Nurse�s Manual Of Laboratory And Diagnostic S 4th Ed 2003
Nurse%92s manual of laboratory and diagnostic s 4th Ed 2003 manual pdf -FilePursuit
User Manual: manual pdf -FilePursuit
Open the PDF directly: View PDF .
Page Count: 688
Download | |
Open PDF In Browser | View PDF |
Copyright © 2003 F.A. Davis Company Nurse’s Manual of Laboratory and Diagnostic Tests EDITION Bonita Morrow Cavanaugh, PhD, RN Clinical Nurse Specialist Nursing Education The Children’s Hospital Denver, Colorado Clinical Faculty University of Colorado Health Sciences Center School of Nursing Denver, Colorado Affiliate Professor University of Northern Colorado School of Nursing Greeley, Colorado F.A. Davis Company • Philadelphia Copyright © 2003 F.A. Davis Company F. A. Davis Company 1915 Arch Street Philadelphia, PA 19103 www.fadavis.com Copyright © 2003 by F. A. Davis Company Copyright © 1999, 1995, 1989 by F. A. Davis Company. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America Last digit indicates print number: 10 9 8 7 6 5 4 3 2 1 Publisher: Lisa Deitch Developmental Editor: Diane Blodgett Cover Designer: Louis J. Forgione As new scientific information becomes available through basic and clinical research, recommended treatments and drug therapies undergo changes. The author and publisher have done everything possible to make this book accurate, up to date, and in accord with accepted standards at the time of publication. The author, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of the book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised always to check product information (package inserts) for changes and new information regarding dose and contraindications before administering any drug. Caution is especially urged when using new or infrequently ordered drugs. Library of Congress Cataloging-in-Publication Data Cavanaugh, Bonita Morrow, 1952– Nurse’s manual of laboratory and diagnostic tests. – 4th ed. / Bonita Morrow Cavanaugh. p. cm. Rev. ed. of: Nurse’s manual of laboratory and diagnostic tests / Juanita Watson. 3rd. ed. c1995. Includes bibliographical references and index. ISBN 0-8036-1055-6 (pbk.) 1. Diagnosis, Laboratory —Handbooks, manuals, etc. 2. Nursing-Handbook, manuals, etc. I. Watson, Juanita, 1946– Nurse’s manual of laboratory and diagnostic tests. II. Title. [DNLM: 1. Laboratory Techniques and Procedures nurses’ instruction handbooks. QY 39 C377n 1999] RT48.5.W38 1999 616.07′5—dc21 DNLM/DLC for Library of Congress 98-50920 CIP Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by F. A. Davis Company for users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, provided that the fee of $.10 per copy is paid directly to CCC, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payment has been arranged. The fee code for users of the Transactional Reporting Service is: 8036-1055/03 0 + $.10. Copyright © 2003 F.A. Davis Company To Laurie O’Neil Good, the finest nurse I have ever known. Love, Bonnie Copyright © 2003 F.A. Davis Company This page intentionally left blank Copyright © 2003 F.A. Davis Company Preface This book is designed to provide both students and practitioners of nursing with the information they need to care for individuals undergoing laboratory and diagnostic tests and procedures. The content is presented as a guiding reference for planning care, providing specific interventions, and evaluating outcomes of nursing care. In this edition, the background information and description of the test or procedure are followed directly by the clinical applications data, starting with reference values, for each test or group of tests. The introductory sections include the anatomic, physiological, and pathophysiological content necessary for a thorough understanding of the purpose of and indications for specific tests and procedures. The inclusion of this information makes this book unlike many other references on this subject matter. This feature enhances the integration of basic science knowledge with an understanding of and application to diagnostic testing. This is extremely helpful for nursing students in developing critical thinking and clinical judgment. For each test or study within the respective sections, reference values, including variations related to age or gender, are provided. Critical values, where appropriate, are highlighted. Both conventional units and international units are provided. Readers are encouraged to be aware of some variation in laboratory values from agency to agency. For all tests, interfering factors are noted where appropriate. Contraindications and Nursing Alerts are included to provide information crucial to safe and reliable testing and nursing care. Other features of this manual that contribute to its practical use are presentation of detailed content in tabular format when appropriate and the use of appendices to provide essential information applicable to most, if not all, tests and procedures. Every effort has been made to include tests and procedures currently in use in practice settings. It is recognized that newer tests and procedures may have become available after this manuscript was prepared. Readers are encouraged to keep abreast of current literature and consult with laboratories and agencies in their area for new developments in the field of diagnostic tests. BONITA MORROW CAVANAUGH v Copyright © 2003 F.A. Davis Company This page intentionally left blank Copyright © 2003 F.A. Davis Company Acknowledgments This book would not have been possible without the help, support, and encouragement of a number of people. Special appreciation is due to the staff of the F. A. Davis Company. I am particularly indebted to Lisa Deitch, Publisher, for her major contribution in developing the unique format of this text, for her encouragement, and for always being available for help when I needed it. I would also like to acknowledge Robert Martone, Nursing Publisher, who encouraged me to pursue this project, and Robert H. Craven, Jr., President, for his support and patience as the book evolved. Special thanks are also due to Ruth De George, Editorial Assistant, and Michele Reese, Editorial Aide, for their invaluable assistance. Many other individuals at the F. A. Davis Company contributed to the production of this book, and I wish to extend to all of them my sincere appreciation for their expertise and dedication to the high standards necessary to produce a good book. Special recognition in this regard is due to Jessica Howie Martin, Production Editor, and Bob Butler, Director of Production. I thank the consultants who served as reviewers of the manuscript for their thoroughness and generosity in sharing their ideas and suggestions. Your comments proved invaluable! Finally, a special thanks to those family members, friends, and associates who offered and gave their support, patience, and encouragement. B.M.C. vii Copyright © 2003 F.A. Davis Company This page intentionally left blank Copyright © 2003 F.A. Davis Company Consultants Janice Brownlee, BScN, MAEd Dolores Philpot, BSMT, AND, MSN Professor Canadore College of Applied Arts and Technology North Bay, Ontario, Canada Instructor University of Tennessee Knoxville, Tennessee Sylvan L. Settle, RN Marie Colucci, BS, MS, EdD Associate Professor Riverside Community College Riverside, California Vocational Teacher Tennessee Technology Center Memphis, Tennessee Joyce Taylor, RN, MSN, DSN, BA Mary Jo Goolsby, MSN, ARNP, EdD Instructor Florida State University Tallahassee, Florida Associate Professor Henderson State University Arkadelphia, Arkansas Shelley M. Tiffin, ART (CSMLS), BMLSc Shelby Hawk, RN, MSN Instructor Mid Michigan Community College Harrison, Michigan Priscilla Innocent, RN, MSN Associate Professor Indiana Wesleyan University Marion, Indiana Dr. Fran Keen, RN, DNSc Bachelor of Medical Laboratory Science Program Department of Pathology and Laboratory Medicine University of British Columbia Vancouver, British Columbia, Canada Donna Yancey, BSN, MSN, DNS Assistant Professor Purdue University West Lafayette, Indiana Associate Professor University of Miami Coral Gables, Florida ix Copyright © 2003 F.A. Davis Company This page intentionally left blank Copyright © 2003 F.A. Davis Company Contents SECTION I • Laboratory Tests, 1 CHAPTER 1 Hematology and Tests of Hematopoietic Function ......................................................................3 CHAPTER 2 Hemostasis and Tests of Hemostatic Functions ........................................................................39 CHAPTER 3 Immunology and Immunologic Testing ........................................................................................60 CHAPTER 4 Immunohematology and Blood Banking......................................................................................96 CHAPTER 5 Blood Chemistry..............................................................................................................................103 CHAPTER 6 Studies of Urine ..............................................................................................................................221 CHAPTER 7 Sputum Analysis ............................................................................................................................268 CHAPTER 8 Cerebrospinal Fluid Analysis ......................................................................................................274 CHAPTER 9 Analysis of Effusions ....................................................................................................................283 CHAPTER 10 Amniotic Fluid Analysis ................................................................................................................297 CHAPTER 11 Semen Analysis ..............................................................................................................................305 CHAPTER 12 Analysis of Gastric and Duodenal Secretions..........................................................................311 xi Copyright © 2003 F.A. Davis Company xii Contents CHAPTER 13 Fecal Analysis ................................................................................................................................321 CHAPTER 14 Analysis of Cells and Tissues ......................................................................................................332 CHAPTER 15 Culture and Sensitivity Tests........................................................................................................352 SECTION II • Diagnostic Tests and Procedures, 361 CHAPTER 16 Endoscopic Studies........................................................................................................................363 CHAPTER 17 Radiologic Studies ........................................................................................................................397 CHAPTER 18 Radiologic Angiography Studies ................................................................................................438 CHAPTER 19 Ultrasound Studies ........................................................................................................................458 CHAPTER 20 Nuclear Scan and Laboratory Studies ......................................................................................482 CHAPTER 21 Non-Nuclear Scan Studies ..........................................................................................................528 CHAPTER 22 Manometric Studies ......................................................................................................................545 CHAPTER 23 Electrophysiologic Studies ..........................................................................................................558 CHAPTER 24 Studies of Specific Organs or Systems......................................................................................577 CHAPTER 25 Skin Tests ........................................................................................................................................615 APPENDICES APPENDIX I Obtaining Various Types of Blood Specimens..........................................................................625 APPENDIX II Obtaining Various Types of Urine Specimens ..........................................................................631 APPENDIX III Guidelines for Isolation Precautions in Hospitals ..................................................................634 APPENDIX IV Units of Measurement (Including SI Units) ..............................................................................636 Copyright © 2003 F.A. Davis Company Contents APPENDIX V Profile or Panel Groupings and Laboratory Tests ....................................................................644 APPENDIX VI Nursing Care Plan for Individuals Experiencing Laboratory and Diagnostic Testing ............................................................................................649 INDEX ..............................................................................................................................................651 xiii Copyright © 2003 F.A. Davis Company SECTION Laboratory Tests 1 Copyright © 2003 F.A. Davis Company This page intentionally left blank Copyright © 2003 F.A. Davis Company CHAPTER Hematology and Tests of Hematopoietic Function TESTS COVERED Bone Marrow Examination, 7 Reticulocyte Count, 9 Iron Studies, 11 Vitamin B12 and Folic Acid Studies, 13 Complete Blood Count, 14 Erythrocyte (RBC) Count, 20 Hematocrit, 21 Hemoglobin, 21 Red Blood Cell Indices, 22 Stained Red Blood Cell Examination, 24 Hemoglobin Electrophoresis, 26 Osmotic Fragility, 29 Red Blood Cell Enzymes, 30 Erythrocyte Sedimentation Rate, 31 White Blood Cell Count, 33 Differential White Blood Cell Count, 34 White Blood Cell Enzymes, 37 INTRODUCTION Blood constitutes 6 to 8 percent of total body weight. In terms of volume, women have 4.5 to 5.5 L of blood and men 5 to 6 L. In infants and children, blood volume is 50 to 75 mL/kg in girls and 52 to 83 mL/kg in boys. The principal functions of blood are the transport of oxygen, nutrients, and hormones to all tissues and the removal of metabolic wastes to the organs of excretion. Additional functions of blood are (1) regulation of temperature by transfer of heat to the skin for dissipation by radiation and convection, (2) regulation of the pH of body fluids through the buffer systems and facilitation of excretion of acids and bases, and (3) defense against infection by transportation of antibodies and other substances as needed. Blood consists of a fluid portion, called plasma, and a solid portion that includes red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Plasma makes up 45 to 60 percent of blood volume and is composed of water (90 percent), amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes.1 Of the “solid” or cellular portion of the blood, more than 99 percent consists of red blood cells. Leukocytes and thrombocytes, although functionally essential, occupy a relatively small portion of the total blood cell mass.2 Erythrocytes remain within the blood throughout their normal life span of 120 days, transporting oxygen in the hemoglobin component and carrying away carbon dioxide. Leukocytes, while they are in the blood, are merely in transit, because they perform their functions in body tissue. Platelets exert their effects at the walls of blood vessels, performing no known function in the bloodstream itself.3 Hematology is traditionally limited to the study of the cellular elements of the blood, the production of these elements, and the physiological derangements that affect their functions. Hematologists also are concerned with blood volume, the flow properties of blood, and the physical relationships of red cells and plasma. The numerous substances dissolved or suspended in plasma fall within the province of other laboratory disciplines.4 3 Copyright © 2003 F.A. Davis Company 4 SECTION I—Laboratory Tests HEMATOPOIESIS Hematopoiesis is the process of blood cell formation. In normal, healthy adults, blood cells are manufactured in the red marrow of relatively few bones, notably the sternum, ribs, vertebral bodies, pelvic bones, and proximal portions of the humerus and the femur. This production is in contrast to that taking place in the embryo, in which blood cells are derived from the yolk sac mesenchyme. As the fetus develops, the liver, the spleen, and the marrow cavities of nearly all bones become active hematopoietic sites (Fig. 1–1). In the newborn, hematopoiesis occurs primarily in the red marrow, which is found in most bones at that stage of development. Beginning at about age 5 years, the red marrow is gradually replaced by yellowish fat-storage cells (yellow marrow), which are inactive in the hematopoietic process. By adulthood, blood cell production normally occurs in only those bones that retain red marrow activity.5 Adult reticuloendothelial cells retain the potential for hematopoiesis, although in the healthy state reserve sites are not activated. Under conditions of hematopoietic stress in later life, the liver, the spleen, and an expanded bone marrow may resume the production of blood cells. All blood cells are believed to be derived from the pluripotential stem cell,6 an immature cell with the capability of becoming an erythrocyte, a leukocyte, or a thrombocyte. In the adult, stem cells in hematopoietic sites undergo a series of divisions and maturational changes to form the mature cells found in the blood (Fig. 1–2). As they achieve the “blast” stage, stem cells are committed to becoming a specific type of blood cell. This theory also explains the origin of the several types of white blood cells (neutrophils, monocytes, eosinophils, basophils, and lymphocytes). As the cells mature, they lose their ability to reproduce and cannot further divide to replace themselves. Thus, there is a need for continuous hematopoietic activity to replenish worn-out or damaged blood cells. Erythropoiesis, the production of red blood cells (RBCs), and leukopoiesis, the production of white blood cells (WBCs), are components of the hematopoietic process. Erythropoiesis maintains a population of approximately 25 1012 circulating RBCs, or an average of 5 million erythrocytes per cubic millimeter of blood. The production rate is about 2 million cells per second, or 35 trillion cells per day. With maximum stimulation, this rate can be increased sixfold to eightfold, or one volume per day equivalent to the cells contained in 0.5 pt of whole blood. The level of tissue oxygenation regulates the production of RBCs; that is, erythropoiesis occurs in response to tissue hypoxia. Hypoxia does not, Figure 1–1. Location of active marrow growth in the fetus and adult. (From Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia, 1996, p 2, with permission.) Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology and Tests of Hematopoietic Function 5 Image/Text rights unavailable however, directly stimulate the bone marrow. Instead, RBC production occurs in response to erythropoietin, precursors of which are found primarily in the kidney and to a lesser extent in the liver. When the renal oxygen level falls, an enzyme, renal erythropoietic factor, is secreted. This enzyme reacts with a plasma protein to form erythropoietin, which subsequently stimulates the bone marrow to produce more RBCs. Specifically, erythropoietin (1) accelerates production, differentiation, and maturaTABLE 1–1 • tion of erythrocytes; (2) reduces the time required for cells to enter the circulation, thereby increasing the number of circulating immature erythrocytes such as reticulocytes (see Fig. 1–2); and (3) facilitates the incorporation of iron into RBCs. When the number of produced erythrocytes meets the body’s tissue oxygenation needs, erythropoietin release and RBC production are reduced. Table 1–1 lists causes of tissue hypoxia that may stimulate the release of erythropoietin. Causes of Tissue Hypoxia That May Stimulate Erythropoietin Release Acute blood loss Impaired oxygen–carbon dioxide exchange in the lungs Low hemoglobin levels Impaired binding of oxygen to hemoglobin Impaired release of oxygen from hemoglobin Excessive hemolysis of erythrocytes due to hypersplenism or hemolytic disorders of antibody, bacterial, or chemical origin Certain anemias in which abnormal red blood cells are produced (e.g., hereditary spherocytosis) Compromised blood flow to the kidneys Copyright © 2003 F.A. Davis Company 6 SECTION I—Laboratory Tests Threats to normal erythropoiesis occur if sufficient amounts of erythropoietin cannot be produced or if the bone marrow is unable to respond to erythropoietic stimulation. People without kidneys or with severe impairment of renal function are unable to produce adequate amounts of renal erythropoietic factor. In these individuals, the liver is the source of erythropoietic factor. The quantity produced, however, is sufficient to maintain only a fairly stable state of severe anemia that responds minimally to hypoxemia. Inadequate erythropoiesis may occur also if the bone marrow is depressed because of drugs, toxic chemicals, ionizing radiation, malignancies, or other disorders such as hypothyroidism. Also, in certain anemias and hemoglobinopathies, the bone marrow is unable to produce sufficient normal erythrocytes. Other substances needed for erythropoiesis are vitamin B12, folic acid, and iron. Vitamin B12 and TABLE 1–2 • folic acid are required for DNA synthesis and are needed by all cells for growth and reproduction; because cellular reproduction occurs at such a high rate in erythropoietic tissue, formation of RBCs is particularly affected by a deficiency of either of these substances. Iron is needed for hemoglobin synthesis and normal RBC production. In addition to dietary sources, iron from worn-out or damaged RBCs is available for reuse in erythropoiesis.7 Leukopoiesis, the production of WBCs, maintains a population of 5,000 to 10,000 leukocytes per cubic millimeter of blood, with the capability for rapid and dramatic change in response to a variety of stimuli. No leukopoietic substance comparable to erythropoietic factor has been identified, but many factors are known to influence WBC production, with a resultant excess (leukocytosis) or deficiency (leukopenia) in leukocytes (Table 1–2). Note that WBC levels vary in relation to diurnal Causes of Altered Leukopoiesis Physiological Leukocytosis Pathological Pregnancy All types of infection Early infancy Anemias Emotional stress Cushing’s disease Strenuous exercise Erythroblastosis fetalis Menstruation Leukemias Exposure to cold Polycythemia vera Ultraviolet light Transfusion reactions Increased epinephrine secretion Inflammatory disorders Parasitic infestations Leukopenia Diurnal rhythms Bone marrow depression Toxic and antineoplastic drugs Radiation Severe infection Viral infections Myxedema Lupus erythematosus and other autoimmune disorders Peptic ulcers Uremia Allergies Malignancies Metabolic disorders Malnutrition Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology rhythms; thus, the time at which the sample is obtained may influence the results. Overall, leukocytes may increase by as many as 2000 cells per milliliter from morning to evening, with a corresponding overnight decrease. Eosinophils decrease until about noon and then rise to peak between midnight and 3 AM. This variation may be related to adrenocortical hormone levels, which peak between 4 and 8 AM, because an increase in these hormones can cause circulating lymphocytes and eosinophils to disappear in a few hours. Evaluation of Hematopoiesis Abnormal results of studies such as a complete blood count (CBC)) and WBC count and differential indicate the need to determine the individual’s hematopoietic function. Evaluation of hematopoiesis begins with the examination of a bone marrow sample and may subsequently require other studies and a sample of peripheral blood, either venous or capillary. Although the collection of blood specimens is usually the responsibility of the laboratory technician or phlebotomist, it is often the responsibility of the nurse in emergency departments, critical TABLE 1–3 Cell Type Reticulocytes Neutrophils (total) • and Tests of Hematopoietic Function care units, and community and home care settings. A detailed description of procedures for obtaining peripheral blood samples is provided in Appendix I. BONE MARROW EXAMINATION Bone marrow examination (aspiration, biopsy) requires removal of a small sample of bone marrow by aspiration, needle biopsy, or open surgical biopsy. Cells normally present in hematopoietic marrow include erythrocytes and granulocytes (neutrophils, basophils, and eosinophils) in all stages of maturation; megakaryocytes (from which platelets develop); small numbers of lymphocytes; and occasional plasma cells (Fig. 1–2). Nucleated WBCs in the bone marrow normally outnumber nucleated (immature) RBCs by about 3:1. This is called the myeloid-to-erythroid (M:E) ratio.8 Causes of increased and decreased values on bone marrow examination are presented in Table 1–3. Various stains followed by microscopic examination can be performed on bone marrow aspirate to diagnose and differentiate among the different types of leukemia. A Sudan B stain differentiates between acute granulocytic and lymphocytic