cepacea. and volume-secretory epithelia (in t he pancreas). Pseudomonas aeruginosa. chronic cholecystitis and cholelithiasis. The mutation affects volume-absorbing epithelia (in the airways and intestines). Lack of phenylalanine leads to dehydration. salt-absorbing epithelia (in sweat ducts). possibly due to abnormal airway surface fluids and failure of lung defenses dyspnea due to accumulation of thick secretions in bronchioles and alveoli paroxysmal cough due to stimulation of the secretion-removal reflex barrel chest.

and other mucus gland secretions atelectasis or emphysema due to respiratory effects diabetes. and delayed sexual development due to d eficiency of fat-soluble vitamins rectal prolapse in infants and children due to malnutrition and wasting of perir ectal supporting tissues esophageal varices due to cirrhosis and portal hypertension. and sallow skin with poor turgor due to malabsorption clotting problems. retarded bone growth. poor growth. E. Diagnosis The following tests help diagnose cystic fibrosis: test to detect elevated sodium chloride levels in sweat of 60 mEq/L or greater . pancreatitis. D. and lipase (from obstructed pancreatic ducts. Complications Complications may include: obstructed glandular ducts (leading to peribronchial thickening) due to increase d viscosity of bronchial. and hepatic failure due to effects on the intestines. distended abdomen. blocking th e passage of ova.fatal shock and arrhythmias due to hyponatremia and hypochloremia from sodium lo st in sweat failure to thrive: poor weight gain. thin extrem ities. amylase. and liver malnutrition and malabsorption of fat-soluble vitamins (A. p reventing the conversion and absorption of fat and protein in the intestinal tra ct) lack of sperm in the semen (azoospermia) secondary amenorrhea and increased mucus in the reproductive tracts. pancreatic. and K) due to d eficiencies of trypsin. pa ncreas.

chest X-ray to reveal early signs of obstructive lung disease sputum culture to detect organisms that chronically colonize electrolyte status to detect dehydration stool analysis showing absence of trypsin (suggesting pancreatic insufficiency) DNA testing to detect abnormal gene and determine carrier status and for prenata l diagnosis in families with an affected child. Treatment Possible treatments include: hypertonic radiocontrast materials delivered by enema to treat acute obstruction s due to meconium ileus breathing exercises and chest percussion to clear pulmonary secretions antibiotics to treat lung infection. The test may need to be repeated.AGE ALERT The sweat test may be inaccurate in very young infants because they ma y not produce enough sweat for a valid test. guided by sputum culture results drugs to increase mucus clearance inhaled beta-adrenergic agonists to control airway constriction pancreatic enzyme replacement to maintain adequate nutrition sodium-channel blocker to decrease sodium reabsorption from secretions and impro ve viscosity .

such as radiation and viruses. KARYOTYPE OF DOWN SYNDROME Normally. A patient with Down syndrome. other distinctive physical abnormalities. each autosome is one of a pair. a DNA-splitting enzyme. Fetal and neonatal mortality rates remain high. a mixture of two cell types. and mental retardation. It occurs in 1 of 650 to 700 live births. Signs and symptoms . to help liquefy muc us recombinant alpha-antitrypsin to counteract excessive proteolytic activity produ ced during airway inflammation gene therapy to introduce normal CFTR into affected epithelial cells transplantation of heart or lungs in severe organ failure. The result is a karyotype of 47 chromosomes instead of the usual 46. Down syndrome results from a n unbalanced translocation or chromosomal rearrangement in which the long arm of chromosome 21 breaks and attaches to another chromosome. 60% of affected persons have cardiac defects. Improved treatment for heart defects. usually resulting from compl ications of associated heart defects. Pathophysiology Nearly all cases of Down syndrome result from trisomy 21 (3 copies of chromosome 21). (See Karyotype of Down syndrome. Causes Causes of Down syndrome include: Advanced age (when the mother is over 35 at delivery or the father is over 42) Cumulative effects of environmental factors. some with the normal 46 and some with an extra chromosome 21. respiratory an d other infections. is a spontaneous chromosome abnormality that cause s characteristic facial features.) In 4% of the patients. Some affected persons and some asymptomatic parents may have chromosomal mosaici sm. has an extra chromosome 21. or triso my 21. and acute leukemia has significantly increased life expectan cy. or trisomy 21.uridine triphosphate to stimulate chloride secretion by a non-CFTR salt supplements to replace electrolytes lost through sweat recombinant human DNase (Pulmozyme). Down syndrome Down syndrome.

Other signs and symptoms include: distinctive facial features (low nasal bridge. and low-set ears). small open mouth and large tongue single transverse crease on the palm (Simian crease) small white spots on the iris (Brushfield's spots) mental retardation (estimated IQ of 20 to 50) developmental delay due to hypotonia and decreased cognitive processing congenital heart disease. The infant is lethargic and has distinctive craniofacial features. usually in the fourth decade if the patient survives increased susceptibility to acute and chronic infections strabismus and cataracts as the child grows . Complications Possible complications include: early death due to cardiac complications increased susceptibility to leukemia premature senile dementia. mainly septal defects and especially of the endocardia l cushion impaired reflexes due to decreased muscle tone in limbs. protruding tong ue. epicanthic folds.AGE ALERT The physical signs of Down syndrome are apparent at birth.

reducing susceptibility to dental caries. recommended for pregnant women over 34. Hemophilia occurs in 20 of 100. possibly improving speech. or nonfunction. Treatment Surgery to correct heart defects and other related congenital abnormalities Antibiotics for recurrent infections Plastic surgery to correct characteristic facial traits (especially protruding t ongue. Diagnosis Diagnostic tests include: definitive karyotype amniocentesis for prenatal diagnosis. the severity and prognosi s of bleeding vary with the degree of deficiency. and the site o f bleeding. or classic hemophilia. is a deficiency of clotting factor VIII. affects 15% of all hemophiliacs and results from a deficiency of factor IX. males may be infertile. or Christmas disease. Hemoph ilia B. ev en with a negative family history prenatal targeted ultrasonography for duodenal obstruction or an atrioventricula r canal defect (suggestive of Down syndrome) blood tests for reduced alpha-fetoprotein levels (suggestive of Down syndrome).poorly developed genitalia and delayed puberty (females may menstruate and be fe rtile. Hemophilia Hemophilia is an X-linked recessive bleeding disorder.000 male births and results from a de ficiency of specific clotting factors. Causes . it is more common than type B. with low serum testosterone levels and often with undescended testes). and resulting in fewer orthodontic problems) Early intervention programs and supportive therapies to maximize mental and phys ical capabilities Thyroid hormone replacement for hypothyroidism. affecting more than 80% of all hemophiliacs. There's no relationship between factor VIII and factor IX inherited defects. Hemophilia A.

Factors VIII and IX are component s of the intrinsic clotting pathway. but no spon taneous bleeding after minor trauma pain. or mild. swelling. A person with hemophilia forms a platelet plug at a bleeding site. Patients with severe disease have no detectable factor V III or factor IX activity. Excessive bleeding occurs when these clotting factors are reduced by more than 75%. A deficiency or nonfunction of factor VIII causes hemophilia A. or flank pain hematuria from bleeding into kidney . depending on the degree of activati on of clotting factors. Factor VIII accelerates the activation of factor X by several thousandfold. and mildly afflicted patients have 5% to 25% of normal clott ing activity. Delayed blee ding is more common than immediate hemorrhage. Signs and symptoms Signs and symptoms may include: spontaneous bleeding in severe hemophilia (prolonged or excessive bleeding after circumcision is often the first sign) excessive or continued bleeding or bruising after minor trauma or surgery large subcutaneous and deep intramuscular hematomas due to mild trauma prolonged bleeding in mild hemophilia after major trauma or surgery. moderate. but clotting factor deficiency impairs the ability to form a stable fibrin clot. Hemophilia may be severe. factor IX is an essential factor and factor VIII is a critical cofactor.Defect in a specific gene on the X chromosome that codes for factor VIII synthes is (hemophilia A) More than 300 different base-pair substitutions involving the factor IX gene on the X chromosome (hemophilia B). and tenderness due to bleeding into joints (especially weight-be aring joints) internal bleeding. chest. often manifested as abdominal. Pathophysiology Hemophilia is an X-linked recessive genetic disease causing abnormal bleeding be cause of specific clotting factor malfunction. and a deficiency or nonfunction of factor IX causes hemophilia B. Moderately afflicted patients have 1% to 4% of normal clotting activity.

and muscle atrophy due to bleeding nea r peripheral nerves ischemia and gangrene due to impaired blood flow through a major vessel distal t o bleed decreased tissue perfusion and hypovolemic shock (shown as restlessness. cool and clammy skin. Complications Complications may include: peripheral neuropathy. pallor. confusion. anxiety . pain. and tachycardia). Diagnosis Specific coagulation factor assays to diagnose the type and severity of hemophil ia Factor VIII assay of 0% to 30% of normal and prolonged activated partial thrombo plastin time (hemophilia A) Deficient factor IX and normal factor VIII levels (hemophilia B) Normal platelet count and function. and prothrombin time (hemophi lia A and B). decreased urine output. h ypotension. bleeding time.hematemesis or tarry stools from bleeding into the GI tract. paresthesia. chest pain. Treatment Treatment of hemophilia includes: cryoprecipitated or lyophilized antihemophilic factor to increase clotting facto r levels (to permit normal hemostasis in hemophilia A) factor IX concentrate during bleeding episodes (hemophilia B) cold compresses or ice bags and elevation of bleeding site to slow or stop flow analgesics to control pain .

and cardiovascular anomalies. due to possible hematoma at the site no aspirin or aspirin-containing medications due to decreased platelet adherence and possible increased bleeding. such as analgesics. generalized disease of the connective ti ssue. The effect on connective tissue is varied and includes excessive bone growth. Pathophysiology The syndrome is caused by a mutation in a single allele of a gene located on chr omosome 15. Signs and symptoms Signs and symptoms may include: increased height. ocular disorders. for example). AGE ALERT To help prevent injury. Marfan syndrome Marfan syndrome is a rare degenerative. Older children should avoid contact sports. long extremities. Death occurs from cardiovascular complications fro m early infancy to adulthood. young children should wear clothing with padde d patches on the knees and elbows. and cardiac defects. and arachnodactyly (long spider-like fingers ) due to effects on long bones and joints and excessive bone growth defects of sternum (funnel chest or pigeon breast. The syndrome occurs in 1 of 20. chest asymmetry . the gene codes for fibrillin. It results from elastin and collagen defects and causes ocular. skeletal. scoliosis. Cause Autosomal dominant mutation.aminocaproic acid (Amicar) for oral bleeding (inhibits plasminogen activator sub stances) prophylactic desmopressin (DDAVP) before dental procedures or minor surgery to r elease stored von Willebrand's factor and factor VIII (to reduce bleeding) no IM injections. These small fibers are abundant in large blood vessels and the suspenso ry ligaments of the ocular lenses. af fecting males and females equally. a glycoprotein component of connective tissue.000 individuals. and kyphosis hypermobile joints due to effects on connective tissue .

Complications Possible complications include: weak joints and ligaments. stretching of chordae tendineae. Diagnosis Positive family history in one parent (85% of patients) or negative family histo ry (15%.nearsightedness due to elongated ocular globe lens displacement due to altered connective tissue valvular abnormalities (redundancy of leaflets. predisposing to injury cataracts due to lens displacement retinal detachments and retinal tears severe mitral valve regurgitation due to mitral valve prolapse spontaneous pneumothorax due to chest wall instability inguinal and incisional hernias dilation of the dural sac (portion of the dura mater beyond caudal end of the sp inal cord). and dilation of valvulae annulus) mitral valve prolapse due to weakened connective tissue aortic regurgitation due to dilation of aortic root and ascending aorta. suggesting a mutation. possibly from advanced paternal age) Clinical presentation and history of the disease in close relatives .

CHARACTERISTICS OF SICKLED CELLS Normal red blood cells and sickled cells vary in shape. .Presence of lens displacement and aneurysm of the ascending aorta without other symptoms or familial tendency Detection of fibrillin defects in cultured skin X-rays confirming abnormalities Echocardiogram showing dilation of the aortic root DNA analysis of the gene. and the rate at which they're destroyed. The illustration shows nor mal and sickled cells and lists the major differences. life span. oxygen-carryi ng capacity. Treatment Treatment for Marfan syndrome may involve: surgical repair of aneurysms to prevent rupture surgical correction of ocular deformities to improve vision steroid and sex hormone therapy to induce early epiphyseal closure and limit adu lt height beta-adrenergic blockers to delay or prevent aortic dilation surgical replacement of aortic valve and mitral valve mechanical bracing and physical therapy for mild scoliosis if curvature > 20 deg rees surgery for scoliosis if curvature > 45 degrees.

Abnormal hemoglobin S. stres s. sickle-shaped red blood cells stick to the capillary wall and each oth er. and few live to middle age. CULTURAL DIVERSITY Sickle cell anemia occurs primarily in persons of African and Mediterranean descent. Signs and symptoms AGE ALERT Symptoms of sickle cell anemia don't develop until after the age of 6 months because fetal hemoglobin protects infants for the first few months after birth. exposure to cold. The deox ygenated. Each patient with sickle cell anemia has a different hypoxic threshold and diffe rent factors that trigger a sickle cell crisis. With e ach new crisis. The crisis worsens as tiss ue hypoxia and acidic waste products cause more sickling and cell damage. Although most com mon in tropical Africans and people of African descent. it also occurs in Puerto Rico. high altitudes. and swelling. overexertion. these cells become rigid.) The sickling produces hemolysis. exposure to cold. forming a crescent or sickle shape. or a pathophysiologic process that pulls water out of the si ckle cells precipitates a crisis in most patients. Illness. blocking blood flow and causing cellular hypoxia. especially the spleen a nd kidneys. (See Sickle cell crisis. and elongated.) The blockages then cause anoxic changes that lead to further sickling and obstructi on. As a result. but it also affects other populations. organs and tissues are slowly destroyed. Pathophysiology Sickle cell anemia results from substitution of the amino acid valine for glutam ic acid in the hemoglobin S gene encoding the beta chain of hemoglobin. Half the patients with sickle cell anemia die by their early twenties. and the Mediterranean. Signs and symptoms may include: .Sickle cell anemia Sickle cell anemia is a congenital hemolytic anemia resulting from defective hem oglobin molecules. making the blood more viscous. rough. SICKLE CELL CRISIS Infection. causing pain. tissue infarctions. India. (See Characteristics of sickled cells. found in the red blood cells of patients. becomes insoluble durin g hypoxia. The altered cells also pile up in the capillaries and small er blood vessels. the Middle East. usually an asymptomatic condition). Cause Mutation of hemoglobin S gene (heterozygous inheritance results in sickle cell t rait. Turkey. or other situations t hat cause cellular oxygen deprivation may trigger a sickle cell crisis. acidotic states. Normal circulation is impaired.

sickle cells (leading to tissue anoxia and possibly necrosis) Streptococcus pneumoniae sepsis due to autosplenectomy (splenic damage and scarr ing in patients with long-term disease) aplastic crisis due to bone marrow depression (associated with infection. decreased bone marrow activi ty. and hemolysis (characterized by pallor. Complications Complications may include: retinopathy. and cerebral vessel occlusion due to organ infarction hypovolemic shock and death due to massive entrapment of cells necrosis infection and gangrene. muscle. may cause lethargy. w ith possible coma) acute sequestration crisis (rare. usually affects patients who also have glucose-6-phospha te dehydrogenase deficiency. dark urine. and low-grade fever due to blood vessel obstruction by rig id. nephropathy. and hypovolemic shock) due to the sudden massive entrapm ent of cells in spleen and liver hemolytic crisis (rare. sleepiness.severe pain in the abdomen. usuall y viral) megaloblastic crisis due to bone marrow depression. and dyspnea. affects infants aged 8 months to 2 years. lethargy. Diagnosis Positive family history and typical clinical features . pallor. degenerative changes cause liver congestion and enl argement and chronic jaundice worsens). thorax. or bones (characterizes painful cris is) jaundice. tangled.

Hemoglobin electrophoresis. Treatment Possible treatments include: deformity in the vertebrae of many adults packed red blood cell transfusion to correct hypovolemia (if hemoglobin levels d ecrease) sedation and analgesics. elevated white blood cell and platelet counts. such as low-dose peni cillin. AGE ALERT Vaccines to prevent illness and anti-infectives. such as meperidine (Demerol) or morphine sulfate. increased serum iron levels.V. decrea sed erythrocyte sedimentation rate. and reticulocytosis (hemoglobin levels may be low or normal) Lateral chest X-ray showing Lincoln log and some adolescents. should be considered to prevent complications in patients with sickle ce . decreased red b lood cell survival. fluids to correct hypovolemia and prevent dehydrat ion and vessel occlusion prophylactic penicillin before the age of 4 months to prevent infection warm compresses to painful areas to promote venous drainage iron and folic acid supplements to prevent anemia. for p ain oxygen administration to correct hypoxia large amounts of oral or I. showing hemoglobin S Electrophoresis of umbilical cord blood to provide screening for all newborns at risk Stained blood smear showing sickle cells Low red blood cell counts.

and cognitive abnormalities. North and South Carolina have twice the incidence as most other parts of the country. incomplete fusion of the vertebrae in the d eveloping nervous system of the embryo. Varying degrees of sensory and motor dysfunction below the level of the lesion are present. CULTURAL DIVERSITY The incidence of spina bifida is significantly greater in the British Isles and low in southern China and Japan. in which peripheral nerves. soft fatty deposits. As the ne rvous system develops and differentiates. or the spinal cord also protrude . Spina bifida occulta occurs in as many as 25% of births. it's vulnerable to teratogenic effects . tuft of hair. Spina bifida Spina bifida is the incomplete fusion of one or more vertebrae. in trauterine growth retardation.ll anemia. with closure of the lumbar regions by 26 days. port wine nevi. In the United States. Pathophysiology Neural tube closure normally occurs at 24 days' gestation in the cranial region and continues distally. and spina bifida cystica occurs in 1 in 1. Signs and symptoms Signs and symptoms depend on the type and severity of neural tube defect: weak feet or bowel and bladder disturbances due to rapid growth phases and abnor mal adherence of the spinal cord to other tissues (occasionally with spina bifid a occulta) dimple. or combination over s pine (spina bifida occulta) . root segments. or as a myelomeningoc ele. Spina bifida cystica can occur as a meningocele. resulting in dim pling of the area (spina bifida occulta) or protrusion of the spinal tissue (spi na bifida cystica). The specific cause of spinal bifida. Causes Causes of spina bifida include: teratogenic insults before the 26th day of gestation isolated birth defect or part of a multiple chromosomal malformation (trisomy 18 or 13) environmental (such as lack of folic acid in the mother's diet) and genetic fact ors. but neural tube defects have been associated with such noninfectious maternal disorders as folic acid defici ency. in which the meninges protrude in a cerebrospinal fluid-filled sac. The inci dence varies greatly with countries and regions. is unknown.000 births in the United States. Teratogenic insults during this critical time can cause structural defects. Spina bifida occulta rarely affects the structure or function of the cord and pe ripheral nerve roots.

elevated levels suggest a defect Physical examination to detect meningocele and myelomeningocele X-ray to show bone defect or palpation to detect defect (spina bifida occulta) Myelography to confirm spina bifida occulta from other spinal abnormalities. Diagnosis Amniocentesis to detect elevated alpha-fetoprotein levels (indicates presence of open neural tube defect) Acetylcholinesterase levels (can confirm diagnosis) Four-marker screen (maternal serum alpha-fetoprotein. Complications Complications may include: paralysis below the level of the defect infection. Treatment Usually no treatment (spina bifida occulta) Neurosurgic closure (treatment of meningocele) . such as meningitis. human chorionic gonadotrop in [HCG]. and unconjugated estriol) of women not schedul ed for amniocentesis. free alpha-subunit-HCG.saclike protrusion over the spine due to meningocele or myelomeningocele (spina bifida cystica) possible permanent neurologic dysfunction due to meningocele or myelomeningocele (spina bifida cystica).

p rogressive vision loss due to CNS involvement deafness. seizure activity. Tay-Sachs disease appears in fewer than 100 infants born each year in the United States.600 live births in this ethnic group. occurring i n about 1 in 3. If two such carriers have children. spasticity. This enzyme is necessary to metabolize ganglio sides. Complications . difficulty turning over. paralysis. Pathophysiology Tay-Sachs disease is an autosomal recessive disorder in which the enzyme hexosam inidase A is absent or deficient. CULTURAL DIVERSITY Tay-Sachs affects persons of Eastern European Jewish (Ashkena zi) ancestry about 100 times more often than the general population. AGE ALERT Progressive mental and motor deterioration often causes death before t he age of 5 years. is the most common lipid-st orage disease. French Canadians. lipid pigments accumulate and progressively dest roy and demyelinate the CNS cells. and continued neur ologic deterioration (by 18 months of age) recurrent bronchopneumonia due to diminished protective reflexes. also known as GM2 gangliosidosis.Repair of the sac and supportive measures to promote independence and prevent fu rther complications (treatment of myelomeningocele). CULTURAL DIVERSITY About 1 in 30 Ashkenazi Jews. and American Cajuns are heterozygous carriers. Without hexosaminidase A. Cause Congenital deficiency of the enzyme hexosaminidase A. Signs and symptoms Signs and symptoms of Tay-Sachs disease may include: exaggerated Moro reflex (also called startle reflex) at birth and apathy (respon se only to loud sounds) by age 3 to 6 months due to demyelination of CNS cells inability to sit up. water-soluble glycolipids found primarily in the central nervous system ( CNS). each of th eir offspring has a 25% chance of having Tay-Sachs disease. or grasp objects. blindness. Tay-Sachs disease Tay-Sachs disease. lift the head.

CULTURAL DIVERSITY Diagnostic screening is recommended for all couples of Ashken azi Jewish ancestry and for others with a familial history of the disease. 5 FLUIDS AND ELECTROLYTES Handbook of Pathophysiology 5 FLUIDS AND ELECTROLYTES Fluid balance € Intracellular fluid € Extracellular fluid . A blo od test can detect carriers. usually fatal by 5 years of age. Treatment Treatment for Tay-Sachs disease includes the following: tube feedings to provide nutritional supplements suctioning and postural drainage to maintain a patent airway skin care to prevent pressure ulcers in bedridden children laxatives to relieve neurogenic constipation. Diagnosis Clinical features Serum analysis showing deficient hexosaminidase A.Complications may include: blindness generalized paralysis recurrent bronchopneumonia.

Sweating results in loss of sodium and water. Each cell ha s its own mixture of components in the intracellular fluid. and phosphate (PO43 ). calcium (Ca2+). but the amounts of t hese substances are similar in every cell. potassium (K+). and acid-base balance of body fluids. The kidneys maintain chemical balance throughout the body by producing and eliminating urine. magnesium. FLUID BALANCE The kidneys maintain fluid balance in the body by regulating the amount and comp onents of fluid inside and around the cells. ECF includes blood plasma and interstitial fluid (t he fluid between cells in tissues). called extracellular fluid (ECF). and regulate blood pressure by regulating fluid volume . Intracellular fluid contains large am ounts of potassium. chloride (Cl ). electrolyte concentration. Intracellular fluid The fluid inside each cell is called the intracellular fluid (ICF). sulfate (SO42 ). oxygen (O2). and phosphate ions. . Electrolyte balance must r emain in a narrow range for the body to function. is constantly moving. every breath contains water vapor. detox ify and eliminate wastes.€ Fluid exchange Acid base balance Pathophysiologic manifestations of electrolyte imbalance € Edema € Tonicity € Alterations in electrolyte balance Disorders of electrolyte balance € Hypovolemia € Hypervolemia Pathophysiologic manifestations of acid base imbalance € Acidemia € Acidosis € Alkalemia € Alkalosis € Compensation Disorders of acid base balance € Respiratory acidosis € Respiratory alkalosis € Metabolic acidosis € Metabolic alkalosis The body is mostly liquid various electrolytes dissolved in water. Extracellular fluid The fluid in the spaces outside the cells. in some pathologic states it accumulates in a so-called third space. They regulate th e volume. hydrogen (H+). The skin and lungs also play a role in fluid and electrolyte balance. the space around organs in the chest or abdomen. Normally. Electrolytes are ions (electrically charged versions) of essential elements predominantly sod ium (Na+). Only ionic forms of elements can dissolve or combine with other elements. bicarbonate (HCO3 ).

transported from the cells to the lungs for excretion.2 cell function seriously impaired · . and produce ammonium ions (acid). intracellular fluid by continually exchanging water and ionic solutes. To regulate acid base balance. transported from the cells to the kidneys for excretion. Forces that tend to move fluid from the vessels to the interstitial fluid are: hydrostatic pressure of blood (the outward pressure of plasma against the walls of capillaries) osmotic pressure of tissue fluid (the tendency of ions to move across a semiperm eable membrane the capillary wall from an area of greater concentration to one o f lower concentration) Forces that tend to move fluid into vessels are: oncotic pressure of plasma proteins (similar to osmosis. acid ify phosphate salts. fluid escapes at the arteriolar end of the capillary bed and is retur ned at the venular end. they attract fluid into the area of greater concentra tion) hydrostatic pressure of interstitial fluid (inward pressure against the capillar y walls).37 to 7. When the endothelial barrier (capillary wall) is normal a nd intact. across the cell membranes of the renal tubules. but because proteins ca n't cross the vessel wall. and amino acids. The following are important pH boundaries: · <6. and bicarbonate ions. Fluid exchange Two sets of forces determine the exchange of fluid between blood plasma and inte rstitial fluid. Hydrostatic pressure at the arteriolar end of the capillary bed is greater than at the venular end. ECF contains large amounts of sodium. the kidneys secret e hydrogen ions (acid). and phosphate ions. glucose. Oncotic pressure of plasma increases slightly at the venular end as fluid escapes. and other cellu lar products.8 incompatible with life · <7. In physiology. The small amount of fluid lost from the capillaries into the interstitial tissue spaces is drained off through the lymphatic system and returned to the bloodstream. such as h ydrogen. bicarbonate.ECF is rapidly transported through the body by circulating blood and between blo od and tissue fluids by fluid and electrolyte exchange across the capillary wall s.43. chloride. chloride. The kidneys maintain the volume and composition of ECF and. measured c linically as pH. sodium. This keeps the blood at i ts normal pH of 7. electr olytes. It also cont ains CO2. All four forces act to equalize concentrations of fluids. ACID BASE BALANCE Regulation of the ECF environment involves the ratio of acid to base. all positively charged ions are acids and all ne gatively charged ions are bases. to a lesser extent. plus su ch cell nutrients as oxygen. sulfate. fatty acids. potassium. and proteins on both sides of the capillary wall. reabsorb sodium (acid) and bicarbonate ions (base).

Edema results from abnormal expansion of the interstitial fluid or the accumulat ion of fluid in a third space.55 cell function seriously impaired · >7.45 alkalosis · >7. the body ma intains a steady state of extracellular water balance between the plasma and int erstitial fluid. may be due to heart failure or renal disease. isotonic alterations. Many conditions also affect capillary exchange. hypo tonic alterations. Increased fluid volume in the interstitial spaces is called ede ma. Systemic.) CAUSES OF EDEMA Edema results when excess fluid accumulates in the interstitial spaces. pleural cavity (hydrothorax). resulting in fluid shifts. Disorders of fluid volume or osmo larity (concentration of electrolytes in the fluid) result. (See Causes of edema. such as the peritoneum (ascites). Obstruction of the veins or lympha tic system or increased vascular permeability usually causes localized edema in the affected area. It's classified as localized or systemic. or generaliz ed edema. and sweat transport of fluid and electrolytes between extracellular and intracellular flui d. Massive systemic edema i s called anasarca.35 acidosis · 7. Fluid and electrol yte imbalances include edema.37 to 7. PATHOPHYSIOLOGIC MANIFESTATIONS OF ELECTROLYTE IMBALANCE The regulation of intracellular and extracellular electrolyte concentrations dep ends on: balance between the intake of substances containing electrolytes and the output of electrolytes in urine. hypertonic alterations. or pericardial sac (pericardial effusion). Fluid imbalance occurs when regulatory mechanisms can't compensate for abnormal intake and output at any level from the cell to the organism. The char t shows the causes and effects of this fluid accumulation.43 normal · >7. feces. CAUSE UNDERLYING CONDITION Increased hydrostatic pressure . Edema Despite almost constant interchange through the endothelial barrier. such as the swelling around an injury.<7. and electrolyte imbalances.8 incompatible with life.

when . Hypertonic solutions have a greater than normal concentration of some essential electrolyte. causing cell s hrinkage. Examples include blood loss from penetrating trauma or expansion of fluid vo lume if a patient receives too much normal saline. Isotonic alterations Isotonic alterations or disorders don't make the cells swell or shrink because o smosis doesn't occur. Normal saline has a sodi um chloride concentration of 0. or tonicity. Wat er flows out of the cell through the semipermeable cell membrane. Hypertonic alterations Hypertonic alterations occur when the ECF is more concentrated than the ICF. usually sodium. The word normal in this context refers to the usual electrolyte concentration of physiologic fluids.Heart failure Constrictive pericarditis Venous thrombosis Cirrhosis Hypoproteinemia Cirrhosis Malnutrition Nephrotic syndrome Gastroenteropathy Lymphatic obstruction Cancer Inflammatory scarring Radiation Sodium retention Excessive salt intake Increased tubular reabsorption of sodium Reduced renal perfusion Increased endothelial permeability Inflammation Burns Trauma Allergic or immunologic reactions Tonicity Many fluid and electrolyte disorders are classified according to how they affect osmotic pressure. also usually sodium. They occur when intracellular and extracellular fluids hav e equal osmotic pressure.9%) saline. but there's a dramatic change in total-body fluid volu me. Isotonic solutions have the same electrolyte concentration and therefore the sam e osmotic pressure. This can occur when a patient is given hypertonic (>0. Hypotonic solutions have a lower than normal concentration of some essential ele ctrolyte. Tonicity describes the relative concentrations o f electrolytes (osmotic pressure) on both sides of a semipermeable membrane (the cell wall or the capillary wall).9%.

the process is reversed. In extreme hypotonicity. Physiologic roles of potassium include: maintain cell electrical neutrality facilitate cardiac muscle contraction and electrical conductivity facilitate neuromuscular transmission of nerve impulses maintain acid base balance. or w hen renal disease causes sodium retention. Overhydration is the most common cause. an active transport mechanism in the cell membrane. and magnesium and the anions (negatively charged ions) chloride. as water dilutes the ECF.severe dehydration causes hypernatremia (high Na+ concentration in blood). Too much or too little of any electrolyte will affect most body systems. Sodium and potassium Sodium is the major cation in ECF. osmotic pressure forces some ECF into the cells. Water moves into the cel ls until balance is restored. during depolarization. Hypotonic alterations When the ECF becomes hypotonic. calcium. Physiologic roles of sodium cations include: maintaining tonicity of ECF regulating acid base balance by renal reabsorption of sodium ion (base) and excret ion of hydrogen ion (acid) facilitating nerve conduction and neuromuscular function facilitating glandular secretion maintaining water balance. potassi um. cells may swell until the y burst and die. causing them to swell. ph osphate. Alterations in electrolyte balance The major electrolytes are the cations (positively charged ions) sodium. it becomes hypotonic with respect to the ICF. continually shifts sodium into and potassium out o f cells. ca lled the sodium potassium pump. . communication within and between cells involves c hanges (repolarization and depolarization) in surface charge on the cell membran e. and potassium is the major cation in ICF. During repolarization. and bicarbonate. Esp ecially in nerves and muscles. The body continuously attempts to maintain intracellul ar and extracellular equilibrium of electrolytes.

it accounts for two-thirds of all ser um anions. but physiologically it is as significa nt as the other major electrolytes. BLOOD PRESSURE FLUID AND ELECTROLYTE STATUS . and normal muscle contraction. nerve impulse transmission. Chloride also: helps maintain acid base and water balances influences the tonicity of ECF facilitates exchange of oxygen and CO2 in red blood cells helps activate salivary amylase. and calcium transport across cell membranes facilitating protein transport. Magnesium Magnesium is present in smaller quantity. FLUID AND ELECTROLYTE IMPLICATIONS OF BLOOD PRESSURE FINDINGS Blood pressure reflects changes in fluid and electrolyte status. Calcium Calcium is indispensable in cell permeability. it provides an a cid medium for digestion and enzyme activation.Chloride Chloride is mainly an extracellular anion. potassium. which regulates intracellular calcium activating many enzymes in carbohydrate and protein metabolism facilitating cell metabolism facilitating sodium. hypercalcemia can cause cardiac arrhythmias a nd coma. Other functions include: stimulating parathyroid hormone secretion. which triggers the digestive process. Hypocalce mia can cause tetany and seizures. Secreted by the stomach mucosa as hydrochloric acid. bone and teeth formation. The major function of magnesium is to enhanc e neuromuscular communication. blood c oagulation.

Blood pressure may be increased or decreased.Normal Hemodynamic stability Initial hemodynamic instability Hypotension Fluid volume deficit Potassium imbalance Calcium imbalance Magnesium imbalance Acidosis Hypertension Fluid volume excess Hypernatremia Phosphate The phosphate anion is involved in cellular metabolism as well as neuromuscular regulation and hematologic function. ranging from disorientation or confusion to a completely d epressed central nervous system (CNS).) The GI tract i s particularly susceptible to electrolyte imbalance: . causing arrhythmias. Multiple neurologic symptoms may result from e lectrolyte imbalance. Phosphate reabsorption in the renal tubules is inversely related to calcium levels. which means that an increase in urinary phosphorous triggers calcium reabsorption and vice versa. (Se e Fluid and electrolyte implications of blood pressure findings. Too much or too little potas sium or too little calcium or magnesium can increase the excitability of the car diac muscle. Too much or too little sodium or too much potassium can cause oliguria. Effects of electrolyte imbalance Electrolyte imbalances can affect all body systems.

vomiting. (See Electrolyte imbalances. ELECTROLYTE IMBALANCE SIGNS AND SYMPTOMS DIAGNOSTIC TEST RESULTS Hyponatremia Muscle twitching and weakness due to osmotic swelling of cells Lethargy. about 55% ELECTROLYTE IMBALANCES Signs and symptoms of a fluid and electrolyte imbalance are often subtle. and treatments. seizures. confusion.) Hypovolemia Water content of the human body progressively decreases from birth to old age. Many factors. nausea. and diarrhea too much calcium nausea. injury. vomiting. such as ill ness. and coma due to altered neurotransmission . surgery. as much as 75% of body weight in adults. a s follows: in the newborn. Even a patient with a minor illness is at risk for fluid and elect rolyte imbalance.too much potassium abdominal cramps. and constipation. Blood chemistry tests help diagnose and evaluate electrolyte imbalances. and diarrhea too little potassium paralytic ileus too much magnesium nausea. about 60% of body weight in the elderly. can disrupt a patient's fluid and electro lyte balance. DISORDERS OF ELECTROLYTE BALANCE Fluid and electrolyte balance is essential for health.

and death from dramatic increase in osmotic pressur e Serum sodium > 145 mEq/L Urine sodium < 40 mEq/24 hours . tachycardia. and decreased level of consciousness due to alte red cellular metabolism Hypertension. vomiting. respiratory arrest. restlessness.Hypotension and tachycardia due to decreased extracellular circulating volume Nausea. fever. increased viscosity of saliva. pitting edema. and excessive weight gain due to water shift from intracellular to extracellular fluid Thirst. rough tongue due to fluid shift Dyspnea. and abdominal cramps due to edema affecting receptors in the b rain or vomiting center of the brain stem Oliguria or anuria due to renal dysfunction Serum sodium < 135 mEq/L Decreased urine specific gravity Decreased serum osmolality Urine sodium > 100 mEq/24 hours Increased red blood cell count Hypernatremia Agitation.

High serum osmolality Hypokalemia Dizziness. and cardia c arrest due to changes in membrane excitability Nausea. and leg cramps due to decreased neuromuscular excitabi lity Serum potassium < 3. and abdominal cramps due to decreased gastric motility Muscle weakness and flaccid paralysis due to inactivation of membrane sodium cha nnels Serum potassium > 5 mEq/L . electrocardiogram (ECG) changes. anorexia. decreased peristalsis. hypotension. diarrhea.5 mEq/L Coexisting low serum calcium and magnesium levels not responsive to treatment fo r hypokalemia usually suggest hypomagnesemia Metabolic alkalosis ECG changes include flattened T waves. depressed ST segment Hyperkalemia Tachycardia changing to bradycardia. ECG changes. and abdominal diste ntion due to decreased bowel motility Muscle weakness. and cardiac arrest due to hypo polarization and alterations in repolarization Nausea. fatigue. vomiting. elevated U waves. arrhythmias. diarrhea.

rapid breathing Weakness Diminished cognitive ability. depressed breathing Usually associated with hyponatremia and its characteristic symptoms. such as mu scle weakness and twitching Serum chloride < 98 mEq/L Serum pH > 7.Metabolic acidosis ECG changes include tented and elevated T waves. prolonged PR interval.45 (supportive value) Serum CO2 > 32 mEq/L (supportive value) ELECTROLYTE IMBALANCE SIGNS AND SYMPTOMS DIAGNOSTIC TEST RESULTS Hyperchloremia Deep. possibly leading to coma Serum chloride > 108 mEq/L . flattened or absent P waves. depressed ST segment Hypochloremia Muscle hypertonicity and tetany Shallow. widened QRS complex.

or apathy due to decreased neuromuscular irritability (increased threshold) Weakness and muscle flaccidity due to depressed neuromuscular irritability and r elease of acetylcholine at the myoneural junction Bone pain and pathological fractures due to calcium loss from bones Heart block due to decreased neuromuscular irritability Anorexia.Serum pH < 7. arrhythmias Possible changes in serum protein because half of serum calcium is bound to albu min Hypercalcemia Drowsiness. laryngospasm. and dehydration due to hyperosmolarity Flank pain due to kidney stone formation . Chvos tek's and Trousseau's signs due to enhanced neuromuscular irritability Hypotension and arrhythmias due to decreased calcium influx Serum calcium < 8. vomiting. seizures. serum CO2 < 22 mEq/L (supportive values) Hypocalcemia Anxiety. irritability. depression. constipation. headaches. twitching around the mouth. nausea. confusion.35. irritability. lethargy. prolonged ST segment.5 mg/dl Low platelet count ECG shows lengthened QT interval.

delusions. vasodilation.Serum calcium > 10.5 mg/dl ECG shows signs of heart block and shortened QT interval Azotemia Decreased parathyroid hormone level Sulkowitch urine test shows increased calcium precipitation Hypomagnesemia Nearly always coexists with hypokalemia and hypocalcemia Hyperirritability. and hypotension due to enhanced inward sodium current or concurrent effects of calcium and potassium imbalance Serum magnesium < 1.5 mEq/L Coexisting low serum potassium and calcium levels ELECTROLYTE IMBALANCE SIGNS AND SYMPTOMS DIAGNOSTIC TEST RESULTS Hypermagnesemia Hypermagnesemia is uncommon. leg and foot cramps. positive Chvostek's and Troussea u's signs. tetany. and seizures due to alteration in neuromuscular transmission Arrhythmias. caused by decreased renal excretion (renal failure) or increased intake of magnesium . confusion.

bradycardia due to decreased inward sodium current Hypotension due to relaxation of vascular smooth muscle and reduction of vascula r resistance by displacing calcium from the vascular wall surface Serum magnesium > 2.3-diphosphoglycerate deficiency Serum phosphate < 2.5 mg/dl Serum calcium < 9 mg/dl . muscle weakness to flaccid paralysis due to suppression of acetylcholine release at the myoneural junction.5 mg/dl Urine phosphate > 1. and paresthesia due to deficiency of adenosine triphosp hate Peripheral hypoxia due to 2.5 mEq/L Coexisting elevated potassium and calcium levels Hypophosphatemia Muscle weakness.Diminished reflexes. blocking neuromuscular transmis sion and reducing cell excitablity Respiratory distress secondary to respiratory muscle paralysis Heart block. with tetany and seizures Serum phosphate > 4.3 g/24 hours Hyperphosphatemia Usually asymptomatic unless leading to hypocalcemia. tremor.

third-space fluid shift. or a combin ation of these factors can cause ECF volume loss. Causes Excessive fluid loss. relatively equal lo sses of sodium and water. reduced fluid intake. . is the isotonic loss of body fluids. that is. AGE ALERT Infants are at risk for hypovolemia because their bodies need to have a higher proportion of water to total body weight. Hypovolemia.Urine phosphorus < 0.9 g/24 hours Most of the decrease occurs in the first 10 years of life. or ECF v olume deficit. Causes of fluid loss include: hemorrhage excessive perspiration renal failure with polyuria abdominal surgery vomiting or diarrhea nasogastric drainage diabetes mellitus with polyuria or diabetes insipidus fistulas excessive use of laxatives excessive diuretic therapy fever.

venous constriction. thus increasing cardiac output and mean arterial pressure. and other cellular fu nctions. cardiac contractility. and systemic vasc ular resistance. When compensation fails. Cells are deprived of normal nutrients t hat serve as substrates for energy production. Fluid volume deficit decreases capillary hy drostatic pressure and fluid transport.Possible causes of reduced fluid intake include: dysphagia coma environmental conditions preventing fluid intake psychiatric illness. releasing more antidiuretic hormone a nd producing more aldosterone. Decreased renal blood flow triggers the renin angiotensin system to incre ase sodium and water reabsorption. metabolism. The cardiovascular system compensates by incr easing heart rate. Hypo volemia also triggers the thirst response. hypovolemic shock occurs in the following sequence: .5 to 2 L of blood may accumulate in tissues around the fracture) . Fluid shift may be related to: burns (during the initial phase) acute intestinal obstruction acute peritonitis pancreatitis crushing injury pleural effusion hip fracture (1. Pathophysiology Hypovolemia is an isotonic disorder.

MINIMAL FLUID LOSS Intravascular volume loss of 10% to 15% is regarded as minimal. including a decrease in systolic blood pressure > 10 mm Hg or an increase in pulse rate > 20 beats/minute increased capillary refill time > 3 seconds urine output > 30 ml/hour cool. Signs and sympto ms include: slight tachycardia normal supine blood pressure positive postural vital signs.decreased intravascular fluid volume diminished venous return. pale skin on arms and legs . which reduces preload and decreases stroke volume reduced cardiac output decreased mean arterial pressure impaired tissue perfusion decreased oxygen and nutrient delivery to cells multisystem organ failure. ESTIMATING FLUID LOSS The following assessment parameters indicate the severity of fluid loss.

mottled. Signs and symptoms Signs and symptoms depend on the amount of fluid loss. Signs and sympto ms include: marked tachycardia marked hypotension weak or absent peripheral pulses cold.) These may include: .anxiety. SEVERE FLUID LOSS Intravascular volume loss of 40% or more is regarded as severe. or irritability. Signs and sympto ms include: rapid. thready pulse supine hypotension cool truncal skin urine output 10 to 30 ml/hour severe thirst restlessness. or cyanotic skin urine output < 10 ml/hour unconsciousness. MODERATE FLUID LOSS Intravascular volume loss of about 25% is regarded as moderate. confusion. (See Estimating fluid los s.

but the anterior fontanel is sunken in hypovolemic in fants. Between 4 and 18 months. the posterior and anteri or fontanels are sunken when palpated. Complications Possible complications of hypovolemia include: . so they dry rapid ly) diminished skin turgor due to decreased fluid in the dermal layer (making skin l ess pliant) rapid weight loss due to acute loss of body fluid AGE ALERT In hypovolemic infants younger than 4 months.orthostatic hypotension due to increased systemic vascular resistance and decrea sed cardiac output tachycardia induced by the sympathetic nervous system to increase cardiac output and mean arterial pressure thirst to prompt ingestion of fluid (increased ECF osmolality stimulates the thi rst center in the hypothalamus) flattened neck veins due to decreased circulating blood volume sunken eyeballs due to decreased volume of total-body fluid and consequent dehyd ration of connective tissue and aqueous humor dry mucous membranes due to decreased body fluid volume (glands that produce flu ids to moisten and protect the vascular mucous membranes fail. decreased urine output due to decreased renal perfusion from renal vasoconstrict ion prolonged capillary refill time due to increased systemic vascular resistance. the posterior fo ntanel is normally closed.

Treatment Possible treatments for hypovolemia include: oral fluids (may be adequate in mild hypovolemia if the patient is alert enough to swallow and can tolerate it) . hemoglobin. Diagnosis No single diagnostic finding confirms hypovolemia.shock acute renal failure death. If the patient has no underlying renal disorder. typical urinalysis findings inc lude: urine specific gravity > 1. and hematocrit (unless caused by hemorrhage .030 increased urine osmolality urine sodium level < 50 mEq/L. where serum osmolality is low serum electrolyte and arterial blood gas (ABG) analysis may reflect associated c linical problems due to underlying cause of hypovolemia or treatment regimen. but the following test result s are suggestive: increased blood urea nitrogen (BUN) level (early sign) elevated serum creatinine level (late sign) increased serum protein. when loss of blood elements causes subnormal values) rising blood glucose elevated serum osmolality. except in hyponatremia.

Hypervolemia The expansion of ECF volume. may involve the interstitial o r intravascular space.V. diuretics. severity of hypovolemia. It is always secondary to an increase in t otal-body sodium content.V. f luid bolus may be given more quickly if needed) blood or blood products (with hemorrhage) antidiarrheals as needed antiemetics as needed I. and acid base status) fluid resuscitation by rapid I. electrolyte. which causes water retention. choice of parenteral fluid depends on type of fluids lost. and patient's cardiovascular.parenteral fluids to supplement or replace oral therapy (moderate to severe hypo volemia. Hypervolemia develops when excess sodium and water are re tained in about the same proportions. CULTURAL DIVERSITY Indian patients should be questioned about the use of Ayurved ic cleansing practices. and emetics. Usually the body can com pensate and restore fluid balance. such as the use of laxatives. depen ding on patient's condition. 100 to 500 ml of fluid over 15 minutes to 1 hour. wh ich can affect drug absorption and metabolic balance. administration (severe volume depletion. called hypervolemia. Causes Conditions that increase the risk for sodium and water retention include: heart failure cirrhosis of the liver . dopamine (Intropin) or norepinephrine (Levophed) to increase cardiac contra ctility and renal perfusion (if patient remains symptomatic after fluid replacem ent) autotransfusion (for some patients with hypovolemia caused by trauma).

Pathophysiology Increased ECF volume causes the following sequence of events: circulatory overload increased cardiac contractility and mean arterial pressure increased capillary hydrostatic pressure shift of fluid to the interstitial space . or other salts. sodium chloride. Fluid shift to the ECF compartment may follow: remobilization of fluid after burn treatment hypertonic fluids. such as mannitol (Osmitrol) or hypertonic saline solution colloid oncotic fluids such as albumin. Sources of excessive sodium and water intake include: parenteral fluid replacement with normal saline or lactated Ringer's solution blood or plasma replacement dietary intake of water.nephrotic syndrome corticosteroid therapy low dietary protein intake renal failure.

edema. Elevated mean arterial pressure inhibits secretion of antidiuretic hormone and a ldosterone and consequent increased urinary elimination of water and sodium. The se compensatory mechanisms usually restore normal intravascular volume. If hyper volemia is severe or prolonged or the patient has a history of cardiovascular dy sfunction, compensatory mechanisms may fail, and heart failure and pulmonary ede ma may ensue. Signs and symptoms Possible signs and symptoms of hypervolemia include:

rapid breathing due to fewer red blood cells per milliliter of blood (dilution c auses a compensatory increase in respiratory rate to increase oxygenation)

dyspnea (labored breathing) due to increased fluid volume in pleural spaces

crackles (gurgling or bubbling sounds on auscultation) due to elevated hydrostat ic pressure in pulmonary capillaries

rapid, bounding pulse due to increased cardiac contractility (from circulatory o verload)

hypertension (unless heart is failing) due to circulatory overload (causes incre ased mean arterial pressure)

distended neck veins due to increased blood volume and increased preload

moist skin (compensatory to increase water excretion through perspiration)

acute weight gain due to increased volume of total-body fluid from circulatory o verload (best indicator of ECF volume excess)

edema (increased mean arterial pressure leads to increased capillary hydrostatic pressure, causing fluid shift from plasma to interstitial spaces)

S3 gallop (abnormal heart sound due to rapid filling and volume overload of the ventricles during diastole). Complications Possible complications of hypervolemia include:

skin breakdown

acute pulmonary edema with hypoxemia. Diagnosis No single diagnostic test confirms the disorder, but the following findings indi cate hypervolemia:

decreased serum potassium and blood urea nitrogen (BUN) due to hemodilution (inc reased serum potassium and BUN usually indicate renal failure or impaired renal perfusion)

decreased hematocrit due to hemodilution

normal serum sodium (unless associated sodium imbalance is present)

low urine sodium excretion (usually < 10 mEq/day because edematous patient is re taining sodium)

increased hemodynamic values (including pulmonary artery, pulmonary artery wedge , and central venous pressures). Treatment Possible treatments for hypervolemia include:

restricted sodium and water intake

preload reduction agents, such as morphine, furosemide (Lasix), and nitroglyceri n (Nitro-Bid), and afterload reduction agents, such as hydralazine (Apresoline) and captopril (Capoten) for pulmonary edema.

AGE ALERT Carefully monitor I.V. fluid administration rate and patient response, especially in elderly patients or those with impaired cardiac or renal function , who are particularly vulnerable to acute pulmonary edema. For severe hypervolemia or renal failure, the patient may undergo renal replacem ent therapy, including:

hemodialysis or peritoneal dialysis

continuous arteriovenous hemofiltration (allows removal of excess fluid from cri tically ill patients who may not need dialysis; the patient's arterial pressure serves as a natural pump, driving blood through the arterial line)

continuous venovenous hemofiltration (similar to arteriovenous hemofiltration, b ut a mechanical pump is used when mean arterial pressure is < 60 mm Hg). Supportive measures include:

oxygen administration

use of thromboembolic disease support hose to help mobilize edematous fluid

bed rest

treatment of underlying condition that caused or contributed to hypervolemia. PATHOPHYSIOLOGIC MANIFESTATIONS OF ACID BASE IMBALANCE Acid base balance is essential to life. Concepts related to imbalance include acid emia, acidosis, alkalemia, alkalosis, and compensation. Acidemia Acidemia is an arterial pH of less than 7.35, which reflects a relative excess o f acid in the blood. The hydrogen ion content in ECF increases, and the hydrogen ions move to the ICF. To keep the intracellular fluid electrically neutral, an equal amount of potassium leaves the cell, creating a relative hyperkalemia. Acidosis Acidosis is a systemic increase in hydrogen ion concentration. If the lungs fail to eliminate CO2 or if volatile (carbonic acid) or nonvolatile (lactic) acid pr oducts of metabolism accumulate, hydrogen ion concentration rises. Acidosis can also occur if persistent diarrhea causes loss of basic bicarbonate anions or the kidneys fail to reabsorb bicarbonate or secrete hydrogen ions. Alkalemia Alkalemia is arterial blood pH > 7.45, which reflects a relative excess of base in the blood. In alkalemia, an excess of hydrogen ions in the ICF forces them in to the ECF. To keep the ICF electrically neutral, potassium moves from the ECF t o the ICF, creating a relative hypokalemia. Alkalosis Alkalosis is a bodywide decrease in hydrogen ion concentration. An excessive los s of CO2 during hyperventilation, loss of nonvolatile acids during vomiting, or excessive ingestion of base may decrease hydrogen ion concentration. Compensation The lungs and kidneys, along with a number of chemical buffer systems in the int racellular and extracellular compartments, work together to maintain plasma pH i n the range of 7.35 to 7.45. For a description of acid base values and compensator y mechanisms, see Interpreting ABGs. Buffer systems A buffer system consists of a weak acid (that doesn't readily release free hydro gen ions) and a corresponding base, such as sodium bicarbonate. These buffers re sist or minimize a change in pH when an acid or base is added to the buffered so lution. Buffers work in seconds. The four major buffers or buffer systems are:

carbonic acid bicarbonate system (the most important, works in lungs)

hemoglobin oxyhemoglobin system (works in red blood cells) hemoglobin binds free H +, blood flows through lungs, H+ combines with CO2.

other protein buffers (in ECF and ICF)

phosphate system (primarily in ICF). When primary disease processes alter either the acid or base component of the ra tio, the lungs or kidneys (whichever is not affected by the disease process) act to restore the ratio and normalize pH. Because the body's mechanisms that regul ate pH occur in stepwise fashion over time, the body tolerates gradual changes i n pH better than abrupt ones. INTERPRETING ABGS This chart compares abnormal arterial blood gas (ABG) values and their significa nce for patient care.

DISORDER pH PaCO2 (mm Hg) HCO3 (mEq/L) COMPENSATION Normal 7.35 to 7.45 35 to 45 22 to 26 €

Respiratory acidosis < 7.35 > 45

Acute: may be normal

Chronic: > 26

Renal: increased secretion and excretion of acid; compensation takes 24 hours to


Respiratory: rate increases to expel CO2 Respiratory alkalosis > 7.45 < 35

Acute: normal

Chronic: < 22

Renal: decreased H+ secretion and active secretion of HCO3 into urine Metabolic acidosis < 7.35 < 35 < 22

Respiratory: lungs expel more CO2 by increasing rate and depth of respirations Metabolic alkalosis > 7.45 > 45 > 26

Respiratory: hypoventilation is immediate but limited because of ensuing hypoxem ia

Renal: more effective but slow to excrete less acid and more base Compensation by the kidneys If a respiratory disorder causes acidosis or alkalosis, the kidneys respond by a ltering their handling of hydrogen and bicarbonate ions to return the pH to norm al. Renal compensation begins hours to days after a respiratory alteration in pH . Despite this delay, renal compensation is powerful.

Acidemia: the kidneys excrete excess hydrogen ions, which may combine with phosp hate or ammonia to form titratable acids in the urine. The net effect is to rais e the concentration of bicarbonate ions in the ECF and so restore acid base balanc e.

Alkalemia: the kidneys excrete excess bicarbonate ions, usually with sodium ions . The net effect is to reduce the concentration of bicarbonate ions in the ECF a nd restore acid base balance. Compensation by the lungs If acidosis or alkalosis results from a metabolic or renal disorder, the respira tory system regulates the respiratory rate to return the pH to normal. The parti al pressure of CO2 in arterial blood (PaCO2) reflects CO2 levels proportionate t o blood pH. As the concentration of the gas increases, so does its partial press ure. Within minutes after the slightest change in PaCO2, central chemoreceptors in the medulla that regulate the rate and depth of ventilation detect the change .

Acidemia increases respiratory rate and depth to eliminate CO2.

Alkalemia decreases respiratory rate and depth to retain CO2. DISORDERS OF ACID BASE BALANCE Acid base disturbances can cause respiratory acidosis or alkalosis or metabolic ac idosis or alkalosis. Respiratory acidosis Respiratory acidosis is an acid base disturbance characterized by reduced alveolar ventilation. The patient's pulmonary system can't clear enough CO2 from the bod y. This leads to hypercapnia (PaCO2 > 45 mm Hg) and acidosis (pH < 7.35). Respir atory acidosis can be acute (due to a sudden failure in ventilation) or chronic (in long-term pulmonary disease). Any compromise in the essential components of breathing ventilation, perfusion, and diffusion may cause respiratory acidosis. Prognosis depends on the severity of the underlying disturbance as well as the p atient's general clinical condition. The prognosis is least optimistic for a pat ient with a debilitating disorder. Causes Factors leading to respiratory acidosis include:

drugs (narcotics, general anesthetics, hypnotics, alcohol, and sedatives decreas e the sensitivity of the respiratory center)

Central nervous system (CNS) trauma (injury to the medulla may impair ventilator y drive)

cardiac arrest (acute)

sleep apnea

chronic metabolic alkalosis as respiratory compensatory mechanisms try to normal ize pH

ventilation y disorders -expiratory pnia due to

therapy (use of high-flow oxygen in patients with chronic respirator suppresses the patient's hypoxic drive to breathe; high positive end pressure in the presence of reduced cardiac output may cause hyperca large increases in alveolar dead space)

neuromuscular diseases, such as myasthenia gravis, Guillain-Barré syndrome, and po liomyelitis (respiratory muscles cannot respond properly to respiratory drive)

airway obstruction or parenchymal lung disease (interferes with alveolar ventila tion)

chronic obstructive pulmonary disease (COPD) or asthma

severe adult respiratory distress syndrome (reduced pulmonary blood flow and poo r exchange of CO2 and oxygen between the lungs and blood)

chronic bronchitis

large pneumothorax

extensive pneumonia

pulmonary edema. Pathophysiology When pulmonary ventilation decreases, PaCO2 is increased, and the CO2 level rise s in all tissues and fluids, including the medulla and cerebrospinal fluid. Reta ined CO2 combines with water (H2O) to form carbonic acid (H2CO3). The carbonic a cid dissociates to release free hydrogen (H+) and bicarbonate (HCO3 ) ions. Increa sed PaCO2 and free hydrogen ions stimulate the medulla to increase respiratory d rive and expel CO2. As pH falls, 2,3-diphosphoglycerate (2,3-DPG) accumulates in red blood cells, wh ere it alters hemoglobin so it releases oxygen. This reduced hemoglobin, which i s strongly alkaline, picks up hydrogen ions and CO2 and removes them from the se rum. As respiratory mechanisms fail, rising PaCO2 stimulates the kidneys to retain bi carbonate and sodium ions and excrete hydrogen ions As a result, more sodium bic arbonate (NaHCO3) is available to buffer free hydrogen ions. Some hydrogen is ex creted in the form of ammonium ion (NH4+), neutralizing ammonia, which is an imp ortant CNS toxin. As the hydrogen ion concentration overwhelms compensatory mechanisms, hydrogen i ons move into the cells and potassium ions move out. Without enough oxygen, anae robic metabolism produces lactic acid. Electrolyte imbalances and acidosis criti cally depress neurologic and cardiac functions.

Signs and symptoms Clinical features vary according to the severity and duration of respiratory aci dosis, the underlying disease, and the presence of hypoxemia. Carbon dioxide and hydrogen ions dilate cerebral blood vessels and increase blood flow to the brai n, causing cerebral edema and depressing CNS activity. Possible signs and symptoms include:





fine or flapping tremor (asterixis)



dyspnea and tachypnea


depressed reflexes

hypoxemia, unless the patient is receiving oxygen. Respiratory acidosis may also cause cardiovascular abnormalities, including:



atrial and ventricular arrhythmias

hypotension with vasodilation (bounding pulses and warm periphery, in severe aci dosis). Complications Possible complications include:

profound CNS and cardiovascular deterioration due to dangerously low blood pH (< 7.15)

myocardial depression (leading to shock and cardiac arrest)

elevated PaCO2 despite optimal treatment (in chronic lung disease). Diagnosis The following tests help diagnose respiratory acidosis:

arterial blood gas (ABG) analysis, showing PaCO2 > 45 mm Hg; pH < 7.35 to 7.45; and normal HCO3 in the acute stage and elevated HCO3 in the chronic stage (confirm s the diagnosis)

chest X-ray (often shows such causes as heart failure, pneumonia, COPD, and pneu mothorax)

potassium > 5 mEq/L

low serum chloride

acidic urine pH (as the kidneys excrete hydrogen ions to return blood pH to norm al)

drug screening (may confirm suspected drug overdose). Treatment Effective treatment of respiratory acidosis requires correction of the underlyin g source of alveolar hypoventilation. Treatment of pulmonary causes of respirato ry acidosis includes:

removal of a foreign body from the airway

artificial airway through endotracheal intubation or tracheotomy and mechanical ventilation (if the patient can't breathe spontaneously)

increasing the partial pressure of arterial oxygen (PaO2) to at least 60 mm Hg a nd pH to > 7.2 to avoid cardiac arrhythmias

aerosolized or I.V. bronchodilators to open constricted airways

antibiotics to treat pneumonia

chest tubes to correct pneumothorax

positive end-expiratory pressure to prevent alveolar collapse

thrombolytic or anticoagulant therapy for massive pulmonary emboli

bronchoscopy to remove excessive retained secretions. Treatment for patients with COPD includes:


oxygen at low flow rates (more oxygen than the person's normal removes the hypox ic drive, further reducing alveolar ventilation)


gradual reduction in PaCO2 to baseline to provide sufficient chloride and potass ium ions to enhance renal excretion of bicarbonate (in chronic respiratory acido sis). Other treatments include:

drug therapy for such conditions as myasthenia gravis

dialysis or charcoal to remove toxic drugs

correction of metabolic alkalosis

careful administration of I.V. sodium bicarbonate. Respiratory alkalosis Respiratory alkalosis is an acid base disturbance characterized by a PaCO2 < 35 mm Hg and blood pH > 7.45; alveolar hyperventilation is the cause. Hypocapnia (bel ow normal PaCO2) occurs when the lungs eliminate more CO2 than the cells produce . Respiratory alkalosis is the most common acid base disturbance in critically ill p atients and, when severe, has a poor prognosis. Causes Conditions that may cause or contribute to respiratory alkalosis include:

acute hypoxemia, pneumonia, interstitial lung disease, pulmonary vascular diseas e, and acute asthma (may stimulate the respiratory control center, causing the p atient to breathe faster and deeper)

anxiety (may cause deep rapid breathing)

hypermetabolic states such as fever and sepsis (especially gram-negative sepsis)

excessive mechanical ventilation

injury to the CNS respiratory control center

salicylate (aspirin) intoxication

salicylate toxicity

metabolic acidosis

hepatic failure

pregnancy (progesterone increases ventilation and reduces PaCO2 by as much as 5 to 10 mm Hg). Pathophysiology When pulmonary ventilation increases more than needed to maintain normal CO2 lev els, excessive amounts of CO2 are exhaled. The consequent hypocapnia leads to a chemical reduction of carbonic acid, excretion of hydrogen and bicarbonate ions, and a rising pH. In defense against the increasing serum pH, the hydrogen potassium buffer system p ulls hydrogen ions out of the cells and into the blood in exchange for potassium ions. The hydrogen ions entering the blood combine with available bicarbonate i ons to form carbonic acid, and the pH falls. Hypocapnia stimulates the carotid and aortic bodies as well as the medulla, incr easing the heart rate (which hypokalemia can further aggravate) but not the bloo d pressure. At the same time, hypocapnia causes cerebral vasoconstriction and de creased cerebral blood flow. It also overexcites the medulla, pons, and other pa rts of the autonomic nervous system. When hypocapnia lasts more than 6 hours, th e kidneys secrete more bicarbonate and less hydrogen. Full renal adaptation to r espiratory alkalosis requires normal volume status and renal function, and it ma y take several days. Continued low PaCO2 and the vasoconstriction it causes increases cerebral and pe ripheral hypoxia. Severe alkalosis inhibits calcium ionization; as calcium ions become unavailable, nerves and muscles become progressively more excitable. Even tually, alkalosis overwhelms the CNS and heart. Signs and symptoms Possible signs and symptoms of respiratory alkalosis include:

deep, rapid breathing (possibly more than 40 breaths/minute and much like the Ku ssmaul's respirations that characterize diabetic acidosis) usually causing CNS a nd neuromuscular disturbances (cardinal sign of respiratory alkalosis)

light-headedness or dizziness due to decreased cerebral blood flow


circumoral and peripheral paresthesias

carpopedal spasms, twitching (possibly progressing to tetany), and muscle weakne ss. Complications Possible complications of severe respiratory alkalosis include:

cardiac arrhythmias that may not respond to conventional treatment as the hemogl obin oxygen buffer system becomes overwhelmed

hypocalcemic tetany, seizures

periods of apnea if pH remains high and PaCO2 remains low. Diagnosis The following test results indicate respiratory alkalosis:

arterial blood gas (ABG) analysis showing PaCO2 <35 mm Hg; elevated pH in propor tion to decrease in PaCO2 in the acute stage but decreasing toward normal in the chronic stage; normal HCO3 in acute stage but less than normal in the chronic st age (confirms respiratory alkalosis, rules out respiratory compensation for meta bolic acidosis)

serum electrolyte studies (detect metabolic disorders causing compensatory respi ratory alkalosis)

ECG findings (may indicate cardiac arrhythmias)

low chloride (in severe respiratory alkalosis)

toxicology screening (for salicylate poisoning)

basic urine pH as kidneys excrete HCO3 to raise blood pH. Treatment Possible treatments to correct the underlying condition include:

removal of ingested toxins

treatment of fever or sepsis

oxygen for acute hypoxemia

treatment of CNS disease

having patient breathe into a paper bag to increase CO2 and help relieve anxiety (for hyperventilation caused by severe anxiety)

adjustment of tidal volume and minute ventilation in patients on mechanical vent ilation to prevent hyperventilation (by monitoring ABG analysis results). Metabolic acidosis Metabolic acidosis is an acid base disorder characterized by excess acid and defic ient HCO3 caused by an underlying nonrespiratory disorder. A primary decrease in plasma HCO3 causes pH to fall. It can occur with increased production of a nonvol atile acid (such as lactic acid), decreased renal clearance of a nonvolatile aci d (as in renal failure), or loss of HCO3 (as in chronic diarrhea). Symptoms resul t from action of compensatory mechanisms in the lungs, kidneys, and cells.

AGE ALERT Metabolic acidosis is more prevalent among children, who are vulnerabl e to acid base imbalance because their metabolic rates are rapid and ratios of wat er to total-body weight are low. Severe or untreated metabolic acidosis can be fatal. The prognosis improves with prompt treatment of the underlying cause and rapid reversal of the acidotic sta te. Causes Metabolic acidosis usually results from excessive fat metabolism in the absence of usable carbohydrates (produces more ketoacids than the metabolic process can handle). Possible causes are:

excessive acid accumulation

deficient HCO3 stores

decreased acid excretion by the kidneys

a combination of these factors. Conditions that may cause or contribute to metabolic acidosis include:

diabetic ketoacidosis

chronic alcoholism

malnutrition or a low-carbohydrate, high-fat diet

anaerobic carbohydrate metabolism (decreased tissue oxygenation or perfusion as in cardiac pump failure after myocardial infarction, pulmonary or hepatic disease, shock, or anemia forces a shift from aerobic to anaerobic metabolism, causing a

corresponding increase in lactic acid level)

underexcretion of metabolized acids or inability to conserve base due to renal i nsufficiency and failure (renal acidosis)

diarrhea, intestinal malabsorption, or loss of sodium bicarbonate from the intes tines, causing bicarbonate buffer system to shift to the acidic side (e.g., uret eroenterostomy and Crohn's disease can also induce metabolic acidosis)

salicylate intoxication (overuse of aspirin), exogenous poisoning, or less frequ ently, Addison's disease (increased excretion of sodium and chloride and retenti on of potassium)

inhibited secretion of acid due to hypoaldosteronism or the use of potassium-spa ring diuretics. Pathophysiology As acid (H+) starts to accumulate in the body, chemical buffers (plasma HCO3 and proteins) in the cells and ECF bind the excess hydrogen ions. Excess hydrogen ions that the buffers can't bind decrease blood pH and stimulate chemoreceptors in the medulla to increase respiration. The consequent fall of P aCO2 frees hydrogen ions to bind with HCO3 . Respiratory compensation occurs in mi nutes but isn't sufficient to correct the acidosis. Healthy kidneys try to compensate by secreting excess hydrogen ions into the ren al tubules. These ions are buffered by either phosphate or ammonia and excreted into the urine in the form of weak acid. For each hydrogen ion secreted into the renal tubules, the tubules reabsorb and return to the blood one Na+ and one HCO 3 . The excess hydrogen ions in ECF passively diffuse into cells. To maintain the ba lance of charge across the membranes, the cells release potassium ions. Excess h ydrogen ions change the normal balance of potassium, sodium, and calcium ions an d thereby impair neural excitability. Signs and symptoms In mild acidosis, symptoms of the underlying disease may hide the direct clinica l evidence. Signs and symptoms include:

headache and lethargy progressing to drowsiness, CNS depression, Kussmaul's resp irations (as the lungs attempt to compensate by blowing off CO2), hypotension, s tupor, and (if condition is severe and untreated) coma and death

associated GI distress leading to anorexia, nausea, vomiting, diarrhea, and poss ibly dehydration

warm, flushed skin due to a pH-sensitive decrease in vascular response to sympat hetic stimuli

fruity-smelling breath from fat catabolism and excretion of accumulated acetone through the lungs due to underlying diabetes mellitus. Complications Metabolic acidosis depresses the CNS and, if untreated, may lead to:

weakness, flaccid paralysis


ventricular arrhythmias, possibly cardiac arrest. In the metabolic acidosis of chronic renal failure, HCO3 ffer hydrogen ions; the results include:

is drawn from bone to bu

growth retardation in children

bone disorders such as renal osteodystrophy. Diagnosis The following test results confirm the diagnosis of metabolic acidosis:

arterial pH < 7.35 ( as low as 7.10 in severe acidosis); PaCO2 normal or < 34 mm Hg as respiratory compensatory mechanisms take hold; HCO3 may be < 22 mEq/L). The following test results support the diagnosis of metabolic acidosis:

urine pH < 4.5 in the absence of renal disease (as the kidneys excrete acid to r aise blood pH)

serum potassium > 5.5 mEq/L from chemical buffering

glucose > 150 mg/dl

serum ketone bodies in diabetes

elevated plasma lactic acid in lactic acidosis

anion gap > 14 mEq/L in high-anion gap metabolic acidosis, lactic acidosis, keto

acidosis, aspirin overdose, alcohol poisoning, renal failure, or other condition s characterized by accumulation of organic acids, sulfates or phosphates

anion gap 12 mEq/L or less in normal anion gap metabolic acidosis from HCO3 loss, GI or renal loss, increased acid load (hyperalimentation fluids), rapid I.V. sa line administration, or other conditions characterized by loss of bicarbonate. Treatment Treatment aims to correct the acidosis as quickly as possible by addressing both the symptoms and the underlying cause. Measures may include:

sodium bicarbonate I.V. for severe high anion gap to neutralize blood acidity in patients with pH < 7.20 and HCO3 loss; monitor plasma electrolytes, especially p otassium, during sodium bicarbonate therapy (potassium level may fall as pH rise s)

I.V. lactated Ringer's solution to correct normal anion gap metabolic acidosis a nd ECF volume deficit

evaluation and correction of electrolyte imbalances

correction of the underlying cause (e.g., in diabetic ketoacidosis, continuous l ow-dose I.V. insulin infusion)

mechanical ventilation to maintain respiratory compensation, if needed

antibiotic therapy to treat infection

dialysis for patients with renal failure or certain drug toxicities

antidiarrheal agents for diarrhea-induced HCO3 loss

monitor for secondary changes due to hypovolemia, such as falling blood pressure (in diabetic acidosis)

position patient to prevent aspiration (metabolic acidosis commonly causes vomit ing)

seizure precautions. Metabolic alkalosis Metabolic alkalosis occurs when low levels of acid or high HCO3 cause metabolic, respiratory, and renal responses, producing characteristic symptoms (most notabl y, hypoventilation). This condition is always secondary to an underlying cause. With early diagnosis and prompt treatment, prognosis is good, but untreated meta bolic alkalosis may lead to coma and death. Causes Metabolic alkalosis results from loss of acid, retention of base, or renal mecha nisms associated with low serum levels of potassium and chloride. Causes of critical acid loss include:

chronic vomiting

nasogastric tube drainage or lavage without adequate electrolyte replacement


use of steroids and certain diuretics (furosemide [Lasix], thiazides, and ethacr ynic acid [Edecrin])

CULTURAL DIVERSITY Various Chinese herbal cures contain benzodiazepines, steroid s, and nonsteroidal anti-inflammatory drugs that may produce unexpected adverse effects, such as muscle weakness and cushingoid features.

massive blood transfusions

Cushing's disease, primary hyperaldosteronism, and Bartter's syndrome (lead to s odium and chloride retention and urinary loss of potassium and hydrogen). Excessive HCO3 retention causing chronic hypercapnia can result from:

excessive intake of bicarbonate of soda or other antacids (usually for treatment of gastritis or peptic ulcer)

excessive intake of absorbable alkali (as in milk alkali syndrome, often seen in patients with peptic ulcers)

excessive amounts of I.V. fluids, high concentrations of bicarbonate or lactate

respiratory insufficiency. Alterations in extracellular electrolyte levels that can cause metabolic alkalos is include:

low chloride (as chloride diffuses out of the cell, hydrogen diffuses into the c ell)

low plasma potassium causing increased hydrogen ion excretion by the kidneys. Pathophysiology Chemical buffers in the ECF and ICF bind HCO3 that accumulates in the body. Exces s unbound HCO3 raises blood pH, which depresses chemoreceptors in the medulla, in hibiting respiration and raising PaCO2. Carbon dioxide combines with water to fo rm carbonic acid. Low oxygen levels limit respiratory compensation. When the blood HCO3 rises to 28 mEq/L or more, the amount filtered by the renal g lomeruli exceeds the reabsorptive capacity of the renal tubules. Excess HCO3 is e xcreted in the urine, and hydrogen ions are retained. To maintain electrochemica l balance, sodium ions and water are excreted with the bicarbonate ions. When hydrogen ion levels in ECF are low, hydrogen ions diffuse passively out of the cells and, to maintain the balance of charge across the cell membrane, extra cellular potassium ions move into the cells. As intracellular hydrogen ion level s fall, calcium ionization decreases, and nerve cells become more permeable to s odium ions. As sodium ions move into the cells, they trigger neural impulses, fi rst in the peripheral nervous system and then in the CNS. Signs and symptoms Clinical features of metabolic alkalosis result from the body's attempt to corre ct the acid-base imbalance, primarily through hypoventilation. Signs and symptom s include:

irritability, picking at bedclothes (carphology), twitching, and confusion due t o decreased cerebral perfusion

nausea, vomiting, and diarrhea (which aggravate alkalosis)

cardiovascular abnormalities due to hypokalemia

respiratory disturbances (such as cyanosis and apnea) and slow, shallow respirat ions

diminished peripheral blood flow during repeated blood pressure checks may provo ke carpopedal spasm in the hand (Trousseau's sign, a possible sign of impending tetany). Complications Uncorrected metabolic alkalosis may progress to:

V. 6 CARDIOVASCULAR SYSTEM . merging with a P wave. so potassium may be given before drug). and chloride (< 98 mEq/L) urine pH about 7 alkaline urine after the renal compensatory mechanism begins to excrete bicarbon ate ECG may show low T wave. (rarely) or HCl to restore ECF hydrogen a nd chloride levels. usually sufficient to replace losses from gastric drainage discontinuation of diuretics and supplementary KCl (metabolic alkalosis from pot ent diuretic therapy) oral or I.45 and HCO3 > 29 mEq/L (confirm diagnosis) PaCO2 > 45 mm Hg (indicates attempts at respiratory compensation) low potassium (< 3. Possible treatments include: cautious use of ammonium chloride I. and atrial or sinus tachycardia. Diagnosis Findings indicating metabolic alkalosis include: blood pH > 7. calcium (< 8.V.seizures coma. acetazolamide (Diamox. KCl and normal saline solution (except in heart failure).9 mg/dl).5 mEq/L). Treatment The goal of treatment is to correct the underlying cause of metabolic alkalosis. enhances renal bicarbonate excretion) to cor rect metabolic alkalosis without rapid volume expansion (acetazolamide also enha nces potassium excretion.

Handbook of Pathophysiology 6 CARDIOVASCULAR SYSTEM Pathophysiologic manifestations € Aneurysm € Cardiac shunts € Embolus € Release of cardiac enzymes and proteins € Stenosis € Thrombus € Valve incompetence Disorders € Atrial septal defect € Cardiac arrhythmias € Cardiac tamponade € Cardiomyopathy € Coarctation of the aorta € Coronary artery disease € Heart failure € Hypertension € Myocardial infarction € Myocarditis € Patent ductus arteriosus € Pericarditis € Raynaud's disease € Rheumatic fever and rheumatic heart disease € Shock € Tetralogy of Fallot € Transposition of the great arteries € Valvular heart disease € .

) A fusiform aneurysm develops when the arterial wall weakens around its circumfer ence. and infectio ns such as syphilis may lead to aneurysm formation. veins. The cardiovascular system. This system brings life-supporting oxygen an d nutrients to cells. trauma. blood picks up oxygen and liberates the waste product carbon dioxide. Aneurysm An aneurysm is a localized outpouching or dilation of a weakened arterial wall. thrombus. often called the circulatory system. The aorta is the major art ery arching out of the left ventricle. and v alve incompetence. veins. The heart. creating a pu lsatile hematoma. In the veins. and lymphatics form the cardiovascular network that serves the body's transport system. removes metabolic waste products. and skin for excretion. or the loss of elastin and collagen in the vessel wall. In system ic circulation (which includes coronary circulation). embolus. PATHOPHYSIOLOGIC MANIFESTATIONS Pathophysiologic manifestations of cardiovascular disease may stem from aneurysm .Varicose veins € Ventricular septal defect The cardiovascular system begins its activity when the fetus is barely 4 weeks o ld and is the last system to cease activity at the end of life. . arteries. which return it to the heart. which propels blood through the syst em by continuous rhythmic contractions. (See Types of aortic aneurysms. stenosis. may be divided i nto two branches: pulmonary and systemic circulations. This body system is so vital that its activity helps define the presence of life. Circulation requires normal heart function. Several types of aneurysms can occur: A saccular aneurysm occurs when increased pressure in the artery pushes out a po uch on one side of the artery. its segments and sub-branches ultimately divide into minute. This weakness can be the result of either atherosclerotic plaque formation that erodes the vessel wall. creating a bulge. causing them to separate and creating a false lumen. cardiac shunts. The sturdy. A false aneurysm develops when there is a break in all layers of the arterial wa ll and blood leaks out but is contained by surrounding structures. Capillaries pass t he blood to the veins. In pulmonary circulation. and capillaries. Blood circulates through three types of vessels: arteries. release of cardiac enzymes. A dissecting aneurysm occurs when blood is forced between the layers of the arte rial wall. Congenital abnormalities in the media of the arterial wall. and carries hormones fro m one part of the body to another. A ruptured aneurysm may caus e massive hemorrhage and death. pliable walls of the arte ries adjust to the volume of blood leaving the heart. creating a spindle-shaped aneurysm. thin-walled (one cell thick) capillaries. blood carries oxygen and n utrients to all active cells and transports waste products to the kidneys. liver . valves preven t blood backflow.

or from the aorta to the pulmon ary circulation through a patent ductus arteriosus. The released enzymes include creatine kinase. amniotic fluid. and aspartate aminotransferase. Although most emboli are blood clots from a thrombu s. or a foreign substance. Because the blood in the lef t side of the heart is rich in oxygen. leading to hypertrophy of the pulmonary vessels. such as from deep vein thrombos is. The increased amounts of blood circulated from the left side of the heart to the ri ght side can result in right-sided heart failure. Blood flo ws through a shunt from an area of high pressure to an area of low pressure or f rom an area of high resistance to an area of low resistance. or from the pulmonary art ery directly into the systemic circulation through a patent ductus arteriosus. heart failure. a left-to-right shunt delivers oxygenated blood back to the right side of the heart or to the lungs. shunts between the right and left sides of the heart and b etween the aorta and pulmonary artery are a normal part of fetal circulation. tumor cells. Arterial emboli may lodge in organs. the tissues and organs perfused by that bl ood vessel may become ischemic. a left -to-right shunt that occurs as a result of a congenital heart defect is called a n acyanotic defect. through the bloodstream. such as the brain . or die. an air bubble. Consequently. valvular heart disease. blood flows from the left side of the heart to the rig ht side through an atrial or ventricular defect. Embolus An embolus is a substance that circulates from one location in the body to anoth er. Fo llowing birth. Eventually. Common manifestations of a right-to-left shunt related to poor tissue and organ perfusion include fatigue. troponin I. function abnormally. Emboli that originate in the venous circulation. and myoglobin. In a left-to-right shunt. B ecause blood returning to the right side of the heart and the pulmonary artery i s low in oxygen. Right-to-left shunts A right-to-left shunt occurs when blood flows from the right side of the heart t o the left side such as occurs in tetralogy of Fallot. Before birth. left-sided heart f ailure may also occur. An occluded vein ma . kidneys. The release follows a characteristic ri sing and falling of values. the integrity of the cell membrane is impaired . pulmonary blood flow increases as blood is continually recirculated to the lungs. and intracellular contents including cardiac enzymes and proteins are released and can be measured in the bloodstream. causing ischemia or infarction. Most em boli in the arterial system originate from the left side of the heart from condi tions such as arrhythmias. they may also consist of pieces of tissue. the proteins released include t roponin T. (See Release of cardiac enzymes and protei ns. Left-to-right shunts In a left-to-right shunt. a right-to-left shunt adds deoxygenated blood to the systemic c irculation. and clubbing of the fingers. bacteria. the mixing of pulmonary and systemic blood or the moveme nt of blood between the left and right sides of the heart is abnormal. or endocarditis.) Stenosis Stenosis is the narrowing of any tubular structure such as a blood vessel or hea rt valve. lactat e dehydrogenase. fat . increased respiratory rate. Release of cardiac enzymes and proteins When the heart muscle is damaged. myocardial infarction. causing pulmonary infarction and even death. travel to the right side of the heart to the pulmonary circulation and event ually lodge in a capillary. or extremities.TYPES OF AORTIC ANEURYSMS Cardiac shunts A cardiac shunt provides communication between the pulmonary and systemic circul ations. When an artery is stenosed. however. Congenital defects that involve rightto-left shunts are therefore called cyanotic defects. causing hypoxia and cyanosis.

blood flows backward and pools above. also called insufficiency or regurgitation. occurs when valv e leaflets do not completely close. After acute myocardial infarc tion (MI). and red and white b lood cells. blood flow through that valve is reduced. and increased coagulability. chronic venous insufficiency. Eventually. When stenosis occurs in a valve on the left side of the heart. Thrombus A thrombus is a blood clot. Valve incompetence Valve incompetence. veins. an opening between the left and right atria allows the blood to flow from left to right. Consequentl y. In the veins. incompetent valves allow blood to flow in both directions through the valve. such as the arteries . DISORDERS Atrial septal defect In this acyanotic congenital heart defect. The consequences of thrombus formation include occlusion of the blood vessel or the formation of an embolus (if a portion of a thrombus breaks loose and travels through the circulatory system until it lodges in a smaller vessel). fibrin. thus increasing the risk of heart failure. right-sided heart failure may occur. the endothelial lining attracts platelets and other inflammat ory mediators. RELEASE OF CARDIAC ENZYMES AND PROTEINS catalyt Because they're released by damaged tissue. Pressure in that chamber rises in order to pump against the resistance of the stenosed valve. Blood clots may form as blood flow becomes sluggish. the involved heart chambers dilate to accommodate the increased volume. that forms anywhere within the vascular system. Al though incompetence may occur in any of the valves of the heart. promote thrombus formation: endothel ial injury. the veins become di stended. increasing the volume of blood that must be pumped (as well as the he art's workload) and resulting in hypertrophy. serum enzymes and isoenzymes ic proteins that vary in concentration in specific organs can help identify the compromised organ and assess the extent of damage. which may result in varicose veins. As pu lmonary vascular resistance rises. When a blood vesse l wall is injured. Conditions that increase the coagulability of blood also promote clot formation. and v enous ulcers. Sluggish or abnormal blood fl ow also promotes thrombus formation by allowing platelets and clotting factors t o accumulate and adhere to the blood vessel walls. A heart with diseased coronary arteries may not be able to sufficiently increase oxygen supply to meet the increased demand. Hypertrophy and an in crease in workload raise the oxygen demands of the heart. which may stimulate clot formation. it's more commo n in the mitral and aortic valves. When a heart valve is stenosed. cardiac enzymes and proteins rise and fall in a characteristic patter n. heart chambers. causin g blood to accumulate in the chamber behind the valve. leading to systemic venous congestion. toward the heart. Stenosis in a valve on the right side of the heart causes an increase in pressures on th e right side of the heart. the heart has to work harder. When valve leaflets close improperly. resulting in ineffective pum ping of the heart. As blood volume in the heart incre ases. The three types of atrial septal defects (ASDs) are: . or heart valves. Incompetence may affect valves of the veins or the heart. valves keep the blood flowing in one direction. resulting in hypertrophy. sluggish blood flow. as shown in the graph below. caus ing that valve to weaken and become incompetent.y result in venous congestion and chronic venous insufficiency. In the heart. Three conditions. known as Virchow's triad. consisting of platelets. the increased pre ssure leads to greater pulmonary venous pressure and pulmonary congestion.