Causes of Alterations in Bone Marrow Cells Increased Values Decreased Values Compensated RBC loss Aplastic crisis of sickle cell disease or hereditary spherocytosis Response to vitamin B12 therapy Aplastic anemia Myeloid (chronic) leukemias Leukemias (monocytic and lymphoblastic) Acute myeloblastic leukemia Lymphocytes Lymphatic leukemia Lymphosarcoma Lymphomas Mononucleosis Aplastic anemia Plasma cells Myeloma Normoblasts Polycythemia vera Deficiency of folic acid or vitamin B12 Aplastic anemia Hemolytic anemia Eosinophils 7 Bone marrow carcinoma Lymphadenoma Myeloid leukemia Copyright © 2003 F.A. Davis Company 8 SECTION I—Laboratory Tests leukemia. A periodic acid–Schiff stain assists in the diagnosis of acute lymphocytic leukemia and erythroleukemia. A terminal deoxynucleotidyl transferase test differentiates between lymphoblastic leukemia and lymphoma.9 Because bone marrow examination involves an invasive procedure with risks of infection, trauma, and bleeding, a signed consent is required. INDICATIONS FOR BONE MARROW EXAMINATION Evaluation of abnormal results of CBC (e.g., anemia), of WBC count with differential (e.g., increased numbers of leukocyte precursors), or of both tests Monitoring of effects of exposure to bone marrow depressants Monitoring of bone marrow response to antineoplastic or radiation therapy for malignancies Evaluation of hepatomegaly (enlarged liver) or splenomegaly (enlarged spleen) Identification of bone marrow hyperplasia or hypoplasia, although the study may not indicate the cause of the quantitative abnormality Determination of marrow differential (proportion of the various types of cells present in the marrow) and M:E ratio Diagnosis of various disorders associated with abnormal hematopoiesis: Multiple myeloma Most leukemias, both acute and chronic Disseminated infections (granulomatous, bacterial, fungal) Lipid or glycogen storage diseases Reference Values Cell Type (%) Adults Infants Children 0–1.0 — — 0.5–2.5 — — 56.5 32.4 57.1 Myeloblasts 0.3–5.0 0.62 1.2 Promyelocytes 1.4–8.0 0.76 1.4 Myelocytes 4.2–15.0 2.5 18.4 Neutrophilic 5.0–19.0 — — Eosinophilic 0.5–3.0 — — 0–0.5 — — Bands (stabs) 13.0–34.0 14.1 0 Lymphocytes 14.0–16.0 49.0 16.0 Monocytes 0.3–6.0 — — Plasma cells 0.3–3.9 0.02 0.4 Megakaryocytes 0.1–3.0 0.05 0.1 2.3–3.5:1 4.4:1 2.9:1 0.2–1.3 0.1 0.5 25.6 8.0 23.1 Basophilic 1.4–4.0 0.34 1.7 Polychromatophilic 6.0–29.0 6.9 18.2 Orthochromic 1.0–4.6 0.54 2.7 Eosinophils 0.5–3.0 2.6 3.6 0–0.2 0.07 0.06 Undifferentiated Reticulocytes Neutrophils (total) Basophilic M:E ratio Pronormoblasts Normoblasts Basophils Note: There may be differences in normal values among individuals and in values obtained by different laboratory techniques. Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology Hypoplastic anemia (which may be caused by chronic infection, hypothyroidism, chronic renal failure, advanced liver disease, and a number of “idiopathic” conditions) Erythropoietic hyperplasia (which may be caused by iron deficiency, thalassemias, hemoglobinopathies, disorders of folate and vitamin B12 metabolism, hypersplenism, glucose-6phosphate dehydrogenase [G-6-PD] deficiency, hereditary spherocytosis, and antibody-mediated bacterial or chemical hemolysis) Lupus erythematosus Porphyria erythropoietica Parasitic infestations Amyloidosis Polycythemia vera Aplastic anemia (which may be caused by drug toxicity, idiopathic marrow failure, or infection) CONTRAINDICATIONS Known coagulation defects, although the test may be performed if the importance of the information to be obtained outweighs the risks involved in carrying out the test NURSING CARE BEFORE THE PROCEDURE Explain to the client: The purpose of the study That it will be done at the bedside by a physician and requires about 20 minutes The general procedure, including the sensations to be expected (momentary pain as the skin is injected with local anesthetic and again as the needle penetrates the periosteum, the “pulling” sensation as the specimen is withdrawn) That discomfort will be minimized with local anesthetics or systemic analgesics That the site may remain tender for several weeks Ensure that a signed consent has been obtained. Then: Take and record vital signs. Provide a hospital gown if necessary to provide access to the biopsy site or to prevent soiling of the client’s clothes with the solution used for skin preparation. Administer premedication prescribed for pain or anxiety. and Tests of Hematopoietic Function 9 preferred. In adults, the sternum or iliac crests are the preferred sites. The prone or side-lying position is used if the spinous processes are the sites to be used. (These sites are preferred if more than one specimen is to be obtained.) The client may also be sitting, supported by a pillow on an overbed table for a spinous process site. The side-lying position is used if the iliac crest or tibia is the site. For sternal punctures, the supine position is used. The skin is prepared with an antiseptic solution, draped, and anesthetized, preferably with procaine, which is painless when injected. Asepsis must be meticulous to prevent systemic infection. For aspiration, a large needle with stylet is advanced into the marrow cavity. Penetration of the periosteum is painful. The stylet is removed and a syringe is attached to the needle. An aliquot of 0.5 mL of marrow is withdrawn. At this time, the discomfort is a “pulling” sensation rather than pain. The needle is removed and pressure applied to the site. The aspirate is immediately smeared on slides and, when dry, sprayed with a fixative. For needle biopsy, the local anesthetic is introduced deeply enough to include the periosteum. A special cutting biopsy needle is introduced through a small skin incision and bored into the marrow cavity. A core needle is introduced through the cutting needle and a plug of marrow is removed. The needles are withdrawn and the specimen placed in a preservative solution. Pressure is applied to the site for 5 to 10 minutes and a dressing applied. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client to lie on the biopsied side, if the iliac crest was entered, or supine, if the vertebral bodies were used, to maintain pressure on the site for 10 to 15 minutes. For sternal punctures, place the client in the supine position or other position of comfort. Provide bed rest for at least 30 minutes after the procedure. Assess puncture site every 10 to 15 minutes for bleeding. Apply an ice bag to the puncture site to alleviate discomfort and prevent bleeding. Assess for infection at the site; note any redness, swelling, or drainage. Administer analgesics to alleviate discomfort. THE PROCEDURE The client is assisted to the desired position depending on the site to be used. In young children, the most frequently chosen site is the proximal tibia; in older children, vertebral bodies T10 to L4 are RETICULOCYTE COUNT Reticulocytes are immature RBCs. As RBC precursors mature (Fig. 1–2), the cell nucleus decreases in size and eventually becomes a dense, structureless Copyright © 2003 F.A. Davis Company 10 SECTION I—Laboratory Tests mass.10 At the same time, the hemoglobin content of the cell increases. Reticulocytes are cells that have lost their nuclei but still retain fragments of mitochondria and other organelles. They also are slightly larger than mature RBCs.11 RBCs normally enter the circulation as reticulocytes and attain the mature form (erythrocytes) in 1 to 2 days. Under the stress of anemia or hypoxia, an increased output of erythropoietin may lead to an increased number of circulating reticulocytes (see Table 1–1). The extent of such an increase depends on the functional integrity of the bone marrow, the severity and duration of anemia or hypoxia, the adequacy of the erythropoietin response, and the amount of available iron.12 For example, a normal reticulocyte count in the presence of a normal hemoglobin level indicates normal marrow activity, whereas a normal reticulocyte count in the presence of a low hemoglobin level indicates an inadequate response to anemia. This may be a result of defective erythropoietin production, bone marrow function, or hemoglobin formation. After blood loss or effective therapy for certain kinds of anemia, an elevated reticulocyte count (reticulocytosis) indicates that the bone marrow is normally responsive and is attempting to replace cells lost or destroyed. Individuals with defects of RBC maturation and hemoglobin production may show a low reticulocyte count (reticulocytopenia) because the cells never mature sufficiently to enter the peripheral circulation. Performing a reticulocyte count involves examining a stained smear of peripheral blood to determine the percentage of reticulocytes in relation to the number of RBCs present. Reference Values Newborns 3.2% of RBCs, declining by 2 mo Infants 2–5% Children 0.5–4% Adults 0.5–2% of RBCs; can be higher in pregnant women Reticulocyte index 1.0 Critical values 20% increase INDICATIONS FOR RETICULOCYTE COUNT Evaluation of the adequacy of bone marrow response to stressors such as anemia or hypoxia: A normal response is indicated by an increase in the reticulocyte count. Failure of the reticulocyte count to increase may indicate depressed bone marrow functioning, defective erythropoietin production, or defective hemoglobin production. Evaluation of anemia of unknown etiology to determine the type of anemia: Elevated reticulocyte counts are found in hemolytic anemias and sickle cell disease. Decreased counts are seen in pernicious anemia, thalassemia, aplastic anemia, and severe iron-deficiency anemia. Monitoring response to therapy for anemia: In iron-deficiency anemia, therapeutic administration of iron should produce reticulocytosis within 3 days and the count should remain elevated until normal hemoglobin levels are achieved. Vitamin B12 therapy for pernicious anemia should cause a prompt, continuing reticulocytosis. Monitoring physiologic response to blood loss: After a single hemorrhagic episode, reticulocytosis should begin within 24 to 48 hours and peak in 4 to 7 days. Persistent reticulocytosis or a second rise in the count indicates continuing blood loss. Confirmation of aplastic crisis in clients with known aplastic anemia as evidenced by a drop in the usually high level of reticulocytes, indicating that RBC production has stopped despite continuing RBC destruction13 NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE If the client is an adult, a venipuncture is performed and the sample is collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal values: Note and report fatigue, weakness, and color changes associated with a decrease in counts and pain, and changes in mental state and visual perception associated with an increase in counts. Increased counts in 4 to 7 days indicate Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology that the therapy to treat loss of RBCs is effective, whereas decreased counts indicate an ineffective production of RBCs, and further testing and evaluation are needed to determine the cause. Assess for continuing blood loss (pulse, blood pressure, skin color, weakness, dizziness). Critical values: Polycythemia with reticulocyte increases of greater than 20 percent requires immediate communication to the physician. Prepare the client for possible phlebotomy to reduce volume of blood and intravenous fluids to reduce viscosity of blood. Administer ordered myelosuppressive drugs. IRON STUDIES Iron plays a principal role in erythropoiesis, because it is necessary for proliferation and maturation of RBCs and for hemoglobin synthesis. Of the body’s normal 4 g of iron (somewhat less in women), about 65 percent resides in hemoglobin and about 3 percent in myoglobin. A tiny but vital amount of iron is found in cellular enzymes, which catalyze the oxidation and reduction of iron. The remainder is stored in the liver, bone marrow, and spleen as ferritin or hemosiderin.14 Except for blood transfusions, the only way iron enters the body is orally. Normally, only about 10 percent of ingested iron is absorbed, but up to 20 percent or more can be absorbed in cases of irondeficiency anemia. The body is never able to absorb all ingested iron, no matter how great its need for iron. In addition to dietary sources, iron from wornout or damaged RBCs is available for reuse in erythropoiesis.15 SERUM IRON, TRANSFERRIN, AND TOTAL IRON-BINDING CAPACITY Any iron present in the serum is in transit among the alimentary tract, bone marrow, and available ironstorage forms. Iron travels in the bloodstream bound to transferrin, a protein (-globulin) manufactured by the liver. Unbound iron is highly toxic to the body, but generally much more transferrin is available than that needed for iron transport. Usually, transferrin is only 30 to 35 percent saturated, with a normal range of 20 to 55 percent. If excess transferrin is available in relation to body iron, the percentage saturation is low. Conversely, in situations of iron excess, both serum iron and percentage saturation are high. Measurement of serum iron is accomplished by using a specific color of reagent to quantitate iron after it is freed from transferrin. Transferrin may be measured directly through immunoelectrophoretic and Tests of Hematopoietic Function 11 techniques or indirectly by exposure of the serum to sufficient excess iron such that all the transferrin present can combine with the added iron. The latter result is expressed as total iron-binding capacity (TIBC). The percentage saturation is calculated by dividing the serum iron value by the TIBC value. FERRITIN Iron is stored in the body as ferritin or hemosiderin. Many individuals who are not anemic and who can adequately synthesize hemoglobin may still have decreased iron stores. For example, menstruating women, especially those who have borne children, usually have less storage iron. In contrast, persons with disorders of excess iron storage such as hemochromatosis or hemosiderosis have extremely high serum ferritin levels.16 Serum ferritin levels are used to measure ironstorage status and are obtained by either radioimmunoassay or enzyme-linked immunoassay. The amount of ferritin in the circulation usually is proportional to the amount of storage iron (ferritin and hemosiderin) in body tissues. Note that serum ferritin levels vary according to age and gender (Fig. 1–3). INDICATIONS FOR IRON STUDIES Anemia of unknown etiology to determine cause and type of anemia: Decreased serum iron with increased transferrin levels is seen in iron-deficiency anemia and blood loss. Decreased serum iron and decreased transferrin levels may be seen in disorders involving diminished protein synthesis or defects in iron absorption (e.g., chronic diseases, infections, widespread malignancy, malabsorption syndromes, malnutrition, nephrotic syndrome). Percentage saturation of transferrin Figure 1–3. Serum ferritin levels according to sex and age. (From Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia, 1996, p 64, with permission.) Copyright © 2003 F.A. Davis Company 12 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units Serum Iron Newborns 350–500 mg/dL 62.7–89.5 mmol/L Children 40–200 mg/dL 7.2–35.8 mmol/L Men 60–170 mg/dL 10.7–30.4 mmol/L Women 50–130 mg/dL 9.0–23.3 mmol/L Elderly persons 40–80 mg/dL 7.2–14.3 mmol/L Newborns 60–170 mg/dL 0.6–1.7 g/L Adults 250–450 mg/dL 2.5–4.5 g/L Newborns 65% saturation 0.65 Adults 20–55% saturation 0.20–0.55 Children 100–350 mg/dL 18–63 mmol/L Adults 300–360 mg/dL 54–64 mmol/L Elderly persons 200–310 mg/dL 36–56 mmol/L 20–40 mg/dL 20–40 mg/L Men 50–200 mg/dL 50–200 mg/L (average 100 mg/dL) (avg 100 mg/L) Women (menstruating) 12–100 mg/dL (average 30 mg/dL) (avg 30 mg/L) Adults Transferrin % Saturation (of Transferrin) TIBC Ferritin Children Adults may be normal if serum iron and transferrin levels are proportionately decreased; if the problem is solely one of protein homeostasis (with normal iron stores), percentage saturation will be high. Support for diagnosing hemochromatosis or other disorders of iron metabolism and storage: Serum iron and ferritin levels may be elevated in hemochromatosis and hemosiderosis; percentage saturation of transferrin is elevated, whereas TIBC is decreased. Serum iron levels can be elevated in lead poisoning, after multiple blood transfusions, and in severe hemolytic disorders that cause release of iron from damaged RBCs. 12–100 mg/L Monitoring hematologic responses during pregnancy, when serum iron is usually decreased, transferrin levels are increased (in the third trimester), percentage saturation is low, TIBC may be increased, and ferritin may be decreased (Note: Transferrin levels may be increased in women taking oral contraceptives, whereas ferritin levels may be decreased in women who are menstruating or who have borne children.) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology and Tests of Hematopoietic Function 13 Reference Values Conventional Units SI Units Vitamin B12 Serum 200–900 pg/mL 148–664 pmol/L Folic acid Serum 1.8–9 ng/mL 4–20 nmol/L RBCs 95–500 ng/mL 215–1133 nmol/L Blood for serum iron and TIBC should be drawn in the morning, in the fasting state, and 24 hours or more after discontinuing iron-containing medications.17 THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Food, fluids, and medications withheld before the test may be resumed after the sample is obtained. Complications and precautions: Note and report signs and symptoms of anemia: decreases in test levels, fatigue and weakness, increased pulse, exertional dyspnea, and dizziness. If anemia is caused by blood loss, prepare to administer a transfusion of blood products. If anemia is caused by iron deficiency, administer ordered oral or parenteral (intramuscular) iron supplement and instruct client in dietary inclusion of foods high in iron content. After 4 to 7 days, check iron studies, RBC count, reticulocyte count, and hemoglobin levels to see whether iron stores have been replenished. VITAMIN B12 AND FOLIC ACID STUDIES Vitamin B12 (cyanocobalamin) and folic acid (pteroylglutamic acid) are essential for the production and maturation of erythrocytes. Both must be present for normal DNA replication and cell division. In humans, vitamin B12 is obtained only by eating animal proteins, milk, and eggs, which places strict vegetarians at risk for developing cobalamin deficiency; hydrochloric acid (HCl) and intrinsic factor are required for absorption. Folic acid (or folate) is present in liver and in many foods of vegetable origin such as lima beans, kidney beans, and dark-green leafy vegetables. Note that canning and prolonged cooking destroy folate. Normally functioning intestinal mucosa is necessary for absorption of both vitamin B12 and folic acid. Vitamin B12 is normally stored in the liver in sufficient quantity to withstand 1 year of zero intake. In contrast, most of the folic acid absorbed goes directly to the tissues, with a smaller amount stored in the liver. Folate stores are adequate for only 2 to 4 months. INDICATIONS FOR VITAMIN B12 AND FOLIC ACID STUDIES Determination of the cause of megaloblastic anemia: Diagnosis of pernicious anemia, a megaloblastic anemia characterized by vitamin B12 deficiency despite normal dietary intake Diagnosis of megaloblastic anemia caused by deficient folic acid intake or increased folate requirements (e.g., in pregnancy and hemolytic anemias) or both, as indicated by decreased serum levels of folic acid Monitoring response to disorders that may lead to vitamin B12 deficiency (e.g., gastric surgery, agerelated atrophy of the gastric mucosa, surgical resection of the ileum, intestinal parasites, overgrowth of intestinal bacteria) Monitoring response to disorders that may lead to folate deficiency (e.g., disease of the small intestine, sprue, cirrhosis, chronic alcoholism, uremia, some malignancies)18 Monitoring effects of drugs that are folic acid antagonists (e.g., alcohol, anticonvulsants, antimalarials, and certain drugs used to treat leukemia)19 Monitoring effects of prolonged parenteral nutrition NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company 14 SECTION I—Laboratory Tests Samples should be drawn after the client has fasted for 8 hours and before injections of vitamin B12 have been given. Alcohol also should be avoided for 24 hours before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. The difference between men and women results partly from menstrual blood loss in women and partly from the effects of androgens in men. Castration of men usually causes hemoglobin and hematocrit to decline to nearly the same levels as those of women. Note that a decline in erythrocytes is experienced by both genders in old age.21 More detailed discussions of the RBC and WBC components of the CBC are included in succeeding sections of this chapter. Platelets are discussed in Chapter 2. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Foods and drugs withheld before the test may be resumed after the sample is obtained. Complications and precautions (anemia): Note and report folic acid levels of less than 4 ng and a normal level of vitamin B12, indicating folic acid anemia. Prepare to administer ordered oral replacement therapy of folic acid; dosage and duration depend on the cause of the deficiency. Perform nursing activities for vitamin B12 deficiency as in pernicious anemia diagnosed by the Schilling test (see Chapter 20). COMPLETE BLOOD COUNT A CBC includes (1) enumeration of the cellular elements of the blood, (2) evaluation of RBC indices, and (3) determination of cell morphology by means of stained smears. Counting is performed by automated electronic devices capable of rapid analysis of blood samples with a measurement error of less than 2 percent.20 Reference values for the CBC vary across the life cycle and between the genders. In the neonate, when oxygen demand is high, the number of erythrocytes also is high. As demand decreases, destruction of the excess cells results in decreased erythrocyte, hemoglobin, and hematocrit levels. During childhood, RBC levels again rise, although hemoglobin levels may decrease slightly. In prepubertal children, normal erythrocyte and hemoglobin levels are the same for boys and girls. During puberty, however, values for boys rise, whereas values for girls decrease. In men, these higher values persist to age 40 or 50, decline slowly to age 70, and then decrease rapidly thereafter. In women, the drop in hemoglobin and hematocrit that begins with puberty reverses at about age 50 but never rises to prepubertal levels or to that of men of the same age. Reference Values The components of the CBC and their reference values across the life cycle are shown in Table 1–4. INDICATIONS FOR A COMPLETE BLOOD COUNT Because the CBC provides much information about the overall health of the individual, it is an essential component of a complete physical examination, especially when performed on admission to a health-care facility or before surgery. Other indications for a CBC are as follows: Suspected hematologic disorder, neoplasm, or immunologic abnormality History of hereditary hematologic abnormality Suspected infection (local or systemic, acute or chronic) Monitoring effects of physical or emotional stress Monitoring desired responses to drug therapy and undesired reactions to drugs that may cause blood dyscrasias (Table 1–5) Monitoring progression of nonhematologic disorders such as chronic obstructive pulmonary disease, malabsorption syndromes, malignancies, and renal disease NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children, as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the Copyright © 2003 F.A. Davis Company TABLE 1–4 • Reference Values for Complete Blood Count Adult CBC Component Red blood cells (RBCs) Newborn 1 Mo 4.8–7.1 million/mm3 4.8–7.1 10 /L (SI units) 12 6 Mo 1–10 Yr Male Female 4.1–6.4 million/mm3 3.8–5.5 million/mm3 4.5–4.8 million/mm3 4.6–6.2 million/mm3 4.2–5.4 million/mm3 35–49% 30–40% 35–41% 40–54% 38–47% Hemoglobin (Hgb) 14–24 g/L (SI units) 11–20 g/dL 10–15 g/dL 11–16 g/dL 13.5–18 g/dL 12–16 g/dL 140–240 g/L (SI units) 110–200 g/L 100–150 g/L 110–160 g/L 135–180 g/L 120–160 g/L 96–108 m3 82–91 3 — — 80–94 m3 81–99 m3 96–108 fL (SI units) 82–91 fL — — 80–94 fL 81–99 fL 32–34 pg 27–31 pg — — 27–31 pg 32–33% 32–36% — — 32–36% 320–330 S/L (SI units) 320–360 S/L RBC indices MCV* † MCH MCHC ‡ Stained RBC examination White blood cells (WBCs) 320–360 S/L Normochromic and normocytic for all age groups and both sexes (see p. 23) 9,000–30,000/mm3 6,000–18,000/mm3 6,000–16,000/mm3 5,000–13,000/mm3 5,000–10,000/mm3 9,000–30,000 10 /L (SI units) 9 (Continued on following page) and Tests of Hematopoietic Function 4.4–64% CHAPTER 1—Hematology Hematocrit (Hct) 15 Copyright © 2003 F.A. Davis Company 16 • Reference Values for Complete Blood Count (Continued) Adult CBC Component Newborn 1 Mo 6 Mo 1–10 Yr Male Female Neutrophils 45% by 1 wk 40% by 4 wk 32% 60% after age 2 yr — 54–75% (3000–7500/mm3) Bands — — — — — 3–8% (150–700/mm3) Eosinophils — — — 0–3% — 1–4% (50–400/mm3) Basophils — — — 1–3% — 0–1% (25–100/mm3) Monocytes — — — 4–9% — 2–8% (100–500/mm3) Lymphocytes 41% by 1 wk 56% by 4 wk 61% 59% after age 2 yr — 25–40% (1500–4500/mm3) T lymphocytes — — — — — 60–80% of lymphocytes B lymphocytes — — — — Platelets 140,000–300,000/mm3 150,000–390,000/ mm3 200,000–473,000/ mm3 150,000–450,000/ mm3 150,000–450,000/mm3 140–300 109/L (SI units) 150–390 109/L 200–473 109/L 150–450 109/L 150–450 109/L * Mean corpuscular volume. † Mean corpuscular hemoglobin. ‡ Mean corpuscular hemoglobin concentration. 