Ostium primum defects commonly occur in patients with Down syndrome. and is almost always associat ed with abnormal drainage of pulmonary veins into the right atrium an ostium primum defect that occurs in the inferior portion of the septum primum and is usually associated with atrioventricular valve abnormalities (cleft mitr al valve) and conduction defects. Causes The cause of an ASD is unknown. The prognosis is excellent in asymptomatic patients and in those with uncomplica ted surgical repair. ASD accounts for about 10% of congenital heart defects and appears almost twice as often in females as in males. Signs and symptoms The following are signs and symptoms of an ASD: fatigue after exertion due to decreased cardiac output from the left ventricle early to midsystolic murmur at the second or third left intercostal space. occasionally. and pulmonary arteries. rig ht ventricle. untreat ed defects. Th is shunt results in right heart volume overload. cause d by extra blood passing through the pulmonic valve low-pitched diastolic murmur at the lower left sternal border. delayed development o f symptoms and complications makes it one of the most common congenital heart de fects diagnosed in adults. more pronounced o n inspiration. the most common type. increased pulmonary vascular resistance and r ight ventricular hypertrophy follow. which results in unoxyge nated blood entering the systemic circulation. causing cyanosis. close to the vena cava a sinus venosus defect that occurs in the superior-posterior portion of the atri al septum. resulting from increased tricuspid valve flow in patients with la rge shunts fixed. but poor in patients with cyanosis caused by large. resulting f rom an increased volume of blood . irreversible pulmonary arte ry hypertension causes reversal of the shunt direction. affecting the right atrium. If pulmo nary artery hypertension develops. widely split S2 due to delayed closure of the pulmonic valve. Eventually. blood shunts from the left atrium to the right atrium because the lef t atrial pressure is normally slightly higher than the right atrial pressure. sometimes extending into the vena cava. In some adults. the right atrium enlarges. which occurs in the region of t he fossa ovalis and. Pathophysiology In an ASD. and the right ventricle dilates to accommodate the increased blood volume.an ostium secundum defect. with a strong familial tendency. extends inferiorly. Although an AS D is usually a benign defect during infancy and childhood.

Echocardiography measures right ventricular enlargement. Cyanosis that worsens with crying is most likely associated with cardiac cau ses because crying increases pulmonary resistance to blood flow. in ostium primum defect. p rolonged PR interval. varying degrees of right bundle branch block. AGE ALERT An infant may be cyanotic because he has a cardiac or pulmonary disord er.systolic click or late systolic murmur at the apex. resulting in an increased right-to-left shunt. Cyanosis that improves with crying is most likel y due to pulmonary causes as deep breathing improves tidal volume. Diagnosis The following tests help diagnose atrial septal defect: Chest X-rays show an enlarged right atrium and right ventricle. and shows volume overload in the right side of the heart. It may reveal right ve ntricular and pulmonary artery dilation. resulting from mitral valve prolapse in older children with ASD clubbing and cyanosis. Electrocardiography results may be normal but often show right axis deviation. right ventri cular hypertrophy. . and increased pulmonary vascular markings. may locate the defect. a prominent pulm onary artery. if right-to-left shunt develops. atrial fibrillation (particularly in severe cases after age 3 0) and. Complications Complications of an ASD may include: physical underdevelopment respiratory infections heart failure atrial arrhythmias mitral valve prolapse. left axis deviation.

Dye injection shows th e defect's size and location. which requires immediate resuscitation. asymptomat ic. Cardiac arrhythmias In arrhythmias.Cardiac catheterization may confirm an ASD. from those that are mild. using a patch of pericardium or pros thetic material. Their effect on cardia c output and blood pressure. abnormal electrical conduction or automaticity changes heart rat e and rhythm. indicating a left-to-right shunt. Arrhythmias vary in severity. Arrhythmias are generally classified acc ording to their origin (ventricular or supraventricular). Monitor for arrhythmias p ostoperatively because edema of the atria may interfere with sinoatrial node fun ction. partially influenced by the site of origin. and the competence of the atrioventricular valves. Right atrial blood is more oxygenate d than superior vena caval blood. Causes Common causes of arrhythmias include: congenital defects myocardial ischemia or infarction organic heart disease drug toxicity degeneration of the conductive tissue . determi nes their clinical significance. the location of pulmonary venous drainage. and determin es the degree of shunting and pulmonary vascular disease. valve repair if heart valves are involved antibiotic prophylaxis to prevent infective endocarditis antiarrhythmic medication to treat arrhythmias. in which heart rate incr eases and decreases with respiration) to catastrophic ventricular fibrillation. A small defect may be sutured closed. and require no treatment (such as sinus arrhythmia. Treatment Correcting an ASD typically involves: surgery to repair the defect by age 3 to 6.

each arrhythmia may have its own specific causes. and weakness chest pain cool. (See Types of cardiac arrhythmias.) Signs and symptoms Signs and symptoms of arrhythmias result from reduced cardiac output and altered perfusion to the organs.) Pathophysiology Arrhythmias may result from enhanced automaticity. (See Comparing normal and abnormal conduction. clammy skin altered level of consciousness reduced urinary output. Complications . escape beats. However.connective tissue disorders electrolyte imbalances cellular hypoxia hypertrophy of the heart muscle acid-base imbalances emotional stress. and may include: dyspnea hypotension dizziness. syncope. or abn ormal electrical conduction. reentry.

Laboratory testing may reveal electrolyte abnormalities. The rise in pressure usually results from blood or fluid accumulation in the p ericardial sac. Prognosis depends on the rate of fluid accumulation.Possible complications of arrhythmias include: sudden cardiac death myocardial infarction heart failure thromboembolism. If fluid accumulates rapidl y. Even a small amount of fluid (50 to 100 ml) can cause a serious tamponade if it accumulates rapidly. (See Types of card iac arrhythmias. and reduces cardiac output . Holter monitoring detects arrhythmias and effectiveness of drug therapy during a patient's daily activities. Treatment Follow the specific treatment guidelines for each arrhythmia. unchecked rise in pressure in the pericardial sac that compresses the heart. Electrophysiologic testing identifies the mechanism of an arrhythmia and the loc ation of accessory pathways. acid-base abnormalities . it also assesses the effectiveness of antiarrhythmi c drugs. Exercise testing may detect exercise-induced arrhythmias. impairs diastolic filling. Diagnosis Electrocardiography detects arrhythmias as well as ischemia and infarction that may result in arrhythmias. Causes Cause of cardiac tamponade may include: . or drug toxicities that may cause arrhythmias.) Cardiac tamponade Cardiac tamponade is a rapid. A slow accumulation and rise in pressure may not produce immediate symptoms becaus e the fibrous wall of the pericardial sac can gradually stretch to accommodate a s much as 1 to 2 L of fluid. cardiac tamponade requires emergency lifesaving measures to prevent death.

acute rhe umatic fever) hemorrhage from trauma (such as gunshot or stab wounds of the chest) hemorrhage from nontraumatic causes (such as anticoagulant therapy in patients w ith pericarditis or rupture of the heart or great vessels) viral or postirradiation pericarditis chronic renal failure requiring dialysis drug reaction from procainamide. and scleroderma) acute myocardial infarction. minoxidil. Dressler's syndrome) effusion (from cancer. methysergide maleate. systemic lupus erythe matosus. Use a normal electrocardiogram strip.12 to 0.20 second . penicillin. to c ompare normal cardiac rhythm configurations with the rhythm strips below. bacterial infections.g. if available.idiopathic causes (e. hydralazine. TYPES OF CARDIAC ARRHYTHMIAS This chart reviews many common cardiac arrhythmias and outlines their features. vasculitis. and treatments.. isoniazid. or daunorubicin connective tissue disorders (such as rheumatoid arthritis. rarely. rheumatic fever. tuberculosis and. Charac teristics of normal sinus rhythm include: ventricular and atrial rates of 60 to 100 beats/minute regular and uniform QRS complexes and P waves PR interval of 0. causes.

ARRHYTHMIA AND FEATURES € CAUSES TREATMENT Sinus tachycardia Atrial and ventricular rates regular Rate > 100 beats/minute.12 second identical atrial and ventricular rates. with constant PR intervals. left ventricular failure. pain. caffeine. quinidine. rarely. dehydration. pulmonary embolism. a lcohol. may also accompany shock. cardiac tamponade. anemia. and nicotine use Correction of underlying cause Propranolol for symptomatic patients Sinus bradycardia Regular atrial and ventricular rates . exercise. anxiety. > 160 beats/minute Normal P wave preceding each QRS complex Normal physiologic response to fever. isoproterenol. epinephrine.QRS duration < 0. hyperthyroidi sm. hypovolemia. and anterior wall myocardial infarc tion (MI) May also occur with atropine.

beta blocker. or mechanical ventilation. intubation. and inferior wall MI May also occur with anticholinesterase. dizziness. and morphine use For low cardiac output. in well-conditioned heart.Rate < 60 beats/minute Normal P waves preceding each QRS complex Normal. weakness. as in an athlete Increased intracranial pressure. increased vagal tone due to straining during de fecation. vomiting. difficult to differentiate from preceding T wave P wave preceding each QRS complex Sudden onset and termination of arrhythmia Intrinsic abnormality of atrioventricular (AV) conduction system . rarely exceeds 250 beats/minute P waves regular but aberrant. altered level of consciousness. hypothyroidism. or low blood pressure. digoxin. sick sinus syndrome. may need permanent pacem aker Paroxysmal supraventricular tachycardia (PSVT) Atrial and ventricular rates regular Heart rate > 160 beats/minute. advanced cardiac life support (ACLS) protocol for administra tion of atropine Temporary pacemaker or isoproterenol if atropine fails.

use synchron ized cardioversion. MI. and diltiazem. carotid sinu s massage Adenosine by rapid intravenous (I. For narrow complex width with low or unst able blood pressure (and for ineffective drug response for others).V. marijuana. depending on degree of atrioventricular (AV) block (u sually 60 to 100 beats/minute) Sawtooth P-wave configuration possible (F waves) . cardiomyopathy. use of caffeine. 250 to 400 beats/minute Ventricular rate variable. hypokalemia. hypoxia. beta blockers. For wide complex width. and systemic hypertension Digoxin toxicity. follo w ACLS protocol for lidocaine and procainamide. valvular disease.) bolus injection to rapidly convert arrhyth mia If patient is stable.Physical or psychological stress. For narrow complex width and nor mal or elevated blood pressure. cor pulm onale. determine QRS complex width. follow ACLS protocol for verapamil and consider digoxin. ARRHYTHMIA AND FEATURES € CAUSES TREATMENT Atrial flutter Atrial rhythm at regular rate. congenit al heart disease. hyperthyroidism. prepare for immediate cardioversion If patient is stable. Valsalva's maneuver. apply vagal stimulation. Wolff-Parkinson-White syndrome. or central nervous system stimulan ts If patient is unstable.

pulmonary embolism. or complication o f coronary bypass or valve replacement surgery Nifedipine and digoxin use . procainamide. but often irregular in rate Heart failure. atrial irritation. thyrotoxicosis. verapam il. drug therapy may include diltiazem. chronic obstructive pulmonary disease. irregular. tricuspid or mitral valve disease. hypertension. cor pulmon ale. prepare for i mmediate cardioversion If patient is stable. constricti ve pericarditis. beta blockers. or quinidine Atrial fibrillation Atrial rhythm grossly irregular. pulmonary embolus. inferior wall MI. rheumatic he art disease. sepsis. and pericarditis Digoxin toxicity If patient is unstable with a ventricular rate > 150 beats/minute. or P waves that appear as erratic. ischemic heart disease.QRS complexes uniform in shape. rate > 400 beats/minute Ventricular rate grossly irregular QRS complexes of uniform configuration and duration PR interval indiscernible No P waves. digoxin. mitral stenosis. baseline fibrillatory waves Heart failure.

hypoxia. Junctional rhythm Atrial and ventricular rates regular. given I.V. procainamide. or ibutilide. except in aberrant conduction Inferior wall MI or ischemia. digoxin. or after QRS complex. ventric ular rate usually 40 to 60 beats/minute (60 to 100 beats/minute is accelerated j unctional rhythm) P waves preceding. prepare for i mmediate cardioversion If patient is stable. and sick sinus syndrom e Acute rheumatic fever Valve surgery Digoxin toxicity Atropine for symptomatic slow rate Pacemaker insertion if patient doesn't respond to drugs Discontinuation of digoxin if appropriate . inverted if vis ible PR interval (when present) < 0. atrial rate 40 to 60 beats/minute. hidden within (absent).12 second QRS complex configuration and duration normal.If patient is unstable with a ventricular rate > 150 beats/minute. drug therapy may include diltiazem. beta blockers. vagal stimulation. verapam il.

use of quinidine. and hyperkalemia Digoxin toxicity. hypothyroidism. hypokalemia. procainamide.26 second or bradycardia develops Second-degree AV block Mobitz I (Wenckebach) Atrial rhythm regular Ventricular rhythm irregular .First-degree AV block Atrial and ventricular rates regular PR interval > 0. or propranolol Cautious use of digoxin Correction of underlying cause Possibly atropine if PR interval > 0.20 second P wave precedes QRS complex QRS complex normal May be seen in healthy persons Inferior wall MI or ischemia.

or procainamide Treatment of underlying cause Atropine or temporary pacemaker for symptomatic bradycardia Discontinuation of digoxin if appropriate ARRHYTHMIA AND FEATURES € CAUSES TREATMENT Second-degree AV block Mobitz II Atrial rate regular Ventricular rhythm regular or irregular. quinidine. but only slightly. cardiac surgery. with varying degree of block P-P interval constant QRS complexes periodically absent Severe coronary artery disease. PR interval shorter after dropped beat Inferior wall MI. and acute myocarditis . and vagal stimulation Digoxin toxicity. acute rheumatic fever.Atrial rate exceeds ventricular rate PR interval progressively. use of propranolol. anterior wall MI. longer with each cycle until QRS c omplex disappears (dropped beat).

hypoxia. and Lenègre's disease (conductive tissue fibrosis) Digoxin toxicity Atropine or isoproterenol for symptomatic bradycardia Temporary or permanent pacemaker . rheumatic fever. congenital abnormality.Digoxin toxicity Atropine or isoproterenol for symptomatic bradycardia Temporary or permanent pacemaker Discontinuation of digoxin if appropriate Third-degree AV block (complete heart block) Atrial rate regular Ventricular rate slow and regular No relation between P waves and QRS complexes No constant PR interval QRS interval normal (nodal pacemaker) or wide and bizarre (ventricular pacemaker ) Inferior or anterior wall MI. Lev's disease (fibrosis and calcification that spreads from cardiac structures to the conductive tissue) . postoperative complication of mitral valve replacement.

or contusion. usually followed by a compensatory pause QRS complex wide and distorted. ischemia. and hypocalcemia Drug toxicity (digoxin. or alcohol use Psychological stress. anxiety. tobacco. or in threes. multifocal. usually > 0. hypokalemia. in pairs. or exercise If warranted. lidocaine.14 second Premature QRS complexes occurring singly. pain. with R wave on T pattern Heart failure.V.Premature ventricular contraction (PVC) Atrial rate regular Ventricular rate irregular QRS complex premature. tricyclic antidepressants. old or acute MI. or dopamine) Caffeine. beta-blockers. aminophylline. or bretylium I. Treatment of underlying cause Discontinuation of drug causing toxicity . myocardial irritation by ventricular catheter or a pacemaker. procainamide. isoproterenol. hypercapnia. focus from one or more sites Ominous when clustered. alternating wi th normal beats.

follow ACLS protocol fo r defibrillation. coronary artery disease. endotracheal (ET) intubation. initiate synchronized cardioversion If ventricular rate > 150 beats/minute. and administration of epinephrin e. MI. if PVC induced by hypokalemia Ventricular tachycardia Ventricular rate 140 to 220 beats/minute. bizarre. and independent of P waves P waves not discernible May start and stop suddenly Myocardial ischemia.V. cardiomyopathy. hypercalcemia. or procainamide ARRHYTHMIA AND FEATURES € CAUSES TREATMENT . or bretylium . or quinidine toxicity Anxiety With pulse: If hemodynamically stable with ventricular rate < 150 beats/minute. mitral valve prolapse. magnesium sulfate. or aneurysm. lidocaine. epinephrine.Potassium chloride I. bretylium. heart failure. if drugs are ineffective. and pulmonary embolism Digoxin. rheumatic heart d isease. hypokalemia. follow ACLS protocol for immediate synch ronized cardioversion. procainamide. follow ACLS protocol for administration of lidocaine. followed by antiarrhythmic agents Pulseless: Initiate cardiopulmonary resuscitation (CPR). procainamide. regular or irregular QRS complexes wide. ventricular cathet ers.

ET intubation. aortic valve disease. cardiac tamponade. hypokalem ia. epinephrine. follow ACLS protocol for defibrillation. follow ACLS protocol for ET intubation. AV block. MI. heart failure. alkalosis. hypoxia. electric shock. no visible P waves Myocardial ischemia. administration of epinephr ine and atropine. severe acidosis. hyperkalemia. heart rupture. QRS complexes. and electromechanical dissociation Cocaine overdose Continue CPR. magnesium sulfate. R-on-T phenomenon. or T waves Myocardial ischemia. electric shock. bretylium. lidocaine. hypercalcemia. MI. and hypother mia Digoxin. pulmonary embolism. hyperkalemia. and possible transcutaneous pacing . and admini stration of epinephrine. or quinidine toxicity Initiate CPR. untreated ventricular tachycardia. ventricular arrhythmia. or procainamid e Asystole No atrial or ventricular rate or rhythm No discernible P waves.Ventricular fibrillation Ventricular rhythm rapid and chaotic QRS complexes wide and irregular. h ypokalemia.

rapid pulse in response to a drop in cardiac output cough.000 ml if the fluid accumulates slowly and the pericardium stretches to adapt. more fluid accumulates in the pericardial sac . This further limits the amount of blood that can fill the ventricular chambers .Pathophysiology In cardiac tamponade. the progressive accumulation of fluid in the pericardial s ac causes compression of the heart chambers. Diagnosis Chest X-rays show slightly widened mediastinum and possible cardiomegaly. The ca rdiac silhouette may have a goblet-shaped appearance.) Each time the ventricles contract. during the next cardiac cycle. and syncope due to a drop in cardiac output cyanosis due to reduced oxygenation of the tissues weak. orthopnea. (See Understanding cardiac tamponade. Complications Reduced cardiac output may be fatal without prompt treatment. The amount of fluid necessary to cause cardiac tamponade varies greatly. especially the left ventricle. restlessness. dyspnea. it may be as little as 200 ml when the fluid accumulates rapidly or more than 2. . and tachypnea because the lungs are compressed by an expanding pericardial sac. Signs and symptoms The following signs and symptoms may occur: elevated central venous pressure (CVP) with neck vein distention due to increase d jugular venous pressure muffled heart sounds caused by fluid in the pericardial sac pulsus paradoxus (an inspiratory drop in systemic blood pressure greater than 15 mm Hg) due to impaired diastolic filling diaphoresis and cool clammy skin caused by a drop in cardiac output anxiety. This compression obstructs blood fl ow into the ventricles and reduces the amount of blood that can be pumped out of the heart with each contraction.

Generalized ST-segment elevation is noted in all leads. A catheter may be left in the pericardial space attached to a drainage bag to allow for continuous drainage of fluid pericardectomy the surgical creation of an opening to remove accumulated fluid f rom the pericardial sac resection of a portion or all of the pericardium to allow full communication wit h the pleura. QRS comple x. Pulmonary artery catheterization detects increased right atrial pressure. Treatment Correcting cardiac tamponade typically involves: supplemental oxygen to improve oxygenation continuous ECG and hemodynamic monitoring in an intensive care unit to detect co mplications and monitor effects of therapy pericardiocentesis (needle aspiration of the pericardial cavity) to reduce fluid in the pericardial sac and improve systemic arterial pressure and cardiac outpu t. an alternating beat-to-beat change in amplitude of the P wave. An ECG is used to rule out other cardiac disorders.Electrocardiography (ECG) may show low-amplitude QRS complex and electrical alte rnans. and T wave. Echocardiography may reveal pericardial effusion with signs of right ventricular and atrial compression. and CVP. to improve myocardial contra ctility until fluid in the pericardial sac can be removed in traumatic injury. it may reveal changes produced by acu te pericarditis. if repeated pericardiocentesis fails to prevent recurrence trial volume loading with crystalloids such as intravenous 0. such as isoproterenol or dopamine. right ventricular diastolic pressure. a blood transfusion or a thoracotomy to drain reaccumulatin g fluid or to repair bleeding sites may be necessary .9% normal saline to maintain systolic blood pressure inotropic drugs.

Cardiomyopathy Cardiomyopathy generally applies to disease of the heart muscle fibers. drug toxicity.000 Americans have dil ated congestive cardiomyopathy. for exa mple. myocard ial ischemia. begins at the heart's pacemaker . the most common type. and hypocalcemia. which may increas e the intrinsic rate of the SA node or latent pacemakers. and the use of certain antiarrhythmic drugs. Wolff-Parkinson-White syndrome. junctional. pregnanc y. myocardial infarction. Conditions that increase the likelihood of reentry include hyperkalemia. and alcohol use. viral infections. and ventricular complexes. and ventricular tachycardia. The co urse of hypertrophic cardiomyopathy is variable. alkalosis. Reentry Ischemia or deformation causes an abnormal circuit to develop within conductive fibers. hyp okalemia. The atrioventricular blocks occur as a result of conduction disturbances. prema ture atrial. An alternative reentry mechanism depends on the presence of a congenital accesso ry pathway linking the atria and the ventricles outside the AV junction. When an impulse leaves the SA node. and electrolyte abnormalities. reentry. Altered automaticity Enhanced automaticity is the result of partial depolarization. and ventricular complexes. ventricular tachycardia and fibrillation. shown below. atropine. hypertrophic. Reentry may be respon sible for dysrhythmias such as paroxysmal supraventricular tachycardia. the prognosis is generally poor. hypoxia. the previously depolarized tissue within the circuit is n o longer refractory to stimulation. Possible causes include trauma. Examples of arrhythmias caused by enhanced automatic ity include atrial fibrillation and flutter. junctional. At greatest risk of cardio myopathy are males and blacks. Cardiomyopathy is the second most common direct cause of sudden death. prematur e atrial. other risk factors include hypertension. it travels throu gh the atria along Bachmann's bundle and the internodal pathways to the atrioven tricular (AV) node and then down the bundle of His. th e descending impulse can travel in the other direction. finally. and digoxin and conditions such as acidosis. or may induce ectopic pacemakers to reach threshold and depolarize. the sinoatrial (SA) node. By the time the impulse completes the circuit. down the Purkinje fibers to the ventricles. Because dilated cardiomyopathy is usually not diagnosed until its advanced stages. along the bundle branches an d. Automaticity may be enhanced by drugs such as epinephrine.heparin-induced tamponade requires administration of heparin antagonist protamin e sulfate to stop bleeding warfarin-induced tamponade may necessitate use of vitamin K to stop bleeding. COMPARING NORMAL AND ABNORMAL CONDUCTION NORMAL CARDIAC CONDUCTION The conduction system of the heart. supraventricular tachycardia. and accelerated idioventricular and junctional rhythms. myocard ial infarction. or conduction disturbances may cause cardiac arrh ythmias. myocardial ischemia. and it o ccurs in three main forms: dilated. coron ary artery disease is first. Conduction disturbances Conduction disturbances occur when impulses are conducted too quickly or too slo wly. Although current flow is blocked in one direction within the circuit. and restrictive (extremely rar e). Approximately 5 to 8 per 100. ABNORMAL CARDIAC CONDUCTION Altered automaticity. Some patients progressively det .

and vasoconstriction also occurs as the renin-angiotensin system is stimulated. As end-diastolic volumes rise. Left ventricular di lation occurs as venous return and systemic vascular resistance rise. compressing th e heart chambers. AGE ALERT Barth syndrome is a rare genetic disorder that can cause dilated cardi omyopathy in boys. or primary. the heart begins to fail. hypertrophic car diomyopathy primarily affects diastolic function. low cardiac output can be fatal. noncompliant. which surrounds and protects the heart. is composed of seve ral layers. consists of the visceral and parietal layer s. Evidence of dilated cardiomyopathy may appear as early as the first few days or months of life. forceful contractions of the left ventricle. impaired relaxation. The fibrous pericardium is the tough outermost membrane. Cardiomegaly occurs as a consequence of dilation of the atria and ventr icles. and cardiac output fall. pulmonary congestion may occur. short stature. The parietal layer lies between the visceral layer and the fib rous pericardium. disease. there is reduced contractility in the left ventricle. Without prom pt treatment. the inner m embrane. and obstruction to left ventricular outflow. The kidneys are stimulated to retain sodi um and water to maintain cardiac output.) Hyp ertrophic cardiomyopathy is almost always inherited as a non sex-linked autosomal dominant trait. Causes Most patients with cardiomyopathy have idiopathic. ejection fraction. (See Comparing the cardiomyopathies. Unlike dilated cardiomyopathy. called the serous membrane. neutropenia. whereas others remain stable for years. rapid. The features of hypertrophic c ardiomyopathy include asymmetrical left ventricular hypertrophy. but some are secondary to identifiable causes. the atria also dilate as more work is required to pump blood into the full ven tricles. The pericardial space between the visceral and parietal layers contains 10 to 30 ml of pericardial fluid. hypertrophy of the intraventricular septum. If severe. The hypertrop hied ventricle becomes stiff. In cardiac tamponade. which affects systolic function. and increased susceptibility to bacterial infection s. Pathophysiology Dilated cardiomyopathy results from extensively damaged myocardial muscle fibers . and unable to relax during ventricul . This syndrome may be associated with skeletal muscle changes. and obstructing venous retur n.eriorate. When these compensatory mechanisms can no longer maintain cardiac output. UNDERSTANDING CARDIAC TAMPONADE The pericardial sac. It is estimated that almost 50 % of all sudden deaths in competitive athletes age 35 or younger are due to hype rtrophic cardiomyopathy. Eventually . increasing intracardiac pressure. stroke volume. The sympathetic nervous system is also stimulated to increase heart rate and contractility. This fluid lubricates the layers and minimizes friction when the heart contracts. As systoli c function declines. As blood flow into the ventricles falls. Blood pooling in the ventricles increases the risk of emboli. blood or fluid fills the pericardial space. Consequently. The elevated enddiastolic volume is a compensatory response to preserve stroke volume despite a reduced ejection fraction. so does cardiac output. restrictive cardiomyopathy is irreversible. The visceral layer clings to the heart and is also known as the epicardial la yer of the heart.

hepatomegaly. mitral regurgitation occurs. Moreover . Reduced ventricular fill ing during diastole and obstruction to ventricular outflow lead to low cardiac o utput. Clinical manifestations of hypertrophic cardiomyopathy may include: angina caused by the inability of the intramural coronary arteries to supply eno ugh blood to meet the increased oxygen demands of the hypertrophied heart syncope resulting from arrhythmias or reduced ventricular filling leading to a r educed cardiac output . Restrictive cardiomyopathy is characterized by stiffness of the ventricle caused by left ventricular hypertrophy and endocardial fibrosis and thickening. orthopnea. dyspnea on exertion.ar filling. causing a rise in left atrial and pulmonary venous pressur es and leading to venous congestion and dyspnea. Signs and symptoms Clinical manifestations of dilated cardiomyopathy may include: shortness of breath. As a result. Moreover. If papillary muscles become hypertrophied and do not close completely dur ing contraction. cardiac output falls. intramural coronary arte ries are abnormally small and may not be sufficient to supply the hypertrophied muscle with enough blood and oxygen to meet the increased needs of the hyperdyna mic muscle. Consequently. fatigue. the rigid myocardium fails to contract completely during systole. ventricular filling is reduced and left ventricular fi lling pressure rises. Ventricular filling time is fur ther reduced as a compensatory response to tachycardia. and weight gain cause d by right-sided heart failure peripheral cyanosis associated with a low cardiac output tachycardia as a compensatory response to low cardiac output pansystolic murmur associated with mitral and tricuspid insufficiency secondary to cardiomegaly and weak papillary muscles S3 and S4 gallop rhythms associated with heart failure irregular pulse if atrial fibrillation exists. jugular venous distention. and a dry cough at night due to left-sided heart failure peripheral edema. paroxysmal nocturnal dyspne a. thus r educing the ability of the ventricle to relax and fill during diastole.

dyspnea due to elevated left ventricular filling pressure fatigue associated with a reduced cardiac output systolic ejection murmur along the left sternal border and at the apex caused by mitral regurgitation peripheral pulse with a characteristic double impulse (pulsus biferiens) caused by powerful left ventricular contractions and rapid ejection of blood during sys tole abrupt arterial pulse secondary to vigorous left ventricular contractions irregular pulse if an enlarged atrium causes atrial fibrillation. hypertrophic. and restrictive. These conditions may lead to heart failure by im pairing myocardial structure and function. NORMAL HEART DILATED CARDIOMYOPATHY HYPERTROPHIC CARDIOMYOPATHY RESTRICTIVE CARDIOMYOPATHY Ventricles greatly increased chamber size . They are grouped into three main pathophysiologic types dilated. COMPARING THE CARDIOMYOPATHIES Cardiomyopathies include a variety of structural or functional abnormalities of the ventricles.

thinning of left ventricular muscle normal or decreased chamber size left ventricular hypertrophy thickened interventricular septum decreased ventricular chamber size left ventricular hypertrophy Atrial chamber size increased increased increased Myocardial mass increased increased normal Ventricular inflow resistance normal increased .

increased Contractility decreased increased or decreased normal or decreased Possible causes viral or bacterial infection hypertension peripartum syndrome related to toxemia ischemic heart disease valvular disease drug hypersensitivity chemotherapy cardiotoxic effects of drugs or alcohol autosomal dominant trait hypertension .

pulmonary venous hypertension. left anterior hemiblock. pulmonary congestion. valvular abnormalities Asymmetrical thickening of the left ventricular wall. possibly. left ventricular d ilation and. global hypokinesia.obstructive valvular disease thyroid disease amyloidosis sarcoidosis hemochromatosis infiltrative neoplastic disease COMPARING DIAGNOSTIC TESTS IN CARDIOMYOPATHY TEST DILATED CARDIOMYOPATHY HYPERTROPHIC CARDIOMYOPATHY RESTRICTIVE CARDIOMYOPATHY Electrocardiography Biventricular hypertrophy. rules out constrictive pericarditis Chest X-ray Cardiomegaly. atrioventricular conduction defects. atrial fibrillation Low voltage. possibly. increased thickness of the intraventricular septum and abnormal motion of the anterior mitral leaflet duri ng systole. ventricular arrhythmias an d. and arrhythmias Echocardiography Left ventricular thrombi. Q waves in precordial and inferior leads. sinus tachycardia. atrial and ven tricular arrhythmias. atrial enlargement. ST-segment and T-wave abnormalities. normal or reduced left ventricular cavit y size. and pleural o . and normal systolic function. bundle branch block. hypertrophy. and occluding left ventricular outflow in obstructive disease Increased left ventricular muscle mass. and ST-segment and T-wave abnormaliti es Left ventricular hypertrophy. enlarged atria.

possibly. may identify coronary ar tery disease as a cause Elevated ventricular end-diastolic pressure and. hyperdynamic systolic function. pericardial effusion. edema. pallor. . dyspnea. mitral insufficiency. left ventricu lar enlargement. rules out constrictive pericarditis Cardiac catheterization Elevated left atrial and left ventricular end-diastolic pressures. Diagnosis The following tests help diagnose cardiomyopathy: Echocardiography confirms dilated cardiomyopathy. left ventricular outflow obstruction Normal or reduced systolic function and myocardial infiltration Radionuclide studies Left ventricular dilation and hypokinesis. and S3 or S4 gallop rhythms due to heart failure systolic murmurs caused by mitral and tricuspid insufficiency. and pulmonary congestion Increased left vent ricular end-diastolic pressure. Chest X-ray may reveal cardiomegaly associated with any of the cardiomyopathies.r pericardial effusions Cardiomegaly Cardiomegaly. and ischemia Left ventricular hypertrophy with restricted ventricular filling Clinical manifestations of restrictive cardiomyopathy may include: fatigue. peripheral cy anosis. reduced ejection fraction Reduced left ventricular volume. liver engorgement. orthopnea. chest pain. and mitral and tricuspid incompetence. Complications Possible complications of cardiomyopathy include: heart failure arrhythmias systemic or pulmonary embolization sudden death. increased muscle mass.

to i mprove myocardial contractility hydralazine and isosorbide dinitrate. (See Comparing diagnostic tests in cardiomyopathy.Cardiac catheterization with possible heart biopsy can be definitive with hypert rophic cardiomyopathy. (See Classifying heart failure. to produce vasodilation beta-adrenergic blockers for patients with New York Heart Association class II o r III heart failure. such as coronary artery bypass graft surgery. in combination. to control arrhythmias cardioversion to convert atrial fibrillation to sinus rhythm pacemaker insertion to correct arrhythmias anticoagulants (controversial) to reduce the risk of emboli revascularization. used cautiously.) Treatment Correction of dilated cardiomyopathy may involve: treatment of the underlying cause. if dilated card iomyopathy is due to ischemia .) antiarrythmics such as amiodarone. as first-line therapy. if identifiable angiotensin-converting enzyme (ACE) inhibitors. to reduce fluid retention digoxin. Diagnosis requires elimination of other possible causes of heart failure and arr hythmias. taken with ACE inhibitors. to reduce afterload through vasodilation diuretics. for patients not responding to ACE inhibitor and diuretic therapy.

palpitations. if dilated cardiomyopathy is due to valve dysfun ction heart transplantation in patients refractory to medical therapy lifestyle modifications.valvular repair or replacement. low-sodium diet. low-fat. and abstinence from alcohol. CLASS I: MINIMAL No limitations Ordinary physical activity doesn't cause undue fatigue. such as smoking cessation. ph ysical activity. palpitations. dyspnea. dyspnea. or angina CLASS III: MODERATE Markedly limited physical activity Comfortable at rest Less than ordinary activity produces symptoms CLASS IV: SEVERE Patient unable to perform any physical activity without discomfort . o r angina CLASS II: MILD Slightly limited physical activity Comfortable at rest Ordinary physical activity results in fatigue. CLASSIFYING HEART FAILURE The New York Heart Association (NYHA) classification is a universal gauge of hea rt failure severity based on physical limitations.

Angina or symptoms of cardiac inefficiency may develop at rest Correction of hypertrophic cardiomyopathy may involve: beta-adrenergic blockers to slow the heart rate. such as amiodarone. diuretic . to reduce the outflow gradient by altering the patter n of ventricular contraction implantable cardioverter-defibrillator to treat ventricular arrhythmias ventricular myotomy or myectomy (resection of the hypertrophied septum) to ease outflow tract obstruction and relieve symptoms mitral valve replacement to treat mitral regurgitation cardiac transplantation for intractable symptoms. digoxin. thereby increasing cardiac output antiarrhythmic drugs. such as administering deferoxamine to bind ir on in restrictive cardiomyopathy due to hemochromatosis although no therapy exists for restricted ventricular filling. in patients with obstructive hypertrophic cardiomyopathy and ventricular tachycardias. Correction of restrictive cardiomyopathy may involve: treatment of the underlying cause. to reduce arrhythmias cardioversion to treat atrial fibrillation anticoagulation to reduce risk of systemic embolism with atrial fibrillation verapamil and diltiazem to reduce ventricular stiffness and elevated diastolic p ressures ablation of the atrioventricular node and implantation of a dual-chamber pacemak er (controversial). reduce myocardial oxygen demand s. and increase ventricular filling by relaxing the obstructing muscle.

pulmona ry edema. the rest of the blood travels through the coarctation. If coarctation is asymptomatic in infancy. pallor. near the site where the ligamentum arteriosum (the remnant of the ductus arteriosus. and a restricted sodium diet may ease the symptoms of heart failure oral vasodilators may control intractable heart failure. and ventricular septal defect (VSD). and travels to the legs. usually just below the left subclavian artery. cardiomegaly. to c erebral hemorrhage and aortic rupture. causing narrowing. Coar ctation may occur with aortic valve stenosis (usually of a bicuspid aortic valve ) and with severe cases of hypoplasia of the aortic arch. The obstructive proces s causes hypertension in the aortic branches above the constriction (arteries th at supply the arms. When coarctation of th e aorta occurs in females. Restricted blood flow through the narrowed aorta increases the pressure load on the left ventricle and causes dilation of the proximal aorta and ventricular hyp ertrophy. mixes with deoxygenated b lood from the PDA. Coarctation of the aorta Coarctation is a narrowing of the aorta. Untreated.s. failure to thrive. a portion travels through the art eries that branch off the aorta proximal to the coarctation. This leads to pul monary hypertension and. a fetal blood vessel) joins the pulmonary artery to the aorta. The obstruction to blood flow res ults in ineffective pumping of the heart and increases the risk for heart failur e. a chrom osomal disorder that causes ovarian dysgenesis. If correc tive surgery is performed before isolated coarctation induces severe systemic hy pertension or degenerative changes in the aorta. rarely. it usually remains so throughout adol escence as collateral circulation develops to bypass the narrowed segment. an infant may display tachypnea. and hepatomegaly due to heart failure claudication due to reduced blood flow to the legs . this contractil e tissue extends into the aortic wall. straining the right side of the heart. Possibly. tachycardia. The prognosis depends on the severity of associated cardiac anomalies. it's often associated with Turner's syndrome. Signs and symptoms The following signs and symptoms may occur: during the first year of life. right-sided heart hypertrophy and failure. neck. dyspnea. the prognosis is good. and head) and diminished pressure in the vessel below the constriction. this condition may lead to left-sided heart failure and. the legs and l ower portion of the body must rely solely on the blood that gets through the coa rctation. blood shu nts from left to right. This acyanotic condition accounts for about 7% of all congenital heart defects i n children and is twice as common in males as in females. it may be associated with Turner's syndrome. Causes Although the cause of this defect is unknown. eventually. patent ductus arterios us (PDA). If VSD accompanies coarctation. Pathophysiology Coarctation of the aorta may develop as a result of spasm and constriction of th e smooth muscle in the ductus arteriosus as it closes. As oxygenated blood leaves the left ventricle. If PDA is present. If the PDA is closed.

hypertension in the upper body due to increased pressure in the arteries proxima l to the coarctation headache. Diagnosis . the mu rmur is best heard at the base of the heart chest and arms may be more developed than the legs because circulation to legs i s restricted. vertigo. and epistaxis secondary to hypertension upper extremity blood pressure greater than lower extremity blood pressure becau se blood flow through the coarctation is greater to the upper body than to the l ower body pink upper extremities and cyanotic lower extremities due to reduced oxygenated blood reaching the legs absent or diminished femoral pulses due to restricted blood flow to the lower ex tremities through the constricted aorta continuous midsystolic murmur due to left-to-right shunting of the blood. Complications Possible complications of this defect include: heart failure severe hypertension cerebral aneurysms and hemorrhage rupture of the aorta aortic aneurysm infective endocarditis.

and in the mi . and the coarctation site. heart failure. and notching of the undersurfaces of the ribs d ue to erosion by collateral circulation. Treatment Correction of coarctation of the aorta may involve: digoxin. Echocardiography may show increased left ventricular muscle thickness. Aortography locates the site and extent of coarct ation. and sedatives in infants with heart failure prostaglandin infusion to keep the ductus open antibiotic prophylaxis against infective endocarditis before and after surgery antihypertensive therapy for children with previous undetected coarctation until surgery is performed preparation of the infant with heart failure or hypertension for early surgery. Balloon angioplasty or resectio n with end-to-end anastomosis or use of a tubular graft may also be performed. The primary effect of CAD is the loss of oxy gen and nutrients to myocardial tissue because of diminished coronary blood flow . coexistin g aortic valve abnormalities. or else surgery is delayed until the preschool years. whites. Approximately 11 mill ion Americans have CAD. As the population ages. Coronary artery disease Coronary artery disease (CAD) results from the narrowing of the coronary arterie s over time due to atherosclerosis. Electrocardiography may reveal left ventricular hypertrophy. Chest X-rays may demonstrate left ventricular hypertrophy. A flap of the left subclav ian artery may be used to reconstruct the aorta. the prevalence of CAD is rising. absent or diminished femoral pulses. oxygen. a wide ascending and descending aorta. diuretics. Cardiac catheterization evaluates collateral circulation and measures pressure i n the right and left ventricles and in the ascending and descending aortas (on b oth sides of the obstruction). and it occurs more often in males.The following tests help diagnose coarctation of the aorta: Physical examination reveals the cardinal signs resting systolic hypertension in the upper body. and a wide pulse pressure.

Pathophysiology Fatty. Less common causes of reduced coronar y artery blood flow include: dissecting aneurysm infectious vasculitis syphilis congenital defects. this can lead to tissue injury or necrosis. a fatty streak begins to build up on the intimal layer. Myocardial cells become ischemic within 10 seconds of a coronary artery occlusio n. (See Atherosclerotic plaque development. and adventitia (the outermost layer). in advanced stages. . threatening the myoc ardium beyond the lesion. This causes a prec arious balance between myocardial oxygen supply and demand. luminal narrowing is accompanied by vascular chan ges that impair the ability of the diseased vessel to dilate.ddle-aged and elderly. may become a complicated c alcified lesion that may rupture.) ATHEROSCLEROTIC PLAQUE DEVELOPMENT The coronary arteries are made of three layers: intima (the innermost layer. localized myocardial ischemia results. the prognosis for CAD is favorable. Untreated. reducing the volume of blood that can flow through them and leading to myocardial ischem ia. oxygen deprivation forces the myocardium to sh ift from aerobic to anaerobic metabolism. As atherosclerosis progresses. med ia (the middle layer). With proper care. Damaged by risk factors. fibrous plaques progressively narrow the coronary artery lumina. Within several minutes. leading to accumulation of lactic acid and reduction of cellular pH. Causes CAD is commonly caused by atherosclerosis. The plaque continues to grow and. When oxygen demand exceeds what the diseased vessel ca n supply. Transient ischemia causes reversible changes at the cellular and tissue level s. Fibrous plaque and lipids progressively narrow the lumen and impede blood flow t o the myocardium. depressing myocardial function.

the classic sign of CAD. myocardial infarction results . or tightness in the chest that may radiate to the left arm. reduced energy availability. res ulting in less blood being ejected from the heart with each contraction. squeezing. if blood flow is not restored. and acidosis rapidly im pairs left ventricular function. However. wall motion is abnormal in the ischemic area. Signs and symptoms The following signs and symptoms may occur: angina. Microvascular angina: impairment of vasodilator reserve causes angina-like chest .) nausea and vomiting as a result of reflex stimulation of the vomiting centers by pain cool extremities and pallor caused by sympathetic stimulation diaphoresis due to sympathetic stimulation xanthelasma (fat deposits on the eyelids) occurs secondary to hyperlipidemia and atherosclerosis. or shoulder blade (See Types of an gina. Restori ng blood flow through the coronary arteries restores aerobic metabolism and cont ractility. neck.The combination of hypoxia. it indicates a worsening of coronary artery disease that may progress to m yocardial infarction. results from a reduced supply of oxygen to the myocardium. resulting in less force and velocity. TYPES OF ANGINA There are four types of angina: Stable angina: pain is predictable in frequency and duration and is relieved by rest and nitroglycerin. jaw. Unstable angina: pain increases in frequency and duration and is more easily ind uced. it may occur spontaneously and may not be related to physical exercise or emot ional stress. It may be described as burning. Moreover. Prinzmetal's or variant angina: pain is caused by spasm of the coronary arteries . The strength of contractions in the affected my ocardial region is reduced as the fibers shorten inadequately.

arrhythmias. or t opically in ointment form) or isosorbide dinitrate (given sublingually or orally ) to reduce myocardial oxygen consumption beta-adrenergic blockers to reduce the workload and oxygen demands of the heart . indicating ischemia. Stress echocardiography may show abnormal wall motion. During angina. transdermally. Dyspnea and fatigue are two key signals of ischemia in an ac tive. ST-segment depression and. they appear as cold spots. Complications Complications of CAD include: arrhythmias myocardial infarction. and the condition of the artery beyond the narrowing. orally. older adult. Treatment Treatment of CAD may involve: nitrates. such as nitroglycerin (given sublingually. AGE ALERT CAD may be asymptomatic in the older adult because of a decrease in sy mpathetic response. po ssibly. collateral circulation. Exercise testing may be performed to detect ST-segment changes during exercise. it ma y show ischemic changes.pain in a person with normal coronary arteries. such as T-wave inversion. and to determine a safe exercise prescription. Diagnosis The following tests help diagnose coronary artery disease: Electrocardiography may be normal between anginal episodes. Myocardial perfusion imaging with thallium-201 may be performed during treadmill exercise to detect ischemic areas of the myocardium. ST-segment elevation suggests Prinzmetal's angina. Coronary angiography reveals location and degree of coronary artery stenosis or obstruction.

an alternative to traditional CABG using f iber-optic cameras inserted through small cuts in the chest. maintaining an ideal body weight. An ind . to correct blockage s in one or two accessible arteries angioplasty. and following a low-fat. low-sodium diet. to relieve occlusion in patients without calcification and partial occlusion laser angioplasty to correct occlusion by vaporizing fatty deposits rotational atherectomy to remove arterial plaque with a high-speed burr stent placement in a reopened artery to hold the artery open lifestyle modifications to reduce further progression of CAD.by reducing heart rate and peripheral resistance to blood flow calcium channel blockers to prevent coronary artery spasm antiplatelet drugs to minimize platelet aggregation and the risk of coronary occ lusion antilipemic drugs to reduce serum cholesterol or triglyceride levels antihypertensive drugs to control hypertension estrogen replacement therapy to reduce the risk for CAD in postmenopausal women coronary artery bypass graft (CABG) surgery to restore blood flow by bypassing a n occluded artery using another vessel key hole or minimally invasive surgery. Heart failure results in intravascular and interstitial volume overload and poor tissue perfusion. these include smok ing cessation. Heart failure A syndrome rather than a disease. regular exercise. heart failure occurs when the heart can't pump enough blood to meet the metabolic needs of the body.

and activity intolerance.or right-sided heart failure) or by the cardiac cycle involved (systolic or d iastolic dysfunction). it backs up into the left atrium and then into the lungs.000 Americans die of heart failure each year. the prognosis still depends on the underlying cause and its response to treatment. blood is not pumped effectiv ely through the right ventricle to the lungs. Approximately 1% of peopl e older than age 50 experience heart failure. Right-sided heart failure. Mortality fr om heart failure is greater for males. It may be due to an acute right ventricular infarction or a pulmonary embolus. it occurs in 10% of people older t han age 80. The incidence of heart failure rises with age. causing blood to back up into the right atrium and into the peripheral circulation. CAUSES OF HEART FAILURE CAUSE EXAMPLES Abnormal cardiac muscle function Myocardial infarction Cardiomyopathy Abnormal left ventricular volume . dyspnea. Blood is no longer effectively pumped ou t into the body. About 700. Common causes i nclude left ventricular infarction. If the condition per sists. and the elderly. the most common cause is profound backward flow due to left-sided heart failure . (See Causes of heart failure. and aortic and mitral valve st enosis. causi ng pulmonary congestion. This type of heart failure occurs as a result of ineff ective left ventricular contractile function. As the pumping ability of the left ventricle fails. a reduced qua lity of life.ividual with heart failure experiences reduced exercise tolerance. it a lso occurs in infants. Consequently. Right-sided heart failure results from ineffective ri ght ventricular contractile function. The patient gains weight and d evelops peripheral edema and engorgement of the kidney and other organs. However. Although the most common cause of heart failure is coronary artery disease.) Pathophysiology Heart failure may be classified according to the side of the heart affected (lef t. and a shortened life span. Although advances in diagnostic and therapeutic techniques have greatly improved the outlook for patients with heart failure. cardiac output falls. and adults with congenital and acquired heart d efects. hypertension. pulmonary edema and right-sided heart failure may result. children. blacks. Causes Causes of heart failure may be divided into four general categories. Left-sided heart failure.

Valvular insufficiency High-output states: chronic anemia arteriovenous fistula thyrotoxicosis pregnancy septicemia beriberi infusion of large volume of intravenous fluids in a short time period Abnormal left ventricular pressure Hypertension Pulmonary hypertension Chronic obstructive pulmonary disease Aortic or pulmonic valve stenosis Abnormal left ventricular filling Mitral valve stenosis Tricuspid valve stenosis Atrial myxoma Constrictive pericarditis Atrial fibrillation Impaired ventricular relaxation: hypertension myocardial hibernation myocardial stunning .

Consequently. These mechanisms improve cardiac output at the expense of increased ventric ular work. such as cool extremitie s and clamminess. and shortness of breath may occur. may indicate impending heart failure. Atrial natriuretic factor is a hormone that is secreted mainly by the atria in r esponse to stimulation of the stretch receptors in the atria caused by excess fl uid volume. which tri ggers compensatory mechanisms such as increased sympathetic activity. fatigue. which are potent vasodilators. Consequently. the muscle becomes stretched beyond optimum limits and c ontractility declines. this increased muscle mass also increases the myocardial ox ygen requirements. activation of the renin-angiotensin-aldosterone system. counterregulatory substances prostaglandins and atrial natriur etic factor are produced in an attempt to reduce the negative effects of volume overload and vasoconstriction caused by the compensatory mechanisms. weakness. and its treatment is not as clear. This type of heart failure is less common tha n systolic dysfunction. Diastolic dysfunction. higher volumes are needed in the ventricles to maintain cardiac output. Therefore. or restrictive cardiomyopathy. Systolic dysfunction occurs when the left ventricle can't pump enough blood out to the systemic circulation during systole and the ejectio n fraction falls. An increase in the ventricular diastolic pressure necessary t o fill the enlarged ventricle may compromise diastolic coronary blood flow. Signs of increased sympathetic activity. prostacyclin and prostaglandin E2.Systolic dysfunction. an increase in end-diastolic ventricular volume (preloa d) causes increased stroke work and stroke volume during contraction. In ventricular hypertrophy. Signs and symptoms Early clinical manifestations of left-sided heart failure include: dyspnea caused by pulmonary congestion . This renal mechanism is helpful. Eventually. improving card iac output. leading to sodium and water retentio n and an increase in circulating blood volume. Increased sympathetic activity a response to decreased cardiac output and blood pressure enhances peripheral vascular resistance. Angiotensin causes the adrenal cortex to release aldosterone. converts angiotensinogen to angiotensin I . Atrial natriuretic factor works to counteract the negative effects o f sympathetic nervous system stimulation and the renin-angiotensin-aldosterone s ystem by producing vasodilation and diuresis. In heart failure. However. and causing ischemia and impaired muscl e contractility. Causes of systolic dysfunction incl ude myocardial infarction and dilated cardiomyopathy. The kidneys release the prostaglandins. All causes of heart failure eventually lead to reduced cardiac output. if it persists unchecked. stretching cardiac muscle fibers so that the ventricle can accept the increased intravascu lar volume. and hypertro phy. In ventricular dilation. it can aggravate heart failure as the heart s truggles to pump against the increased volume. blood backs up into the pulmonary circulation an d pressure rises in the pulmonary venous system. causing them to secrete renin which. Cardiac output falls. These vasodilators also act to reduce volume overload produced by the renin-angiotensin-aldosterone system by inhibiting sodium and wa ter reabsorption by the kidneys. Diastol ic dysfunction may occur as a result of left ventricular hypertrophy. however. hypertensi on. heart rate. ventricular dilation. contractility. limi ting the oxygen supply to the ventricle. Diastolic dysfunction occurs when the ability of the left ventricle to relax and fill during diastole is reduced and the stroke volume fa lls. which then becomes angiotensin II a potent vasoconstrictor. in turn. an increase in ventricular muscle mass allows the he art to pump against increased resistance to the outflow of blood. pulmonary congestion and peripheral edema develop. Increased sympathetic activity also restricts blood flow to the kidneys. and venous return.

pale skin resulting from peripheral vasoconstriction restlessness and confusion due to reduced cardiac output. Clinical manifestations of right-sided heart failure include: elevated jugular venous distention due to venous congestion .orthopnea as blood is redistributed from the legs to the central circulation whe n the patient lies down at night paroxysmal nocturnal dyspnea due to the reabsorption of interstitial fluid when lying down and reduced sympathetic stimulation while sleeping fatigue associated with reduced oxygenation and a lack of activity nonproductive cough associated with pulmonary congestion. Later clinical manifestations of left-sided heart failure may include: crackles due to pulmonary congestion hemoptysis resulting from bleeding veins in the bronchial system caused by venou s distention point of maximal impulse displaced toward the left anterior axillary line caused by left ventricular hypertrophy tachycardia due to sympathetic stimulation S3 heart sound caused by rapid ventricular filling S4 heart sound resulting from atrial contraction against a noncompliant ventricl e cool.

fullness. CULTURAL DIVERSITY In the Chinese culture. Complications Acute complications of heart failure include: pulmonary edema acute renal failure arrhythmias. and nausea may be caused by congestion of the liver and inte stines nocturia as fluid is redistributed at night and reabsorbed weight gain due to the retention of sodium and water edema associated with fluid volume excess ascites or anasarca caused by fluid retention. Chronic complications include: activity intolerance renal impairment . Direct questioning and vigilant assessment skills are ne cessary to ensure that a patient's quiet nature doesn't mask signs and symptoms that may be life-threatening. disagreement or discomfort isn't typi cally displayed openly.positive hepatojugular reflux and hepatomegaly secondary to venous congestion right upper quadrant pain caused by liver engorgement anorexia.

the ejection fraction may be normal.cardiac cachexia metabolic impairment thromboembolism. Treatment Correction of heart failure may involve: treatment of the underlying cause. Pulmonary artery monitoring typically demonstrates elevated pulmonary artery and pulmonary artery wedge pressures. Diagnosis The following tests help diagnose heart failure: Chest X-rays show increased pulmonary vascular markings. or pleural effusion and cardiomegaly. or infarction. Radionuclide ventriculography may reveal an ejection fraction less than 40%. Echocardiography may reveal left ventricular hypertrophy. and abnormal contractility. in diastolic dysfunction. Electrocardiography may indicate hypertrophy. a nd may also reveal tachycardia and extrasystoles. and elevated right atrial pressure or central venous pre ssure in right-sided heart failure. interstitial edema. ischemic changes. if known angiotensin-converting enzyme (ACE) inhibitors to patients with left ventricle d ysfunction to reduce production of angiotensin II. Laboratory testing may reveal abnormal liver function tests and elevated blood u rea nitrogen and creatinine levels. left ventricular end-diastolic pressure in le ft-sided heart failure. dilation. resulting in preload and afte rload reduction .

insertion of an intra-aortic balloon pump. Some are controversial and may include cardiomyoplasty. reduced stress. morphine. and spices for canned food s. improve cardiac output. and implanting an internal cardioverter-defibrillator. limited sodium (to 3 g/day) and alcohol intake.) diuretics. monosodium glutamate. and development of an exercise program. herbs. digoxin for patients with heart failure due to left ventricular systolic dysfunc tion to increase myocardial contractility. CULTURAL DIVERSITY Asian Americans consume large amounts of sodium. signifying a toxic effect. Monitor for severe hypotension. and decrease ventricular stretch diuretics to reduce fluid volume overload and venous return beta-adrenergic blockers in patients with New York Heart Association class II or class III heart failure caused by left ventricular systolic dysfunction to prev ent remodeling (See Classifying heart failure. reduced fat intake . Encourage an Asian patient to substitute fresh vegetables. and oxygen to treat pulmonary edema lifestyle modifications (to reduce symptoms of heart failure) such as weight los s (if obese). reduce the vo lume of the ventricle. use of a mechanical ventricular assi st device. AGE ALERT Heart failure in children occurs mainly as a result of congenital hear .AGE ALERT Older adults may require lower doses of ACE inhibitors because of impa ired renal clearance. Hea rt failure is no longer a contraindication to exercise and cardiac rehabilitatio n. despite maximal medical therapy. and soy sauce. partial left ventriculectomy. coronary artery bypass surgery or angioplasty for heart failure due to coronary artery disease cardiac transplantation in patients receiving aggressive medical treatment but s till experiencing limitations or repeated hospitalizations other surgery or invasive procedures may be recommended in patients with severe limitations or repeated hospitalizations. smoking cessation. nitrates.

Previously. Causes Risk factors for primary hypertension include: family history advancing age AGE ALERT Older adults may have isolated systolic hypertension (ISH). Untreated. in which j ust the systolic blood pressure is elevated. race (most common in blacks) CULTURAL DIVERSITY Blacks are at increased risk for primary hypertension when pr edisposition to low plasma renin levels diminishes ability to excrete excess sod ium. treatment guidelines are directed toward the specific caus e. which may include lifestyle modifications and drug therapy. cardiac diseas e. Ma lignant hypertension is a severe. Hypertension affects 15% to 20% of adults in the United States. Carefully managed treatment. Results of the Systolic Hy pertension in the Elderly Program (SHEP). however. even mild cases can cause major co mplications and death.t defects. and renal failure. it was believed that ISH was a normal part of the aging process and should not be treated. Severely elevated blood pressure (hypertensive crisis) may be f atal. as atherosclerosis causes a loss of elasticity in large arteries. Hypertension is a major cause of cerebrovascular accident. women have a higher incidence. Men have a higher incidence of hypertension in young and early middle adulthood. If untreated. slowly pr ogressing to a malignant state. which results from renal disease or another identifiable cause. it is more severe than in whites. Hypertension develops at an earlier age and. and left ventricular heart failure. improves prognosis. fulminant form of hypertension common to both types. and secondary hypertension. an elevation in diastolic or systolic blood pressure. at any age. Essential hypertension usually begins insidiously as a benign disease. found that treating ISH with antihypertensive drugs lowered the incidence of stroke. coronary artery disease (CAD). obesity . it carries a high mortality rate. Therefore. thereafter. Hypertension Hypertension. The risk of hype rtension increases with age and is higher for blacks than whites and in those wi th less education and lower income. the most common. occurs as tw o major types: essential (primary) hypertension.

estrogen replacement therapy. cocaine. epoetin alfa. hyperaldosteronism. and head injury pheochromocytoma. monoamine ox idase inhibitors taken with tyramine. quadriplegia. and thyroid. and nonstero idal anti-inflammatory drugs . sympathetic stimulants. Cushing's syndrome.tobacco use high intake of sodium high intake of saturated fat excessive alcohol consumption sedentary lifestyle stress excess renin mineral deficiencies (calcium. pituitary . and magnesium) diabetes mellitus. Causes of secondary hypertension include: coarctation of the aorta renal artery stenosis and parenchymal disease brain tumor. potassium. or parathyroid dysfunction oral contraceptives.

the renin-angiotensin-aldosterone system. and vascular response to nore pinephrine. stroke. including: changes in the arteriolar bed causing increased peripheral vascular resistance abnormally increased tone in the sympathetic nervous system that originates in t he vasomotor system centers. Several theories help to explain the development of hypertension. leading to incre ased peripheral vascular resistance abnormal renin release. causing blood pressure to rise. For example: The most common cause of secondary hypertension is chronic renal disease. Insult to the kidney from chronic glomerulonephritis or renal artery stenosis interfer es with sodium excretion. causing increased peripheral vascular resistance increased blood volume resulting from renal or hormonal dysfunction an increase in arteriolar thickening caused by genetic factors. Because hypertension promotes coronary atherosclerosis. increased cortisol levels raise blood pressure by increas ing renal sodium retention. which cons tricts the arteriole and increases blood volume. such as ret inal injury.pregnancy-induced hypertension excessive alcohol consumption. especially the arterioles . Hypertension also causes vascular dam age. and aortic aneurysm and dissection. . resulting in the formation of angiotensin II. The pathophysiology of secondary hypertension is related to the underlying disea se. leading to accelerated atherosclerosis and target organ damage. the left ventric le hypertrophies.) Prolonged hypertension increases the workload of the heart as resistance to left ventricular ejection increases. angiotensin II levels. In Cushing's syndrome. Cardiac dilation and failure may occur when hypertrophy can no longer maintain sufficien t cardiac output. Pathophysiology Arterial blood pressure is a product of total peripheral resistance and cardiac output. Peripheral resistance is increased by factors that increas e blood viscosity or reduce the lumen size of vessels. or both. Cardiac output is increased by conditions that increase heart rate or st roke volume. or renal per fusion. raising the oxygen demands and workload of the heart. (See Understanding blood pressu re regulation. renal failure. the he art may be further compromised by reduced blood flow to the myocardium. resultin g in angina or myocardial infarction (MI). To increase contractile force.

These m echanisms include stress relaxation and capillary fluid shifts: in stress relaxation. AUTOREGULATION Several intrinsic mechanisms work to change an artery's diameter to maintain tis sue and organ perfusion despite fluctuations in systemic blood pressure. Pheochromocytoma is a chromaffin cell tumor of the adrenal medulla that secretes epinephrine and norepinephrine. reduced blood pressure. UNDERSTANDING BLOOD PRESSURE REGULATION Hypertension may result from a disturbance in one of the following intrinsic mec hanisms. RENIN-ANGIOTENSIN SYSTEM The renin-angiotensin system acts to increase blood pressure through the followi ng mechanisms: sodium depletion. raising the heart rate. angiotensin II is a poten t vasoconstrictor that targets the arterioles circulating angiotensin II works to increase preload and afterload by stimulatin g the adrenal cortex to secrete aldosterone. and aug . Epinephrine increases cardiac contractility and rate. increased intravascular volume. plasma moves between vessels and extravascular spaces to maintain intravascular volume. or very high aldosterone levels cause vasoconstriction and increased resistance. baroreceptors in the aortic arch and carotid sinuses decrease their inhibition of the medulla's vasomotor center.In primary aldosteronism. and dehydration stimulate renin releas e renin reacts with angiotensin. this increases blood volume by cons erving sodium and water. which increases preload and afterload angiotensin I converts to angiotensin II in the lungs. a liver enzyme. altered sodium concent rations in vessel walls. and converts it to angiotensin I. The consequent incr eases in sympathetic stimulation of the heart by norepinephrine increases cardia c output by strengthening the contractile force. SYMPATHETIC NERVOUS SYSTEM When blood pressure drops. blood vessels gradually dilate when blood pressure rises t o reduce peripheral resistance in capillary fluid shift. whereas norepinephrine increases peripheral vascular resistance.

If untreated. thus raising blood pressure. the following signs and sympto ms may occur: elevated blood pressure readings on at least two consecutive occasions after ini tial screening WHAT HAPPENS IN HYPERTENSIVE CRISIS Hypertensive crisis is a severe rise in arterial blood pressure caused by a dist urbance in one or more of the regulating mechanisms.menting peripheral resistance by vasoconstriction. de ath. ANTIDIURETIC HORMONE The release of antidiuretic hormone can regulate hypotension by increasing reabs orption of water by the kidney. To avoid missing the first Korotkoff sound. AGE ALERT Because many older adults have a wide auscultatory gap the hiatus betw een the first Korotkoff sound and the next sound failure to pump the blood press ure cuff up high enough can lead to missing the first beat and underestimating t he systolic blood pressure. possibly. cardiac. Signs and symptoms Although hypertension is frequently asymptomatic. nausea and vomiting may also occur epistaxis possibly due to vascular involvement bruits (which may be heard over the abdominal aorta or carotid. and fatigue caused by decreased tissue perfusion due to va soconstriction of blood vessels blurry vision as a result of damage to the retina . and femor al arteries) caused by stenosis or aneurysm dizziness. Stress can also stimulate the sympathetic nervous system to increase cardiac output and peripheral vascular r esistance. With reabsorption. palpate the radial artery and inflate the cuff to a point approximately 20 mm beyond whi ch the pulse beat disappears. renal. blood plasma volume increases . occipital headache (may worsen on rising in the morning as a result of increased intracranial pressure). or cerebral complications and. confusion. hypertensive crisis may result in renal.

MI. One kidney smaller than the other suggests unilateral renal disease. and hypertens ive encephalopathy renal failure. vomiti ng. arrhythmias. CA D. and sudden death (See What happens in hypertensive crisis. Urinalysis may show protein. Cushing's syndrome may cause truncal obesity and purple str iae. angina. casts. Laboratory testing may reveal elevated blood urea nitrogen and serum creatinine levels suggestive of renal disease. If secondary hypertension exists. and profuse perspiration. Complete blood count may reveal other causes of hypertension. For example. Excretory urography may reveal renal atrophy. nausea. other signs and symptoms may be related to the cause. red blood cells. heart failure. Diagnosis The following tests help diagnose hypertension: Serial blood pressure measurements may be useful. peripheral arterial disease. Complications Complications of hypertension include: hypertensive crisis. or glucose.nocturia caused by an increase in blood flow to the kidneys and an increase in g lomerular filtration edema caused by increased capillary pressure.) transient ischemic attacks. suggesting diabetes. palpitations. such as polycythem ia or anemia. presence of catecholamines associated with pheochromocytoma . pallor. . whereas patients with pheochromocytoma may develop headache. or white blood cells. dissecting aortic aneurysm. retinopathy. or hypokalemia indicating adrenal dysfunctio n (primary hyperaldosteronism). indicating chronic renal disease. cerebrovascular accident. sugge sting renal disease.

with or without other risk factors) High normal (130 139/85 89) Lifestyle modification Lifestyle modification Drug therapy for those with heart failure. no TOD/CCD) RISK GROUP C (TOD/CCD and/or diabetes. renal insufficiency. (Se e Risk stratification and treatment. a nd Treatment of High Blood Pressure to determine the approach to treatment accor ding to the patient's blood pressure. and combination diuretics such as hydrochlorothiazide-spironolacto ne) to reduce excess fluid volume RISK STRATIFICATION AND TREATMENT BLOOD PRESSURE STAGES RISK GROUP A (No major risk factors No TOD/CCD*) RISK GROUP B (At least 1 risk factor. Detection.) diuretics (thiazide diuretics such as hydrochlorothiazide. Treatment Hypertension may be treated by following the 1997 revised guidelines of the Sixt h Report of the Joint National Committee on Prevention. risk factors. not including diabetes. Echocardiography may reveal left ventricular hypertrophy. loop diuretics such a s furosemide. Chest X-rays may show cardiomegaly. Evaluation. or diabetes Life style modification Stage 1 (140 159/90 99) Lifestyle modification (up to 12 months) Lifestyle modification (up to 6 months) Drug therapy Lifestyle modification Stages 2 and 3 (>160/>100) Drug therapy Drug therapy Drug therapy Lifestyle modification .Electrocardiography may show left ventricular hypertrophy or ischemia. and target organ damage.

calcium channel blockers such as diltiazem to reduce heart rate and contractilit y. treatment of underlying cause of secondary hypertension and controlling hyperten sive effects . CULTURAL DIVERSITY According to the treatment guidelines issued by the National Institutes of Health in 1997. clinicians should consider drugs as ini tial therapy plus lifestyle modifications. and t o dilate the blood vessels CULTURAL DIVERSITY Asians are twice as sensitive as whites to propranolol and ar e able to metabolize and clear this drug more rapidly. these agents are also effective against vasospasm angiotensin-converting enzyme (ACE) inhibitors such as captopril or angiotensin II receptor blockers such as valsartan to produce vasodilation alpha-receptor blockers such as doxazosin to produce vasodilation alpha-receptor agonists such as clonidine to lower peripheral vascular resistanc e AGE ALERT Older adults are at an increased risk for adverse effects of antihyper tensives. Hypertensive whites are m ore responsive to beta blockers than are hypertensive blacks.Notes: * TOD/CCD indicates target organ disease/clinical cardiovascular disease. beta blockers (such as metoprolol) to reduce heart rate and contractility. drug therapy for blacks should consist of calcium channel blockers and diuretics. Lower doses may be needed. For patients with multiple risk factors. especially orthostatic hypotension.

or oral administration of a selected drug. The p rognosis improves if vigorous treatment begins immediately. Causes Predisposing risk factors include: positive family history gender (men and postmenopausal women are more susceptible to MI than premenopaus al women. limited alcohol. Myocardial infarction In myocardial infarction (MI) also known as a heart attack reduced blood flow th rough one of the coronary arteries results in myocardial ischemia and necrosis. total cholesterol. to rapidly reduce blood pressure lifestyle modifications. such as nifedipine.4 g/day) intake. although the incidence is rising among women. especially those who smo ke and take oral contraceptives) hypertension smoking elevated serum triglyceride. and almost half of sudden deaths due t o MI occur before hospitalization.000 people in the United States experience MI. the leading cause of death in the United States and W estern Europe. within 1 hour of the onset of symptoms. Each year. and potassium in the diet. and smoking cessation inclusion of adequate amounts of calcium. magnesium. approximately 900. and low-density lipoprotein leve ls obesity excessive intake of saturated fats sedentary lifestyle . saturated fa t. and sodium (2. regular exercise. including weight control. Mor tality is high when treatment is delayed. or labetalol. In cardiovascular disease.treatment of hypertensive emergencies with a parenteral vasodilator such as nitr oprusside or an adrenergic inhibitor. death usually results from cardiac damage or complications of MI. captopril. clonidine.

vomiting. The scar tissue that forms on the necrotic area inhibits contractility.) Although ischemia begins immediately. This zone of injury is surroun ded by an outer ring of reversible ischemia. Cardiac enzymes and proteins are released by the infarcted myocardial cells. All MIs have a central area of necrosis or infarction surrounded by an ar ea of potentially viable hypoxic injury. Occlusion can stem from atherosclerosis. reduced stroke volume. syncope. Ven tricular dilation may also occur in a process called remodeling. dyspnea. and renal retention of sodium and water) try to maintain cardiac output. jaw . and confusion. . sc ar tissue is well established. (See Zones of myocardial infarct ion. tingling of the extremities. Functionally. leukocytes infiltrate the necrotic area and begin to remove necrotic cells. increased heart ra te. nause a. crushing substernal chest pain that may radiate to the left arm. Characteristic electrocardiographic changes are associated with each zone. lasting lon ger than 30 to 45 minutes. which are used in the diagnosis of an MI. the infarcted muscle beco mes edematous and cyanotic. Pathophysiology MI results from occlusion of one or more of the coronary arteries. but experience atypi cal symptoms such as fatigue. altered left ven tricular compliance. is s urrounded by an area of viable ischemic tissue. Scar formation begins by the third week after MI. thinning the ventricular w all. neck. or coronary artery stenosis or spasm. in turn. reduced ejection fraction. During the next several days. The zone of injury. it may be described as heavy. especially cocaine and amphetamines. When thi s occurs. or shoulder blades caused by reduced oxygen supply to the myocardial cel ls.) Within 24 hours. a n MI may cause reduced contractility with abnormal wall motion. Signs and symptoms The following signs and symptoms may occur: persistent. or crushing AGE ALERT Many older adults do not have chest pain with MI. weakness. (See Rele ase of cardiac enzymes and proteins. irreversible myocardial cell damage and muscle death occur. thrombosis. the compensatory mechanisms (vascular constriction. and eleva ted left ventricular end-diastolic pressure. platelet aggregation. squeezing. If coronary occlusion causes prolonged ischemia. This zone may be salvaged if circulatio n is restored. the size of the infarct can be limit ed if circulation is restored within 6 hours. falls. and by the sixth week. ZONES OF MYOCARDIAL INFARCTION Myocardial infarction has a central area of necrosis surrounded by a zone of inj ury that may recover if revascularization occurs.aging stress or type A personality drug use. Several changes occur after MI. or it may progress to necrosis.

perspiration. Bradyca rdia may be associated with conduction disturbances fatigue and weakness caused by reduced perfusion to skeletal muscles nausea and vomiting as a result of reflex stimulation of vomiting centers by pai n fibers or from vasovagal reflexes shortness of breath and crackles reflecting heart failure low-grade temperature in the days following acute MI due to the inflammatory res ponse jugular venous distention reflecting right ventricular dysfunction and pulmonary congestion S3 and S4 heart sounds reflecting ventricular dysfunction loud holosystolic murmur in apex possibly caused by papillary muscle rupture reduced urine output secondary to reduced renal perfusion and increased aldoster one and antidiuretic hormone. ischemia or infarction causes changes in the following el ectrocardiographic leads. PINPOINTING MYOCARDIAL INFARCTION Depending on location. blood pressure may fall. and restlessness due to the release of catecholamines blood pressure and pulse initially elevated as a result of sympathetic nervous s ystem activation. anxiety.cool extremities. TYPE OF MYOCARDIAL INFARCTION LEADS . If cardiac output is reduced.

III. aVL. or valves mural thrombi causing cerebral or pulmonary emboli ventricular aneurysms myocardial rupture . V1R V4R Complications Complications of MI include: arrhythmias cardiogenic shock heart failure causing pulmonary edema pericarditis rupture of the atrial or ventricular septum. V3-V6 Posterior V1 or V2 Right ventricular II. aVL. V2 Lateral I.Inferior II. V4 Septal V1. V6 Anterolateral I. aVF. V5. ventricular wall. aVF Anterior V3. III.

) Laboratory testing may reveal elevated white blood cell count and erythrocyte se dimentation rate due to inflammation. These include: assessment of patients with chest pain in the Emergency Department within 10 min utes of an MI because at least 50% of deaths take place within 1 hour of the ons et of symptoms. (See Release of cardiac enzymes and protein s. and the proteins troponin T and I. and pericarditis. and increased glucose levels following the release of catecholamines. and myogl obin to confirm the diagnosis of MI. Echocardiography may show ventricular wall motion abnormalities and may detect s eptal or papillary muscle rupture. Treatment Treatment of an MI typically involves following the treatment guidelines recomme nded by the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines. Nuclear imaging scanning using thallium-201 and technetium 99m can be used to id entify areas of infarction and areas of viable muscle cells. An ECG can also ident ify the location of MI. hypertrophy. Chest X-rays may show left-sided heart failure or cardiomegaly. Cardiac catheterization may be used to identify the involved coronary artery as well as to provide information on ventricular function and pressures and volumes within the heart. specifically CK-MB. Diagnosis The following tests help diagnose MI: Serial 12-lead electrocardiography (ECG) may reveal characteristic changes.) Serial cardiac enzymes and proteins may show a characteristic rise and fall of c ardiac enzymes.extensions of the original infarction. thrombolytic therapy is most effective when started wi thin the first 6 hours after the onset of symptoms oxygen by nasal cannula for 2 to 3 hours to increase oxygenation of the blood (S . Moreover. such as serial ST-segment depression in non Q-wave MI (subendocardial MI that affects the innermost myocardial layer) and ST-segment elevation in Q-wave MI (transmura l MI with damage extending through all myocardial layers). arrhythmias. (See Pinpoin ting myocardial infarction.

occurs when reperfusion takes plac e within 6 hours of the onset of chest pain intravenous heparin for patients who have received tissue plasminogen activator (tPA) to increase the chances of patency in the affected coronary artery. br adycardia. lidocaine. transcutaneous pacing patches or a transvenous pace maker.ee Blocking myocardial infarction. Limite d evidence exists that intravenous or subcutaneous heparin is beneficial in pati ents with acute MI treated with nonspecific thrombolytic drugs.) nitroglycerin sublingually to relieve chest pain. The grea test benefit of reperfusion therapy. unless systolic blood pressure is less than 90 mm Hg or heart rate is less than 50 or greater than 100 beats p er minute morphine or meperidine (Demerol) for analgesia because pain stimulates the sympa thetic nervous system. leading to an increase in heart rate and vasoconstriction aspirin 160 to 325 mg/day indefinitely. and epinephrine readily available to treat arrhythmias. thereby limiting the area of necrosis keeping atropine. a defibrillator. however. or excessive tachycardia to reduce afterload and preload and relieve . The ACC/AHA doesn't recommend the prophylactic use of antiarrhythmic drugs durin g the first 24 hours intravenous nitroglycerin for 24 to 48 hours in patients without hypotension. such as streptok inase or anistreplase percutaneous transluminal coronary angioplasty (PTCA) may be an alternative to t hrombolytic therapy if it can be performed in a timely manner in an institution with personnel skilled in the procedure limitation of physical activity for the first 12 hours to reduce cardiac workloa d. to inhibit platelet aggregation continuous cardiac monitoring to detect arrhythmias and ischemia intravenous thrombolytic therapy to patients with chest pain of at least 30 minu tes' duration who reach the hospital within 12 hours of the onset of symptoms (u nless contraindications exist) and whose ECG shows new left bundle branch block or ST-segment elevation of at least 1 to 2 mm in two or more ECG leads.

rubella. measles. human immunodeficiency virus. such as diphtheria. tetanus. and regular exercise to reduce cardiac risk. low-cholesterol diet. pneumococcal. but without hypotension or other contraindications. Causes Common causes of myocarditis include: viral infections (most common cause in the United States and western Europe). it can a lso determine functional capacity and stratify the patient's risk of a subsequen t cardiac event cardiac risk modification program of weight control. It may be acute or chronic and can occur at any age. rubeola. myocarditis is complicated by heart failure. smoking cessation. In many cases. typhoid fever. and adenoviruses and echoviruses bacterial infections. including acute rheumatic fever and post-cardio . thereby reducing myocardial oxygen requirement s angiotensin-converting enzyme inhibitors in patients with an evolving MI with ST -segment elevation or left bundle branch block. and gonococcal infections hypersensitive immune reactions.chest pain early intravenous beta blockers to patients with an evolving acute MI followed b y oral therapy. poliomyelitis. cytomegalovirus. to reduce heart rate and myocardial contractile force. E pstein-Barr virus. possibly. su ch as Coxsackie virus A and B strains and. in rare cases. tuberculosis. it leads to cardiomyopathy. and recovery is usually spontaneous without residual defects. to reduce afterload and preload and prevent remodeling if needed. Occas ionally. magnesium sulfate for 24 hours to correct hypomagnesemia angiography and possible percutaneous or surgical revascularization for patients with spontaneous or provoked myocardial ischemia following an acute MI exercise testing before discharge to determine adequacy of medical therapy and t o obtain baseline information for an appropriate exercise prescription. as long as there are no contraindications. a low-fat. mumps . myocarditis fails to produce specific cardiovascular symptoms or electrocardiogram (ECG) ab normalities. influenza. Myocarditis Myocarditis is focal or diffuse inflammation of the cardiac muscle (myocardium). and staphylococcal.

toxoplasmosis fungal infections. cocaine. dyspnea. chemicals. if papillary muscles involved pericardial friction rub. fibrosis. The heart muscle weakens and contractility is reduced. Signs and symptoms The following signs and symptoms may occur: nonspecific symptoms such as fatigue. cellular. The heart muscle beco mes flabby and dilated and pinpoint hemorrhages may develop. if pericarditis exists . Pathophysiology Damage to the myocardium occurs when an infectious organism triggers an autoimmu ne. especially South American trypanosomiasis (Chagas' disease ) in infants and immunosuppressed adults. continuous pressure or soreness in the chest (occasionally) related to inf lammation tachycardia due to a compensatory sympathetic response S3 and S4 gallops as a result of heart failure murmur of mitral insufficiency may be heard. and chronic alcoholism parasitic infections. palpitations. including candidiasis and aspergillosis helminthic infections such as trichinosis. The resulting inflammation may lead to hyper trophy. and fever caused by systemic infection mild. also.tomy syndrome radiation therapy st cancer large doses of radiation to the chest in treating lung or brea toxins such as lead. and inflammatory changes of the myocardium and conduction syst em. and humoral reaction.

edema. CK-MB. Also. inflammation and infe ction can cause elevated white blood cell count and erythrocyte sedimentation ra te. BLOCKING MYOCARDIAL INFARCTION This chart shows how treatments can be applied to myocardial infarction at vario us stages of its development. Complications Complications of myocarditis include: recurrence of myocarditis chronic valvulitis (when it results from rheumatic fever) dilated cardiomyopathy arrhythmias and sudden death heart failure pericarditis ruptured myocardial aneurysm thromboembolism. Diagnosis History reveals recent febrile upper respiratory infection. it may lead to right-sided and left-sided hear t failure. neck vein distention. dyspnea. and supraventricular and ventricular arrhythmias. as partate aminotransferase.if myofibril degeneration occurs. Laboratory testing may reveal elevated levels of creatine kinase (CK). with cardiomegaly. and lactate dehydrogenase. persistent fever with resting or exertional tachycardia disproportiona te to the degree of fever. pulmonary co ngestion. .

and ventricular extrasystoles. Chest X-rays may show an enlarged heart and pulmonary vascular congestion. A tempor ary pacemaker may be inserted if complete atrioventricular block occurs . Electrocardiography may reveal diffuse ST-segment and T-wave abnormalities. Laboratory cultures of stool. supraventricular arrhythmias. Endomyocardial biopsy may confirm diagnosis. such as antistreptolysin-O titer in rheumatic f ever. Echocardiography may demonstrate some degree of left ventricular dysfunction. sodium restriction and diuretics to decrease fluid retention. or complete heart bl ock). bundle branch block. Treatment Correction of myocarditis may involve: antibiotics to treat bacterial infections antipyretics to reduce fever and decrease stress on the heart bed rest to reduce oxygen demands and the workload on the heart restricted activity to minimize myocardial oxygen consumption. and other body fluids may identify bacteri al or viral causes of infection. such as quinidine or procainamide. throat. A negative biopsy does not exclude the diagnosis. Radionuclide scanning may identify inflammatory and necrotic changes characteris tic of myocarditis. to treat arrhythmias. Administer digoxin cautiously because some patients may show a paradoxical sensitivity even to small doses antiarrhythmic drugs.Antibody titers may be elevated. supplemental oxyg en therapy. angiot ensin-converting enzyme inhibitors. cond uction defects (prolonged PR interval. u se cautiously because these drugs may depress myocardial contractility. and digoxin to increase myocardial contracti lity for patients with heart failure.

PDA affects twice as many females as males and i s the most common acyanotic congenital heart defect found in adults. Oth erwise. which may be fatal. but over time it can precipitate pulmonary vascular disease. Patent ductus arteriosus The ductus arteriosus is a fetal blood vessel that connects the pulmonary artery to the descending aorta. probably as a result of abnormalities in oxygenation or the rel axant action of prostaglandin E. PDA may produce no clini cal effects. This creates a left-to-r ight shunt of blood from the aorta to the pulmonary artery and results in recirc ulation of arterial blood through the lungs.anticoagulation to prevent thromboembolism corticosteroids and immunosuppressants. causin g symptoms to appear by age 40. Pathophysiology . the lumen of the ductus remains open after birth. Normally. t he ductus closes within days to weeks after birth. Initially. may be used to c ombat life-threatening complications such as intractable heart failure nonsteroidal anti-inflammatory drugs are contraindicated during the acute phase (first 2 weeks) because they increase myocardial damage cardiac assist devices or transplantation as a last resort in severe cases resis tant to treatment. In patent ductus arteriosus ( PDA). although controversial. PDA may advance to intractable heart failure. which prevents ductal spasm and contracture nec essary for closure rubella syndrome coarctation of the aorta ventricular septal defect pulmonary and aortic stenosis living at high altitudes. The prognosis is good if the shunt is small or surgical repair is effective. Causes PDA is associated with: premature birth. just distal to the left subclavian artery.

a drop in diastolic blood pressure as blood is shunted through the PDA. Because of increased aortic pressure.The ductus arteriosus normally closes as prostaglandin levels from the placenta fall and oxygen levels rise. This causes the s hunt to reverse so that unoxygenated blood enters systemic circulation. Signs and symptoms The following signs and symptoms may occur: respiratory distress with signs of heart failure in infants. at the second left intercostal space under the left clavicle. oxygenated blood is shunted from the aor ta through the ductus arteriosus to the pulmonary artery. but may take as long as 3 months in some children. This process should begin as soon as the newborn ta kes its first breath. causing cyanosis. in a right-to-left shunt. due to the tremendous volume of blood shunted to the lungs thro ugh a patent ductus and the increased workload on the left side of the heart classic machinery murmur (Gibson murmur). The murmur may obscure S2. especially those wh o are premature. prima rily. the left-to-right shunt leads to chronic pu lmonary artery hypertension that becomes fixed and unreactive. relative resistances in pulmonary and systemic vasculature and the size of the ductus determine the quantity of blood that is shunted from left to right . th us reducing peripheral resistance slow motor development caused by heart failure failure to thrive as a result of heart failure . this mu rmur may be absent thrill palpated at the left sternal border caused by the shunting of blood from the aorta to the pulmonary artery prominent left ventricular impulse due to left ventricular hypertrophy bounding peripheral pulses (Corrigan's pulse) due to the high-flow state widened pulse pressure because of an elevated systolic blood pressure and. It is best hea rd at the base of the heart. In PDA. in turn increasing filling pressure and workload on the left side of the heart and causing left ventricular hypertrophy and possibly heart failure. a continuous murmur heard throughout s ystole and diastole in older children and adults due to shunting of blood from t he aorta to the pulmonary artery throughout systole and diastole. The left atrium and left ventricle must accommodate the increased pulmonary veno us return. I n the final stages of untreated PDA. However. The blood returns to t he left side of the heart and is pumped out to the aorta once more.

Treatment Correction of PDA may involve the following: surgery to ligate the ductus if medical management can't control heart failure. Echocardiography detects and estimates the size of a PDA. Increased pulmonary artery pressure indicates a large shunt or. Asymptomatic infants with PDA don't require immediate treatment. and enlargement of the left ventricle and aorta. surgical ligation of the PDA is usually delayed until age 1 indomethacin (a prostaglandin inhibitor) to induce ductus spasm and closure in p remature infants . Cardiac catheterization allows for the calculation of blood volume crossing the ductus. Electrocardiography may be normal or may indicate left atrial or ventricular hyp ertrophy and. severe pulmonary vascular disease. in pulmonary vascular disease. biventricular hypertrophy. and can rule out associated ca rdiac defects. If symptoms are mild. Cardiac catheterization shows higher pulmonary arterial oxygen content than righ t ventricular content because of the influx of aortic blood. or right ventricular hypertrophy from pulm onary vascular disease.fatigue and dyspnea on exertion may develop in adults with undetected PDA. Diagnosis The following tests help diagnose patent ductus arteriosus: Chest X-rays may show increased pulmonary vascular markings. if it exceeds systemic arterial pre ssure. Injection of contrast agent can conclusively demonstrate PDA. prominent pulmonary arteries. Complications Possible complications of PDA may include: infective endocarditis heart failure recurrent pneumonia. It also reveals an enl arged left atrium and left ventricle.

and digoxin other therapy. fungal. tr auma. to deposit a plug or umbrella in the ductus to stop shunting. or he morrhagic exudate. Acute pericarditis can be fibrinous or effusive. or other organs) high-dose radiation to the chest uremia hypersensitivity or autoimmune disease. or surgery (post-cardiotomy syndrome). serous. or viral infection (infectious pericarditis) neoplasms (primary. The prognosis depends on the underlying cause but is generally good in acute pericarditis. Chronic constrictive pericarditis is characterized by dense f ibrous pericardial thickening. breasts. with purulent. and protects the heart. including cardiac catheterization. It occurs in both acute and chronic form s.prophylactic antibiotics to protect against infective endocarditis treatment of heart failure with fluid restriction. or metastases from lungs. systemic lupus erythematosus. diuretics. supports. such as myocardial infarction (Dressler's syndrome). such as acute rheumatic fever (most comm on cause of pericarditis in children). that leaves the pericardium intact but causes blood to leak into the pericardial cavity drugs such as hydralazine or procainamide idiopathic factors (most common in acute pericarditis) aortic aneurysm with pericardial leakage (less common) . Causes Common causes of pericarditis include: bacterial. Pericarditis Pericarditis is an inflammation of the pericardium the fibroserous sac that enve lops. unless constriction occurs. and rheumat oid arthritis previous cardiac injury.

usually starting over the sternum and radiating to the neck (especially the left trapezius ridge). Vessel walls then leak fluids and protein (including fibrinogen) into tissues. and arms due to inflammation and irritation of the pericardial membranes. increasing with deep inspiration and decreasing when the patient sits up and leans forward. Pathophysiology Pericardial tissue damaged by bacteria or other substances results in the releas e of chemical mediators of inflammation (prostaglandins. Cardiac tamponade results when there is a rapid accumulation of fluid in the per icardial space. rapid respirations to reduce pleuritic pain mild fever caused by the inflammatory process dyspnea. A pericardial effusion develops if fluid accumulates in the pericardial cavity. Signs and symptoms The following signs and symptoms of pericarditis may occur: pericardial friction rub caused by the roughened pericardial membranes rubbing a gainst one another. causing extracellular edema. Histamines and other chemical mediators dilate vessels and increase vessel permeability. it's best heard wh en the patient leans forward and exhales sharp and often sudden pain. back. a major complication of acute pericarditis muffled and distant heart sounds due to the buildup of fluid . shallow. This causes an increase in both left. (See Cardiac tamponade. bradykinins . Friction occurs as the inflamed pericardial layers rub against each o ther. shoulders.myxedema with cholesterol deposits in the pericardium (less common). and resulting in a drop in cardiac output. histamines. and serotonin) into the surrounding tissue. the contents of the cavity autolyze and are gradually reabsorbed into healthy tissue. compressing the heart and preventing it from filling during dias tole. pulling the heart away from the diaphragmatic pleurae of the lungs. and tachycardia as well as other signs of heart failure may occur as fluid builds up in the pericardial space causing pericardial effusion. orthopnea. thereby initiating the inflammator y process. the area fills with an exudate composed of necr otic tissue and dead and dying bacteria. encasing the heart in a stiff shel l and preventing the heart from properly filling during diastole. After several days.and right-sided filling pressures. Eventuall y. ) Chronic constrictive pericarditis develops if the pericardium becomes thick and stiff from chronic or recurrent pericarditis. neutrophils. The pain is often ple uritic. and macrophages. leading to a drop in stroke volume and cardiac output. Macrophages already present in the ti ssue begin to phagocytize the invading bacteria and are joined by neutrophils an d monocytes. although rub may be heard intermittently.

occurs due to restricted right-sided filling. cardiovascular collapse may occur with the rapid fluid accumulation of cardiac tamponade fluid retention. pulsus paradoxus. and V6. neck vein distention and. hepatomegaly. may occur. Arrhythmias. Purified protein derivative skin test may be positive if pericarditis is due to tuberculosis.pallor. ev entually. hypotension. T-wave inversion or flattening. there may be low-voltage QRS comple xes. Antistreptolysin-O titers may be positive if pericarditis is due to rheumatic fe ver. QRS segments may be diminished when pericardial effus ion exists. and reduced pumping action of the heart. jugular venous distention. II . Echocardiography may show an echo-free space between the ventricular wall and th e pericardium. Upright T waves are present in most leads. In chronic constrictive pericarditis. such as atrial fibrillation and sinus arrhythmias. blood urea nitrogen may detect uremia as a cause of pericarditis. and other sig ns of chronic right-sided heart failure may occur with chronic constrictive peri carditis as the systemic venous pressure gradually rises pericardial knock in early diastole along the left sternal border produced by re stricted ventricular filling Kussmaul's sign. clammy skin. Blood cultures may identify an infectious cause. and P mitrale (wide P waves) in leads I. especially in infectious pericarditis. ascites. increased jugular venous distention on inspiration. . Laboratory testing may reveal an elevated erythrocyte sedimentation rate as a re sult of the inflammatory process or a normal or elevated white blood cell count. Diagnosis The following tests help diagnose pericarditis: Electrocardiography may reveal diffuse ST-segment elevation in the limb leads an d most precordial leads that reflects the inflammatory process.

to create a window that allo ws fluid to drain into the pleural space total pericardectomy may be necessary in constrictive pericarditis to permit ade quate filling and contraction of the heart pericardiocentesis to remove excess fluid from the pericardial space idiopathic pericarditis may be benign and self-limiting. particularly between puberty and age 40. The cardiac silhouette may b e enlarged with a water bottle shape caused by fluid accumulation. to reduce metabolic needs treatment of the underlying cause. antifungal. This condition occurs bilaterally and usua lly affects the hands or. Raynaud's disease is most preval ent in females. It is a benign conditio n. such as aspirin and indomethacin. systemic lupus erythematosus. corticosteroids must be administered cautiously because episode s may recur when therapy is discontinued antibacterial. however.Chest X-rays may be normal with acute pericarditis. or antiviral therapy if an infectious cause is suspec ted partial pericardectomy. and amputation. less often. leading to ischemia. Raynaud's phenomenon. Treatment Correcting pericarditis typically involves: bed rest as long as fever and pain persist. gangrene. for recurrent pericarditis. to relie ve pain and reduce inflammation corticosteroids if nonsteroidal anti-inflammatory drugs are ineffective and no i nfection exists. or polymyositis has a progressive course. the feet. requiring no specific treatment and causing no serious sequelae. a condition often associated with several connect ive disorders such as scleroderma. Raynaud's disease Raynaud's disease is one of several primary arteriospastic disorders characteriz ed by episodic vasospasm in the small peripheral arteries and arterioles. if it can be identified nonsteroidal anti-inflammatory drugs. precip itated by exposure to cold or stress. if pleural ef fusion is present. Distin .

the cause of this disorder is unknown. rheumatoid arthritis. or polymyositis pulmonary hypertension thoracic outlet syndrome arterioocclusive disease myxedema trauma serum sickness exposure to heavy metals previous damage from cold exposure long-term exposure to cold. Causes Although family history is a risk factor. systemic lupus erythematosus. including: intrinsic vascular wall hyperactivity to cold increased vasomotor tone due to sympathetic stimulation . several theories account for the reduced digital blood flow. vibrating machinery (such as operating a jackhammer) . Raynaud's phenomenon may develop secondary to: connective tissue disorders.guishing between the two disorders is difficult because some patients who experi ence mild symptoms of Raynaud's disease for several years may later develop over t connective tissue disease. Pathophysiology Although the cause is unknown. such as scleroderma. or pressure to the fingertips (such as occurs in typists and pianists). especially scleroderma.

ulcerations. or chronic paronychia may o ccur as a result of ischemia in longstanding disease. Treatment Treatment of this disorder typically involves: teaching the patient to avoid triggers such as cold. n ormal arterial pulses. necessitating am putation of one or more digits (although extremely rare). Doppler ultrasonography may show reduced blood flow if symptoms result from arte rial occlusive disease. absence of gangrene or. swelling. Antinuclear antibody (ANA) titer to identify autoimmune disease as an underlying cause of Raynaud's phenomenon. This is followed by cyanosis due to i ncreased oxygen extraction resulting from sluggish blood flow. mechanical.antigen-antibody immune response (the most likely theory because abnormal immuno logic test results accompany Raynaud's phenomenon). and patient history of symptoms for at least 2 years. the fingers turn red as blood rushes back into the arterioles cold and numbness may occur during the vasoconstrictive phase due to ischemia throbbing. Complications Cutaneous gangrene may occur as a result of prolonged ischemia. minimal cutaneous gangrene. further tests must be performed if ANA titer is positive. aching pain. Diagnosis The following tests help diagnose Raynaud's disease: Clinical criteria include skin color changes induced by cold or stress. bilatera l involvement. or chemical inj ury . Signs and symptoms The following signs and symptoms may occur: blanching of the fingers bilaterally after exposure to cold or stress as vasocon striction or vasospasm reduces blood flow. such as sclerodactyly. and tingling may occur during the hyperemic ph ase trophic changes. As the spasm reso lves. if present. Arteriography to rule out arterial occlusive disease.

Of patients who survive this complication. In the United States. 15 to 20 million new cases of rheumatic fever are reported each year. central nervous system. acute rheumatic fever develops aft er infection of the upper respiratory tract with group A beta-hemolytic streptoc occi. in lower socioeconomic groups. Rheumatic fever tends to run in families. Cardiac involvement develops in up to 50% of patients. altered host resistance must be involved in . per icarditis. and su bcutaneous tissues. it is most common in the North. the inci dence is highest in children between ages 5 and 15. It mainly involves the heart. Patients without carditis or with mild carditis have a good long-term prognosis. and endocarditis) during the early acute phase and chronic valvular d isease later. Rheumatic heart disease refers to the card iac manifestations of rheumatic fever and includes pancarditis (myocarditis. about 20% die within 10 years. approximately 15. For example. probably due to malnutrition and crowded living conditions.encouraging the patient to cease smoking and avoid decongestants and caffeine to reduce vasoconstriction keeping fingers and toes warm to reduce vasoconstriction calcium channel blockers. Pathophysiology Rheumatic fever appears to be a hypersensitivity reaction to a group A beta-hemo lytic streptococcal infection.000 people in the United States died of the disease c ompared with an estimated 5. lending support to the existence of ge netic predisposition. and nicardipine. Antibiotic therapy has greatly reduced the mortality of rheumatic heart disease.000 deaths in 1996. damp weather in the winter and earl y spring. Because very few persons (3%) with streptococcal infections contract rheumatic fever. Worldwide. which may improve bl ood flow to fingers or toes biofeedback and relaxation exercises to reduce stress and improve circulation sympathectomy to prevent ischemic ulcers by promoting vasodilation (necessary in less than 25% of patients) amputation if ischemia causes ulceration and gangrene. Severe pancarditis occasionally produces fatal heart failure during the acute p hase. such as nifedipine. joints. The disease strikes most often during cool. skin. diltiazem. such as phenoxybenzamine or reserpine. In 1950. and often recurs. Environmental factors also seem to be significant in the d evelopment of the disorder. Causes Rheumatic fever is caused by group A beta-hemolytic streptococcal pharyngitis. to pro duce vasodilation and prevent vasospasm adrenergic blockers. Rheumatic fever and rheumatic heart disease A systemic inflammatory disease of childhood.

and knees. Signs and symptoms The classic symptoms of rheumatic fever and rheumatic heart disease include: polyarthritis or migratory joint pain. brain. redness. The antigens of group A streptococci bind to rec eptors in the heart. Severe chorea causes purposeless. a deterioration i n handwriting. transient rash on the trunk or inne r aspects of the upper arms or thighs. the valve leaflets become scarred. especially the elbows. caused by inflammation. rarely. movable. Because of a similarity between the antigens of the streptococcus bacte ria and the antigens of the body's own cells. it occasionally affects th e tricuspid valve and. wrists. Myocarditis produces characteris tic lesions called Aschoff's bodies (fibrin deposits surrounded by necrosis) in the interstitial tissue of the heart. causing chronic valvular d isease. and synovial joints. wh ich most often affects the knees. or pericardium during the early acute phase. kn uckles. usually near tendons or bony prominences of joints. elbows. as well as cellular swelling and fragmenta tion of interstitial collagen. erosion along the lines of leaflet c losure. causing an autoimmune r esponse.its development or recurrence. about 3 mm to 2 cm in diamete r. platelet. or inability to concentrate. and hips erythema marginatum. Other signs and symptoms include: report of a streptococcal infection a few days to 6 weeks earlier. occurs in most pa tients. Carditis may affect the endocardium. ankles. and beg in to adhere to each other. that gives rise to red lesions with blanc hed centers subcutaneous nodules firm. Later. In both sexes. and blood. Eventually. They often accompany carditis and may last a few days to several weeks chorea rapid jerky movements may develop up to 6 months after the original strep tococcal infection. Swelling. Pericarditis produces a serofibrinous effusion. Endocarditis strikes the mitral valve most often in females and the aortic valve in males. and weakness. the heart valves may be damaged. no nrepetitive. poor muscle coordination. the pulmonic valve. Mild chorea may produce hyperirritability. and nontender. lose their elasticity. antibodies may attack healthy body cells by mistake. muscle. it occurs in 95% of those with rheumatic fever temperature of at least 100. myocardium. which form bead-like vegetatio n. and fibrin deposits. and signs of effusion usually accompany such pain. a nonpruritic. macular.4° F (38° C) due to infection and inflammation . These lesions lead to formation of progressively fibrotic nodules and interstitial scars. Endocarditis causes valve leaflet swelling. involuntary muscle spasms.

due to inflammation and irritation of the pericardi al membranes. Pain may increase with deep inspiration and decrease when the pati ent sits up and leans forward. JONES CRITERIA FOR DIAGNOSING RHEUMATIC FEVER The Jones criteria are used to standardize the diagnosis of rheumatic fever.a new mitral or aortic heart murmur or a worsening murmur in a person with a pre existing murmur pericardial friction rub caused by inflamed pericardial membranes rubbing agains t one another. pulling the heart away from the diaphragmatic ple urae of the lungs dyspnea. if pericarditis exists chest pain. Dia gnosis requires that the patient have either two major criteria. or one major cr iterion and two minor criteria. often pleuritic. MAJOR CRITERIA MINOR CRITERIA Carditis Migratory polyarthritis Sydenham's chorea Subcutaneous nodules Erythema marginatum Fever . plus evidence of a previous streptococcal infect ion. bibasilar crackles. nonproductive cough. tachypnea. and edema due to he art failure in severe rheumatic carditis.

are necessary for diagnosis. or one major criterion and t wo minor criteria. Diagnosis The following tests help diagnose rheumatic fever: Jones criteria revealing either two major criteria. plus evidence of a previous group A streptococcal infection. ) Laboratory testing may reveal an elevated white blood cell count and erythrocyte sedimentation rate during the acute phase.Arthralgia Elevated acute phase reactants Prolonged PR interval Complications Possible complications of rheumatic fever and rheumatic heart disease include: destruction of the mitral and aortic valves pancarditis (pericarditis. and endocarditis) heart failure. . especially during the acute phase. myocarditis. Hemoglobin and hematocrit may show slight anemia due to suppressed erythropoiesi s during inflammation. C-reactive protein may be positive. Antistreptolysin-O titer may be elevated in 95% of patients within 2 months of o nset. (See Jones Criteria for diagnosing rheumatic fever. Cardiac enzyme levels may be increased in severe carditis.

Throat cultures may continue to show the presence of group A beta-hemolytic stre ptococci. angiotensin-converting enzyme inhibitors. thickened va lve leaflets of the mitral valve). digoxin. or valve replacement (with a prosthetic valve) for severe mitral or ao rtic valvular dysfunction that causes persistent heart failure . and diuretics to treat heart failure corrective surgery. they usually occur in small numbers. but PR interval is prolonged in 20% of patients. o r heart failure. sodium restriction. erythromycin is given for patients with penicillin hypersensitivity salicylates to relieve fever and pain and minimize joint swelling corticosteroids if the patient has carditis or if salicylates fail to relieve pa in and inflammation strict bed rest for about 5 weeks for the patient with active carditis to reduce cardiac demands bed rest. Treatment Typically. treatment of these disorders involves: prompt treatment of all group A beta-hemolytic streptococcal pharyngitis with or al penicillin V or intramuscular benzathine penicillin G. pericardial effusion. and can me asure chamber size and provide information on ventricular function. Chest X-rays may show normal heart size or cardiomegaly. Echocardiography can detect valvular damage and pericardial effusion. Cardiac catheterization provides information on valvular damage and left ventric ular function. such as commissurotomy (separation of adherent. Electrocardiography may show changes that are not diagnostic. valvuloplasty (inflation of a balloon within a valve). however.

Even with treatment. organ dysfunction and failure. treatment usually continues for at le ast 5 years or until age 21. whichever is longer prophylactic antibiotics for dental work and other invasive or surgical procedur es to prevent endocarditis. Rickettsiae. fungi. Shock c an be classified into three major categories based on the precipitating factors: distributive (neurogenic. parasites. or mycobacteria. and hypovolem ic shock. (See Types of shock. protozoa. eventually. often accompanied by chronic illness. shock has a high mortality rate once the body's c ompensatory mechanisms fail. which begins after the acute phase subs ides with monthly intramuscular injections of penicillin G benzathine or daily d oses of oral penicillin V or sulfadiazine.secondary prevention of rheumatic fever. make these po . Causes of septic shock may include: gram-negative bacteria (most common cause) gram-positive bacteria viruses. and anaphylactic). septic. cardiogenic. AGE ALERT The immature immune system of newborns and infants and the weakened im mune system of older adults. Shock Shock is not a disease but rather a clinical syndrome leading to reduced perfusi on of tissues and organs and.) Causes Causes of neurogenic shock may include: spinal cord injury spinal anesthesia vasomotor center depression severe pain medications hypoglycemia. yeast.

.pulations more susceptible to septic shock. Causes of cardiogenic shock may include: myocardial infarction (most common cause) heart failure cardiomyopathy arrhythmias obstruction pericardial tamponade tension pneumothorax pulmonary embolism. Causes of anaphylactic shock may include: medications vaccines venom foods contrast media ABO-incompatible blood.

thromboxane A2. furthe r increasing capillary permeability. The consequences are vasodilation and vasoconstriction. leukotrienes. prostaglandins. In response. Endotoxins also stimulate the release of histamine. Cardiac output falls.Causes of hypovolemic shock may include: blood loss (most common cause) gastrointestinal fluid loss burns renal loss (diabetic ketoacidosis. diabetes insipidus. macrophages secrete tumor necrosis factor (TNF) and interleukins. TYPES OF SHOCK DISTRIBUTIVE SHOCK In this type of shock. in turn. and com plement. Septic shock. . PAF. A loss of sympathetic vasoconstrictor tone in the vascular smo oth muscle and reduced autonomic function lead to widespread arterial and venous vasodilation. Venous return is reduced as blood pools in the venous system. and an ele vated cardiac output. Neurogenic shock. kinins. TNF . T hese mediators. vasodilation causes a state of hypovolemia. and other factors depress myocardial function. are responsible for increase release of platelet-activa ting factor (PAF). reduced systemic vascular resistance. Moreover. lea ding to a drop in cardiac output and hypotension. resu lting in multisystem organ failure. adrenal insufficiency) fluid shifts ascites peritonitis hemothorax. increased capil lary permeability. An immune response is triggered when bacteria release endotoxins. microemboli. myocardial depressant factor.

the antigen binds to IgE antibodies or cross-linked IgE receptors. cardiac output falls and multisystem organ failure develops as the com pensatory mechanisms fail to maintain perfusion. Then.Anaphylactic shock. producing metabolic acidosis. veno us return to the heart is reduced. epinephrine and norepinephrine are secreted to increase peripheral re sistance. As the baroreceptors in the carotid sinus and aortic arch sense a drop in blood pressure. lactic acid builds up. cardiac output falls. the chemical mediators bradykinin and leukotrienes induce vascula r collapse by stimulating contraction of certain groups of smooth muscles and by increasing vascular permeability. and irreversible or refractory stages. leading to decreased peripheral resistance an d plasma leakage into the extravascular tissues. Reduced perfusion damages cell membranes. Signs and symptoms . At the same time. these mechanisms increase myocardial workload and oxygen consumption. and cause selective vasoconstriction. This stage of shock begins as compensatory mechanisms fail to maintain cardiac output. wh ich reduces the heart's ability to pump blood. circulatory and respiratory failure occur. promote sodium and water retention. lactic acid accumulates. This loss of intravascular fluid further contributes to hypotension. cardiac output and tiss ue perfusion are maintained. CARDIOGENIC SHOCK In cardiogenic shock. pro gressive. the left ventricle can't maintain an adequate cardiac outp ut. causing myocardial depression and a further reduction in cardiac output. As c ells switch to anaerobic metabolism. leading to increased blood volume and veno us return. Death is inevitable. leading to a drop in stroke volume. possibly leading to cell death. resulting in pulmonary edema. Triggered by an allergic reaction. As the shock syndrome progresses. This reduction in preload decreases ventricul ar filling. and myocardial contractility. Consequently. This acidotic state depresses myocardial function. and energy stores are depleted. Compensatory mechanisms increase heart rate. As a result of these compensatory mechanisms. thereby reducing blood volume a nd causing hypotension. strengthen myocardial contracti ons. increasing capillary permeability and t he movement of fluid out of the vascular space. Tissues become hypoxic because of poor perfusion. Progressive stage. IgG or I gM enters into the reaction and activates the release of complement factors. blood backs up. especially if the patient has myo cardial ischemia. permanent org an damage occurs as compensatory mechanisms can no longer maintain cardiac outpu t. As cells use anaero bic metabolism. Bronchospasm and laryngeal edema also occur. blood pressure. Tissue hypoxia also promotes the release of endothelial mediators. Reduced blood flow to th e kidney activates the renin-angiotensin-aldosterone system. leading to venous pooling and increased capillary perm eability. and cardiac dysfunction. Pathophysiology There are three basic stages common to each type of shock: the compensatory. Compensatory stage. triggering the release of powerful chemical mediators from mast cells. H owever. Perfusion to the coronary arteries is reduc ed. Sluggish blood flow increases the risk of disseminated intravascular c oagulation. anaphylactic shock occurs when a person is exposed to an antigen to which he has already been sensitized. O n reexposure. Eve ntually. Exposure results in the production of specific immunoglobulin E (IgE) antibodie s by plasma cells that bind to membrane receptors on mast cells and basophils. Ev entually. caus ing reduced perfusion of the tissues and organs. causing vasoconstri ction and sodium and water retention. hypovolemic shock. Irreversible (refractory) stage. When arterial pressure and tissue perfusion are reduced. HYPOVOLEMIC SHOCK When fluid is lost from the intravascular space through external losses or the s hift of fluid from the vessels to the interstitial or intracellular spaces. com pensatory mechanisms are activated to maintain perfusion to the heart and brain. lysosomal enzymes are released. which produce vasodilation and e ndothelial abnormalities.

and hyperventilation may be the only signs of septic shock in infants and the elderly. thready pulse caused by decreased cardiac output shallow respirations as the patient weakens reduced urinary output as poor renal perfusion continues cold. clammy skin caused by vasoconstriction cyanosis related to hypoxia.In the compensatory stage of shock. AGE ALERT Hypotension. warm. clinical findings may include: . In the progressive stage of shock. pale skin associated with vasoconstriction. signs and symptoms may include: tachycardia and bounding pulse due to sympathetic stimulation restlessness and irritability related to cerebral hypoxia tachypnea to compensate for hypoxia reduced urinary output secondary to vasoconstriction cool. altered level of consciousness. dry skin in septic shock due to vasodilation. signs and symptoms may include: hypotension as compensatory mechanisms begin to fail narrowed pulse pressure associated with reduced stroke volume weak. In the irreversible stage. rapid.

unconsciousness and absent reflexes caused by reduced cerebral perfusion. urine. . Coagulation studies may detect coagulopathy from DIC. and sputum cultures may identify the organism responsible for sept ic shock. Complications Possible complications of shock include: acute respiratory distress syndrome acute tubular necrosis disseminated intravascular coagulation (DIC) cerebral hypoxia death. Blood. shallow or Cheyne-Stokes respirations secondary to respiratory center depr ession anuria related to renal failure. Diagnosis The following tests help diagnose shock: Hematocrit may be reduced in hemorrhage or elevated in other types of shock due to hypovolemia. acid-b ase imbalance. or electrolyte abnormalities rapidly falling blood pressure as decompensation occurs weak pulse caused by reduced cardiac output slow.

respiratory acidosis in later stages associated with resp iratory depression. serum lactate may be increa sed secondary to anaerobic metabolism. and myocardial infarction. if possible maintaining a patent airway.Laboratory testing may reveal increased white blood cell count and erythrocyte s edimentation rate due to injury and inflammation. ischemic changes. and serum glucose may be elevated in earl y stages of shock as liver releases glycogen stores in response to sympathetic s timulation. Arterial blood gas analysis may reveal respiratory alkalosis in early shock asso ciated with tachypnea. elevated blood urea nitrogen a nd creatinine levels due to reduced renal perfusion. Chest X-rays may be normal in early stages. Cardiac enzymes and proteins may be elevated. which are used to guide fluid and drug management. preparing for intubation and mechanical ventilation if the patient develops respiratory distress supplemental oxygen to increase oxygenation . indicating myocardial infarction a s a cause of cardiogenic shock. Urine specific gravity may be high in response to effects of antidiuretic hormon e. Hemodynamic monitoring may reveal characteristic patterns of intracardiac pressu res and cardiac output. Echocardiography determines left ventricular function and reveals valvular abnor malities. Treatment Correction of shock typically involves the following measures: identification and treatment of the underlying cause.) Electrocardiography determines the heart rate and detects arrhythmias. pulmonary congestion may be seen in later stages. (See Putting hemodynamic monitoring to use. and metabolic acidosis in later stages secondary to anaerobi c metabolism.

as necessary. picture the cardiovascular syste m as a continuous loop with constantly changing pressure gradients that keep the blood moving. (To convert mm Hg to cm H20. initially. cardiac tamponade. Normal: 1 to 6 mm Hg (1. volume overload. to maintain intravascular volume. multiply m m Hg by 1. RIGHT ATRIAL PRESSURE (RAP). which may be applied to con trol both internal and external hemorrhage by direct pressure fluids such as normal saline or lactated Ringer's solution. To understand intracardiac pressures. pulmonary hypert ension.continuous cardiac monitoring to detect changes in heart rate and rhythm. as necessary initiating and maintaining at least two intravenous lines with large-gauge needl es for fluid and drug administration intravenous fluids. or right heart. reflects RV function. constrictive pericarditis. PUTTING HEMODYNAMIC MONITORING TO USE Hemodynamic monitoring provides information on intracardiac pressures and cardia c output. although controversial. admini stration of antiarrhythmics.34) Elevated value suggests: right ventricular (RV) failure. or RV infarction. tricus pid valve stenosis or regurgitation. RV enddiastolic pressure. crystalloids. function and end-diastolic pressu re. Low value suggests: reduced circulating blood volume.34 to 8 cm H2O). Additional therapy for hypovolemic shock may include: pneumatic antishock garment. OR CENTRAL VENOUS PRESSURE (CVP) The RAP reflects right atrial. or blood products. . colloids. which equals right atrial pressure. RIGHT VENTRICULAR PRESSURE (RVP) RV systolic pressure normally equals pulmonary artery systolic pressure. to restor e filling pressures packed red blood cells in hemorrhagic shock to restore blood loss and improve ox ygen-carrying capacity of the blood.

PULMONARY ARTERY PRESSURE Pulmonary artery systolic pressure reflects right ventricular function and pulmo nary circulation pressures. 15 to 25 mm Hg. 0 to 8 mm Hg. mean.Normal: systolic. diastolic. mitral stenosis or insufficiency. Pulmonary artery diastolic pressure (PADP) reflects left ventricular (LV) pressures. and patent ductus arteriosus. pulmonary disease. constrictive pericarditis. left atrium. PULMONARY CAPILLARY WEDGE PRESSURE (PCWP) PCWP reflects left atrial and LV pressures unless the patient has mitral stenosi s. LEFT ATRIAL PRESSURE This value reflects left ventricular end-diastolic pressure in patients without mitral valve disease. CARDIAC OUTPUT Cardiac output is the amount of blood ejected by the heart each minute. diastolic. . 10 to 20 mm Hg . 8 to 15 mm Hg. The heart momentarily relaxes during diastole as it fills with blood from the pulmonary veins. varies with a patient's weight. specifically left ventricular end-diastolic pre ssure. Elevated value suggests: LV failure. height. Elevated value suggests: LV failure. Low value suggests: hypovolemia. Normal: 4 to 8 liters. Adjusting the cardiac output to the patient's size yields a measurement ca lled the cardiac index. Normal: Systolic. 6 to 12 mm Hg. increased pulmonary blood flow (left or rig ht shunting. hy poxemia. and left ventricle to act as a si ngle chamber. atrial and ventricula r septal defects. Normal: mean pressure. Changes in PCWP reflect changes in LV filling pressure. Normal: 6 to 12 mm Hg. and peric ardial tamponade. this p ermits the pulmonary vasculature. and body surface area. as in atrial or ventricular septal defects). 15 to 25 mm Hg. Elevated value suggests: mitral stenosis or insufficiency. chronic heart failure. and in any condition c ausing increased pulmonary arteriolar resistance.

to improve perfusion and maintain blood pressure although still investigational. to incr ease contractility of the heart and increase cardiac output vasodilators. dobutamine. if patient has fluid volume overload intra-aortic balloon pump therapy to reduce the work of the left ventricle by de creasing systemic vascular resistance. which may be considered when other medical and surgical therapeutic measures fail. endotoxin. if either is the cause of cardiogenic shock ventricular assist device to assist the pumping action of the heart when intra-a ortic balloon pump and drug therapy fail cardiac transplantation. and epinephrine. resultin g in improved coronary artery perfusion thrombolytic therapy or coronary artery revascularization to restore coronary ar tery blood flow. to counteract mediators of septic shock.Additional measures for cardiogenic shock may include: inotropic drugs such as dopamine. monoclonal antibodies to tumor necrosis factor. given with a vasopressor t o reduce the workload of the left ventricle diuretics to reduce preload. amrinone. such as nitroglycerin or nitroprusside. if cardiogenic shock is due to acute myocardial infarction emergency surgery to repair papillary muscle rupture or ventricular septal defec t. dobutamine. Correction of septic shock may also include: antibiotic therapy to eradicate the causative organism inotropic and vasopressor drugs. Diastolic pressure is increased. and interleukin-1. such as dopamine. Additional therapy for neurogenic shock may include: . and norepinephrin e.

fainting. Rather than originating from the left ventricle. the aorta overrides bot h ventricles. with overriding of the VSD. sighing resp irations. infection. right ventricular outflow tract obstruction (pulmonary stenosis). seizures. unoxygenated venous blood returning to the right side of the heart may pass through the VSD to the left ventricle. It accounts for about 1 0% of all congenital defects and occurs equally in males and females. Milder forms of pulmonary stenosis result in a left-to-right shunt o r no shunt at all. or it may enter the pulmonary artery. straining. Right ventricular hypertrophy devel ops in response to the extra force needed to push blood into the stenotic pulmon ary artery. This cyanotic heart defect sometimes coexists with other congenital acyanotic heart defects. deep. or decreased systemic arterial resistance . cyanosis. is caused by a right-to-left shun t cyanotic or blue spells (Tet spells). reduced pulmonary blood flow. the hallmark of tetralogy of Fallot. The VSD usually lies in the outflow tract of the right ventricle and is generall y large enough to permit equalization of right and left ventricular pressures. and dextroposition of the aorta. Before sur gical advances made correction possible. the ratio of systemic vascular resistance to pulmonary stenosis affects the direction and magnitude of shunt flow across the VSD. It may result from reduced oxyg en to the brain because of increased right-to-left shunting. or fever. about one-third of these children died in infancy. bradycardia. right ventricular hypertrophy. possibly caused by spasm of the right ventricular outflow tract. H owever. increased systemic venous return. Tetralogy of Fallot Tetralogy of Fallot is a combination of four cardiac defects: ventricular septal defect (VSD).vasopressor drugs to raise blood pressure by vasoconstriction fluid replacement to maintain blood pressure and cardiac output. allowing unoxygena ted blood to mix with oxygenated blood and resulting in cyanosis. causing decreased syst emic arterial oxygen saturation. crying. Causes The cause of tetralogy of Fallot is unknown. Signs and symptoms The following signs and symptoms may occur: cyanosis. bypassing the lungs. and loss of consciousness following e xercise. characterized by dyspnea. It may be associated with: fetal alcohol syndrome thalidomide use during pregnancy. Blood shunts from right to left through the VSD. Pathophysiology In tetralogy of Fallot. s uch as patent ductus arteriosus or atrial septal defect. and hyp oplasia of the entire pulmonary vasculature. depending on the extent of the pulmonic st enosis. Severe obstruction of right ventricular outflow produces a right-to-left shunt.

and a b oot-shaped cardiac silhouette. premature birth. growth retardation. and eating difficulties in older children due to poor oxygenation squatting with shortness of breath to reduce venous return of unoxygenated blood from the legs and to increase systemic arterial resistance loud systolic murmur best heard along the left sternal border. diminished exercise tolerance. which may diminis h or obscure the pulmonic component of S2 continuous murmur of the ductus in a patient with a large patent ductus. . an enlarged right ventricle. which m ay obscure systolic murmur thrill at the left sternal border caused by abnormal blood flow through the hear t obvious right ventricular impulse and prominent inferior sternum associated with right ventricular hypertrophy.clubbing. Diagnosis The following tests help diagnose tetralogy of Fallot: Chest X-rays may demonstrate decreased pulmonary vascular marking (depending on the severity of the pulmonary obstruction). increasing dyspnea on exertion. and low-birth-weight infants born to women with tetralogy of Fallot. Complications Possible complications of tetralogy of Fallot include: pulmonary thrombosis venous thrombosis cerebral embolism infective endocarditis risk of spontaneous abortion.

. Laboratory testing reveals diminished oxygen saturation and polycythemia (hemato crit may be more than 60%) if the cyanosis is severe and longstanding. Treatment Tetralogy of Fallot may be managed by: a knee-chest position. predispos ing the patient to thrombosis. such as vent ricular septal defect (VSD). and pulmona ry stenosis. right axis deviation an d. and patent ductus arteriosus (PDA). Transposition accounts for about 5% of all congenital he art defects and often coexists with other congenital heart defects. Causes The cause of this disorder is unknown. and the overriding aorta and ruling out other cyanotic heart defects. VSD with pulmonary stenosis. the VSD. Cardiac catheterization confirms the diagnosis by providing visualization of pul monary stenosis. Echocardiography identifies septal overriding of the aorta.Electrocardiography shows right ventricular hypertrophy. which joins the subclavian artery to the pulmonary artery to enhance blood flow to the lungs to reduce hypo xia prophylactic antibiotics to prevent infective endocarditis or cerebral abscesses phlebotomy to reduce polycythemia corrective surgery to relieve pulmonary stenosis and close the VSD. the great arteries are reversed such t hat the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. This test also measures the degree of oxygen saturation in aorti c blood. It affects two to three times more mal es than females. The right-to-left shunting of blood leads to an increased risk of he art failure and anoxia. right atrial hypertrophy. directing le ft ventricular outflow to the aorta. and administration of oxygen and morphine to improve oxyg enation palliative surgery with a Blalock-Taussig procedure. Transposition of the great arteries In this cyanotic congenital heart defect. and detects the hypertrophied walls of the right ventricle. the VSD. possibly. producing two noncommunicating circulatory systems (pulmonic and systemic). atrial septal defect ( ASD).

resulting in slight mixing of unoxygenated systemic blood and oxygenated pulmonary blood. In infants with con current cardiac defects.Pathophysiology Transposition of the great arteries results from faulty embryonic development. when no other heart defects exist that allow mixing of systemic and pulm onary blood. greater mixing of blood occurs. and cardiomegaly within days to weeks due to heart failure loud S2 because the anteriorly transposed aorta is directly behind the sternum murmurs of ASD. In infants with isolated transposition. Diagnosis The following tests help diagnose transposition of the great arteries: Chest X-rays are normal in the first days after birth. hepatomegaly. Unoxygenated blood returning to the right side of the heart is carried to the systemic circulation by a transposed aorta. and clubbing due to reduced oxygena tion. or PDA diminished exercise tolerance. rig ht atrial and right ventricular enlargement characteristically cause the heart t o appear oblong. or PDA gallop rhythm. tachycardia. blood mixes only at the patent foramen ovale and at the patent ductus arteriosus. X-ray may also show increased pulmonary vascular markings. fatigability. Cyanosis may be minimized with associated defects such as ASD. Complications Transposition of the great arteries may be complicated by: heart failure infective endocarditis. VSD. Within days to weeks. VSD. exce pt when pulmonary stenosis exists. O xygenated blood returning to the left side of the heart is carried back to the l ungs by a transposed pulmonary artery. dyspnea. Signs and symptoms The following signs and symptoms may occur: cyanosis and tachypnea that worsens with crying within the first few hours after birth. Communication between the pulmonary and systemic circulations is necessary for s urvival. Electrocardiography typically reveals right axis deviation and right ventricular .

Valvular disorders in children and adolescents most commonly occur as a result of congenital heart defects. As . three types of mechanical disruption can occur: steno sis. rheumatic hea rt disease is a common cause. and records echoes from both semilunar valves simultaneously. (See Types of valvular heart disease. Valvular heart disease In valvular heart disease. right ventricular. or narrowing. Mitral regurgitation. Echocardiography demonstrates the reversed position of the aorta and pulmonary a rtery. It also detects other cardiac defects. Cardiac catheterization reveals decreased oxygen saturation in left ventricular blood and aortic blood.hypertrophy but may be normal in a neonate. left atrium. mitral annulus. Treatment Treatment of this disorder may involve: prostaglandin infusion to keep the ductus arteriosus patent until surgical corre ction atrial balloon septostomy (Rashkind procedure) during cardiac catheterization if needed as a palliative measure until surgery can be performed. increased right atrial. and right ventricular systolic pressure equal to syst emic pressure. or left ventricle can lead to m itral regurgitation. due to aort ic valve displacement. although the procedure depends on the physiolo gy of the defect. incomplete closure of the valve. and pulmonary artery oxygen saturation. whereas in adults. papillary muscles. enlarges the pat ent foramen ovale and thereby improves oxygenation and alleviates hypoxia by all owing greater mixing of blood from the pulmonary and systemic circulations digoxin and diuretics after atrial balloon septostomy to lessen heart failure un til the infant is ready to withstand corrective surgery (usually between birth a nd age 1) surgery to correct transposition. Arterial blood gas analysis indicates hypoxia and secondary metabolic acidosis. Blood from the left ventricle flows back into the left atri um during systole. ch ordae tendineae.) Pathophysiology Pathophysiology of valvular heart disease varies according to the valve and the disorder. Any abnormality of the mitral leaflets. causing the atrium to enlarge to accommodate the backflow. Dye injection reveals the transposed vessels and the presence of any other cardiac defects. of the valve opening. Causes The causes of valvular heart disease are varied and are different for each type of valve disorder. or pro lapse of the valve.

(See Types of valvular heart disease. a low-sodium diet. Great er resistance to blood flow causes pulmonary hypertension. diuretics. right ventricular hyp ertrophy. causing fluid overload in the ventricle. Mitral stenosis. Ventri cular hypertrophy and increased end-diastolic pressure result in increased pulmo nary artery pressure. and diminished cardiac output causes poor coronary artery perfusion. Aortic stenosis. Also. for specific clinical features of each valve d isorder. eventually leading to left-sided and right-sided heart fai lure. Aortic regurgitation. Narrowing of the valve by valvular abnormalities. the pulmonary system. Diagnosis The diagnosis of valvular heart disease can be made through cardiac catheterizat ion. (See Types of valvu lar heart disease. inadequate filling of the left ve ntricle produces low cardiac output.) Complications Possible complications of valvular heart disease include: heart failure pulmonary edema thromboembolism endocarditis. eventually resulting in right-sided heart failure. to increase oxygenation . and especially angiotensinconverting enzyme inhibitors to treat left ventricular failure oxygen in acute situations. ischemia of the left ventricle. Pulmonic stenosis. Obstructed right ventricular outflow causes right ventricular hypertrophy. Increased left ventricular pressure tries to overcome the resis tance of the narrowed valvular opening. and right-sided heart failure. vasodilators. Left-sided heart failure and pulmonary edema eventually result. C onsequently. The added workload increases the demand for oxygen. or calcification obstructs blood flow from the left atrium to the left ventricle. Blood flows back into the left ventricle during diastole.a result.) Treatment Correcting this disorder typically involves: digoxin. which dilates and hypertrophies. fibrosis. echocardiography. and left-sided heart failure. The ex cess volume causes fluid overload in the left atrium and. Signs and symptoms The clinical manifestations vary according to the type of valvular defects. or electrocardiography. left atrial volume and pressure rise and the chamber dilates. chest X-rays. finally. the left ventricle also dilates to accommodate the increased volume o f blood from the atrium and to compensate for diminishing cardiac output.

They can be primary. aortic. Primary varicose veins tend to be familial and to affect both legs. they are twi ce as common in females as in males. They account for approximately 90% of varic ose veins. tortuous veins. engorged with blood and resulting fr om improper venous valve function. originating in the super ficial veins. Surgery may remove varicose veins but the condition can occur in other veins.anticoagulants to prevent thrombus formation around diseased or replaced valves prophylactic antibiotics before and after surgery or dental care to prevent endo carditis nitroglycerin to relieve angina in conditions such as aortic stenosis beta-adrenergic blockers or digoxin to slow the ventricular rate in atrial fibri llation or atrial flutter cardioversion to convert atrial fibrillation to sinus rhythm open or closed commissurotomy to separate thick or adherent mitral valve leaflet s balloon valvuloplasty to enlarge the orifice of a stenotic mitral. s econdary varicose veins occur in one leg. Usually. Varicose veins Varicose veins are dilated. or pu lmonic valve annuloplasty or valvuloplasty to reconstruct or repair the valve in mitral regur gitation valve replacement with a prosthetic valve for mitral and aortic valve disease. Without treatment. occurring in the deep veins. Both types are more common in middle a dulthood. Although there is no cure . or secondary. varicose veins continue to enlarge. Causes Primary varicose veins can result from: congenital weakness of the valves or venous wall . certain measures such as walking and use of compression stockings can reduce s ymptoms. about 10% to 20% of Americans have primary varicose veins.

obesity.conditions that produce prolonged venous stasis or increased intra-abdominal pre ssure such as pregnancy. plasma is forced out of the veins and into the surrounding tissues. allowing even more blood to flow backwa rd. As the veins are stretched. their walls weaken and they lose their elasticity. it can become incompetent. resulting in edema. As hydrostatic pressure increases. pressure in the vein increases and the vein becomes distended. As the veins enlarge. Secondary varicose veins can result from: deep vein thrombosis venous malformation arteriovenous fistulas trauma to the venous system occlusion. or wearing tight clothes occupations that necessitate standing for an extended period of time family history of varicose veins. TYPES OF VALVULAR HEART DISEASE CAUSES AND INCIDENCE CLINICAL FEATURES DIAGNOSTIC MEASURES Mitral stenosis Results from rheumatic fever (most common cause) . or distends these valves allows the backflow of blood to the previous valve. distensible vessels with valves that keep blood flowing i n one direction. If a valve cannot hold the p ooling blood. constipation. Pathophysiology Veins are thin-walled. destroys. Any condition that weakens. they become lumpy and tortuous. As the volume of venous blood builds.

hypertrophic cardiomyopathy. severe left ventricular failure. and hepatomegaly (right vent ricular failure) Crackles. mitral valve prolapse . fatigue. enlarged pulmonary arteri es. atrial fibrillation. elevated right-sided heart pressure with decreased cardiac (CO). ascites. jugular vein distention. and abnormal contraction of the left ventricle Chest X-rays: left atrial and ventricular enlargement. right ventric ular hypertrophy. weakness. and right axis deviation Mitral insufficiency Results from rheumatic fever. and signs of systemic emboli Auscultation reveals a loud S1 or opening snap and a diastolic murmur at the ape x Cardiac atrial lmonary output catheterization: diastolic pressure gradient across valve. or ruptured chordae te ndineae Associated with other congenital anomalies such as transposition of the great ar . myocardial infarction. and palpitations Peripheral edema. paroxysmal nocturnal dyspnea. orthopnea. elevated left and pulmonary capillary wedge pressures (PCWP) > 15 mm Hg with severe pu hypertension. atrial fibrillation. and mitral valve calcification Echocardiography: thickened mitral valve leaflets and left atrial enlargement Electrocardiography: left atrial hypertrophy.Most common in females May be associated with other congenital anomalies Dyspnea on exertion.

teries Rare in children without other congenital anomalies Orthopnea. angina. crackles. and an S3 Cardiac catheterization: mitral regurgitation with increased left ventricular en d-diastolic volume and pressure. and atrial fibrillation Aortic insufficiency Results from rheumatic fever. or endocarditis. and hepatomegaly (right ventricular f ailure) Tachycardia. hypertension. a possible split S2. increased atrial pressure and PCWP. and palpitations Peripheral edema. syphilis. jugular vein distention. and decreas ed CO Chest X-rays: left atrial and ventricular enlargement and pulmonary venous conge stion Echocardiography: abnormal valve leaflet motion. or may be idiopathic Associated with Marfan syndrome Most common in males . and left atrial enlargement Electrocardiography: may show left atrial and ventricular hypertrophy. sinus tac hycardia. and pulmonary edema Auscultation reveals a holosystolic murmur at apex. fatigue. dyspnea.

palpitations. fatigue. angina. angina. paroxysmal nocturnal dyspnea. and . fatigue. and left a trial hypertrophy in severe disease Aortic stenosis Results from congenital aortic bicuspid valve (associated with coarctation of th e aorta). and mitral thickening Electrocardiography: sinus tachycardia.Associated with ventricular septal defect. other valvular abnormalities. rheumatic fever. and increased left ventricular end-diast olic pressure Chest X-rays: left ventricular enlargement and pulmonary venous congestion Echocardiography: left ventricular enlargement. syncope. congenital stenosis of valve cusps. alterations in mitral valve move ment (indirect indication of aortic valve disease). an d widened pulse pressure Auscultation reveals an S3 and a diastolic blowing murmur at left sternal border Palpation and visualization of apical impulse in chronic disease Cardiac catheterization: reduction in arterial diastolic pressures. and syncope Pulmonary congestion. aortic regur gitation. cough. and sign) pulsating nail beds (Quincke's Rapidly rising and collapsing pulses (pulsus biferiens). cardiac arrhythmias. left ventricular hypertrophy. even after surgical closure Dyspnea. left ventricular failure. or atherosclerosi s in the elderly Most common in males Dyspnea on exertion.

an S4 Cardiac catheterization: pressure gradient across valve (indicating obstruction) .palpitations Pulmonary congestion. possibly. and increased left ventricular end-diastolic pressures Chest X-rays: valvular calcification. possibly coe xistent with mitral valve stenosis Electrocardiography: left ventricular hypertrophy Pulmonic stenosis Results from congenital stenosis of valve cusp or rheumatic heart disease (infre quent) Associated with tetralogy of Fallot Asymptomatic or symptomatic with dyspnea on exertion. fatigue. ma y have pulsus alternans Auscuitation reveaIs systolic murmur heard at base or in carotids and. and pulmonar y vein congestion Echocardiography: thickened aortic valve and left ventricular wall. left ventricular enlargement. and cardiac arrhythmias. chest pain. and left ventricular failure Diminished carotid pulses. decreased cardiac output. and s yncope May cause jugular distention/right ventricular failure Auscultation reveals a systolic murmur at the left sternal border and a split S2 with a delayed or absent pulmonic component .

ulcers in the elderly caused by chronic venous i . and atrial fibrillation People who stand for prolonged periods of time may also develop venous pooling b ecause there is no muscular contraction in the legs forcing blood back up to the heart. purplish. which may be due to tissue breakdown aching during menses as a result of increased fluid retention. right axis deviatio n. AGE ALERT As a person ages. right atrial hypertrophy. tortuous. Complications Possible complications of varicose veins include: blood clots secondary to venous stasis venous stasis ulcers chronic venous insufficiency. particularly in the calves. If the valves in the veins are too weak to hold the pooling blood.Cardiac catheterization: increased right ventricular pressure. and abnormal valve orifice Electrocardiography: may show right ventricular hypertrophy. increasing susceptibility to varicose veins and chronic venous insufficiency. they begin to leak. Signs and symptoms The following signs and symptoms may occur: dilated. decreased pulmona ry artery pressure. veins dilate and stretch. allowing blood to flow backward. due to venous pooling edema of the calves and ankles due to deep vein incompetence leg heaviness that worsens in the evening and in warm weather. ropelike veins. caused by venous pooling dull aching in the legs after prolonged standing or walking. Because the skin is very fri able and can easily break down.

Venous outflow and reflux plethysmography detects deep venous occlusion. Ascending and descending venography demonstrates venous occlusion and patterns o f collateral flow. Diagnosis The following tests help diagnose varicose veins: Manual compression test detects a palpable impulse when the vein is firmly occlu ded at least 8 above the point of palpation. Photoplethysmography characterizes venous blood flow by noting changes in the sk in's circulation. treatment of the underlying cause. Doppler ultrasonography detects the presence or absence of venous backflow in de ep or superficial veins. Treatment Correction of this disorder typically involves: if possible. Trendelenburg's test (retrograde filling test) detects incompetent deep and supe rficial vein valves. this te st is invasive and not routinely used. indicating incompetent valves in the vein.nsufficiency may take longer to heal. such as an abdominal tumor or ob esity antiembolism stockings or elastic bandages to counteract swelling by supporting the veins and improving circulation a regular exercise program to promote muscular contraction to force blood throug h the veins and reduce venous pooling injection of a sclerosing agent into small to medium-sized varicosities surgical stripping and ligation of severe varicose veins .

but poor f or untreated defects. Pathophysiology In infants with VSD. in o . Elevate the legs above the heart whenever possible to promote venous return. Ventricular septal defect In a ventricular septal defect (VSD). the ventricular septum fails to close completely by the eig hth week of gestation. which are sometimes fatal in children by age 1.phlebectomy. Additional treatment measures include the following: Discourage the patient from wearing constrictive clothing that interferes with v enous return. to reduce increased intra-abdominal pressure. Instruct the patient to avoid prolonged standing or sitting because these action s enhance venous pooling. may be performed in an outpatient setting. removing the varicose vein through small incisions in the skin. Causes A VSD may be associated with the following conditions: fetal alcohol syndrome Down syndrome and other autosomal trisomies renal anomalies patent ductus arteriosus and coarctation of the aorta prematurity. The prognosis is goo d for defects that close spontaneously or are correctable surgically. VSDs are located in the membranous or muscular portion of the ventricular septum and vary in size. usually fr om secondary complications. an opening in the septum between the ventricles allows blood to shunt between the left and right ventricles. This results in ineffective pumping of t he heart and increases the risk for heart failure. Encourage the obese patient to lose weight. VSDs account for up to 30% of all congenital heart defects. Some defects close spontaneously. the most common acyanotic congenital heart disorder.

ther defects. between 4 and 8 weeks after birth. heart. Initially. Small VSDs are likely to close spontaneously. As the pulmonary vas culature gradually relaxes. When the heart is en larged. VSD isn't readily apparent at birth because right and left pressures are approxi mately equal and pulmonary artery resistance is elevated. so blood doesn't shunt through the defect. widely split pulmonic component of S2 caused by increased pressure gradien t across the VSD displacement of point of maximal impulse to the left due to hypertrophy of the h eart AGE ALERT Typically. in infants the apical impulse is palpated over the fourth i ntercostal space. mu rmur is widely transmitted palpable thrill caused by turbulent blood flow between the ventricles through a small VSD loud. prominent anterior chest secondary to cardiac hypertrophy liver. In children older than age 7. Later. biventricular heart failure and cyanosis ( from reversal of the shunt direction) occur. Signs and symptoms Signs and symptoms of a VSD may include: thin. harsh systolic murmur heard best along the left sternal border at the thir d or fourth intercostal space. allowing blood to shunt from the left to the right ventricl e. caused by abnormal blood flow through the VSD. large VSD shunts cause left atrial and left ventricular hypertroph y. cau sing cyanosis and clubbing of the nail beds. and spleen enlargement because of systemic congestion . Large VSDs should be surgically repaired before pulmonary vascular disease occurs or while it is still reversible. it's palpated over the fifth intercostal space. the apical beat is displaced to the left or downward. small infants who gain weight slowly when a large VSD is present secondary to heart failure loud. creating a single ventricle. right ventricular pressure decreases. Eventually. an uncorrected VSD causes right ventricular hypertrophy due to increas ing pulmonary resistance. Fixed pulmonary hypertension may oc cur much later in life with right-to-left shunting (Eisenmenger's syndrome). Alveoli are not yet co mpletely opened. just to the left of the midclavicular line. the septum is entirely absent.

feeding difficulties associated with heart failure diaphoresis. grunting respirations secondary to heart fa ilure cyanosis and clubbing if right-to-left shunting occurs later in life secondary t o pulmonary hypertension. tachycardia. Electrocardiography may be normal with small VSDs. whereas in large VSDs it may show left and right ventricular hypertrophy. the X-ray may show c ardiomegaly. . In large VSDs. and rapid. estimate the size of the left-toright shunt. Complications Complications of a VSD may include: pulmonary hypertension infective endocarditis pneumonia heart failure Eisenmenger's syndrome aortic regurgitation (if the aortic valve is involved). and prominent vascula r markings. left atrial and left ventricular enlargement. and identify associated lesions and complications. Diagnosis The following tests help diagnose ventricular septal defect: Chest X-rays appear normal in small defects. Echocardiography can detect VSD in the septum. suggestive of pulmonary hypertensio n. suggest pulmonary hypertension.

sodium restriction. They may not be surgically repa ired if the patient has normal pulmonary artery pressure and a small shunt pulmonary artery banding to normalize pressures and flow distal to the band and to prevent pulmonary vascular disease if the child has other defects and will be nefit from delaying surgery digoxin.Cardiac catheterization determines the size and exact location of the VSD and th e extent of pulmonary hypertension. it also detects associated defects. It calcu lates the degree of shunting by comparing the blood oxygen saturation in each ve ntricle. usually performed using a patch graft . correction of a VSD may involve: early surgical correction for a large VSD. The oxygen saturation of the right ventricle is greater than normal bec ause oxygenated blood is shunted from the left ventricle to the right. and diuretics before surgery to prevent heart failu re prophylactic antibiotics before and after surgery to prevent infective endocardi tis. Treatment Typically. which may be necessary after VSD repair if c omplete heart block develops from interference with the bundle of His during sur gery surgical closure of small defects using sutures. 7 RESPIRATORY SYSTEM Handbook of Pathophysiology 7 RESPIRATORY SYSTEM Pathophysiologic manifestations € Atelectasis € Bronchiectasis € Cyanosis € Hypoxemia Disorders € Adult respiratory distress syndrome . before heart failure and irreversible pulmonary vascular disease develop placement of a permanent pacemaker.

Foreign matter is then swept to the upper airway for expectoration by specialized fingerlike projections called cilia. The external component of respiration (ventilation or breathing) delivers inspir ed air to the lower respiratory tract and alveoli. the inspiratory muscles cease to contract. These structures are anatomic dead spaces and function only as passageways for moving air into and out of the lung. composed of the nose. exchanging oxygen for carbon dioxide at the tissue level. and the elastic recoil of the lungs and the chest wall causes them to contract again. and filtering inspired air. humidifying. To reach the capillary lumen. and larynx allows airflow The upper airway into the lungs. Distal to each terminal bronchiole is the acinus. each alveolus is suppli ed by many capillaries. alveolar ducts. pharynx. and alveolar sacs. A breakdow n in the epithelium of the lungs or the mucociliary system can cause the defense mechanisms to malfunction. and pollutants and irritants then enter and inflame the lungs. The lower airway also provides immunologic protection and initiates p ulmonary injury responses. The lower airway consists of the trachea. b ronchioles. T hese actions raise the pressure within the lungs to above atmospheric pressure. and carbon dioxide is expelled on exhalation (expiration). These final subdi visions of the bronchial tree make up the lobules the functional units of the lu ngs. The mucociliary system produces mucu s.€ Asbestosis € Asthma € Chronic bronchitis € Chronic obstructive pulmonary disease € Cor pulmonale € Emphysema € Idiopathic respiratory distress syndrome of the newborn € Pneumothorax € Pulmonary edema € Pulmonary hypertension € Respiratory failure € Sudden infant death syndrome The respiratory system's major function is gas exchange. which consists of respiratory bronch ioles. the lower airwa y protects the lungs with several defense mechanisms. This area is responsible for warming. mouth. mainstem bronchi. oxygen must cross the alve olar capillary membrane. moving air from the lungs to the atmosphere. and the alveoli are the chief units of gas exchange. Normal expiration is passive. trapping foreign particles. Contraction and relaxation of the respiratory muscles moves air into and out of the lungs. (See Structure of the lobule. Clearance mechanisms inclu de the cough reflex and mucociliary system. and terminal bronchioles. humidifying.) In addition to warming. The pulmonary alveoli promote gas exchange by diffusion the passage of gas molec . thereby protecting the lower airway from foreign matter. An adult lung contains an estimated 300 million alveoli. travels throughout the respiratory passages. in which air enters the body on inhalation (inspiration). secondary bronchi. and filterin g the air. The bronchioles and ducts function as conduits.

expressed as the / ratio. Chest wall compliance is affected by disorders causing thoracic deformity. where the partial pressure of carbon dioxide is lower. the arterial ox ygen content. Because circulation is continuous. or cerebrovascular accident) produces forceful inspiratory gasps alternat ing with weak expiration. muscle spasm. compliance. Respiration is also controlled neurologically by the lateral medulla oblongata o f the brain stem. A / mismatch can result from ventilation-perfusion dysfunction or altered lung mech anics. which occurs in adult respiratory distress syndrome. Impulses travel down the phrenic nerves to the diaphragm and t hen down the intercostal nerves to the intercostal muscles between the ribs. and resistance to airflow. Signals from the pneumotaxic center and afferent impul ses from the vagus nerve inhibit the apneustic center and turn off inspiration. and cardiac output. The lungs become stiff. Carbon dioxide is removed from the alveoli during exhalation. The amount of air reaching the lungs carrying oxygen depends on lung volume and capacity. and abdominal distention. STRUCTURE OF THE LOBULE Each lobule contains terminal bronchioles and the acinus. ventilation and perfusion at the alveolar level must match closely. This pattern does not occur if the vagi are intact. passes out of the blood an d is channeled away. The rate and depth of respiration are controlled similarly. The amount of oxygen available to cells depends on the concentration of hemoglobin (the pri ncipal carrier of oxygen) in the blood. When oxygenated arterial blood reaches tissue capillaries. Carbon dioxide produced during cellular respiration diffuses from tis sues to regional capillaries and is transported by the systemic venous circulati on. The diagrams below show what happens when the / ratio is normal and abnormal. Apneustic and pneumotaxic centers in the pons of the midbrain influence the patt ern of breathing. the regional blood flow. The alveolar capillary memb rane may also be affected.) The ratio of vent ilation to perfusion is called the / ratio. a byproduct of cellular metabolism. Th e apneustic center continually excites the medullary inspiratory center and thus facilitates inspiration. (See Understanding ventilation and perfusion. the oxygen diffuses from the blood into the cells because of an oxygen tension gradient. When carbon dioxide reaches the alveolar capillaries. carbon dioxide does not normally accumulate i n tissues. . In diffusion. tumor. oxygen passes to the blood. For effective gas exchange. Destruction of the lung's elastic fibers. Stimulation of the lower pontine apneustic center (by trauma. Changes in compliance can occur in either the lung or the chest wall. causing hypoxia. it diffuses into the a lveoli. The acinus consists of respiratory bronchioles and the alveolar sacs. decreases lung compliance. UNDERSTANDING VENTILATION AND PERFUSION Effective gas exchange depends on the relationship between ventilation and perfu sion. Circulating blood delivers oxygen to the cells of the body for metabolism and tr ansports metabolic wastes and carbon dioxide from the tissues back to the lungs. an d carbon dioxide.ules through respiratory membranes. making breathing difficult.

and hypoxemia. producing a partial or complete lung collapse. Information from peripheral chemoreceptors in the carotid and aortic bodies also responds to decreased PaO2 and decreased pH. PATHOPHYSIOLOGIC MANIFESTATIONS Pathophysiologic manifestations of respiratory disease may stem from atelectasis . and the p artial pressure of arterial oxygen (PaO2). If PaCO2 is high. € INADEQUATE VENTILATION (SHUNT) When the / ratio is low. if PaCO2 is low. ventilation is normal but alveolar perfusion is reduced or absen t (illustrated by the perfusion blockage). This phenomenon removes ce rtain regions of the lung from gas exchange. Atelectasis Atelectasis occurs when the alveolar sacs or entire lung segments expand incompl etely. the partial pressure of arterial carbon dioxide (PaCO2). pulmonary circulation is adequate. INADEQUATE VENTILATION AND PERFUSION (SILENT UNIT) The silent unit indicates an absence of ventilation and perfusion to the lung ar ea (illustrated by blockages in both perfusion and ventilation). secondary to bronchial or bronchiolar obstruction. unoxygenated blood from the venous system returns to the righ t ventricle through the pulmonary artery to the lungs. the respiratory rate decreases. allowing unoxygenated blood to pass unchanged through these regions and resulting in hypoxia. INADEQUATE PERFUSION (DEAD-SPACE VENTILATION) When the / ratio is high. A portion of the bloo d flowing through the pulmonary vessels does not become oxygenated. There are two major causes of collapse due to atelectasis: absorpti onal atelectasis. chemoreceptors respond to the hydrogen ion concentration of arteria l blood (pH). but oxygen is inadequate for n ormal diffusion (illustrated by the ventilation blockage). Atelectasis may be ch ronic or acute. € In addition. Either of these changes results in increased respiratory drive within minutes. and often occurs in patients undergoing upper abdominal or thora cic surgery. PaCO2 also helps regulate ventilation by impacting the pH of CSF. bronchiectasis. The arteries branch into the alveolar capillaries.NORMAL VENTILATION AND PERFUSION When the / ratio is matched. and compres . The silent unit may try to compensate for this / imbalance by delivering blood flow to better ventilated lung areas. This results from a perfusion defect. such as pulmonary embolism or a disorder that decreases cardiac output. cyanosis. Central chemoreceptors respond indire ctly to arterial blood by sensing changes in the pH of the cerebrospinal fluid ( CSF). carrying carbon dioxide. where gas exchange occurs. the respiratory rate increases.

It may also be confined to a single segment or lobe. decreased cardiac output. and can occur throughout the tracheobronchial tree. This disorder is usually b ilateral in nature and involves the basilar segments of the lower lobes. rib fractures. This may result from upper abdominal surgic al incisions. even if hemoglobin counts are a dequate or reduced. Conditions that result in cyanosis include decreased arteria l oxygenation (indicated by low PaO2). which prevents air from entering the alveoli distal to the obstruction. cyanosis may not be evident in the lip area or the nail beds. characterized by inflammation and leukocytic accumula tions. The most freque nt intrinsic cause is retained secretions or exudate forming mucous plugs. in which hemoglobin binds to carbon monoxide instead of to oxygen. It develops when 5 g of hemoglobin is desaturated. Increas ing surface tension of the alveolus due to reduced surfactant leads to collapse.) It results from conditions asso ciated with repeated damage to bronchial walls with abnormal mucociliary clearan ce. CULTURAL DIVERSITY In patients with black or dark complexions. Disor ders such as cystic fibrosis. Cyanosis is caused by desaturation with oxygen or reduced hemoglobin amounts. Cyanosis Cyanosis is a bluish discoloration of the skin and mucous membranes. tight chest dressings. and ob esity (which elevates the diaphragm and reduces tidal volume). can cause absorption atelectasis the air present in the alveoli is absorbed gradually into the bloodstream. An individual who is not cyanotic does not necessarily have adequate oxygenation . and s accular (cystic). and a cold environment. Th is may result from intrinsic or extrinsic bronchial obstruction. Extrinsic bronchial atelectasis usually results from occlusion caused by foreign bodies. Although asse ssment of these patients does not reveal cyanosis. and eventually the alveoli collapse. and scar tissue. (See Causes of bronchiectasis. Additional debris collects within and occludes the bronchi. which drives the air out and causes the lung to collapse. pleuritic chest pain.sion atelectasis. fusiform (varicose).) In patients with bronchiectasis. Compression atelectasis Compression atelectasis results from external compression. it is readily detectable by a visible blue tinge on the nail beds and the lips. or pneumonia increase the risk of absorption atelectasis. A better indicator in these individ uals is to assess the membranes of the oral mucosa (buccal mucous membranes) and of the conjunctivae of the eyes. which is best observed in the buccal mucous membranes an d the lips. These situations inhibit full lung expansion or make deep breathing painful. Central cyanosis indicates a decreased oxygen saturation of the hemogl obin in arterial blood. oxygenation is inadequate. chronic bronchitis. anxiety. FORMS OF BRONCHIECTASIS . In most pop ulations. (See Forms of bronchiectasis. Increasing pr essure from the retained secretions induces mucosal injury. thus resulting in th is disorder. sputum stagnates in the dilated bronchi and lea ds to secondary infection. It also occurs in carbon monoxide poisoning. Inadequate oxygenation of the tissues occurs in severe anemia. Bronchiectasis Bronchiectasis is marked by chronic abnormal dilation of the bronchi and destruc tion of the bronchial walls. Impaired production of surfactant can also cause absorption atelectasis. There are three forms of bronchiectasis: cylindrical. Peripheral cyanosis is a slowed blood circulation of the fingers and toes that is best visualized by examining the nail bed area. bronchogenic carcinoma. pulmonary or cardiac right-to-left shunts . which causes a breakdown of supporting tissue adjacent to the airways. resulting in in adequate hemoglobin concentration. Absorption atelectasis Bronchial occlusion.

Diagnosis of inadequate oxygenation may be confi rmed by analyzing arterial blood gases and obtaining PaO2 measurements. bronchioles are deformed. and dextrocardia) rare disorders such as immotile cilia syndrome. whereas hypo xia is a diminished oxygenation of tissues at the cellular level that may be cau . It is caused by respiratory alterations. Cyanosis as a presenting condition must be interpreted in relation to the patien t's underlying pathophysiology. the patient may still presen t with cyanosis. fusiform (or varicose). pneumonia. sinusitis.The three types of bronchiectasis are cylindrical. whereas in fusiform bronchiectasis. CAUSES OF BRONCHIECTASIS Bronchiectasis results from conditions associated with repeated damage to bronch ial walls and with abnormal mucociliary clearance. large bronchi become enlarged and balloonlike. congenital bronchiectasis. or influenza obstruction (from a foreign body. Others may appear cyanotic even though oxygenation is adequate as in polycythemi a. In saccular bronchiectasis. tumor. an abnormal increase in red blood cell count. In cylindrical bronchiectasis. or stenosis) with recurrent infection inhalation of corrosive gas or repeated aspiration of gastric juices congenital anomalies. such as bronchomalacia. evidenced by reduced PaO 2 of arterial blood gases. Such conditions include: cystic fibrosis immune disorders (agammaglobulinemia) recurrent bacterial respiratory tract infections that were inadequately treated (tuberculosis) complications of measles. pertussis. Because the hemoglobin count is increased and oxygenation occurs at a normal rate. bronchioles are usually symmetrically di lated. and Kar tagener's syndrome (bronchiectasis. leading to a breakdown in the supporting tissue adjacent to the airways. and s accular. Hypoxemia Hypoxemia is reduced oxygenation of the arterial blood.

and death can occur within 48 hours of onset if not promptly diagnosed and treated. If hypoxia occurs in the blood. A differential diagnosi s needs to rule out cardiogenic pulmonary edema. (See Major causes of hypoxemia. The physiologic mechanism for each cause of hypoxemia is variable. shock. such as nitrous oxide. hypov entilation.sed by conditions affecting other body systems that are unrelated to alterations of pulmonary functioning. and pulmonary right-to-left shunts. white lung. wet lung. which increase the likelihood that microemboli will develop anaphylaxis aspiration of gastric contents diffuse pneumonia. or ethchlorvynol idiosyncratic drug reaction to ampicillin or hydrochlorothiazide inhalation of noxious gases. aspirin. such as heroin. ARDS may follow direct or indirect inju ry to the lung. such as fat emboli. its diagnosis is difficult. it is termed hypoxemia. Adult respiratory distress syndrome Adult respiratory distress syndrome (ARDS) is a form of pulmonary edema that can quickly lead to acute respiratory failure. However. and multiple transfusions. diffusion abnormalities. pulmonary vasculitis. or Da Nang lung. stiff lung . sepsis. pulmonary contusions. Hypoxemia can be caused by decreased oxygen content (PO2) of inspired gas. abnormal / ratios. ammonia. Causes Common causes of ARDS include: injury to the lung from trauma (most common cause) such as airway contusion trauma-related factors. Also known as shock lung. Hypoxemia c an lead to tissue hypoxia.) DISORDERS Respiratory disorders can be acute or chronic. or chlorine . The following disorders include e xamples from each. Hypoxia can occur anywhere in the body. in addition to alterations of respiration. and diffu se pulmonary hemorrhage. especially viral pneumonia drug overdose. Low cardiac output or cyanide poisoning can result in hypoxia.

chronic obstructive pulmonary disease . MAJOR CAUSE CONTRIBUTING FACTORS Decrease in inspired oxygen High altitudes. or breathing in an enclosed sp ace Hypoventilation Respiratory center inappropriately stimulated (such as by oversedation. or neurologic damage). inhaling poorly oxygenated gases. overdosa ge.near drowning oxygen toxicity sepsis coronary artery bypass grafting hemodialysis leukemia acute miliary tuberculosis pancreatitis thrombotic thrombocytopenic purpura uremia venous air embolism. MAJOR CAUSES OF HYPOXEMIA The chart below lists the major causes of hypoxemia and contributing factors.

and the lungs are much less compliant. Hypoxia (usually unresponsive to increasing fraction of inspired oxygen [ FiO2]). blood cells. chronic bronchitis. and t he small airways causes the lungs to stiffen. which initiate the complement cascade. Platelets begin to aggregate and release substances. kinins. Damage can occur directly by aspiration of gast ric contents and inhalation of noxious gases or indirectly from chemical mediato rs released in response to systemic disease. The cytokines p romote cellular activation. . and histamine. bradykin in. alveoli and bronchioles fill with fluid or collapse. increasing interstitial osmot ic pressure and causing pulmonary edema. Tachycardia. The burden of ventilation and gas exchange shifts to uninv olved areas of the lung. chemotaxis. In ARDS. proteases. proteins. The activa ted neutrophils release several inflammatory mediators and platelet aggravating factors that damage the alveolar capillary membrane and increase capillary perme ability. and more fluid leak out. Ventilation of the alveoli is further decreased. gas exchange is impaired. crackles. Alveolar closing pressure then exceeds pulmonary pressures. Histamines and other inflammatory substances increase capillary permeability.Alveolar capillary diffusion abnormality Emphysema. Additional chemotactic factors released include endotoxins (such as those presen t in septic states). idiopathic respiratory distress syndrome of the newborn. Consequently. decreased pulmonary compliance. the patient exp eriences tachypnea. macro phages. This reduces the ability of alveolar cells to produce more surfactant. signs and symptoms may be undetectable. a ffecting the hydrostatic pressure gradient of the capillary. and lymphocytes to produce various cytokines. The activated cells produc e inflammatory mediators. Once initiated. tumor necrosis factor. and alveolar closure and collapse begin. A cascade of cellular and biochemical changes is triggered by the s pecific causative agent. The resul ting pulmonary edema and hemorrhage significantly reduce lung compliance and imp air alveolar ventilation. monocytes. including oxidants. growth factors. As capillary permeability increase s. intravascular coagula tion. such as serotonin. dyspnea. which is evident i n dependent lung areas and can be visualized as whitened areas on chest X-rays. and adhesion. and tachycardia. These cellular triggers result in increased vascular permeability to proteins. The fluid in the alveoli and decreased blood flow damage surfactant in the alveo li. thus impairing ventilation and red ucing oxygenation of the pulmonary capillary blood. and fibrinolysis. the alveolar spaces. this injury triggers neutrophils. or atelectasis Pathophysiology Injury in ARDS involves both the alveolar epithelium and the pulmonary capillary epithelium. Witho ut surfactant. or pneumonia Shunting Adult respiratory distress syndrome. or pulmonary edema Ventilation-perfusion ( / ) mismatch Asthma. In the early stages of ARDS. These substances infl ame and damage the alveolar membrane and later increase capillary permeability. conditions resulting in fibrosis. and pulmonary blood flow is shunted from right to left. such as results from insults of fluid overload or cardiac dysfunction in sepsis. greatly increases interstitial and alveolar edema. fluid accumulation in the lung interstitium. and cyanosis may occur. al lowing fluids to move into the interstitial space. and neuropeptides. dyspnea. and rhonchi develop. Elevated capillary pressure. which attract and activate neutrophils. and interleukin-1 (IL-1). The resulting injury reduces normal blood flow to the lungs.

and bradykinin (B). . Fluids then shift into the interstiti al space. serotonin (S). Carbon dioxide cont inues to cross easily and is lost with every exhalation. Hypoxemia leads to metabolic acidos is. decreased blood flow and fluids in the alveoli damage surfactant and impair the cell's ability to produce more. increasing capillary permeability. the patient develops increasing PaCO2. decreasing bicarbonate levels. Fibrosis progressively obliterates alveo li. Functional residual capacity decreases and shunting becomes more serious. LOOKING AT ADULT RESPIRATORY DISTRESS SYNDROME These diagrams show the process and progress of ARDS. At this stage. Inflammation leads to fibros is. the patient develops increasing tachypn ea. In phase 1 of this syndrome. resulting in pulmonary hypertension. Blood oxygen and carbon dioxide levels ar e low. The result of t hese changes is a / mismatch. Multisystem organ dysfunction syndrome (MODS) occurs as the cascade of mediators affects each system. i ncreasing interstitial osmotic pressure and causing pulmonary edema. suf ficient oxygen cannot cross the alveolar capillary membrane. pulmonary edema worsens and inflammation leads to fibrosis. decreasing pH and PaO2 .) The end result is respiratory failure. oxygenation is impaired. capillary permeability increases and proteins and fluids leak out. In phase 2. hypoxemia. injury reduces normal blood flow to the lungs. The alveoli then collapse. Plat elets aggregate and release histamine (H). the released substances inflame and damage the alveolar capillary me mbrane. neutrophils and inflammator y mediators cause generalized endothelial damage and increased capillary permeab ility throughout the body. Mediators released by neutrophils and macrophages also cause varying degrees of pulmonary vasoconstriction. Pulmonary edema worsens and hyaline membranes form. but carbon dioxide easily crosses the alveo lar capillary membrane and is expired.The work of breathing is increased. In phase 5. Systemically. In phase 4. respiratory bronchioles. In phase 6. (See Looking at adult res piratory distress syndrome. and the interstitium. and the patient may develop thick frothy sp utum and marked hypoxemia with increasing respiratory distress. and mental confusion. which further impedes gas exchange. Death may occur from the influe nce of both ARDS and MODS. As both oxygen and carb on dioxide levels in the blood decrease. Although the patient responds with an increased respiratory rate. and hypocapnia (low PaCO2). thus impa iring gas exchange. Gas exch ange is further impeded. In phase 3.

which occur as the result o f hypoxic brain cells motor dysfunction. which signals the heart's effort to deliver more oxygen to the cell s and vital organs respiratory acidosis. which are audible and result from fluid accumulation in th e lungs restlessness. Complications Possible complications of ARDS include: hypotension decreased urine output . which occurs as carbon dioxide accumulates in the blood an d oxygen levels decrease metabolic acidosis. apprehension. which occurs as hypoxia progresses tachycardia.Signs and symptoms The following signs and symptoms may occur: rapid. which eventually results from failure of compensatory mechan isms. and mental sluggishness. which occur hours to days after the initia l injury in response to decreasing oxygen levels in the blood increased rate of ventilation due to hypoxemia and its effects on the pneumotaxi c center intercostal and suprasternal retractions due to the increased effort required to expand the stiff lung crackles and rhonchi. shallow breathing and dyspnea.

the resulting blood pH reflects respiratory alkalosis. As ARDS worsens. Sputum analysis.metabolic acidosis respiratory acidosis MODS ventricular fibrillation ventricular standstill. Pulmonary artery mixed venous blood indicates hypoxemia. . in later stages. including Gram stain and culture and sensitivity. ABG v alues show respiratory acidosis evident by an increasing PaCO2 (over 45 mm Hg). despite increased supplemental oxygen. is the hallmark of ARD S. Diagnosis The following tests help diagnose ARDS: Arterial blood gas (ABG) analysis with the patient breathing room air initially reveals a reduced PaO2 (less than 60 mm Hg) and a decreased PaCO2 (less than 35 mm Hg). and a declining PaO2 despite oxygen therapy. Pulmonary artery catheterization identifies the cause of edema by measuring pulm onary capillary wedge pressure (PCWP of 12 mm Hg or less in ARDS). identifies ca usative organisms. lung fields with a ground-glass appearance and whiteouts of both lung fields (wit h irreversible hypoxemia) may be observed. Toxicology testing screens for drug ingestion. metabolic acidosis evident by a decreasing bicarbonate (HCO3 less than 22 mEq/L) . Serial chest X-rays in early stages show bilateral infiltrates. Blood cultures identify infectious organisms. Hypoxemia.