10–20% of lymphocytes Tests Differential WBC SECTION I—Laboratory TABLE 1–4 Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology TABLE 1–5 • and Tests of Hematopoietic Function 17 Drugs That May Cause Blood Dyscrasias Generic Name or Class Trade Names Acetaminophen and acetaminophen compounds Bancap, Capital, Colrex, Comtrex, Darvocet-N, Datril, Dolene, Duradrin, Duradyne, Esgic, Excedrin, Liquiprin, Midrin, Neopap Supprettes, NyQuil, Ornex, Panadol, Parafon Forte, Percogesic, Phrenilin, Sedapap, Sinarest, Sinutab, Supac, Tylenol, Tempra, Tylenol with Codeine, Valadol, Vanquish, Wygesic Acetophenazine maleate Tindal Aminosalicylic acid Pamisyl, PAS, Rezipas Amphotericin B Fungizone, Mysteclin F Antineoplastic agents Arsenicals Carbamazepine Tegretol Chloramphenicol Chloromycetin Chloroquine Aralen Ethosuximide (methsuximide, phensuximide) Zarontin Furazolidone Furoxone Haloperidol Haldol Hydantoin derivatives Ethotoin Peganone Mephenytoin Mesantoin Phenytoin Dilantin, Diphenylan Hydralazine Apresazide, Apresoline, Bolazine, Ser-Ap-Es, Serpasil-Apresoline Hydroxychloroquine sulfate Plaquenil Indomethacin Indocin Isoniazid INH, Nydrazid, Rifamate MAO inhibitors Eutonyl, Nardil, Parnate Mefenamic acid Ponstel Mepacrine Atabrine Mephenoxalone Lenetron Mercurial diuretics Thiomerin Metaxalone Skelaxin Methaqualone Quaalude, Sopor Methyldopa Aldoclor, Aldomet, Aldoril Nitrites Nitrofurantoin Cyantin, Furadantin, Macrodantin Novobiocin Albamycin Oleandomycin Matromycin (Continued on following page) Copyright © 2003 F.A. Davis Company 18 SECTION I—Laboratory TABLE 1–5 • Tests Drugs That May Cause Blood Dyscrasias (Continued) Generic Name or Class Trade Names Oxyphenbutazone Oxalid, Tandearil Paramethadione Paradione Penicillamine Cuprimine, Depen Penicillins Phenacemide Phenurone Phenobarbital Phenylbutazone Azolid, Butazolidin Phytonadione AquaMEPHYTON, Konakion Primaquine Primidone Mysoline Pyrazolone derivatives Butazolidin, Tandearil, Oxalid Pyrimethamine Daraprim Rifampin Rifadin, Rifamate, Rimactane Radioisotopes Spectinomycin Trobicin Sulfonamides Mafenide Sulfamylon cream Phthalylsulfathiazole Sulfathalidine Sulfabenzamide Sultrin vaginal cream Sulfacetamide Bleph-10, Cetamide ointment, Isopto Cetamide, Sulamyd, Sultrin vaginal cream Sulfachloropyridazine Sonilyn Sulfacytine Renoquid Sulfadiazine Silvadene Sulfameter Sulla Sulfamethiozole Thiosulfil Forte Sulfamethoxazole Azo Gantanol, Bactrim, Gantanol, Septra Sulfamethoxypyridazine Midicel Sulfanilamide AVC vaginal cream Sulfasalazine Azulfidine Sulfathiazole Sultrin vaginal cream, Triple Sulfa cream Sulfinpyrazone Anturane Sulfisoxazole Azo Gantrisin, Gantrisin Sulfones Dapsone DDS Sulfoxone Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology TABLE 1–5 • and Tests of Hematopoietic Function 19 Drugs That May Cause Blood Dyscrasias Generic Name or Class Trade Names Sulfonylureas Acetohexamide Dymelor Chlorpropamide Diabinese Tolazamide Tolinase Tolbutamide Orinase Tetracyclines Achromycin Chlortetracycline Aureomycin Demeclocycline Declomycin Doxycycline Doxychel, Doxy, Vibramycin, Vibra-Tabs Meclocycline Meclan Methacycline Rondomycin Minocycline Minocin Oxytetracycline Oxlopar, Terramycin Thiazide diuretics (rare hematologic side effects) Ademol, Diuril, Enduron, Exna, Naturetin, Naqua, Renese, Saluron Thiocyanates Trimethadione Tridione Tripelennamine Pyribenzamine, PBZ Troleandomycin Cyclamycin, Tao capsules and suspension Valproic acid Valproate Vitamin A Aquasol A, Alphalin same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal range of values: Note and report decreases in individual or entire CBC (pancytopenia) panel. Prepare to administer drugs and treatments, or both, that have been ordered to manage anemia (RBC, hematocrit [Hct], hemoglobin [Hgb], RBC indices), clotting process (platelet), or infectious process (WBC, differential). ERYTHROCYTE STUDIES The mature RBC (erythrocyte) is a biconcave disk with an average life span of 120 days. Because it lacks a nucleus and mitochondria, it is unable to synthesize protein, and its limited metabolism is barely enough to sustain it. Erythrocytes function primarily as containers for Hgb. As such, they transport oxygen from the lungs to all body cells and transfer carbon dioxide from the cells to the organs of excretion. The RBC is resilient and capable of extreme changes in shape. It is admirably designed to survive its many trips through the circulation.22 Old, damaged, and abnormal erythrocytes are removed mainly by the spleen and also by the liver and the red bone marrow. The iron is returned to plasma transferrin and is transported back to the erythroid marrow or stored within the liver and spleen as ferritin and hemosiderin. The bilirubin component of Hgb is carried by plasma albumin to the liver, where it is conjugated and excreted into the bile. Most of this conjugated bilirubin is ultimately excreted in the stool, although some appears in the urine or is returned to bile. The hematologist determines the numbers, structure, color, size, and shape of erythrocytes; the types Copyright © 2003 F.A. Davis Company 20 SECTION I—Laboratory Tests and amount of Hgb they contain; their fragility; and any abnormal components. INDICATIONS FOR AN ERYTHROCYTE (RBC) COUNT Routine screening as part of a CBC Suspected hematologic disorder involving RBC destruction (e.g., hemolytic anemia) Monitoring effects of acute or chronic blood loss Monitoring response to drug therapy that may alter the RBC count (see Table 1–5) Monitoring clients with disorders associated with elevated RBC counts (e.g., polycythemia vera, chronic obstructive pulmonary disease) Monitoring clients with disorders associated with decreased RBC counts (e.g., malabsorption syndromes, malnutrition, liver disease, renal disease, hypothyroidism, adrenal dysfunction, bone marrow failure) ERYTHROCYTE (RBC) COUNT The erythrocyte (RBC) count, a component of the CBC, is the determination of the number of RBCs per cubic millimeter. In international units, this is expressed as the number of RBCs per liter of blood. The test is less significant by itself than it is in computing Hgb, Hct, and RBC indices. Many factors influence the level of circulating erythrocytes. Decreased numbers are seen in disorders involving impaired erythropoiesis excessive blood cell destruction (e.g., hemolytic anemia), and blood loss, and in chronic inflammatory diseases. A relative decrease also may be seen in situations with increased body fluid in the presence of a normal number of RBCs (e.g., pregnancy). Increases in the RBC count are most commonly seen in polycythemia vera, chronic pulmonary disease with hypoxia and secondary polycythemia, and dehydration with hemoconcentration. Excessive exercise, anxiety, and pain also produce higher RBC counts. Many drugs can cause a decrease in circulating RBCs (see Table 1–5), whereas a few drugs, such as methyldopa and gentamicin, can cause an increase.23 NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. INTERFERING FACTORS NURSING CARE AFTER THE PROCEDURE Excessive exercise, anxiety, pain, and dehydration may lead to false elevations. Hemodilution in the presence of a normal number of RBCs may lead to false decreases (e.g., excessive administration of intravenous fluids, normal pregnancy). Many drugs may cause a decrease in circulating RBCs (see Table 1–5). Drugs such as methyldopa and gentamicin may cause an elevated RBC count. Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Anemia: Note and report signs and symptoms of anemia associated with decreased counts in combination with Hgb and Hct decreases. Prepare to administer ordered oral or parenteral iron preparation or a transfusion of whole blood or packed RBCs. Prepare for phlebotomy if levels are Reference Values Conventional Units SI Units Newborns 4.8–7.1 million/mm 3 4.8–7.1 1012/L 1 mo 4.1–6.4 million/mm3 4.1–6.4 1012/L 6 mo 3.8–5.5 million/mm3 3.8–5.5 1012/L 1–10 yr 4.5–4.8 million/mm3 4.5–4.8 1012/L Men 4.6–6.2 million/mm3 4.6–6.2 1012/L Women 4.2–5.4 million/mm3 4.2–5.4 1012/L Adults Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology increased in polycythemia vera or secondary polycythemia. HEMATOCRIT Blood consists of a fluid portion (plasma) and a solid portion that includes RBCs, WBCs, and platelets. More than 99 percent of the total blood cell mass is composed of RBCs. The Hct or packed RBC volume measures the proportion of RBCs in a volume of whole blood and is expressed as a percentage. Several methods can be used to perform the test. In the classic method, anticoagulated venous blood is pipetted into a tube 100 mm long and then centrifuged for 30 minutes so that the plasma and blood cells separate. The volumes of packed RBCs and plasma are read directly from the millimeter marks along the side of the tube. In the micro method, venous or capillary blood is used to fill a small capillary tube, which is then centrifuged for 4 to 5 minutes. The proportions of plasma and RBCs are determined by means of a calibrated reading device. Both techniques allow visual estimation of the volume of WBCs and platelets.24 With the newer, automated methods of cell counting, the Hct is calculated indirectly as the product of the RBC count and mean cell volume. Although this method is generally quite accurate, certain clinical situations may cause errors in interpreting the Hct. Abnormalities in RBC size and extremely elevated WBC counts may produce false Hct values. Elevated blood glucose and sodium may produce elevated Hct values because of the resultant swelling of the erythrocyte.25 Normally, the Hct parallels the RBC count. Thus, factors influencing the RBC count also affect the results of the Hct. Reference Values Conventional Units SI Units Newborns 44–64% 0.44–64 1 mo 35–49% 0.35–0.49 6 mo 30–40% 0.30–0.40 1–10 yr 35–41% 0.35–0.41 Men 40–54% 0.40–0.54 Women 38–47% 0.38–0.47 Adults and Tests of Hematopoietic Function 21 INTERFERING FACTORS Abnormalities in RBC size and extremely elevated WBC counts may alter Hct values. Elevated blood glucose and sodium may produce elevated Hct values because of swelling of the erythrocyte. Factors that alter the RBC count such as hemodilution and dehydration also influence the Hct. INDICATIONS FOR A HEMATOCRIT TEST Routine screening as part of a CBC Along with an Hgb (i.e., an “H and H”), to monitor blood loss and response to blood replacement Along with an Hgb, to evaluate known or suspected anemia and related treatment Along with an Hgb, to monitor hematologic status during pregnancy Monitoring responses to fluid imbalances or to therapy for fluid imbalances: A decreased Hct may indicate hemodilution. An increased Hct may indicate dehydration. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE The volume of the sample needed depends on the method used to determine the Hct. With the exception of the classic method of Hct determination, a capillary sample is usually sufficient to perform the test. If a venipuncture is performed, the sample is collected in a lavender-topped tube. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Critical values: Notify the physician at once if the Hct is greater than 60 percent or less than 14 percent. Prepare the client for possible transfusion of blood products or infusion of intravenous fluids and for further procedures to evaluate the cause or source of the blood loss or hemoconcentration. HEMOGLOBIN Critical values 14% or 60% 0.14–0.60 Note: Values vary across the life cycle and between genders. Hemoglobin is the main intracellular protein of the RBC. Its primary function is to transport oxygen to the cells and to remove carbon dioxide from them for excretion by the lungs. The Hgb molecule consists of two main components: heme and globin. Copyright © 2003 F.A. Davis Company 22 SECTION I—Laboratory Tests Heme is composed of the red pigment porphyrin and iron, which is capable of combining loosely with oxygen. Globin is a protein that consists of nearly 600 amino acids organized into four polypeptide chains. Each chain of globin is associated with a heme group. Each RBC contains approximately 250 million molecules of hemoglobin, with some erythrocytes containing more hemoglobin than others. The oxygen-binding, -carrying, and -releasing capacity of Hgb depends on the ability of the globin chains to shift position normally during the oxygenation–deoxygenation process. Structurally abnormal chains that are unable to shift normally have decreased oxygen-carrying ability. This decreased oxygen transport capacity is characteristic of anemia. Hemoglobin also functions as a buffer in the maintenance of acid–base balance. During transport, carbon dioxide (CO2) reacts with water (H2O) to form carbonic acid (H2CO3). This reaction is speeded by carbonic anhydrase, an enzyme contained in RBCs. The carbonic acid rapidly dissociates to form hydrogen ions (H) and bicarbonate ions (HCO3–). The hydrogen ions combine with the Hgb molecule, thus preventing a buildup of hydrogen ions in the blood. The bicarbonate ions diffuse into the plasma and play a role in the bicarbonate buffer system. As bicarbonate ions enter the bloodstream, chloride ions (Cl) are repelled and move back into the erythrocyte. This “chloride shift” maintains the electrical balance between RBCs and plasma.26 Hemoglobin determinations are of greatest use in the evaluation of anemia, because the oxygen-carrying capacity of the blood is directly related to the Hgb level rather than to the number of erythrocytes. To interpret results accurately, the Hgb level must be determined in combination with the Hct level. Normally, Hgb and Hct levels parallel each other and are commonly used together to express the degree of anemia. The combined values are also useful in evaluating situations involving blood loss and related treatment. The Hct level is normally three times the Hgb level. If erythrocytes are abnormal in shape or size or if Hgb manufacture is defective, the relationship between Hgb and Hct is disproportionate.27,28 Reference Values Conventional Units SI Units Newborns 14–24 g/dL 140–240 g/L 1 mo 11–20 g/dL 110–200 g/L 6 mo 10–15 g/dL 100–150 g/L 1–10 yr 11–16 g/dL 110–160 g/L 13.5–18 g/dL 135–180 g/L 12–16 g/dL 120–160 g/L 6.0 g/dL 200 g/dL 60 g/L 200 g/L Adults Men Women Critical values Note: Ratio of hemoglobin to hematocrit 3:1. ate known or suspected anemia and related treatment Along with an Hct, to monitor blood loss and response to blood replacement Along with an Hct, to monitor hematologic status during pregnancy NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Critical values: Notify the physician at once if the Hgb is less than 6.0 g/dL. Prepare the client for possible transfusion of blood products and for further procedures to evaluate cause or source of blood loss. INTERFERING FACTORS Factors that alter the RBC count may also influence Hgb levels INDICATIONS FOR HEMOGLOBIN DETERMINATION Routine screening as part of a CBC Along with an Hct (i.e., an “H and H”), to evalu- RED BLOOD CELL INDICES RBC indices are calculated mean values that reflect the size, weight, and Hgb content of individual erythrocytes. They consist of the mean corpuscular volume (MCV), the mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology TABLE 1–6 Microcytic, normochromic Microcytic, hypochromic Macrocytic, normochromic 23 Classification of Anemias MCV* (mm3) MCH† (pg) MCHC‡ (%) Sepsis, hemorrhage, hemolysis, drug-induced aplastic anemia, radiation, hereditary spherocytosis 82–92 25–30 32–36 Renal disease, infection, liver disease, malignancies 80 20–25 27 Iron deficiency, lead poisoning, thalassemia, rheumatoid arthritis 50–80 12–25 25–30 95–150 30–50 32–36 Anemia Normocytic, normochromic • and Tests of Hematopoietic Function Examples of Causes Vitamin B12 and folic acid deficiency, some drugs, pernicious anemia * Mean corpuscular volume. † Mean corpuscular hemoglobin. ‡ Mean corpuscular hemoglobin concentration. concentration (MCHC). MCV indicates the volume of the Hgb in each RBC, MCH is the weight of the Hgb in each RBC, and MCHC is the proportion of Hgb contained in each RBC. MCHC is a valuable indicator of Hgb deficiency and of the oxygen-carrying capacity of the individual erythrocyte. A cell of abnormal size, abnormal shape, or both may contain an inadequate proportion of Hgb. RBC indices are used mainly in identifying and classifying types of anemias. Anemias are generally classified according to RBC size and Hgb content. Cell size is indicated by the terms normocytic, microcytic, and macrocytic. Hemoglobin content is indicated by the terms normochromic, hypochromic, and hyperchromic. Table 1–6 shows anemias classified according to these terms and in relation to the results of RBC indices. To calculate the RBC indices, the results of an RBC count, Hct, and Hgb are necessary. Thus, factors that influence these three determinations (e.g., abnormalities of RBC size or extremely elevated WBC counts) may result in misleading RBC indices. For this reason, a stained blood smear may be used to compare appearance with calculated values and to determine the etiology of identified abnormalities. INTERFERING FACTORS Because RBC indices are calculated from the results of the RBC count, Hgb, and Hct, factors that influ- Reference Values Men MCV Women 80–94 m 3 Newborns 81–99 m 3 SI Units 96–108 m 3 81–99 fL (women) 96–108 fL (newborns) MCH 27–31 pg 27–31 pg 32–34 pg 32–34 pg (women) 32–34 pg (newborns) MCHC 32–36% 32–36% 32–33% 320–360 g/L (women) 320–330 g/L (newborns) Normal values for RBC indices are shown in Table 1–4 in relation to the CBC and also are repeated above for adults. Values in newborn infants are slightly different, but adult levels are achieved within approximately 1 month of age. Copyright © 2003 F.A. Davis Company 24 SECTION I—Laboratory Tests ence the latter three tests (e.g., abnormalities of RBC size, extremely elevated WBC counts) also influence RBC indices. INDICATIONS FOR RED BLOOD CELL INDICES Routine screening as part of a CBC Identification and classification of anemias (see Table 1–6) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). TABLE 1–7 Descriptive Term Macrocytosis • STAINED RED BLOOD CELL EXAMINATION The stained RBC examination (RBC morphology) involves examination of RBCs under a microscope. It is usually performed to compare the actual appearance of the cells with the calculated values for RBC indices. Cells are examined for abnormalities in color, size, shape, and contents. The test is performed by spreading a drop of fresh anticoagulated blood on a glass slide. The addition of stain to the specimen is used to enhance RBC characteristics. As with RBC indices, RBC color is described as normochromic, hypochromic, or hyperchromic, indicating, respectively, normal, reduced, or elevated amounts of Hgb. Cell size may be described as normocytic, microcytic, or macrocytic, depending on whether cell size is normal, small, or abnormally large, respectively. Cell shape is described using terms such as poikilocyte, anisocyte, leptocyte, and spherocyte (Table 1–7). The cells are examined also for inclusions or abnormal cell contents, for example, Heinz bodies, Howell-Jolly bodies, Cabot’s rings, and siderotic granules (Table 1–8). Red Blood Cell Abnormalities Seen on Stained Smear Observation Significance Cell diameter 8 m Megaloblastic anemias MCV* 95 m3 Severe liver disease Hypothyroidism Microcytosis Cell diameter 6 m Iron-deficiency anemia MCV 80 m Thalassemias MCHC† 27 Anemia of chronic disease Hypochromia Increased zone of central pallor Diminished Hgb content Hyperchromia Microcytic, hyperchromic cells Chronic inflammation Increased bone marrow stores of iron Defect in ability to use iron for Hgb synthesis Polychromatophilia Presence of red cells not fully hemoglobinized Reticulocytosis Poikilocytosis Variability of cell shape Sickle cell disease 3 Microangiopathic hemolysis Leukemias Extramedullary hematopoiesis Marrow stress of any cause Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology TABLE 1–7 • 25 Red Blood Cell Abnormalities Seen on Stained Smear Descriptive Term Anisocytosis and Tests of Hematopoietic Function Observation Significance Reticulocytosis Variability of cell size Transfusing normal blood into microcytic or macrocytic cell population Leptocytosis Spherocytosis Hypochromic cells with small central zone of Hgb (“target cells”) Thalassemias Cells with no central pallor, loss of biconcave shape Loss of membrane relative to cell volume Obstructive jaundice Hereditary spherocytosis Schistocytosis MCHC high Accelerated red blood cell destruction by reticuloendothelial system Acanthocytosis Presence of cell fragments in circulation Increased intravascular mechanical trauma Echinocytosis Irregularly spiculated surface Microangiopathic hemolysis Irreversibly abnormal membrane lipid content Liver disease Abetalipoproteinemia Regularly spiculated cell surface Reversible abnormalities of membrane lipids High plasma-free fatty acids Bile acid abnormalities Effects of barbiturates, salicylates, and so on Stomatocytosis Elongated, slitlike zone of central pallor Hereditary defect in membrane sodium metabolism Severe liver disease Elliptocytosis Oval cells Hereditary anomaly, usually harmless Source: Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000 p. 68, with permission. * Mean corpuscular volume. †Mean corpuscular hemoglobin concentration. Reference Values In a normal smear, all cells are uniform in color, size, and shape and are free of abnormal contents. A normal RBC may be described as a normochromic, normocytic cell. INDICATIONS FOR A STAINED RED BLOOD CELL EXAMINATION Abnormal calculated values for RBC indices Evaluation of anemia and related disorders involving RBCs (see Tables 1–6, 1–7, and 1–8) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary Copyright © 2003 F.A. Davis Company 26 SECTION I—Laboratory TABLE 1–8 • Tests Types of Abnormal Red Blood Cell Inclusions and Their Causes Type (Composition) Heinz bodies (denatured Hgb) Causes of Inclusions -Thalassemia G-6-PD deficiency Hemolytic anemias Methemoglobinemia Splenectomy Drugs: analgesics, antimalarials, antipyretics, nitrofurantoin (Furadantin), nitrofurazone (Furacin), phenylhydrazine, sulfonamides, tolbutamide, vitamin K (large doses) Basophilic stippling (residual cytoplasmic RNA) Anemia caused by liver disease Lead poisoning Thalassemia Howell-Jolly bodies (fragments of residual DNA) Splenectomy Intense or abnormal RBC production resulting from hemolysis or inefficient erythropoiesis Cabot’s rings (composition unknown) Same as for Howell-Jolly bodies Siderotic granules (ironcontaining granules) Abnormal iron metabolism Abnormal hemoglobin manufacture sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). HEMOGLOBIN ELECTROPHORESIS The Hgb molecule consists of four polypeptide globin chains and four heme components containing iron and the red pigment porphyrin. Hemoglobin formation is genetically determined, and the types of globin chains normally formed are termed alpha ( ), beta (), gamma ( ), and delta ( ). Combinations of these chains form various types of Hgb. Disorders of synthesis and production of globin chains result in the formation of abnormal Hgb. Hemoglobin electrophoresis is a technique for identifying the types of Hgb present and for determining the percentage of each type. Exposed to an electrical current, the several types of Hgb migrate toward the positive pole at different rates. The patterns created are compared with standard patterns. At birth, most RBCs contain fetal hemoglobin (Hgb F), which is made up of two chains and two chains. Within a few months, through sequential suppression and activation of individual genes, Hgb F largely disappears and is replaced by adult hemoglobin (Hgb A). Hgb A, composed of two chains and two chains, makes up more than 95 percent of Hgb in adults. A minor type of Hgb, Hgb A2, consisting of two chains and two chains, also is found in small amounts (2 to 3 percent) in adults. Traces of Hgb F persist throughout life (Fig. 1–4).29 More than 150 genetic abnormalities in the Hgb molecule have been identified. These are termed thalassemias and hemoglobinopathies. Thalassemias are genetic disorders in globin chain synthesis that result in decreased production rates of - or globin chains. Hemoglobinopathies refer to disorders involving an abnormal amino acid sequence in the globin chains. In -thalassemia, for example, production of chains and Hgb A is decreased. The oversupply of chains results in the formation of hemoglobin H (Hgb H), which consists of four chains (Fig. 1–5). Complete absence of a chain production (homozygous thalassemia A) is incompatible with life and generally results in stillbirth during the second trimester of pregnancy. The cord blood of such fetuses shows high levels of hemoglobin Barts, a type Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology Figure 1–4. Changes in hemoglobin with development. (From Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia, 