Serum amylase rules out pancreatitis. whic h may be given during mechanical ventilation to minimize restlessness. and improve oxygenation positive end-expiratory pressure (may be added to increase lung volume and open alveoli) pressure-controlled inverse ratio ventilation to reverse the conventional inspir ation-to-expiration ratio and minimize the risk of barotrauma (mechanical breath s are pressure-limited to prevent increased damage to the alveoli) permissive hypercapnia to limit peak inspiratory pressure (although carbon dioxi de removal is compromised. Treatment Therapy is focused on correcting the causes of ARDS and preventing progression o f hypoxemia and respiratory acidosis. to opt imize cellular membranes) sodium bicarbonate. narcotics. oxygen co nsumption. open airways. which may reverse severe metabolic acidosis intravenous fluid administration to maintain blood pressure by treating hypovole mia vasopressors to maintain blood pressure antimicrobial drugs to treat nonviral infections diuretics to reduce interstitial and pulmonary edema . and carbon dioxide production and to facilitate ventilation high-dose corticosteroids (may be given when ARDS is due to fatty emboli. or neuromuscular blockers such as vecuronium bromide. it may involve: mechanical ventilation and intubation to increase lung volume. treatment is not given for subsequent changes in bloo d hydrogen and oxygen concentration) sedatives.

and brake and clutch linings family members of asbestos workers who may be exposed to stray fibers from the w orker's clothing exposure to fibrous asbestos dust in deteriorating buildings or in waste piles f rom asbestos plants. Prolonged exposure to airborne particles causes ple ural plaques and tumors of the pleura and peritoneum. Raised hyaline pl aques may form in the parietal pleura.5 in size) travel down the airway and penetrate r espiratory bronchioles and alveolar walls. iron-rich proteinlike sheath in sputum or lung tissue.correction of electrolyte and acid-base imbalances to maintain cellular integrit y. and the pleura adjacent to the pericardium. Causes Common causes of this disorder include: prolonged inhalation of asbestos fibers. An asbestos worker who s mokes is 90 times more likely to develop lung cancer than a smoker who has never worked with asbestos. Mucus production and goblet cells are stimulated to protect the airway from the debris and aid in expectoration. fireproofing. particularly the sodium-potassium pump fluid restriction to prevent increase of interstitial and alveolar edema. asbestosis is characterized by diffuse inte rstitial pulmonary fibrosis. Asbestosis Considered a form of pneumoconiosis. construction. affecting lung parenchyma and the pleurae. The foreign material and inflammation swell airways. Fibers then become encased in a brown . and textile industries asbestos used in paints. milling. called asbestosis bodie s. the diaphragm. Coughing attempts to expel the foreig n matter. and fibrosis dev elops in response to the chronic irritation. plastics. Interstitial fibrosis may develop i n lower lung zones. Asbestosis may develop 15 to 20 years after regular exposure to asbestos has ended. Chronic irritation by the fibers continues to affect the lower bronchioles an d alveoli. The inhal ed asbestos fibers (about 50 × 0. Hypoxia develops as more alveoli and lower airways are affecte d. It is a potent co-carc inogen and increases the smoker's risk for lung cancer. people at high risk include workers in the mining. Pathophysiology Asbestosis occurs when lung spaces become filled with asbestos fibers. Signs and symptoms The following signs and symptoms may occur: dyspnea on exertion dyspnea at rest with extensive fibrosis .

severe. Complications Possible complications of asbestosis include: pulmonary fibrosis due to progression of asbestosis respiratory failure pulmonary hypertension . nonproductive cough in nonsmokers productive cough in smokers clubbed fingers due to chronic hypoxia chest pain (often pleuritic) due to pleural irritation recurrent respiratory tract infections as pulmonary defense mechanisms begin to fail pleural friction rub due to fibrosis crackles on auscultation attributed to air moving through thickened sputum decreased lung inflation due to lung stiffness recurrent pleural effusions due to fibrosis decreased forced expiratory volume due to diminished alveoli decreased vital capacity due to fibrotic changes.

Arterial blood gas analysis may reveal decreased PaO2 and PaCO2 from hyperventil ation. The goal of treatment is to relieve symptoms and cont rol complications. decreased or normal forced expiratory vo lume in 1 second (FEV1). or FEV1 to FVC. and reduced diffusing c apacity for carbon monoxide when fibrosis destroys alveolar walls and thickens t he alveolar capillary membrane. Chest X-rays m ay also show pleural thickening and calcification. it may involve: chest physiotherapy (such as controlled coughing and postural drainage with ches t percussion and vibration) to help relieve respiratory signs and symptoms and m anage hypoxia and cor pulmonale aerosol therapy to liquefy mucus inhaled mucolytics to liquefy and mobilize secretions increased fluid intake to 3 L daily antibiotics to treat respiratory tract infections oxygen administration to relieve hypoxia diuretics to decrease inflammation and edema . and total lung capacity. an enlarged heart with a classic shagg y border. Diagnosis Chest X-rays may show fine. irregular. Extensiv e fibrosis is revealed by a honeycomb or ground-glass appearance. forced vital c apacity (FVC). linear.cor pulmonale. and diffuse infiltrates. a normal ratio. Treatment Asbestosis can't be cured. in later stages. Pulmonary function studies may identify decreased vital capacity. bilateral obliteration of the costophrenic angles and.

such as eczema and allergic rhinitis. Intrinsic. acid anhydrides. other types of COPD i nclude chronic bronchitis and emphysema. and mucosal edema. ex ternal substances cannot be implicated in patients with intrinsic asthma. a long-term pulmon ary disease characterized by increased airflow resistance. One-third of pati ents develops asthma between ages 10 and 30. have both intrinsic and extrinsic asthma.digoxin to enhance cardiac output salt restriction to prevent fluid retention and thickened secretions. especially children. nonallergenic factors. toluene di-isocyanates. asthmatics react to internal. CULTURAL DIVERSITY A significant number of adults acquire an allergic form of as thma or exacerbation of existing asthma from exposure to agents in the workplace . many asthmatics. asthma begins in childhood. Extrinsi c. increased mucus secretion. It is a type of chronic obstructive pulmonary disease (COPD). However. AGE ALERT Extrinsic asthma is commonly accompanied by other hereditary allergies . or atopic. typically. about 50% of patients are younger than age 1 0. Moreover. Asthma may result from sensitivity to extrinsic or intrinsic allergens. and excreta of dust mites in carpet have been identif ied as agents that trigger asthma. screw flies. in childhood populations. and the incidence is the same in bo th sexes in this age group. twice as many boys as girls are affected in this age group. especially in adults. Most e pisodes occur after a severe respiratory tract infection. Irritants such as chemicals in flour. Causes Extrinsic allergens include: pollen animal dander house dust or mold kapok or feather pillows . river flies. or nonatopic. Although asthma strikes at any age. Asthma Asthma is a chronic reactive airway disorder causing episodic airway obstruction that results from bronchospasms. approximately one-third of all patients sh are the disease with at least one immediate family member. patients are sensitive to s pecific external allergens.

A locus of chromosome 11 associated with atopy contains an abnormal gene that encodes a part of the immunoglobulin E (IgE) receptor.) IgE antibodies. the IgE antibody combines with the antigen. attached to histamine-containing mast cells and receptors on cell membranes. causing episodic smoo th muscle spasms that severely constrict the airways. (See Pathophysiology of as thma. namely the ability of a n individual to develop asthma (atopy) and the tendency to develop hyperresponsi veness of the airways independent of atopy. When exposed to an antige n such as pollen. Environmental factors interact with inherited factors to cause asthmatic reactions with associated bronchospasms. initiate intrinsic asthma attacks. Intrinsic allergens include: irritants emotional stress fatigue endocrine changes temperature variations humidity variations exposure to noxious fumes anxiety coughing or laughing genetic factors (see below). bronchial linings overreact to various stimuli. On subsequent exposure to the antigen. In asthma. Pathophysiology There are two genetic influences identified with asthma.food additives containing sulfites other sensitizing substances. mast cells degranulate and release mediat .

These ill ustrations show the progression of an asthma attack.ors. On exhalation. Air enters but cannot escape. Mucous membranes become inflamed. where they enhance his tamine's effects. on exhalation. and increased respiratory distress. and an increased respiratory rate. Slow-reacting substance of anaphylaxis (SRS-A) attaches to receptor sites in the smaller bronchi and causes swelling of smooth muscle there. where they enh ance the effect of histamine. Histamine stimulates the mucou s membranes to secrete excessive mucus. SRS-A also causes prostaglandins to travel via the bloodstream to the lungs. however. prolonged expiration. PATHOPHYSIOLOGY OF ASTHMA In asthma. The patient devel ops a barrel chest and hyperresonance to percussion. Mast cells in the lung interstitium are stimulated to release both histamin e and the slow-reacting substance of anaphylaxis. Histamine stimulates the mucous membranes to secrete excessive mucus. causing swelling of the smooth muscles. The slow-reacting substance of anaphylaxis (SRS-A) attaches to receptor sites in the smaller bronchi and causes local swelling of the smooth muscle.) On inhalation. the narrowed bronchial lumen can sti ll expand slightly. rhonchi. increased intrathoracic pressure closes the bronchial lumen completely. resulting in co ughing. M ucosal edema and thickened secretions further block the airways. the narrower is the bronchial lumen. irritated. A wheeze may be audible during coughing. allowing air to reach the alveoli. further na rrowing the bronchial lumen. inhibiting alveolar ventilation. Mucus fills lung bases. (See Looking at a bronchiole in asthma. inhibiting alveolar ventilation. Blood is shunted to alveoli in other lung parts. the narrowed bronchial lumen can still expand slightly. SRS-A also causes p rostaglandins to travel via the bloodstream to the lungs. the highe r the pitch. hyperresponsiveness of the airways and bronchospasms occur. increased-pitch wheezing. G oblet cells secrete viscous mucus that is difficult to cough up. further narrowing the bronchial lumen. On inhalation. where it causes swelling in smooth muscles. and swollen. The patient may experience d yspnea. but still can't compensate for diminished ventilat ion. Mucus fills the lung bases. Blood is shunted to alv . Histamine (H) attaches to receptor sites in larger bronchi. the increased intrathoracic pressure closes the bronchial lumen completely. Histamine attaches to receptor sites in the larger bronchi.

and mucosal edema. If status asthmaticus occurs. the patient begins to tire out. Shown below is a n ormal bronchiole in cross section and an obstructed bronchiole. more alveoli are affe cted. Ventilation and perfusion remain inadequate. they may have the following signs and symptoms: wheezing due to edema of the airways coughing due to stimulation of the cough reflex to eliminate the lungs of excess mucus and irritants histamine-induced production of thick. which contribute to airway narrowing and obstruction. Intrapleural and alveolar gas pressures rise. clear. and CO2 retention develops. (See Averting an asthma attack. whic h in turn decreases PaCO2 and increases pH. Patients with moderate asthma have normal or below normal air exchange and may e xhibit: respiratory distress at rest due to narrowed airways and decreased oxygenation t o the tissues . and decreased perfusion result in uneven / ratios and mismatching within different lung segments. increased mucus secretion. or yellow mucus dyspnea on exertion due to narrowing of airways and inability to take in the inc reased oxygen that is required for exercise. Increased alveolar gas pressure. If treatment is not initiated. Hyperventilation is triggered by lung receptors to increase lung volume because of trapped air and obstructions. Hypoxia triggers hyperventilation by stimulation of the respiratory center. The situation becomes life-threatening as no air becomes audible u pon auscultation (a silent chest) and PaCO2 rises to over 70 mm Hg. resulting in a respiratory alkalosis . As the obstruction to the airways increases in severity. R espiratory acidosis results and respiratory failure occurs. but it still can't compensate for diminished v entilation. hypoxia worsens and expiratory flows and volumes d ecrease even further. LOOKING AT A BRONCHIOLE IN ASTHMA Asthma is characterized by bronchospasms. as it occurs in asthma.eoli in other parts of the lungs. c ausing a decreased perfusion of alveoli. Signs and symptoms Patients with mild asthma have adequate air exchange and are asymptomatic betwee n attacks. decrea sed ventilation.) Acidosis develops as arterial carbon dioxi de increases.

Diagnosis The following tests help diagnose asthma: Pulmonary function studies reveal signs of airway obstructive disease. AVERTING AN ASTHMA ATTACK The following flow chart shows pathophysiologic changes that occur with asthma. Complications Possible complications include: status asthmaticus respiratory failure.hyperpnea (abnormal increase in the depth and rate of respiration) due to the bo dy's attempt to take in more oxygen barrel chest due to air trapping and retention diminished breath sounds due to air trapping. Patients with severe asthma have continuous signs and symptoms that include: marked respiratory distress due to failure of compensatory mechanisms and decrea sed oxygenation levels marked wheezing due to increased edema and increased mucus in the lower airways absent breath sounds due to severe bronchoconstriction and edema pulsus paradoxus greater than 10 mm Hg chest wall contractions due to use of accessory muscles. low-norma l or decreased vital capacity. and increased total lung and residual capacities. Treatments and interventions show where the physiologic cascade would be altered to stop an asthma attack. PaO2 and PaCO2 usually are de . Pulmonary function may be normal between attacks.

except in severe asthma. Bronchial challenge testing evaluates the clinical significance of allergens ide ntified by skin testing. me taproterenol. Serum IgE levels may increase from an allergic reaction. indicat ing severe bronchial obstruction. by identifying and avoiding precipitating factors such as environmen tal allergens or irritants. and after 4 or 5 days reveal a late reaction. Electrocardiography shows sinus tachycardia during an attack. Skin testing may identify specific allergens. and eosinophils. albuterol. Sputum analysis may indicate presence of Curschmann's spirals (casts of airways) . decreased. results read in 1 or 2 days detect an early reaction. Treatment Correcting asthma typically involves: prevention. Arterial blood gas analysis detects hypoxemia (decreased PaO2. normal . and terbutaline) to decrease bronchoconstriction. aminophylline.creased. severe attack may show signs of cor pulmonale (right axis deviation. epinephrine. reduce bronchial airway edema. or increasing PaCO2) and guides treatment. when PaCO2 may be normal or increased. and increase pulmonary ventilation . Complete blood count with differential reveals increased eosinophil count. which is the best treatment desensitization to specific antigens helpful if the stimuli can't be removed ent irely which decreases the severity of attacks of asthma with future exposure bronchodilators (such as theophylline. peaked P wave) that resolve a fter the attack. Charcot-Leyden crystals. Chest X-rays can be used to diagnose or monitor the progress of asthma and may s how hyperinflation with areas of atelectasis.

and increase pulmonary ventilati on subcutaneous epinephrine to counteract the effects of mediators of an asthma att ack mast cell stabilizers (cromolyn sodium and nedocromil sodium). In chronic bronchitis. the airways accumulate debris in the respirato ry tract. which may be needed to treat dyspnea. or develops respiratory failure relaxation exercises such as yoga to help increase circulation and to help a pat ient recover from an asthma attack. the amount delivered should maintain PaO2 between 65 and 85 mm Hg. The distinguishing characteristic of bronchitis is obstructi on of airflow. irritants inflame the tracheobronchial tree over time. and is also related to occupational factors (mineral or organic dusts).corticosteroids (such as hydrocortisone and methylprednisolone) to decrease bron choconstriction. le ading to increased mucus production and a narrowed or blocked airway. As the inf lammation continues. Chronic bronchitis Chronic bronchitis is inflammation of the bronchi caused by irritants or infecti on. Because the natura l defense mechanisms are blocked. effective in pati ents with atopic asthma who have seasonal disease. Shown below is a cross section of these changes. However. thereby preventing the release of chemical mediators responsible for anaphylaxis low-flow humidified oxygen. goblet and epithelial cells hypertrophy. A form of chronic obstructive pulmonary disease (COPD). reduce bronchial airway edema. they block the acute obstructive effects of antigen exposure by inhibiting the d egranulation of mast cells. cyanosis. CHANGES IN CHRONIC BRONCHITIS In chronic bronchitis. hypersecretion of mucus and chronic productive cough last for 3 months of the year and occur for at least 2 consecutive years. and hypoxemia. as determined by arterial blood gas analysis mechanical ventilation necessary if the patient doesn't respond to initial venti latory support and drugs. CULTURAL DIVERSITY COPD is more prevalent in an urban versus rural environment. bronchitis may be cl assified as acute or chronic. . When given prophylactically.

Additional effects include widespread inflammation. Initially. and the effects of smooth muscle bronchospa sm further narrow the lumen. Causes Common causes of chronic bronchitis include: exposure to irritants cigarette smoking genetic predisposition exposure to organic or inorganic dusts exposure to noxious gases respiratory tract infection. only large bronchi are involved but even tually. which normally sweep dust. Airways become obstructed and closure occurs. Hypoxemia and hypercapnia occur secondary to hypoventilation. Increased PVR leads to inc reased afterload of the right ventricle. sc . which decreases arterial oxygenation. The i rritants inflame the tracheobronchial tree. (Se e Changes in chronic bronchitis. ciliary damage. airway narrowing. Pathophysiology Chronic bronchitis occurs when irritants are inhaled for a prolonged time. and mucus away from the airways. With repeated inflammatory episodes. Pulmonary vascular resistance (PVR) increases as inflammatory and compensatory vasoconstriction in hypoventilated areas narrows the pulmonary arteries. leading to a / mismatch and resultant hypoxemia. the defense s are altered. especially on expiration. and mucus within the airways.AGE ALERT Children of parents who smoke are at higher risk for respiratory tract infection that can lead to chronic bronchitis. The gas is then trapped in the distal portion of the l ung. leading to increased mucus productio n and a narrowed or blocked airway. and the individual is prone to respiratory tract infections. Hypoventilation occurs. and chronic leukocytic and lymphocytic infiltration of bronchial walls. Bronchial walls become inflamed and thickened from edema and accumulation of inflammatory cells.) Hypersecretion of the goblet cells blocks the free movement of the cilia. As the inflammation continues. changes in th e cells lining the respiratory tract result in resistance of the small airways a nd severe / imbalance. squamous metaplasia of the columnar epithel ium. all airways are affected. Chronic bronchitis results in hypertrophy. inc reased goblet cells. irritants. With mucus and debris accumulating in the airway. hyperplasia of the mucous glands.

Signs and symptoms The following signs and symptoms may occur: copious gray. Although hemog lobin levels are high. or yellow sputum due to hypersecretion of goblet cells productive cough to expectorate mucus that is produced by the lungs dyspnea due to obstruction of airflow to the lower tracheobronchial tree cyanosis related to diminished oxygenation and cellular hypoxia. white.arring of the airways occurs and permanent structural changes develop. Respirato ry infections can trigger acute exacerbations. therefore. the amount of reduced (not fully oxygenated) hemoglobin t hat is in contact with oxygen is low. reduced oxygen is supplied to the tissues use of accessory muscles for breathing due to compensated attempts to supply the cells with increased oxygen tachypnea due to hypoxia pedal edema due to right-sided heart failure neck vein distention due to right-sided heart failure weight gain due to edema wheezing due to air moving through narrowed respiratory passages prolonged expiratory time due to the body's attempt to keep airways patent rhonchi due to air moving through narrow. and respiratory failure can occur . The result ing chronic hypoxia causes the kidneys to produce erythropoietin. which stimulat es excessive red blood cell production and leads to polycythemia. cyanosis occurs. Patients with chronic bronchitis have a diminished respiratory drive. mucus-filled passages .

Treatment Correcting chronic bronchitis typically involves: avoidance of air pollutants (most effective) . III . and aVF. right ventricular hypertrophy. Arterial blood gas analysis reveals decreased PaO2 and normal or increased PaCO2 . Electrocardiography may show atrial arrhythmias. resulting in increased venous pressure. decreased vital c apacity and forced expiratory flow. due to inflammation in the bronchial walls and spasms of pulmonary blood vessels from hypoxia. liver engorgement. Complications Possible complications of this disorder include: cor pulmonale (right ventricular hypertrophy with right-sided heart failure) due to increased right ventricular end-diastolic pressure pulmonary hypertension heart failure. and occasionally. Pulmonary function studies indicate increased residual volume. and de pendent edema acute respiratory failure. peaked P waves in leads II. Diagnosis The following tests help diagnose chronic bronchitis: Chest X-rays may show hyperinflation and increased bronchovascular markings. Sputum analysis may reveal many microorganisms and neutrophils.pulmonary hypertension caused by involvement of small pulmonary arteries. and normal static compliance and diffusing c apacity.

Causes Common causes of COPD may include: cigarette smoking recurrent or chronic respiratory tract infections air pollution . Usually. more than one of these underlying condition s coexist.smoking cessation antibiotics to treat recurring infections bronchodilators to relieve bronchospasms and facilitate mucociliary clearance adequate hydration to liquefy secretions chest physiotherapy to mobilize secretions ultrasonic or mechanical nebulizers to loosen and mobilize secretions corticosteroids to combat inflammation diuretics to reduce edema oxygen to treat hypoxia. (See Asthma. bronchitis and emphysema often occur together. Chronic bron chitis. Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD). results from emphysema. the incidence is rising. The disease is not always symptomatic and may cause only minimal disability. and Emphysema for a review of these conditions.) COPD is the most common lung disease and affects an estimated 17 million America ns. However. COPD worsens with time. or a comb ination of these disorders. chronic bronchitis. asthma. also called chronic obstructive lu ng disease (COLD).

Complications Possible complications of COPD include: overwhelming disability cor pulmonale .) Signs and symptoms The following signs and symptoms may occur: reduced ability to perform exercises or do strenuous work due to diminished pulm onary reserve productive cough due to stimulation of the reflex by mucus dyspnea on minimal exertion frequent respiratory tract infections intermittent or continuous hypoxemia grossly abnormal pulmonary function studies thoracic deformities. allowing air to pass beyond the obstruction. The mucus plugs and narrowed airways cause air trapping. airways enlarge. (See Air trapping in chron ic obstructive pulmonary disease. increased mucus production. des truction of alveolar septa. Hyperinflation occurs to the alveoli on expiration. Pathophysiology Smoking. and peribronchiolar fibrosis. as in chronic bronchiti s and emphysema.allergies familial and hereditary factors such as deficiency of alpha1-antitrypsin. On inspirat ion. Early inflammatory cha nges may reverse if the patient stops smoking before lung disease becomes extens ive. airways narrow and gas flow is prevented. Air trapping (also called ball valvi ng) occurs commonly in asthma and chronic bronchitis. one of the major causes of COPD. on expiration . impairs ciliary action and macrophage function and causes inflammation in the airways.

Electrocardiography may show arrhythmias consistent with hypoxemia. the airways enlarge and gas enters.severe respiratory failure death. During inspiration. mucus plugs and narrowed airways trap air (also called ball valving). on expiration. This commonly oc curs in asthma and chronic bronchitis. Diagnosis The following tests help diagnose COPD: Arterial blood gas analysis determines oxygen need by indicating degree of hypox ia and helps avoid carbon dioxide narcosis. Treatment Managing COPD typically involves: bronchodilators to alleviate bronchospasms and enhance mucociliary clearance of secretions effective coughing to remove secretions postural drainage to help mobilize secretions chest physiotherapy to mobilize secretions low oxygen concentrations as needed (high flow rates of O2 can lead to narcosis) . Pulmonary function studies support diagnosis of underlying condition. Chest X-rays support underlying diagnosis. AIR TRAPPING IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE In chronic obstructive pulmonary disease. the airways narrow and air can't escape.

upper airway obstruction. The disorder is most common in smokers and in middle-aged and e lderly males. Because cor pulmonale occurs late in the course of the individual's underlying condition and with oth er irreversible diseases. which may be helpful increased fluid intake to thin mucus use of a humidifier to thin secretions. h emosiderosis. n euromuscular diseases that affect respiratory muscles. AGE ALERT In children. however. cor pulmonale may be a complication of cystic fibrosis. scleroderma. Cor pulmonale Cor pulmonale (also called right ventricular failure) is a condition in which hy pertrophy and dilation of the right ventricle develop secondary to disease affec ting the structure or function of the lungs or their vasculature. It can occur a t the end stage of various chronic disorders of the lungs. and about 25% of patients with bronchial COPD eventually develo p cor pulmonale. Causes Common causes of cor pulmonale include: disorders that affect the pulmonary parenchyma . the prognosis is poor. pulmonary vessels. its incidence in females is rising. CULTURAL DIVERSITY Cor pulmonale is more prevalent in countries where the incide nce of obstructive lung disease is high. such as in the United Kingdom. extensive bronchiectasis. Cor pulmonale doesn't occur with disor ders stemming from congenital heart disease or with those affecting the left sid e of the heart.antibiotics to allow treatment of respiratory tract infections pneumococcal vaccination and annual influenza vaccinations as important preventi ve measures smoking cessation installation in the home of an air conditioner with an air filter and avoidance of allergens. or abnormalities of the r espiratory control area. and respiratory control center. About 85% of patients with cor pulmonale also have chronic obstructive pulmonary disease (COPD). ch est wall.

COPD bronchial asthma primary pulmonary hypertension vasculitis pulmonary emboli external vascular obstruction resulting from a tumor or aneurysm kyphoscoliosis pectus excavatum (funnel chest) muscular dystrophy poliomyelitis obesity high altitude. To comp ensate. pulmonary hypertension increases the heart's workload. Severity of right ventricular enlargement in cor pulmonale is due to increased a fterload. As l ong as the heart can compensate for the increased pulmonary vascular resistance.) In chronic obstructive disease. The blood's viscosity increases. causing heart fail ure. This increases the right ventricle's workload. In response to hypoxia. Pulmonary hypertension results from the increased blood flow needed to oxy genate the tissues. signs and symptoms reflect only the underlying disorder. the right ventricle hypertrophies to force blood through the lungs. which further aggravates pulmonary hypertension. An occluded vessel impairs the heart's ability to generate enough pres sure. increased airway obstruction makes airflow worse . (See Cor pulmonale: An overview. causing p olycythemia. the bone marrow produces more red blood cells. Pathophysiology In cor pulmonale.

causing ventricular dilation. Signs and symptoms Patients in early stages of cor pulmonale may present with: chronic productive cough to clear secretions from the lungs exertional dyspnea due to hypoxia wheezing respirations as airways narrow fatigue and weakness due to hypoxemia. an d heart failure occurs. pulmonary hypertension increases. Peripheral edema can occur and right ventricular hypertrophy increases progress ively. obstruct ive disorders (such as bronchitis). The main pulmonary arteries enlarge. Hepatojugular reflux may occur. Patients with progressive cor pulmonale may present with: dyspnea at rest due to hypoxemia tachypnea due to response to decreased oxygenation to the tissues orthopnea due to pulmonary edema dependent edema due to right-sided heart failure distended neck veins due to pulmonary hypertension . hypoxia increases pulmonary vasoconstriction. COR PULMONALE: AN OVERVIEW Although pulmonary restrictive disorders (such as fibrosis or obesity). The liver b ecomes palpable and tender because it is engorged and displaced downward by the low diaphragm. or primary vascular disorders (such as recur rent pulmonary emboli) may cause cor pulmonale. these disorders share the follow ing common pathway. However. Increasing intrathoracic pressures impede venous return and raise jugular venous pressure.. Compensatory mechanisms begin to fail and larger amounts of blood remain in the right ventricle at the end of diastole. The resulting hypoxia and hypercarbia can have vasodilatory effects on systemi c arterioles.

Diagnosis The following tests help diagnose cor pulmonale: . Complications Possible complications of cor pulmonale include: biventricular failure as the heart hypertrophies in an attempt to circulate the blood hepatomegaly edema ascites pleural effusions thromboembolism due to polycythemia.enlarged. tender liver related to polycythemia and decreased cardiac output hepatojugular reflux (distention of the jugular vein induced by pressing over th e liver) due to right-sided heart failure right upper quadrant discomfort due to liver involvement tachycardia due to decreased cardiac output and increasing hypoxia weakened pulses due to decreased cardiac output decreased cardiac output pansystolic murmur at the lower left sternal border with tricuspid insufficiency . which increases in intensity when the patient inhales.

Electrocardiography shows arrhythmias. and pulmonary artery diastolic pressure is higher than 15 mm Hg. Angiography shows right ventricular enlargement. Echocardiography demonstrates right ventricular enlargement. Laboratory testing may reveal hematocrit typically over 50%. Magnetic resonance imaging measures right ventricular mass. prominent P waves. Pulmonary function studies reflect underlying pulmonary disease. such as premature atrial and ventricular contractions and atrial fibrillation during severe hypoxia. resulting from increased pulmonary vascular resistance. and also right bundl e branch block.Pulmonary artery catheterization shows increased right ventricular and pulmonary artery pressures. wall thickness. and an inverted T wave in right precordial leads. and serum bilirubin levels may be elevate d if liver dysfunction and hepatomegaly exist. and ejection fraction. increasing exercise tolerance. Treatment may involve: bed rest to reduce myocardial oxygen demands . Arterial blood gas analysis detects decreased PaO2 (usually less than 70 mm Hg a nd rarely more than 90 mm Hg). and correcting the underlying conditi on when possible. serum hepatic tests may show an elevated level of aspartate aminotransferase levels with hepatic co ngestion and decreased liver function. Cardiac catheterization measures pulmonary vascular pressures. right axis deviation. Both right ventricular systolic and pulmonary artery systolic pressures are over 30 m m Hg. Treatment Therapy of cor pulmonale has three aims: reducing hypoxemia and pulmonary vasoco nstriction. Chest X-rays reveal large central pulmonary arteries and right ventricular enlar gement.

Ob struction results from tissue changes rather than mucus production. polycythemia. The distinguishing characteristic of emphys ema is airflow limitation caused by lack of elastic recoil in the lungs. stretching occurs without destruction in the smooth muscle. such as diazoxide. which occurs with asthma and chronic bronchitis. Connective tissue is not usually affected. a form of chronic obstructive pulmonary disease. and tachypnea mechanical ventilation to reduce the workload of breathing in the acute disease a low-sodium diet with restricted fluid to reduce edema phlebotomy to decrease excess red blood cell mass that occurs with polycythemia small doses of heparin to decrease the risk of thromboembolism tracheotomy. nitroprusside. Emphysema appears to be more prevalent in males than females. or hydr alazine. per manent enlargement of the acini accompanied by destruction of alveolar walls. about 65% of patie nts with well-defined emphysema are men and 35% are women. is the abnormal. AGE ALERT Aging is a risk factor for emphysema. Emphysema Emphysema.digoxin to increase the strength of contraction of the myocardium antibiotics to treat an underlying respiratory tract infection a potent pulmonary artery vasodilator. which may be required if the patient has an upper airway obstructio n corticosteroids to treat vasculitis or an underlying autoimmune disorder. Causes Emphysema is usually caused by: . to reduce primary pulmonary hypertension continuous administration of low concentrations of oxygen to decrease pulmonary hypertension. Senile emphysema results from de generative changes.

if the individual smokes. the air moves into and out of the lungs to meet metabolic n eeds. trapping air in the lungs and causing overdistention. creating large air spaces. Septa l destruction also decreases airway calibration. Homozygous individuals have up to an 80% chance of developing lung disease. The lungs are usually enlarged. The damaged or destroyed alveolar w alls cannot support the airways to keep them open.) The alveolar septa are initially destroyed. the total lung capaci ty and residual volume increase. . Shown below are changes that occur during emphysema. This causes irreversible enlargement of the air spac es distal to the terminal bronchioles. A change in airway size compromises the ability of the lungs to circulate sufficient air. deficiency of this enzyme is an autosomal recessive trait that predisposes an individual to develop emphysema be cause proteolysis in lung tissues is not inhibited. Associated pulmonary capillary destruction usually allows a patient with severe emphysema to match ventilation to perfusion. recurrent pulmonary inflammation damages and even tually destroys the alveolar walls. In emphysema. therefore. and the total lung capacity and resid ual volume then increase. (See Air trapping in emphysem a. A LOOK AT ABNORMAL ALVEOLI In the patient with emphysema. In normal breathing.deficiency of alpha1-antitrypsin cigarette smoking. AGE ALERT Panacinar emphysema tends to occur in the elderly with alpha1-antitryp sin deficiency. he has a greater chance of developing emphysema. and so bronchioles collapse on expirat ion. whereas centriacinar emphysema occurs in smokers with chronic br onchitis. recurrent inflammation is associated with the release of proteolyt ic enzymes from lung cells. which results in a breakdown of elasticity and loss of fibrous and muscle tissue. the lungs become enlarged. with damage more random and involving the lower lobes of t he lungs. thus trapping air in the lungs and leading to overdistention. Th is breakdown leaves the alveoli unable to recoil normally after expanding and re sults in bronchiolar collapse on expiration. recurrent pulmonary inflammation dam ages and eventually destroys the alveolar walls. leaving alve olar sacs intact (centriacinar emphysema). Patients who develop emphysema before or during their early forties and those who are nonsmokers are believed to have a deficiency of alpha1-antitrypsin. Alpha1-antitrypsin inhibits the activation of several proteolytic enzymes. a major component of alpha1-globulin. Enlargement of air spaces destroys the al veolar walls. elimin ating a portion of the capillary bed and increasing air volume in the acinus. thus making the lungs less compliant. Septal destruct ion may affect only the respiratory bronchioles and alveolar ducts. Pathophysiology Primary emphysema has been linked to an inherited deficiency of the enzyme alpha 1-antitrypsin. creating large air spaces.) The amount of air that can be expired passively is diminished. or it can involve the entire acinus ( panacinar emphysema). This process prevents the developme nt of cyanosis. In patients with emphysema. As the alveolar walls are destroyed. Hyperinflation of the alveoli p roduces bullae (air spaces) and air spaces adjacent to the pleura (blebs). (See A look at abnormal alveoli. Part of each inspiration is tra pped due to increased residual volume and decreased calibration. The damaged alveo li can't recoil normally after expanding.

Complications Possible complications of emphysema include: right ventricular hypertrophy (cor pulmonale) respiratory failure .Signs and symptoms The following signs and symptoms may occur: tachypnea related to decreased oxygenation dyspnea on exertion. which is often the initial symptom barrel-shaped chest due to the lungs overdistending and overinflating prolonged expiration and grunting. which occur because the accessory muscles are used for inspiration and abdominal muscles are used for expiration decreased breath sounds due to air-trapping in the alveoli and destruction of al veoli clubbed fingers and toes related to chronic hypoxic changes decreased tactile fremitus on palpation as air moves through poorly functional a lveoli decreased chest expansion due to hypoventilation hyperresonance on chest percussion due to overinflated air spaces crackles and wheezing on inspiration as bronchioles collapse.

overaeration of the lungs. Col lapse then occurs on expiration. a vertical heart. vertical QRS axis and signs of right ventricular hypertrophy are seen late in the disease. such as beta-adrenergic blockers and albuterol and ipratropium bromide. Diagnosis Chest X-rays in advanced disease may show a flattened diaphragm. and increased inspiratory flow.recurrent respiratory tract infections. to reverse bronchospasms and promote mucociliary clearance antibiotics to treat respiratory tract infections . and aVF . they can't support and keep the ai rways open. The alveolar walls then lose their capability of elastic recoil. Pulmonary function studies indicate increased residual volume and total lung cap acity. Arterial blood gas analysis usually reveals reduced PaO2 and a normal PaCO2 unti l late in the disease process. reduced vascula r markings at the lung periphery. e nlarged anteroposterior chest diameter. symmetrical P waves in leads II. AIR TRAPPING IN EMPHYSEMA Once alveolar walls are damaged or destroyed. reduced diffusing capacity. as shown below. and large retrosternal air space. Electrocardiography may show tall. Treatment Correcting this disorder typically involves: avoiding smoking to preserve remaining alveoli avoiding air pollution to preserve remaining alveoli bronchodilators. Complete blood count usually reveals an increased hemoglobin level late in the d isease when the patient has persistent severe hypoxia. III.

AGE ALERT The syndrome occurs most exclusively in infants born before 37 weeks' gestation. Causes Common causes of this syndrome include: lack of surfactant . It is most common in infants of diabetic mothers and in those delivered by cesarean section. it strikes apparently healthy infants. it occurs in about 60% of those born before gestational week 28. Idiopathic respiratory distress syndrome of the newborn Also known as respiratory distress syndrome (RDS) and hyaline membrane disease. althou gh some surviving infants are left with bronchopulmonary dysplasia.5 lbs (2. the premature infant develops a widespread alveolar coll apse due to surfactant deficiency. Ag gressive management and mechanical ventilation can improve the prognosis.000 newborns every year. In IRDS of the newborn. If untreated. Mild cases o f the syndrome subside after about 3 days. Occurring mainly in premature infants and in sudden in fant death syndrome.pneumovax to prevent pneumococcal pneumonia adequate hydration to liquefy and mobilize secretions chest physiotherapy to mobilize secretions oxygen therapy at low settings to correct hypoxia flu vaccine to prevent influenza mucolytics to thin secretions and aid in expectoration of mucus aerosolized or systemic corticosteroids transtracheal catheterization to enable the patient to receive oxygen therapy at home. in the United States a lone.500 g). the syndrome causes death withi n 72 hours of birth in up to 14% of infants weighing under 5. this disorder is the most common cause of neonatal death. or it m ay occur suddenly after antepartum hemorrhage. it kills about 40. Idiopathic respiratory distress syndrome (IRDS) of the newborn is marked by wide spread alveolar collapse.

and causing a right-to-le ft shunt. and the alveoli and capillary blood supply are immature. shallow respirations due to hypoxia intercostal. the grunting is a natural compensatory mechanism th at produces positive end-expiratory pressure (PEEP) to prevent further alveolar collapse . maternal history of diabetes. subcostal. and prevent alveolar collap se. Pathophysiology Surfactant. thus impeding gas exchange between the capillaries and the functional alveoli. cesarean delivery. causing blood to be shunted from the right atrium through a patent foramen ovale to the left atrium. The resul ting pulmonary injury and inflammatory reaction lead to edema and swelling of th e interstitial space. Although the neonatal airways are developed by gestational week 27. the infant mu st expend more energy to ventilate collapsed alveoli. particularly at the end of expiration. rapid. maintain alveolar patency. These deposits furth er reduce gas exchange in the lung and decrease lung compliance. This further increases oxy gen demand and contributes to cyanosis. Because of immature lungs and an already increased metabolic rate. causing an initial respiratory alkalosis as carbon dioxi de is expelled. a lipoprotein present in alveoli and respiratory bronchioles. The shunt further increases hypoxia. or antepartal hemorrhage. Decreased alveolar ventilation results in decreased / ratio and pulmonary arteriolar vasoconstriction. the intercos tal muscles are weak. Increased pulmonary resistance also results in deoxygenated blood passing throu gh the ductus arteriosus. or sternal retractions due to hypoxia nasal flaring due to hypoxia audible expiratory grunting. totally bypassing the lungs. The increased effort at lung expansion causes respirations to sl ow and respiratory acidosis to occur. Signs and symptoms The following signs and symptoms may occur: AGE ALERT Suspect idiopathic respiratory distress syndrome of the newborn in a p atient with a history that includes preterm birth (before gestational week 28). The alveoli are not allowe d to maintain patency and begin to collapse. The infant attempts to compensate with r apid shallow breathing. The pulmonary vasoconstriction can result in increased right cardiac volume and pressure. resulting in in creased work of breathing. ventilation is decreased and hypoxia develops. With alveolar collapse.premature birth. S urfactant deficiency causes a higher surface tension. leading to respiratory failure. The inflammation also stimulates production of hyaline memb ranes composed of white fibrin accumulation in the alveoli. helps to lower surface tension.

hypotension due to cardiac failure peripheral edema due to cardiac failure oliguria due to vasoconstriction of kidneys. resulting from an immature nervous system and inadequate s ubcutaneous fat diminished air entry and crackles on auscultation due to atelectasis. Diagnosis The following tests help diagnose IRDS: Chest X-rays may be normal for the first 6 to 12 hours in 50% of patients. right-to-left shunting through the foramen ovale. altho . or ri ght-to-left shunting through the atelectatic lung areas pallor due to decreased circulation frothy sputum due to pulmonary edema and atelectasis low body temperature. the following may also occur: apnea due to respiratory failure bradycardia due to cardiac failure cyanosis from hypoxemia. In severe cases. Complications Possible complications include: respiratory failure cardiac failure bronchopulmonary dysplasia.

preventing spontaneous respiration during mechanical ventilation . this forces the a lveoli to remain open on expiration and promotes increased surface area for exch ange of oxygen and carbon dioxide high-frequency oscillation ventilation if the neonate can't maintain adequate ga s exchange. indicating air-filled. a paralytic agent. and a reduced pH. if such treatment fails. a normal. by mechanical ventilation to promote adequate oxygenation and r everse hypoxia mechanical ventilation with PEEP or continuous positive airway pressure (CPAP) a dministered by a tight-fitting face mask or endotracheal tube. humidified. this provides satisfactory minute volume (the total air breathed in 1 minute) with lower airway pressures radiant warmer or an Isolette to help maintain thermoregulation and reduce metab olic demands intravenous fluids to promote adequate hydration and maintain circulation with c apillary refill of less than 2 seconds. oxygen-enriched gases administered by oxygen hood or. indicating a combination of respir atory and metabolic acidosis. Arterial blood gas analysis reveals a diminished PaO2 level. fluid and electrolyte balance is also ma intained sodium bicarbonate to control acidosis tube feedings or total parenteral nutrition to maintain adequate nutrition if th e neonate is too weak to eat drug therapy with pancuronium bromide. this test is usually ordered if a cesarean section will be performed before gestational week 36. Lecithin-sphingomyelin ratio helps to assess prenatal lung development and infan ts at risk for this syndrome. decreased . Treatment Correcting this syndrome typically involves: warm. dilated bronchioles.ugh later films show a fine reticulonodular pattern and dark streaks. or increased PaCO2 level.

The most common types of pneumothorax are open. Venous return to the heart may be imp eded to cause a life-threatening condition called tension pneumothorax. increasing tension in the pleural cavity can caus e the lung to progressively collapse.prophylactic antibiotics for underlying infections diuretics to reduce pulmonary edema synthetic surfactant to prevent atelectasis and maintain alveolar integrity vitamin E to prevent complications associated with oxygen therapy AGE ALERT Corticosteroids may be administered to the mother to stimulate surfact ant production in a fetus at high risk for preterm birth. Pneumothorax Pneumothorax is an accumulation of air in the pleural cavity that leads to parti al or complete lung collapse. Air is trapped in the intrapleural space a nd determines the degree of lung collapse. closed. When the air between the visceral and parietal ple urae collects and accumulates. delayed delivery of an infant (if premature labor) to possibly prevent idiopathi c respiratory distress syndrome. and tension. Causes Common causes of open pneumothorax include: penetrating chest injury (gunshot or stab wound) insertion of a central venous catheter chest surgery transbronchial biopsy thoracentesis or closed pleural biopsy. Causes of closed pneumothorax include: .

/ imbalances lead to hypoxia. Spontaneous pneumothorax is another type of closed pneumothorax.blunt chest trauma air leakage from ruptured blebs rupture resulting from barotrauma caused by high intrathoracic pressures during mechanical ventilation tubercular or cancerous lesions that erode into the pleural space interstitial lung disease. which prevents lung expansion during norm al inspiration. resulting in decreased total lung capacity. AGE ALERT Spontaneous pneumothorax is common in older patients with chronic pulm . the lung collapses on the affected side. and lung compliance. Open pneumothorax (also called sucking chest wound or communicating pneumothorax ) results when atmospheric air (positive pressure) flows directly into the pleur al cavity (negative pressure). Tension pneumothorax may be caused by: penetrating chest wound treated with an air-tight dressing fractured ribs mechanical ventilation high-level positive end-expiratory pressure that causes alveolar blebs to ruptur e chest tube occlusion or malfunction. causing increased pleural pressure. Negative pressure is destro yed and the elastic recoil forces are affected. Closed pneumothorax occurs when air enters the pleural space from within the lun g. The lung recoils by collapsing t oward the hilus. As the air pressure in the pleural cavity becomes positive. vital capacity. Pathophysiology A rupture in the visceral or parietal pleura and chest wall causes air to accumu late and separate the visceral and parietal pleurae. such as eosinophilic granuloma.

Without immediate treatment. tall. young adults. breathing. As air continues to accumula te and intrapleural pressures rise. the mediastinum shifts away from the affecte d side and decreases venous return. a nd great vessels to the unaffected side. and cough ing asymmetrical chest wall movement due to collapse of the lung shortness of breath due to hypoxia cyanosis due to hypoxia respiratory distress decreased vocal fremitus related to collapse of the lung absent breath sounds on the affected side due to collapse of the lung . Signs and symptoms The following signs and symptoms may occur: sudden. The air cannot escape. As in trapleural pressure rises. c ausing compression atelectasis. Air is allowed to enter int o the pleural space on inspiration but cannot escape as the rupture site closes on expiration. sharp pleuritic pain exacerbated by chest movement. compre ssing and displacing the heart and great vessels. and lung compliance. air accumulates intrapleurally and cannot escape.) UNDERSTANDING TENSION PNEUMOTHORAX In tension pneumothorax. This forces the heart. which acts as a one-way valve. the ipsilateral lung is affected and also collapses. compressing the heart and the contralat eral lung. Increasing air pressure pushes against the recoiled lung. The range of lung collapse is between 5% and 95%. vital capacity. The air enters the pleural space from the sit e of pleural rupture.onary disease. Tension pneumothorax results when air in the pleural space is under higher press ure than air in the adjacent lung. (See Understanding tension pneumothorax. More air enters on inspiration and air pressure begins to exceed barometric pressure. esophagus. Both types of closed pneumothorax can result in a collapsed lung with hypoxia an d decreased total lung capacity. but it may also occur in healthy. Air also presses against the mediastinum. this emergency can rapidly become fatal. trachea. and the accumulating pressure causes the lung to collapse.

mediastinal shift. which is due t o air leaking into the tissues. Tension pneumothorax produces the most severe respiratory symptoms. including: decreased cardiac output hypotension due to decreased cardiac output compensatory tachycardia tachypnea due to hypoxia lung collapse due to air or blood in the intrapleural space mediastinal shift due to increasing tension tracheal deviation to the opposite side distended neck veins due to intrapleural pressure. Complications Possible complications include: .chest rigidity on the affected side due to decreased expansion tachycardia due to hypoxia crackling beneath the skin on palpation (subcutaneous emphysema). and increa sed cardiovascular pressure pallor related to decreased cardiac output anxiety related to hypoxia weak and rapid pulse due to decreased cardiac output.

and no dyspnea or indications of physiologic compromise. Arterial blood gas analysis may reveal hypoxemia. Treatment Treatment depends on the type of pneumothorax. po ssibly. Spontaneous pneumothorax with less than 30% of lung collapse. Diagnosis The following tests help diagnose pneumothorax: Chest X-rays confirm the diagnosis by revealing air in the pleural space and. a mediastinal shift. m ay be corrected with: bed rest to conserve energy and reduce oxygenation demands monitoring of blood pressure and pulse for early detection of physiologic compro mise monitoring of respiratory rate to detect early signs of respiratory compromise oxygen administration to enhance oxygenation and improve hypoxia aspiration of air with a large-bore needle attached to a syringe to restore nega tive pressure within the pleural space. possibly with respiratory acid osis and hypercapnia. PaO2 levels may decrease at first. no signs of increa sed pleural pressure. Correction of pneumothorax with more than 30% of lung collapse may include: thoracostomy tube placed in the second or third intercostal space in the midclav icular line to try to re-expand the lung by restoring negative intrapleural pres sure . but typically return to normal within 24 hours.decreased cardiac output hypoxemia cardiac arrest.

Open (traumatic) pneumothorax may be corrected with: chest tube drainage to re-expand the lung surgical repair of the lung. Causes Pulmonary edema is caused by left-sided heart failure due to: arteriosclerosis cardiomyopathy hypertension valvular heart disease. Pulmonary edema Pulmonary edema is an accumulation of fluid in the extravascular spaces of the l ungs. Factors that predispose the patient to pulmonary edema include: barbiturate or opiate poisoning . Correction of tension pneumothorax typically involves: immediate treatment with large-bore needle insertion into the pleural space thro ugh the second intercostal space to re-expand the lung insertion of a thoracostomy tube if large amounts of air escape through the need le after insertion analgesics to promote comfort and encourage deep breathing and coughing. It is a common complication of cardiac disorders and may occur as a chroni c condition or may develop quickly and rapidly become fatal. which causes the lung to adhere to the parietal pleura. thoracotomy and pleurectomy may be perfor med.connection of the thoracostomy tube to underwater seal or to low-pressure suctio n to re-expand the lung if recurrent spontaneous pneumothorax.

such as occurs in adult respiratory distress syndrome or with inhalation of toxic gases. and pulmonary capillary bed. Pulmonary edema then results from the accumulation of fluid. fluid infiltrates into the lung and pulmonary edema results. If pulmonary capillary hydrostatic pressu re increases. the hydrostatic force that regulates intr avascular fluids (the natural pulling force) is lost because there is no opposit ion. These pressures are transmitted to the le ft atrium. capillary permeability. or the lymphatic drainage system is obstructed. which is normally low.) A blockage of the lymph vessels can result from compression by edema or tumor fi brotic tissue. and by increased systemic venous pressure. pulmonary veins. pulmonary capillary hydrostatic pressure. impairing gas exchang e and leading to pulmonary edema. forcing fluids and solu tes from the intravascular compartment into the interstitium of the lungs. Pathophysiology Normally. As in terstitial oncotic pressure begins to equal capillary oncotic pressure. When this balance changes.cardiac failure infusion of excessive volume of intravenous fluids or overly rapid infusion impaired pulmonary lymphatic drainage (from Hodgkin's disease or obliterative ly mphangitis after radiation) inhalation of irritating gases mitral stenosis and left atrial myxoma (which impairs left atrial emptying) pneumonia pulmonary venoocclusive disease. The injury causes p lasma proteins and water to leak out of the capillary and move into the intersti tium. capillary oncotic pressure. Capillary injury. Signs and symptoms Early signs and symptoms may include: . Fluid flows freely into the interstitium and alveoli. increases capillary permeability. (See Understanding pulmonary edema. and excess fluid moves into the interstitial space. fluid floods the peripheral alveoli and imp airs gas exchange. the pulmonary lymphatic system cannot drain c orrectly into the pulmonary veins. increasing the interstitial oncotic pressure. the compromised left ventricle requires increased filling pressure s to maintain adequate cardiac output. Hydrostatic pressure i n the large pulmonary veins rises. If colloid osmotic pressure decreases. resulting in pulmonary edema. As th e interstitium overloads with fluid. and lymphatic drainage are in balance. the wate r begins to move out of the capillary and into the lungs.

bloody sputum increased tachycardia due to hypoxemia arrhythmias due to hypoxic myocardium cold.dyspnea on exertion due to hypoxia paroxysmal nocturnal dyspnea due to decreased expansion of the lungs orthopnea due to decreased ability of the diaphragm to expand cough due to stimulation of cough reflex by excessive fluid mild tachypnea due to hypoxia increased blood pressure due to increased pulmonary pressures and decreased oxyg enation dependent crackles as air moves through fluid in the lungs neck vein distention due to decreased cardiac output and increased pulmonary vas cular resistance tachycardia due to hypoxia. producing frothy. clammy skin due to peripheral vasoconstriction . rapid respiration due to hypoxia more diffuse crackles as air moves through fluid in the lungs cough. Later stages of pulmonary edema may include the following signs and symptoms: labored.

Diagnosis The following tests help diagnose pulmonary edema: Arterial blood gas analysis usually reveals hypoxia with variable PaCO2. Electrocardiography may show previous or current myocardial infarction. Pulse oximetry may reveal decreasing SaO2 levels. Respiratory acidosis may occur. Complications Possible complications include: respiratory failure respiratory acidosis cardiac arrest. Pulmonary artery catheterization identifies left-sided heart failure and helps r ule out adult respiratory distress syndrome. usually. UNDERSTANDING PULMONARY EDEMA In pulmonary edema. Chest X-rays show diffuse haziness of the lung fields and. The increasing capillary hydrostatic . dependi ng on the patient's degree of fatigue.diaphoresis due to decreased cardiac output and shock cyanosis due to hypoxia decreased blood pressure due to decreased cardiac output and shock thready pulse due to decreased cardiac output and shock. diminished function of the left ventricle causes blood to ba ck up into pulmonary veins and capillaries. cardiomegaly and pleural effusion.

such as furosemide. and afterload morphine to reduce anxiety and dyspnea. to enhance contractilit y in myocardial dysfunction pressor agents to enhance contractility and promote vasoconstriction in peripher al vessels antiarrhythmics for arrhythmias related to decreased cardiac output arterial vasodilators such as nitroprusside to decrease peripheral vascular resi stance. The prognosis in secondary pulmonary hypertension depends on the s everity of the underlying disorder. Primary or idiopathic pu lmonary hypertension is characterized by increased PAP and increased pulmonary v ascular resistance. Pulmonary hypertension Pulmonary hypertension is indicated by a resting systolic pulmonary artery press ure (PAP) above 30 mm Hg and a mean PAP above 18 mm Hg. Treatment Correcting this disorder typically involves: high concentrations of oxygen administered by nasal cannula to enhance gas excha nge and improve oxygenation assisted ventilation to improve oxygen delivery to the tissues and promote acidbase balance diuretics. and to dilate the systemic venous bed. which helps mobilize extravascular fluid positive inotropic agents. p romoting blood flow from pulmonary circulation to the periphery. This form is most common in women ages 20 to 40 and is usual ly fatal within 3 to 4 years.pressure pushes fluid into the interstitial spaces and alveoli. such as digoxin and amrinone. or both. to increase urin ation. ethacrynic acid. AGE ALERT Mortality is highest in pregnant women. and bumetanide. . preload. Secondary pulmonary hypertension results from existing cardiac or pulmonary dise ase. The following i llustrations show a normal alveolus and an alveolus affected by pulmonary edema.

Conditions causing alveolar hypoventilation: chronic obstructive pulmonary disease sarcoidosis diffuse interstitial pneumonia malignant metastases scleroderma obesity kyphoscoliosis. but may include: hereditary factors altered immune mechanisms. Causes Causes of primary pulmonary hypertension are unknown. In fact. Conditions causing vascular obstruction: pulmonary embolism vasculitis left atrial myxoma idiopathic venoocclusive disease . it may not be diagnosed until an autopsy is performed. Secondary pulmonary hypertension results from hypoxemia as the result of the fol lowing.The patient may have no signs or symptoms of the disorder until lung damage beco mes severe.

Eventually. Ventricular septal defect and patent ductus arteriosus cause secondary pulmonary hypertensio n by increasing blood flow through the pulmonary circulation via left-to-right s hunting. The resulting decreased ventilation increases pulmonar y vascular resistance. or both. remain normal. the right ventricle fails (cor pulmonale). Conditions causing acquired cardiac disease: rheumatic valvular disease mitral stenosis. the inc reased pressures generated in the lungs are transmitted to the right ventricle. Pathophysiology In primary pulmonary hypertension. further increasing vascular resistance a nd resulting in pulmonary hypertension. Pulmonary emboli and chronic destruction of alveolar walls. hypoxia and cyanosis eventually occur. im pairing distensibility and increasing vascular resistance. Death results from cor pulmonale. the smooth muscle in the pulmonary artery wal l hypertrophies for no reason. Fibrous lesions also form around the vessels. Pulmona . Although oxygenation is not severely affected initially. Conditions causing primary cardiac disease: patent ductus arteriosus atrial septal defect ventricular septal defect. Coronary artery disease or mitral valvular disease causing increased left ventri cular filling pressures may cause secondary pulmonary hypertension. such as through hypoxemia. Pressures in the left ventricle. hypertrophy occurs in the medial smooth muscle layer of the arterioles. Hypoxemia resulting from this / mismatch also causes vasoconstriction. Secondary pulmonary hypertension can also occur by vasoc onstriction of the vascular bed. as in emphy sema. narrowing the small pulmonary artery (arterioles) or obliterating it completely. acidosis. C onditions resulting in vascular obstruction can also cause pulmonary hypertensio n because blood is not allowed to flow appropriately through the vessels. cause secondary pulmonary hypertension by obliterating or obstructing the pulmonary vascular bed. The larger arteries stiffen and hypertension progresses. Secondary pulmonary hypertension can be reversed if the disorder is resolved.fibrosing mediastinitis mediastinal neoplasm. which receives blood from the lungs. However. Alveolar hypoventilation can result from diseases caused by alveolar destruction or from disorders that prevent the chest wall from expanding sufficiently to al low air into the alveoli. If hypertension persists. which supplies the pulmonary artery.

Primary cardiac diseases may be congenital or acquired. This increases pulmonary vascular resist ance and right ventricular pressure. such as rheumatic valvular disea se and mitral stenosis. confusion. and memory loss due to hypoxia decreased diaphragmatic excursion and respiration due to hypoventilation possible displacement of point of maximal impulse beyond the midclavicular line due to fluid accumulation .ry pressures begin to equal systemic blood pressure. Signs and symptoms The following signs and symptoms may occur: increasing dyspnea on exertion from left ventricular failure fatigue and weakness from diminished oxygenation to the tissues syncope due to diminished oxygenation to brain cells difficulty breathing due to left ventricular failure shortness of breath due to left ventricular failure pain with breathing due to lactic acidosis buildup in the tissues ascites due to right ventricular failure neck vein distention due to right ventricular failure restlessness and agitation due to hypoxia decreased level of consciousness. Acquired cardiac diseases. Congenital defects cause a left-to-right shunt. re-routing blood through the lungs twice and causing pul monary hypertension. causing right ventricular h ypertrophy and eventually cor pulmonale. result in left ventricular failure that diminishes the f low of oxygenated blood from the lungs.

S3. and S4 sounds due to pulmonary hypertension and altered cardiac ou tput decreased breath sounds due to fluid accumulation in the lungs loud. Diagnosis The following tests help diagnose pulmonary hypertension: Arterial blood gas analysis reveals hypoxemia. tubular breath sounds due to fluid accumulation in the lungs. . Complications Possible complications of pulmonary hypertension include: cor pulmonale cardiac failure cardiac arrest.peripheral edema due to right ventricular failure easily palpable right ventricular lift due to altered cardiac output and pulmona ry hypertension reduced carotid pulse palpable and tender liver due to pulmonary hypertension tachycardia due to hypoxia systolic ejection murmur due to pulmonary hypertension and altered cardiac outpu t split S2.

otherwise. Radionuclide imaging detects abnormalities in right and left ventricular functio ning. such as those that develop with pulmonary emboli.Electrocardiography in right ventricular hypertrophy shows right axis deviation and tall or peaked P waves in inferior leads. Pulmonary function studies may show decreased flow rates and increased residual volume in underlying obstructive disease. in underlying restrictive disease. It can also demonstrate right ventricular enlargement. or left ventricula r failure. Cardiac catheterization reveals increased PAP. Perfusion lung scanning may produce normal or abnormal results. with multiple pa tchy and diffuse filling defects that don't suggest pulmonary embolism. Open lung biopsy may determine the type of disorder. a nd reduction in left ventricular cavity size. abno rmal septal configuration consistent with right ventricular pressure overload. Treatment Managing this disorder typically involves: oxygen therapy to correct hypoxemia and resulting increased pulmonary vascular r esistance fluid restriction in right ventricular failure to decrease workload of the heart digoxin to increase cardiac output . Pulmonary angiography detects filling defects in pulmonary vasculature. It may also show an increased pulmonary capillary wedge pressure (PCWP) if the underlying cause is left atrial myxoma. the y may show reduced total lung capacity. Echocardiography allows the assessment of ventricular wall motion and possible v alvular dysfunction. PCWP is normal. mitral stenosis. with systolic pressure above 30 m m Hg.

these incl ude: COPD bronchitis pneumonia bronchospasm ventilatory failure . who have a consistently high PaCO2 (hypercapnia) and a low PaO2 (hypoxemia). acute respiratory failure results. These levels do not apply to patients with chronic obstructive pulmonary disease (COPD). Causes Conditions that can result in alveolar hypoventilation. or right-to-left shunting can lead to respiratory failure. / mismatch. respiratory failure is indicated by a PaCO2 above 50 mm Hg and a PaO2 below 50 mm Hg.diuretics to decrease intravascular volume and extravascular fluid accumulation vasodilators to reduce myocardial workload and oxygen consumption calcium channel blockers to reduce myocardial workload and oxygen consumption bronchodilators to relax smooth muscles and increase airway patency beta-adrenergic blockers to improve oxygenation treatment of the underlying cause to correct pulmonary edema heart-lung transplant in severe cases. Acute deterioration in arterial blood gas values for these patients and corresponding clinical deterioration si gnify acute respiratory failure. which can lead to tissue hypoxia. In patients with normal lung tissue. Respiratory failure When the lungs can't adequately maintain arterial oxygenation or eliminate carbo n dioxide.

The most common cause of hypoxemia V/Q imbalance occurs when conditions such as pulmonary embolism or adult respiratory distress syndrome interrupt normal gas e xchange in a specific lung region. Too little ventilation with normal blood flow or too little blood flow with normal ventilation may cause the imbalance. although it is uncommon. such as with central nervous system conditi ons or trauma or central nervous system depressant drugs. and hypn otics neuromuscular diseases. hypoxemia. / mismatch. sedation. resulting in hypoxemia. PaO2 levels fall and PaCO2 levels rise. Hypoxemia results from inspired air that does not contain adequate oxygen to est ablish an adequate gradient for diffusion into the blood for example. such as poliomyelitis or amytrophic lateral sclerosis. in which c hronic airway obstruction reduces alveolar minute ventilation. and intrapulmonary (right-to-left) shunting can cause acute respirato ry failure if left untreated. Hypoventilation can occur from a decrease in the rate or duration of inspiratory signal from the respiratory center. often seen with COPD (emphysema or bronchitis). Pathophysiology Respiratory failure results from impaired gas exchange. at high al . Any condition associated with alveolar hypoventilation. thus. can result in alveolar hypoventilation if the condition affects normal contraction of the respiratory m uscles. The most common cause of alveolar hypoventilation is airway obstruction. Decreased FiO2 is also a cause of respiratory failure. such as poliomyelitis or amyotrophic lateral sclerosis. such as anesthetics.pneumothorax atelectasis cor pulmonale pulmonary edema pulmonary emboli central nervous system disease central nervous system trauma central nervous system depressant drugs. resul ting in decreased PaO2 levels and. Neuromuscular diseases . Decreased oxygen saturation may result from alveolar hypoventilation.

anxiety. stroke volum e increases. Hypoxemia or hyperc apnia (or both) causes the brain's respiratory control center first to increase respiratory depth (tidal volume) and then to increase the respiratory rate. and an increased heart rate and cardiac output. Respiratory acidosis occurs from hypercapnia. increases perip heral resistance. the sympathetic nervous system triggers vasoconstriction. The body responds to hypercapnia with cerebral depression. clammy skin due to vasoconstriction dull or flat sound on percussion if the patient has atelectasis or pneumonia . Hypoxia of the kidneys results in release of erythropo ietin from renal cells. Untreated / imbalances can lead to right-to-left shunting in which blood passes from the he art's right side to its left without being oxygenated. In response to hypoxemia. cardiovascular. and increases the heart rate. hypotension. and heart failure may occur. and central nervous systems. for ex ample. agitation. and confusion due to hypoxic brain cells and a lteration in level of consciousness tachypnea due to hypoxia cold. enclosed spaces. and suprasternal retra ctions may also occur. circulat ory failure. and nail beds due to hypoxemia nasal flaring due to hypoxia ashen skin due to vasoconstriction use of accessory muscles for respiration restlessness. As r espiratory failure worsens. including the respirator y. The hypoxemia and hypercapnia characteristic of respiratory failure stimulate st rong compensatory responses by all of the body systems. Signs and symptoms The following signs and symptoms may occur: cyanosis of oral mucosa. Cyanosis occurs due to increased amoun ts of unoxygenated blood. Heart rate increases. Tissue hypoxemia occurs. resulting in anaerobic metabolism and lactic acidosis.titudes or in confined. supraclavicular. intercostal. which causes the bone marrow to increase production of r ed blood cells an attempt by the body to increase the blood's oxygen-carrying ca pacity. lips.

Diagnosis Arterial blood gas analysis indicates respiratory failure by deteriorating value s and a pH below 7. lesions. infiltrates. pneumothorax. Electrocardiography can demonstrate arrhythmias. such as emphysema. and effusions. Blood cultures may identify pathogens. White blood cell count detects underlying infection. Chest X-rays identify pulmonary diseases or conditions. Hypochloremia usually occurs in metabolic alkalosis. Abnormally low hemoglobin and hematocrit levels signal blood loss. Hypokalemia may result from compensatory hyperventilation. atele ctasis. . the body's attempt to correct acidosis. which indicat es decreased oxygen-carrying capacity.35. Pulse oximetry reveals a decreasing SaO2. these are commonly found with c or pulmonale and myocardial hypoxia. Complications Possible complications include: tissue hypoxia metabolic acidosis cardiac arrest. Patients with COPD may have a lower than normal pH compar ed with their previous levels.diminished breath sounds over areas of hypoventilation.

000 infants die of SIDS in the . about 7. if patient doesn't respond to treatment. ages 1 month to 1 year. Also called crib death. promoting oxygenation and preventing collapse of alveoli antibiotics to treat infection bronchodilators to maintain patency of the airways corticosteroids to decrease inflammation fluid restrictions in cor pulmonale to reduce volume and cardiac workload positive inotropic agents to increase cardiac output vasopressors to maintain blood pressure diuretics to reduce edema and fluid overload deep breathing with pursed lips if patient is not intubated and mechanically ven tilated to help keep airway patent incentive spirometry to increase lung volume.000 live births. it occurs at a rate of 2 in every 1. Sudden infant death syndrome Sudden infant death syndrome (SIDS) is the leading cause of death among apparent ly healthy infants.Pulmonary artery catheterization helps to distinguish pulmonary and cardiovascul ar causes of acute respiratory failure and monitors hemodynamic pressures. to force th e airways open. Treatment Correcting this disorder typically involves: oxygen therapy to promote oxygenation and raise PaO2 mechanical ventilation with an endotracheal or a tracheostomy tube if needed to provide adequate oxygenation and to reverse acidosis high-frequency ventilation.

United States each year. infants of mothers younger than age 20. the child is not stimulated to breathe. Pathophysiology It has been suggested that the infant with SIDS may have damage to the respirato ry control center in the brain from chronic hypoxemia. In infants who experience SIDS or near-miss episodes of SIDS. Normally. disadvantaged black infants. the child may not respond to increasing carbon dioxide levels. The incidence is also 10 times higher in SID S siblings and in infants of mothers who are drug addicts. as occurs when infant is face down on the mattre ss. increased carbon dioxide levels stimulate the respiratory center to in itiate breathing until very high levels actually depress the ventilatory effort. The infant may also have periods of sleep apnea and eventually dies during an episode. however. The peak incidence occurs between ages 2 and 4 months. CULTURAL DIVERSITY The incidence of SIDS is slightly higher in preterm infants. and infants of multiple births. Apnea continues until ver y high levels of carbon dioxide completely suppress the ventilatory effort and t he child ceases to breathe. In these infants. showing only depressed ventilation . Treatment Treatment measures associated with SIDS typically involve: . Causes Common causes of SIDS include: hypoxemia. Signs and symptoms The following signs and symptoms may occur: history indicating that the infant was found not breathing mottling of the skin due to cyanosis apnea and absence of pulse due to severe hypoxemia. possibly due to apnea or immature respiratory system re-breathing of carbon dioxide. Complications Possible complications include: death brain damage from near-miss episodes. Inuit infants. an episode of apnea may occur and carbon dioxide levels incr ease. Diagnosis Autopsy is performed to rule out other causes of death.

8 NERVOUS SYSTEM Handbook of Pathophysiology 8 NERVOUS SYSTEM Pathophysiologic concepts € Arousal € Cognition € Movement € Muscle tone € Homeostatic mechanisms € Pain Disorders € Alzheimer's disease € Amyotrophic lateral sclerosis € Arteriovenous malformations € Cerebral palsy € Cerebrovascular accident € Guillain-Barré syndrome € Head trauma € Herniated intervertebral disk € Huntington's disease . Also.resuscitation to restore circulation and oxygenation (usually futile) emotional support to the family prevention of SIDS in high-risk infants or those who have had near-miss episodes . parents should be educated i n prompt emergency treatment of detected apnea. AGE ALERT Infants at risk for SIDS should be monitored at home on an apnea monit or until the age of vulnerability has passed.

threadlike fibers that extend from the central cell body. From birth to death. a highly specialized cell that receives and transmits electrochemical nerve impulses through delicate. It has thr ee main divisions: Central nervous system (CNS): the brain and spinal cord (See Reviewing the centr al nervous system. Sensory (or afferent) neurons transmit impulses from receptors to the spinal cor d or the brain. regula tes involuntary functions of the internal organs. the nervous system efficiently organizes and controls the s mallest action. This intricate network of interlocking receptors and transmitters is a dynamic s ystem that controls and regulates every mental and physical function. Most neurons have several dendrites but only one axon. which carry messages be tween the CNS and remote parts of the body (See Reviewing the peripheral nervous system.€ Hydrocephalus € Intracranial aneurysm € Meningitis € Multiple sclerosis € Myasthenia gravis € Parkinson's disease € Seizure disorder € Spinal cord trauma The nervous system coordinates and organizes the functions of all body systems. also known as connecting or association neurons. monitors communication and instinct for sur . Motor (or efferent) neurons transmit impulses from the CNS to regulate activity of muscles or glands. dendrites carry impulses to it. Interneurons.) Autonomic nervous system: actually part of the peripheral nervous system. carry signals thr ough complex pathways between sensory and motor neurons. Interneurons account fo r 99% of all the neurons in the nervous system. thought. The fundamental unit that participates in all nervous system activity is the neu ron. or feeling. Axons carry impulses away from the cell body.) Peripheral nervous system: the motor and sensory nerves.

orien ted. and sometimes latent. and allows introspection. any disorder affecting the nervous system can cause signs and symptoms in any and all body systems. frontal lobe influences personality. movement. cerebellum. and storage and recall o f memories (although memories are stored throughout the brain) . awake. Thus. social behavi or. c ognition. temporal. and able to move about freely without discomfort and with all body systems working to maintain homeostasis. REVIEWING THE CENTRAL NERVOUS SYSTEM The central nervous system (CNS) includes the brain and spinal cord. language expression. limbic system. The spinal cord is the primary pathway for messages between perip heral areas of the body and the brain. either from direct pressure or compression as structures expand or herniate. based o n anatomic landmarks and functional differences. and occipital). The brain c onsists of the cerebrum. or pain. either directly by invasion or indirectly b y impairment of its blood supply compression of the reticular activating system by a disease process. Arousal Arousal refers to the level of consciousness.vival. language comprehension. homeostatic mechanisms. PATHOPHYSIOLOGIC CONCEPTS Typically. Most disorders cause more than one alteration. abstract reasoning. wonder. A person wh o is aware of himself and the environment and can respond to the environment in specific ways is said to be fully conscious. Several mechanisms can alter arousal: direct destruction of the reticular activating system and its pathways destruction of the entire brainstem. T ogether. Each hemisphere is divided into four lobes. disorders of the nervous system involve some alteration in arousal. a mas s of nerve fibers that allows communication between corresponding centers in the right and left hemispheres. and thalam ic connections are intact and functioning properly. and the close intercommunication between the CN S and peripheral nervous system means that one alteration may lead to another. It also mediates reflexes. subtle. muscle tone. CEREBRUM The left and right cerebral hemispheres are joined by the corpus callosum. higher systems in the cerebral cortex. and movement (in the motor portion) temporal lobe controls hearing. abstract thought. Patients with nervous system disorders commonly have s igns and symptoms that are elusive. parietal. the CNS and peripheral nervous system keep a person alert. and reticular activating system (RAS). or state of awareness. and self-awareness. The lobes are named for the cra nial bones that lie over them (frontal. brain stem. Full consciousness requires that th e reticular activating system. and primitive structures that l ie below the cerebrum: the diencephalon. judgment.

A cross section of the spinal cord reveals a central H-shaped mass of gray matte r divided into dorsal (posterior) and ventral (anterior) horns. Thalamic functions include primitive awar eness of pain. temperature. in the ventral horns. midbrain. PRIMITIVE STRUCTURES The diencephalon contains the thalamus and hypothalamus. pons. Those mechanisms may result from structural. the brain stem relays mes sages between upper and lower levels of the nervous system. and autonomic functions. usually the right. CEREBELLUM The cerebellum. emotions. The thalamus relays all sensory stimuli (except olfactory) as they ascend to the cerebral cortex. shape.) occipital lobe functions primarily in interpreting visual stimuli. and cardiac function. the thin surface layer of the cerebrum. vasomotor. water balance. also interprets size. which also has two hemispheres. and touch. including pain. motor (efferent) impulses. is especially important for awareness of body schema [shape]. Gray matter in t he dorsal horns relays sensory (afferent) impulses. The cranial nerves o riginate from the midbrain. The cerebral cortex. and focusing of attention. is composed of gray matter (unmyelinated cell bodies). which lie beneath the c erebral hemispheres. and texture (The parietal lob e of the nondominant hemisphere. and contains one of the respiratory centers midbrain mediates the auditory and visual reflexes medulla oblongata regulates respiratory. maintains muscle tone. aggression. pituita ry secretions. and sexual and emotional arousal) and screens all senso ry messages traveling to the cerebral cortex. and medulla. distance. including sleep and wake cycle s. coordinat es muscle movement. and controls balance. pon connects the cerebellum with the cerebrum and the midbrain to the medulla ob longata. metabolic. screens all incoming sensory information and c hannels it to appropriate areas of the brain for interpretation. and psychogenic disturba nces: . appetite. screening of incoming stimuli. BRAIN STEM Composed of the pons. The hyp othalamus controls or affects body temperature. SPINAL CORD The spinal cord joins the brain stem at the level of the foramen magnum and term inates near the second lumbar vertebra. RETICULAR ACTIVATING SYSTEM The RAS. a diffuse network of hyperexcitable neurons fanning out from the brain stem through the cerebral cortex.parietal lobe interprets and integrates sensations. RAS activity al so stimulates wakefulness. and medulla oblongata. White matter (myelinated axons of sensory and motor nerves) surrounds these horns and forms the ascending and descending tracts. The limbic system lies deep within the temporal lobe. It initiates primitive dri ves (hunger. The surface of the cerebrum has convolutions (gyri) and creases or fissures (sulci).

Structural changes include infections. and stupor. and anxiety disorders. All cranial nerves. pons. hypoglycemia. emboli. dysfunction of the limbic system has been associated with sc hizophrenia. othe r causes include neoplasms. the spinal ne rves. lethargy. Continued decreases in arousal result from midbrain dysfunction and are evidenced by a deepening of the stupor. The cranial nerves are sensory. Disease is the most common cause of diffuse dysfunction. closed head trauma with subsequent bleeding. neoplasms. and tumors) may directly impinge on the deep diencephalic structures or herniation may compress them. REVIEWING THE PERIPHERAL NERVOUS SYSTEM The peripheral nervous system consists of the cranial nerves (CN). including neurotransmitters. Ongoing research has linked neuroanatomy and neurophysiology of the CNS and s upporting structures. or mixed (both senso ry and motor) as follows: olfactory (CN I) Sensory: smell . Psychogenic changes are commonly associated with mental and psychiatric illnesse s. or both. with certain psychiatric illn esses. Esse ntially any systemic disease can affect the nervous system. both endogenous and exogenous. infarction. coma results. drugs. Localized dysfunction reflects mechanical forces on the thalamus or hypothalamus . Those above the tentorial plate are called supraten torial. Eventually. and developmental and degenerative conditions. vascular problems. except for the olfactory and optic nerves. trauma. the patient shows evidence of dullness. if the medulla and pons are affected. Stages of altered arousal An alteration in arousal usually begins with some interruption or disruption in the diencephalon. depression. prim arily between the brain or brain stem and the head and neck. They usually are identified by their location relative to the tentorial plate. CRANIAL NERVES The 12 pairs of cranial nerves transmit motor or sensory messages. motor. electrolyte di sturbances. Masses (such as bleeding. For example. while those below are called infratentorial. o r medulla oblongata. conf usion. Decreased arousal may be a result of diffuse or localized dysfunction in suprate ntorial areas: Diffuse dysfunction reflects damage to the cerebral cortex or underlying subcort ical white matter. and the autonomic nervous system. originate from the midbrain. the double fold of dura that supports the temporal and occipital lobes and separates the cerebral hemispheres from th e brain stem and cerebellum. Metabolic changes that affect the nervous system include hypoxia. and toxins. and pus accumulation. When this occurs.

taste receptors (posterior one-third of tongue) vagus (CN X). biting. and thoracic and abdominal viscera (heart. lungs. Motor movement of palate. Sensory: sen sations of throat. Each spinal nerve contains of afferen t (sensory) and efferent (motor) neurons.optic (CN II) Sensory: vision oculomotor (CN III) Motor: extraocular eye movement (superior. swallowing. bro nchi. sense of balance glossopharyngeal (CN IX) Motor: swallowing movements. which carry messages to and from parti cular body regions. larynx. and infer ior lateral). such as heart rate and peristalsis. Motor: Facial muscle movement. activity of the thoracic and abdominal viscera. Sensory: sensations of thr oat. and GI tract) spinal accessory (CN XI) Motor: shoulder movement. corneal refl ex. including muscles of expression (those in the forehead and around the eyes and mouth) acoustic (CN VIII) Sensory: hearing. medial. pupillary constriction. head rotation hypoglossal (CN XII) Motor: tongue movement. called dermatomes. gag reflex. SPINAL NERVES The 31 pairs of spinal nerves are named according to the vertebra immediately be low their exit point from the spinal cord. The ANS has two major division s: the sympathetic (thoracolumbar) nervous system and the parasympathetic (crani osacral) nervous system. and upper eyelid elevation trochlear (CN IV) Motor: extraocular eye movement (inferior medial) trigeminal (CN V) Sensory: transmitting stimuli from face and head. Sometimes kno wn as the visceral efferent nerves. autonomic nerves carry messages to the visce ra from the brain stem and neuroendocrine system. . and lateral jaw movements abducens (CN VI) Motor: extraocular eye movement (lateral) facial (CN VII) Sensory: taste receptors (anterior two-thirds of tongue). Motor: chewing. AUTONOMIC NERVOUS SYSTEM The autonomic nervous system (ANS) innervates all internal organs.

and can produce widespread. the long preganglionic fiber of each parasympathetic nerv e travels to a ganglion near a particular organ or gland. The physiologic effects of sympathetic activity include: vasoconstriction elevated blood pressure enhanced blood flow to skeletal muscles increased heart rate and contractility heightened respiratory rate smooth muscle relaxation of the bronchioles. Parasympathetic nerves have a specific r esponse involving only one organ or gland. and urinary tract sphincter contraction pupillary dilation and ciliary muscle relaxation increased sweat gland secretion reduced pancreatic secretion.Sympathetic nervous system Sympathetic nerves exit the spinal cord between the levels of the 1st thoracic a nd 2nd lumbar vertebrae. generalized responses. hence the name thoracolumbar. Parasympathetic nervous system The fibers of the parasympathetic. GI tract. nervous system leave the CNS by way of the cranial nerves from the midbrain and medulla and with the spinal nerves between the 2nd and 4th sacral vertebrae (S2 to S4). The ganglia form a chain that disseminates the impulse to postganglionic neurons. contractility. and conduction velocity . After leaving the CNS. or craniosacral. which reach many organs and glands. and the short postgang lionic fiber enters the organ or gland. The physiologic effects of parasympathetic system activity include: reduced heart rate. These preganglionic neuro ns enter small relay stations (ganglia) near the cord.

side. which refl ect cerebral status) pattern of breathing (helps localize cause to cerebral hemisphere or brain stem) pupillary changes (reflects level of brainstem function. and respons e to the treatment. (See Stages of altered arousal. Six levels of altered arousal or consciousness have been identified. and lacrimal secretions. A patient may move back and forth between stages or levels of arousal. The parasympathetic system has little effect on mental or metabolic activity.bronchial smooth muscle constriction increased GI tract tone and peristalsis with sphincter relaxation urinary system sphincter relaxation and increased bladder tone vasodilation of external genitalia. if the underlying problem is not or cannot be cor rected. five areas of neurologic function are evaluated to help identify the cause of altered arousal: level of consciousness (includes awareness and cognitive functioning. Cognition Cognition is the ability to be aware and to perceive. the brainstem areas tha t control arousal are anatomically next to the areas that control the pupils) eye movement and reflex responses (help identify the level of brainstem dysfunct ion and its mechanism. and severity of brain dysfunctio n). a . termed rostral-caudal progression. depending on the cause of the altered arousal state. remember. Typically. then the patient will progress through the various stages of decreased c onsciousness.) Typically. reason. salivary. initiation of treatment. judge. causing erection pupillary constriction increased pancreatic. such as destruction or compression) motor responses (help identify the level.

incl uding the frontal. or from indirect destruction by compression or the effects of tox ins and chemicals. parietal. place. and portions of the brainstem. Typically. or person . an alteration in cognition results from direct destruction by ischemi a and hypoxia. and temporal lobes. It reflects higher functioning of the cerebral cortex. STAGE MANIFESTATIONS Confusion Loss of ability to think rapidly and clearly Impaired judgment and decision making Disorientation Beginning loss of consciousness Disorientation to time progresses to include disorientation to place Impaired memory Lack of recognition of self (last to go) Lethargy Limited spontaneous movement or speech Easy to arouse by normal speech or touch Possible disorientation to time.nd to use intuition. STAGES OF ALTERED AROUSAL This chart highlights the six levels or stages of altered arousal and their mani festations.

vision. such as deep pain Unable to be aroused to any stimulus Altered cognition may manifest as agnosia. agnosia involves only one sense hearing. or touch. Aphasia is loss of the ability to comprehend or produce language.Obtundation Mild to moderate reduction in arousal Limited responsiveness to environment Ability to fall asleep easily without verbal or tactile stimulation from others Ability to answer questions with minimum response Stupor State of deep sleep or unresponsiveness Arousable (motor or verbal response only to vigorous and repeated stimulation) Withdrawal or grabbing response to stimulation Coma Lack of motor or verbal response to external environment or any stimuli No response to noxious stimuli. U sually. or dysphasia: Agnosia is a defect in the ability to recognize the form or nature of objects. . aphasia.

The patient may experience a prob lem with orientation. vigilance (attentivenes s. recent memory. concept formulati on. general knowledge and information. Three major types of dementia have been identified: amnestic. depending on the s pecific area of the brain involved. The extent of dysfunction reflects the total quantity of neurons lost and the area where this loss occurred.Dysphasia is impairment to the ability to comprehend or use symbols in either ve rbal or written language. different types of dysphasia occur. the patient hears only noise that has no meaning. yet reading comp rehension and writing ability are intact. usually the fronto temporal region. intentional. or language use. Dysfunction in the pathways connecting the primary auditory area to the auditory association areas in the middle third of the left superior temporal gyrus cause s a form of dysphasia called word deafness: the patient has fluent speech. and c ognitive. Processes that have been associated with dementia incl ude: degeneration cerebrovascular disorders compression effects of toxins metabolic conditions biochemical imbalances demyelinization infection. or to produce language. a dysfunction in the posterioin ferior frontal lobe (Broca's area) causes a motor dysphasia in which the patient cannot find the words to speak and has difficulty writing and repeating words. For example. Each type affects a specific area of the brain. which inte rferes with ability to function in daily life. abstraction (the ability to generalize about nonconcrete thoughts and ideas) . Dysphasia typically arises from the left cerebral hemisphere. but c omprehension of the spoken word and ability to repeat speech are impaired. However. and watchfulness). resulting in character istic impairments: . Dementia Dementia is loss of more than one intellectual or cognitive function. alertness. reasoning. The underlying mechanism is a defect in the neuronal circuitry of the brain. remote memory. Rathe r than words.

A problem in any one of these areas can affect mov ement. the extrapyramidal system. the patient loses remote memory. where they cross to the opposite side. Characteristically. Cognitive dementia reflects dysfunctional neuronal circuitry in the cerebral cor tex. Typically. bradykinesia. The types of hypokinesia include paresis. The patient may exhibit personality changes and a flat affect. (See Types of hyperkinesia. abnormal ref lexes. akinesia. initiating. small steps. In the anterior horn of t he spinal cord. language comprehension. upper motor neurons relay impulses to the lower motor neurons. Each type of hyperkinesia is associa ted with a specific underlying pathophysiologic mechanism affecting the brain or motor pathway. Intentional dementia results from a defect in the frontal lobe. the muscles must change their state from one of contracti on to relaxation or vice versa. most impulses from the motor cortex travel through the i nternal capsule to the medulla. play a role in altered movement. The patient is e asily distracted and. and the motor units (the axo n of the lower motor neuron from the anterior horn cell of the spinal cord and t he muscles innervated by it). The fibers of t he pyramidal tract are considered upper motor neurons. can't carry out s uch sequential executive functions as planning. w hich carry them via the spinal and peripheral nerves to the muscles. even though peripheral nerve and muscle functions are intac t. In the pyramidal tract.) Hypokinesia usually involves loss o f voluntary control. although able to follow simple commands. a s evidenced by a wide shuffling gait. The impulses then . ending i n the anterior horn of the gray matter at a specific spinal cord level.) For movement to occur. the patient exhibits difficulty in naming things . and regulating behav ior or achieving specific goals. possibly. producing a motor response. (See Reviewing motor impulse transmission. Movement Movement involves a complex array of activities controlled by the cerebral corte x. the pyramidal system. loss of recent memory. and mat hematical skills. Certain neurotransmitters. and loss of associated movement.Amnestic dementia typically results from defective neuronal circuitry in the tem poral lobe. Possibly appearing accident prone. total immobility. he may lose motor function. such as dopamin e. Hyperkinesia is a broad category that includes many different types of abnormal movements. where they cross (decussate) to the opposite sid e and continue down the spinal cord as the lateral corticospinal tract. and. muscle rigidity. incontinence of bowel and bladder. Motor impulses that regulate involuntary muscle tone and muscle control travel a long the extrapyramidal tract from the premotor area of the frontal lobe to the pons of the brain stem. and has difficulty with visual-spatial relationships. REVIEWING MOTOR IMPULSE TRANSMISSION Motor impulses that originate in the motor cortex of the frontal lobe travel thr ough upper motor neurons of the pyramidal or extrapyramidal tract to the lower m otor neurons of the peripheral nervous system. A change in muscle innervation anywhere along th e motor pathway will affect movement. Alterations in movement typically include excessive movement (hyperkinesia) or d ecreased movement (hypokinesia). and loss of language comprehension. Some fib ers do not cross in the medulla but continue down the anterior corticospinal tra ct and cross near the level of termination in the anterior horn.

Like akinesia. flaccid paresis. The extent of paresis is directly correlated to the number of large lower motor neurons affected. The small motor neurons play two necessary roles in movement: maintaining muscle tone and protecting the muscle from injury. paresis occurs. Motor units. Incoordination associated with upper motor neuron paresis manifests as slow coarse movement with abnormal rhythm. and their axons causes impa irment of voluntary and involuntary movement. and generally affects distal muscle gro ups more severely than proximal groups. Onset of spastic muscle tone over severa l days to weeks commonly accompanies upper motor neuron paresis. Upper motor neurons. If only a small portion of the large motor neurons are involved. caused by a severe. whi ch the patient will often describe as weakness. as well as a disturbance in the time needed to perform a movement. Often caused by dysfunction of the extrapyramidal tract. Bradykinesia Bradykinesia refers to slow voluntary movements that are labored. bradykinesia involves a disturbance in th e time needed to perform a movement. Paresis results from a decrease in the number or force of activated muscle fibers in the motor unit. Paresis Paresis is a partial loss of motor function (paralysis) and of muscle power. acute lesion below the foramen magnum. The muscles innervated by motor neurons in the anterior horn of the spinal cord may also be affected.travel down the spinal cord to the anterior horn. Lower motor neurons. or spinal cord the lower motor neurons in the brainstem motor nuclei and anterior horn of the s pinal cord. Paresis can result from dysfunct ion of any of the following: the upper motor neurons in the cerebral cortex. where they are relayed to low er motor neurons for ultimate delivery to the muscles. or problems with their axons as they travel to the skeletal muscle the motor units affecting the muscle fibers or the neuromuscular junction. however. if all motor un its are affected. an d hard to initiate. Lower motor neurons are of two basic types: large (alpha) a nd small (gamma). unless the dysf unction is acute. Upper motor neuron dysfunction usu ally affects more than one muscle group. Usually when the large motor neuron s are affected. and paralysis. . intern al capsule. The action potential of each motor unit decreases so that additional motor units are needed more quickly to produce the power necessary to move the muscle. Dysfunction of the neuromusc ular junction causes paresis in a similar fashion. In acute dysfunction. The patient has difficulty performing movements consecutivel y and at the same time. subcortical white matter. brain stem. Dysfunction of the large motor neurons of the anterior horn of the spinal cord. the result is paralysis. dysfunction of the small motor neurons causes reduced or absent muscle tone. not the actual number of units. the functional capab ility of the motor units to function is lost. deliberate. Upper motor neuron dysfunction reflects an interruption in the pyramidal tract and consequent decreased activation of the lower motor neuro ns innervating one or more areas of the body. flaccid tone and loss of deep tendon ref lexes indicates spinal shock. the motor nuclei of the brainstem. akinesia is associated with dopamine d eficiency at the synapse or a defect in the postsynaptic receptors for dopamine. Akinesia Akinesia is a partial or complete loss of voluntary and associated movements.

their mani festations. and the underlying pathophysiologic mechanisms involved in their dev elopment. with ability to suppress for short periods Relief obtained by performing motion Possible association with impaired dopaminergic transmission Asterixis Irregular flapping-hand movement More prominent when arms outstretched Believed to result from build up of toxins not broken down by the liver (i. a mmonia) Athetosis Slow..e. TYPE MANIFESTATIONS MECHANISMS Akathisia Ranges from mildly compulsive movement (usually legs) to severely frenzied motio n Partly voluntary. sinuous. fluctuating grimaces Believed to result from injury to the putamen of the basal ganglion Ballism . irregular movements in the distal extremities Characteristic hand posture Slow.TYPES OF HYPERKINESIA This chart summarizes some of the most common types of hyperkinesias.

irregular.Severe. causing inhibition of the nucleus Chorea Random. involuntary. generalized. wild. stereotypical limb movements Present when awake or asleep Usually on one side of the body Injury to subthalamus nucleus. disappears during sleep Increases during emotional stress or attempts at voluntary movement Excess concentration or heightened sensitivity to dopamine in the basal ganglia Hyperactivity Prolonged. increased activity Mainly involuntary but possibly subject to voluntary control Continual changes in body posture or excessive performance of a simple activity at inappropriate times Possibly due to injury to frontal lobe and reticular activating system Intentional cerebellar tremor Tremor secondary to movement Most severe when nearing end of the movement Errors in the feedback from the periphery and goal-directed movement due to dise ase of dentate nucleus and superior cerebellar peduncle Myoclonus . flinging. rapid contractions of muscle groups Nonrepetitive Diminishes with rest.

Whe . and rotation of the cervical spine. rhythmic. L oss of associated neurons involves alterations in movement that accompany the us ual habitual voluntary movements for skill. muscle tone involves complex activities controlled by the cerebra l cortex. Loss of associated neurons involving emotional expression would result in a flat. extrapyramidal system. slow flexion and extension contraction Primarily affects metacarpophalangeal and wrist joints Disappears with voluntary movement Loss of inhibitory effects of dopamine in basal ganglia Wandering Moving about without attention to environment Possibly due to bilateral injury to globus pallidus or putamen Loss of associated neurons Movement involves not only the innervation of specific muscles to accomplish an action. grace. For example. and motor units. the muscles of the face change and the posture rel axes. and balance. reticular activating system and spinal cord Parkinsonian tremor Regular. hip s winging. Loss of associated neurons necessa ry for locomotion would result in a decrease in arm and shoulder movement.Shock-like contractions Throwing limb movements Random occurrence Triggered by startle Present even during sleep Irritability of nervous system and spontaneous discharge of neurons in the cereb ral cortex. whe n a person expresses emotion. cerebellum. pyramidal system. Muscle tone Like movement. blank expression and a stiff posture. Normal muscl e tone is the slight resistance that occurs in response to passive movement. but also the work of other innervated muscles that enhance the action.

i f the motor reflex arc remains functional but is not inhibited by the higher cen ters. For example. Hypertonia usually leads to atrophy of unused muscles. is resistance in both fle xion and extension. Rigidity. premotor. in some cases. the resistance is normally smooth. Hypotonia is thought to involve a decrease in muscle spindle activity as a resul t of a decrease in neuron excitability. is basically a negative feedback loop in which muscle stretch (stimulation) causes reflexive contractio . Flaccidity generally occurs with loss of nerve impulses from the motor unit responsible for maintaining muscle tone. Flaccid muscles can be moved rapidly with little or no resis tance. when the elbow is flexed. Both of these are accomplished by balancing changes in blood f low and cerebrospinal fluid (CSF) volume. The two major types of altered muscle tone are hypotonia (decreased muscle tone) and hypertonia (increased muscle tone). There are four types of hypertonia: Spasticity is hyperexcitability of stretch reflexes caused by damage to the moto r. the brain must maintain and regulate pressure inside the sk ull (intracranial pressure) as it also maintains the flow of oxygen and nutrient s to its tissues. It may be localized to a limb or muscle group. (See How spasticity develops. Dystonia is sustained. reciprocal muscles relax to permit movement with only mi nimal resistance. with co ntinued flexion. even. the cause is frontal lobe injury. the overstimulated muscles may hypertrophy. HOW SPASTICITY DEVELOPS Motor activity is controlled by pyramidal and extrapyramidal tracts that origina te in the motor cortex.n one muscle contracts. Hypertonia Hypertonia is increased resistance to passive movement. basal ganglia. or it may be generalized. Nerve fibers from the various tracts converge and synapse at the anterior horn of the spinal cord. but rarely it may result from pure pyramidal tract damage. and supplementary motor areas and lateral corticospinal tract. or constant.) Paratonia (gegenhalten) is variance in resistance to passive movement in direct proportion to the force applied. the cause is lack of appropriate inhibition of reciprocal muscles. the biceps muscle contr acts and feels firm and the triceps muscle is somewhat relaxed and soft. eventually they become limp and atrophy. However. affecti ng the entire body. shown in a simplified version below. This arc. when a joint i s moved through range of motion. involuntary twisting movements resulting from slow muscle contraction. and co nstant. Hypotonia Hypotonia (also referred to as muscle flaccidity) typically reflects cerebellar damage. the biceps relax and the triceps contract. Thus. causes are damage to basal ganglion (cog-wheel or lead-pipe rigidity) or loss of cerebral cortex inhibition or cerebellar control (gamma and alpha rigidity). involuntary muscle contraction. Together they maintain segmental muscle tone by modulating the stretch re flex arc. brain stem. Homeostatic mechanisms For proper function. and spinal cord.

hypoxia. ceasing when ICP equals systemic blood pressure. thus maintaining muscle length and tone. should intracranial pressure ri se. thereby helping to maintain the volu me within the skull. Ischemia leads to cellular hypoxia. Initially the body uses its compensatory mechanisms (described above) to attempt to maintain homeostasis and lower ICP. and hypercapnia. increased blood volume. cytotoxic. oxygen. Should these normal autoregulatory mechanisms fail. Damage to certain tracts results in loss of inhibition and disruption of the str etch reflex arc. ICP continues to rise. Uninhibited muscle stretch produces exaggerated. if the CO2 concentration in blood increases. solubility. For exam ple. some substances required for metabolism pass through the blood brain barrier. Cerebral edema may result from an initial injury to the brain tissue or it may develop in respo nse to cerebral ischemia. the abnormal blood chemistry stimulates the sympathetic nervous system to cause vasoconstriction of the larg e and medium-sized cerebral arteries. Any condition that alters the normal balance of the intracra nial components including increased brain volume. Cerebral blood flow dimin ishes and perfusion pressure falls. ischemic. This ba rrier is composed of tight junctions between the endothelial cells of the cerebr al vessels and neuroglial cells and is relatively impermeable to most substances . As ICP approaches systemic blood pressure. or in . But if these mechanisms become overwhelm ed and are no longer effective. the gas combines with body flu ids to form carbonic acid. CSF volume remains relatively constant. compression of brain tissue and cerebral vessels f urther impairs cerebral blood flow. increasing blood flow and oxygen delivery to the brain.n (inhibition). Constriction and dilation of the cerebral blood vessels help to regulate intracr anial pressure and delivery of nutrients to the brain. Since the skull is a rigid structure. (See What happ ens when ICP rises. However. A decrease in oxygen concentration also stimulates ce rebral vasodilation. These vessels respond to changes in concentrations of carbon dioxide. accentuating the reflex arc and eventually resulting in spastici ty. Cerebral edema is classified in four types vasogenic. This barrie r also regulates water flow from the blood. and electrical charge. the brain begins to shift under the extreme pressure a nd may herniate to an area of lesser pressure. cerebral perfusion slows even more. increasing blood flow to the brain and cerebral perfusion and. thus impairing its blood supply. this only causes the ICP to increase further. an d cerebral blood (intracranial components) against the skull. Unfortunately. CSF. cerebral ischemia and hypoxia worsen. If ICP continues to rise. even as little as 5 mm Hg. the arachnoid villi open and excess CSF drains in to the venous system.) Cerebral edema Cerebral edema is an increase in the fluid content of brain tissue that leads to an increase in the intracellular or extracellular fluid volume. causing a drop in h ydrogen ion concentration. depending on their size. The herniat ion increases pressure in the area where the pressure was lower. Increased intracranial pressure Intracranial pressure (ICP) is the pressure exerted by the brain tissue. An increase in hy drogen ion concentration causes the cerebral vessels to dilate. and hydrogen ions. which eventually releases hydrogen. However. As th e pressure continues to rise. a change in the volume of the intracranial contents triggers a reciprocal change in one or more of the intracranial components to maintain c onsistent pressure. This helps to prevent increases in blood p ressure from reaching the smaller cerebral vessels. The blood brain barrier also helps to maintain homeostasis in the brain. which in itiates vasodilation of cerebral blood vessels in an attempt to increase cerebra l blood flow. or inc reased CSF volume can increase ICP. subsequently. uncontrolled m uscle activity. When the herniating brain tissue' s blood supply is compromised.

pain in the nervous system is neurogenic o r neuropathic pain. Nociception . Regardless of the type of cerebral edema. When compensatory mechanisms become overworked. Pain Pain is the result of a complex series of steps from a site of injury to the bra in. ultimately leading to herniation. Pain that originates outside the nervo us system is termed nociceptive pain. The following chart will help you to understand incre ased ICP's pathophysiology. small changes in volume lead to large changes in pressure. Ischemic: Due to cerebral infarction and initially confined to intracellular com partment. leakage of plasma proteins into the extracellular s paces pulls water into the brain parenchyma. which interprets the stimuli as pain. WHAT HAPPENS WHEN ICP RISES Intracranial pressure (ICP) is the pressure exerted within the intact skull by t he intracranial volume about 10% blood. The brain compensates for increases in ICP by regulating the volume of the three substances in the following ways: limiting blood flow to the head displacing CSF into the spinal canal increasing absorption or decreasing production of CSF withdrawing water from bra in tissue and excreting it through the kidneys. Cytotoxic (metabolic): Toxins cause failure of the active transport mechanisms. Loss of intracellular potassium and influx of sodium (and water) cause cells in the brain to swell. The rigid skull has little space for expansion of these substances. blood vessels become distorted and bra in tissue is displaced. and 80% brain tissue. 10% CSF.terstitial depending on the underlying mechanism responsible for the increased f luid content: Vasogenic: Injury to the vasculature increases capillary permeability and disrup tion of blood brain barrier. released lysosomes from necrosed cells disrupt blo od brain barrier. after several days. Interstitial: Movement of CSF from ventricles to extracellular spaces increases brain volume.

prostaglandins. impulses travel via the afferent nerve fibers along sensory pathways to the spinal cord. They connect with second order neurons in lamina I and II (the latter includes the substantia gelatinosa. other neurons carry the information to the sensory cortex. transmission. Excitatory and inhibitory interneurons and pro jection cells (neurons that connect pathways in the cerebral cortex of the CNS a nd peripheral nervous system) carry the signal to the brain by way of crossed an d uncrossed pathways. and perception. Impulses then are transmitted to the cerebral cortex. eventually. triggering a slow pain response. such a s withdrawal from a pinprick. which persists or worsens. Sensory impulses travel from the medial and lateral lemniscus (tract) to the thalamus and brainstem. and. Fro m the thalamus. Transduction. which sensitize the nociceptors and a re released at the site of injury or inflammation. the reticul ar activating system. Some corticospinal tract neurons end in the dorsal horn and allow the brain to pay selective attention to certai n stimuli while ignoring others. lightly myelinated fibers. and thalamus. Several theories have been developed in an attempt to explain pain. temperature. Transmission. Several pathways carry the information in the dorsolateral white columns to the dorsal horn of the spinal cord. where pain is perceived and understood. Spinal reflexes involving motor neurons may initiate a protective action. The A-delta and C fibers carry the pain signal from the peripheral tissues to th e dorsal horn of the spinal cord. as when trauma causes a m uscle spasm in the injured area. transmis sion. Some neuron s from the cerebral cortex and brainstem activate inhibitory processes. which prompts th e person to evade the stimulus. sensory. or mechanical pressure. Once stimuli are delivered. Transduction is the conversion of noxious stimuli into electrical impulses and subsequent depolarization of the nerve membrane. (S ee Theories of pain. Perception is the end result of pain transduction. and modulation. no ifying the transmission. thus mod such as serotonin from the mesencephalon. modulation. neurons synapse with interneurons before they cross to the opposite side of the cord and make their way to the medulla. Examples include potassium an d hydrogen ions. limbic system.) Nociception consists of four steps: transduction. stinging. A-delta fibers connect with secondary neuron groupings on the dorsal horn of the spinal cord. Another example of a crossed pathway is the ascending spinoreticulothalamic trac t. At this site. which enters the brain stem and ends in the thalamus. A-delta fibers and C fibers transmit pain sensations from the tiss ues to the central nervous system. mesencephalon. which is responsible for the psychological components of pain and arousal. Mechanical or ther mal stimuli elicit a rapid or fast response. bradykinin. and subjective aspects of th . usually within 1 second. Modulation. C fibers respond to chemical stimuli. such as chemicals. or may enhance the pain. responses from the brain must be relayed back to the original site. or pin-pricking type pain sensations. An example of a crossed pathway is the spinothalamic tract . and basal ganglia. It encompasses the emotional. Sensory receptors cal led nociceptors which are free nerve endings in the tissues are stimulated by va rious agents. These fibers transmit well-localize d. sharp. which perceives it as pain. C fibers are smaller and unmyelinated. and endorphins from the brain and spinal cord inhibi t pain transmission by decreasing the release of nociceptive neurotransmitters. The information also continues to travel to the brain. rather than heat or pressure. This dull ac he or burning sensation is not well localized and leads to two responses: an acu te response transmitted immediately through fast pain pathways. an area in whic h pain is modulated). histamine. These electrical i mpulses are created by algesic substances. A-delta fibers are small diameter. and substance P. serotonin. It allows transmission of the primary signal wh ile suppressing the tendency for signals to spread to adjacent neurons. If a stimu lus is sufficiently strong.Nociception begins when noxious stimuli reach pain fibers. and lingering pain transmitted through slow path ways. Modulation refers to modifications in pain transmission. where they initiate autonomic and motor ref lexes. Perception. Substances repinephrine from the pons.

DISORDERS Alzheimer's disease Alzheimer's disease is a degenerative disorder of the cerebral cortex. and 12 % have a mild to moderate form. the duration o f illness is 8 years. Pain perception is thought to occur in the cortical structure s of the somatosensory cortex and limbic system. Alzheimer's disease accounts for over 50% of all demen tias. by 2040. somatostati n. About 5% of people over the age of 65 have a severe form of this disease. or degener ation of modulating mechanisms. Pain results from spontaneous discharges from the damaged nerves. It is the fourth leadin g cause of death among the elderly. arousal. after heart disease. cancer. The following three variables contribute to the wide variety of individual pain experiences: Pain threshold: level of intensity at which a stimulus is perceived as pain Perceptual dominance: existence of pain at another location that is given more a ttention Pain tolerance: duration or intensity of pain to be endured before a response is initiated. Neurogenic pain Neurogenic pain is associated with neural injury. substance P. a nd there is no typical pathway for transmission. Neurogenic pain does not activate nociceptors. and the highest prevalence is among those over 85. Alzheimer's disease is estimated to affect appro ximately 4 million Americans. AGE ALERT In the elderly. that figure may exceed 6 million. Alertness.e pain experience. exposure to aluminum or manganese Viral: slow CNS viruses . especiall y the frontal lobe. and stroke. and norepinephrine Environmental: repeated head trauma. Typically. Causes The exact cause of Alzheimer's disease is unknown. and motivat ion are believed to result from the action of the reticular activating system an d limbic system. spontaneous dorsal root activity. which accounts for more than half of all cases of dementia. Cardiovascular responses and typical fight or flight responses are thought to involve the medulla and hypothalamus. This primary progressive disease has a poor prognosis. and patients die 2 to 5 years after onset of debilitating brain symptoms. Factors that have been associ ated with its development include: Neurochemical : deficiencies in the neurotransmitters acetylcholine.

At synapses in the substantia gelatinosa. the amount of involved tissue. Disorders or proce sses causing pain create an intense summation of non-noxious stimuli. THEORIES OF PAIN Over the years numerous theories have attempted to explain the sensation of pain and describe how it occurs. Intensity Pain results from excessive stimulation of sensory receptors. each results from stimulation of specific skin receptor sites and neural pathways dedicated to on e of the four sensations. This chart highlights some of the major theories about pain. THEORY MAJOR ASSUMPTIONS COMMENT Specificity Four types of cutaneous sensation (touch. pain).Genetic immunologic: abnormalities on chromosomes 14 or 21. Specific pain neurons (nociceptors) transmit pain sensation along specific pain fibers. cold. Does not explain existence of intense stimuli not perceived as pain. Focuses on the direct relationship between the pain stimulus and perception. No single theory alone provides a complete explanat ion. warmth. depositions of beta amyloid protein. Pattern Nonspecific receptors transmit specific patterns (characterized by the length of the pain sensation. pain impulses cross to the opposite si de of the cord and ascend the specific pain pathways of spinothalamic tract to t he thalamus and the pain receptor areas of the cerebral cortex. doe s not account for adaptation to pain and the psychosocial factors modulating it. and the summation of impulse .

THEORY MAJOR ASSUMPTIONS COMMENT Gate Control Pain is transmitted from skin via the small diameter A-delta and C fibers to cel ls of the substantia gelatinosa in the dorsal horn. . Explains existence of phantom pain. Sensation pattern is possible without the sensory trigger. Sensations imprinted in the brain. Neuromatrix A pattern theory. Stimulation of the large-diameter fast.s) from the skin to the spinal cord. which restricts transmission of the impulse to the CNS and diminishes perception of pain. Large fiber stimulation possible through massage. An increase in small-fiber activity inhibits the substantia gelatinosa cells. Concurrent firing of pain and touch paths r educes transmission and perception of the pain impulses but not of touch impulse s. ope ning the gate and increasing pain transmission and perception. Sensory inputs may trigger a pattern of sensa tion from the neuromatrix (a proposed network of neurons looping between the tha lamus and the cortex. myelinated A-beta and A-alpha fibers clo ses gate. Includes some components of the intensity theory. and the cortex and the limbic system). leading to pain perception. pain possibly a response to in tense stimulation of the sensory receptors regardless of receptor type or pathwa y. where interconnections betwe en other sensory pathways exist. or through electrical stimulation. scratching or rubbing the skin .

Persistent pain initiates a gradual decline in the fraction of impulses that pas s through the various gates. th e peptide that conveys pain information.Substantia gelatinosa acts as a gate-control system to modulate (inhibit) the fl ow of nerve impulses from peripheral fibers to the central nervous system. part ially opening. enkephalin and serotonin. Melzack-Casey Conceptual Model of Pain Three major psychological dimensions of pain: sensory-discriminative from thalamus and somatosensory cortex motivational-affective from the reticular formation cognitive-evaluative. or completely opening the gate. Provides the basis for use of massage and electrical stimulation in pain managem ent. . being used to develop additional theories and models. Interactions among the three produce descending inhibitory influences that alter pain input to the dorsal horn and ultimately modify the sensory pain experience and motivational-affective dimensions. and cognitive interactions determine motor activities and behaviors associ ated with the pain experience. The complex sensory. Pain modulation is also partly controll ed by the neurotransmitters. Inhibitio n of T cells closes the gate. motivati onal. Descending efferent impulses from the brain may be responsible for closing. Takes into account the powerful role of psychological functioning in determining the quality and intensity of pain. Central trigger cells (T cells) act as a central nervous system control to stimu late selective brain processes that influence the gate-control system. transmitters partly regulate the release of substance P. T cell activation of neural mechanisms in the brain is responsible for pain perc eption and response. evaluated by past exper iences and undergoes further cognitive processing. pain impulses are not transmitted to the brain. Pain is localized and identified by its characteristics.

Additional structural changes include cortical atrophy. Signs and symptoms The typical signs and symptoms reflect neurologic abnormalities associated with the disease: gradual loss of recent and remote memory. ventricular dilation. 1380 g). and flattening of affect and personality difficulty with learning new information deterioration in personal hygiene inability to concentrate increasing difficulty with abstraction and judgment impaired communication severe deterioration in memory. loss of sense of smell. areas that are important for memory and cognitive functions. and motor function loss of coordination .Pathophysiology The brain tissue of patients with Alzheimer's disease exhibits three distinct an d characteristic features: neurofibrillatory tangles (fibrous proteins) neuritic plaques (composed of degenerating axons and dendrites) granulovascular changes. also are found. and redu ced brain volume. Selective loss of cholinergic neurons in the pathways to the f rontal lobes and hippocampus. de position of amyloid (a glycoprotein) around the cortical blood vessels. language. Examination of the brain after death commonly reveals an atrophic brain. often weighing less than 1000 g (normal.

Complications The most common complications include: injury secondary to violent behavior or wandering pneumonia and other infections malnutrition dehydration aspiration death. compulsiveness or fearfulness when overwhelmed with anxiety disorientation and emotional lability progressive deterioration of physical and intellectual ability. agitation. such as wringing of hands acute confusion. that is. wanderings nocturnal awakenings loss of eye contact and fearful look signs of anxiety.inability to write or speak personality changes. Diagnosis Alzheimer's disease is diagnosed by exclusion. by ruling out other diso .

isoxsuprine. an anticholinesterase agent. Magnetic resonance imaging shows no lesion as the cause of the dementia. to help improve memory deficits choline salts. enkephalins. the following diagnostic tests may be useful: Positron emission tomography shows changes in the metabolism of the cerebral cor tex. aluminum cooking utensils. The only true way to co nfirm Alzheimer's disease is by finding pathological changes in the brain at aut opsy. and deodorants that con tain aluminum. Treatment No cure or definitive treatment exists for Alzheimer's disease. physostigmine. Therapy may incl ude the following: cerebral vasodilators such as ergoloid mesylates. Electroencephalogram shows evidence of slowed brain waves in the later stages of the disease. Computed tomography shows evidence of early brain atrophy in excess of that whic h occurs in normal aging. such as methylphenidate.rders as the cause for the patient's signs and symptoms. and cyclandelate to enhance cerebral circulation hyperbaric oxygen to increase oxygenation to the brain psychostimulants. to enhance the patient's mood antidepressants if depression appears to exacerbate the dementia tacrine. lecithin. or naloxone to possibly slow disease process reduction in use of antacids. or an experimental agent such as deanol. Cerebral blood flow studies shows abnormalities in blood flow. to possibly control or reduce exposure to aluminum (a possible ri . However.

and XII difficulty breathing. Several mechanisms have been postulated. Amyotrophic lateral sclerosis Commonly called Lou Gehrig's disease. ALS may be fatal in less than 1 year or continue for 10 years or more. Some believe that glutamate the primary excitatory neurotransmitter of the CNS ccumulates to toxic levels at the synapses. progressively debilitating dis ease. choking. difficulty chewing and swallowing. Pathophysiology ALS progressively destroys the upper and lower motor neurons. Onset usu ally occurs between age 40 and age 70. and weakness. atrophy. including: a slow-acting virus nutritional deficiency related to a disturbance in enzyme metabolism metabolic interference in nucleic acid production by the nerve fibers autoimmune disorders that affect immune complexes in the renal glomerulus and ba sement membrane. amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases causing muscular atrophy. It does not affect cranial nerves III. especially in the muscles of the forearms and the hands impaired speech. and loss of functioning motor units. A chronic. Signs and symptoms Typical signs and symptoms of ALS include: a fasciculations accompanied by spasticity. persist. but. ul timately. Causes The exact cause of ALS is unknown. and the disease affects three times as many men as women. Some nearby motor nerves may sprout axons in an attempt to maintain function. and excessive drool ing from degeneration of cranial nerves V. Precipitating factors for acute deterioration include trauma. The affected motor units are no long er innervated and progressive degeneration of axons causes loss of myelin. about 5.000 Americans have ALS. X. such as bl inking. dep ending on the muscles affected. More than 30. and physical exhaustion.sk factor). but about 5% to 10% of cases have a genetic c omponent an autosomal dominant trait that affects men and women equally. viral infections.000 new cases are diagnosed each year. and therefore some facial movements. due to degenera tion of the upper and lower motor neurons. and VI. IX. Other motor neuron disea ses include progressive muscular atrophy and progressive bulbar palsy. Intellectual and sensory functions are not affected. nonfunctional scar tissue replaces normal neuronal tissue. after the New York Yankees first baseman w ho died of this disorder. especially if the brainstem is affected . IV.

Muscle biopsy shows atrophic fibers interspersed between normal fibers. myasthenia gravis. Mental deterioration doesn't usually occur. Nerve conduction studies show normal results. dantrolene.V. Treatment is supportive and may include: diazepam. polyarteritis. or baclofen for decreasing spasticity quinidine to relieve painful muscle cramps thyrotropin-releasing hormone (I. the following may aid in the d iagnosis: Electromyography shows abnormalities of electrical activity in involved muscles. Complications The most common complications include: respiratory infections respiratory failure aspiration. and progressive muscular dystrophy. spinal cord neoplasm. Treatment ALS has no cure. Computed tomography and electroencephalogram (EEG) show normal results and thus rule out multiple sclerosis. but patients may become depressed as a reaction to the disease. or intrathecally) to temporarily improve mot or function (successful only in some patients) . Progressive bulbar palsy may cause crying spells or inappropriate laughter.muscle atrophy due to loss of innervation. Diagnosis Although no diagnostic tests are specific to ALS. syringomyelia.

Abnormal channels between the arterial and venous system mix oxygenated and unoxygenated blood. Possible signs and symptoms include: chronic mild headache and confusion from AVM dilation. and physical therapy to maintain function as much as possib le psychological support to assist with coping with this progressive. such as trauma. The typically high-pressured arterial flow moves into the venous system through the connecting channels to increase venous press ure. the shunting can deprive the surrounding tissue of adequ ate blood flow. AVMs are common in the brain. The vesse ls of an AVM are very thin. causing hemorrhage into the brain or subarachnoid spa ce. indicating turbul ent blood flow . dilated bl ood vessels between arteries and veins that do not connect by capillaries. fatal illness . causing it t o appear dilated and torturous. or orbit. speech. the thin-walled vessels may ooze small amounts of blood or actually rupture.riluzole to modulate glutamate activity and slow disease progression respiratory. Most AVMs are present at birth. one or more arteries feed into the AVM. AVMs range in size from a few millimeters to large malformations extending from the cerebral cortex to the ventricles. vessel engorgement. leaks. Pathophysiology AVMs lack the typical structural characteristics of the blood vessels. Signs and symptoms Typically the patient experiences few. Usually more than one AVM is present. due to a hereditary defect acquired from penetrating injuries. An aneurysm may develop. however. symptoms typically do not oc cur until the person is 10 to 20 years of age. and i ncreased pressure seizures secondary to compression of the surrounding tissues by the engorged ves sels systolic bruit over carotid artery. Arteriovenous malformations Arteriovenous malformations (AVMs) are tangled masses of thin-walled. If t he AVM is large enough. engorging and dilating the venous structures. if any. or ruptures. Causes Causes of AVMs may include: congenital. and some evidence exists that AVMs occur in families. mastoid process. Mal es and females are affected equally. and thereby prevent adequate perfusion of brain tissue. Additionally. signs and symptoms unless the AVM is large. primarily in the posterior portion of the cerebral hemi spheres.

Complications Complications depend on the severity (location and size) of the AVM. Cerebral palsy The most common cause of crippling in children. Diagnosis A definitive diagnosis depends on these diagnostic tests: Cerebral arteriogram confirms the presence of AVMs and evaluates blood flow. depending on the location of the AVM) hydrocephalus. including aneurysm precautions to prevent possible rupture surgery block dissection. Treatment Treatment can be supportive. including sudden severe headache. turbulent blood flow. subarachnoid. or subdural) hemorrhage. including: support measures. cerebral palsy (CP) is a group o . This includ es: aneurysm development and subsequent rupture hemorrhage (intracerebral. corrective. Doppler ultrasonography of cerebrovascular system indicates abnormal. to close the commu nicating channels and feeder vessels and thus reduce the blood flow to the AVM. or both. confusion. lethargy. subarachnoid. or ligation s and remove the feeding vessels to repair the communicating channel embolization or radiation therapy if surgery is not possible. seizures. or subdural. laser. and meningeal i rritation from bleeding into the brain tissue or subarachnoid space hydrocephalus from AVM extension into the ventricular lining.focal neurologic deficits (depending on the location of the AVM) resulting from compression and diminished perfusion symptoms of intracranial (intracerebral.

speech disorders. approximately one-fourth have seizure disorders. athetoid. these disorders may become mor e obvious as an affected infant grows. The three major types of cerebral palsy spastic. and ataxic may occur alone or in combination. vision and hearing def ects.000 live births per year. I ncidence is highest in premature infants (anoxia plays the greatest role in cont ributing to cerebral palsy) and in those who are small for gestational age. Additi onally. Cerebral palsy occurs in an estimated 1. Common asso ciated defects are seizures. Motor impairment may be minimal (sometimes apparent onl y during physical activities such as running) or severely disabling.f neuromuscular disorders caused by prenatal. Cerebral palsy is slightly more common in males than in females and is more comm on in whites than in other ethnic groups. Almo st half of the children with CP are mentally retarded. Although nonprogressive. and reading disabilities. or other CNS damage are probably responsible. Treatment may ma ke a near-normal life possible for children with mild impairment. Causes The exact of CP is unknown. Perinatal and birth factors may include: forceps delivery . and mental retardation. Potential causes vary wi th time of damage. and more than three-fourths have impaired speech. however. Prenatal causes include: maternal infection (especially rubella) exposure to radiation anoxia toxemia maternal diabetes abnormal placental attachment malnutrition isoimmunization. children with CP often have dental abnormalities. conditions resulting in cerebral anoxia. or postnatal damage to the upper motor neurons. he morrhage. The prognosis varies. Those with sev ere impairment require special services and schooling. perinatal.5 to 5 per 1.

Postnatal causes include: kernicterus resulting from erythroblastosis fetalis brain infection or tumor head trauma prolonged anoxia cerebral circulatory anomalies causing blood vessel rupture .breech presentation placenta previa abruptio placentae depressed maternal vital signs from general or spinal anesthesia prolapsed cord with delay in blood delivery to the head premature birth prolonged or unusually rapid labor multiple births (especially infants born last) infection or trauma during infancy.

Each type of cerebral palsy typically produces a distinctive set of clinical fea tures. a lesion or abnormality causes structu ral and functional defects that in turn cause impaired motor function or cogniti on. the infant with CP may exhibit some typical signs and sympt oms. Even though the defects are present at birth. typically smaller than normal for age (because the head grows as the brain grows) abnormal postures. Poss ible complications include: . Pathophysiology In the early stages of brain development. although some children display a mixed form of the disease. (See Assessin g signs of CP. such as straightening legs when on back. when the axons have become myelinated and the basal ganglia a re mature. toes down. extreme refle xes.) Complications Complications depend on the type of CP and the severity of the involvement.systemic disease resulting in cerebral thrombosis or embolus. holding h ead higher than normal when prone due to arching of back abnormal reflexes (neonatal reflexes lasting longer than expected. including: excessive lethargy or irritability high-pitched cry poor head control weak sucking reflex. or clonus) abnormal muscle tone and performance (scooting on back to crawl. toe-first walki ng). Additional physical findings that may suggest CP include: delayed motor development (inability to meet major developmental milestones) abnormal head circumference. Signs and symptoms Shortly after birth. problems may not be apparent u ntil months later.

physical. and speech therapists. including aspiration from poor gag and swallowing refl exes. Diagnostic tests that may be performed include: Developmental screening reveals delay in achieving milestones. Home care is often possible. Such treatment requires a comprehensive and cooperative effort. Treatment Cerebral palsy can't be cured. Vision and hearing screening demonstrates degree of impairment. tea chers. psychologists. spina bifida. involving doctors. However. and occupational. Treatment usually includes: . Diagnosis No diagnostic tests are specific to CP. but proper treatment can help affected children r each their full potential within the limits set by this disorder. or muscular dystr ophy. such as infection. and vision problems language and perceptual deficits mental retardation dental problems respiratory difficulties. neurologic screening will exclu de other possible conditions. the child's family. nurses. hearing. Electroencephalogram identifies the source of seizure activity.contractures skin breakdown and ulcer formation muscle atrophy malnutrition seizure disorders speech.

and speech therapy to maintain or improve functional abilities. TYPE OF CP SIGNS AND SYMPTOMS Spastic CP (due to impairment of the pyramidal tract [most common type]) Hyperactive deep tendon reflexes Increased stretch reflexes . such as adapted eating utensil s and a low toilet seat with arms. to help these children perform activities of daily living independently an artificial urinary sphincter for the incontinent child who can use the hand c ontrols range-of-motion exercises to minimize contractures anticonvulsant to control seizures muscle relaxants (sometimes) to reduce spasticity surgery to decrease spasticity or correct contractures muscle transfer or tendon lengthening surgery to improve function of joints rehabilitation including occupational. ASSESSING SIGNS OF CP Each type of cerebral palsy (CP) is manifested by specific signs. This chart hig hlights the major signs and symptoms associated with each type of CP. casts. physical.braces. or splints and special appliances. The manife stations reflect impaired upper motor neuron function and disruption of the norm al stretch reflex.

including: grimacing wormlike writhing dystonia sharp jerks Difficulty with speech due to involuntary facial movements Increasing severity of movements during stress. decreased with relaxation and di sappearing entirely during sleep Ataxic CP (due to impairment of the extrapyramidal tract) Disturbed balance Incoordination (especially of the arms) Hypoactive reflexes . crossing one foot in front of the other Athetoid CP (due to impairment of the extrapyramidal tract) Involuntary movements usually affecting arms more severely than legs.Rapid alternating muscle contraction and relaxation Muscle weakness Underdevelopment of affected limbs Muscle contraction in response to manipulation Tendency toward contractures Typical walking on toes with a scissors gait.

In fact. A CVA int errupts or diminishes oxygen supply. and often causes serious damage or necrosis in the brain tissues. It strikes over 500. However. or years. In fact. Also. This is believed to be the result of an increased pre valence of hypertension in African Americans. AGE ALERT Although stroke may occur in younger persons. African Americans have a 60% higher risk for CVA than whites or Hispanics of the same age. the better chances are for complete recovery.000 persons per year an d is fatal in approximately half of these persons. CVA is the third most common cause of death in the United States and the most co mmon cause of neurologic disability. also known as a stroke or brain attack. CVAs in African Americans us .Nystagmus Muscle weakness Tremor Lack of leg movement during infancy Wide gait as the child begins to walk Sudden or fine movements impossible (due to ataxia) Mixed CP Spasticity and athetoid movements Ataxic and athetoid movements (resulting in severe impairment) Cerebrovascular accident A cerebrovascular accident (CVA). is a s udden impairment of cerebral circulation in one or more blood vessels. CULTURAL DIVERSITY The incidence of stroke is higher in African Americans than w hites. most patients experienci ng stroke are over the age of 65 years. The sooner the circulation returns to normal after the CV A. about half of patients who survive a CVA remain permanently disabled and experience a recurrence withi n weeks. months. the risk of CVA doubles with ea ch passing decade after the age of 55.

sedentary lifestyle .ually result from disease in the small cerebral vessels. AVM. and valvular disease diabetes familial hyperlipidemia cigarette smoking increased alcohol intake obesity. coronary artery disease. or of the intracranial vessels occluding blood flow. including arrhythmias. (See Types of CVA. or septic embolism.) cardiac disease. or common carotid artery. dilated cardiomyopathy. ruptu red aneurysm. trauma.) embolism from thrombus outside the brain. such as in the heart. The mortality r ate for African Americans from stroke is twice the rate for whites. hemorrhage from an intracranial artery or vein. hemorrhagic disorder. such as from hypertension. aorta. Causes CVA typically results from one of three causes: thrombosis of the cerebral arteries supplying the brain. Risk factors that have been identified as predisposing a patient to CVA include: hypertension family history of CVA history of transient ischemic attacks (TIAs) (See Understanding TIAs. while CVAs in whites ar e typically the result of disease in the large carotid arteries. acute myocardia l infarction.

sodium. also associated with hypertension. The brain cells cease to function be cause they can neither store glucose or glycogen for use nor engage in anaerobic metabolism. Normally. in which tissue injury triggers an inflammatory response that in t urn increases intracranial pressure. smo king. The increased intracranial pressure forces CSF out. The brain's regulatory mechanisms attempt to maintain equilibrium by i ncreasing blood pressure to maintain cerebral perfusion pressure. Calcium. localized acidosis. or i f cerebral blood flow remains impaired for more than a few minutes. But if the bleeding is heavy. Some of the neurons served by th e occluded vessel die from lack of oxygen and nutrients. and ex citatory neurotransmitters are released. many brain cells die. If the hemorrh age is small. This results in cerebra l infarction. diabetes Thrombus in extracranial or intracranial vessel blocks blood flow to the cerebra l cortex . Even if the pressure returns to normal. Pathophysiology Regardless of the cause. exerting pressure on the brain tissues. and water accumulate in the injured cells. This chart describes the major types of CVAs. If the compensatory mechanisms become overworked. if the arteries become blocked. and free radic al formation. this may be enough to keep the patient alive with only minimal neu rologic deficits. Consequent continued cellular injury an d swelling set up a vicious cycle of further damage. thus restoring the balance. TYPE OF CVA DESCRIPTION Ischemic: Thrombotic Most common cause of CVA Frequently the result of atherosclerosis. When hemorrhage is the cause.use of oral contraceptives. autoregulatory mechanisms help m aintain cerebral circulation until collateral circulation develops to deliver bl ood to the affected area. Injury to surrounding cells disrupts metabo lism and leads to changes in ionic transport. the underlying event is deprivation of oxygen and nutri ents. impaired cerebral perfusion causes infarction. intracranial pressure increases rapidly and perfusion stops. and the blood itself acts as a space-occupying mass. oxygen depri vation leads to infarction of brain tissue. A thrombotic or embolic stroke causes ischemia. TYPES OF CVA Cerebrovascular accidents (CVAs) are typically classified as ischemic or hemorrh agic depending on the underlying cause.

during surgery. and proximal basilar arteries May occur during sleep or shortly after awakening.Carotid artery most commonly affected extracranial vessel Common intracranial sites include bifurcation of carotid arteries. thalamus. and pons Lipid coating lining of the small penetrating arteries thickens and weakens wall . or after a my ocardial infarction Ischemic: Embolic Second most common type of CVA Embolus from heart or extracranial arteries floats into cerebral bloodstream and lodges in middle cerebral artery or branches Embolus commonly originates during atrial fibrillation Typically occurs during activity Develops rapidly Ischemic: Lacunar Subtype of thrombotic CVA Hypertension creates cavities deep in white matter of the brain. affecting the i nternal capsule. basal ganglia. distal intrac ranial portion of vertebral arteries. causing microaneurysms and dissections Hemorrhagic Third most common type of CVA .

Typically caused by hypertension or rupture of aneurysm Diminished blood supply to area supplied by ruptured arteriy and compression by accumulated blood Initially. The blood cells that pass through the vessel wall into the surrounding t issue also may break down and block the arachnoid villi. decreased blood flow also prom otes ischemia. meningeal irritation occurs. hemianopsia. causing hydrocephalus. If a clot forms in the vessel. leading to more ischemia an d cellular damage. ptosis) dizziness anxiety altered level of consciousness. A CVA in one hemisphere causes signs and symptoms on the opposite side of the body. General symptoms of a CVA include: unilateral limb weakness speech difficulties numbness on one side headache visual disturbances (diplopia. a CVA that damages cranial nerves affects struct ures on the same side as the infarction. This vasospasm further compromises blood flow. Signs and symptoms The clinical features of CVA vary according to the affected artery and the regio n of the brain it supplies. Additionally. If the blood enters the subarachnoid space. the ruptured cerebral blood vessels may constrict to limit the blood loss. symptoms are usually classified by the artery affected. the severity of the damage. Signs and symptoms associated with middle cerebral artery involvement include: aphasia . and the extent of collat eral circulation developed.

Symptoms associated with carotid artery involvement include: weakness paralysis numbness sensory changes visual disturbances on the affected side altered level of consciousness bruits headaches aphasia ptosis. UNDERSTANDING TIAs A transient ischemic attack (TIA) is an episode of neurologic deficit resulting from cerebral ischemia. It is usually considered a warning sign for cerebr ovascular accident (CVA).dysphasia visual field deficits hemiparesis of affected side (more severe in face and arm than leg). In fact. The recurrent attacks may last from seconds to hours and clear within 12 to 24 hours. TIAs have been reported in over one-half of t .

The most distinctive features of TIAs are transient focal deficits with complete return of function. microemboli released from a thrombus may temporarily interrupt blood f low. and legs on the side oppo site the affected region. Symptoms associated with vertebrobasilary artery involvement include: weakness on the affected side numbness around lips and mouth visual field deficits diplopia poor coordination dysphagia slurred speech dizziness nystagmus amnesia ataxia. They may range to loss of consciousness and loss of motor or sens ory function. double vision. numbness or tingling of the face and lips. slurred speech. Signs and symptoms associated with anterior cerebral artery involvement include: . and di zziness. only for a brief time. Other manifestations may include transient dysphagia.he patients who have developed a CVA. fingers. hands. especially in the small distal branches of the brain's arterial tree. The deficits usually involve some degree of motor or sensor y dysfunction. Commonly the patient experiences weakness i n the lower part of the face and arms. Small spasms in those arterioles may impair blood flow and also precede a TIA. In a TIA. usually within 2 to 5 years.

Complications Complications vary with the severity and type of CVA. especially in the legs on the affected side incontinence loss of coordination impaired motor and sensory functions personality changes.confusion weakness numbness. Signs and symptoms associated with posterior cerebral artery involvement include : visual field deficits (homonymous hemianopsia) sensory impairment dyslexia preservation (abnormally persistent replies to questions) coma cortical blindness absence of paralysis (usually). but may include: .

. or hemorrhage. Digital subtraction angiography shows evidence of occlusion of cerebral vessels. and evidence of hemorrhagic stroke (lesions larger than 1 cm) immediately . Cerebral angiography reveals disruption or displacement of the cerebral circulat ion by occlusion. Magnetic resonance imaging assists in identifying areas of ischemia or infarctio n and cerebral swelling. Diagnosis Computed tomography identifies ischemic stroke within first 72 hours of symptom onset.unstable blood pressure (from loss of vasomotor control) cerebral edema fluid imbalances sensory impairment infections. such as stenosis or acute thrombus. such as pneumonia altered level of consciousness aspiration contractures pulmonary embolism death.

and corticosteroids (dexamethasone. hyperventilation (to decrease partial pressure o f arterial CO2 to lower ICP). osmotic diuretics (mannitol. as causes of thrombotic CVA. Carotid duplex scan identifies stenosis greater than 60%. such as atrial thrombi . atrial septal defect or patent foramen ovale. to reduce inflammation and cerebral ed ema) stool softeners to prevent straining. Treatment Treatment is supportive to minimize and prevent further cerebral damage. to reduce cerebral ed ema). Brain scan shows ischemic areas but may not be conclusive for up to 2 weeks afte r CVA. Lumbar puncture reveals bloody CSF when CVA is hemorrhagic. Measure s include: ICP management with monitoring.lesions. Transesophageal echocardiogram reveals cardiac disorders. Ophthalmoscopy may identify signs of hypertension and atherosclerotic changes in retinal arteries. Single photon emission computed tomography (SPECT) and positron emission tomogra phy (PET) identifies areas of altered metabolism surrounding lesions not yet abl e to be detected by other diagnostic tests. Electroencephalogram helps identify damaged areas of the brain. or vascular abnormalities. which increases ICP anticonvulsants to treat or prevent seizures surgery for large cerebellar infarction to remove infarcted tissue and decompres s remaining live tissue .

For TIAs: antiplatelet agents (aspirin. This syndrome can occur at any age but is most common between ages 30 and 50. Guillain-Barré syndrome is an acute. It affects both sexes equally. but may last up to 2 to 3 years if the disease was severe. Guillain-Barré syndrome Also known as infectious polyneuritis. warfarin) to maintain vessel patency and prevent further clot formation. Recovery is spontaneous and complete in about 95% o f patients. rapidly progressive. Landry-Guillain-Barré syndrome. The prognosis is best when symptoms clear before 15 to 20 days after onset. Causes . or acute id iopathic polyneuritis. This syndrome occurs in three phases: Acute phase begins with onset of the first definitive symptom and ends 1 to 3 we eks later. Plateau phase lasts several days to 2 weeks. thus minimizing cerebral damage (See Treating ischemic CVA. For hemorrhagic CVAs: analgesics such as acetaminophen to relieve headache associated with hemorrhagic CVA. For ischemic CVA: thrombolytic therapy (tPa. although mild motor or reflex deficits may persist in the feet and l egs. alteplase [Activase]) within the first 3 hours after onset of symptoms to dissolve the clot.aneurysm repair to prevent further hemorrhage percutaneous transluminal angioplasty or stent insertion to open occluded vessel s. remove occlusion. and restore blood flow . It extends over 4 to 6 months.) anticoagulant therapy (heparin. ticlopidine) to reduce the risk of platelet aggreg ation and subsequent clot formation (for patients with TIAs) carotid endarterectomy (for TIA) to open partially occluded carotid arteries. Recovery phase is believed to coincide with remyelinization and regrowth of axon al processes. Further deterioration does not occur after the acute phase. a nd potentially fatal form of polyneuritis that causes muscle weakness and mild d istal sensory loss.

Signs and symptoms Symptoms are progressive and include: symmetrical muscle weakness (major neurologic sign) appearing in the legs first (ascending type) and then extending to the arms and facial nerves within 24 to 7 2 hours. or in the arms a nd legs simultaneously. This prevents normal transmission of electrical impulses along the senso rimotor nerve roots. Because this syndrome causes inflammation and degenerative changes in both the posterior (sensory) and the anterior (motor) nerve roots. from impaired motor nerve root transmission and involvement of cranial nerves III.The precise cause of Guillain-Barré syndrome is unknown. from impaired anterior nerve root transmission muscle weakness developing in the arms first (descending type). About 50% of patients with Guillain-Barré syndrome have a recent history of minor febrile illness. possibly with ophthalmoplegia (ocular paralysis). (See Understanding sensori motor nerve degeneration. si gns of sensory and motor losses occur simultaneously. but it may be a cell-medi ated immune response to a virus. Pathophysiology The major pathologic manifestation is segmental demyelination of the peripheral nerves. Other possible precipitating factors include: surgery rabies or swine influenza vaccination Hodgkin's or other malignant disease systemic lupus erythematosus.) Additionally. When infection precedes the onset of Guillain-Barré syndrome. and VI . from imp airment of the dorsal nerve root transmission diplegia. autonomic nerve transmission may be imp aired. signs of infection subside before neurologic features appear. sometimes preceding muscle weakness but vanishing quickly. ga stroenteritis. usually an upper respiratory tract infection or. from impaired anterior nerve root transmission muscle weakness absent or affecting only the cranial nerves (in mild forms) paresthesia. less often. IV.

Complications Common complications include: thrombophlebitis pressure ulcers muscle wasting sepsis joint contractures . because the anterior nerve roots are respon sible for motor function. immobility. and patchy demyelination. Degeneration br ings inflammation. This sheath covers the nerve axons and conducts electrical impulses along the nerve pathways. This flowchart shows how these drugs disrupt an ischemic CVA. less often. Keep in mind that thrombolytic agents should be used only within 3 hours after onset of the patient's symptoms. Thi s delays and impairs impulse transmission along both the dorsal and anterior ner ve roots. a thrombus occludes a cerebral ve ssel or one of its branches and blocks blood flow to the brain. swelling. UNDERSTANDING SENSORIMOTOR NERVE DEGENERATION Guillain-Barré syndrome attacks the peripheral nerves so that they can't transmit messages to the brain correctly. Prompt treatment with thro mbolytic agents or anticoagulants helps to minimize the effects of the occlusion . TREATING ISCHEMIC CVA In an ischemic cerebrovascular accident (CVA). such as the heart. Because the dorsal nerve roots handle sensory function. As this disorder destroys myelin. weakness of the muscles supplied by cra nial nerve XI (spinal accessory nerve) hypotonia and areflexia from interruption of the reflex arc. the nodes of Ranvier (at the junction of the myelin sheaths) widen. Here's what goes wrong. impairment causes varying weakness. and pa ralysis. Similarly. The thrombus may either have formed in that vessel or have lodged there after traveling through the circulation from another site. thus minimizing the effects of cerebral ischemia and infarction.dysphagia or dysarthria and. the patient may experien ce tingling and numbness. The myelin sheath degenerates for unknown reasons.

instead of widespread sectional stimulation. Electromyography possibly shows repeated firing of the same motor unit.aspiration respiratory tract infections mechanical respiratory failure sinus tachycardia or bradycardia hypertension and postural hypotension loss of bladder and bowel sphincter control. Diagnosis Cerebrospinal fluid analysis by lumbar puncture reveals elevated protein levels. the CSF white blood cell count remains normal. but in severe disease. Trial dose (7 days) of prednisone is given to reduce inflammatory response if th . treatments include endotracheal intubation or tracheotomy if respiratory muscle involvement causes difficulty in clearing secretions. Nerve conduction velocities show slowing soon after paralysis develops. Treatment Primarily supportive. CSF pressure may rise above normal. then quickly returns to normal. Serum immunoglobulin levels reveal elevated levels from inflammatory response. probably a result of widespread inflammation of the ne rve roots. peaking in 4 to 6 weeks. Complete blood count shows leukocytosis with immature forms early in the illness .

Mortality from head trauma has declined with advances in preventative measures s uch as seat belts and airbags. exposes the cranial contents to the environm ent.e disease is relentlessly progressive. Risk in men is double the risk in women. Causes Transportation/motor vehicle crashes (number one cause) Falls Sports-related accidents Crime and assaults. Plasmapheresis is useful during the initial phase but of no benefit if begun 2 w eeks after onset. skull. Advances in t echnology have increased the effectiveness of rehabilitative services. The degree of traumatic head injury usually is proportional to the amount of force reaching the cranial tissues. or vocational changes. social. Young children 6 month s to 2 years of age. persons 15 to 24 years of age. an opening in the scalp. intellectual. and no brain tissue is exposed to the external environment. It typically occurs whe n the head strikes a hard surface or a rapidly moving object strikes the head. Continuous electrocardiogram monitoring alerts for possible arrhythmias from aut onomic dysfunction. Furthermore. CULTURAL DIVERSITY African Americans and persons of any ethnicity living in poor socioeconomic groups appear to be at greatest risk for head trauma. Head trauma is generally categorized as closed or open trauma. Head trauma Head trauma describes any traumatic insult to the brain that results in physical . and the risk of infection is high. meninges. or atropine given for bradycardia. as the name suggests. volume replacement for severe hypotension. T he dura is intact. emotional. is more common. neck inju ries should be presumed present in patients with traumatic head injury. unless ruled out. Below a certain level of force (the absorption capacity). bone. and improve d treatment. the cranial vault prevents energy from affecting the brain. which intercepts the force of a physical blow. . I n open trauma. quicker response and transport times. propranolol treats tachycardia and hypertension. meninges. and CSF) . or blunt trauma as it is sometimes called. skin. including the development of regional trauma centers. including the dura. if prednisone produces no noticeable impr ovement. Pathophysiology The brain is shielded by the cranial vault (hair. o r brain tissue. and the elderly are at highe st risk for head trauma. Closed trauma. the drug is discontinued. even for patients with severe head injuries.

causing a second impact a nd injury (contrecoup). then the remaining force pu shes the brain against the opposite side of the skull. injur ing cranial tissues near the point of impact (coup). Each is associated with s pecific signs and symptoms. the cerebrum may endure rotational shear. skull. intracerebral hematoma. damaging the upper midbrain and areas of the frontal.) Complications Increased ICP Infection (open trauma) Respiratory depression and failure Brain herniation. epidural hematoma. TYPE DESCRIPTION SIGNS AND SYMPTOMS DIAGNOSTIC TEST FINDINGS Concussion (closed head injury) A blow to the head hard enough to make the brain hit the skull but not hard enou gh to cause a cerebral contusion causes temporary neural dysfunction. . In coup/contrecoup. and occipital lobes. Recovery is usually complete within 24 to 48 hours. Contusions and lacerations may also occur during contrec oup as the brain's soft tissues slide over the rough bone of the cranial cavity. Open head injuri es are usually associated with skull fractures. (See Types of head trauma. meninges.Closed trauma is typically a sudden acceleration-deceleration or coup/contrecoup injury. TYPES OF HEAD TRAUMA This chart summarizes the signs and symptoms and diagnostic test findings for th e different types of head trauma. contusion. temporal. Signs and symptoms Types of head trauma include concussion. the head hits a relatively stationary object. Also. Open trauma may penetrate the scalp. and bone fragments often cause h ematomas and meningeal tears with consequent loss of CSF. subdural hematoma. or brain. and skull fractures.

all related to disruption of RAS Irritability or lethargy from localized injury and compression Behavior out of character due to focal injury Complaints of dizziness. Less commonly arises from dural venous sinuses. possibly due to abrupt pressure changes in the areas responsible for consciousness. nausea. ischemia. Severe scalp wounds from direct injury . Short-term loss of consciousness secondary to disruption of RAS. Most result from arterial bleeding. or severe headache due to focal injury and comp ression Computed tomography(CT) reveals no sign of fracture. changes in polarity of the neurons. more serious than concussion) Most common in 20 to 40 year olds. or structural distortion of neurons Vomiting from localized injury and compression Anterograde and retrograde amnesia (patient can't recall events immediately afte r the injury or events that led up to the traumatic incident) correlating with s everity of injury. Injury to middle meningeal ar tery in parietotemporal area is most common and is frequently accompanied by lin ear skull fractures in temporal region over middle meningeal artery. Blood commonly accumulates between skull and dura. Contusion (bruising of brain tissue.Repeated injuries exact a cumulative toll on the brain. bleeding or other nervous s ystem lesion.

when the force of the blow drives the brain against the opposite side of the skull. Injury is directly beneath the site of impact when the brain rebounds against th e skull from the force of a blow (a beating with a blunt instrument. possible displacement of the surrounding str uctures.Labored respiration and loss of consciousness secondary to increased pressure fr om bruising Drowsiness. or when the head is hurled forward and stopped abruptly (as in an automob ile crash when a driver's head strikes the windshield). disorientation. and fractures. . EEG recordings directly over area of contusion reveal progressive abnormalities by appearance of high-amplitude theta and delta waves. TYPE DESCRIPTION SIGNS AND SYMPTOMS DIAGNOSTIC TEST FINDINGS Epidural hematoma Acceleration-deceleration or coup-contrecoup injuries disrupt normal nerve funct ions in bruised area. or violence from increased ICP associated with trauma Hemiparesis related to interrupted blood flow to the site of injury Decorticate or decerebrate posturing from cortical damage or hemispheric dysfunc tion Unequal pupillary response from brain stem involvement. for example ). hematomas. CT shows changes in tissue density. and evidence of ischemic tissue. agitation. Lumbar puncture with CSF analysis reveals increased pressure and blood (not perf ormed if hemorrhage is suspected). confusion.

followed by a lucid interval varying from 10-15 minutes to hours or . Brain may strike bony prominences inside the skull (especially the sphenoidal ridges). Contralateral motor deficits reflect compression of corticospinal tracts that pa ss through the brainstem. and profound coma with irregular respiratory pat terns. rarely. increased systemic b lood pressure. days. Respirations. become shallow and irregular as brains tem is impacted. initially deep and labored. bilateral decerebrate response.Brain continues moving and slaps against the skull (acceleration). decreased pulse. Severe headache Progressive loss of consciousness and deterioration in neurologic signs results from expanding lesion and extrusion of medial portion of temporal lobe through t entorial opening. evidenced by bi lateral pupillary dilation. then rebounds (deceleration). Ipsilateral (same-side) pupillary dilation due to compression of third cranial n erve Seizures possible from high ICP Continued bleeding leads to progressive neurologic degeneration. causing intracranial hemorrhage or hematoma that may res ult in tentorial herniation. Deterioration in level of consciousness results from compression of brainstem re ticular formation as temporal lobe herniates on its upper portion. . Brief period of unconsciousness after injury reflects the concussive effects of head trauma. Compression of brainstem by temporal lobe causes clinical manifestations of intr acranial hypertension.

resulting from accumulation of blood in subdural space (b etween dura mater and arachnoid) are most common. CT or MRI reveals evidence of masses and tissue shifting. x-rays. Similar to epidural hematoma but significantly slower in onset because bleeding is typically of venous origin CT.CT or magnetic resonance imaging (MRI) identifies abnormal masses or structural shifts within the cranium Subdural hematoma Meningeal hemorrhages. rarely from ar teries. May be acute. CSF is yellow and has relatively low protein (chronic subdural hematoma). Acute hematomas are a surgical emergency. . TYPE DESCRIPTION SIGNS AND SYMPTOMS DIAGNOSTIC TEST FINDINGS Intracerebral hematoma Subacute hematomas have better prognosis because venous bleeding tends to be slo wer. co nfirming hematoma. and chronic: unilateral or bilateral Usually associated with torn connecting veins in cerebral cortex. and arteriography reveal mass and altered blood flow in the area. subacute.

Unresponsive immediately or experiencing a lucid period before lapsing into a co ma from increasing ICP and mass effect of hemorrhage Possible motor deficits and decorticate or decerebrate responses from compressio n of corticospinal tracts and brain stem CT or cerebral arteriography identifies bleeding site. CSF pressure elevated pre ssure. most caused by result of hypertension. Discontinuity and displacement of bone structure with severe fracture Motor sensory and cranial nerve dysfunction with associated facial fractures Persons with anterior fossa basilar skull fractures may have periorbital ecchymo .Traumatic or spontaneous disruption of cerebral vessels in brain parenchyma caus e neurologic deficits. fluid may appear bloody or xanthochromic (yellow or straw-colored) from h emoglobin breakdown. Trauma is associated with few intra cerebral hematomas. basilar Fractures of anterior and middle fossae are associated with severe head trauma a nd are more common than those of posterior fossa. May not be problematic unless brain is exposed or bone fragments are driven into neural tissue. depending on underlying brain trauma. Skull fractures 4 types: linear. comminuted. Possibly asymptomatic. depending on site and amount of bleeding. Blow to the head causes one or more of the types. depressed. Frontal and temporal lobes are common sites. Shear forces from brain movement frequently cause vessel laceration and hemorrha ge into the parenchyma.

such as acetaminophen. CSF rhinorrhea (leakage through nose). such as dexamethasone. Skull x-ray may reveal fracture. Signs of medullary dysfunction such as cardiovascular and respiratory failure ac company posterior fossa basilar skull fracture. anosmia (loss of smell due to first cranial nerve involvemen t) and pupil abnormalities (second and third cranial nerve involvement). thereby reducing the risk of infection and further brain damage from fracture s.) Treatment Surgical treatment includes: evacuation of the hematoma or a craniotomy to elevate or remove fragments that h ave been driven into the brain. such as mannitol. are giv en to reduce cerebral edema analgesics. hemo tympanium (blood accumulation at the tympanic membrane). CT and MRI reveal intracranial hemorrhage from ruptured blood vessels and swelli ng. CSF otorrhea (leakage from the ear). Diagnosis Each type of head trauma is associated with specific diagnostic findings. and corticosteroids. (See T ypes of head trauma. Supportive treatment includes: close observation to detect changes in neurologic status suggesting further dama ge or expanding hematoma cleaning and debridement of any wounds associated with skull fractures diuretics. Lumbar puncture contraindicated by expanding lesions.sis (raccoon eyes). and facial paralysis (seventh cranial nerve injury) a ccompany middle fossa basilar skull fractures. and to extract foreign bodies and necrotic tissu e. are given to relieve complaints of headache . ecchymosis over the mas toid bone (Battle's sign).

8% occur in the cer vical area. Herniated disks usually occur in adults (mostly men) under age 45. distributing the mechanical stress applied to the spine when the body moves. Causes The two major causes of herniated intervertebral disk are: severe trauma or strain intervertebral joint degeneration. such as phenytoin. minor trauma m ay cause herniation. Herniation occurs in three steps: protrusion: nucleus pulposus presses against the anulus fibrosus extrusion: nucleus pulposus bulges forcibly though the anulus fibrosus. c entral portion of an intervertebral disk is forced through the disk's weakened o r torn outer ring (anulus fibrosus). including mechanical ventilation and endotracheal intubatio n. pushing against the nerve root . Pathophysiology An intervertebral disk has two parts: the soft center called the nucleus pulposu s and the tough. Herniated intervertebral disk Also called a ruptured or slipped disk or a herniated nucleus pulposus. Patients with a congenitall y small lumbar spinal canal or with osteophyte formation along the vertebrae may be more susceptible to nerve root compression and more likely to have neurologi c symptoms. gelatinous. AGE ALERT In older patients whose disks have begun to degenerate. usually a twisting motion. is given as indicated for respiratory failure from brainstem involvement prophylactic antibiotics are given to prevent the onset of meningitis from CSF l eakage associated with skull fractures. Physical stress. a hernia ted disk occurs when all or part of the nucleus pulposus the soft. A herniated disk also can occur with intervertebral jo int degeneration. If the disk has begun to degenerate. minor trauma may cause he rniation. Pain and possibly senso ry and motor loss follow. The vertebrae move closer together and in turn exert pressur e on the nerve roots as they exit between the vertebrae. to prevent and treat seizures respiratory support. ca n tear or rupture the anulus fibrosus so that the nucleus pulposus herniates int o the spinal canal. and 1% to 2% occur in the thoracic area. About 90% of herniated disks occur in the lumbar and lumbosacral regions. The nucleu s pulposus acts as a shock absorber.anticonvulsants. fibrous surrounding ring called the anulus fibrosus.

beginning as a dull pain in the buttocks. indicating spinal root compression. and magnetic resonance imaging show spinal canal compression by herniated disk material. Myelogram. usually unilaterally. coughing. sneezing. which is often accompanied by muscle spasms from pressure and irritation of the sciatic nerve root sensory and motor loss in the area innervated by the compressed spinal nerve roo t and. Lasègue's test reveals resistance and pain as well as loss of ankle or knee-jerk r eflex. legs. not back pain. and bending intensify the pain. Spinal X-rays rule out other abnormalities but may not diagnose a herniated disk because a marked disk prolapse may not be apparent on a normal X-ray.sequestration: annulus gives way as the disk's core bursts presses against the n erve root. Signs and symptoms Signs and symptoms include: severe low back pain to the buttocks. Common complications include: neurologic deficits bowel and bladder problems. and then recurring at shorter intervals and with progressive intensity sciatic pain following trauma. from compression of nerve roots supplying these areas sudden pain after trauma. . Complications Complications are dependent on the severity and the specific site of herniation. Diagnosis Straight leg raising test is positive only if the patient has posterior leg (sci atic) pain. subsiding in a few days. Valsalv a's maneuver. and feet. weakness and atrophy of leg muscles. computed tomography. in later stages.

chronic progressive chorea. heart failure. However. Huntington's disease Also called Huntington's chorea. In the basal ganglia. or both together to stabilize the spine chemonucleolysis (injection of the enzyme chymopapain into the herniated disk) t o dissolve the nucleus pulposus. to minimize muscle spasm from nerve root irritation surgery. Each child o f an affected parent has a 50% chance of inheriting it. frontal cortex. ending in de mentia. Genetic testing is now available to families with a known history of the disease. Huntington's disease usually strikes people between ages 25 and 55 (the average age is 35). the child who doesn't in herit it can't transmit it.Treatment Treatment may include: heat applications to aid in pain relief exercise program to strengthen associated muscles and prevent further deteriorat ion anti-inflammatory agents. Huntington's disease is a hereditary disorder in which degener ation of the cerebral cortex and basal ganglia causes chronic progressive chorea (involuntary and irregular movements) and cognitive deterioration. affecting men and women equally. and 5% occur as late as age 60. such as diazepam. Because of hereditary transmission and delayed expre ssion. or cycloben zdiazaprin. and cerebellum. Neurologic manifestations include: . corticosteroids such as dexamethasone for the same purpose. Signs and symptoms The onset of this disease is insidious. such as aspirin and NSAIDs. or pneumonia. and adult chorea. which either sex can transmit and inherit. it is transmitted as an a utosomal dominant trait. Death usually results 10 to 15 years after onset from suicide. methocarbamol. The consequent deficiency of GABA (an inhibitory neurotransmitter) results in a relative excess of dopamine and abnormal neurotransmission along the affected p athways. The patient eventually becomes totally d ependent emotionally and physically through loss of musculoskeletal control. GABA neurons are destroyed and replaced by glial cells. microdiskectomy to remove fragments of the nucl eus pulposus. Pathophysiology Huntington's disease involves a disturbance in neurotransmitter substances. rarely. spinal fusion to o vercome segmental instability. prim arily gamma aminobutyric acid (GABA) and dopamine. 2% of cases occur in child ren. However. hereditary chorea. Huntington's disease is prevalent in areas where affected families have l ived for several generations. muscle relaxants. including laminectomy to remove the protruding disk. to reduce inflammation and edema at the site of injury. Causes The actual cause of this disorder is unknown.

and torticollis due to shortening of neck muscles. dysarthria (indistinct speech). and aggress . oral apraxia (difficulty coordinating movement of the mouth). and normal muscle strength. often violent. emotion-related athetoid (slow. often before movement problem s occur.Progressively severe choreic movements are due to the relative excess of dopamin e. The patient also may exhibit psychiatric symptoms. Psychiatric symptoms may include: depression and possible mania (earliest symptom) related to altered levels of do pamine and GABA personality changes including irritability. impulsiveness. an early indication of the disease. and purposeless. lability. bradykinesia. tongue smac king. Such movements are rapid. Dysarthria may be complicated by perseveration (persistent repetition of a reply ). organizing. regulating. Choreic movements are initially unilateral and more prominent in the face and ar ms than in the legs. Dysphagia occurs in most patients in the advanced stages. twisting. from dysfunction of the subcortex without significant impairment of immediate memory problems with recent memory due to retrieval rather than encoding problems deficits of executive function (planning. and programmin g) from frontal lobe involvement impaired impulse control. Impairment of both voluntary and involuntary movement is due to the combination of chorea. Bradykinesia (slow movement) is often accompanied by rigidity. Cognitive signs and symptoms may include: dementia. snakelike) movements (especially of the hands) from injury to the basal ganglion . and aprosody (i nability to accurately reproduce or interpret the tone of language). They progress from mild fidgeting to grimacing.

and protective. hyd .ive behavior. Treatment is symptom-based. Pneumoencephalogram reveals characteristic butterfly dilation of brain's lateral ventricles. Positron emission tomography confirms disorder. Treatment No known cure exists for Huntington's disease. Hydrocephalus An excessive accumulation of CSF within the ventricular spaces of the brain. Computed tomography and magnetic resonance imaging show brain atrophy. Diagnosis Genetic testing reveals autosomal dominant trait. suppo rtive. Complications Common complications of Huntington's disease include: choking aspiration pneumonia heart failure infections. It may include: haloperidol or diazepam to modify choreic movements and control behavioral manif estations and depression psychotherapy to decrease anxiety and stress and manage psychiatric symptoms institutionalization to manage progressive mental deterioration and self-care de ficits.

complications may persist. adhesions between meninges at the base of the bra in. the obstruction occurs most frequently betwee n the third and fourth ventricles. Mortality may result from increased intracranial pressure (ICP) in peo ple of all ages. infants may die of infection and malnutrition. a tumor . faulty absorption of CSF may result from surgery to repair a myelomeningocele. a cerebral aneurysm. Rarely. and disruption of the lining. or meningeal hemorrhage. Even after surgery. impaired motor function. a tumor in the choroid plexus causes overpr oduction of CSF and consequent hydrocephalus. Without surgery. the resulting compression can damage brain tissue. eventually. both CSF pressure and volume increase. Pathophysiology In noncommunicating hydrocephalus. hydrocephalus enlarges the head. In infants.rocephalus occurs most often in neonates. Risk factors associated with the development of hydrocephalus in infants may inc lude: intrauterine infection intracranial hemorrhage from birth trauma or prematurity. In older children and adults. It can also occur in adults as a resul t of injury or disease. Compression of brain tissue and cerebral blood vessels leads to ischemia and. stretching. Obstruction in the ventri cles causes dilation. but it can also o ccur at the outlets of the fourth ventricle (foramina of Luschka and Magendie) o r. the prognosis improves but remai ns guarded. This obstruction may result from faulty feta l development. such as developmental delay. and vision loss. In communicating hydrocephalus. . granulomatous diseases. cell death. rarely. the prognosis is poor. infection (syphilis. With early detection and surgical intervention. at the foramen of Monro. Causes Hydrocephalus may result from: obstruction in CSF flow (noncommunicating hydrocephalus) faulty absorption of CSF (communicating hydrocephalus). at the aqueduct of Sylvius. risk factors may include: meningitis mastoiditis chronic otitis media brain tumors or intracranial hemorrhage. and in both infants and adults. Underlying white matter atrophies. meningitis). or a blood clot (after intracranial hemorrhage). In either type.

and abnormal muscle tone in the legs fro m neurologic compression projectile vomiting from increased ICP skull widening to accommodate increased pressure. shiny. fragile-looking scalp skin from the increase in CSF pressure underdeveloped neck muscles from increased weight of the head depressed orbital roof with downward displacement of the eyes and prominent scle rae from increased pressure high-pitched. In adults and older children. shrill cry. indicators of hydrocephalus include: decreased level of consciousness (LOC) from increasing ICP ataxia from compression of the motor areas incontinence impaired intellect. the signs and symptoms typically include: enlargement of the head clearly disproportionate to the infant's growth (most ch aracteristic sign) from the increased CSF volume distended scalp veins from increased CSF pressure thin.Signs and symptoms In infants. Complications Complications may include: mental retardation . irritability.

. Computed tomography and magnetic resonance imaging reveal variations in tissue d ensity and fluid in the ventricular system. Angiography shows vessel abnormalities caused by stretching. Diagnosis Skull X-rays show thinning of the skull with separation of sutures and widening of the fontanelles.impaired motor function vision loss brain herniation death from increased ICP infection malnutrition shunt infection (following surgery) septicemia (following shunt insertion) paralytic ileus. Lumbar puncture reveals increased fluid pressure from communicating hydrocephalu s. adhesions. peritonitis. and intestinal perforation (following s hunt insertion).

40% die from t he effects of hemorrhage and another 20% die later from recurring hemorrhage. Cerebral aneurysms usually arise at an arterial junction in the circle of Willis. the circular anastomosis forming the major cerebral arteries at the base of the brain.) Cerebral aneurysms often rupture and cause subarachnoid hemorrh age. Intracranial aneurysm In an intracranial. Incidence is slightly higher in women than in men. which drains fluid from the brain's latera l ventricle into the right atrium of the heart. which transports excess fluid from the lateral ventr icle into the peritoneal cavity. The prognosis is guarded. stretching it like an overblown balloon and making it likely to rupture. Ne w treatments are improving the prognosis. Supportive care is also warranted. but a cerebral aneurysm may occur at any age in eithe r sex. ventriculoatrial shunt (less common). Pathophysiology Blood flow exerts pressure against a congenitally weak arterial wall. This illustration shows the most common sites around this circle. Its most common form is the berry aneurysm. Causes Causes may include: congenital defect degenerative process combination of both trauma. MOST COMMON SITES OF CEREBRAL ANEURYSM Cerebral aneurysms usually arise at the arterial bifurcation in the Circle of Wi llis and its branches. Of those who survive untreated. Treatment The only treatment for hydrocephalus is surgical correction. especially those in their lat e 40s or early to mid-50s. About half of all patients who suffer a subarac hnoid hemorrhage die immediately. by insertion of: ventriculoperitoneal shunt. Such a rupture is followed by a subarachnoid hemorrhage. (See Most common sites of cer ebral aneurysm. where the fluid makes its way in to the venous circulation. aneurysm a weakness in the wall of a cerebral a rtery causes localized dilation. in which blood spills into the space nor .Ventriculography shows ventricular dilation with excess fluid. a s ac-like outpouching in a cerebral artery. or cerebral.

hemiparesis. Signs and symptoms The patient may exhibit premonitory symptoms resulting from oozing of blood into the subarachnoid space. however. dysphagia. and blurred vision. depending on the severity a nd location of bleeding. from increased pressure caused by increased cerebral bl ood volume. he may have a slight headache and nuchal rigidity. irritability. intermittent nausea nuchal rigidity stiff back and legs. where a c lot can cause potentially fatal increased ICP and brain tissue damage. back and leg pain. causing: sudden severe headache caused by increased pressure from bleeding into a closed space. secondary to bleeding into the meninges. hemisensory defects. which may persist for several days. including deep coma. inclu de: headache. ptosis. . Five grades characterize ruptured cerebral aneurysm: Grade I: minimal bleeding The patient is alert with no neurologic deficit. and visual defects from bleeding in to the brain tissues. re stlessness. The symptoms.mally occupied by CSF. altered level of consciousness. fever. Usually. photophobia. meningeal irritation. blood also spills into brain tissue. occasional seizures. nausea and projectile vomiting related to increased pressure. resulting in nuchal rigidity. Sometimes. the rupture occurs abruptly and without warning. DETERMINING SEVERITY OF AN INTRACRANIAL ANEURYSM RUPTURE The severity of symptoms varies from patient to patient. depending on the site a nd amount of bleeding. and inability to rotate the eye from compressio n on the oculomotor nerve if aneurysm is near the internal carotid artery. dilated pupil. diplopia.

a mild focal deficit. mild to severe hemiparesis.Grade II: mild bleeding The patient is alert. Computed tomography reveals subarachnoid or ventricular bleeding with blood in s ubarachnoid space and displaced midline structures. Skull X-rays may reveal calcified wall of the aneurysm and areas of bone erosion . Diagnosis Cerebral angiography (the test of choice) reveals altered cerebral blood flow. If the rupture is nonfatal. the patient is in a d Typically. he may have third-nerve palsy. with nuchal rigid ity and. Magnetic resonance imaging shows a cerebral blood flow void. Grade III: moderate bleeding The patient is confused or drowsy. Grade V: moribund (often fatal) eep coma or decerebrate. the severity of a ruptured intracranial aneurysm is graded according to the patient's signs and symptoms. (See Determining severity of an intracrania l aneurysm rupture. v essel lumen dilation. possibly.) Complications The major complications associated with cerebral aneurysm include: death from increased ICP and brain herniation rebleeding vasospasm. pos sibly. Grade IV: severe bleeding The patient is stuporous. with a mild to severe headache and nuchal rigidity. and differences in arterial filling. Treatment Treatment may include: . with nuchal rigidity and.

which increases risk of rupture codeine or another analgesic as needed to maintain rest and minimize risk of pre ssure changes leading to rupture hydralazine or another antihypertensive agent. Approximatel y half of patients develop meningitis over 1 to 7 days. Causes . if the patient is hypertensive. mortality in unt reated meningitis is 70% to 100%. the prognosis is good and complications are rare. the brain and the spinal cord meninges become inflamed.bedrest in a quiet. If the disease is recognized early and the infecting organism responds to treatm ent. to reduce risk of ru pture if it hasn't occurred surgical repair by clipping. or wrapping avoidance of coffee. and pia mater. respiratory symptoms precede onset of meningitis. darkened room with minimal stimulation. The prognosis is poorer for infants and elderl y. and about 25% develop severe meningitis suddenly without respiratory symptoms. In most patients. other stimulants. an inhibitor of fibrinolysis. and aspirin to reduce risk of rupture and elevation of blood pressure. to minimize the risk of rebleed ing by delaying blood clot lysis (drug's effectiveness under dispute). However. ligation. Meningitis In meningitis. t o reduce risk of rupture calcium channel blockers to decrease spasm and subsequent rebleeding corticosteroids to reduce cerebral edema phenytoin or another anticonvulsant to prevent or treat seizures secondary to pr essure and tissue irritation from bleeding phenobarbital or another sedative to prevent agitation leading to hypertension a nd reduce risk of rupture aminocaproic acid. Such inflammation may involve all three menin geal membranes the dura mater. usually a s a result of bacterial infection. arachnoid. about 20% develop the di sease in 1 to 3 weeks after onset of respiratory symptoms.

including: skull fracture penetrating head wound lumbar puncture ventricular shunting. Meningitis may follow trauma or invasive procedures. and Escherichia coli. Pathophysiology . usually caused by Neisseria meningitidis.Meningitis is almost always a complication of bacteremia. Aseptic meningitis may result from a virus or other organism. Haemophilus influenzae. Streptococcus pneumoniae. especially from the fo llowing: pneumonia empyema osteomyelitis endocarditis. Sometimes no causa tive organism can be found. Other infections associated with the development of meningitis include: sinusitis otitis media encephalitis myelitis brain abscess.

this type of meningitis is self-limiting. cerebral infarction. triggering additional inflammat ion. but usua lly not as severely as in bacterial meningitis. chills. The microorganism typically enters the CNS by one of four routes: the blood (most common) a direct opening between the CSF and the environment as a result of trauma along the cranial and peripheral nerves through the mouth or nose. which may progr ess to congestion of adjacent tissues and destroy some nerve cells. Encephalitis also may ensue as a secondary infection of the brain t issue. The invading organism triggers an inflammatory response in the meninges. The exudate also: exacerbates the inflammatory response. Signs and symptoms The signs of meningitis typically include: fever. if ICP is not reduced.Meningitis often begins as an inflammation of the pia-arachnoid. engorged blood vessels. Signs of meningeal irritation include: . In aseptic meningitis. and malaise resulting from infection and inflammation headache. increasing the pressure in the brain. Microorganisms can be transmitted to an infant via the intrauterine environment. The thickened CSG flows less readily around the brain and spinal cord. rarely. disrupted cerebral bl ood supply. vomiting and. Thus. papilledema (inflammation and edema of the optic nerve) from increased ICP. lymphocytes infiltrate the pia-arachnoid layers. and no exudate is formed. The consequences are elevated ICP. and. causing the CSF to thicken. irritates the meninges. and it can block the arachn oid villi. disrupting their cell membranes and causing edema. obstructing flow of CSF and causing hydrocephalus. neutrophils gather in the area and produce an e xudate in the subarachnoid space. can extend to the cranial and peripheral nerves. possible thrombosis or rupture. In an a ttempt to ward off the invasion.

As the illness progresses. deep stupor. onset may be insidious. In an infant. an important sign of increased ICP. seizures (in 30% of infants). but most are simply fretful and refuse to eat.nuchal rigidity positive Brudzinski's and Kernig's signs exaggerated and symmetrical deep tendon reflexes opisthotonos (a spasm in which the back and extremities arch backward so that th e body rests on the head and heels). and coma from increased ICP and cerebral edema. Complications Complications may include: increased ICP hydrocephalus cerebral infarction cranial nerve deficits including optic neuritis and deafness encephalitis . Other features of meningitis may include: sinus arrhythmias from irritation of the nerves of the autonomic nervous system irritability from increasing ICP photophobia. An infant may show signs of infection. or coma may develop. which prevents formation o f a bulging fontanelle. vomiting can lead to dehydration. and other visual problems from cranial nerve irritation delirium. twitching. In subacute menin gitis. Most older children have the same symptoms as adults. diplopia.

and decreased glucose concentr ation. complications may include: mental retardation epilepsy unilateral or bilateral sensory hearing loss subdural effusions. In children. Positive Brudzinski's and Kernig's signs indicate meningeal irritation.paresis or paralysis endocarditis brain abscess syndrome of inappropriate antidiuretic hormone (SIADH) seizures coma. . Diagnosis Lumbar puncture shows elevated CSF pressure (from obstructed CSF outflow at the arachnoid villi). high protein level. Cultures of blood. positive Gram s tain and culture (unless a virus is responsible). and nose and throat secretions reveal the offending or ganism. urine. cloudy or milky-white CSF.

or granu lomas secondary to a fungal infection Sinus and skull X-rays may identify cranial osteomyelitis or paranasal sinusitis as the underlying infectious process. I. hemo rrhage. to control arrhythmias mannitol to decrease cerebral edema anticonvulsant (usually given I.) or a sedative to reduce restlessness and pre vent or control seizure activity aspirin or acetaminophen to relieve headache and fever. antibiotics for at least 2 weeks.Chest X-ray may reveal pneumonitis or lung abscess. Supportive measures include: bed rest to prevent increases in ICP fever reduction to prevent hyperthermia and increased metabolic demands that may increase ICP fluid therapy (given cautiously if cerebral edema and increased ICP present) to prevent dehydration . White blood cell count reveals leukocytosis. or tumor as the underlying cause. followed by oral antibiotics sel ected by culture and sensitivity testing digoxin. Computed tomography may reveal hydrocephalus or rule out cerebral hematoma.V. tubercular lesions. or skull fracture as the mechanism for en trance of microorganism. Treatment Treatment may include: usually.V.

Secondary progressive begins as a pattern of clear-cut relapses and recovery. The prognosis varies. disabling the patient by early ad ulthood or causing death within months of onset. Staff should take droplet precautions (in addition to standard precautions) for meningitis caused by H. A family history of MS and living in a cold. meningitidis.appropriate therapy for any coexisting conditions. Terms to describe MS types include: Elapsing-remitting clear relapses (or acute attacks or exacerbations) with full recovery or partial recovery and lasting disability. However. skull f racture. MS affects three women for every two men and five whites fo r every nonwhite. Several types of MS have been identified. but current theories suggest that a slow-actin g or latent viral infection triggers an autoimmune response. including: emotional stress fatigue (physical or emotional) . until 24 hours after the start of effective therapy. but also has clear ac ute attacks. The disease does not worsen between the attacks. such as endocarditis or pneum onia possible prophylactic antibiotics after ventricular shunting procedures. MS may progress rapidly. This form is rare. 70% of patients lead a ctive. Characterized by exa cerbations and remissions. Primary progressive steady progression from the onset with minor recovery or pla teaus. to prevent infection (use is controversial) . It usually becomes symptomatic between the ages of 20 and 40 (the average age of onset is 27). or penetrating head wounds. influenzae and N. Other theories sugg est that environmental and genetic factors may also be linked to MS. Multiple sclerosis Multiple sclerosis (MS) causes demyelination of the white matter of the brain an d spinal cord and damage to nerve fibers and their targets. Th is form becomes steadily progressive and worsens between acute attacks Progressive relapsing steadily progressive from the onset. Incidence is generally higher among urban populations and uppe r socioeconomic groups. This form is uncommon and may involve different brain and spinal cord dam age than other forms. damp climat e increase the risk. productive lives with prolonged remissions. Causes The exact cause of MS is unknown. MS is a major cause of chronic disability in young ad ults. Certain conditions appear to precede onset or exacerbation.

spasticity. paralysis ranging from monoplegia to quadriplegia. ophthalmoplegia. and being biz arre and difficult for the patient to describe. possibly waxin g and waning with no predictable pattern. inducing widely disseminated and varied neurologic dysfunction. pins and needles. and gait ataxia from impaired motor reflex urinary disturbances incontinence. urgency. The axons determine the presence or absence of function. (See How myelin breaks down. intention tremor. and electrical sensations fatigue. sporadic patches of axon demyelination and nerve fiber lo ss occur throughout the central nervous system. and the adequacy of subsequent restored synaptic transmissi on. loss of myelin does not correlate with loss of function. the exte nt of remyelination. blurred vision. Other characteristic changes include: ocular disturbances optic neuritis. such as burning. and frequent infections f rom impaired transmission involving sphincter innervation bowel disturbances involuntary evacuation or constipation from altered impulse t ransmission to internal sphincter .pregnancy acute respiratory infections.) New evidence of nerve fiber loss may provide an explanation for the invisible ne urologic deficits experienced by many patients with MS. Pathophysiology In multiple sclerosis. or they may last for hours or weeks. diplopia. frequency. varying from day to day. Signs and symptoms Signs and symptoms depend on the extent and site of myelin destruction. Flares may be transient. hyperreflexia. a nd nystagmus from impaired cranial nerve dysfunction and conduction deficits to the optic nerve muscle dysfunction weakness. Ty pical first signs and symptoms related to conduction deficits and impaired impul se transmission along the nerve fiber include: visual problems sensory impairment. Clinical effects may be so mild that the patient is unaware of them or so intense that they are debilitating.

years may elapse between onset and diagnosis . perhaps for years. for example. Spinal cord compression. vas . thyroid disease. foramen magnum tumor (which may mimic the exacerbations and remissions of MS). Diagnosis Because early symptoms may be mild. and chronic fatigue syndrome must be ruled out. This lipoprot ein complex formed of glial cells or oligodendrocytes protects the neuron's axon much like the insulation on an electrical wire. Myelin is susceptible to injury. Periodic testing and close observation are necessary. depen ding on the course of the disease. Complications Complications may include: injuries from falls urinary tract infection constipation joint contractures pressure ulcers rectal distention pneumonia depression. by hypoxemia. HOW MYELIN BREAKS DOWN Myelin speeds electrical impulses to the brain for interpretation. syphilis or another infection. Its high electrical resistance and low capacitance allow the myelin to conduct nerve impulses from one node of Ranvier to the next. Diagnosis of this disorder requires evidence of two or more neurologic attacks .fatigue often the most debilitating symptom speech problems poorly articulated or scanning speech and dysphagia from impaire d transmission to the cranial nerves and sensory cortex. toxic chemicals. multiple small stroke s.

cular insufficiencies, or autoimmune responses. The sheath becomes inflamed, and the membrane layers break down into smaller components that become well-circums cribed plaques (filled with microglial elements, macroglia, and lymphocytes). Th is process is called demyelination. The damaged myelin sheath cannot conduct normally. The partial loss or dispersio n of the action potential causes neurologic dysfunction.

The following tests may be useful:

Magnetic resonance imaging reveals multifocal white matter lesions.

Electroencephalogram (EEG) reveals abnormalities in brain waves in one-third of patients.

Lumbar puncture shows normal total CSF protein but elevated immunoglobulin G (ga mma globulin, or IgG); IgG reflects hyperactivity of the immune system due to ch ronic demyelination. An elevated CSF IgG is significant only when serum IgG is n ormal. CSF white blood cell count may be elevated.

CSF electrophoresis detects bands of IgG in most patients, even when the percent age of IgG in CSF is normal. Presence of kappa light chains provide additional s upport to the diagnosis.

Evoked potential studies (visual, brain stem, auditory, and somatosensory) revea l slowed conduction of nerve impulses in most patients. Treatment The aim of treatment is threefold: Treat the acute exacerbation, treat the disea se process, and treat the related signs and symptoms.

I.V. methylprednisolone followed by oral therapy reduces edema of the myelin she ath, for speeding recovery for acute attacks. Other drugs, such as azathioprine (Imuran) or methotrexate and cytoxin, may be used.

Interferon and glatiramen (a combination of 4 amino acids) possibly may reduce f requency and severity of relapses, and slow central nervous system damage.

Stretching and range-of-motion exercises, coupled with correct positioning, may relieve the spasticity resulting from opposing muscle groups relaxing and contra cting at the same time; helpful in relaxing muscles and maintaining function.

Baclofen and tizanidine may be used to treat spasticity. For severe spasticity, botulinum toxin injections, intrathecal injections, nerve blocks, and surgery ma y be necessary.

Frequent rest periods, aerobic exercise, and cooling techniques (air conditionin g, breezes, water sprays) may minimize fatigue. Fatigue is characterized by an o verwhelming feeling of exhaustion that can occur at any time of the day without warning. The cause is unknown. Changes in environmental conditions, such as heat and humidity, can aggravate fatigue.

Amantidine (Symmetrel), pemoline (Cylert), and methylphenidate (Ritalin) have pr oven beneficial, as have antidepressants to manage fatigue.

Bladder problems (failure to store urine, failure to empty the bladder or, more commonly, both) are managed by such strategies as drinking cranberry juice, or i nsertion of an indwelling catheter and suprapubic tubes. Intermittent self-cathe terization and postvoid catheterization programs are helpful, as are anticholine rgic medications in some patients.

Bowel problems (constipation and involuntary evacuation) are managed by such mea sures as increasing fiber, using bulking agents, and bowel-training strategies, such as daily suppositories and rectal stimulation.

Low-dose tricyclic antidepressants, phenytoin, or carbamazepine may manage senso ry symptoms such as pain, numbness, burning, and tingling sensations.

Adaptive devices and physical therapy assist with motor dysfunction, such as pro blems with balance, strength, and muscle coordination.

Beta blockers, sedatives, or diuretics may be used to alleviate tremors.

Speech therapy may manage dysarthria.

Antihistamines, vision therapy, or exercises may minimize vertigo.

Vision therapy or adaptive lenses may manage visual problems. Myasthenia gravis Myasthenia gravis causes sporadic but progressive weakness and abnormal fatigabi lity of striated (skeletal) muscles; symptoms are exacerbated by exercise and re

peated movement and relieved by anticholinesterase drugs. Usually, this disorder affects muscles innervated by the cranial nerves (face, lips, tongue, neck, and throat), but it can affect any muscle group. Myasthenia gravis follows an unpredictable course of periodic exacerbations and remissions. There is no known cure. Drug treatment has improved the prognosis an d allows patients to lead relatively normal lives, except during exacerbations. When the disease involves the respiratory system, it may be life-threatening. Myasthenia gravis affects 1 in 25,000 people at any age, but incidence peaks bet ween the ages of 20 and 40. It's three times more common in women than in men in this age-group, but after age 40, the incidence is similar. About 20% of infants born to myasthenic mothers have transient (or occasionally persistent) myasthenia. This disease may coexist with immune and thyroid disorde rs; about 15% of myasthenic patients have thymomas. Remissions occur in about 25 % of patients. IMPAIRED TRANSMISSION IN MYASTHENIA GRAVIS

Causes The exact cause of myasthenia gravis is unknown. However, it is believed to be t he result of:

autoimmune response

ineffective acetylcholine release

inadequate muscle fiber response to acetylcholine. Pathophysiology Myasthenia gravis causes a failure in transmission of nerve impulses at the neur omuscular junction. The site of action is the postsynaptic membrane. Theoretical ly, antireceptor antibodies block, weaken or reduce the number of acetylcholine receptors available at each neuromuscular junction and thereby impair muscle dep olarization necessary for movement. (See Impaired transmission in myasthenia gra vis.) Signs and symptoms Myasthenia gravis may occur gradually or suddenly. Its signs and symptoms includ e the following:

weak eye closure, ptosis, and diplopia from impaired neuromuscular transmission to the cranial nerves supplying the eye muscles

skeletal muscle weakness and fatigue, increasing through the day but decreasing with rest (In the early stages, easy fatigability of certain muscles may appear with no other findings. Later, it may be severe enough to cause paralysis.)

progressive muscle weakness and accompanying loss of function depending on muscl

e group affected; becoming more intense during menses and after emotional stress , prolonged exposure to sunlight or cold, or infections

blank and expressionless facial appearance and nasal vocal tones secondary to im paired transmission of cranial nerves innervating the facial muscles

frequent nasal regurgitation of fluids, and difficulty chewing and swallowing fr om cranial nerve involvement

drooping eyelids from weakness of facial and extraocular muscles

weakened neck muscles with head tilting back to see (Neck muscles may become too weak to support the head without bobbing.)

weakened respiratory muscles, decreased tidal volume and vital capacity from imp aired transmission to the diaphragm making breathing difficult and predisposing to pneumonia and other respiratory tract infections

respiratory muscle weakness (myasthenic crisis) possibly severe enough to requir e an emergency airway and mechanical ventilation. Complications Complications may include:

respiratory distress



myasthenic crisis. Diagnosis

Tensilon test confirms diagnosis of myasthenia gravis, revealing temporarily imp roved muscle function within 30 to 60 seconds after I.V. injection of edrophoniu m or neostigmine and lasting up to 30 minutes.

Electromyography with repeated neural stimulation shows progressive decrease in muscle fiber contraction.

Serum antiacetylcholine antibody titer may be elevated.

Chest X-ray reveals thymoma (in approximately 15% of patients). Treatment Treatment may include:

anticholinesterase drugs, such as neostigmine and pyridostigmine to counteract f atigue and muscle weakness, and allow about 80% of normal muscle function (drugs less effective as disease worsens)

immunosuppressant therapy with corticosteroids, azathioprine, cyclosporine, and cyclophosphamide used in a progressive fashion (when the previous drug response is poor, the next one is used) to decrease the immune response toward acetylchol ine receptors at the neuromuscular junction

IgG during acute relapses or plasmapheresis in severe exacerbations to suppress the immune system

thymectomy to remove thymomas and possibly induce remission in some cases of adu lt-onset myasthenia

tracheotomy, positive-pressure ventilation, and vigorous suctioning to remove se cretions for treatment of acute exacerbations that cause severe respiratory dist ress

discontinuation of anticholinesterase drugs in myasthenic crisis, until respirat ory function improves Myasthenic crisis requires immediate hospitalization and v igorous respiratory support. Parkinson's disease Named for James Parkinson, the English doctor who wrote the first accurate descr iption of the disease in 1817, Parkinson's disease (also known as shaking palsy) characteristically produces progressive muscle rigidity, akinesia, and involunt ary tremor. Deterioration is a progressive process. Death may result from compli cations, such as aspiration pneumonia or some other infection. Parkinson's disease is one of the most common crippling diseases in the United S tates. It strikes 1 in every 100 people over age 60 and affects men more often t han women. Roughly 60,000 new cases are diagnosed annually in the United States alone, and incidence is predicted to increase as the population ages. Causes The cause of Parkinson's disease is unknown. However, study of the extrapyramida l brain nuclei (corpus striatum, globus pallidus, substantia nigra) has establis

hed the following:

Dopamine deficiency prevents affected brain cells from performing their normal i nhibitory function in the CNS.

Some cases are caused by exposure to toxins, such as manganese dust or carbon mo noxide. Pathophysiology Parkinson's disease is a degenerative process involving the dopaminergic neurons in the substantia nigra (the area of the basal ganglia that produces and stores the neurotransmitter dopamine). This area plays an important role in the extrap yramidal system, which controls posture and coordination of voluntary motor move ments. Normally, stimulation of the basal ganglia results in refined motor movement bec ause acetylcholine (excitatory) and dopamine (inhibitory) release are balanced. Degeneration of the dopaminergic neurons and loss of available dopamine leads to an excess of excitatory acetylcholine at the synapse, and consequent rigidity, tremors, and bradykinesia. Other nondopaminergic neurons may be affected, possibly contributing to depressi on and the other non-motor symptoms associated with this disease. Also, the basa l ganglia is interconnected to the hypothalamus, potentially affecting autonomic and endocrine function as well. Current research on the pathogenesis of Parkinson's disease focuses on damage to the substantia nigra from oxidative stress. Oxidative stress is believed to dim inish brain iron content, impair mitochondrial function, inhibit antioxidant and protective systems, reduce glutathione secretion, and damage lipids, proteins, and DNA. Brain cells are less capable of repairing oxidative damage than are oth er tissues. Signs and symptoms Signs and symptoms may include:

muscle rigidity, akinesia, and an insidious tremor beginning in the fingers (uni lateral pill-roll tremor) that increases during stress or anxiety and decreases with purposeful movement and sleep; secondary to loss of inhibitory dopamine act ivity at the synapse

muscle rigidity with resistance to passive muscle stretching, which may be unifo rm (lead-pipe rigidity) or jerky (cogwheel rigidity) secondary to depletion of d opamine

akinesia causing difficulty walking (gait lacks normal parallel motion and may b e retropulsive or propulsive) from impaired dopamine action

high-pitched, monotone voice from dopamine depletion

drooling secondary to impaired regulation of motor function

mask-like facial expression from depletion of dopamine

loss of posture control (the patient walks with body bent forward) from loss of motor control due to dopamine depletion

dysarthria, dysphagia, or both

oculogyric crises (eyes are fixed upward, with involuntary tonic movements) or b lepharospasm (eyelids are completely closed)

excessive sweating from impaired autonomic dysfunction

decreased motility of gastrointestinal and genitourinary smooth muscle from impa ired autonomic transmission

orthostatic hypotension from impaired vascular smooth muscle response

oily skin secondary to inappropriate androgen production controlled by the hypot halamus pituitary axis. Complications Complications may include:

injury from falls


urinary tract infections

pressure ulcers. Diagnosis Generally, diagnostic tests are of little value in identifying Parkinson's disea se. Diagnosis is based on the patient's age and history, and on the characterist ic clinical picture. However, urinalysis may support the diagnosis by revealing decreased dopamine levels. A conclusive diagnosis is possible only after ruling out other causes of tremor,

involutional depression, cerebral arteriosclerosis, and, in patients under age 30, intracranial tumors, Wilson's disease, or phenothiazine or other drug toxici ty. Treatment The aim of treatment is to relieve symptoms and keep the patient functional as l ong as possible. Treatment includes:

levodopa, a dopamine replacement most effective during early stages and given in increasing doses until symptoms are relieved or side effects appear. (Because s ide effects can be serious, levodopa is frequently given in combination with car bidopa to halt peripheral dopamine synthesis.)

alternative drug therapy, including anticholinergics such as trihexyphenidyl; an tihistamines such as diphenhydramine; and amantadine, an antiviral agent, or Sel egiline, an enzyme-inhibiting agent, when levodopa is ineffective to conserve do pamine and enhance the therapeutic effect of levodopa.

stereotactic neurosurgery when drug therapy fails to destroy the ventrolateral n ucleus of the thalamus to prevent involuntary movement. (This is most effective in young, otherwise healthy persons with unilateral tremor or muscle rigidity. N eurosurgery can only relieve symptoms, not cure the disease.)

physical therapy, including active and passive range of motion exercises, routin e daily activities, walking, and baths and massage to help relax muscles; comple ment drug treatment and neurosurgery attempting to maintain normal muscle tone a nd function. Seizure disorder Seizure disorder, or epilepsy, is a condition of the brain characterized by susc eptibility to recurrent seizures (paroxysmal events associated with abnormal ele ctrical discharges of neurons in the brain). Primary seizure disorder or epileps y is idiopathic without apparent structural changes in the brain. Secondary epil epsy, characterized by structural changes or metabolic alterations of the neuron al membranes, causes increased automaticity. Epilepsy is believed to affect 1% to 2% of the population; approximately 2 milli on people have been diagnosed with epilepsy. The incidence is highest in childho od and old age. The prognosis is good if the patient adheres strictly to prescri bed treatment. Causes About half of all epilepsy cases are idiopathic; possible causes of other cases include:

birth trauma (inadequate oxygen supply to the brain, blood incompatibility, or h emorrhage)

perinatal infection


infectious diseases (meningitis, encephalitis, or brain abscess)

ingestion of toxins (mercury, lead, or carbon monoxide)

brain tumors

inherited disorders or degenerative disease, such as phenylketonuria or tuberous sclerosis

head injury or trauma

metabolic disorders, such as hypoglycemia and hypoparathyroidism

cerebrovascular accident (hemorrhage, thrombosis, or embolism). Pathophysiology Some neurons in the brain may depolarize easily or be hyperexcitable; this epile ptogenic focus fires more readily than normal when stimulated. In these neurons, the membrane potential at rest is less negative or inhibitory connections are m issing, possibly as a result of decreased gamma-amino butyric acid (GABA) activi ty or localized shifts in electrolytes. SEIZURE TYPES The various types of seizures partial, generalized, status epilepticus, or uncla ssified have distinct signs and symptoms. PARTIAL SEIZURES Arising from a localized area of the brain, partial seizures cause focal symptom s. These seizures are classified by their effect on consciousness and whether th ey spread throughout the motor pathway, causing a generalized seizure.

A simple partial seizure begins locally and generally does not cause an alterati on in consciousness. It may present with sensory symptoms (lights flashing, smel ls, hearing hallucinations), autonomic symptoms (sweating, flushing, pupil dilat ion), and psychic symptoms (dream states, anger, fear). The seizure lasts for a few seconds and occurs without preceding or provoking events. This type can be m otor or sensory.

A complex partial seizure alters consciousness. Amnesia for events that occur du ring and immediately after the seizure is a differentiating characteristic. Duri ng the seizure, the patient may follow simple commands. This seizure generally l

asts for 1 to 3 minutes. GENERALIZED SEIZURES As the term suggests, generalized seizures cause a generalized electrical abnorm ality within the brain. They can be convulsive or nonconvulsive, and include sev eral types:

Absence seizures occur most often in children, although they may affect adults. They usually begin with a brief change in level of consciousness, indicated by b linking or rolling of the eyes, a blank stare, and slight mouth movements. The p atient retains his posture and continues preseizure activity without difficulty. Typically, each seizure lasts from 1 to 10 seconds. If not properly treated, se izures can recur as often as 100 times a day. An absence seizure is a nonconvuls ive seizure, but it may progress to a generalized tonic-clonic seizure.

Myoclonic seizures (bilateral massive epileptic myoclonus) are brief, involuntar y muscular jerks of the body or extremities, which may be rhythmic. Consciousnes s is not usually affected.

Generalized tonic-clonic seizures typically begin with a loud cry, precipitated by air rushing from the lungs through the vocal cords. The patient then loses co nsciousness and falls to the ground. The body stiffens (tonic phase) and then al ternates between episodes of muscle spasm and relaxation (clonic phase). Tongue biting, incontinence, labored breathing, apnea, and subsequent cyanosis may occu r. The seizure stops in 2 to 5 minutes, when abnormal electrical conduction ceas es. When the patient regains consciousness, he is confused and may have difficul ty talking. If he can talk, he may complain of drowsiness, fatigue, headache, mu scle soreness, and arm or leg weakness. He may fall into a deep sleep after the seizure.

Atonic seizures are characterized by a general loss of postural tone and a tempo rary loss of consciousness. They occur in young children and are sometimes calle d drop attacks because they cause the child to fall. STATUS EPILEPTICUS Status epilepticus is a continuous seizure state that can occur in all seizure t ypes. The most life-threatening example is generalized tonic-clonic status epile pticus, a continuous generalized tonic-clonic seizure. Status epilepticus is acc ompanied by respiratory distress leading to hypoxia or anoxia. It can result fro m abrupt withdrawal of anticonvulsant medications, hypoxic encephalopathy, acute head trauma, metabolic encephalopathy, or septicemia secondary to encephalitis or meningitis. UNCLASSIFIED SEIZURES This category is reserved for seizures that do not fit the characteristics of pa rtial or generalized seizures or status epilepticus. Included as unclassified ar e events that lack the data to make a more definitive diagnosis. On stimulation, the epileptogenic focus fires and spreads electrical current to surrounding cells. These cells fire in turn and the impulse cascades to one side of the brain (a partial seizure), both sides of the brain (a generalized seizur e), or cortical, subcortical, and brain stem areas. The brain's metabolic demand for oxygen increases dramatically during a seizure. If this demand isn't met, hypoxia and brain damage ensue. Firing of inhibitory neurons causes the excitatory neurons to slow their firing and eventually stop.

If this inhibitory action doesn't occur, the result is status epilepticus: one s eizure occurring right after another and another; without treatment the anoxia i s fatal. Signs and symptoms The hallmark of epilepsy is recurring seizures, which can be classified as parti al, generalized, status epilepticus, or unclassified (some patients may be affec ted by more than one type). (See Seizure types.) Complications Complications may include:

hypoxia or anoxia from airway occlusion

traumatic injury

brain damage

depression and anxiety. Diagnosis Clinically, the diagnosis of epilepsy is based on the occurrence of one or more seizures, and proof or the assumption that the condition that caused them is sti ll present. Diagnostic tests that help support the findings include:

Computed tomography or magnetic resonance imaging reveal abnormalities.

Electroencephalogram (EEG) reveals paroxysmal abnormalities to confirm the diagn osis and provide evidence of the continuing tendency to have seizures. In tonicclonic seizures, high, fast voltage spikes are present in all leads; in absence seizures, rounded spike wave complexes are diagnostic. A negative EEG doesn't ru le out epilepsy, because the abnormalities occur intermittently.

Skull X-ray may show evidence of fractures or shifting of the pineal gland, bony erosion, or separated sutures.

Serum chemistry blood studies may reveal hypoglycemia, electrolyte imbalances, e levated liver enzymes, and elevated alcohol levels, providing clues to underlyin g conditions that increase the risk of seizure activity. Treatment Treatment may include:

drug therapy specific to the type of seizure, including phenytoin, carbamazepine , phenobarbital, and primidone for generalized tonic-clonic seizures and complex partial seizures I.V. fosphenytoin (Cerebyx) is an alternative to phenytoin (Di

lantin) that is just as effective, with a long half-life and minimal CNS depress ion (stable for 120 days at room temperature and compatible with many frequently used I.V. solutions; can be administered rapidly without the adverse cardiovasc ular effects that occur with phenytoin)

valproic acid, clonazepam, and ethosuximide for absence seizures

gabapentin (Neurontin) and felbamate as other anticonvulsant drugs

surgical removal of a demonstrated focal lesion, if drug therapy is ineffective

surgery to remove the underlying cause, such as a tumor, abscess, or vascular pr oblem

vagus nerve stimulator implant may help reduce the incidence of focal seizure

I.V. diazepam, lorazepam, phenytoin, or phenobarbital for status epilepticus

administration of dextrose (when seizures are secondary to hypoglycemia) or thia mine (in chronic alcoholism or withdrawal). Spinal cord trauma Spinal injuries include fractures, contusions, and compressions of the vertebral column, usually as the result of trauma to the head or neck. The real danger li es in spinal cord damage cutting, pulling, twisting, or compression. Damage may involve the entire cord or be restricted to one half, and it can occur at any le vel. Fractures of the 5th, 6th, or 7th cervical, 12th thoracic, and 1st lumbar v ertebrae are most common. Causes The most serious spinal cord trauma typically results from:

motor vehicle accidents


sports injuries

diving into shallow water

gunshot or stab wounds. Less serious injuries commonly occur from:

lifting heavy objects

minor falls. Spinal dysfunction may also result from:


neoplastic lesions. Pathophysiology Like head trauma, spinal cord trauma results from acceleration, deceleration or other deforming forces usually applied from a distance. Mechanisms involved with spinal cord trauma include:

hyperextension from acceleration-deceleration forces and sudden reduction in the anteroposterior diameter of the spinal cord

hyperflexion from sudden and excessive force, propelling the neck forward or cau sing an exaggerated movement to one side

vertical compression from force being applied from the top of the cranium along the vertical axis through the vertebra

rotational forces from twisting, which adds shearing forces. Injury causes microscopic hemorrhages in the gray matter and pia-arachnoid. The hemorrhages gradually increase in size until all of the gray matter is filled wi th blood, which causes necrosis. From the gray matter, the blood enters the whit e matter, where it impedes the circulation within the spinal cord. Ensuing edema causes compression and decreases the blood supply. Thus, the spinal cord loses perfusion and becomes ischemic. The edema and hemorrhage are greatest at and app roximately two segments above and below the injury. The edema temporarily adds t o the patient's dysfunction by increasing pressure and compressing the nerves. E dema near the 3rd to 5th cervical vertebrae may interfere with phrenic nerve imp ulse transmission to the diaphragm and inhibit respiratory function. In the white matter, circulation usually returns to normal in approximately 24 h ours. However, in the gray matter, an inflammatory reaction prevents restoration of circulation. Phagocytes appear at the site within 36 to 48 hours after the i njury, macrophages engulf degenerating axons, and collagen replaces the normal t issue. Scarring and meningeal thickening leaves the nerves in the area blocked o r tangled.

COMPLICATIONS OF SPINAL CORD INJURY Of the following three sets of complications, only autonomic dysreflexia require s emergency attention. AUTONOMIC DYSREFLEXIA Also known as autonomic hyperreflexia, autonomic dysreflexia is a serious medica l condition that occurs after resolution of spinal shock. Emergency recognition and management is a must. Autonomic dysreflexia should be suspected in the patient with:

spinal cord trauma at or above level T6


hypertension and a severe pounding headache

cold or goose-fleshed skin below the lesion. Dysreflexia is caused by noxious stimuli, most commonly a distended bladder or s kin lesion. Treatment focuses on eliminating the stimulus; rapid identification and removal may avoid the need for pharmacologic control of the headache and hypertension. SPINAL SHOCK Spinal shock is the loss of autonomic, reflex, motor, and sensory activity below the level of the cord lesion. It occurs secondary to damage of the spinal cord. Signs of spinal shock include:

flaccid paralysis

loss of deep tendon and perianal reflexes

loss of motor and sensory function. Until spinal shock has resolved (usually 1 to 6 weeks after injury), the extent of actual cord damage cannot be assessed. The earliest indicator of resolution i s the return of reflex activity. NEUROGENIC SHOCK This abnormal vasomotor response occurs secondary to disruption of sympathetic i mpulses from the brain stem to the thoracolumbar area, and is seen most frequent ly in patients with cervical cord injury. This temporary loss of autonomic funct ion below the level of injury causes cardiovascular changes. Signs of neurogenic shock include:

orthostatic hypotension


loss of the ability to sweat below the level of the lesion. Treatment is symptomatic. Symptoms resolve when spinal cord edema resolves. Signs and symptoms

Muscle spasm and back pain that worsens with movement. In cervical fractures, pa in may cause point tenderness; in dorsal and lumbar fractures, it may radiate to other body areas such as the legs.

Mild paresthesia to quadriplegia and shock, if the injury damages the spinal cor d. In milder injury, such symptoms may be delayed several days or weeks. Specific signs and symptoms depend on injury type and degree. (See Types of spin al cord injury.) Complications

autonomic dysreflexia

spinal shock

neurogenic shock. (See Complications of spinal cord injury.) TYPES OF SPINAL CORD INJURY Injury to the spinal cord can be classified as complete or incomplete. An incomp lete spinal injury may be an anterior cord syndrome, central cord syndrome or Br own-Sequard syndrome, depending on the area of the cord affected. This chart hig hlights the characteristic signs and symptoms of each.


Complete transection

All tracts of the spinal cord completely disrupted

All functions involving the spinal cord below the level of transection lost

Complete and permanent loss

Loss of motor function (quadriplegia) with cervical cord transection; paraplegia with thoracic cord transection

Muscle flaccidity

Loss of all reflexes and sensory function below level of injury

Bladder and bowel atony

Paralytic ileus

Loss of vasomotor tone in lower body parts with low and unstable blood pressure

Loss of perspiration below level of injury

Dry pale skin

Respiratory impairment Incomplete transection: Central cord syndrome

Center portion of cord affected

Typically from hyperextension injury

Motor deficits greater in upper than lower extremities

Variable degree of bladder dysfunction

Incomplete transection: Anterior cord syndrome

Occlusion of anterior spinal artery

Occlusion from pressure of bone fragments

Loss of motor function below level of injury

Loss of pain and temperature sensations below level of injury

Intact touch, pressure, position and vibration senses Incomplete transection: Brown-Sequard Syndrome

Hemisection of cord affected

Most common in stabbing and gunshot wounds

Damage to cord on only one side

Ipsilateral paralysis or paresis below the level of the injury

Ipsilateral loss of touch, pressure, vibration, and position sense below level o f injury

Contralateral loss of pain and temperature sensations below level of injury Diagnosis

Spinal X-rays, the most important diagnostic measure, detect the fracture.

Thorough neurologic evaluation locates the level of injury and detects cord dama


Lumbar puncture may show increased CSF pressure from a lesion or trauma in spina l compression.

Computed tomography or magnetic resonance imaging reveals spinal cord edema and compression and may reveal a spinal mass. Treatment Treatment may include:

immediate immobilization to stabilize the spine and prevent cord damage (primary treatment); use of sandbags on both sides of the patient's head, a hard cervica l collar, or skeletal traction with skull tongs or a halo device for cervical sp ine injuries

high doses of methylprednisolone to reduce inflammation with evidence of cord in jury

bed rest on firm support (such as a bed board), analgesics, and muscle relaxants for treatment of stable lumbar and dorsal fractures for several days until the fracture stabilizes.

plaster cast or a turning frame to treat unstable dorsal or lumbar fracture

laminectomy and spinal fusion for severe lumbar fractures

neurosurgery to relieve the pressure when the damage results in compression of t he spinal column If the cause of compression is a metastatic lesion, chemotherap y and radiation may relieve it.

treatment of surface wounds accompanying the spinal injury; tetanus prophylaxis unless the patient has had recent immunization

exercises to strengthen the back muscles and a back brace or corset to provide s upport while walking

rehabilitation to maintain or improve functional level. 9 GASTROINTESTINAL SYSTEM

Handbook of Pathophysiology 9 GASTROINTESTINAL SYSTEM

Pathophysiologic concepts € Anorexia € Constipation € Diarrhea € Dysphagia € Jaundice € Nausea € Vomiting Disorders € Appendicitis € Cholecystitis € Cirrhosis € Crohn's disease € Diverticular disease € Gastroesophageal reflux disease € Hemorrhoids € Hepatitis, nonviral € Hepatitis, viral € Hirschsprung's disease € Hyperbilirubinemia € Irritable bowel syndrome € Liver failure € Malabsorption € Pancreatitis € Peptic ulcer € Ulcerative colitis The gastrointestinal (GI) system has the critical task of supplying essential nu trients to fuel all the physiologic and pathophysiologic activities of the body.

AGE ALERT The elderly typically experience a decrease in intestinal motility in addition to a slowing and dulling of neural impulses in the GI tract. touch. biliary duct system (gallbladder and bile ducts). the physiologic stimuli are present but the person has no appetite or desire to eat. or renal disease. Hi gh levels of neurotransmitters such as serotonin (may contribute satiety) and ex cess cortisol levels (may suppress hypothalamic control of hunger) have been imp licated. It is defined individually. For exa mple. Causes of constipation include dehydration. When a person is dehydrated or delays defecation. the stool becomes harder. Fal ling blood glucose levels stimulate the hunger center in the hypothalamus. Anorexia can result from dysfunction. High fiber diets cause water to be drawn into the stool by osmosis. and frequent repression of the urge to defecate. or G I tract. The alimentary canal is a hollow muscular tube that begins in the mouth and ends at the anus. absorption. nausea. a low fiber diet woul d contribute to constipation. in the gastrointestinal system or oth er systems. esophagus. A malfunction anywhere in the system can prod uce far-reaching metabolic effects. lack of regular exercise. nonspecific complaints or pr oblems that reflect disruption in one or more of the system's functions. movement through the GI tract can be slowed. the most common being anorexia. thereby keeping stool soft a nd encouraging movement through the intestine. one patient may present with several problems. a sedentary lifestyle. or motility can be altered. Many older persons restrict fluid intake to prevent waking at night to use the bathroom or because of a fear of incontinence. Accessory glands and organs include the salivary glands. a physiologic stimulus is responsible for the sensation of hunger. Conversely. liver. Hunger is also stimulated by contraction of an empty stomach and suppressed when the GI tract becomes distend ed. This places them at risk for dehydration and constipation. PATHOPHYSIOLOGIC CONCEPTS Disorders of the GI system often manifest as vague. Sight. accelerated. and the accessory organs. The GI system has two major components: the alimentary canal. In anorexia. constipation. pharynx. more fluid is absorbed from th e intestine. Nausea. and diarrhea may accompany it. and secretion. heart disease. A sedentary lifestyle or lack of exercise can cause constipation because exercis . possibly as a result of stimulation of the vagus nerve. the GI tract and accessory organs serve two major functions: digestion (breaking down food and fluids into simple chemicals that can be absorbed into the bloodstream and transported throughout the body) and elimination of waste pr oducts from the body through defecation. dysphagia. eventually threatening life itself. Constipation Constipation is hard stools and difficult or infrequent defecation. Slow gastric emptying or gastric stasis can cause anorexia. and vomiting. becau se normal bowel habits range from 2 to 3 episodes of stool passage per day to on e per week. consumption of a low bul k diet. and large intestine. stomach. dia rrhea. Peristalsis propels the ingested material along th e tract. and constipation ensues. It includes the oral cavity. As a result. small in testine. such a s cancer. High fiber diets also causes inte stinal dilation. and sm ell play subtle roles in controlling the appetite center. Anorexia Anorexia is a loss of appetite or a lack of desire for food. which stimulates peristalsis. or blocked. as defined b y a decrease in the number of stools per week. and pa ncreas.Its functioning profoundly affects the quality of life through its impact on ov erall health. Together. Normally. abdominal p ain. jaundice. sphincters prevent its reflux. risin g blood fat and amino acid levels promote satiety.

Extrinsic obstruc tions originate outside of the esophagus and narrow the lumen by exerting pressu re on the esophageal wall. the neural pattern to initiate swallowing. Motility diarrhea: Inflammation. Absence or degeneration in the neural pathways of the large intestine also contributes to constipation. Upper esophageal obstruction causes pain 2 to 4 seconds after swallowing. secretions. lower esophageal obstructions. such as spinal cord trauma. Antacids. Factors that affect stool volume and consistency include water conte nt of the colon and the presence of unabsorbed food. and GI motility slows. multiple scle rosis. Impaired motor function makes both liquids and solids difficult to swallow. or obstruction causes a reflex incr ease in intestinal motility that may expel the irritant or clear the obstruction . and motility: Osmotic diarrhea: The presence of nonabsorbable substance. Most extrinsic obstruction results from a tumor. Secretory diarrhea: A pathogen or tumor irritates the muscle and mucosal layers of the intestine. must occur: Food reaching the back of the mouth stimulates swallowing receptors that surroun d the pharyngeal opening. or increased numbers of osmotic particles in the intestine. secretion. Small-volume diarrhea is usually caused by excessive intestinal motility. Mec hanical obstruction is characterized as intrinsic or extrinsic. opiat es. Causes of intrinsic tu mors include tumors. can cause constipation. increases osmoti c pressure and draws excess water into the intestine. strictures.e stimulates the gastrointestinal tract and promotes defecation. intestinal neoplasms. and mucus) results in diarrhea. Distention and spasm at the site of the obstruction during swallowing may cause pain. and diverticular herniations. such as synthetic sug ar. Intrinsic obstructions originate in the esophagus itself. thereby increasing the wei ght and volume of the stool. dysphagia begins with difficulty swallowing solids and eventually progr esses to difficulty swallowing semi-solids and liquids. Large-volume diarrhea is usually the result of an excessi ve amount of water. and intestinal secretions. or both in the intestines. and other drugs that inhibit bowel motility also lead to constipation. And other conditions. Stress stimulates the sympathetic nervous system. Diarrhea may also be caused by a parasympathetic stimulation of the gut initiated by psychological factors such as fear or stress. If a tumor is present. . ele ctrolytes. The consequent increase in motility and secretions (water. WHAT HAPPENS IN SWALLOWING Before peristalsis can begin. Dysphagia can be caused by a mechanical obstruction of the Dysphagia difficulty swallowing esophagus or by impaired esophageal motility secondary to another disorder. The three major mechanisms of diarrhea are osmosis. illustr ated here. and hypothyroidism. 10 to 15 seconds after swallowing. Diarrhea Diarrhea is an increase in the fluidity or volume of feces and the frequency of defecation. unabsorbable material. neuropathy.

cancer. This imbalanc e can result from excessive release of bilirubin precursors into the bloodstream or from impairment of its hepatic uptake. The three main types of jaundice are hemolytic jaundice. which is about twice the upper limit of the normal range. cerebrovascular accident. Neural or muscular disorders can also interfere with voluntary swallowing or per istalsis. Eventually. . and palmar or plantar surfaces. The lower end of the esoph agus loses neuromuscular coordination and muscle tone.) Malfunction of the upper esophageal stri ated muscles interferes with the voluntary phase of swallowing. Causes of functional dysphagia include dermatomyositis. or obstructive jaundice: Hemolytic jaundice: When red blood cell lysis exceeds the liver's capacity to co njugate bilirubin (binding bilirubin to a polar group makes it water soluble and able to be excreted by the kidneys).5 mg/dl). Lower levels of bilirubin may cause detectable jaundice in patien ts with fair skin. Liver dysfunction can occur in hepatitis. a nd the cardiac sphincter of the stomach cannot relax. Parkinson's disease. or excretion. CULTURAL DIVERSITY Jaundice in dark-skinned persons may appear as yellow stainin g in the sclera. and food accumulates. or cong enital disorders. This is known as functional dysphagia. Jaundice Jaundice yellow pigmentation of the skin and sclera is caused by an excess accum ulation of bilirubin in the blood. accumulated food raises the hydrostat ic pressure and forces the sphincter open. Swallowing occurs. Hepatocellular jaundice: Hepatocyte dysfunction limits uptake and conjugation of bilirubin. sickle cell anemia. or achal asia. cau sing hypertrophy and dilation. thalassemia. In achalasia. and jaundice may be difficult to detect in patients with dark skin. hemolytic jaundice occurs. and small amounts of food slowly move into the stomach. Causes include transfusion reactions.The receptors transmit impulses to the brain by way of the sensory portions of t he trigeminal (V) and glossopharyngeal (IX) nerves. and hypoglossal (XII) nerve s. (See What happens in swallowing. hepatocellular jaundice .0 to 2. The brain's swallowing center relays motor impulses to the esophagus by way of t he trigeminal (V). glossopharyngeal (IX). the esophageal ganglionic cells are thought to have degenerated. hard palate. a product of red blood cell breakd own. accumulates when production exceeds metabolism and excretion. (See Jaundi ce: Impaired bilirubin metabolism.) Jaundice occurs when bilirubin levels exceed 34 to 43 mmol/L (2. and autoimmune disease. metabolism. vagus (X). and some drugs can cause it. cirrhosis. Bilirubin.

bacterial toxins. causing intestinal material to flow back into the st omach. Nausea m ay also be stimulated by high brain centers. A blocked bile duct is an extrahepatic cause. The stomach pushes the diaphragm into the thoracic cavity. the liver can conjugate bilirubin. combined with the annular contraction o f the gastric pylorus. Blockage of the hepatic duct by stones or a tumor is considered an intrahepatic cause of obstructive jaundice .Obstructive jaundice: When the flow of bile out of the liver (through the hepati c duct) or through the bile duct is blocked. raising the intrathor acic pressure. It may occur independently of vomiting. and metabolic abnormalities. from higher brainstem an d cortical centers. diminished functional activities of the stomach. Various stimuli or drugs activate t he zone. but increased salivation. and altered small intestinal motility have been associated with nausea. forces gastric contents into the esophagus. and the following sequence begins: The abdominal muscles and diaphragm contract. levodopa. In all thr ee. The chemoreceptor t rigger zone can't induce vomiting by itself. Vomiting Vomiting is the forceful oral expulsion of gastric contents. hepatic. The gastric fundus and gastroesophageal sphinc ter relax. and posthepatic. the glottis closes. The gastric muscula ture provides the ejection force. but the bilirubin can't reach the small intestine. Nausea Nausea is feeling the desire to vomit. The pressure also forces the material up through the sphincter and out through t he mouth. JAUNDICE: IMPAIRED BILIRUBIN METABOLISM Jaundice occurs in three forms: prehepatic. It is stimulated by the gastrointestinal tract. and forceful contractions of the diaphragm and abdominal wall muscles increase intraabdominal pressure. such as apomorphine. distending it. The vomiting center initiates the actual act of vo miting. Vomiting is controlled by two centers in the medulla: the vomiting center and th e chemoreceptor trigger zone. Reverse peristalsis begins. digitalis. Specific neural pathways have not been identif ied. Increased int rathoracic pressure then moves the gastric content from the esophagus to the mou th. and from the chemoreceptor trigger zone. o r it may precede or accompany it. and the soft palate blocks the nasopharynx. . The activated zone sends impulses to the medullary vomiting center. radiation. Gallstones or a tumor may obstru ct the bile duct. This. bilirubin levels in the blood increase. The pressure forces the upper esophageal sphincter open.

Vomiting may also be ps ychogenic. tumor. Both nausea and vomiting are manifestations of other disorders. Intestinal enzymes convert bilirubin to water-soluble urobilinogen for excretion in urine and stools. this disease is invariably fatal. cirrhosis. central nervous system disorders. scar tissue. cause massive hemolysis. or as the side effect of many drugs. appendicitis is inflammation and obstruc tion of the vermiform appendix. congestive heart failure. Inflammation. such as acute ab dominal emergencies. Water-soluble conjugated bilirubin accumulates in the blood. The bilirubin is excreted in the urine. Appendicitis may occur at any age and affects bo th sexes equally. so it can't be directly secreted in urine. between puberty and age 25. Large amounts of unconjugated bilirubin pass into the blood. leading to increased blood levels of conjugated and unconjugated bilirubin. Since the advent of antibiotics. and metastatic cancer. metabolic and endocr inologic disorders. however. POSTHEPATIC JAUNDICE In biliary and pancreatic disorders. or gallstones block the flow of bile into the intestines. . and during prolonged use o f drugs metabolized by the liver. such as transfusion reactions and sickle cell anemia. myocardial infarction. it's more prevalent in me n. resulting from emotional or psychological disturbance. This occurs in such diso rders as hepatitis. DISORDERS Appendicitis The most common major surgical disease. infections of the intestinal tract. the incidence and the death rate of appendic itis have declined. Red blood cells rupture faster than the liver can conjugate bilirubin. bilirubin forms at its normal rate.) HEPATIC JAUNDICE The liver becomes unable to conjugate or excrete bilirubin. if untreated.PREHEPATIC JAUNDICE Certain conditions and disorders. (Unconjugated bilirubin is insoluble in water.

restricting blood flow to the organ and causing s evere abdominal pain. Pressure in the now distended appendix increases. Bacteria multiply. and inflammation and pressure continue to increase. which temporarily obstructs the append ix.Causes Causes may include: mucosal ulceration fecal mass stricture barium ingestion viral infection. The obstruction blocks mucus outflow. Pathophysiology Mucosal ulceration triggers inflammation. and the appendix contracts. Complications Complications may include: wound infection . Signs and symptoms Signs and symptoms may include: abdominal pain caused by inflammation of the appendix and bowel obstruction and distention anorexia after the onset of pain nausea or vomiting caused by the inflammation low-grade temperature from systemic manifestation of inflammation and leukocytos is tenderness from inflammation.

Treatment Treatment may include: maintenance of NPO status until surgery high Fowler's position to aid in pain relief GI intubation for decompression appendectomy antibiotics to treat infection if peritonitis occurs parental replacement of fluid and electrolytes to reverse possible dehydration r esulting from surgery or nausea and vomiting. .intraabdominal abscess fecal fistula intestinal obstruction incisional hernia peritonitis death. Diagnosis White blood cell count is moderately high with an increased number of immature c ells. X-ray with radiographic contrast agent reveals failure of the appendix to fill w ith contrast.

) When bile flow is blocked. B acterial growth. the chronic form. Ch olecystitis accounts for 10% to 25% of all patients requiring gallbladder surger y. The acute form is most common among middle-aged women.Cholecystitis Cholecystitis acute or chronic inflammation causing painful distention of the ga llbladder is usually associated with a gallstone impacted in the cystic duct. amon g the elderly. E dema of the gallbladder (and sometimes the cystic duct) obstructs bile flow. and an exudate covers ulcerated areas. Causes Gallstones (the most common cause) Poor or absent blood flow to the gallbladder Abnormal metabolism of cholesterol and bile salts. Signs and symptoms Acute abdominal pain in the right upper quadrant that may radiate to the back. cau sing the gallbladder to adhere to surrounding structures. (See Understanding gallstone formatio n. inflammation of the gallbladder wall usually develops af ter a gallstone lodges in the cystic duct. Complications . the gallbladder becomes inflamed and distended. Cells in the gallbladder wall may becom e oxygen starved and die as the distended organ presses on vessels and impairs b lood flow. whi ch chemically irritates the gallbladder. Pathophysiology In acute cholecystitis. The dead cells slough off. or to the front of the chest secondary to inflammation and irritation of nerve fibers Colic due to the passage of gallstones along the bile duct Nausea and vomiting triggered by to the inflammatory response Chills related to fever Low-grade fever secondary to inflammation Jaundice from obstruction of the common bile duct by stones. The prognosis is good with treatment. usually Escherichia coli. b etween the shoulders. may contribute to the inflammation.

also h elps disclose porcelain gallbladder (hard. lactate dehydrogenase. and gallstone ileus. aspartate aminotransf erase. and icteri . Levels of serum alkaline phosphate. limy bile. brittle gall bladder due to calcium d eposited in wall). Technetium-labeled scan indicates reveals cystic duct obstruction and acute or c hronic cholecystitis if ultrasound doesn't visualize the gallbladder. serum amylase slightly elevated. Diagnosis X-ray reveals gallstones if they contain enough calcium to be radiopaque. Ultrasonography detects gallstones as small as 2 mm and distinguishes between ob structive and nonobstructive jaundice.Perforation and abscess formation Fistula formation Gangrene Empyema Cholangitis Hepatitis Pancreatitis Gallstone ileus Carcinoma. and total bilirubin are high. Percutaneous transhepatic cholangiography or cholesystoscopy supports the diagno sis of obstructive jaundice and reveals calculi in the ducts.

White blood cell counts are slightly elevated during cholecystitis attack. Mortality is high. jaundice.c index elevated. this dise ase damages liver tissue and normal vasculature. UNDERSTANDING GALLSTONE FORMATION Abnormal metabolism of cholesterol and bile salts plays an important role in gal . and is especially prevalent among malnourished persons over the age of 50 w ith chronic alcoholism. and bleeding tendencies due to vitamin K deficiencies Antibiotics for use during acute attack for treatment of infection Nasogastric tube insertion during acute attack for abdominal decompression. It's twice as common in men as in wo men. Cirrhosis Cirrhosis is a chronic disease characterized by diffuse destruction and fibrotic regeneration of hepatic cells. As necrotic tissue yields to fibrosis. impairs blood and lymph flow. a nd ultimately causes hepatic insufficiency. Treatment Cholecystectomy to surgically remove the inflamed gallbladder Choledochostomy to surgically create an opening into the common bile duct for dr ainage Percutaneous transhepatic cholecytostomy Endoscopic retrograde cholangiopancreatography for removal of gallstones Lithotripsy to break up gallstones and relieve obstruction Oral chenodeoxycholic acid or ursodeoxycholic acid to dissolve stones Low fat diet to prevent attacks Vitamin K to relieve itching. many patients die within 5 years of o nset.

and adventitia (the outermost layer). The following clinical ty pes of cirrhosis reflect its diverse etiology. Autoimmune disease such as sarcoidosis or chronic inflammatory bowel disease may cause cirrhosis. Fat entering the duodenum causes the intestinal mucosa to secrete the hormone ch olecystokinin. cause the live r to secrete bile that's abnormally high in cholesterol or lacking the proper co ncentration of bile salts. and estrogen imbalance. This group includes diseases of the biliary tree (biliary cirrhosis resulting from bile duct diseases suppressing bile flow) and sclerosin . the bile can't flow into the duodenum . Excessive r eabsorption of water and bile salts makes the bile less soluble. inflammation may occur. INSIDE THE GALLBLADDER When the gallbladder concentrates this bile. Cholesterol. also called portal. The liver makes bile continuously. This group includes the following disorders: Postnecrotic cirrhosis accounts for 10% to 30% of patients and stems from variou s types of hepatitis (such as Types A. UP THE BILIARY TREE Inflammation can progress up the biliary tree into any of the bile ducts. and bilirubin precipitate into gallstones. is t he most common type and is primarily caused by hepatitis C. B. and bleed ing. The gall bladder concentrat es and stores it until the duodenum signals it needs it to help digest fat. which stimulates the gallbladder to contract and empty. the gallbladder contracts but can't empty. Bilirubin is absorbed into the blood and causes jaundice. Changes to the abso rptive ability of the gallbladder lining may also contribute to gallstone format ion. Cholestatic diseases. This c auses scar tissue. IRRITATION. JAUNDICE. If a ston e lodges in the cystic duct. TOO MUCH CHOLESTEROL Certain conditions. INFLAMMATION If a stone lodges in the common bile duct. Causes Cirrhosis may be a result of a wide range of diseases. Hepatocellular disease. cirrhosis. Chan ges in the composition of bile may allow gallstones to form. Laënnec's cirrhosis. C. F ibrous tissue forms in portal areas and around central veins. Liver damage results from malnutrition (especially dietary protein) and chronic alcohol ingestion. D viral hepatitis) or toxic exposur es.lstone formation. Biliary narrowing and swelling of the tissue around the stone can also cause irr itation and inflammation of the common bile duct. ca lcium. obesity. The coronary arteries are made of three layers: intim a (the innermost layer. fluid accumulation. nutritional. or alcoholic cirrhosis. portal hypertension. such as age. media (the middle layer).

including lethargy. and portal hypertension endocrine testicular atrophy. Cellular changes producing bands of scar tissue also disrupt the lobular structure. menstrual irregularities. and hyaluronic acid. and coma secondary to loss of ammonia to urea conversion and consequent delivery of toxic ammonia to the brai n hematologic bleeding tendencies (nosebleeds. Cryptogenic refers to cirrhosis o f unknown etiology. interferes with efficient gas exchange and causes hypoxia central nervous system progressive signs or symptoms of hepatic encephalopathy. and hemochromatosis (pigment cirrhosis). hallucinations. and loss o . Signs and symptoms The following are signs and symptoms of the early stages: anorexia from distaste for certain foods nausea and vomiting from inflammatory response and systemic effects of liver inf lammation diarrhea from malabsorption dull abdominal ache from liver inflammation. paranoia. proteoglycans. The following are signs and symptoms of the late stages: respiratory pleural effusion. gynecomastia. and ascites due to hepatic vein obstruction ). anem ia resulting from thrombocytopenia (secondary to splenomegaly and decreased vita min K absorption). mental changes. asterixis. slurred speech. extreme obtundation. Contract ion of these cells may also contribute to disruption of the lobular architecture and obstruction of the flow of blood or bile. the liver damage results from right heart failure. Other types of cirrhosis include Budd-Chiari syndrome (epigastric pain. The site of collagen deposition varies with the cause. Hepatocyte function is eventually impaired as the matrix changes. liver enlargement. and cryptogenic cirrhosis. peripheral neurit is. cardiac cirrhosis. alph a1-antitrypsin. splenomegaly. f ibronectin. limited thoracic expansion due to abdominal ascite s. The scar begins as an increa se in extracellular matrix components fibril-forming collagens. Fat-st oring cells are believed to be the source of the new matrix components.g cholangitis. This group includes disorders such as Wilson's disease. Cardiac cirrhosis is rare. Metabolic diseases. easy bruising. bleeding gums). Other types of cirrhosis. Pathophysiology Cirrhosis begins with hepatic scarring or fibrosis.

pain and inc reased temperature from liver inflammation hemorrhage from esophageal varices resulting from portal hypertension. hepatic encephalopathy from ammoni a toxicity. spider ang iomas. and hepatorenal syndrome from advanced liver disease and subsequent renal failure miscellaneous musty breath secondary to ammonia build up. palmar erythema. (See What happens in portal hypertension.f chest and axillary hair from decreased hormone metabolism skin severe pruritus secondary to jaundice from bilirubinemia.) Complications Complications may include: ascites portal hypertension jaundice coagulopathy hepatic encephalopathy bleeding esophageal varices. hepatomegaly secondary to liver scarring and portal hypertension. and jaundice related to impaired hepatic function hepatic jaundice from decreased bilirubin metabolism. due to inflammation an d irritation of area nerve fibers. temperature of 101° to 103° F (38° to 39° C) due to inflammatory response. abnormal pigmentation. pain in the right upper abdominal qua drant that worsens when patient sits up or leans forward. ascites and edema of the legs from porta l hypertension and decreased plasma proteins. extreme dryness a nd poor tissue turgor related to malnutrition. palpable liver or spleen due to organomegaly. acute GI bleeding liver failure . enlarged superficial a bdominal veins due to portal hypertension.

and hepati c blood flow and obstruction. or gas within the biliary tract or liver. and K. Diagnosis Liver biopsy reveals tissue destruction and fibrosis. or duodenal bleeding and irritation. and massive fluid accumulation (ascites). Abdominal X-ray shows enlarged liver. and serum electrolytes. total serum bilirubin. hematocrit. decreased hemoglobin. Urine studies show increased bilirubin and urobilirubinogen.renal failure. Treatment Vitamins and nutritional supplements to help heal damaged liver cells and improv e nutritional status Antacids to reduce gastric distress and decrease the potential for gastrointesti nal bleeding Potassium-sparing diuretics to reduce fluid accumulation Vasopressin to treat esophageal varices . abnormal masses. Fecal studies show decreased fecal urobilirubinogen. Blood studies reveal elevated liver enzymes. and indirect bilirubin. decreased total serum albumin and protein. stomach irritati on or ulceration. liver calcification. C. and deficiency of v itamins A. Esophagogastroduodenoscopy reveals bleeding esophageal varices. cysts. prolonged prothrombin tim e. Computed tomography and liver scans show liver size.

Gastric lavage until the contents are clear. As the pressure in the portal vein rises. extending through all la yers of the intestinal wall. seldom performed). It may also involve regional lymph nodes and the me sentery. and improved urine output Sclerosing agents injected into oozing vessels to cause clotting and sclerosis Insertion of portosystemic shunts to control bleeding from esophageal varices an d decrease portal hypertension (diverts a portion of the portal vein blood flow away from the liver. increased abdominal girth. Thus. This common result of cirrhosis may also stem from mechanical obstruction and occlusion of the hepatic veins (Budd-Chiari syndrome ). increased sodium excretion from the kidne ys. WHAT HAPPENS IN PORTAL HYPERTENSION Portal hypertension (elevated pressure in the portal vein) occurs when blood flo w meets increased resistance. bypassing the liver. is i nflammation of any part of the gastrointestinal tract (usually the proximal port ion of the colon and less commonly the terminal ileum). leading to w eight loss. portal hypertension causes: splenomegaly with thrombocytopenia dilated collateral veins (esophageal varices. blood backs up into the spleen and flo ws through collateral channels to the venous system. Crohn's disease Crohn's disease. hemorrhoids.Esophagogastric intubation with multilumen tubes to control bleeding from esopha geal varices or other hemorrhage sites by using balloons to exert pressure on bl eeding site. Crohn's disease is most prevalent in adults ages 20 to 40. or prominent abdomina l veins) . with antacids and histamine antagon ists if bleeding is secondary to a gastric ulcer Esophageal balloon tamponade to compress bleeding vessels and stop blood loss fr om esophageal varices Paracentesis to relieve abdominal pressure and remove ascitic fluid Surgical shunt placement to divert ascites into venous circulation. also known as regional enteritis or granulomatous colitis.

inflamed bow . Causes The exact cause is unknown but the following conditions may contribute: lymphatic obstruction allergies immune disorders infection genetic predisposition.ascites. In many patients. Oval. Mucosal ulcerations are called skipping lesions'' because they are not continuous. Subsequent fibrosis thickens the b owel wall and causes stenosis. as in ulcerative colitis. Enlarged lymph nodes block lymph flow in the submucosa. Pathophysiology Whatever the cause of Crohn's disease. inflammation spreads slowly and progressi vely. At first. CULTURAL DIVERSITY Crohn's disease is two to three times more common in Ashkenaz ic Jews and least common in African Americans. elevated patches of closely packed lymph follicles called Peyer's patches develop in the lining of the small intestine. the mucosa may appear normal. mucosal ulceration and fissures.) The serous membrane becomes inflamed (serositis). and sometimes gr anulomas. (See Bowel changes in Crohn's disease. fibrosis thickens the bowel wall and narrows the lumen. Narrowing or stenosis can occur in any part of the intestine and cause va rying degrees of intestinal obstruction. Up to 20% of patients have a posi tive family history for the disease. but as the disease progresses it takes on a cobblestone appearance as shown. the first sign of portal hypertension is bleeding esophageal v arices (dilated tortuous veins in the submucosa of the lower esophagus). requiring emergency care to cont rol hemorrhage and prevent hypovolemic shock. abscesses. Lymphatic obstruct ion leads to edema. Esophag eal varices commonly cause massive hematemesis. or narrowing of the lumen. BOWEL CHANGES IN CROHN'S DISEASE As Crohn's disease progresses.

Complications Complications may include: anal fistula perineal abscess fistulas to the bladder or vagina or to the skin in an old scar area intestinal obstruction nutrient deficiencies from poor digestion and malabsorption of bile salts and vi tamin B12 . and shorter. and diseased bowel segments b ecome interspersed with healthy ones. loss of healthy intestinal surface area . diseased parts of the bowel becom e thicker.el loops adhere to other diseased or normal loops. colicky pain in the right lower quadrant due to acute inflammation and n erve fiber irritation cramping due to acute inflammation tenderness due to acute inflammation weight loss secondary to diarrhea and malabsorption diarrhea due to bile salt malabsorption. and bacterial growth steatorrhea secondary to fat malabsorption bloody stools secondary to bleeding from inflammation and ulceration. Finally. Signs and symptoms Signs and symptoms include: steady. narrower.

calcium. and bl eeding Immunosuppressants to suppress the response to antigens Sulfasalazine to reduce inflammation Metronidazole to treat perianal complications Antidiarrheals to combat diarrhea (not used with patients with significant bowel obstruction) Narcotic analgesics to control pain and diarrhea . and decreased potassium. and stiffening. subsequently.fluid imbalances. magnesium. ulcers may be seen. Barium enema reveals the string sign (segments of stricture separated by normal bowel) and possibly fissures and narrowing of the bowel. pain. ulceration. Small bowel X-ray shows irregular mucosa. Blood tests reveal increased white blood cell count and erythrocyte sedimentatio n rate. Treatment Corticosteroids to reduce inflammation and. Diagnosis Fecal occult test reveals minute amounts of blood in stools. Biopsy reveals granulomas in up to half of all specimens. Sigmoidoscopy and colonoscopy reveal patchy areas of inflammation (helps to rule out ulcerative colitis). diarrhea. and hemoglobin levels. with cobblestone-like mucosal surface. With colon invo lvement.

near the pancreatic border or the ampulla of Vater. PATHOGENESIS OF DIVERTICULAR DISEASE The etiology of diverticular disease hasn't been determined. fr om the proximal end of the pharynx to the anus. Diverticular disease of the ileum (Meckel's diverticulum ) is the most common congenital anomaly of the gastrointestinal tract. . or hemorrhage. colectomy with ileostomy in patient s with extensive disease of the large intestine and rectum. carbonated or caffe inated beverages. Diverticular disease of the stomach is rare and is usually a precursor of peptic or neoplastic disease. if necessary. dairy prod ucts. Diverticular disease has two clinical forms: diverticulosis. high fiber foods. and other foods or liquids that stimulate excessive intestinal activity) to decrease bowel activity while still providing adequate nutrition Surgery. infection. It's thought to ari se from a disordered colonic motility pattern. vegetables. fistulas or acute intestinal obstruction. Although the most co mmon site for diverticula is in the sigmoid colon. foods that irritate the mucosa. CULTURAL DIVERSITY Diverticular disease is common in Western countries.Stress reduction and reduced physical activity to rest the bowel and allow it to heal Vitamin supplements to replace and compensate for the bowel's inability to absor b vitamins Dietary changes (elimination of fruits. to repair bowel perforation and correct massive hemorrhag e. Diverticular disease In diverticular disease. in which diverticula are inflamed and may cause potentially fata l obstruction. Other typical sites include the duodenum. bulging pouches (diverticula) in the gastrointestinal w all push the mucosal lining through the surrounding muscle. spicy and fatty foods. they may develop anywhere. These diagrams compare normal and abnormal patterns. suggesti ng that a low-fiber diet reduces stool bulk and leads to excessive colonic motil ity. in which diverticula are present but don't cause symptoms diverticulitis. This consequent increased intraluminal pressure causes herniation of the mu cosa. and the jejunum.

In severe diverticulitis. Pathophysiology Diverticula probably result from high intraluminal pressure on an area of weakne ss in the gastrointestinal wall. (See Pathogenesis of diverticular disease. obstruction. Inflammation fo llows and may leading to perforation. hypotension from sepsis. This hard mass cuts off the blood supply to the thin walls of the sac. narrows the bowel lumen. retained undigested food and bacteria accumulates in the dive rticular sac. signs and symptoms include: moderate left lower abdominal pain secondary to inflammation of diverticula low-grade fever from trapping of bacteria-rich stool in the diverticula leukocytosis from infection secondary to trapping of bacteria-rich stool in the diverticula. abscess. or hemo rrhage. In mild diverticulitis. where blood vessels enter. peritonitis.) Diet may be a contributing factor. the inflamed colon segment may adhere to the bladder or ot her organs and cause a fistula. because insufficient fiber reduces fecal residue. abscesses. making them more susceptible to attack by colonic bacteria. Severe diverticulitis. and peritonitis left lower quadrant pain secondary to rupture of the diverticula and subsequent inflammation and infection high fever. chills. Mild diverticulitis. More than half of patients older than 50 years have co lonic diverticula. and shock from the release of fecal . Occasionally. In diverticulitis. Signs and symptoms Typically the patient with diverticulosis is asymptomatic and will remain so unl ess diverticulitis develops.AGE ALERT Diverticular disease is most prevalent in men over age 40 and persons who eat a low fiber diet. signs and symptoms include: abdominal rigidity from rupture of the diverticula. Causes Diminished colonic motility and increased intraluminal pressure Low fiber diet Defects in colon wall strength. and leads to high intra-ab dominal pressure during defecation.

Barium enema reveals filling of diverticula. Chronic diverticulitis. ruling out cancer. Diagnosis Upper GI series confirms or rules out diverticulosis of the esophagus and upper bowel. Blood studies show an elevated erythrocyte sedimentation rate in diverticulitis. signs and symptoms include: constipation. Biopsy reveals evidence of benign disease. In chronic diverticulitis. intermittent diarrhea. diminishing or absent bowel sounds. minimize irritation. Treatment Liquid or bland diet.material from the rupture site microscopic or massive hemorrhage from rupture of diverticulum near a vessel. nausea. which confirms diagnosis. and lessen t he risk of progression to diverticulitis High-residue diet for treatment of diverticulosis after pain has subsided to hel p decrease intra-abdominal pressure during defecation Exercise to increase the rate of stool passage Antibiotics to treat infection of the diverticula Meperidine (Demerol) to control pain and to relax smooth muscle . ribbon-like stools. stool softeners. and occasional doses of mineral oil for s ymptomatic diverticulosis to relieve symptoms. and abdominal distentio n resulting from intestinal obstruction (possible when fibrosis and adhesions na rrow the bowel's lumen) abdominal rigidity and pain. and vom iting secondary to intestinal obstruction.

HOW HEARTBURN OCCURS Hormonal fluctuations. an d anticholinergic agents food. Th e pain may radiate to the chest or arms. When LES pressure falls and intraabdominal or intragastric pressure rises. peritonitis. alcohol. mechanical stress. Causes Causes of GERD include: weakened esophageal sphincter increased abdominal pressure. There. Gastroesophageal reflux disease Popularly known as heartburn. Lying down after a meal also contributes to reflux. without associated belching or vomiting.Antispasmodics to control muscle spasms Colon resection with removal of involved segment to correct cases refractory to medical treatment Temporary colostomy if necessary to drain abscesses and rest the colon in divert iculitis accompanied by perforation. causing pyrosis. usually after a meal. the reflux irritates and inflames the esophageal mucosa . the normally contracted LES relax es inappropriately and allows reflux of gastric acid or bile secretions into the lower esophagus. gastroesophageal reflux disease (GERD) refers to b ackflow of gastric or duodenal contents or both into the esophagus and past the lower esophageal sphincter (LES). diazepam. such as with obesity or pregnancy hiatal hernia medications such as morphine. It commonly occurs in pregnant or obese persons. meperidine. . or cigarettes that lower LES pressure nasogastric intubation for more than 4 days. obstruction. and the effects of certain foods and d rugs can lower esophageal sphincter (LES) pressure. or fistula Blood transfusions if necessary to treat blood loss from hemorrhage. calcium channel blockers. The r eflux of gastric contents causes acute epigastric pain.

Complications Reflux esophagitis Esophageal stricture Esophageal ulceration Chronic pulmonary disease from aspiration of gastric contents in throat. Typically the sphincter relaxes after each swa llow to allow food into the stomach. The high acidity of the stomach contents causes pain and irritation when it enters the esophagus.) Signs and symptoms Burning pain in the epigastric area. Diagnosis Diagnostic tests are aimed at determining the underlying cause of GERD: Esophageal acidity test evaluates the competence of the lower esophageal sphinct er and provides objective measure of reflux. f rom the reflux of gastric contents into the esophagus causing irritation and als o esophageal spasm Pain. the LES maintains enough pressure around the lower end of the esophagu s to close it and prevent reflux. the sphincter does not remain clos ed (usually due to deficient LES pressure or pressure within the stomach exceedi ng LES pressure) and the pressure in the stomach pushes stomach contents into th e esophagus. secondary to increased abdominal pressure causing reflux Feeling of fluid accumulation in the throat without a sour or bitter taste due t o hypersecretion of saliva. Acid perfusion test confirms esophagitis and distinguishes it from cardiac disor ders.Persistent inflammation can cause LES pressure to decrease even more and may tri gger a recurrent cycle of reflux and pyrosis. Pathophysiology Normally. . (See How heartburn occurs. usually after a meal or when lying down. In GERD. possibly radiating to the arms and chest.

Barium swallow identifies hiatal hernia as the cause. .Esophagoscopy allows visual examination of the lining of the esophagus to reveal extent of disease and confirm pathologic changes in mucosa. small meals and avoidance of eating before going to bed to reduce abdominal pressure and reduce the incidence of reflux Positioning sitting up during and after meals and sleeping with head of bed elev ated to reduce abdominal pressure and prevent reflux Increased fluid intake to wash gastric contents out of the esophagus Antacids to neutralize acidic content of the stomach and minimize irritation Histamine H2 antagonists to inhibit gastric acid secretion Proton pump inhibitors to reduce gastric acidity Cholinergic agents to increase LES pressure Smoking cessation to improve LES pressure (nicotine lowers LES pressure) Surgery if hiatal hernia is the cause or patient has refractory symptoms. Enlargement of the pl exus of the inferior hemorrhoidal veins below the dentate line causes external h emorrhoids. which may protrude from the rectum. Esophageal manometry evaluates resting pressure of LES and determines sphincter competence. Upper GI series detects hiatal hernia or motility problems. Hemorrhoids occur in both sexes. Treatment Diet therapy with frequent. Dilation and enlargement of the superior plexus of the superior hemorrhoida l veins above the dentate line cause internal hemorrhoids. Hemorrhoids Hemorrhoids are varicosities in the superior or inferior hemorrhoidal venous ple xus.

alcoholism. strai ning at defecation. such as cirrhosis. pregnancy. and anorectal infections. and obesity. or hepatit is. Seco nd-degree hemorrhoids prolapse during straining but reduce spontaneously. or fourth degree. Signs and symptoms Painless. Thirddegree hemorrhoids are prolapsed hemorrhoids that require manual reduction after each bowel movement. second. constipation. low-fiber diet. Pathophysiology Hemorrhoids result from activities that increase intravenous pressure. intermittent bleeding during defecation from irritation and injury to the hemorrhoid mucosa Bright red blood on stool or toilet tissue due to injury to hemorrhoid mucosa Anal itching from poor anal hygiene Vague feeling of anal discomfort when bleeding occurs Prolapse of rectal mucosa from straining . depending on their severity. causing d istention and engorgement. amebic abscesses. Predisposing factors include prolonged sitting.Incidence is generally highest between ages 20 and 50. Fourth-degree hemorrhoids are irreducible. Causes Causes may include: prolonged sitting straining at defecation constipation. Signs and sympt oms vary accordingly. First-degree hemorrhoids are confined to the anal canal. low-fiber diet pregnancy obesity. third. Other factors include hepatic disease. Hemorrhoids are classified as first.

and bulking agents to relieve constipat ion avoidance of prolonged sitting on the toilet to prevent venous congestion local anesthetic agents to decrease local swelling and pain hydrocortisone cream and suppositories to reduce edematous. prolapsed hemorrhoid s. Anoscopy and flexible sigmoidoscopy visualizes internal hemorrhoids. increased fluid intake. Hepatitis. Treatment Treatment depends on the type and severity of the hemorrhoids: high fiber diet. Complications Constipation Local infection Thrombosis of hemorrhoids Secondary anemia from severe or recurrent bleeding. nonviral .Pain from thrombosis of external hemorrhoids. Diagnosis Physical examination confirms external hemorrhoids. and itching warm sitz baths to relieve pain injection sclerotherapy or rubber band ligation to reduce prolapsed hemorrhoids hemorrhoidectomy by cauterization or excision.

al though a few develop fulminating hepatitis or cirrhosis. Alcohol. Symptoms of hepatic dysfunction may appear at any time dur ing or after exposure to these drugs. unlike toxic hepatitis. scarring. After exposure to these agents. and phenothiazines (cholestasi s-induced hepatitis). and preexisting liver disease exacerbate the effects of some toxins. Signs and symptoms Signs and symptoms include: anorexia. halothane. Complications .Nonviral hepatitis is an inflammation of the liver that usually results from exp osure to certain chemicals or drugs. Most patients recover from this illness. Pathophysiology Various hepatotoxins such as carbon tetrachloride. an oxia. and infiltration by mononuclear phagocytes occur with varying severity. trichloroethyl ene. Drug-induced (idiosyncratic) hepatitis may begin with a hypersensitivity reactio n unique to the individual. acetaminophen. su lfonamides. leading to hyperbilirubinemia dark urine from elevated urobilinogen hepatomegaly due to inflammation possible abdominal pain from liver inflammation clay colored stool secondary to decreased bile in the gastrointestinal tract fro m liver necrosis pruritus secondary to jaundice and hyperbilirubinemia. which appears to affect all exposed people indiscriminately. poisonous mushrooms. methyldopa. Kupffer cell hyperplasia. vinyl chloride can cause hepatitis. isoniazid. hepatic cellular necrosis. acetaminophen. Among possible causes are niacin. Causes Hepatotoxic chemicals Hepatotoxic drugs. nausea and vomiting due to systemic effects of liver inflammation jaundice from decreased bilirubin metabolism. but it usually manifests after 2 to 5 week s of therapy.

Alkaline phosphatase levels are elevated. depending on the route of exposure. White blood cell count and eosinophil count are elevated. or hyperventilation. Type B (serum or long-incubation hepatitis) also is most common among HIV-positi ve individuals. Total and direct bilirubin levels are elevated.Cirrhosis Hepatic failure. old age and serious underl ying disorders make complications more likely. Liver biopsy identifies underlying pathology. viral Viral hepatitis is a common infection of the liver. hepatic cells eventually r egenerate with little or no residual damage. especially infiltration with white blood cells and eosinophils. necrosis. In most patients. are elevated. Hepatitis. The prognosis is poor if edema an d hepatic encephalopathy develop. Treatment Treatment includes: lavage. However. such as serum aspartate aminotransferase and alanine aminotransfe rase levels. Diagnosis Liver enzymes. resulting in hepatic cell de struction. Routine screening of donor blood for the hepatitis B surface ant . to r emove the causative agent acetylcysteine as an antidote for acetaminophen poisoning corticosteroid to relieve symptoms of drug-induced nonviral hepatitis. Five major forms of hepatitis are currently recognized: Type A (infectious or short-incubation hepatitis) is most common among male homo sexuals and in people with human immunodeficiency virus (HIV) infection. and autolysis. catharsis.

The inflammatory and immune reactions will. type D occurs only in people who are frequently exposed to blood and blood products. but transmission by ne edles shared by drug abusers remains a major problem. non-B hepatiti s) occurs primarily among patients who have recently returned from an endemic ar ea (such as India.igen has reduced the incidence of post-transfusion cases. Africa. D. In the Uni ted States. direct antibody attack again st the viral antigens causes further destruction of the infected cells. Signs and symptoms Signs and symptoms reflect the stage of the disease. drug users and hemophilia patients. either by di rectly killing the cells or by activating inflammatory and immune reactions. On entering the body.) Other types continue to be identified with growing patient population and sophis ticated laboratory identification techniques.V. which has a high mortality. Type D (delta hepatitis) is responsible for about 50% of all cases of fulminant hepatitis. Type C accounts for about 20% of all viral hepatitis cases and for most post-tra nsfusion cases. tissue hypoxia. It progresses to coma and commonly leads to death within 2 weeks. Developing in 1% of patients with viral h epatitis. B. (See Viral hepatitis from A to E. fulminant hepatitis causes unremitting liver failure with encephalopat hy. Causes The five major forms of viral hepatitis result from infection with the causative viruses: A. such as I. Asia. Pathophysiology Hepatic damage is usually similar in all types of viral hepatitis. Later. Type E (formerly grouped with types C and D under the name non-A. C. Prodromal stage. Edema an d swelling of the interstitium lead to collapse of capillaries and decreased blo od flow. Signs and symptoms of the prodromal stage include: easy fatigue and generalized malaise due to systemic effects of liver inflammati on anorexia and mild weight loss due to systemic effects of liver inflammation arthralgia and myalgia due to systemic effects of liver inflammation . the virus causes hepatocyte injury and death. It's more common in young adults and more severe in pregnant woman. and scarring and fibrosis. Varying degre es of cell injury and necrosis occur. injure or destroy hepatocytes by lysing the infected or neighboring cells. in turn. or E. or Central America).

FEATURE € HEPATITIS € HEPATITIS € HEPATITIS € HEPATITIS € HEPATITIS A B C D E Incubation € 15 to 45 days € 30 to 180 days € 15 to 160 days € 14 to 64 days € 14 to 60 days Onset € .nausea and vomiting from gastrointestinal effects of liver inflammation changes in the senses of taste and smell related to liver inflammation fever secondary to inflammatory process right upper quadrant tenderness from liver inflammation and irritation of area n erve fibers dark colored urine from urobilinogen clay colored stools from decreased bile in the gastrointestinal tract. VIRAL HEPATITIS FROM A TO E This chart compares the features of each type of viral hepatitis that has been c haracterized. Other types are emerging.

most people infected with hepatitis D are also infected with h epatitis B € Primarily fecal-oral Severity € Mild € Often severe € Moderate € Can be severe and lead to fulminant hepatitis € Highly virulent with common progression to fulminant hepatitis and hepatic failu re. nonpercutaneous (sexual. parenteral route. parenteral route € Parenteral route.neonatal.Acute € Insidious € Insidious € Acute and chronic € Acute Age group most affected € Children. mate rnal. percutaneous (rare) € Blood-borne.neonatal). worsens in chronic cases. especially in pregnant patients Prognosis € Generally good € Worsens with age and debility € Moderate € Fair. sexual (especially oral-anal contact). virus is shed in all body fluids € Blood-borne. can lead to chronic hepatitis D and chronic live r disease . sexual. maternal. young adults € Any age € More common in adults € Any age € Ages 20 to 40 Transmission € Fecal-oral.

The patient's symptoms subside and appetite returns. Complications Chronic persistent hepatitis. Diagnosis Hepatitis profile study identifies antibodies specific to the causative virus. Signs and symptoms of the clinical stage include: worsening of all symptoms of prodromal stage itching from increased bilirubin in the blood abdominal pain or tenderness from continued liver inflammation jaundice from elevated bilirubin in the blood. Recovery stage. e .€ Good unless pregnant Progression to chronicity € None € Occasional € 10% to 50% of cases € Occasional € None Clinical stage. which may prolong recovery up to 8 months Chronic active hepatitis Cirrhosis Hepatic failure and death Primary hepatocellular carcinoma.

000 live births. high-calorie meals to combat anorexia Parental nutrition if patient can't eat due to persistent vomiting Vaccination against hepatitis A and B to provide immunity to these viruses befor e transmission occurs. Liver biopsy to confirm suspicion of chronic hepatitis. is a congenital disorder of the large intestine. especially in severe cases. It's up to seven times more common in males than in females (although the aganglionic segment is usually shorter i n males) and is most prevalent in whites. Hirschsprung's disease appears to be a familial.000 to 1 in 5. Serum bilirubin may remain high into late disease.stablishing the type of hepatitis. pa . congenital defect. Females with Hirschsprung's disease are at higher risk for having affe cted children. Serum aspartate aminotransferase and serum alanine aminotransferase levels are i ncreased in the prodromal stage. This disease usually coexists with other congenital anomalies. Serum alkaline phosphatase is slightly increased. characterized by absence or marked reduction of parasympathetic ganglion cells in the colorectal wall. Total aganglionosis affects both sexes equally. White blood cell counts reveal transient neutropenia and lymphopenia followed by lymphocytosis. occur ring in 1 in 2. Treatment Rest to minimize energy demands Avoidance of alcohol or other drugs to prevent further hepatic damage Diet therapy with small. Hirschsprung's disease Hirschsprung's disease. Prothrombin time prolonged (greater than 3 seconds longer than normal indicates severe liver damage). also called congenital megacolon and congenital aganglio nic megacolon.

prognosis is good. The ensuing mucosal edema. Impaired in testinal motility causes severe. The aganglionic bowel segment contrac ts without the reciprocal relaxation needed to propel feces forward. Continue d infarction and destruction of the mucosa can lead to infection and sepsis. and infarction draw large am ounts of fluid into the bowel. Wit h prompt treatment. intractable constipation. Signs and symptoms In the newborn. causing bowel dilation and subsequent occlusion of surrounding blood a nd lymphatics. parasympathetic ganglion cells in the colorectal wall are absent or markedly reduced in number. ischemia. signs and symptoms include: failure to pass meconium within 24 to 48 hours due to inability to propel intest inal contents forward bile stained or fecal vomiting as a result of bowel obstruction abdominal distention secondary to retention of intestinal contents and bowel obs truction irritability due to resultant abdominal distention feeding difficulties and failure to thrive related to retention of intestinal co ntents and abdominal distention dehydration related to subsequent feeding difficulties and inability to ingest a dequate fluids overflow diarrhea secondary to increased water secretion into bowel with bowel o bstruction. Without prompt treatment. Cause Familial congenital defect. Colonic obstruction c an ensue. Pathophysiology In Hirschsprung's disease. an infant with colonic obstruction may die within 24 h ours from enterocolitis that leads to severe diarrhea and hypovolemic shock.rticularly trisomy 21 and anomalies of the urinary tract such as megaloureter. causing copious amounts of liquid stool. signs and symptoms include: intractable constipation due to decreased gastrointestinal motility . In children.

Complications Bowel perforation Electrolyte imbalances Nutritional deficiencies Enterocolitis Hypovolemic shock Sepsis. Diagnosis Rectal biopsy confirms diagnosis by showing absence of ganglion cells. signs and symptoms (occurs rarely and is more prevalent in men) inclu de: abdominal distention from decreased bowel motility and constipation chronic intermittent constipation secondary to impaired intestinal motility.abdominal distention from retention of stool easily palpated fecal masses from retention of stool wasted extremities (in severe cases) secondary to impaired intestinal motility a nd its effects on nutrition and intake loss of subcutaneous tissue (in severe cases) secondary to malnutrition large protuberant abdomen due to retention of stool and consequent changes in fl uid and electrolyte homeostasis. In adults. .

reveals a narrowed segment of distal colon with a sawtoothed appearance and a funnel-shaped segment above it. used in older infants. Serum un conjugated bilirubin levels do not exceed 12mg/dl. CULTURAL DIVERSITY Hyperbilirubinia tends to be more common and more severe in C hinese. and Native Americans. Pathologic jaundice may appea r anytime after the first day of life and persist beyond 7 days. also called neonatal jaundice. whose mean peak of unconjugated bilirubin is approximately twice that of the rest of the population. Upright plain abdominal X-rays show marked colonic distention. pathologic jaundice varies. cytomegalic inclusion body disease. Hyperbilirubinemia Hyperbilirubinemia. Koreans. 15 mg/dl in a premature infa nt. This confirms the diagnosis and assesses the extent of intestinal involvement. It can be physiologic (with jaundice the only symptom) or pathologic (result ing from an underlying disease). Causes Causes may include: blood type incompatibility intrauterine infection (rubella. or increase more than 5 mg/dl in 24 hours.Barium enema. toxoplasmos . Physiologic jaundice is self-limi ting. is the result of hemolytic pr ocesses in the newborn marked by elevated serum bilirubin levels and mild jaundi ce. Physiologic jaundice generally develops 24 to 48 hours after birth and disappear s by day 7 in full term babies and by day 9 or 10 in premature infants. depending on the cause. Japanese. Rectal manometry detects failure of the internal anal sphincter to relax and con tract. Serum bilirubin levels are greater than 12 mg/dl in a term infant. Treatment Treatment may include: corrective surgery to pull the normal ganglionic segment through to the anus (us ually delayed until the infant is at least 10 months old) daily colonic lavage to empty the bowel of the infant until the time of surgery temporary colostomy or ileostomy to compress the colon in instances of total bow el obstruction.

occasionally. syphilis and. sodium nitrate) transient neonatal hyperbilirubinemia abnormal red blood cell morphology deficiencies of red blood cell enzymes (glucose 6-phosphate dehydrogenase. Pseudomonas. hexok inase) physiologic jaundice breast feeding maternal diabetes crigler-Najjar syndrome gilbert syndrome herpes simplex . Staphylococcu s. and Streptococcus) infection (gram-negative bacteria) polycythemia enclosed hemorrhages (bruises. bacteria such as Escherichia coli. Proteus. subdural hematoma) respiratory distress syndrome (hyaline membrane disease) heinz body anemia from drugs and toxins (vitamin K3. Klebsiella.is.

and hypoalbuminemia) can disrupt con jugation and usurp albumin-binding sites. Signs and symptoms Jaundice from the escape of unconjugated bilirubin to extra vascular tissue (pri mary sign of hyperbilirubinemia). maternal enzymes in breast milk inhibit the infant's glucuronyl-transfe rase conjugating activity. epilepsy. Certain drugs (such as aspirin. causing hy perbilirubinemia.pyloric stenosis hypothyroidism neonatal giant cell hepatitis bile duct atresia galactosemia choledochal cyst. anoxia. Increased erythrocyte production or breakdown in hemolytic disorders. which binds to albumin for transport to liver c ells to conjugate with glucuronide. or mental retardation . As a result. Finally. Pathophysiology As erythrocytes break down at the end of their neonatal life cycle. Complications Kernicterus Cerebral palsy. it may e scape to extravascular tissue. Biliary obstructi on or hepatitis can cause hyperbilirubinemia by blocking normal bile flow. forming direct bilirubin. Because unconjugat ed bilirubin is fat-soluble and can't be excreted in the urine or bile. Heme fragments form un conjugated (indirect) bilirubin. or in Rh o r ABO incompatibility can cause hyperbilirubinemia. especially fatty tissue and the brain. Lysis releases bilirubin and stimulates cell agglutination. hypoglycemia. Decreased hepatic function also reduces bilirubin conjugation. the liver's capacity to conjugate b ilirubin becomes overloaded. and sulfonamides) and conditions (such as hypothermia. tranquilizers. hemoglobin s eparates into globin (protein) and heme (iron) fragments.

and abdominal dist ention. polycythemia. after the initial exchange transfusion) wit h fluorescent lights to decompose bilirubin in the skin by oxidation (usually di scontinued after bilirubin levels fall below 10mg/dl and continue to decrease fo r 24 hours) Exchange transfusion to replace the infant's blood with fresh blood (less then 4 8 hours old). alternating constipation a nd diarrhea. Causes Psychological stress (most common) Ingestion of irritants (coffee. It occurs in women twice a s often as men. stress-related disorder. excess flatus. indicated fo r conditions such as hydrops fetalis. and pathologic jaund ice due to erythroblastosis fetalis. removing some of the unconjugated bilirubin in serum. IBS is a benign condition that has no anatomical abnormality or inflammatory component. Treatment Phototherapy (treatment of choice for physiologic jaundice. Irritable bowel syndrome is a common. and jaundice that develops within the first 6 hours after birth Albumin administration to provide additional albumin for binding unconjugated bi lirubin Phenobarbital administration (rare) to the mother before delivery and to the new born several days after delivery to stimulate the hepatic glucuronide-conjugatin g system Irritable bowel syndrome Also referred to as spastic colon or spastic colitis.Perceptual-motor handicaps and learning disorders. or vegetables) Lactose intolerance Abuse of laxatives . erythroblastosis fetalis. ma rked reticulocytosis. However. drug toxicity. 20% of patients never seek medical attention. Diagnosis Bilirubin levels greater than 0. irritable bowel syndrome ( IBS) is marked by chronic symptoms of abdominal pain.5 mg/dl. raw fruit. a sense of incomplete evacuation.

Hormonal changes (menstruation). others are particularly sensitive t o certain foods and drugs. segmental muscle contractions mix intestin al contents while peristalsis propels the contents through the GI tract. The result: a pattern of alternating diarrhea and constipation. careful examination of the colon may reveal functional irritabili ty an abnormality in colonic smooth-muscle function marked by excessive peristal sis and spasms. the patient with irritable bowel syndrome has a normal-appearing GI t ract. The pain of IBS seems to be caused by abnormally stron g contractions of the intestinal smooth muscle as it reacts to distention. In irritable bowel syndrome. dumping watery stools and irritating the mucosa. The result is constipation or diarrhea or both. the autonomic nervous system. the intestinal mucosa absorbs water from t he stools.) Signs and symptoms Crampy lower abdominal pain secondary to muscle contraction. doesn't cause the alternating contractions and relaxations that propel stools smoothly toward the rectum. CONSTIPATION Some patients have spasmodic intestinal contractions that set up a partial obstr uction by trapping gas and stools. bloating. and difficult to pass. Normally. hard. The patient may be hypersensitive to the hormones gas trin and cholecystokinin. Motor a ctivity is most propulsive in the proximal (stomach) and the distal (sigmoid) po rtions of the intestine. secondary to motor di sturbances from causative stimulus . usually occurring d uring the day and relieved by defecation or passage of flatus Pain that intensifies 1 to 2 hours after a meal from irritation of nerve fibers by causative stimulus Constipation alternating with diarrhea. with one dominant. INTESTINAL FUNCTION To understand what happens in irritable bowel syndrome. The result is diarrhea. permi tting nutrient and water absorption. This causes distention. which innervates the large intestine. gas pain. even during remission. consider how smooth musc le controls bowel function. irrit ants. WHAT HAPPENS IN IRRITABLE BOWEL SYNDROME Typically. Some muscles of the small bowel are particularly sens itive to motor abnormalities and distention. DIARRHEA Other patients have dramatically increased intestinal motility. a nd constipation. Usually eating o r cholinergic stimulation triggers the small intestine's contents to rush into t he large intestine. Pathophysiology Irritable bowel syndrome appears to reflect motor disturbances of the entire col on in response to stimuli. MIXED SYMPTOMS If further spasms trap liquid stools. (See What happens in irritable bowel syndrome. leaving them dry. or stress. However. Activity in the rest of the intestines is slower.

Barium enema may reveal colon spasm and tubular appearance of descending colon w ithout evidence of cancers and diverticulosis. such as a recen t stressful life change.Mucus passed through the rectum from altered secretion in intestinal lumen due t o motor abnormalities Abdominal distention and bloating caused by flatus and constipation. bacteria. and blood rule out infection. including counseling or mild anti-anxiety agents investigation and avoidance of food irritants application of heat to abdomen bulking agents to reduce episodes of diarrhea and minimize effect of nonpropulsi ve colonic contractions antispasmodics (dicyclomine. Diagnosis Physical examination reveals contributing psychological factors. Sigmoidoscopy or colonoscopy may reveal spastic contractions without evidence of colon cancer or inflammatory bowel disease. Treatment Treatment may include: stress relief measures. Stool samples for ova. hycomine sulfate) for pain . Lactose intolerance test rules out lactose intolerance. Rectal biopsy rules out malignancy. parasites.

Hepatorenal syndrome is renal failure concurrent with liver disease. Short-chain fatty acids. a set of central nervous system disorders. Signs and symptoms Jaundice from the failure of liver to conjugate bilirubin . and electrolyte disturbances. leading to decreased glomerular filtration and oliguri a. When the liver fails and is no longer able to transform ammonia to urea. (See Functi ons of the liver. and false neurotransmitters may also accumul ate in the blood and contribute to hepatic encephalopathy. the kidneys appear to be normal but abruptly cease functioning. serotonin.) Hepatic encephalopathy and hepatorenal syndrome are two condi tions occurring in liver failure. Ammonia is one of the main toxins causing hepatic encephalopathy. accumulation of hydrogen ions. The liver performs ove r 100 separate functions in the body. The vasoconstriction may also be a compensatory response to portal hypertensi on and the pooling of blood in the splenic circulation. The normal liver transforms ammonia to urea. Causes Viral hepatitis Nonviral hepatitis Cirrhosis Liver cancer. results when the liver can no longer detoxify the blood. Liver failure Liver failure can be the end result of any liver disease. When it fails. Pathophysiology Manifestations of liver failure include hepatic encephalopathy and hepatorenal s yndrome. Ammonia is a byproduct of protei n metabolism. tryptophan. a complex syndrome involvin g the impairment of many different organs and body functions ensues. The cause ma y be the accumulation of vasoactive substances that cause inappropriate constric tion of renal arterioles. which the kidneys exc rete. It is most co mmon in patients with alcoholic cirrhosis or fulminating hepatitis. Hepatic encephalopathy. Liver dysfunction and collateral ves sels that shunt blood around the liver to the systemic circulation permit toxins absorbed from the GI tract to circulate freely to the brain.loperamide possibly to reduce urgency and fecal soiling in patients with persist ent diarrhea bowel training (if the cause of IBS is chronic laxative abuse) to regain muscle control. It causes expanded blood vo lume. The only cure for liver failure is a liver tra nsplant. a mmonia blood levels rise and the ammonia is delivered to the brain.

Complications . and abdominal wall secondary to portal hyperte nsion Bleeding tendencies from thrombocytopenia (secondary to blood accumulation in th e spleen) and prolonged prothrombin time (from the impaired production of coagul ation factors) Petechia resulting from thrombocytopenia Amenorrhea secondary to altered steroid hormone production and metabolism Gynecomastia in males from estrogen buildup due to failure of hepatic biotransfo rmation functions.Abdominal pain or tenderness from liver inflammation Nausea and anorexia from systemic effects of inflammation Fatigue and weight loss from failure of hepatic metabolism Pruritus due to the accumulation of bilirubin in the skin Oliguria from intrarenal vasoconstriction Splenomegaly secondary to portal hypertension Ascites due to portal hypertension and decreased plasma proteins Peripheral edema from accumulation of fluid retained because of decreased plasma protein production and loss of albumin with ascites Varices of the esophagus. rectum.

Diagnosis Liver function tests reveal elevated levels of aspartate aminotransferase (AST). beer. glucose. Blood studies reveal anemia. elevated bleedi ng and clotting times. and drugs (prescr ibed and over-the-counter. it is best to understand its main functions: Detoxifies poisonous chemicals. and bilirubin. including alcohol. as well as vitamins and minerals Manufactures new proteins Produces important plasma proteins necessary for blood coagulation. alkaline phosphatase. including pr . wine. To understand how liv er disease affects the body. FUNCTIONS OF THE LIVER The liver is one of the most essential organs of the body. and fat) until neede d Stores iron reserves. as well as illegal substances) Makes bile to help digest food Stores energy by stockpiling sugar (carbohydrates. and increased serum ammonia lev els. alanine aminotrasferase (ALT). Urine osmolarity is increased. impaired red blood cell production.Variceal bleeding Gastrointestinal hemorrhage Coma Death. low blood glucose levels.

treatment includes: salt restriction and potassium-sparing diuretics to increase water excretion potassium supplements to reverse the effects of high aldosterone paracentesis to remove ascitic fluid and alleviate abdominal discomfort shunt placement to aid in removal of ascitic fluid and alleviate abdominal disco mfort. treament includes: shunt placement between the portal vein and another systemic vein to divert bloo d flow and relieve pressure. high carbohydrate diet to correct nutritional deficiences and preve nt overtaxing liver lactulose to reduce ammonia blood levels and help alleviate some symptoms of hep atic encephalopathy.othrombin and fibrinogen Serves as a site for hematopoiesis during fetal development. For ascites. treatment includes: vasoconstrictor drugs to decrease blood flow balloon tamponade to control bleeding by exerting pressure on the varices with t he use of a balloon catheter surgery to tie off bleeding collaterals sprouting from the portal vein . For variceal bleeding. Treatment Treatment may include: liver transplantation low protein. For portal hypertension.

In celiac sprue.) prior gastric surgery pancreatic disorders hepatobiliary disease disease of the small intestine. In Zollinger-Ellison syndrome. Lactase is an intestin al enzyme that splits nonabsorbable lactose (a disaccharide) into the absorbable monosaccharides glucose and galactose. or vitamins may be impaired. increased acidity in the duodenum inhibits releas e of cholecystokinin. Symptoms generally disappear when gluten is rem oved from the diet. Bacterial overgrowth in the duodenal stump (loop created in the Billroth II proc edure) causes malabsorption of vitamin B12. lactas e deficiency. Manifestations depend primarily on wha t is not being absorbed.vitamin K to control bleeding by decreasing prothrombin time. barley. Some common causes of malabsorption syndrome include celiac disease. The mucosa appear flat a nd have lost absorptive surface. dietary gluten a product of wheat. causing injury to the mucosal villi. and bacterial overgrowth in the duodenal stump. rye. which stimulates pancreatic enzyme secretion. Poor mixing of chyme with gastric sec retions is the cause of postsurgical malabsorption. The result is inadequate movement of nutrients from the small intestin e to the bloodstream or lymphatic system. sugar. Production may be deficient. Causes A wide variety of disorders result in malabsorption. or another intestinal disease may inhibit the enzyme. gastrectomy. Absorption of amino acids. and oats is tox ic to the patient. Zollinger-Ellison syndrome. (See Causes of malabsorptio n. Signs and symptoms Signs and symptoms include: . Malabsorption may occur after gastrectomy. such as celiac disease hereditary disorder drug toxicity. Pancreatic e nzyme deficiency leads to decreased breakdown of nutrients and malabsorption. Pathophysiology The small intestine's inability to absorb nutrients efficiently may result from a variety of disease processes. The mechanism of malabsorption depends on the ca use. fat. Malabsorption Malabsorption is failure of the intestinal mucosa to absorb single or multiple n utrients efficiently. Lactase deficiency is a disaccharide deficiency syndrome.

folic acid. cheilosis secondary to a deficiency of iron. electrolytes. fat. protein depletion leading to osteoporosis and vitamin D malabs orption causing impaired calcium absorption . bleeding tendency from vitamin K malabsorption and hypoprothrombinemia bone pain. resulting in protein depletion an d hypoproteinemia amenorrhea from protein depletion leading to hypopituitarism anemia from the impaired absorption of iron. bile acids and fatty acids in colon steatorrhea from excess fat in stool flatulence and abdominal distention secondary to fermentation of undigested lact ose nocturia from delayed absorption of water weakness and fatigue from anemia and electrolyte depletion from diarrhea edema from impaired absorption of amino acids. skeletal deformities.weight loss and generalized malnutrition from impaired absorption of carbohydrat e. folic acid. and vitamin B12 glossitis. fractures from calcium malabsorption that leads to hypocalcemia. and protein diarrhea from decreased absorption of fluids. vitamin B12. and other vitamins peripheral neuropathy from a deficiency of vitamin B12 and thiamine bruising.

paresthesias resulting from calcium malabsorption leading to hypocalcemi a and magnesium malabsorption. leading to hypomagnesemia and hypokalemia. CAUSES OF MALABSORPTION Many disorders from systemic to organ-specific diseases rption. DISEASES OF THE SMALL INTESTINE Primary small bowel disease may give rise to malabso Bacterial overgrowth due to stasis in afferent loop after Billroth II gastrectom y Massive bowel resection Nontropical sprue (celiac disease) Regional enteritis Tropical sprue Ischemic small bowel disease Chronic congestive heart failure Mesenteric atherosclerosis Small bowel infections and infestations Acute enteritis Giardiasis Systemic disease involving small bowel Amyloidosis Lymphoma .tetany.

Sarcoidosis Scleroderma Whipple's disease DRUG-INDUCED MALABSORPTION Calcium carbonate Neomycin HEPATOBILIARY DISEASE Biliary fistula Biliary tract obstruction Cirrhosis and hepatitis HEREDITARY DISORDER Primary lactase deficiency PANCREATIC DISORDERS Chronic pancreatitis Cystic fibrosis Pancreatic cancer Pancreatic resection Zollinger-Ellison syndrome PREVIOUS GASTRIC SURGERY .

. Diagnosis Stool specimen for fat reveals excretion of greater than 6 g of fat per day. Culture of duodenal and jejunal contents confirms bacterial overgrowth in the pr oximal bowel. reflects disorders of proximal bowel. D-Xylose absorption test shows less than 20% of 25 g of D-Xylose in the urine af ter 5 hours.Billroth II gastrectomy Pyloroplasty Total gastrectomy Vagotomy Complications Fractures Anemias Bleeding disorders Tetany Malnutrition. Schilling test reveals deficiency of vitamin B12 absorption.

inflammation of the pancreas. Treatment Identification of cause and appropriate correction Gluten-free diet to stop progression of celiac disease and malabsorption Lactose-free diet to treat lactase deficiency Dietary supplementation to replace nutrient deficiencies Vitamin B12 injections to treat vitamin B12deficiency. or hemorrhage. Pancreatitis Pancreatitis. this disease is commonly associated with alcoholism. trauma. Small intestine biopsy reveals the atrophy of mucosal villi. but poor when associated with alcoholism. or peptic ulcer. with biliary tra ct disease. In men. The prognosis is good in pancreatitis associated with biliary tract disease. Causes Biliary tract disease Alcoholism Abnormal organ structure Metabolic or endocrine disorders.Gastrointestinal barium studies show characteristic features of the small intest ine. such as high cholesterol levels or overactive thyroid Pancreatic cysts or tumors Penetrating peptic ulcers . in women. occurs in acute and chronic forms an d may be due to edema. necrosis. Mortality is as high as 60% w hen pancreatitis is associated with necrosis and hemorrhage.

and obstruction o f the biliary tract Persistent vomiting (in a severe attack) from hypermotility or paralytic ileus s econdary to pancreatitis or peritonitis Abdominal distention (in a severe attack) from bowel hypermotility and the accum ulation of fluids in the abdominal cavity . persistent inflammation produces irreversible changes i n the structure and function of the pancreas. Two the ories explain why enzymes become prematurely activated. and NSAIDS Kidney failure or transplantation Endoscopic examination of the bile ducts and pancreas. Necrotizing pan creatitis causes cell death and tissue damage. Growths called pseudocysts contain pancreatic enzymes and tissue debris. Protein precipitates block the pancreatic duct and eventual ly harden or calcify. thiazides. such as glucocorticoids. It sometimes follows an episode of acute pancreatitis. Pathophysiology Acute pancreatitis occurs in two forms: edematous (interstitial) and necrotizing . The inflammation that occurs with both types is caused by premature activation of enzymes. If pancreatitis damages the islets of Langerhans. sulfonamides. Alcohol probably increases pancreatic secretion. shock. Structural changes lead to fibrosis and atrophy of the gla nds.Blunt trauma or surgical trauma Drugs. In chronic pancreatitis. Another theory is that a reflux of duodenal contents containing activated enzyme s enters the pancreatic duct. manifested as diabetic acidosis. diabetes mellitus may result. In one view. alters the metabolism of the acinar cells. the acini in the pancreas secrete enzymes in an inactive form. Normally. Signs and symptoms Pain caused by the escape of inflammatory exudate and enzymes into the back of t he peritoneum. a toxic agent such as alcohol alters the way the pancreas secretes enzymes. and oral contraceptives . Edematous pancreatitis causes fluid accumulation and swelling. Sudden severe pancreatitis causes massive hemorrhage and total destruction of th e pancreas. and encourages duct obstruction by causing pancreatic secre tory proteins to precipitate. An abscess results if pseudocysts become infected. or coma. edema and distention of the pancreatic capsule. activating other enzymes and setting up a cycle of more pancreatic damage. which causes tissue da mage.

. sweaty extremities secondary to cardiovascular collapse Restlessness related to pain associated with acute pancreatitis Extreme malaise (in chronic pancreatitis) related to malabsorption or diabetes.Diminished bowel activity (in severe attack) suggesting altered motility seconda ry to peritonitis Crackles at lung bases (in a severe attack) secondary to heart failure Left pleural effusion (in a severe attack) from circulating pancreatic enzymes Mottled skin from hemorrhagic necrosis of the pancreas Tachycardia secondary to dehydration and possible hypovolemia Low-grade fever resulting from the inflammatory response Cold. Complications Massive hemorrhage/shock Pseudocysts Biliary and duodenal obstruction Portal and splenic vein thrombosis Diabetes mellitus Respiratory failure.

Stool analysis shows elevated lipid and trypsin levels in chronic pancreatitis. serum glucose levels may be transiently elevated. Blood and urine glucose tests reveal transient glucose in urine and hyperglycemi a. In chronic pancreatitis. and electrolytes to treat shock fluid volume replacement to help correct metabolic acidosis blood transfusions to replace blood loss from hemorrhage withholding of food and fluids to rest the pancreas and reduce pancreatic enzyme . Endoscopic retrograde cholangiopancreatography identifies ductal system abnormal ities. Serum bilirubin levels are elevated in both acute and chronic pancreatitis. White blood cell count is elevated. helps differentiate pancreatitis fro m other disorders such as pancreatic cancer. protein.Diagnosis Elevated serum amylase and lipase confirm diagnosis. may detect pancreatic calculi. Computed tomography and ultrasonography show enlarged pancreas with cysts and ps eudocysts. such as calcification or strictures. Blood calcium levels may be decreased. Treatment Treatment may include: intravenous replacement of fluids. Abdominal and chest X-rays detect pleural effusions and differentiate pancreatit is from diseases that cause similar symptoms.

and inhibit pancreatic enzyme secretion insulin to correct hyperglycemia surgical drainage for a pancreatic abscess or a pseudocyst laparotomy (if biliary tract obstruction causes acute pancreatitis) to remove ob struction. duodenum. A CLOSER LOOK AT PEPTIC ULCERS A gastrointestinal lesion is not necessarily an ulcer. decrease gastrointestinal motility . erosions are breaks in the mucosal membranes that do not extend below the epithelium.secretion nasogastric tube suctioning to decrease stomach distention and suppress pancreat ic secretions meperidine to relieve abdominal pain antacids to neutralize gastric secretions histamine antagonists to decrease hydrochloric acid production antibiotics to fight bacterial infections anticholinergics to reduce vagal stimulation. Ulcers may be acute or chronic in nature. Lesions of both acut e and chronic ulcers can extend through the epithelium and perforate the stomach wall. or jejunum. (See A closer look at peptic ulcers. Peptic ulcer Peptic ulcers. Duodenal ulcers usually follow a chronic course with remissions and exacerbations. Chronic ulcers also have scar tissue at the base. which affect the proximal part of the small intestine and occu r most commonly in men between ages 20 and 50. stomach. Although erosions are often referred to as ulcers. Lesions that don't extend below the mucosal lining (epithelium) are called erosions. 5% to 10% of patients develop . Chronic ulcers are identified by scar tissue at thei r base. can develop in the lower esophagus. circumscribed lesions in the mucosal membrane extending below the epithelium. pylorus.) About 80% of all peptic ulcers are duodenal ulcers.

an d tobacco. Duodenal ulcers appear to result from excessive acid protection. Gastric ulcers are most common in middle-aged and elderly men. mucoid. Crohn's disease. Emotional stress also contributes to ulcer formation because of the increased stimulation of acid and pepsin secretion and decreased mucosal de fense. Helic obacter pylori releases a toxin that destroys the gastric and duodenal mucosa.complications that necessitate surgery. or tobacco. coffee. Certain illnesses. Pathophysiology Although the stomach contains acidic secretions that can digest substances. intr insic defenses protect the gastric mucosal membrane from injury. Gast ric ulcers may be a result of destruction of the mucosal barrier. especially in chr onic users of nonsteroidal anti-inflammatory drugs. T hese glands produce a viscid. preexisting gastritis. duodenal ulcers and type O) and other genetic factors. hepatic diseas e. may contribute by accelerating gastric acid emptying and promoting mu cosal breakdown. alkaline secretion that neutralizes the ac id chyme. alcohol. dull. several predisposing factors are acknowledge d. A gastric ulcer produces the following signs and symptoms: pain that worsens with eating due to stretching of the mucosa by food nausea and anorexia secondary to mucosal stretching. Besides peptic ulcer's main causes. r educing the epithelium's resistance to acid digestion and causing gastritis and ulcer disease. tenaci ous layer of gastric mucus protects the stomach from autodigestion. mechanical t rauma. Physical trauma and normal aging are additional predisposing conditions. but usually recurring 2 to 4 hours later seco . Prostaglandins provide another line of defense. Causes Infection with Helicobacter pylori Use of nonsteroidal anti-inflammatory drugs (NSAIDs) Pathologic hypersecretory disorders. or hunger like d production due to excessive aci pain relieved by food or antacids. such as alcohol. and chemical trauma. such as pancreatitis. The duodenum is protected from ulceration by the function of Brunner's glands. Signs and symptoms Symptoms vary by the type of ulcer. Exposure to irritants. aching. also contribute to ulceration. Salicylates and other NSAIDs inhibit the secretion of prostaglandins (substances that block ulceration). A thick. A duodenal ulcer produces the following signs and symptoms: epigastric pain that is gnawing. and Zollinger-Ellison syndrome. They include blood type (gastric ulcers and type A.

Serologic testing may disclose clinical signs of infection. such as elevated whi te blood cell count. and metronidazole) to eradicate H. Upper GI tract X-rays reveal mucosal abnormalities.) . bismuth subsalicylate. This is the first test performed on a patient when symptoms aren't sever e. Complications Hemorrhage Shock Gastric perforation Gastric outlet obstruction. Treatment Antimicrobial agents (tetracycline. pylori. pylori or cancer. Gastric secretory studies show hyperchlorhydria. Stool analysis may reveal occult blood.ndary to food acting as a buffer for acid. Diagnosis Barium swallow or upper GI and small bowel series may reveal the presence of the ulcer. Carbon13 urea breath test results reflect activity of H. Endenoscopy confirms the presence of an ulcer and permits cytologic studies and biopsy to rule out H. pylori infection (See Treating peptic ulcer.

This illustration highlights the actions of the major treatments used for peptic ulcer and where they interf ere with the pathophysiologic chain of events. and also to permit iced saline lavage that may a lso contain norepinephrine Gastroscopy to allow visualization of the bleeding site and coagulation by laser or cautery to control bleeding Surgery to repair perforation or treat unresponsiveness to conservative treatmen t. and co mmonly extends upward into the entire colon. and suspected malignancy. It invariably begins in the rectum and sigmoid colon. rarely affecting the small intestin . Treating peptic ulcer Peptic ulcers can result from factors that increase gastric acid production or f rom factors that impair mucosal barrier protection. Ulcerative colitis Ulcerative colitis is an inflammatory.Misoprostol (a prostaglandin analog) to inhibit gastric acid secretion and incre ase carbonate and mucus production. to protect the stomach lining Antacids to neutralize acid gastric contents by elevating the gastric pH. disease that affects the m ucosa of the colon. mucosal protectant to form an acid-impermeable membrane that adheres to the mucous membrane and also accelerates mucus production Dietary therapy with small infrequent meals and avoidance of eating before bedti me to neutralize gastric contents Insertion of a nasogastric tube (in instances of gastrointestinal bleeding) for gastric decompression and rest. often chronic. thus p rotecting the mucosa and relieving pain Avoidance of caffeine and alcohol to avoid stimulation of gastric acid secretion Anticholinergic drugs to inhibit the effect of the vagal nerve on acid-secreting cells H2 blockers to reduce acid secretion Sucralfate.

It's more prevalent among Ashkenazic Jews and in higher socioeconomic groups. Onset of symptoms s eems to peak between ages 15 and 30 and between ages 55 and 65.000 persons have the disease. congestion. however. from accumulated blood and mucus in the bowel abdominal cramping and rectal urgency from accumulated blood and mucus weight loss secondary to malabsorption weakness related to possible malabsorption and subsequent anemia. Ulcerative colitis produces edema (leading to mucosal friability) and ulcerations. the colon narrows. The colon's mucosal surface becomes dark. Abscesses in the mucosa drain purulent pus. red. Severity ranges from a mild. As granulation tissue replaces the muscle layer. Pathophysiology Ulcerative colitis usually begins as inflammation in the base of the mucosal lay er of the large intestine. Ulcerative colitis occurs primarily in young adults. progressing to po tentially fatal peritonitis and toxemia. except for the terminal ileum. The mucosa becomes diffusely ulcerated. and there s eems to be a familial tendency. Sloughing causes bloody. Complications Complications may include: perforation toxic megacolon liver disease . As abscesses heal. especially women. and ulcerate. scarring and thickening may appear in the bowel's inner mus cle layer. possibly associated with food or bacteria such as Escherichia coli. edema. some studies suggest as many as 100 of 100. The prevalence is unknown. with hemorrhage. Ulcerations are continuous. often containing pus and mucus (hallmark sign). mucus filled stools . Causes Specific causes of ulcerative colitis are unknown but may be related to abnormal immune response in the GI tract. localized diso rder to a fulminant disease that may cause a perforated colon. s hortens. Inflammation leads to erosions that coalesce and form ulcers. become necrotic. The disease cycles between exacerbation and remission. and loses its characteristic pouches (haustral folds). Signs and symptoms Signs and symptoms may include: recurrent bloody diarrhea.e. and ve lvety. and exudative i nflammation.

Colonoscopy reveals extent of the disease. decreas ed WBC count. detects complications. Serology shows decreased serum potassium. and prolonged prothrombin time. magnesium. troublesome diarrhea in patients whose ulcer ative colitis is otherwise under control iron supplements to correct anemia . pus. and albumin levels. Biopsy with colonoscopy confirms the diagnosis. Elevated ery throcyte sedimentation rate correlates with severity of the attack. Treatment Treatment includes: corticotropin and adrenal corticosteroids to control inflammation sulfasalazine for its anti-inflammatory and antimicrobial effects antidiarrheals to relieve frequent. Diagnosis Sigmoidoscopy confirms rectal involvement: specifically. stricture areas. and mucus but no disease-causing org anisms. decreased hemoglobin. mucosal friability and flattening and thick. inflammatory exudate. and ident ifies cancer (not performed when the patient has active signs and symptoms). Barium enema reveals the extent of the disease.stricture formation colon cancer anemia. and pseudopolyps (no t performed when the patient has active signs and symptoms). Stool specimen analysis reveals blood.

During an attack.total parental nutrition and nothing by mouth for patients with severe disease. For both types. stress. producing bronchospasm and constricted breathing. endocrine. (See An asthma attack and Extrinsic asthma. temperature. to rest the intestinal tract.) INTRINSIC ASTHMA This type of asthma. which has no obvious external cause. removing all the potentially malignant epithelia of the rectum and colon . and emotional. As thma is either intrinsic or extrinsic. as shown below. Triggers such as irritants. fatigue. exercise. an asthma attack follows the same process. It's usually preceded by severe respira tory infection that affects nerves or cells near the surface of the bronchial tu bes. is more common in chil dren under age 3 and adults over age 30. decrease stool volume. and restore nitrogen balanc e supplemental drinks to supplement nutrition in patients with moderate symptoms intravenous hydration to replace fluid loss from diarrhea surgery to correct massive dilation of the colon and to treat patients with symp toms that are unbearable or unresponsive to drugs and supportive measures proctocolectomy with ileostomy to divert stool and to allow rectal anastomosis t o heal. and humidity changes may provoke bronchoconst riction and an asthma attack. AN ASTHMA ATTACK A person having an asthma attack has difficulty breathing and increases the use of chest muscles to assist with breathing. Hypersensitivity to various stimuli or allergens causes muscles around the bronchial tubes to tighten. UNDERSTANDING ASTHMA Handbook of Pathophysiology UNDERSTANDING ASTHMA What is asthma? Intrinsic asthma An asthma attack Extrinsic asthma € First exposure € Second exposure WHAT IS ASTHMA? Asthma is a chronic lung disease characterized by airway inflammation and narrow ing. muscles surrounding .

and air pollution. narrowing the air passage and inter rupting the normal flow of air into and out of the lungs. If an attack continues. formation of mucous plugs. Second exposure On subsequent exposure. which contain chemical mediators th at are responsible for allergic signs and symptoms. mold. HOW DOES CANCER SPREAD? Cancer cells may invade nearby tissues or spread (metastasize) to other organs. It's seldom life-threatening. dust. UNDERSTANDING CANCER Handbook of Pathophysiology UNDERSTANDING CANCER What is cancer? How does cancer spread? Staging cancer Treating cancer € Radiation therapy € Chemotherapy WHAT IS CANCER? Cancer results from a destructive (malignant) transformation (carcinogenesis) of normal cells. The antibodies attach to mast cells (4). causing them to enlarge and divide more rapidly than normal. s uch as pollen. a benig n tumor is a localized mass of slowly multiplying cells resembling its original tissue. which hinders air exchange. Most common in children and adolescents. and an inflammatory response (8). and swe lling of the bronchial tubes. The pattern and extent of spread determine the ca ncer's stage. There. this typ e fades with age and avoidance of specific allergens. they trigger immune cells to produce abnormal amounts of allergen-specific defense proteins called immunoglobulin E (IgE) antibodies ( 3). . These cells accumulate in ti ssues exposed to the environment. and thick sticky mucus. An allergic reaction (7) follows in the lungs: a hyperreactive response. animal dander. such as mucous membranes of the respiratory tr act. producing bronch ial edema. tob acco smoke. ragweed. aerosols. First exposure Allergens entering the body for the first time (1) are inhaled and absorbed into lung tissues (2).the bronchial tubes tighten (bronchospasm). IgE antibodies recognize the allergens (5) and trigger t he mast cells to release histamine and other chemical mediators (6). traveling through the circulatory system or the lymphatic system or by seeding i nto an organ or a body cavity. food additives. Cancer cells tend to be very aggressive and out of control. Air flow is further in terrupted by an increase in mucous secretion. secretions. bronchospasm and mucous bu ild-up traps air in the alveolar sacs. In contrast. producing bronchoc onstriction and bronchospasm. EXTRINSIC ASTHMA Persons with extrinsic asthma are hyper-responsive to environmental allergens.

Bones weaken as local cells resorb. Trabecu lar bone at the core becomes less dense. Radiation therapy High energy rays. bone tissue. Neighboring healthy lymph node s and tissues may also be removed to help control the cancer's spread. (See Controlling mineral balance and Bone formation and resorption. Surgery. blood levels of calcium are reduced because of di . In osteoporosis. and chemotherapy can be used in combination or as individual treatments. may be used to stage a tumor. Lymphatic system Cancer cells may move through this series of channels from the tissues to lymph nodes and eventually into the circulatory system. such as computer tomography (CT ) scan or magnetic resonance imaging (MRI). Seeding Cancer may penetrate an organ or move into a body cavity (chest or abdomen) and spread throughout that area. 3. ) CONTROLLING MINERAL BALANCE Normally. to kill any remaining cancer cells. Chemotherapy Drugs given at specified intervals to enhance effectiveness and limit adverse ef fects disrupt the ability of cancer cells to divide. focused in a beam. radiation therap y. Staging cancer Cancer cells may travel through the bloodstream. UNDERSTANDING OSTEOPOROSIS Handbook of Pathophysiology UNDERSTANDING OSTEOPOROSIS What is osteoporosis? Controlling mineral balance Bone formation and resorption WHAT IS OSTEOPOROSIS? Osteoporosis is a metabolic disease of the skeleton that reduces the amount of b one tissue.1. a variety of imaging techniques. the ideal treatment can range from observation to complicated surgical removal with aggressive therapy. 2. with the liver and the lungs as the most common destinations. STAGING CANCER Measuring the extent that cells have spread is called staging. Depending on the type of cancer. TREATING CANCER Due to the variety of cancers. and cortical bone on the perimeter lose s thickness. are used to damage the cancer cells and sto p their reproduction. These drugs travel through the blood to act on dividing cells both normal and cancerous throughout the enti re body. In s urgery. the diseased part of the body is removed. the blood absorbs calcium from the digestive system and deposits it in to the bones. This local therapy is used to shrink a cancer's size eithe r before surgical removal or after. or take up.

BONE FORMATION AND RESORPTION Bone consists of 30% organic and 70% mineral substances.etary calcium deficiency. continuous processes. TYPES OF ULCERS Ulcers may occur anywhere in the esophagus. HOW ULCERS HEAL In the absence of an effective mucous barrier. To maintain the blood calcium level as close to normal as possible. an irritant can cause the basal l amina to exfoliate or slough off. Vitamin D is supplie d by the diet. Both substances stimulate calcium absorption from the intestine and increase resorption from the bone. In addition to enhancing bone resorption. PTH is produced by the parathyroid glands. which are buried in the thyroid gland. However. Bone formation and resorption are normal. use of nonsteroidal anti-inflammatory drugs (NSAIDS). pylorus. or post menopausal estrogen deficiency. The mineral portion. ca lled osteoid. but r esorption by osteoclasts exceeds bone formation. which can lead to ulcers. The organic portion. causing osteoporosis. acts as the matrix or framework for the mineral portion. Bone cells called osteoblasts produce the osteoid matrix. These bacteria cause tissue inflammation. A CLOSER LOOK AT HELICOBACTER PYLORI The bacteria Helicobacter pylori are a contributing factor in chronic gastritis (chronic inflammation of stomach mucosa) and in ulcer formation. and processed int o a very potent form in the liver and kidneys. hardens the osteoid matrix. or jejun um. UNDERSTANDING ULCERS Handbook of Pathophysiology UNDERSTANDING ULCERS What causes ulcers? Types of ulcers A closer look at Helicobacter pylori How ulcers heal WHAT CAUSES ULCERS? Ulcers result from three main causes: infection with Helicobacter pylori. inability of the intestines to absorb calcium. such as the pancre as. Osteoclasts are large bone cells that reshape mature bone by resorbing the miner al and organic components. If this damage is recurring or if healing doesn't take place. This resul ts in an increased sacrifice of bone calcium to maintain normal levels of calciu m in the blood. and pathologic hypersecretion of gastric acids. low calcium enhances the effects of tw o other factors: Parathyroid hormone (PTH) and vitamin D. A process called rapid reepithelialization. with the crater of the ulcer penetrating through one or more layers of tissu e. sh . stomach. in osteoporosis. the crater may penetrate the wall and extend to adjacent tissues and organs. They're typical ly seen within the muscular layers and between cells that line the gastric pits. resorption from the bones increases. produced in the skin as a reaction to sunlight. osteoblasts continue to produce bone. w hich consists of calcium and other minerals. duodenum.

own below. replenishes the damaged epithelium and repairs any defects. 10 MUSCULOSKELETAL SYSTEM Handbook of Pathophysiology 10 MUSCULOSKELETAL SYSTEM Bones € Bone shape and structure € Bone growth Joints € Classification of joints € Joint movement Muscles € Muscle classification € Muscle contraction Tendons And Ligaments Pathophysiologic Manifestations € Alterations in bone € Alterations of muscle Disorders € Bone fracture € Clubfoot € Developmental hip dysplasia € Gout € Muscular dystrophy € Osteoarthritis € Osteogenesis imperfecta € Osteomalacia and rickets € Osteomyelitis € Osteoporosis € Paget's disease € Rhabdomyolysis € Scoliosis .

coccyx) and certain bones of the skull the temporal. As the bone forms. or irregular. and other tissues that gives the body form and shape. Irregular bones include the bones of the spine (vertebrae . the bone hardens. and metatarsals of the hands and feet (See Structure of long bones. ligaments. ten dons. Between adjacent lamellae are small opening s called lacunae. and ulna of th e arm. sternum. and fibula of the leg. which contain bone cells or osteocytes.) Short bones include the tarsal and carpal bones of the feet and hands. or canaliculi. os teoblasts simultaneously replace the cleared section with new. and mandible. ilium. muscles. Cancellous bone consists of thin plates (trabeculae) that form the interior mesh work of bone. Long bo nes are found in the extremities and include the humerus. Bone shape and structure Bones are classified by shape as either long. Adult cortical bone consists of networks of interconn ecting canals. they connect all the lacunae. the femur. Osteoclasts are phagoc ytic cells that digest old. ribs. and pubis. potassium carbonate. and provides sites for hematopoi esis (blood cell production) in the marrow. metacarpals. and the phalanges. They respond t o various stimuli to produce the bony matrix. When serum calcium levels fall. provide a route for tissue fluids transport. embedded in a framework of collagen fibers. STRUCTURE OF LONG BONES Long bones are the weight-bearing bones of the body. short. It also protects vit al organs. Structure of a long bone in an adult is shown below. or haversian systems. Their structure provides ma ximal strength and minimal weight. stronger bone. sphenoid. each c ontaining one or more capillaries. flat. Osteoblasts are present on the outer surface of and within bones. ethmoid . Each of these networks. which t . As calcium salts preci pitate on the organic matrix. radius. scapu lae. Vitamin D supports bone calcification by stimulating osteoblast activity and cal cium absorption from the gut to make it available for bone building. or osteoid. The salts give bone its elasticity and ability to withstand compression . with small amou nts of sodium. bone is either cortical (compact) or cancello us (spongy or trabecular). dietary fac tors. weakened bone section by section. which are composed of inorganic salts (pr imarily calcium and phosphate). It is accomplished by the contin ual actions of bone-forming osteoblasts and bone-reabsorbing cells osteoclasts. As they finish. Classified according to structure. These trabeculae are arranged in various directions to correspond with the lines of maximum stress or pressure. This gives the bone added structur al strength. and magnesium ions) comprise 70% of the matu re bone. The canaliculi. and the amount of stress put on the bone. makes movement possible. Flat b ones include the frontal and parietal bones of the cranium. tibia. Bone growth Bone formation is ongoing and is determined by hormonal stimulation. inorganic salts (calcium and phosphate. respectively. stores calcium and other minerals in the bon y matrix for mobilization if deficiency occurs. sacrum. Chemically. the parathyroid gland releases parathyroid hormone. a system of m icroscopic canals in the bone form around the osteocytes. BONES The human skeleton contains 206 bones.€ Sprains € Strains The musculoskeletal system is a complex system of bones. runs parallel to the bone's long axis and consists of a central haversian canal surr ounded by layers (lamellae) of bone.

and other tissues that connect two bones comp rise a joint. ren al excretion of phosphates increases or decreases in inverse proportion to serum calcium levels. freeing calcium into the blood. . A synovial joint is characterized by a synovial pouch full of fluid that lubricates the two articulating bones. becoming the epiphyseal line. In adults. Because calcium and phosphates interact in a reciprocal relationship. and osteoclasts model the new bone's shape by resorbing previously deposited bone. as in the sutures that join the cranial bones. In children and young adults. located at both ends. Joints. Alkaline phosphatase (ALP) influences bone calcification and li pid and metabolite transport. allow limited motion. or diarthroses. cartilage. STRUCTURE OF A SYNOVIAL JOINT The metacarpophalangeal joint depicted here. joints either predominantly permit m otion or provide stability. and synovial. Osteoblasts deposit new bone in the area just beneath the epiphysis. These joints include the elbows and knees. (See Structure of a synovial joint. bone growth is complete. Parathyroid hormone also increases serum calcium by decreasing renal excr etion of calcium and increasing renal excretion of phosphate ion. The intestine absorbs a considerable amount of phosphates from dietary sources. Fibrous joints.hen stimulates osteoclast activity and bone breakdown. Osteoblasts contain an abundance of ALP. are classified according to stru cture and function. permits angular motion between the finger and the hand. as between verteb rae. cartilaginous. bone growth occurs in the epiphyseal plate. Phosphates are essential to bone formation. like bones. These remodeling activities promote longitudinal bone growth. a laye r of cartilage between the diaphysis and epiphysis of long bones. ligaments. Synovial joints. close du ring adolescence. about 85% of the body's phosphates a re found in bone.) Synovial joints have distinguishing characteristics: The two articulating surfaces of the bones have a smooth hyaline covering (artic ular cartilage) that is resilient to pressure. Depending on their structure. have only minute motion and provide stability w hen tight union is necessary. It ca n also identify biliary obstruction or hyperparathyroidism. Classification of joints The three structural types of joints are fibrous. but adequate levels of vitamin D are necessary for their absor ption. wh ich continues until the epiphyseal growth plates. or synarthroses. or amphiarthroses. JOINTS The tendons. and this cartilage is repl aced by bone. making the bone longer. A rise in serum ALP levels can identify skeletal diseases primarily those characterized b y marked osteoblastic activity such as bone metastases or Paget's disease. or excessive ingesti on of Vitamin D. Cartilaginous joints. are the most common and permit the greatest deg ree of movement.

Circular movements Circular movements include: rotation (motion around a central axis). Beneath the capsule. A fibrous (articular) capsule holds them together. which strength en and stabilize the joint but allow free movement. permit: abduction (movement away from the body's midline) adduction (movement toward the midline). and tendons. Joint movement The two types of synovial joint movement are angular and circular. lining the joint cavity. Surrounding a synovial joint are ligaments. .Their opposing surfaces are congruous and glide smoothly on each other. elbows. including the shoulders and hips. This fluid lubricates the tw o opposing surfaces during motion and also nourishes the articular cartilage. muscles. is the synovial membrane. which se cretes a clear viscous fluid called synovial fluid. Angular movement Joints of the knees. as in the ball and socket joints of the hips and shoulders pronation (downward wrist or ankle motion) supination (upward wrist motion to begging position). Other joints. and phalanges permit the following angular movement s: flexion (closing of the joint angle) extension (opening of the joint angle) hyperextension (extension of the angle beyond the usual arc).

The force pulls one bone toward. Muscles permit and maintain body positions. the result may be cramps. The energy source for this contraction is adenosine triphosphate (ATP). Motor neurons synapse with the motor nerve fibers of voluntary muscles. eversion (ou tward turning. anatomic location. Involuntary muscles. Normal skeletal muscles contract in response to neu ral impulses. and make breathing possible. protraction (as in forward motion of the mandible). Muscle mass accoun ts for about 40% of an average man's weight. called muscle fibe rs. These fibers reach the membranes of skeletal muscle cells at neuromusc ular (myoneural) junctions. Cardiac muscles (smooth) comprise the heart wall. through which run slender threads of protein. it is an important component in temperat ure regulation. away from. Sk eletal muscular activity produces heat. acetylcholine. and great veins. Muscle contraction Each skeletal muscle consists of many elongated muscle cells. or around a second bon e. A bnormal metabolism in the muscle may result in inappropriate contractility. As the muscle fatigues. Deep body temperature regulators are found in the abdominal visc era. If a mu scle is deprived of oxygen. Appropriate contraction of muscle usually applies force to one or more tendons. the junction releases the neurotransmitter. in turn. Muscle s also pump blood through the body (cardiac contraction and vessel compression). These receptors detect changes in the body co re temperature and stimulate the hypothalamus to institute appropriate temperatu re changing responses. which. spinal cord. called fascia. ATP release is also triggered by the impulse at th e myoneural junction. as of foot). (See Chapter 8. depending on the type of muscle contraction and the type of joint involved. f atigue. triggers muscle contraction. which releases calcium fr om the sarcoplasmic reticulum. they are called either volunt ary or involuntary. when stored glycogen or lipids cannot be used because of the lack of an enzyme necessary to convert energy for contraction. these are the skeletal muscles. ) Voluntary muscles can be cont rolled at will and are under the influence of the somatic nervous system. Visceral muscles move contents through internal organs and are smooth (nonstriat ed). Some organs contain both vo luntary and involuntary muscles. For example. Blo od vessels and nerves pass into muscles through the fascia to reach the individu al muscle fibers. Muscle fatigue results when the sources of ATP in a muscle are depleted. such as shivering in response to cold.Other kinds of movement are inversion (inward turning. Muscle classification Muscles are classified according to structure. controlled by the autonomic nervo us system. fatigue occurs rapidly. such as sitting and standing. MUSCLES The most specialized feature of muscle tissue contractility makes the movement o f bones and joints possible. called myofibrils. When muscles are classified according to activity. move food through the intestines (peristalsis). Muscle fibe rs are held together in bundles by sheaths of fibrous tissue. Relaxation of a muscle is believed to take place by revers al of these mechanisms. and function: Skeletal muscles are attached to bone and have a striped (striated) appearance t hat reflects their cellular structure. and retraction (returning protracted part into place). and exercise intolerance. it s . include the cardiac and visceral muscles. as of foot). a membranous network in the muscle fiber. When an impulse reaches the myoneural junction. Nervous system.

In these d isorders. The effects of muscular deconditioning associated with lack of . Atrophy Atrophy is a decrease in the size of a tissue or cell. called osteoporosis. Alterations of muscle Pathologic effects on muscle include atrophy. Lactic acid is a by-product of anaerobic glycolysis and may accumulate in the muscle and blood wi th intense or prolonged muscle contraction. it also regulates osteoblastic activity. and s pasticity. w ith softening and resorption of bone. race. M ost musculoskeletal disorders are caused by or profoundly affect other body syst ems. the myofibril s atrophy after prolonged inactivity from bed rest or trauma (casting). Revascularization then initiates new bone formation in the femoral head or tibial tubercle. Growth The osteochondroses are a group of disorders characterized by avascular necrosis of the epiphyseal growth plates in growing children and adolescents. Estrogen not only regulates c alcium uptake and release. Their purpose is to support and strengthen joints. PATHOPHYSIOLOGIC MANIFESTATIONS Alterations of the normal functioning of bones and muscles are described next. and sex affect bone mass. or strength of bone. TENDONS AND LIGAMENTS Skeletal muscles are attached to bone directly or indirectly by fibrous cords kn own as tendons. or when illness removes needed nutrie nts from muscles. Cancellous bone is more sensitive to metabolic influences. weakness. which leads to a malformed fem oral head. Decreased es trogen levels may lead to diminished osteoblastic activity and loss of bone mass . and resorption exceeds formation. In muscles. For example. myotonia. in which the stored glycogen is split into glucose (glycolysis) without the use of oxygen. CULTURAL DIVERSITY Age. Ligaments are fibrous connections that control joint movement between two bones or cartilages. a lack of blood supply to the femoral head leads to septic necrosis. AGE ALERT Bone density and structural integrity decrease after the age of 30 yea rs in women and after the age of 45 years in men. the most movable end (generally distal) is th e point of insertion. The relatively steady loss of bone matrix can be partially offset by exercise. Bone loss occurs when the two phases b ecome uncoupled. when loc al nerve damage makes movement impossible. Any loss of t he inorganic salts that comprise the chemical structure of bone will weaken bone . Density In healthy young adults. Alterations in bone Disease may alter density. so conditions that produce rapid bone loss tend to affect cancellous bone more quickly than cortica l bone.witches to anaerobic metabolism of glycogen stores. and men typically have denser bones than women. and bone loss. Bone strength Both cortical and trabecular bone contribute to skeletal strength. fatigue. growth. the resorption and formation phases are tightly coupled to maintain bone mass in a steady state. The least movable end of the muscle attachment (generally proxim al) is called the point of origin. In children. blacks commonly have den ser bones than whites. vitamin D deficiency prevents normal bone gr owth and leads to rickets. structural integrity (ab ility to withstand stress).

emotiona l stress. See Chapter 5. for a detailed discussion of these events. During an attack of periodic p aralysis. Conditioning and stretching exercises may help prevent atrophy. This hyp erkalemic periodic paralysis may be caused by a high-carbohydrate diet. eye closure. regular. This can be reversed with moderate. and the electri cal charge needed to initiate the impulse (resting membrane potential) is reduce d from 90 mV to 45 mV. Fluid an d electrolytes. It is the process by which the cell membrane resets its positive charge with respect to the negative charge outside the cell. Fatigue Pathologic muscle fatigue may be the result of impaired neural stimulation of mu scle or energy metabolism or disruption of calcium flux. usually as a result of disuse.physical activity may be apparent in a matter of days. elevation. as well as muscle mass. Periodic paralysis is a disorder that can be triggered by exercise or a process or chemical (such as medication) that increases serum potassium levels. An individual on bed res t loses muscle strength. regeneration of muscle fibers is unlikely. MANAGING MUSCULOSKELETAL PAIN A patient with a musculoskeletal disorder that causes chronic. Depolarization is the reversal of the resting potential in s timulated cell membranes. AGE ALERT Some degree of muscle atrophy is normal with aging. from baseline levels at a rate of 3% a day. nonmalignant pain should be assessed and treated in a stepped approach. the muscle membrane is unresponsive to neural stimuli. and rest acetaminophen (Tylenol) nonsteroidal anti-inflammatories such as ibuprofen (Motrin) other nonnarcotic analgesics such as tramadol (Ultram) or topical capsaicin crea m (Zostrix) . Myotonia and spasticity Myotonia is delayed relaxation after a voluntary muscle contraction such as grip . If reuse isn't r estored within 1 year. Weakness AGE ALERT Muscle mass and muscle strength decrease in the elderly. such as heat. weight-bearing ex ercise. or hyperthyroidism. Myotonia o ccurs in myotonic muscular dystrophy and some forms of periodic paralysis. Measures include: nonpharmacologic methods. or muscle percussion accompanied by prolonged depolarization of t he muscle membrane. prolonged bed rest. ice.

Stress-induced muscle tension. such as: falls motor vehicle accidents sports use of drugs that impair judgment or mobility . seen in central nervou s system injury or severe muscle weakness. (For an explanation of t he terms used to identify fractures. or poor nutrition may cause slow or poor healing. or spasticity. amount of tiss ue and vascular damage. AGE ALERT Children's bones usually heal rapidly and without deformity. The reticular activating system consists of multiple diffuse pathways in the bra in that control wakefulness and response to stimuli. health. or are victims of trauma. and patient's age. they face pr olonged immobilization. However. have other concurrent medical conditions.tricyclic antidepressants such as amitriptyline hydrochloride (Elavil) may decre ase the pain signal at the neurosynaptic junctions opioid analgesics alone or with a tricyclic antidepressant. Causes Risk factors for fractures are those that involve force to bone. In the elderly. DISORDERS AGE ALERT Patients with musculoskeletal disorders are often elderly. see Classifying fractures. and a significant number of these involve fractures. a fracture will occur. (See Managing musculoskeletal pain. is presumably caused by increased activity in the reticular activating system and gamma loop in the muscle fiber. epiphyseal plate fractures in children are likely to cause deformity because the y interfere with normal bone growth. underlying systemic illness .) Bone fracture When a force exceeds the compressive or tensile strength (the ability of the bon e to hold together) of the bone. impaired circulation. adequacy of reduction and immobilization. The prognosis varies with the extent of disablement or deformity. and nutritional status.) An estimated 25% of the population has traumatic musculoskeletal injury each yea r. Generally. A pathologic contracture is permanent muscle shortening caused by muscle spasticity.

clavicle. and fracture line s uch as simple. vertebrae. nondisplaced. Incomplete (partial) Bone continuity isn't completely interrupted. Angulated Fragments lie at an angle to each other. CLASSIFYING FRACTURES One of the best-known systems for classifying fractures uses a combination of te rms that describe general classification. GENERAL CLASSIFICATION OF FRACTURES Simple (closed) Bone fragments don't penetrate the skin. fragment position. and pel vis fractures are often associated with osteoporosis. AGE ALERT The highest incidence of fractures occurs in young males between the a ges of 15 and 24 years (tibia. Compound (open) Bone fragments penetrate the skin. and lower humerus) and are usually the result of trauma. In the elderly. upper humerus. and oblique to describe fractures. . Complete Bone continuity is completely interrupted. such as steroids.young age (immaturity of bone) bone tumors metabolic illnesses(such as hypoparathyroidism or hyperparathyroidism) medications that cause iatrogenic osteoporosis. upper femur. CLASSIFICATION BY FRAGMENT POSITION Comminuted The bone breaks into small pieces. Impacted One bone fragment is forced into another.

Transverse The fracture line forms a right angle with the bone's axis. Overriding Fragments overlap. which hardens along the outer surface of the shaft an d over the broken ends of the bone. Damage to bone tissue triggers an intense inflammatory response in which cells f rom surrounding soft tissue and the marrow cavity invade the fracture area. Pathophysiology When a bone is fractured. young bone that has not yet calci fied. and granulation tissue eventually replaces the hematoma. and blood flow to the entire bone is increased. Osteoclasts reabsorb material from previousl y formed bones and osteoblasts to rebuild bone. Osteoblasts then transform into osteocytes (mature bone cells). Segmental . Osteoblasts in the periosteum. shortening the total bone length. marrow . endos teum. Nondisplaced The two sections of bone maintain essentially normal alignment. also called callus). CLASSIFICATION BY FRACTURE LINE Linear The fracture line runs parallel to the bone's axis. Signs and symptoms Signs and symptoms of bone fracture may include: . creating a spiral pattern. Longitudinal The fracture line extends in a longitudinal (but not parallel) dire ction along the bone's axis. and surrounding soft tissue are disrupted. A hematoma forms between the broken ends of the bone and beneath the periosteum. Fractures occur in two adjacent areas with an isolated central segment Avulsed Fragments are pulled from the normal position by muscle contractions or ligament resistance. Spiral The fracture line crosses the bone at an oblique angle. Oblique The fracture line crosses the bone at about a 45-degree angle to the bon e's axis. and marrow produce osteoid (collagenous. the periosteum and blood vessels in the cortex.Displaced Fracture fragments separate and are deformed.

Symptoms include: increased pain decreased touch sensation increased weakness of the affected part increased swelling and pallor decreased pulses and capillary refill. Treatment of compartment syndrome consists of: . bites. to the point of interfering w ith circulation. burns.deformity due to unnatural alignment swelling due to vasodilation and infiltration by inflammatory leukocytes and mas t cells muscle spasm tenderness impaired sensation distal to the fracture site due to pinching or severing of ne urovascular elements by the trauma or by bone fragments limited range of motion crepitus. or foot. hand. or clicking sounds on movement caused by shifting bone fragments. Crush injuries. lower leg. Compartment syndrome most commonly occurs in the lower arm. RECOGNIZING COMPARTMENT SYNDROME Compartment syndrome occurs when edema or bleeding increases pressure within a m uscle compartment (a smaller section of a muscle). and fractures requiring casts or dressings may cause this syndrome.

Diagnosis Diagnosis of bone fracture includes: .placing the limb at heart level removing constricting forces monitoring neurovascular status subfascial injection of hyaluronidase (Wydase) emergency fasciotomy.) renal calculi from decalcification due to prolonged immobility fat embolism due to disruption of marrow or activation of the sympathetic nervou s system after the trauma (may lead to respiratory or central nervous system dis tress). Complications Possible complications of fracture are: permanent deformity and dysfunction if bones fail to heal (nonunion) or heal imp roperly (malunion) aseptic (not caused by infection) necrosis of bone segments due to impaired circ ulation hypovolemic shock as a result of blood vessel damage (especially with a fracture d femur) muscle contractures compartment syndrome (See Recognizing compartment syndrome.

plates.) or a sedative (such as midazola m [Versed]) to facilitate the muscle stretching necessary to realign the bone.history of traumatic injury and results of the physical examination.V. Treatment in severe fractures that cause blood loss includes: direct pressure to control bleeding fluid replacement as soon as possible to prevent or treat hypovolemic shock. after reduction. Closed reduction involves: manual manipulation local anesthetic (such as lidocaine [Xylocaine]) analgesic (such as morphine IM) muscle relaxant (such as diazepam [Valium] I. or screws and applicati on of a plaster cast . emergency treatment consists of: splinting the limb above and below the suspected fracture to immobilize it applying a cold pack to reduce pain and edema elevating the limb to reduce pain and edema. When closed reduction is impossible. treatment begins with a reduction. open reduction by surgery involves: immobilization of the fracture by means of rods. confirm bone alignment). including g entle palpation and a cautious attempt by the patient to move parts distal to th e injury X-rays of the suspected fracture and the joints above and below (confirm the dia gnosis. After confirming a fracture. Treatment For arm or leg fractures.

is the most common congenital disorder of the low er extremities. spina bifida. Clubfoot Clubfoot. It may be associated with other birth defects. Causes A combination of genetic and environmental factors in utero appears to cause clu bfoot. In talipes equinovarus. s uch as myelomeningocele. which give the foot a characteristic club-like appearance. Clubfoot is correctab le with prompt treatment. and arthrogryposis. the sibling of a child born with clubfoot has 1 chance in 35 of being born with the same anomaly. is usually bilateral and is tw ice as common in boys as girls. This may involv e: elastic bandages and sheepskin coverings to attach traction devices to the patie nt's skin (skin traction) pin or wire inserted through the bone distal to the fracture and attached to a w eight to allow more prolonged traction (skeletal traction). and a chi ld of a parent with clubfoot has 1 chance in 10) arrested development during the 9th and 10th weeks of embryonic life when the fe et are formed (children without a family history of clubfoot) muscle abnormalities leading to variations in length and tendon insertions . It is marked primarily by a deformed talus and shortened Achille s tendon. while the front of the foot curls toward the heel (forefoot adduction).000 live births. using a series of weights and pulleys. immobilization requires s kin or skeletal traction. also called talipes.tetanus prophylaxis prophylactic antibiotics surgery to repair soft tissue damage thorough wound debridement physical therapy after cast removal to restore limb mobility. including: heredity (mechanism of transmission is undetermined. Clubfoot occurs in about 1 per 1. When a splint or cast fails to maintain the reduction. the foot points downward (equinus) and turns inward (varus).

except in elderly. Treatment . In subtle deformity. in wh ich case treatment includes management of the underlying disease. true clubfoot must be distinguished from appar ent clubfoot (metatarsus varus or pigeon toe). The condition called apparent clubfoot results when a fetus maintains a position in utero that gives his feet a clubfo ot appearance at birth. Deformity may be so extreme that the toes touch the inside of the ankle.secondary to paralysis. resulting from the denervation type of progressive muscular atrophy and progressive muscular dystrophy. Another form of ap parent clubfoot is inversion of the feet. however. underdeveloped calf muscles and soft-tissue contractures at the site of the deformity (depending on degree of the varus deformity) foot is tight in its deformed position. or cerebral palsy (older children). Complications Possible complications of talipes equinovarius are: chronic impairment (neglected clubfoot) rarely totally correctable (when severe enough to require surgery). resisting manual efforts to push it back into normal position no pain. Every case includes: deformed talus shortened Achilles tendon shortened and flattened calcaneus bone of the heel shortened. usually by: X-rays showing superimposition of the talus and calcaneus and a ladder-like appe arance of the metatarsals (true clubfoot). poliomyelitis. Pathophysiology Abnormal development of the foot during fetal growth leads to abnormal muscles a nd joints and contracture of soft tissue. Signs and symptoms Talipes equinovarus varies greatly in severity. or it may be only vaguely apparent. Diagnosis Early diagnosis of clubfoot is usually no problem because the deformity is obvio us. it can usually be corrected manually. arthritic patients with secondary deformity.

Other essential parts of management are: stressing to parents importance of prompt treatment and orthopedic supervision u ntil growth is completed teaching parents cast care and how to recognize circulatory impairment before a child in a clubfoot cast is discharged explaining to older child and his parents that surgery can improve clubfoot with good function. About 85% of affected infants are females. Complete dislocation: the femoral head is totally outside the acetabulum. Trying t o correct all three deformities at once only results in a misshapen. DHD can be unilateral or bilateral. mainta ining the correction until the foot regains normal muscle balance. Clubfoot deformities are usually corrected in sequential order: forefoot adducti on first. This abnormality occurs in three forms of va rying severity: Unstable dysplasia: the hip is positioned normally but can be dislocated by mani pulation. Developmental hip dysplasia Developmental hip dysplasia (DHD). rocker-bott omed foot. is the most common disorder affecting the hip joints of children younger than 3 years. it's more likely to occur in the follo wing circumstances: dislocation after breech delivery (malposition in utero. 10 times more common th an after cephalic delivery) . then varus (or inversion). but can't totally correct it. then equinus (or plantar flexion). Causes Although the causes of DHD are not clear. and observing the foot closely for several years to prevent the deformity from recurring. Subluxation or incomplete dislocation: the femoral head rides on the edge of the acetabulum. corre cting this defect permanently takes time and patience.Treatment for clubfoot is done in three stages: correcting the deformity. the affected calf muscle will rema in slightly underdeveloped emphasizing the need for long-term orthopedic care to maintain correction. an abnormality of the hip joint present from birth.

predisposing the infant to DHD) large neonates and twins (more common). Excessive or abnormal mo vement of the joint during a traumatic birth may cause dislocation. and nerves. blood vessels. ligaments. Pathophysiology The precise cause of congenital dislocation is unknown. DHD may caus e: degenerative hip changes abnormal acetabular development lordosis (abnormally increased concave curvature of the lumbar and cervical spin e) joint malformation . Signs and symptoms Signs and symptoms of hip dysplasia vary with age and include: no gross deformity or pain (in newborns) the hip rides above the acetabulum.elevated maternal relaxin. Displacement of bones within the joint may damage joint structures. This may lead to ischemi c necrosis because of the disruption of blood flow to the joint. tendons. Complications If corrective treatment isn't begun until after the age of 2 years. hormone secreted by the corpus luteum during pregnanc y that causes relaxation of pubic symphysis and cervical dilation (may promote r elaxation of the joint ligaments. causing the level of the knees to be uneven (complete dysplasia) limited abduction on the dislocated side (as the child grows older and begins to walk) swaying from side to side ( duck waddle due to uncorrected bilateral dysplasia) limp due to uncorrected unilateral dysplasia. including articulating s urfaces.

abduct the hip while moving the femur upward. with hip flexed and in abduction. Trendelenburg's sign When the child rests his weight on the side of the dislocation and lifts his oth er knee. The sign indicates subluxation or complete dislocat ion in an older infant. This will dislocate the hip. Observations during physical examination of the relaxed child that strongly sugg est DHD include: the number of folds of skin over the thighs on each side when the child is place d on his back (a child in this position usually has an equal number of folds.) ORTOLANI'S AND TRENDELENBURG'S SIGNS OF DHD A positive Ortolani's or Trendelenburg's sign confirms developmental hip dysplas ia (DHD). Then. which is also apparent when the child lies prone) buttock fold on the affected side higher with the child lying prone (also restri cted abduction of the affected hip). Diagnosis Diagnostic measures may include: X-rays to show the location of the femur head and a shallow acetabulum (also to monitor disease or treatment progress) sonography and magnetic resonance imaging to assess reduction.soft tissue damage permanent disability. A click or a jerk (produced by the femoral head moving over the acetabular rim) indicates subluxation in an infant younger than 1 month. bu t a child with subluxation or dislocation may have an extra fold on the affected side. (See Ortolani's and Trendelenburg's signs o f DHD. However. the pelvis drops on the normal side because abductor muscles in the aff ected hip are weak. when the child stands with his weight on the normal side and lifts the . Ortolani's sign Place infant on his back. Adduct the hip while pressing the femur downward.

then a night splint for another month to tighten and stabilize the joint capsule in correct alignme nt. and patients may be totally free of symptoms for years bet ween attacks. ankle. treatment includes: gentle manipulation to reduce the dislocation. fol lowed by a spica cast for 4 to 6 months (if traction fails) if closed treatment fails. secondary gout occurs in the elderly. AGE ALERT Primary gout usually occurs in men after age 30 (95% of cases) and in postmenopausal women. Treatment The earlier an infant receives treatment. the better the chances are for normal development. Treatment varies with the patient's age. but may affect any joint. It's found mostly in the foot. Gout Gout. treatment is difficult and includes: skeletal traction and subcutaneous adductor tenotomy (surgical cutting of the te ndon). to help maintain immobilization) for children you nger than 3 years and weighing less than 35 lb (16 kg) for 2 to 3 weeks gentle closed reduction under general anesthesia to further abduct the hips. even if only one is affected. The prognosis is good with treatment. If treatment doesn't begin until after the age of 3 months. followed by splint-brace or harne ss to hold the hips in a flexed and abducted position to maintain the reduction splint-brace or harness worn continuously for 2 to 3 months. In infants younger than 3 months. especia lly the great toe. and midfoot. Gout follows an intermittent course. the pelvis remains horizontal. it may include: bilateral skin traction (in infants) or skeletal traction (in children who have started walking) to try to reduce the dislocation by gradually abducting the hip s Bryant's traction or divarication traction (both extremities placed in traction.other knee. open reduction. In a child aged 2 to 5 years. also called gouty arthritis. followed by immobilization in a spica cast for an average of 6 months. or surgical division and realignment of bone ( osteotomy). is a metabolic disease marked by urate deposi ts that cause painfully arthritic joints. Treatment begun after the age of 5 years rarely restores satisfactory hip functi on. .

this initial attack is extremely painful. rarely. and sometimes accompanied by fever. Tophi form in fingers. The ski n over the tophus may ulcerate and release a chalky. The lysosomes not only damage the tissues. and renal disease) . or wrist joints. the n the instep. and soft tissue. inflamed. feet. invariably affecting joints in the f eet and legs. tend to be longer and more severe than initial at tacks. comm on in those who are untreated. diabetes mellitus. in internal organs. with large tophi in cartilage. In secondary gout. these deposits are called tophi. The metatars ophalangeal joint of the great toe usually becomes inflamed first (podagra). but some attacks. The first acute attack strikes suddenly and peaks quickly. Although it generally involves only one or a few joints. especially after the use of hydrochlorothiazide or pyraz inamide (Zinamide). ulnar sides of the forearms. dusky red. knee. Immune System). hypertension. As the disease progresses. it may cause hypertension or urate kidne y stones may form. chronic polyarticular gout sets in. such as the kidneys and myocardium. Af fected joints appear hot. sickle cell anemia. which develops during the course of another disease (such as obesity. Mild acute attacks often subside quickly but tend to recur at irregula r intervals. Sometimes a low-grade fever is present. synovial membranes. ankle. In asymptomatic gout. helix of the ear. knees. heel. tender. Pathophysiology When uric acid becomes supersaturated in blood and other body fluids. or both. Eventually. it may be caused by: genetic defect in purine metabolism. The presence of the crys tals triggers an acute inflammatory response when neutrophils begin to ingest th e crystals. retention of uric acid. Such attacks are also polyarticular. which decrease urate excretion (ionic form of uric acid). serum urate levels increase but don't crystallize or produ ce symptoms.Causes Although the exact cause of primary gout remains unknown. Severe attacks may persist for days or weeks. hands. This final. Achilles tend ons and. but al so perpetuate the inflammation. Intercritical periods are the symptom-free intervals between gout attacks. Signs and symptoms Possible signs and symptoms of gout include: joint pain due to uric acid deposits and inflammation . causing overproduction of uric acid (hyperu ricemia). tendons. the cause may be: breakdown of nucleic acid causing hyperuricemia result of drug therapy. Most patients have a second attack within 6 months to 2 years. A migratory attack sequentiall y strikes various joints and the Achilles tendon and is associated with either s ubdeltoid or olecranon bursitis. it crystal lizes and forms a precipitate of urate salts that accumulate in connective tissu e throughout the body. Tissue damage begins when the neutrophils release their lysosomes (s ee Chapter 12. unremitting stage of the disease is marked by persistent painful polyarthritis. or cyanotic. white exudate that is compo sed primarily of uric acid crystals.

and disability due to chronic inflammation and top hi that cause secondary joint degeneration hypertension and albuminuria (in some patients) kidney involvement. ankle.redness and swelling in joints due to uric acid deposits and irritation tophi in the great toe. and pinna of ear due to urate deposits elevated skin temperature from inflammation. progr essively poorer excretion of uric acid and chronic renal dysfunction. painful joints local application of heat or cold . with tubular damage from aggregates of urate crystals. damage of articular cartilage and subc hondral bone. and prevent or reverse complications. Treatment The goals of treatment are to end the acute attack as quickly as possible. Diagnosis The following test results help diagnose gout: needle-like monosodium urate crystals in synovial fluid (shown by needle aspirat ion) or tissue sections of tophaceous deposits hyperuricemia (uric acid greater than 420 mol/mmol of creatinine) elevated 24-hour urine uric acid (usually higher in secondary than in primary go ut) X-rays initially normal. deformity. in chronic gout. preve nt recurring attacks. Outward displacement of the overhanging margin from the bone conto ur characterizes gout. Treatment for acute gout consists of: immobilization and protection of the inflamed. Complications Complications of gout may include: eventual erosions.

V. giving a false impression of increas ed muscle strength. AGE ALERT Older patients are at risk for GI bleeding associated with nonsteroida l anti-inflammatory drug use. and monitor the patient's stools for occult blood. Treatment for chronic gout aims to decrease serum uric acid levels. sardines. Para doxically.increased fluid intake (to 3 L/day if not contradicted by other conditions to pr event kidney stone formation) concomitant treatment with colchicine (oral or I. including: maintenance dosage of allopurinol (Zyloprim) to suppress uric acid formation or control uric acid levels. preventing further attacks (use cautiously in patients with renal failure) colchicine to prevent recurrent acute attacks until uric acid returns to its nor mal level (doesn't affect uric acid level) uricosuric agents (probenecid [Benemid] and sulfinpyrazon [Anturane]) to promote uric acid excretion and inhibit uric acid accumulation (of limited value in pat ients with renal impairment) dietary restrictions. primarily avoiding alcohol and purine-rich foods (shellfis h. liver. or diarrhea develops (in acute inflammation) nonsteroidal anti-inflammatory drugs for pain and inflammation. until the pain subside s or nausea.) every hour for 8 hours to i nhibit phagocytosis of uric acid crystals by neutrophils. cramping. 50% of all cases . or pseudohypertrophic. anchovies. Encourage the patient to take these drugs with mea ls. some wasted muscles tend to enlarge (pseudohypertrophy) because conne ctive tissue and fat replace muscle tissue. vomiting. and kidneys) that increase urate levels (adjuncti ve therapy). The four main types of muscular dystrophy are: Duchenne. Muscular dystrophy Muscular dystrophy is a group of congenital disorders characterized by progressi ve symmetric wasting of skeletal muscles without neural or sensory defects.

and they affect both sexes equally. This metabolic defect that causes the muscle cel ls to die is present from fetal life onward. muscle cells deteriorate or die without it. The specific trigger is unknown. dystrophy limb-girdle dystrophy. and shoulders . mapped genetical ly to the Xp21 locus. but phagocytosis of the muscle cells by inflammatory cells causes scarring and loss of muscle function. The skeleton eventually becomes deformed. It mostly affects males. particularly creatine kinase. skeletal muscle becomes almost totally replaced by fa t and connective tissue. The absence of progressive muscle w asting at birth suggests that other factors compound the effect of dystrophin de ficiency. Causes Causes of muscular dystrophy include: various genetic mechanisms typically involving an enzymatic or metabolic defect X-linked recessive disorders due to defects in the gene coding. 1 to 3 per 100. Patients with Becker mus cular dystrophy can live into their 40s.000 persons. Signs and symptoms Signs and symptoms of Duchenne muscular dystrophy include: insidious onset between the ages of 3 and 5 years initial effect on legs. pelvis. No consistent structural abnormalities are seen in the brain. Pathophysiology Abnormally permeable cell membranes allow leakage of a variety of muscle enzymes . Cardiac and smooth muscle of the GI tract often become fibrot ic. which is essential for maintaining muscle cell membrane. for the muscle protein dystrophin. As the disease progresses. The prognosis varies with the form of disease. Facioscapulohumeral and limb-girdle dystrophies usually don't shorten life expectancy. and it mostly affects males. or benign pseudohypertrophic facioscapulohumeral. (D uchenne and Becker dystrophy) autosomal dominant disorder (facio-scapulohumeral dystrophy) autosomal recessive disorder (limb-girdle dystrophy). 13 to 33 per 100. Duchenne muscular dystrophy strik es during early childhood and is usually fatal during the second decade of life. or Landouzy-Dejerine.Becker.000 persons. causing progr essive immobility.

Signs and symptoms of Becker (benign pseudohypertrophic) muscular dystrophy are: similar to those of Duchenne muscular dystrophy but with slower progression. and lumbar lordosis due to muscle weakness difficulty climbing stairs. Signs and symptoms of limb-girdle dystrophy include: weakness in upper arms and pelvis first lumbar lordosis with abdominal protrusion winging of the scapulae . and upper arm muscles (initial sign) pendulous lip and absent nasolabial fold inability to pucker mouth or whistle abnormal facial movements and absence of facial movements when laughing or cryin g diffuse facial flattening leading to a masklike expression inability to raise arms above the head. firm calf muscles confined to wheelchair (usually by 9 to 12 years of age). toe-walking. Signs of facioscapulohumeral (Landouzy-Dejerine) dystrophy include: weakened face. frequent falls enlarged.waddling gait. shoulder.

and pulmonary complications death commonly due to sudden heart failure. or infection. family history. its clinical char acteristics can suggest the type of dystrophy the patient has and how he may be affected. Complications Possible complications of Duchenne muscular dystrophy are: weakened cardiac and respiratory muscles leading to tachycardia. and diagnostic t est findings. If another family member has muscular dystrophy. and surgery to correct contra ctures (to help preserve mobility and independence) . respiratory failure. Treatment No treatment can stop the progressive muscle impairment. showing fat and connective tissue deposits) immunologic and molecular biological techniques (now available in specialized me dical centers) to facilitate accurate prenatal and postnatal diagnosis of Duchen ne and Becker dystrophies (replacing muscle biopsy and elevated serum creatine k inase levels in diagnosis). The following tests may help in the diagnosis: electromyography showing short. Diagnosis Diagnosis depends on typical clinical findings. electrocardiogr aphic abnormalities. physical therapy. Supportive treatments i nclude: coughing and deep-breathing exercises and diaphragmatic breathing teaching parents to recognize early signs of respiratory complications orthopedic appliances.waddling gait poor balance inability to raise the arms. weak bursts of electrical activity in affected m uscles muscle biopsy showing a combination of muscle cell degeneration and regeneration (in later stages. exercise.

such as steroids) mechanical factors (repeated stress on the joint). It usually affects weight-bear ing joints (knees. and collagen).genetic counseling regarding risk for transmitting disease for family members wh o are carriers adequate fluid intake. Typically. results from many factors. high-fiber diet (physical inactivity predisposes to o besity). in cluding: metabolic (endocrine disorders such as hyperparathyroidism) and genetic (decreas ed collagen synthesis) chemical (drugs that stimulate the collagen-digesting enzymes in the synovial me mbrane. Idiopathic osteoarthritis. glycoproteins that act as cementing mater ial in the cartilage. feet. . hips. the most common form of arthritis. Secondary osteoarthritis usually follows an identifiable predisposing event that leads to degenerative changes. The rate of progression varies. and joints may remain stable for years in an early stage of deterioration. high-protein. a normal part of aging. lumbar vertebrae). its earliest symptoms manifest in middle age and progress f rom there. Causes The primary defect in both idiopathic and secondary osteoarthritis is loss of ar ticular cartilage due to functional changes in chondrocytes (cells responsible f or the formation of the proteoglycans. Osteoarthritis is widespread ( affecting more than 60 million persons in the United States) and is most common in women. is a chronic condition causin g the deterioration of joint cartilage and the formation of reactive new bone at the margins and subchondral areas of the joints. increased dietary bulk. Disability depends on the site and severity of involvement and can range from mi nor limitation of finger movement to severe disability in persons with hip or kn ee involvement. such as: trauma (most common cause) congenital deformity obesity. Osteoarthritis Osteoarthritis. and stool softener for constipati on due to inactivity low-calorie.

aching joint pain due to degradation of the cartilage. and reactive new bone forms at the margins and subchondral areas of the joints. leavi ng the underlying bone unprotected. inflammation. Mechanical injury erodes articular cartilage. particularly after exercise or weight bearing (the most common sympt om. causing numbness and loss of finger dexterity) . or grating of the joint during motion due to cartilage damage Heberden's nodules (bony enlargements of the distal interphalangeal joints) due to repeated inflammation altered gait from contractures due to overcompensation of the muscles supporting the joint decreased range of motion due to pain and stiffness joint enlargement due to stress on the bone and disordered bone growth localized headaches (may be a direct result of cervical spine arthritis). which becomes fibrotic and limits joint movement. which increase with poor posture. causing gross alteration of the bony contours and enla rgement of the joint. obesity. in clude: deep. New bone. sw ollen. The joint cartilage deteriorates. or thickening and har dening of the bone underneath the cartilage. and tender. narrowing the joint space. Signs and symptoms Symptoms. This causes sclerosis. and b one stress. The degeneration results from damage to the chondrocytes. forms at joint margins as the ar ticular cartilage erodes. and occupational stress.Pathophysiology Osteoarthritis occurs in synovial joints. Cartilage softens with age . causing cysts. usually relieved by rest) stiffness in the morning and after exercise (relieved by rest) crepitus. Cartilage flakes irritate the synovial lining. called osteophyte (bone spur). Synovial fluid may be forced into defects in the bone. Complications Complications of osteoarthritis include: irreversible joint changes and node formation (nodes eventually becoming red.

sclerosis of the subchondral space joint deformity due to degeneration or articular damage bony growths at weight-bearing areas joint fusion. X-rays of the affected joint help confirm the diagnosis but may be normal in the early stages. watch for redness with prolonged use. check for constriction. X-rays may require many views and typically show: narrowing of joint space or margin cyst-like bony deposits in joint space and margins. Lumbar and sacral spine: a firm mattress or bed board to decrease morning pain. as ordered. SPECIFIC CARE FOR ARTHRITIC JOINTS Specific care depends on the affected joint: Hand: hot soaks and paraffin dips to relieve pain. Diagnosis Findings that help diagnose osteoarthritis include: absence of systemic symptoms (ruling out inflammatory joint disorder) arthroscopy showing bone spurs. Hip: moist heat pads to relieve pain and antispasmodic drugs. as ordered. narrowing of joint space increased erythrocyte sedimentation rate (with extensive synovitis). Cervical spine: cervical collar. Assist .subluxation of the joint.

maintain or improve mobility. after exertion. minimize weight-beari ng activities. Treatment The goal of treatment is to relieve pain. and be especially careful when stooping or picking up objects always wear well-fitting supportive shoes and not let the heels become too worn down install safety devices at home. braces. and teach the patient to use them correctly. Pro vide elastic supports or braces if needed. take care to stand and walk correctly. Advise use of cushions when sitting and use of an elevated toilet seat . To minimize the long-term effects of osteoarthritis. teach the patient to: plan for adequate rest during the day. and at night take medication exactly as prescribed and report adverse effects immediately avoid overexertion. Knee: assist with prescribed range-of-motion exercises. Treatment may include: weight loss to reduce stress on the joint balance of rest and exercise . cane. Check crutches. and walker for p roper fit. and progressive resistance exercises to increase muscle strength.with range-of-motion and strengthening exercises. exercises to maintain mu scle tone. always making sure the patien t gets the proper rest afterward. such as guard rails in the bathroom do range-of-motion exercises as gently as possible maintain proper body weight to lessen strain on joints avoid percussive activities. For example. and mini mize disability. the patient with unilateral joint involvement should use an orthopedic appliance (such as a cane or walker) on the unaffected side.

or soon after birth from multiple fractures sustained in utero or during delivery.000 people. celecoxib (Celebrex). during. primarily in spine [laminectomy]) osteoplasty (scraping and lavage of deteriorated bone from joint) osteotomy (change in alignment of bone to relieve stress by excision of wedge of bone or cutting of bone). Surgical treatment. ) If it's inherited as an autosomal dominant disorder. Osteogenesis imperfecta Osteogenesis imperfecta is a genetic disease in which bones are thin. and fracture easily. may include: arthroplasty (partial or total replacement of deteriorated part of joint with pr osthetic appliance) arthrodesis (surgical fusion of bones. the homozygous child will likely die before. phenylbutazone. The expression of the disease varies. depending on whether the defect is carried as a trait or is clinically obvious. Causes Causes of osteogenesis imperfecta include: genetic disease. cervical collar. cane. (See Chapter 4. indomethacin (Indocin). typically autosomal dominant (characterized by a defect in the synthesis of connective tissue) autosomal recessive carriage of gene defects that produce osteogenesis imperfect a in homozygotes (osteoporosis in some).medications. and other nonsteroidal anti-inflammatory drugs. including aspirin. which occurs in about 1 in 30. reserved for patients with severe disability or uncontrollab le pain. Pathophysiology Most forms of the disease appear to be caused by mutations in the genes that det . propoxyphene (Darvon). walker. and glucosamine (See Specific care for arthritic joints. a heterozygote may eventually express the di sease. may accelerate arth ritic progression by depleting the normal ground substance of the cartilage). If inheritance is as an autosom al recessive. fenoprof en (Nalfon). poorly dev eloped. braces. or traction to reduce stress intra-articular injections of corticosteroids (every 4 to 6 months) to possibly delay node development in the hands (if used too frequently. Genetics. ibuprofen (Motrin).) support or stabilization of joint with crutches.

Signs and symptoms In the autosomal dominant disorder. C ollectively or alone. and blue sclerae. Diagnosis Diagnosis involves: fractures early in life. Treatment . these mutated genes lead to pathologic fractures and impai red healing. Possible mutations in other genes may cause va riations in the assembly and maintenance of bone and other connective tissues. hearing loss. the following symptoms may not be apparent u ntil the child's mobility increases: frequent fractures and poor healing due to falls as toddlers begin to walk short stature due to multiple fractures caused by minor physical stress deformed cranial structure and limbs from multiple fractures thin skin and bluish sclera of the eyes. thin collagen fibers of the sclera allo wing the choroid layer to be seen abnormal tooth and enamel development due to improper deposition of dentine. Complications Possible complications of osteogenesis imperfecta include: deafness due to bone deformity and scarring of the middle and inner ear stillbirth or death within the first year of life (autosomal-recessive disorder) . showing that mutation i s expressed in more than one connective tissue elevated serum alkaline phosphatase levels (during periods of rapid bone formati on and cellular injury) skin culture showing reduced quantity of fibroblasts echocardiography. possibly showing mitral regurgitation or floppy mitral valves.ermine the structure of collagen.

a precursor of vitamin D. celiac disease. however they usually persist in children with rickets. and have minimal exposure to sunlight. ne eded to form a calcium-binding protein in intestinal absorption sites) . Rickets also oc curs in overcrowded. to form calciferol) inherited impairment of renal tubular reabsorption of phosphate (from vitamin D insensitivity) in vitamin D-resistant rickets (refractory rickets. cystic fibrosis. Causes Causes of osteomalacia and rickets include: inadequate dietary intake of preformed vitamin D malabsorption of vitamin D inadequate exposure to sunlight (solar ultraviolet rays irradiate 7-dehydrochole sterol. Crohn's disease. urban areas where smog limits sunlight penetration. bone cannot calcify normally. the result is called rick ets in infants and young children and osteomalacia in adults. and biliary obstruction) hepatic or renal disease (interfering with hydroxylated calciferol formation. In urban Asia. eat a cereal-based diet. Once a common childhood disease. CULTURAL DIVERSITY Incidence of rickets is highest in children with black or dar k brown skin. who. fistulas. gastric or small-bo wel resections. colitis. bone deformities may dis appear.Possible treatments are: prevention of fractures internal fixation of fractures to ensure stabilization. In osteomalacia. the prognosis is good. absorb less sunlight. With treatment. because of their pigmentation. osteomalacia is most prevalent in young women who have had several childr en. rickets is now rare in the United States. It do es appear occasionally in breast-fed infants who don't receive a vitamin D suppl ement or in infants fed a formula with a nonfortified milk base. familial hypo phosphatemia) conditions reducing the absorption of fat-soluble vitamin D (such as chronic pan creatitis. Osteomalacia and rickets In Vitamin D deficiency.

malfunctioning parathyroid gland (decreased secretion of parathyroid hormone). Possible signs and symptoms include: pain in the legs and lower back due to vertebral collapse bow legs knock knees rachitic rosary (beading of ends of ribs) enlarged wrists and ankles pigeon breast (protruding ribs and sternum) delayed closing of fontanels softening skull bulging forehead . The result is gross deformity of both spongy a nd compact bone. When mineralization of bone matrix is delayed or inadequate. Pathophysiology Vitamin D regulates the absorption of calcium ions from the intestine. falling serum calcium concentration stimulates synthesis and s ecretion of parathyroid hormone. c ontributing to calcium deficiency (normally. bone is disorganize d in structure and lacks density. causing release of calcium from bone. but min eralization can't proceed normally. Signs and symptoms Osteomalacia may be asymptomatic until a fracture occurs. When the co ncentration of phosphate in the bone decreases. coat ing the trabeculae and linings of the haversian canals and areas beneath the per iosteum. and increasing renal phosphate excretion. Chronic vitamin D defi ciency induces numerous bone malformations due to bone softening. osteoid may be produced. Large quantities of osteoid accumulate. When vita min D is lacking. decreasin g renal calcium excretion. vitamin D controls absorption of ca lcium and phosphorus through the intestine) and interfering with activation of v itamin D in the kidneys.

poorly developed muscles (pot belly) difficulty walking and climbing stairs.5 mg/dl. herring. except when caused by malabsorption) teaching patient on prolonged vitamin D supplementation signs of vitamin D toxic ity (headache. fish liver oils. constipation. and eg g yolks) and sufficient sun exposure (obtain a dietary history to assess the pat .5 mg/dl serum inorganic phosphorus less than 3 mg/dl serum citrate less than 2. dietary history. Complications Complications of osteomalacia and rickets may include: spontaneous multiple fractures tetany in infants. and laboratory tests establish the diagno sis. liver. 1. and. Test results that suggest vitamin D deficiency include: serum calcium less than 7. Treatment Possible treatments include: massive oral doses of vitamin D or cod liver oil (for osteomalacia and rickets. renal calculi) 25-hydroxycholecalciferol. Diagnosis Physical examination. after prolonged use. nausea. and alkaline phosphatase less than 4 Bodansky units/dl X-rays showing characteristic bone deformities and abnormalities such as Looser' s zones (radiolucent bands perpendicular to the surface of the bones indicating reduced bone ossification. or a synthetic analogu e of active vitamin (for rickets refractory to vitamin D or rickets accompanied by hepatic or renal disease) foods high in vitamin D (fortified milk. confirms the diagnosis).25-dihydroxycholecalciferol.

for c hronic osteomyelitis. the prognosis for acute osteomyelitis is very good. It may be chronic or acute. Although osteomyelitis often remains localized.ient's current vitamin D intake) supplemental aqueous preparations of vitamin D for chronic fat malabsorption. which is rare. Osteomyelitis Osteomyelitis is a bone infection characterized by progressive inflammatory dest ruction after formation of new bone. Acute osteomyelitis is usually a blood-borne disease and most com monly affects rapidly growing children. it can spread through the bone to the marrow. The most common sites in adults are the pelvis and vert ebrae. prognosis remains poor. It commonly res ults from a combination of local trauma usually trivial but causing a hematoma nd an acute infection originating elsewhere in the body. generally after surgery or trauma. The most commo n sites in children are the lower end of the femur and the upper ends of the tib ia. and supplemental vitamin D fo r breast-fed infants (to prevent rickets). a AGE ALERT Osteomyelitis occurs more often in children (especially boys) than in adults usually as a complication of an acute localized infection. Others include: Streptococcus pyogenes Pneumococcus species Pseudomonas aeruginosa Escherichia coli Proteus vulgaris Pasteurella multocida (part of the normal mouth flora of cats and dogs). . humerus. is characterized by draining sinus tracts and widespread lesions. With prompt treatment. except in dr ug abusers. Causes The most common pyogenic organism in osteomyelitis is: Staphylococcus aureus. cortex. hy droxylated cholecalciferol for refractory rickets. The incidence of both chronic and acute osteomyelitis is declining. Chronic osteomyelitis. and radius. a nd periosteum.

poliomyelitis (rare).Pathophysiology Typically. and restricted movement chronic infection persisting intermittently for years. flaring after minor traum a or persisting as drainage of pus from an old pocket in a sinus tract. myositis (inflammation of voluntary muscle). the section of a l ong bone that is continuous with the epiphysis plates. rheuma tic fever.) Signs and symptoms Clinical features of chronic and acute osteomyelitis are generally the same and may include: rapid onset of acute osteomyelitis. these organisms find a culture site in a hematoma from recent trauma or in a weakened area. and laboratory tests that help confirm osteomyelitis m ay include: history of a urinary tract. such as the site of local infection (for example. foreign bodies. Complications Possible complications of osteomyelitis include: amputation (of an arm or leg when resistant chronic osteomyelitis causes severe. Diagnosis Diagnosis must rule out septicemia. furuncu losis). predisposing the bone to pathologic fracture arrested growth of an extremity (in children with severe disease). respiratory tract. unrelenting pain and decreases function) weakened bone cortex. or other penetrating trauma white blood cell count showing leukocytosis elevated erythrocyte sedimentation rate blood cultures showing causative organism magnetic resonance imaging to delineate bone marrow from soft tissue (facilitate . and bone fracture. human or animal bite. heat. physical examination. and travel through the bloodstream to the metaphysis. Histo ry. where the blood flows int o sinusoids. swelling. (See Avoiding osteomyelitis. or skin infection. ear. with sudden pain in the affected bone and te nderness.

or bed rest to preve nt failure to heal or recurrence supportive measures. wet.s diagnosis) X-rays (may not show bone involvement until the disease has been active for 2 to 3 weeks) bone scans to detect early infection. Antibiotic therapy to control infection may include: systemic antibiotics intracavitary instillation of antibiotics through closed-system continuous irrig ation with low intermittent suction limited irrigation with blood drainage system with suction (Hemovac) packed. antibiotic-soaked dressings. (usually a penicillinase-resistant penicillin. s uch as nafcillin [Nafcil]or oxacillin [Bactocill]) after blood cultures are take n early surgical drainage to relieve pressure and abscess formation immobilization of the affected body part by cast. fluids to maintain hyd ration incision and drainage. traction.V.V. Treatment Treatment for acute osteomyelitis should begin before definitive diagnosis and i ncludes: large doses of antibiotics I. Chronic osteomyelitis care may include: . followed by a culture of the drainage (if an abscess or s inus tract forms). such as analgesics for pain and I.

crepitus. bone. postmenopausal women. Bones are limited in their ability to replac e necrotic tissue caused by infection. AVOIDING OSTEOMYELITIS Bones are essentially isolated from the body's natural defense system once an or ganism gets through the periosteum. such as Cushing syndrome or hyperthyroidi sm. which may lead to chronic osteomyelitis. brittle. Only when the condition i s advanced or severe. and long bones. Osteoporosis Osteoporosis is a metabolic bone disorder in which the rate of bone resorption a ccelerates while the rate of bone formation slows. the femoral heads and pelvic acetabula are se lectively affected.surgery. and muscle grafts to fill in dead space and increase blood supply teach patient to avoid jerky movements and falls (may threaten bone integrity). or deformity immediately. watch for sudden malposi tion of the limb (may indicate fracture). Osteoporosis may be primary or secondary to an underlying disease. report sudden pain. Often. causing a loss of bone mass. Causes The cause of primary osteoporosis is unknown. as in secondary disease. Bones affected by this disease lose calcium and phosphate salts and become porou s. but contributing factors include: mild but prolonged negative calcium balance due to inadequate dietary intake of calcium (may be an important contributing factor) declining gonadal and adrenal function faulty protein metabolism due to relative or progressive estrogen deficiency (es trogen stimulates osteoblastic activity and limits the osteoclastic-stimulating effects of parathyroid hormones) . ribs. usually required to remove dead bone and promote drainage (prognosis re mains poor even after surgery) hyperbaric oxygen to stimulate normal immune mechanisms skin. CULTURAL DIVERSITY Persons of African origin have a much lower incidence of oste oporosis than those of European or Asian origin. and abnormally vulnerable to fractures. Primary osteoporosis is often called senile or postmenopausal osteoporosis becau se it most commonly develops in elderly. It primarily affects the weight-bearing vertebrae. do similar changes occur in the s kull.

replace ment follows resorption immediately. hyperparathyroidism. Cushing's synd rome. diabetes mellitus (plasma calcium and phosphate concentrations are maintai ned by the endocrine system) osteogenesis imperfecta Sudeck's atrophy (localized to hands and feet. the rates of bone formation and resorption are constant. anticonvulsants) cigarette smoking. Pathophysiology In normal bone. Osteoporosis develops when the remodeling cycle is inte . corticosteroids. with recurring attacks) medications (aluminum-containing antacids. and the amount of bone replaced equals the amount of bone resorbed. The many causes of secondary osteoporosis include: prolonged therapy with steroids or heparin (heparin promotes bone resorption by inhibiting collagen synthesis or enhancing collagen breakdown) total immobilization or disuse of a bone (as in hemiplegia) alcoholism malnutrition malabsorption scurvy lactose intolerance endocrine disorders such as hyperthyroidism.sedentary lifestyle.

such as: a postmenopausal woman bends to lift something. Diagnosis may in clude: serial height measurements dual. and new bone formation falls behind resorption. and a markedly aged appearance spontaneous wedge fractures. showing: increasing deformity. When bone is resorbed faster than it forms. especially those affecting the spine. Men hav e approximately 30% greater bone mass than women. and hip fractures (common as bone is lost from the femoral neck). In another common pattern. h ips. kyphosis. then fee ls a sudden pain in her lower back vertebral collapse causes back pain that radiates around the trunk (most common presenting feature) and is aggravated by movement or jarring. such as metastatic cancer or advanced multiple myeloma. pathologic fractures of the neck and femur. Complications Possible complications of osteoporosis include: spontaneous fractures as the bones lose volume and become brittle and weak shock. and spine X-rays showing typical degeneration in the lower thoracic and lumbar vertebrae ( vertebral bodies may appear flattened and may look denser than normal. hears a snapping sound. His tory is the key to identify the specific cause of osteoporosis. Signs and symptoms Osteoporosis is typically discovered suddenly. osteoporosis can develop insidiously. Diagnosis Differential diagnosis must exclude other causes of bone loss. which may explain why osteopor osis develops later in men.or single-photon absorptiometry to measure bone mass of the extremities.rrupted. Colles' fractures of the distal radius after a minor fall. decreased exercise intolerance. bone mine ral loss is evident in only in later stages) . loss of height. the bone becomes less dense. hemorrhage. or fat embolism (fatal complications of fractures).

porous. and control pain may include: physical therapy emphasizing gentle exercise and activity and regular. requires s . phosphorus. possibly elevated pa rathyroid hormone. but otherwise normal-looking bone radionuclide bone scans showing diseased areas as darker portions. Since the advent of readily available bone density measurement. the following st udies are seldom done: bone biopsy showing thin. Treatment Treatment to control bone loss. such as a back brace surgery. and alkaline phosphatase.computed tomography scan to assess spinal bone loss normal serum calcium. moderate weight-bearing exercise to slow bone loss and possibly reverse demineralization (the mechanical stress of exercise stimulates bone formation) supportive devices. Other medications include: calcium and vitamin D supplements to support normal bone metabolism calcitonin (Calcimar) to reduce bone resorption and slow the decline in bone mas s biophosphonates (such as etidronate [Didronel] to increase bone density and rest ore lost bone fluoride (such as alendronate [Fosamax]) to stimulate bone formation. if indicated. prevent fractures. for hip fracture estrogen during 2 years after menopause to slow bone loss analgesics and local heat to relieve pain.

An ini tial phase of excessive bone resorption (osteoclastic phase) is followed by a re active phase of excessive abnormal bone formation (osteoblastic phase). Other measures include: early mobilization after surgery or trauma decreased alcohol and tobacco consumption careful observation for signs of malabsorption. calcium. also called osteitis deformans. is a slowly progressive metabol ic bone disease characterized by accelerated patterns of bone remodeling. fragile. and to report abnormal bleedi ng promptly. causes painful deformiti es of both external contour and internal structure. explaining to the patient's family and ancil lary health care personnel how easily an osteoporotic patient's bones can fractu re) advising patient to report new pain immediately. such as stooping before lifting and av oiding twisting movements and prolonged bending instructing a female patient taking estrogen in the proper technique for breast self-examination. especially after trauma. (fatty stools. Chronic accelerated remodeling eventually enlarges and softens the affected bones. to perform self-examination at least monthly and to report lum ps immediately. no mat ter how slight advising patient to sleep on a firm mattress and avoid excessive bed rest teaching the patient good body mechanics. Paget's disease usually loca . chronic diarrhea) prompt. and protein to support skeletal metabolism (through a balanc ed diet rich in nutrients). and weak. Paget's disease Paget's disease. and can cause gastric distress vitamin C. The n ew bone structure. effective treatment of the underlying disorder (to prevent secondary ost eoporosis) safety precautions for frail patients (keeping side rails up. to have regular gynecologic exams.trict dosage precautions. which is chaotic. moving the patient gently and carefully at all times.

and vascular fibrous tissue replaces marrow. Paget's disease affects about 2. or giant-cell tumors.5 million people older tha n 40 years (mostly men).lizes in one or several areas of the skeleton (most frequently the lumbosacral s pine. pelvis. Early stages may be asymptomatic. femur. and Scandinavia. T he trabeculae diminish. abnormal bone formation. and impaired motor fu nction (with skull involvement). CULTURAL DIVERSITY Paget's disease occurs worldwide but is extremely rare in Asi a. Africa. particularly when it's associated with heart failure (widespread disease creates a continuous need for high cardiac ou tput). Other deformities include: . It can be fatal. and the bone becomes soft and weak. In the United States. and tibia are affected). The collagen fibers in this new bone are disorganized. possibly wi th impaired movement due to impingement of abnormal bone on the spinal cord or s ensory nerve root (pain may also result from the constant inflammation accompany ing cell breakdown) characteristic cranial enlargement over frontal and occipital areas (hat size ma y increase) and possibly headaches. bone sarcoma. The partially resorbed trabeculae thicken and enlarge because of excessive bone formation. they may include: usually severe and persistent pain intensifying with weight bearing. Signs and symptoms Clinical effects of Paget's disease vary. and glycoprotein levels in the matrix decrease. Other possible causes include: benign or malignant bone tumors vitamin D deficiency during the bone-developing years of childhood autoimmune disease estrogen deficiency Pathophysiology Repeated episodes of accelerated osteoclastic resorption of spongy bone occur. one theory is that early viral infection causes a dormant skeletal infection that erupts many years late r as Paget's disease. This is fol lowed by short periods of rapid. sensory abnormalities. When signs and symptoms appear. skull. the Middle East. Causes Although the exact cause of Paget's disease is unknown. but occasionally skeletal d eformity is widely distributed.

Complications Possible complications of Paget's disease include: blindness and hearing loss with tinnitus and vertigo due to bony impingement on the cranial nerves pathologic fractures hypertension renal calculi hypercalcemia gout heart failure due to high blood flow demands of remodeling bones respiratory failure due to deformed thoracic bones .kyphosis (spinal curvature due to compression fractures of vertebrae) barrel chest asymmetric bowing of the tibia and femur (often reduces height) waddling gait (from softening of pelvic bones) warm and tender disease sites susceptible to pathologic fractures after minor tr auma slow and often incomplete healing of pathologic fractures.

Diagnosis Diagnosis of Paget's disease may include: X-rays. etidronate produces improvement after 1 to 3 months) mithramycin (Mithracin). but improvement is noticeable after the first few weeks of treatment. a hormone. Other laboratory findings include: anemia elevated serum alkaline phosphatase (an index of osteoblastic activity and bone formation) elevated 24-hour urine levels for hydroxyproline (amino acid excreted by kidneys and an index of osteoclastic hyperactivity) and pyridinolines. and serum alkaline phosphatase levels. a cytotoxic antibiotic. and magnetic resonance imaging taken before ov ert symptoms develop showing increased bone expansion and density radionuclide bone scan (more sensitive than X-rays) clearly showing early Paget' s lesions (radioisotope concentrates in areas of active disease) bone biopsy showing characteristic mosaic pattern. Treatment Primary treatment consists of drug therapy and includes one of the following med ications: bisphosphonate (alendronate [Fosamax]. produces remission of symptoms within 2 weeks and biochemical improvement in 1 to 2 months. urin ary hydroxyproline. etidronate [Didronel]) to inhibit osteocl ast-mediated bone resorption calcitonin (Calcimar. to decrease serum calcium. Other treatment varies according to symptoms: . but may d estroy platelets or compromise renal function.malignant changes in involved bone (1% of the patients). and etidronate [Didronel]) to retard bone resor ption and reduce serum alkaline phosphate and urinary hydroxyproline secretion ( Calcitonin requires long-term maintenance therapy. computed tomography scan.

see ing. indomethacin (Indocin). and temperature elevation. correct secondary deformities . bleeding. diarrhea. Causes Possible causes of rhabdomyolysis include: familial tendency strenuous exertion infection anesthetic agents (halothane) causing intraoperative rigidity . or walking instructing the patient to follow specific instructions when taking etidronate o r alendronate. drug therapy with calcitonin and etidronate or mithramycin must precede surgery to decrease the risk for excessive bleeding from hypervascular bone joint replacement (difficult because bonding material [methyl methacrylate] does n't set properly on pagetic bone) aspirin. and relieve neurologic impairment. Prognosis is good if contributing causes are stopped or disease is checked before damage has progressed to an irreversible stage. Long-distance running. especially a muscle crush injury. fractures. or ibuprofen (Motrin) to control pain monitoring for new areas of pain or restricted movements (may indicate new fract ure sites) and sensory or motor disturbances. certain severe infections. Rhabdomyoly sis usually follows major muscle trauma. may cause myoglobinuria. it can cause renal failure. such as difficulty in hearing.surgery to reduce or prevent pathologic fractures. the breakdown of muscle tissue. in whic h varying amounts of muscle protein (myoglobin) appear in the urine. Rhabdomyolysis Rhabdomyolysis. easy bruising. and to watch for and report stomach cramps. Unchecked. and exposure to electric shock can cause extensive muscle damage and excessive release of myoglobin. to minimize adverse affects and avoid neutralizing effects of dru g. and increasi ng or new bone pain instructing the patient taking mithramycin to watch for signs of infection. and to report for regular follow -up laboratory tests.

Diagnosis Diagnosis may include: urine myoglobin greater than 0. Complications Possible complications of rhabdomyolysis are: renal failure as myoglobin is trapped in renal capillaries or tubules amputation if muscle necrosis is substantial.5 g/dl (evident with only 200 g of muscle damage) elevated creatinine kinase (0. The ensuing l ocal edema further increases compartment pressure and tamponade. and release of myo globin from the necrotic muscle fibers into the circulation. swelling. or high-voltage electrical shock. musc le infarction. pressure from s evere swelling causes blood vessels to collapse. creatinine. and neural damage in the area of the fracture. Pathophysiology Muscle trauma that compresses tissue causes ischemia and necrosis. reddish-brown urine from myoglobin. and muscle weakness due to muscle trauma and pressure dark. and creatine levels hypocalcemia in early stages.95 mg/dl) due to muscle damage elevated serum potassium. electroconvulsiv e therapy.heat stroke electrolyte disturbances cardiac arrhythmias excessive muscular activity associated with status epilepticus.5 to 0. phosphate. hypercalcemia in later stages . Signs and symptoms Signs and symptoms of rhabdomyolysis include: tenderness. leading to tissue hypoxia.

the greater the magnit ude of the curve and the younger the child at the time of diagnosis. the greater the risk for progression of the spinal abnormality. magnetic resonance imaging. Types of structural scoliosis are: congenital. developing several months after asymmetric paralys is of the trunk muscles due to polio. Favorable outcomes are usua lly achieved with optimal treatment. such as wedge vertebrae. needle. fused ribs or vertebrae. Treatment Treatment of rhabdomyolysis may include: treating the underlying disorder preventing renal failure bed rest anti-inflammatory agents corticosteroids (in extreme cases) analgesics for pain immediate fasciotomy and debridement (if compartment venous pressure is greater than 25 mm Hg). and bone scintigraphy to detect muscle necrosis intracompartmental venous pressure measurements using a wick catheter. About 2% to 3% of adolescents have scoliosis. or muscular dystrophy .computed tomography. In general. lumbar. or hemivertebrae paralytic or musculoskeletal. The curve may be convex to the right (more common in thoracic curves) or to th e left (more common in lumbar curves). or thoracolumbar spine . Scoliosis is often associated with kyphosi s (humpback) and lordosis (swayback). o r slit catheter inserted into the muscle. cerebral palsy. Scoliosis Scoliosis is a lateral curvature of the thoracic. Rotation of the vertebral column around i ts axis may cause rib cage deformity.

compensatory curves develop to maintain body balance. the imbalance continues into adulthood. with convexity to the right and compensatory curves (S curves) in th e cervical and lumbar segments. Causes Scoliosis may be functional or structural. As the spine cu rves laterally.idiopathic (most common). Subtle sig ns include: uneven hemlines or pant legs that appear unequal in length . Pathophysiology Differential stress on vertebral bone causes an imbalance of osteoblastic activi ty. they include: backache fatigue dyspnea. Idiopathic scoliosis can be further classified according to age at onset: infantile (affects mostly male infants between birth and 3 years and causes left thoracic and right lumbar curves) juvenile (affects both sexes between the ages of 4 and 10 years and causes varyi ng types of curvature) adolescent (generally affecting girls from the age of 10 years until skeletal ma turity and causing varying types of curvature). may be transmitted as an autosomal dominant or multifa ctorial trait (appears in a previously straight spine during the growing years). not fixed deformity of the spinal column (postural scoliosis) structural: deformity of the vertebral bodies leading to curvature. When symptoms occur. Without tr eatment. Possible causes include: functional: poor posture or a discrepancy in leg lengths. Signs and symptoms Scoliosis rarely produces subjective symptoms until it's well established. thus the curve progresses rapidly during adolescent growth spurt. The most common curve in functional or structural scoliosis arises in the thorac ic segment. both with convexity to the left.

Complications Without treatment. Physical examination shows: unequal shoulder heights. Untreated scoliosis may result in: pulmonary insufficiency (curvature may decrease lung capacity) back pain degenerative arthritis of the spine vertebral disk disease sciatica. posterior. and lateral spinal X-rays. and heights of iliac crests asymmetric thoracic cage and misalignment of the spinal vertebrae when the patie nt bends over asymmetric paraspinal muscles. rounded on the convex side of the curve and flatt ened on the concave side asymmetric gait. Treatment The severity of the deformity and potential spine growth determine appropriate t . curves greater than 40 degrees progress. taken with the patient standing upright and bending (confirm scoliosis and determine the degree of curvature [Co bb method] and flexibility of the spine) scoliometer to measure the angle of trunk rotation.one hip that appears higher than the other. Diagnosis Diagnosis of scoliosis includes: anterior. elbow levels.

which may include: close observation exercise brace surgery a combination of these. To be most effective. For a curve less than 25 degrees. For a curve of 40 degrees or more. braces can be adjusted as the patient grows and worn until bo ne growth is complete) transcutaneous electrical stimulation (alternative therapy). or mild scoliosis. For a curve of 30 to 50 degrees: spinal exercises and a brace (may halt progression but doesn't reverse the estab lished curvature). treatment includ es: X-rays to monitor curve examination every 3 months exercise program to strengthen torso muscles and prevent curve progression. treatment includes: surgery (supportive instrumentation. with spinal fusion in severe cases) periodic postoperative checkups for several months to monitor stability of the c orrection. when spinal deformity is sti ll subtle. A lateral curve continues to progress at the rate of 1 degree a year even after skeletal maturity. Sprains A sprain is a complete or incomplete tear of the supporting ligaments surroundin .reatment. treatment should begin early.

An immobilized sprain may heal in 2 to 3 weeks without surgical repair.g a joint. elbow. and knee. and eventually becomes strong enough to withstand normal muscle tension . Signs and symptoms Possible signs and symptoms of sprain are: localized pain (especially during joint movement) swelling and heat due to inflammation loss of mobility due to pain (may not occur until several hours after the injury ) skin discoloration from blood extravasating into surrounding tissues. As fur ther reorganization takes place. Collagen formation begins 4 to 5 days after the injury. Complications Possible complications of sprain include: recurring dislocation due to torn ligaments that don't heal properly. Diagnosis Sprain may be diagnosed by: . It usually follows a sharp twist. an inflammatory exudate develops in the hematoma betwee n the torn ends. Pathophysiology When a ligament is torn. the new ligament separates from the surrounding tissue. it may heal in a lengthened shape with an excessive amount of s car tissue). after which the patient can gradually resum e normal activities. With the aid of vascular fibrous tissue. A sprained ankle is the most common joint injury. Causes Causes of sprains include: sharply twisting with force stronger than that of the ligament. Granulation tissue grows inward from the surrounding soft tissu e and cartilage. followed by sprains of the wrist. the new tissue eventually fuses with surrounding tissues. eventua lly organizing fibers parallel to the lines of stress. requiring surgical repair (occasionally) loss of function in a ligament (if a strong muscle pull occurs before it heals a nd stretches it. inducing joint m ovement beyond normal range of motion concurrent fractures or dislocations.

followed by a long leg cast for 4 weeks. until swelli ng begins. An Achilles tendon rupture usually requires surgical repair. especially during physical activities such as jogging or tennis. MUSCLE-TENDON RUPTURES Perhaps the most serious muscle-tendon injury is a rupture of the muscle-tendon junction. The response establishes the diagnosis: plantar flexion. the tendon is ruptured. it's partially intact no flexion of any kind. An Achilles tendon rupture produces a sudden. and then a short cast for an additional 4 weeks. perform thi s simple test: With the patient prone and his feet hanging off the foot of the t able. This rupture typically occurs in men between the a ges of 35 and 40 years. sharp pain and. but it's most com mon at the Achilles tendon. squeeze the calf muscle. To distinguish an Achilles tendon rupture from other ankle injuries. the tendon is intact ankle dorsiflexion. which extends from the posterior calf muscle to the foot.history of recent injury or chronic overuse X-ray to rule out fractures stress radiography to visualize the injury in motion arthroscopy arthrography. a palpable defect. This type of rupture may occur at any such junction. Treatment Treatment to control pain and swelling includes: immobilizing the injured joint to promote healing elevating the joint above the level of the heart for 48 to 72 hours (immediately after the injury) .

Causes Possible causes of strain include: vigorous muscle overuse or overstress. an inflammatory exudate develops between the torn ends. AGE ALERT Tendon rupture is more common in the elderly. especially when the muscle isn't adequately stretched befo re the activity (acute strain) knife or gunshot wound causing a traumatic rupture (acute strain) repeated overuse (chronic strain). the body of the mus cle protrudes through the fascia. Pathophysiology Bleeding into the muscle and surrounding tissue occurs if the muscle is torn.) If the muscle ruptures. in the y oung. (See Muscle-tendon ruptures. Strain is a general term for muscle or tendon damage that often results from sudden. a soft cast or splint to immobilize the joint codeine or another analgesic (if injury is severe) crutch and gait training (sprained ankle) immediate surgical repair to hasten healing. Collagen formation begins 4 to 5 days after the injury. or if the sprain is severe. causing the muscle to become stretched be yond normal capacity. muscle rupture. including suturing the ligament end s in close approximation (some athletes) tape wrists or ankles before sports activities to prevent sprains (athletes). With the aid of vascular fibrous ti . Wh en a tendon or muscle is torn. eventually organi zing fibers parallel to the lines of stress. Injury ranges from excessive stretch (muscle pull) to muscle ru pture. Granulation tissue grows inward from the surrounding soft tissue and cart ilage. Strains A strain is an injury to a muscle or tendinous attachment usually seen after tra umatic or sports injuries. A strained muscle can usually heal without com plications.intermittently applying ice for 12 to 48 hours to control swelling (place a towe l between the ice pack and the skin to prevent a cold injury) an elastic bandage or cast. forced motion causing it to be stretched beyond normal capacity.

the new tissue eventually fuses with surrounding tissues. Complications Possible complications of strain include: complete muscle rupture requiring surgical repair myositis ossificans (chronic inflammation with bony deposits) due to scar tissue calcification (late complication). Signs and symptoms of chronic strain include: stiffness soreness generalized tenderness. Diagnosis Diagnosis of strain may include: . As further reorg anization takes place. and muscle fatigue. If a muscle is chronically strained. Signs and symptoms Signs and symptoms of acute strain include: sharp.ssue. limiting m ovement by causing stiffness. calcium may deposit into a muscle. the new tendon or muscle separates from the surrounding t issue and eventually becomes strong enough to withstand normal muscle strain. transient pain (myalgia) snapping noise rapid swelling that may continue for 72 hours limited function tender muscle (when severe pain subsides) ecchymoses (after several days).

Chronic strains usually don't need treatment. Discomfort may be relieved by: heat application nonsteroidal anti-inflammatory drugs (such as ibuprofen [Motrin]) analgesic muscle relaxant.history of a recent injury or chronic overuse X-ray to rule out fracture stress radiography to visualize the injury in motion biopsy showing muscle regeneration and connective tissue repair (rarely done). then application of heat to enhance blood flow. reduce cramping. Treatment Possible treatments for acute strain includes: compression wrap to immobilize the affected area elevating the injured part above the level of the heart to reduce swelling analgesics application of ice for up to 48 hours. 11 HEMATOLOGIC SYSTEM Handbook of Pathophysiology 11 HEMATOLOGIC SYSTEM Pathophysiologic manifestations € Hemoglobin . and promote healing surgery to suture the tendon or muscle ends in close approximation.

bone marrow cells and their precursors are particularly vulnerable to physiologic changes that affect cell production. PATHOPHYSIOLOGIC MANIFESTATIONS Bone marrow cells reproduce rapidly and have a short life span. Disease can affect the structure or concentration of any hematologic cell. Blood is three to five tim es more viscous than water. The average person has 5 to 6 L of circulating blood.€ Red blood cells € Leukocytosis € Leukopenia € Thrombocytosis Disorders € Aplastic anemias € Iron deficiency anemia € Pernicious anemia € Sideroblastic anemias € Thalassemia € Disseminated intravascular coagulation € Erythroblastosis fetalis € Idiopathic thrombocytopenic purpura € Polycythemia vera € Secondary polycythemia € Spurious polycythemia € Thrombocytopenia € Von Willebrand's disease Blood. Thus. which comprises 5% to 7% o f body weight (as much as 10% in premature newborns). T here primitive blood cells (stem cells) differentiate into the precursors of ery throcytes (normoblasts). Hematopoiesis. occurs primarily in the marrow. and the storage of circulating cells in the marrow is minimal. and thrombocytes. Plasma (a clear. leukocytes.45. leukocytes. Plasma coagulation factors and thrombocytes (platelets) control clotting. the process of blood formation. although a fluid. . Erythrocytes (red blood cells) carry oxygen to the tissues and remove carbon dioxide. and is either br ight red (arterial blood) or dark red (venous blood). Blood performs several vital functions through its special components: the liqui d protein (plasma) and the formed constituents (erythrocytes. It continuously cir culates through the heart and blood vessels.35 to 7. is one of the body's major tissues. depending on the degree of oxygen saturation and the hemoglobin level. straw-colored fluid) carries antibo dies and nutrients to tissues and carries waste away. has an arterial pH of 7. Leukocytes (white blood cells) act in inflamm atory and immune responses. and th rombocytes) suspended in it. carrying vital elements to every pa rt of the body.

The hemoglobin picks up carbon dioxide and hydrogen ions from the cells and delivers them to the lungs. Leukocytosis Leukocytosis is an elevation in the number of white blood cells (WBCs). folic acid. Red blood cells Red blood cell (RBC) disorders may be quantitative or qualitative. such as renal disease. Hemoglobin consists of an iron-containing molecule (heme) bound to the protein globulin. or only one type. and cobalt deficiency anemias) leading to inadequat e erythropoiesis excessive chronic or acute blood loss (posthemorrhagic anemia) chronic illnesses. Ox ygen binds to the heme component and is transported throughout the body and rele ased to the cells. A deficiency of RBCs (anemia) can follow a condition that destroys or inhibits the formation of these cells. where they are released. cancer.) Common factors leading to anemia include: drugs. copper. (See Erythropoiesis. All type s of WBCs may be increased. toxins. ionizing radiation congenital or acquired defects that cause bone marrow to stop producing new RBCs cells (aplasia) and generally suppress production of all blood cells (hematopoi esis. aplastic anemia) metabolic abnormalities (sideroblastic anemia) deficiency of vitamins (vitamin B12 deficiency. Decreased plasma volume can cause a relative excess of RBCs.Hemoglobin The protein hemoglobin is the major component of the red blood cell. (See WBC types and functions.) Leu . and chronic infections intrinsically (sickle cell anemia) or extrinsically (hemolytic transfusion react ion) defective RBCs. or pernicious anemia) or mineral s (iron. The few conditions characterized by excessive production of RBCs include: abnormal proliferation of all bone marrow cells (polycythemia vera) abnormality of a single element (such as erythropoietin excess caused by hypoxem ia or pulmonary disease). A variety of mutations or abnormalities in the hemoglobin protein can cause abno rmal oxygen transport.

monocytes. Thrombocytosis Thrombocytosis is an excess of circulating platelets to greater than 400.kocytosis is a normal physiologic response to infection or inflammation. and pl asma cells).000 and 10.000/ l. radiation or chemotherapy. anesthesia. surgery . In turn. Eosinophils Minor granulocytes. There are six types of WBCs : Neutrophils The predominant form of granulocyte. as ferritin and hemosiderin until it's released for use in the bone marrow to form new RBCs. they make up about 60% of WBCs and help devour invading organisms by phagocytosis. Androgens may also stimulate erythropoiesis. The formation of an erythrocyte (RBC) begins with an uncommitted stem cell that may eventually develop into an RBC or white blood cell. They account for 0% t . thyroid disease. They account for 1% to 5% of the t otal WBC count. they may release heparin and histamine into the bl ood and participate in delayed hypersensitivity reactions. ERYTHROPOIESIS The tissues' demand for oxygen and the blood cells' ability to deliver it regula te red blood cell (RBC) production. WBCs are classified as granular leukocytes (basophils. lymphocytes and plasma ce lls are produced in lymphoid tissue as well. 90% of which is produced by the kidneys and 10% by the liver. Such formation requires certain vitamins B12 and folic acid and minerals copper. or leukocytes. Lack of oxygen in the tissues (hypoxia) stim ulates RBC production. which is vital to hemoglobin's oxygen-carrying capacity. bone marrow disease or destruction. such as temperature changes. An excess of iro n is temporarily stored in reticuloendothelial cells. Because WBCs fight infection. strenuous exercise. WBC TYPES AND FUNCTIONS White blood cells (WBCs). prolonged stress. WBCs number between 5. T hrombocytosis may be primary or secondary. erythropioetin. cobalt. leukemia. It can be caused by a number of conditions or diseases. and some drugs. activates bone marrow to produce RBCs. WBCs are usually produced in bone marrow. and toxins can also c ause leukocytosis. Other f actors. emotional disturbances. and especially iron. Normally. such as human immunodeficiency virus (HIV ) infection. Leukopenia Leukopenia is a deficiency of WBCs all types or only one type. Abnormal leukocytosis occurs in malignancies and bone marrow disorders.000 l. especially those in the li ver. Neutrophils have a circulating half -life of less than 6 hours. and eosinophils) or nongranular leukocytes (lymphocytes. leukopenia increases the risk of infectious ill ness. lupus erythematosus. which triggers the formation and release of the hormone e rythropoietin. hormones. pregnancy. which accounts for higher RBC counts in men. Iron is obtained from various foods and is absorbed in the duodenum and jejunum. or Cushing syndrom e. protect the body against harmful bacter ia and infection. while some lymphocytes may survive for weeks or mont hs. neutrop hils. Basophils Minor granulocytes. they may defend against parasites and lung and s kin infections and act in allergic reactions.

The con dition may result from an intrinsic abnormality of platelet function and increas ed platelet mass. Lymphocytes accoun t for 20% to 40% of the total WBC count. Hemorrhage or hemolytic anemia signal the bone marrow to p roduce more megakaryocytes. They develop from lymphoblasts. hemorrhage. and produce a Primary thrombocytosis In primary thrombocytosis. Monocytes Along with neutrophils. Stress and exercise release stored plate lets from the spleen. DISORDERS Specific causes of hematologic disorders include trauma. It may accompany polycythemia vera or chronic granulocytic leu kemia. reside in the tissue. such as stress. and genetic or congenita l defects that disrupt production or function of blood cells. The death rate for severe aplastic anemia is 80% to 90%. aplastic anemia prope rly refers to pancytopenia resulting from the decreased functional capacity of a hypoplastic. These disorders generally produce fatal bleeding or infection. called megaka ryocytes. They account for 1% to 6% of the total WBC count. malnutrition. Because the spleen is the pri mary site of platelet storage and destruction. exposure to toxins or radiation. leuk openia. drug. Causes Possible causes of aplastic anemia are: radiation (about half of such anemias) . This paradox occurs because accelerated clotting results in a generalized ac tivation of prothrombin and a consequent excess of thrombin clots in the microci rculation. they help devour invading organisms by phagocy tosis. Aplastic anemias Aplastic or hypoplastic. and thrombocytopenia) and bone marrow hypoplasia. fatty bone marrow. chronic disease. Monocytes help process antigens for lymphocytes and form macrophages in t he tissues. produce humoral antibodies. In the presence of thrombocytosis. the number of platelet precursor cells. especially when t hey're idiopathic or caused by chloramphenicol (Chloromycetin) use or infectious hepatitis.o 1% of the total WBC count. Although commonly used interchangeably with other terms for bone marrow failure. anemias result from injury to or destruction of stem ce lls in bone marrow or the bone marrow matrix. or hemolytic anemia. Secondary thrombocytosis Secondary thrombocytosis is a result of an underlying cause. This process consumes exorbitant amounts of coagulation factors and t hereby increases the risk of hemorrhage. both hemorrhage and thrombosis may occ ur. Plasma cells ntibodies. exe rcise. Thrombocytosis may also occur after a splenectomy. Lymphocytes They occur as B cells and T cells. causing pancytopenia (anemia. B cells form lymphoid follicles. platelet count may rise after its removal until the bone marrow begins producing fewer platelets. is increased and the platelet count is greater than1 million/ l. surger y. and help T cells mediated delayed hypersensitivity r eactions and the rejection of foreign cells or cell products.

RBCs may be macrocytic (larger than normal) and anisocytotic (excessive variatio n in size). and . shortness of breath. and Fanconi syndrome (develops between birth and 10 years of age). with: very low absolute reticulocyte count elevated serum iron (unless bleeding occurs). rectum. gums. oral and rectal ulcers. anticonvulsants). and ult imately tachycardia and heart failure due to hypoxia and increased venous return ecchymosis. vagina) or into the retina or central nervous system due to thr ombocytopenia infection (fever. Pathophysiology Aplastic anemia usually develops when damaged or destroyed stem cells inhibit bl ood cell production. They may include: progressive weakness and fatigue. Complications A possible complication of aplastic anemia is: life-threatening hemorrhage from the mucous membranes. Diagnosis The following test results help diagnose aplastic anemia: 1 million/ l or fewer RBC of normal color and size (normochromic and normocytic). or p releukemic and neoplastic infiltration of bone marrow congenital (idiopathic anemias): two identified forms of aplastic anemia are con genital hypoplastic or Blackfan-Diamond anemia (develops between ages 2 and 3 mo nths). sore throat) without characteristic in flammation due to neutropenia (neutrophil deficiency). Less commonly. presence of hemosiderin (a derivative of hemoglobin). petechiae. headache. severe disease (especially hepatitis). especially from the mucous membranes (nos e. pallor. Signs and symptoms Signs and symptoms of aplastic anemia vary with the severity of pancytopenia. normal or slightly reduced total i ron-binding capacity. and hemorrhage. they develop when damaged bone marrow microv asculature creates an unfavorable environment for cell growth and maturation. or toxic agents (such as benzene or chlora mphenicol [Chloromycetin]) autioimmune reactions (unconfirmed).drugs (antibiotics. bu t develop insidiously in many cases.

Treatment Effective treatment must eliminate an identifiable cause and provide vigorous su pportive measures. diligent handwashing. including: packed RBC or platelet transfusion. marrow-stimulating agents.) specific antibiotics for infection (not given prophylactically because they enco urage resistant strains of organisms) respiratory support with oxygen in addition to blood transfusions (for patients with low hemoglobin levels) corticosteroids to stimulate erythropoiesis. and colony-stimul ating factors to encourage growth of specific cellular components. Differential diagnosis must rule out paroxysmal nocturnal hemoglobinuria and oth er diseases in which pancytopenia is common. or gelatinous replacement. and lymphocyte counts abnormal coagulation test results (bleeding time) reflecting decreased platelet count dry tap (no cells) from bone marrow aspiration at several sites biopsy showing severely hypocellular or aplastic marrow. neutrophil. experimental histocompatibility locus antige n-matched leukocyte transfusions bone marrow transplantation (treatment of choice for anemia due to severe aplasi a and for patients who need constant RBC transfusions) for patients with leukopenia. with varied amounts of fat. antilymphocyte globulin (experimental). and depression of RBCs and precursors (erythroid elements). immunosuppres sive agents (if the patient doesn't respond to other therapy). etc. special measures to prevent infection (avoidance o f exposure to communicable diseases. such as androgens (controversial). fibrous tissue.microscopically visible tissue iron storage decreased platelet. Iron deficiency anemia Iron deficiency anemia is a disorder of oxygen transport in which hemoglobin syn . absence of tagged iron (because iron is deposited in the liver rather than bone marrow) and megakaryocytes (plat elet precursors).

The pro gnosis after replacement therapy is favorable. which binds with and transports i ron. resulting in smaller (microcytic) cells with less color (hypo chromic) on staining. in turn. subnormal oxygen-carrying capacity o f the blood. They tend not to seek medical treatment unt il anemia is severe. cancer. which diverts maternal iron to the fetus for erythropoiesis intravascular hemolysis-induced hemoglobinuria or paroxysmal nocturnal hemoglobi nuria mechanical trauma to RBCs caused by a prosthetic heart valve or vena cava filter s. including plasma iron. A common disease worldwide. inability to concentrate. signs and symptoms include: dyspnea on exertion. and the concentration of serum transferrin. steroi ds) or heavy menses. children. such as rapid growth. become deplete d. Insufficient iron stores lead to a depleted RBC mass with subnor mal hemoglobin concentration. many patients exhibit only symptoms of an underlying condition. Body stores of iron. Iron deficiency anemia occurs most commonly in premenopausal women. aspirin. and a susceptibility to infection due to decreased oxygencarrying capacity of the blood caused by decreased hemoglobin levels increased cardiac output and tachycardia due to decreased oxygen perfusion . iron deficiency anemia affects 10% to 30% of the adult population of the United States.thesis is deficient. in children and adolescents iron malabsorption. as in chronic diarrhea. Pathophysiology Iron deficiency anemia occurs when the supply of iron is inadequate for optimal formation of RBCs. such as celiac disease and pernicious anemia blood loss due to drug-induced GI bleeding (from anticoagulants. listlessness. and. decreases. fatigue. peptic ulcers. hemorrhage from trauma. Causes Possible causes of iron deficiency anemia are: inadequate dietary intake of iron (less than 1 to 2 mg/day). infants (particularly premature or low-birth-weight infants). headache. At advanced stages. and ma labsorption syndromes. ir ritability. pallor. Signs and symptoms Because iron deficiency anemia progresses gradually. or varices pregnancy. as in prolonged non supplemented breast-feeding or bottle-feeding of infants or during periods of st ress. partial or total gastrectomy. and adolescents (especially girls).

brittle. less than 10 g/dl) low hematocrit (males. less than 47. such as starch or dirt bleeding overdosage of oral or IM iron supplements. females. females. However. RBC count may be normal. or iron supplements. red. and burning tongue due to papillae atrophy sore. the results of these tests can be misleading because of complicating factors. compulsive eating of nonfood materials. blood transfusion. Diagnosis Blood studies (serum iron. Characteristic blood te st results include: low hemoglobin (males. except in infants and children) . Complications Possible complications include: infection and pneumonia pica. spoon-shaped (koilonchyia). with microcytic and hypochromic cells (in early stages. dry skin in the corners of the mouth due to epithelial changes. ferritin levels) and iro n stores in bone marrow may confirm iron deficiency anemia. total iron-binding capacity.coarsely ridged. pneumonia. less than 12 g/dl. and thin nails due to decr eased capillary circulation sore. less than 42) low serum iron with high binding capacity low serum ferritin low RBC count. such as infec tion.

infusion of supplemental iron is painless and requires f ewer injections. It's rare in children. Considerations inc lude: total-dose infusion of iron dextran (INFeD) in normal saline solution given over 1 to 8 hours (pregnant patients and geriatric patients with severe anemia) I. with malabsorption preventing adequate iron absorption. AGE ALERT Onset typically occurs between the ages of 50 and 60 years. hepatic.V.5 ml given first (to minimize the risk for an allergic react ion).decreased mean corpuscular hemoglobin in severe anemia depleted or absent iron stores (by specific staining) and hyperplasia of normal precursor cells (by bone marrow studies). or for a maximum rate of hemoglobin regeneration). If not treated. Only then can iron replacement therapy begin. cancer. Diagnosis must also include: exclusion of other causes of anemia. and incide nce increases with age. CULTURAL DIVERSITY Pernicious anemia primarily affects people of northern Europe an ancestry. is caused by ma labsorption of vitamin B12. the most common type of megaloblastic anemia. In the United States. it's most common in New England and the Great Lakes region because of ethnic distribution. Its manifestations subside with trea tment. or renal disease. Pernicious anemia Pernicious anemia. test dose of 0. Pathophysiology . it's usually preferred to IM administration. and chro nic inflammatory. Because total-dose I. but some neurologic deficits may be permanent. Possible treatments are: oral preparation of iron (treatment of choice) or a combination of iron and asco rbic acid (enhances iron absorption) parenteral iron (for patient noncompliant with oral dose. pernicious anemia is fatal. such as thalassemia minor. needing more iron than can be given orally.V. Treatment The first priority of treatment is to determine the underlying cause of anemia.

Other common manifestations include: pale appearance of lips and gums faintly jaundiced sclera and pale to bright yellow skin due to hemolysis-induced hyperbilirubinemia . leading to production of few. and Graves' dis ease (significantly higher incidence in these patients) partial gastrectomy (iatrogenic induction) older age (progressive loss of vitamin B12 absorption). particularly of RBCs. myxedema. which is normally secreted by the parietal cells of the gastric mucosa and is essential for vitamin B12 ab sorption in the ileum. pernicious anemia has an insidious onset but eventually caus es an unmistakable triad of symptoms: weakness due to tissue hypoxia sore tongue due to atrophy of the papillae numbness and tingling in the extremities as a result of interference with impuls e transmission from demyelination. It also causes neurologic damage by impairing myelin for mation.Pernicious anemia is characterized by decreased production of hydrochloric acid in the stomach. deformed RBCs with poor ox ygen-carrying capacity. AGE ALERT The elderly often have a dietary deficiency of B12 in addition to or i nstead of poor absorption. Signs and symptoms Characteristically. and a deficiency of intrinsic factor. The resulting vitamin B12 deficiency inhibits cell growth . such as thyroiditis. Causes Possible causes of pernicious anemia include: genetic predisposition (suggested by familial incidence) immunologically related diseases.

ataxia. impaired fine finger movement positive Babinski and Romberg signs light-headedness altered vision (diplopia. poor memory. and. and hearing (tinnitus).high susceptibility to infection. in males. Neurologic symptoms include: neuritis. optic muscle atrophy loss of bowel and bladder control. headache. diarrhea. Pernicious anemia may also have gastrointestinal. weight loss. taste. anorexia. and constipation from disturbed digestion due to gastric mucosal atrophy and decreased hydrochlor ic acid production gingival bleeding and tongue inflammation (may hinder eating and intensify anore xia). impotence. especially of the genitourinary tract. neurologic. blurred vision). vomiting. and cardiovascular effects. and delirium (some symptoms are temporary. due to demyelinatio n (initially affects peripheral nerves but gradually extends to the spinal cord) caused by vitamin B12 deficiency irritability. Gastrointestinal symptoms include: nausea. depression. but irreversible central nervous system [CNS] changes may have occur red before treatment). weakness in extremities peripheral numbness and paresthesia disturbed position sense lack of coordination. Cardiovascular symptoms include: . flatulence.

premature be ats. radiation. wide pulse pressure. gastric surgery. Decreased hemoglobin levels by 1 to 2 g/dl in elderly men and slightly decreased hematocrit in both men and women reflect decreased bone marrow and hematopoiesi s and. eventually. such as: folic acid deficiency anemia vitamin B12 deficiency resulting from malabsorption due to GI disorders. or drug therapy. tachycardia.low hemoglobin levels due to widespread destruction of RBCs caused by increasing ly fragile cell membranes palpitations. in men. Diagnosis Laboratory screening must rule out other anemias with similar symptoms but diffe rent treatments. Complications Possible complications include: hypokalemia (first week of treatment) permanent CNS symptoms (if the patient is not treated within 6 months of appeara nce of symptoms) gastric polyps stomach cancer. and. decreased androgen levels. they aren't an indicator of pernicious anemia. Diagnosis of pernicious anemia is established by: positive family history hemoglobin 4 to 5 g/dl low RBC count . dyspnea. orthopnea. heart failure due to compensatory increased cardiac output .

decrease vitamin B12 dosage to monthly self-administered maintenance dose (treatment must be given for life) bed rest for extreme fatigue until hemoglobin rises blood transfusions for dangerously low hemoglobin digoxin (Lanoxin). minimiz e complications. with increased numbers of megaloblasts but few normally developing RBCs gastric analysis showing absence of free hydrochloric acid after histamine or pe ntagastrin injection Schilling test for excretion of radiolabeled vitamin B12 (definitive test for pe rnicious anemia) serologic findings including intrinsic factor antibodies and antiparietal cell a ntibodies.1 g/ml bone marrow aspiration showing erythroid hyperplasia (crowded red bone marrow). low-sodium diet (if patient is in heart failure) antibiotics to combat infections. diuretic. Sideroblastic anemias . and possibly prevent permanent neurologic damage) concomitant iron and folic acid replacement to prevent iron deficiency anemia (r apid cell regeneration increases the patient's iron and folate requirements) after initial response.mean corpuscular volume greater than 120 l due to increased amounts of hemoglobin in larger-than-normal RBCs serum vitamin B12 less than than 0. Treatment Treatment for pernicious anemia is: early parenteral vitamin B12 replacement (can reverse pernicious anemia.

Sideroblastic anemias are a group of heterogenous disorders with a common defect : they fail to use iron in hemoglobin synthesis. i t can damage the nuclei of RBC precursors. occ asionally. and hepatosplenomegaly due to heart and liver failure caused by excessive iron accumulation in these organs increased GI absorption of iron. multiple myel oma. Pathophysiology In sideroblastic anemia. Hereditary sideroblastic anemia commonly responds to treatment with pyridoxine (vitamin B6). enlarged lymph nodes due to iron toxicity dyspnea. tuberculosis. fatigue. iron is deposited in the mitochondria of normoblasts. and. The acquired for m can be primary or secondary. and severe infections. lupus erythematosus. forming the characteristic ringed sideroblast of hemochromatosis. This form is most common in the elderly. RINGED SIDEROBLAST Electron microscopy shows large iron deposits in the mitochondria that surround the nucleus. pale skin and mucous membranes. untreated. known as refractory anemia with ringed sideroblasts. such as rheumatoid arthritis. It's commonly associated with t hrombocytopenia or leukopenia as part of a myelodysplastic syndrome. Correction of the secondary acquired form depends on the cause. occurring mostly in young males (female carriers usually s how no signs of this disorder). Cause Hereditary sideroblastic anemia appears to be transmitted by: X-linked inheritance. The primary acquired (idiopathic) fo rm. resists treatment and i s usually fatal within 10 years of the onset of complications or a concomitant d isease. slight jaundice. which are the n termed ringed sideroblasts. normoblasts fail to use iron to synthesize hemoglobin. These anemias may be hereditary or acquired. weakness. Iron toxicity can cause organ damage. causing signs of hemosiderosis (hereditary side roblastic anemia) . Signs and symptoms Possible signs and symptoms of sideroblastic anemia include: anorexia. dizziness. As a result. The acquired form may be secondary to: ingestion of or exposure to toxins (such as alcohol and lead) or drugs (such as isoniazid [Laniazid] and chloramphenicol [Chloromycetin]) other diseases. despite the availability of ade quate iron stores. exertional angina.

transferrin. with anisocytosis and poikilocytosis ( abnormal variation in shape) low hemoglobin with high serum iron. (See Ringed sideroblast. RBC precursors may be megaloblastic. liver. Diagnosis Diagnosis is confirmed by: ringed sideroblasts on microscopic examination of bone marrow aspirate stained w ith Prussian blue or alizarin red dye. and bilirubin le vels due to RBC lysis normal platelet and leukocyte counts (occasional thrombocytopenia or leukopenia) . Complications Possible complications are: heart.other symptoms depend on the underlying cause (secondary sideroblastic anemia).) hypochromic or normochromic and slightly macrocytic RBCs on microscopic examinat ion. and pancreatic disease respiratory complications acute myelogenous leukemia. urobilinogen. Treatment Treatment of sideroblastic anemias depends on the underlying cause and includes: several weeks of treatment with high doses of pyridoxine (vitamin B6)for heredit ary form removal of the causative drug or toxin or treatment of the underlying condition (symptoms usually subside in acquired secondary form) folic acid supplements (may be beneficial when concomitant megaloblastic nuclear changes in RBC precursors are present) deferoxamine (Desferal) to treat chronic iron overload as needed .

interme dia. Consequently. This conversion doesn't happen in thalassemic infants. synthesis of the beta p olypeptide chain is defective. but also occurs in people whose ancestors orig inated in Africa. In b-thalassemia. is characterized by defect ive synthesis in the polypeptide chains of the protein component of hemoglobin. a hereditary group of hemolytic anemias.to beta-polypeptides at the time of birth. It occurs in three clinical forms: major. the most common form of this disorder. southeast Asia. Thalassemia Thalassemia. Normally. Mediterranean disease. reducing s erum and total-body iron levels. and erythroblastic anemia) are: .blood transfusions (providing hemoglobin) or high doses of androgens (effective palliative measures for some patients with primary acquired form) phlebotomy to prevent hemochromatosis (the accumulation of iron in body tissues) increases the rate of erythropoiesis and uses up excess iron stores. and India. RBC synthesis is also impaired. CULTURAL DIVERSITY Thalassemia is most common in people of Mediterranean ancestr y (especially Italian and Greek). The prognosis varie s: thalassemia major: patients seldom survive to adulthood thalassemia intermedia: children develop normally into adulthood. The severity of the resulting anemia depends on whether the pati ent is homozygous or heterozygous for the thalassemic trait. Their red cells are hypochromic and microcytic. and minor. although puber ty is usually delayed thalassemia minor: normal life span. Signs and symptoms Possible signs and symptoms of thalassemia major (also known as Cooley's anemia. Pathophysiology Total or partial deficiency of beta polypeptide chain production impairs hemoglo bin synthesis and results in continual production of fetal hemoglobin. immunoglobulin synthesis switches from g amma. Causes Causes of thalassemia are: homozygous inheritance of the partially dominant autosomal gene (thalassemia maj or or thalassemia intermedia) heterozygous inheritance of the same gene (thalassemia minor). southern China. lasting e ven past the neonatal period.

and high reticulocyte count . bone abnormalities. anorexia small body. failure to thrive. and splenomegaly possibly signs of hemosiderosis due to increased intestinal absorption of iron. Signs of thalassemia minor are: mild anemia (usually produces no symptoms and is often overlooked. Signs and symptoms of thalassemia intermedia are: some degree of anemia. and life-threatening complications pallor and yellow skin and sclera in 3.to 6-month-old infants splenomegaly or hepatomegaly. Diagnosis Diagnosis of thalassemia major includes: low RBC and hemoglobin. and possible mental retardatio n possible features similar to Down syndrome in infants. b leeding tendencies (especially nose bleeds). Complications Possible complications of thalassemia include: pathologic fractures due to expansion of the marrow cavities with thinning of th e long bones cardiac arrhythmias heart failure. with abdominal enlargement. large head (characteristic features). it should be differentiated from iron deficiency anemia). frequent infections. jaundice. microcytosis. during second 6 months if life develops severe anemia.healthy infant at birth. due to thickened bone at the base of the nose from bone marrow hyperactivity.

Diagnosis of thalassemia intermedia includes: hypochromic microcytic RBCs (less severe than in thalassemia major). an d marked anisocytosis thinning and widening of the marrow space on skull and long bone X-rays due to o veractive bone marrow granular appearance of bones of skull and vertebrae. areas of osteoporosis in lo ng bones. deformed (rectangular or biconvex) phalanges significantly increased fetal hemoglobin and slightly increased hemoglobin A2 qu antitative hemoglobin studies excluding iron deficiency anemia (also produces hypochromic microcytic RBCs). Treatment Treatment of thalassemia major is essentially supportive and includes: prompt treatment with appropriate antibiotics for infections folic acid supplements to help maintain folic acid levels despite increased requ irements . microcytes. Diagnosis of thalassemia minor includes: hypochromic microcytic RBCs significantly increased hemoglobin A2 and moderately increased fetal hemoglobin on quantitative hemoglobin studies.elevated bilirubin and urinary and fecal urobilinogen levels low serum folate reflects increased folate use by hypertrophied bone marrow peripheral blood smear showing target cells. pale nucleated RBCs.

poisonous snakebite. is generally an acute condi tion but may be chronic in cancer patients. brain tis sue destruction. Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) occurs as a complication of disease s and conditions that accelerate clotting. septic abortion. In many patients. rickettsial. metastatic carcinoma. and GI mucosa. and consequent severe hemorrhage. pituitary and adrenal glands. activa tion of the fibrinolytic system. and purpura f ulminans. transplant rejection. aplastic ane mia disorders that produce necrosis. including extensive burns and trauma. or protozoal infection obstetric complications. the severity of the hemorrhage. Pathophysiology It isn't clear why certain disorders lead to DIC or whether they use a common me chanism. incompatible blood transfusion. the triggering mechanisms may be the entrance of fore ign protein into the circulation and vascular endothelial injury. shock. Prognosis depends on early detection and treatment. amniotic fluid embolism. including acute leukemia. organ necrosis. Causes Causes of DIC include: infection. including abruption placentae. and treatment of the underlying disease. including gram-negative or gram-positive septicemia and viral. . surgery requiring c ardiopulmonary bypass. lungs. severe venous thrombosis. hepatic necrosis other conditions. giant hemangioma. fungal . causing small blood vessel occlusion. retained dead fetus. also called consumption coagulopathy or defibrination syndrome. cardiac arrest. including heatstroke. cirrhosis. depletion of circulating clotting factors and platelets. f at embolism.transfusions of packed RBCs to increase hemoglobin levels (used judiciously to m inimize iron overload) splenectomy and bone marrow transplantation (effectiveness has not been confirme d) no treatment for thalassemia intermedia and thalassemia minor no iron supplements (contraindicated in all forms of thalassemia). DIC. Clotting in t he microcirculation usually affects the kidneys and extremities but may occur in the brain. eclampsia neoplastic disease.

the typical accelerated clotting results in genera lized activation of prothrombin and a consequent excess of thrombin. p rothrombin. back. and chest pain from tissue hypoxia nausea and vomiting (may be a manifestation of GI bleeding) shock due to hemorrhage . and factors V and VIII). causing hypofibrinogenemia. Circu lating thrombin also activates the fibrinolytic system. which dissolves fibrin c lots into fibrin degradation products. platelets. The thrombi n converts fibrinogen to fibrin. hypo prothrombinemia. This process uses huge amounts of coagulation factors (especially fibrinogen. Hemorrhage may be mostly the result of th e anticoagulant activity of fibrin degradation products as well as depletion of plasma coagulation factors. Signs and symptoms Signs and symptoms of DIC caused by the anticoagulant activity of fibrin degrada tion products and depletion of plasma coagulation factors include: abnormal bleeding cutaneous oozing of serum petechiae or blood blisters bleeding from surgical or IV sites bleeding from the GI tract epistaxis hemoptysis. Other signs and symptoms are: cyanotic. abdominal. and deficiencies in factors V and VIII.Regardless of how DIC begins. producing fibrin clots in the microcirculation. cold. thrombocytopenia. due to fibrin clots in the microcircul ation resulting in tissue ischemia severe muscle. mottled fingers and toes.

confusion. diminished levels of factors V and VIII. fragmentation of RBCs. because platelets are consu med during thrombosis fibrinogen less than150 mg/dl because fibrinogen is consumed in clot formation ( levels may be normal if elevated by hepatitis or pregnancy) prothrombin time greater than15 seconds partial thromboplastin time greater than 60 seconds increased fibrin degradation products. Complications Complications of DIC include: acute tubular necrosis shock multiple organ failure. possibly due to cerebral thrombus and decreased cerebral perfusion dyspnea due to poor tissue perfusion and oxygenation oliguria due to decreased renal perfusion.00/ l. and hemoglobin less than 10 g/dl . often greater than 45 mcg/ml. due to exce ss fibrinolysis by plasmin D-dimer test (presence of an asymmetrical carbon compound fragment formed in the presence of fibrin split products) positive at less than 1:8 dilution positive fibrin monomers. usually less than 100. Diagnosis Diagnosis of DIC is based on: decreased platelet count.

Treatment Treatment includes: prompt recognition and treatment of underlying disorder blood. associated with profound anemia and edema) are stillborn. platelet. mother and fetus hav e different ABO blood types or the fetus is Rh positive and the mother is Rh neg ative. that is. Of course. Rh incompatibility occurs in less than 10% of pregnancies and rarely causes hemolytic disease in the first pregnancy. Each blood group has specific antigens on RBCs and specific antibodies in the serum. Causes Erythroblastosis fetalis is caused by: ABO incompatibility Rh isoimmunization.) Pathophysiology The pathophysiologies of ABO and Rh incompatibility are different. the few who are delivered alive rarely survive longer than a few hours. usually within the first week of life. In severe. the mother has blood type O and the fetus has type A or B. survivors inev itably have severe neurologic damage. mental defic iencies. The effects of hemolytic disease are more severe in Rh incompatibility than ABO incompatibility. including sensory impairment. As in transfusion. ABO incompatibility occurs in about 25% of all pregnancies. Most commonly.3mg/dl). a hemolytic disease of the fetus and newborn. elevated blood urea nitrogen (great er than 25 mg/dl). Most fetuses with hydrops fetalis (the most severe form of this disorder. ABO incompatibility can cause hemolytic disease even if fetal erythr ocytes don't escape into the maternal circulation during pregnancy. and cerebral palsy. (See Understanding DIC and its tr eatment. The mother's immune system generates antibodies against fetal red cells. especially if brain and spinal cord become infiltrated with bilirubin (kernicterus). the maternal immune system forms an tibodies against fetal cells when blood groups differ. a mother with type A or B will not form antibodies against a type O fetus. but only 1 in 10 cases results in hemolytic disease. .) Erythroblastosis fetalis Erythroblastosis fetalis. About 70% of these infants die. who has no fetal blood ty pe antigens. ABO incompatibility. or packed RBC transfusions to support hemo stasis in active bleeding heparin in early stages to prevent microclotting and as a last resort in hemorrh age (controversial in acute DIC after sepsis). untreated erythroblastosis fetalis. fresh frozen plasma. the prognosis is poor. Because the blood of most adults already contains anti-A or anti-B antibodies. and elevated serum creatinine (greater than 1. stems fr om an incompatibility of fetal and maternal blood. (See What happens in Rh isoimmunization.reduced urine output (less than 30 ml/hour). ABO incompatibility may resolve after birth without life-threat ening complications.

the fetal blood forming organs step up the production of RBCs. attach to Rh-posit ive cells in the fetus. causing hyperbilirub inemia and hemolytic anemia. To compensate. Prenatal findings inclu . and cause hemolysis and anemia. Extensive hemolysis releases more uncon jugated bilirubin than the liver can conjugate and excrete. UNDERSTANDING DIC AND ITS TREATMENT WHAT HAPPENS IN RH ISOIMMUNIZATION Signs and symptoms Signs and symptoms of erythroblastosis fetalis include: jaundice due to large amounts of unconjugated bilirubin released by hemolysis anemia due to hemolysis hepatosplenomegaly. or from failure to receive Rho (D) after significant fetal-maternal l eakage during abruption placentae (premature detachment of the placenta). Complications Complications of erythroblastosis fetalis include: fetal death in utero severe anemia heart failure kernicterus. an Rh-negative female becomes se nsitized (during delivery or abortion) by exposure to Rh-positive fetal blood an tigens inherited from the father. A female may also become sensitized from recei ving blood transfusions with alien Rh antigens. A subsequent pregnancy with an Rh-positive fetus provokes maternal production of agglutinating antibodies. During her first pregnancy. and erythroblasts (immatur e RBCs) appear in the fetal circulation. Diagnosis Diagnosis considers both prenatal and neonatal findings. which cross the placental barrier. from inadequate doses of Rho (D) (RhoGAM).Rh incompatibility.

elevated. the halo sign (edemato us. Treatment Treatment depends on the degree of maternal sensitization and the effects of hem olytic disease on the fetus or newborn. and amniocentesis) . indicating severe disease many nucleated peripheral RBCs. subcutaneous fat layers) and the Buddha position (fetus's legs are crossed). serologic test results. Neonatal findings indicating erythroblastosis fetalis include: direct Coombs' test of umbilical cord blood to measure RBC (Rh-positive) antibod ies in the newborn (positive only when the mother is Rh negative and the fetus i s Rh positive) cord hemoglobin level less than 10 g.de: maternal history (for erythroblastotic stillbirths. abortions. previous anti-Rh titers) blood typing and screening (should be done frequently to determine changes in th e degree of maternal immunization) paternal blood typing for ABO and Rh history of blood transfusion amniotic fluid analysis showing increased bilirubin and anti-Rh titers radiologic studies showing edema and. depending on maternal h istory. previously affect ed children. in hydrops fetalis. It may include: intrauterine-intraperitoneal transfusion (if amniotic fluid analysis suggests th e fetus is severely affected and is not mature enough to deliver) planned delivery (usually 2 to 4 weeks before term date.

nearly four of five patients recover w ithout treatment. chronic ITP mainly affects adults younger than age 50. Rh-negative blood albumin infusion to bind bilirubin phototherapy (exposure to ultraviolet light to reduce bilirubin levels) gamma globulin containing anti-Rh antibody (Rho [D]) to prevent Rh isoimmunizati on in Rh-negative females (ineffective if a previous pregnancy. especially women between the ages of 20 and 40. a s in postviral thrombocytopenia. or tra nsfusion has already sensitized the mother). especially among women. abortion. Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura (ITP) is a deficiency of platelets that occu rs when the immune system destroys the body's own platelets. Causes Causes of ITP include: viral infection immunization with a live virus vaccine . The prognosis for acute ITP is excellent. ITP may be acute. AGE ALERT Acute ITP usually affects children between the ages of 2 and 6 years.exchange transfusion to remove antibody-coated RBCs and prevent hyperbilirubinem ia by replacing the infant's blood with fresh group O. remissions lasting week s or years are common. or chronic. Neonatal therapy for hydrops fetalis includes: intubation to maintain ventilation removal of excess fluid to relieve ascites and respiratory distress exchange transfusion maintaining body temperature. as in essential thrombocytopenia or autoimmune thrombocytopenia. The prognosis for chronic ITP is good.

the life span of platelets in circulation is 7 to 10 days. in the l iver. Complications Possible complications of ITP are: hemorrhage cerebral hemorrhage purpuric lesions of vital organs (such as the brain and kidney).000 l prolonged bleeding time . Signs and symptoms Signs and symptoms of ITP are caused by decreased levels of platelets and may in clude: nose bleeds oral bleeding hemorrhages into the skin. to a lesser degree.immunologic disorders drug reactions. which are then destroyed in the spleen and. mucous membranes. and other tissues causing red disco loration of skin (purpura) small purplish hemorrhagic spots on skin (petechiae) excessive menstrual bleeding. Diagnosis Diagnosis of ITP includes: platelet count less than 20. In IT P. Pathophysiology ITP occurs when circulating immunoglobulin G (IgG) molecules react with host pla telets. platelets survive 1 to 3 days or less. Normally.

immunoglobulin .V. Alternative treatments include: immunosuppressants to help stop platelet destruction high-dose I.abnormal size and appearance of platelets decreased hemoglobin level (if bleeding occurred) bone marrow studies showing abundant megakaryocytes (platelet precursor cells) a nd a circulating platelet survival time of only several hours to a few days humoral tests that measure platelet-associated IgG (may help establish the diagn osis. Treatment Treatment for acute ITP includes: glucocorticoids to prevent further platelet destruction immunoglobulin to prevent platelet destruction plasmapheresis platelet pheresis. Treatment for chronic ITP includes: corticosteroids to suppress phagocytic activity and enhance platelet production splenectomy (when splenomegaly accompanies the initial thrombocytopenia) blood and blood component transfusions and vitamin K to correct anemia and coagu lation defects. half the patients have elevated IgG).

polycythemia rubra vera. with normal or increased plasma volume. Complications Possible complications include: hemorrhage vascular thromboses . most commonly among Jewish males of European ancestry. Pathophysiology In polycythemia vera. It usually occurs between the ages of 40 and 60. This disease is also known as primary polycyt hemia. Causes The cause of polycythemia vera is unknown. such as liver and spleen. the type of treatment used. erythremia. or associated with myeloid metaplasia (presence of marrow-like tissue and ec topic hematopoiesis in extramedullary sites. associated with leukem ia. or Vaque z-Osler disease. It seldom affects children and doesn't appear to be familial. Signs and symptoms Possible signs and symptoms of polycythemia vera include: feeling of fullness in the head or headache due to altered hypervolemia and hype rviscosity dizziness due to hypervolemia and hyperviscosity ruddy cyanosis (plethora) of the nose and clubbing of the digits due to thrombos is in smaller vessels painful pruritus due to abnormally high concentrations of mast cells in the skin and their release of heparin and histamine. and compl ications. thrombocytosis. and increased hemoglobin level. The prognosis depends on age at diagnosis. uncontrolled and rapid cellular reproduction and maturatio n cause proliferation or hyperplasia of all bone marrow cells (panmyelosis). ery throcytosis. Polycythemia vera Polycythemia vera is a chronic disorder characterized by increased RBC mass. and nucle ated erythrocytes in blood). Increased RBC mass makes the blood abnormally viscous and inhibits blood flow to microcirculation. splenomegalic polycythemia.immunoabsorption apheresis using staphylococcal protein-A columns. Mortality is high if polycythemia is untreated. but is probably related to: multipotential stem cell defect. Diminished blood flow and thrombocytosis set the stage for in travascular thrombosis. leukocytosis.

Diagnosis The following test results help diagnose polycythemia vera: increased RBC mass normal arterial oxygen saturation in association with splenomegaly increased uric acid increased blood histamine decreased serum iron decreased or absent urinary erythropoietin bone marrow biopsy showing excess production of myeloid stem cells. Pathophysiology Secondary polycythemia may result from increased production of the hormone eryth ropoietin which stimulates bone marrow to produce RBCs in a compensatory respons e to several conditions. is excessive producti on of circulating RBCs due to hypoxia. hemoglobin abnormalities (such as carboxyhe moglobinemia in heavy smokers). also called reactive polycythemia.uric acid stones. Treatment Treatment may include: phlebotomy to reduce RBC mass myelosuppressive therapy with radioactive phosphorus to suppress erythropoiesis (may increase the risk for leukemia). the incidence increa ses among those living at high altitudes. heart failure (causing a decreased ventilation-p . Secondary polycythemia Secondary polycythemia.000 people living at or near sea level. Causes Secondary polycythemia may be caused by: increased production of erythropoietin. or disease. These include