1996, p. 11, with permission.) of Hgb that evolves from unpaired chains. Hemoglobin Barts itself has such a high affinity for oxygen that it releases none to the tissues. In -thalassemia minor, a decrease is seen in chain production and, therefore, a reduction in the amount of Hgb A formed. In -thalassemia major, all -chain production is lost and no Hgb A is formed. The chains are then used to form Hgb F and Hgb A2. Among the most common Hgb abnormalities are the sickle cell disorders, which exhibit a double gene defect that results in the production of hemoglobin S (Hgb S). In Hgb S, the amino acid valine is substituted for glutamine at a critical position on the globin chain, which causes the chains to “lock” when deoxygenated, deforming the erythrocyte into the sickled shape. Repeated sickling damages RBC membranes and shortens the cells’ life spans. The abnormally shaped cells pass more sluggishly through the circulation, leading to impaired tissue oxygenation. The gene for Hgb S is most prevalent in black populations and may be present as either sickle cell trait (having one recessive gene for Hgb S) or sickle cell disease (having both recessive genes for Hgb S). and Tests of Hematopoietic Function 27 The Sickledex test, a screening test for sickle cell disorders, detects sickled erythrocytes under conditions of oxygen deprivation. Hemoglobin electrophoresis is necessary, however, to differentiate sickle cell trait (20 to 40 percent Hgb S) from sickle cell disease (70 percent Hgb S). Many other types of abnormal Hgb are caused by defects in globin chain synthesis. Hemoglobin C (Hgb C), for example, has an abnormal amino acid substitution on the chain and can lead to a form of mild hemolytic anemia. Other examples of abnormal Hgb resulting from rearrangement or substitution of the amino acids on the globin chains include hemoglobin E (Hgb E), hemoglobin Lepore (chain abnormalities), and hemoglobin Constant Spring ( -chain abnormality).30 Other disorders involving Hgb pertain to the oxygen-combining ability of the heme portion of the molecule. Examples of types of Hgb associated with such disorders are methemoglobin (Hgb M), sulfhemoglobin, and carboxyhemoglobin. Hgb M is formed when the iron contained in the heme portion of the Hgb molecule is oxidized to a ferric instead of a ferrous form, thus impairing its oxygencombining ability. Methemoglobinemia may be hereditary or acquired. The acquired form may be caused by excessive radiation or by the toxic effects of chemicals and drugs (e.g., nitrates, phenacetin, lidocaine). Note that Hgb F is more easily converted to Hgb M than is Hgb A. Sulfhemoglobin is a pigment that results from Hgb combining with inorganic sulfides. It occurs in those who take sulfonamides or acetanilid. Carboxyhemoglobin results when Hgb is exposed to carbon monoxide. Although this type of Hgb is most commonly seen in individuals with excessive exposure to automobile exhaust fumes, it may also occur in heavy smokers.31 Tests other than Hgb electrophoresis are used to determine the presence of Hgb M and carboxyhemoglobin. INDICATIONS FOR HEMOGLOBIN ELECTROPHORESIS Suspected thalassemia, especially in individuals with positive family history for the disorder Differentiation among the types of thalassemias Evaluation of a positive Sickledex test to differentiate sickle cell trait (20 to 40 percent Hgb S) from sickle cell disease (70 percent Hgb S) Evaluation of hemolytic anemia of unknown etiology Diagnosis of Hgb C anemia Identification of the numerous types of abnormal Hgb, most of which do not produce clinical disease Copyright © 2003 F.A. Davis Company 28 SECTION I—Laboratory Tests Figure 1–5. Formation of manual and abnormal hemoglobin. (From Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia, 1996, with permission.) Reference Values The normal values shown for Hgb electrophoresis are for adults. In newborn infants, 60 to 90 percent of Hgb may consist of Hgb F. This amount decreases to 10 to 20 percent by 6 months of age and to 2 to 4 percent by 1 year. Abnormal forms of Hgb (e.g., Hgb S, Hgb H) are not normally present. Conventional Units SI Units Hgb A 95–97% 0.95 Hgb A2 2–3% 0.02–0.03 Hgb F 1% 0.01 Methemoglobin (Hgb M) 2% or 0.06–0.24 g/dL Sulfhemoglobin Minute amounts Carboxyhemoglobin 0–2.3% 4–5% in smokers Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). and Tests of Hematopoietic Function 29 The test is performed by exposing RBCs to increasingly dilute saline solutions. The percentage of the solution at which the cells swell and rupture is then noted. THE PROCEDURE Reference Values A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. Normal erythrocytes rupture in saline solutions of 0.30 to 0.45 percent. RBC rupture in solutions of greater than 0.50 percent saline indicates increased fragility. Lack of rupture in solutions of less than 0.30 percent saline indicates decreased RBC fragility. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Complications and precautions: Note and report signs and symptoms associated with the specific type of anemia identified by electrophoresis. Prepare to instruct in therapy and prevention of complications. Offer information about genetic factors and counseling or both, if appropriate. INDICATIONS FOR OSMOTIC FRAGILITY TEST Confirmation of disorders that alter RBC fragility, including hereditary anemias (see Table 1–9) Evaluation of the extent of extrinsic damage to RBCs from burns, inadvertent instillation of hypotonic intravenous fluids, microorganisms, and excessive exercise NURSING CARE BEFORE THE PROCEDURE OSMOTIC FRAGILITY The osmotic fragility test determines the ability of the RCB membrane to resist rupturing in a hypotonic saline solution. Normal disk-shaped cells can imbibe water and swell significantly before membrane capacity is exceeded, but spherocytes (RBCs that lack the normal biconcave shape) and cells with damaged membranes burst in saline solutions only slightly less concentrated than normal saline. Conversely, in thalassemia, sickle cell disease, and other disorders, RBCs are more than normally resistant to osmotic damage (Table 1–9). TABLE 1–9 • Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom a venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the Causes of Altered Erythrocyte Osmotic Fragility Decreased Fragility Increased Fragility Iron-deficiency anemias Hereditary spherocytosis Hereditary anemias (sickle cell, hemoglobin C, thalassemias) Hemolytic anemias Liver diseases Autoimmune anemias Polycythemia vera Burns Splenectomy Toxins (bacterial, chemical) Obstructive jaundice Hypotonic infusions Transfusion with incompatible blood Mechanical trauma to RBCs (prosthetic heart valves, disseminated intravascular clotting, parasites) Enzyme deficiencies (PK kinase, G-6-PD) Copyright © 2003 F.A. Davis Company 30 SECTION I—Laboratory Tests same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal test results, complications, and precautions: Respond as for any laboratory analysis to determine RBC abnormalities leading to anemia. RED BLOOD CELL ENZYMES To maintain normal shape and flexibility as well as to combine with and release oxygen, RBCs must generate energy. The needed energy is produced almost exclusively through the breakdown of glucose, a process that is catalyzed by a number of enzymes. Deficiencies of these enzymes are associated with hemolytic anemia. Two of the most common deficiencies, both hereditary, involve the RBC enzymes glucose-6-phosphate dehydrogenase and pyruvate kinase. GLUCOSE-6-PHOSPHATE DEHYDROGENASE Glucose-6-phosphate dehydrogenase is an enzyme pivotal in generating the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) through the pentose pathway in glucose metabolism. More than 100 structural and functional variants of the normal G-6-PD molecule (called type B) have been identified, most of which are clinically insignificant. One variant form (called type A) does, however, produce clinical disease. The type A variant is caused by a sex-linked genetic defect. The abnormal gene is carried by women and is transmitted to men who inherit the disorder. Persons with the type A enzyme (15 percent of blacks) experience no difficulty until challenged by an oxidative stressor, which induces rapid intravascular hemolysis of susceptible cells. Among these stressors are systemic infections, septicemia, metabolic acidosis, and exposure to oxidant drugs (aspirin, chloramphenicol [Chloromycetin], nitrofurantoin [Furadantin], phenacetin, primaquine, probenecid [Benemid], quinidine, quinine, sulfonamides, thiazide diuretics, and tolbutamide [Orinase]). A Mediterranean variant also may occur, especially in individuals of Greek and Italian descent and in some small, inbred Jewish populations. This variant severely reduces enzymatic activity and leads to more severe hemolytic episodes, which are triggered by a greater variety of stimuli and are less likely to be self-limited than in persons with the type A variant. In addition to the oxidative stressors just listed, ingestion of fava beans is known to precipitate hemolytic events in individuals with Mediterraneantype G-6-PD deficiency.32 PYRUVATE KINASE Pyruvate kinase (PK) functions in the formation of pyruvate and adenosine diphosphate (ADP) in glycolysis. The pyruvate thus formed is subsequently converted to lactate. RBCs that lack PK have a low affinity for oxygen. Episodes of hemolysis in individuals lacking this enzyme are severe and chronic and are exacerbated by stressors such as infection. The inherited form of this disorder is transmitted as an autosomal recessive trait; both parents must carry the abnormal gene for the child to be affected. The acquired form of PK deficiency is usually caused by either drug ingestion or metabolic liver disease. INTERFERING FACTORS Young RBCs have higher enzyme levels than do older ones; thus, if the tests are performed within 10 days of a hemolytic episode (when the body is actively replacing lost cells through increased erythropoiesis) or after a recent blood transfusion, the results may be falsely normal. INDICATIONS FOR RED BLOOD CELL ENZYMES STUDY Hemolytic anemia of uncertain etiology, especially when it occurs in infancy or early childhood Reference Values Conventional Units G-6-PD 4.3–11.8 IU/g Hgb 0.28–0.76 mm/mol Hgb 125–281 U/dL packed RBCs (PRBCs) 1.25–2.81 kU/L RBC 6 251–511 U/10 cells 1211–2111 IU/mL PRBCs PK SI Units 2.0–8.8 U/g Hgb 0.3–0.91 mg/dL 0.25–0.51 nU/L RBC Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology Suspected G-6-PD or PK deficiency, especially in individuals with positive family history or with jaundice occurring in response to stressors, oxidant drugs, or foods such as fava beans NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be collected in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal test results, complications, and precautions: Respond as for any laboratory analysis to determine RBC abnormalities leading to anemia. ERYTHROCYTE SEDIMENTATION RATE The erythrocyte sedimentation rate (ESR or sed rate) measures the rate at which RBCs in anticoaguTABLE 1–10 • and Tests of Hematopoietic Function lated blood settle to the bottom of a calibrated tube. In normal blood, relatively little settling occurs because the gravitational pull on the RBCs is almost balanced by the upward force exerted by the plasma. If plasma is extremely viscous or if cholesterol levels are very high, the upward trend may virtually neutralize the downward pull on the RBCs. In contrast, anything that encourages RBCs to aggregate or stick together increases the rate of settling. Inflammatory and necrotic processes, for example, cause an alteration in blood proteins that results in clumping together of RBCs because of surface attraction. These clumps are called rouleaux. If the proportion of globin to albumin increases or if fibrinogen 3 levels are especially high, rouleaux formation is enhanced and the sed rate increases.33 Specific causes of altered ESRs are presented in Table 1–10. INTERFERING FACTORS Delays in performing the test after the sample is collected may retard the ESR and cause abnormally low results; the test should be performed within 3 hours of collecting the sample. INDICATIONS FOR ERYTHROCYTE SEDIMENTATION RATE TEST Suspected organic disease when symptoms are vague and clinical findings uncertain Causes of Altered Erythrocyte Sedimentation Rates Increased Rate Decreased Rate Pregnancy (uterine and ectopic) Polycythemia vera Toxemia of pregnancy Congestive heart failure Collagen disorders (immune disorders of connective tissue) Sickle cell, Hgb C disease Inflammatory disorders Degenerative joint disease Infections Cryoglobulinemia Acute myocardial infarction Drug toxicity (salicylates, quinine derivatives, adrenal corticosteroids) Most malignancies Drugs (oral contraceptives, dextran, penicillamine, methyldopa, procainamide, theophylline, vitamin A) Severe anemias Myeloproliferative disorders Renal disease (nephritis) Hepatic cirrhosis Thyroid disorders Acute heavy metal poisoning 31 Copyright © 2003 F.A. Davis Company 32 SECTION I—Laboratory Tests Reference Values Normal values for the ESR follow. Note that several laboratory methods can be used to determine the ESR. Values vary according to the method used. Wintrobe (mm/hr) Westergren (mm/hr) Men Cutler (mm/hr) 0–8 50 yr 0–7 0–15 50 yr 5–7 0–20 Women 0–10 50 yr 0–15 0–20 50 yr 25–30 0–30 Landau Micro Method Smith Micro Method Children Newborn–2 yr 1–6 0–1 (newborns) 4–14 yr 1–9 3–13 Identification of the presence of an inflammatory or necrotic process Monitoring response to treatment for various inflammatory disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus) Support for diagnosing disorders associated with altered ESRs (see Table 1–10) increases, note signs of infection or inflammation (pain, temperature) and activity intolerance (fatigue, weakness), and perform activities that conserve the client’s energy. Administer ordered anti-inflammatory or antibiotic therapy. As the rate decreases, evaluate for improvement in condition and possible increases in client activity. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. The sample should be transported promptly to the laboratory, because the test must be performed within 3 hours of collecting the sample. Delays may retard the ESR and cause abnormally low results. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal values: Note and report increases or decreases in the rate in relation to other test results used to determine the presence of or to monitor the progress of a disease. As the rate LEUKOCYTE STUDIES Leukocytes (white blood cells, WBCs) constitute the body’s primary defense against “foreignness”; that is, leukocytes protect the body from foreign organisms, substances, and tissues. The main types of leukocytes are neutrophils, monocytes, eosinophils, basophils, and lymphocytes. All of these cells are produced in the bone marrow. However, lymphocytes may be produced in additional sites. Each of these types of leukocytes has different functions, and each behaves as a related but different system.34 Neutrophils and monocytes, the most mobile and active phagocytic leukocytes, are capable of breaking down various proteins and lipids such as those in bacterial cell membranes. The function of eosinophils is uncertain, although they are believed to detoxify foreign proteins that enter the body through the lungs or intestinal tract. The function of basophils also is not clearly understood, but the cells themselves are known to contain heparin, histamine, and serotonin. Basophils are believed to cause increased blood flow to injured tissues while preventing excessive intravascular clotting. Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology Lymphocytes play an important role in immunity and may be divided into two main categories, B lymphocytes and T lymphocytes. B lymphocytes are responsible for humoral immunity and antibody production. It is B lymphocytes that ultimately develop into the antibody-producing plasma cells (see Fig. 1–2). T lymphocytes are responsible for cellular immunity and they interact directly with the antigen.35,36 Lymphocytes and related studies are discussed in greater detail in Chapter 3. Note that leukocytes perform their functions outside the vascular bed. Thus, WBCs are merely in transit while in the blood. Because of the many leukocyte functions, alterations in the number and types of cells may be indicative of numerous pathophysiologic problems. WHITE BLOOD CELL COUNT The WBC count determines the number of leukocytes per cubic millimeter of whole blood. The counting is performed very rapidly by electronic devices. The WBC may be performed as part of a CBC, alone, or with differential WBC count. An elevated WBC count is termed leukocytosis; a decreased count, leukopenia. In addition to the normal physiological variations in WBC count, many pathological problems may result in an abnormal WBC count (see Table 1–2). If the WBC count is low, a buffy coat smear can be performed to identify leukemia or solid tumor cells in the blood. An alteration in total WBC count indicates the degree of response to a pathological process but is not specifically diagnostic for any one disorder. A more complete evaluation is obtained through the differential WBC count. INDICATIONS FOR A WHITE BLOOD CELL COUNT Routine screening as part of a CBC Suspected inflammatory or infectious process (see Table 1–2) and Tests of Hematopoietic Function 33 Suspected leukemia, autoimmune disorder, or allergy Suspected bone marrow depression Monitoring response to stress, malnutrition, and therapy for infectious or malignant processes NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. Because of the normal diurnal variation of WBC levels, it is important to note the time when the sample was obtained. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Abnormal test results: Provide support when diagnostic findings are revealed, especially if malignancy is a possibility or is confirmed. Reinforce information given by the physician, and answer questions or direct them to the appropriate professionals. Abnormal values: Note and report signs and symptoms of infection or inflammation associated with an increased count (temperature, chills), including those reflective of the site affected (pain, edema, redness, drainage). Carry out appropriate standard precautions to prevent spread to other sites. Collect a specimen for culture and sensitivities. Administer ordered antipyretic and antibiotic therapy to treat infec- Reference Values The normal range of WBCs for adults is 5,000 to 10,000. Variations in the WBC count across the life cycle are shown in Table 1–4 . Abnormal results may be classified by degree of severity as indicated. Elevations Decreases Conventional Units SI Units Conventional Units SI Units Slight 11,000–20,000 11.0–20.0 109 L 3000–4500 3.4–4.5 109 L Moderate 20,000–30,000 20.0–30.0 109 L 1500–3000 1.5–3.0 109 L 50,000 50.0 109 L Severe 1500 1.5 109 L Copyright © 2003 F.A. Davis Company 34 SECTION I—Laboratory Tests tion. Administer chemotherapeutic agents for malignancy identified and monitored by WBC and differential counts. Note and report decreased count and carry out reverse isolation procedures to protect immunosuppressed client from infection. Critical values: Notify the physician at once if a new client has a WBC count of less than 2,000 per microliter or greater than 50,000 per microliter or if a client whose WBC count was less than 4,000 per microliter has a change of 1,000 per microliter. Take precautions to protect the client from infection. Prepare for further diagnostic procedures to identify the cause or source of increases or decreases in the count. DIFFERENTIAL WHITE BLOOD CELL COUNT The differential WBC count indicates the percentage of each type of leukocyte present per cubic millime- TABLE 1–11 • Causes of Altered White Blood Cell Differential by Cell Type Cell Type Neutrophils ter of whole blood. If necessary for further evaluation of results, the percentage for each cell type can be multiplied by the total WBC count to obtain the absolute number of each cell type present. Causes of alterations in the differential WBC count according to type of leukocyte are presented in Table 1–11. An increase in immature neutrophils (i.e., bands, stabs) indicates the body’s attempt to produce more neutrophils in response to the pathological process. A decreased neutrophil count is fairly common in children during viral infections. An increase in bands is sometimes referred to as a “shift to the left.” This terminology derives from the following traditional headings used on laboratory slips to report WBC differential results: Bands, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes. In contrast, the meaning of a “shift to the right” is less well defined. This may refer to an increase in neutrophils or other granulocytes or to an increase in lymphocytes or monocytes. Increased Levels Stress (allergies, exercise, childbirth, surgery) Acute hemorrhage or hemolysis Bone marrow depression (viruses, toxic chemicals, overwhelming infection, Felty’s syndrome, Gaucher’s disease, myelofibrosis, hypersplenism, pernicious anemia, radiation) Infectious diseases Anorexia nervosa, starvation, malnutrition Inflammatory disorders (rheumatic fever, gout, rheumatoid arthritis, drug reactions, vasculitis, myositis) Folic acid deficiency Tissue necrosis (burns, crushing injuries, abscesses Acromegaly Malignancies Addison’s disease Metabolic disorders (uremia, eclampsia, diabetic ketoacidosis, thyroid crisis, Cushing’s syndrome) Thyrotoxicosis Drugs (epinephrine, histamine, lithium, heavy metals, heparin, digitalis, ACTH) Disseminated lupus erythematosus Toxins and venoms (turpentine, benzene) Drugs (alcohol, phenylbutazone [Butazolidin], phenacetin, penicillin, chloramphenicol, streptomycin, phenytoin [Dilantin], mephenytoin [Mesantoin], phenacemide [Phenurone], tripelennamine [PBZ], aminophylline, quinine, chlorpromazine, barbiturates, dinitrophenols, sulfonamides, antineoplastics) Extremes of temperature Leukemia (myelocytic) Bands (immature neutrophils) Decreased Levels Infections Vitamin B12 deficiency Anaphylaxis None, as bands should be absent or present only in small numbers (Continued ) Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology TABLE 1–11 • and Tests of Hematopoietic Function 35 Causes of Altered White Blood Cell Differential by Cell Type Cell Type Increased Levels Decreased Levels Antineoplastic drugs Any condition that causes neutrophilia Leukemia Basophils None, as normal value is 0–1% Hodgkin’s disease Polycythemia vera Ulcerative colitis Nephrosis Chronic hypersensitivity states Eosinophils Sickle cell disease Disseminated lupus erythematosus Asthma Acromegaly Chorea Elevated steroid levels Hypersensitivity reactions Stress Parasitic infestations Infectious mononucleosis Autoimmune diseases Hypersplenism Addison’s disease Cushing’s syndrome Malignancies Congestive heart failure Sarcoidosis Hyperplastic anemia Chronic inflammatory diseases and dermatoses Hormones (ACTH, thyroxine, epinephrine) Leprosy Hodgkin’s disease Polycythemias Ulcerative colitis Autoallergies Pernicious anemia Splenectomy (Continued on following page) Reference Values The normal percentage of each WBC type in adults is shown next. Variations across the life cycle are listed in Table 1–4. Conventional Units Bands SI Units 3–8% 0.03–0.08 Neutrophils 54–75% 0.54–0.75 Eosinophils 1–4% 0.01–0.04 Basophils 0–1% 0–0.01 2–8% 0.02–0.08 25–40% 0.25–0.40 Monocytes Lymphocytes INDICATIONS FOR DIFFERENTIAL WHITE BLOOD CELL COUNT Routine screening as part of a CBC Abnormal total WBC count to determine the source of the elevation Confirmation of the presence of various disorders associated with increases and decreases in the several types of WBCs (see Table 1–11) Monitoring of response to treatment for acute infections, with a therapeutic response indicated by a decreasing number of bands and a stabilizing number of neutrophils Monitoring of physiological responses to chemotherapy Copyright © 2003 F.A. Davis Company 36 SECTION I—Laboratory TABLE 1–11 • Tests Causes of Altered White Blood Cell Differential by Cell Type (Continued) Cell Type Monocytes Increased Levels Infections (bacterial, viral, mycotic, rickettsial, amebic) Decreased Levels Not characteristic of specific disorders Cirrhosis Collagen diseases Ulcerative colitis Regional enteritis Gaucher’s disease Hodgkin’s disease Lymphomas Carcinomas Monocytic leukemia Radiation Polycythemia vera Sarcoidosis Weil’s disease Systemic lupus erythematosus Hemolytic anemias Thrombocytopenic purpura Lymphocytes Infections (bacterial, viral) Immune deficiency diseases Lymphosarcoma Hodgkin’s disease Ulcerative colitis Rheumatic fever Banti’s disease Aplastic anemia Felty’s syndrome Bone marrow failure Myeloma Gaucher’s disease Lymphomas Hemolytic disease of the newborn Addison’s disease Hypersplenism Thyrotoxicosis Thrombocytopenic purpura Malnutrition Transfusion reaction Rickets Massive transfusions Waldenström’s macroglobulinemia Pernicious anemia Lymphocytic leukemia Septicemia Pneumonia Burns Radiation Toxic chemicals (benzene, bismuth, DDT) Antineoplastic agents Adrenal corticosteroids (high doses) Copyright © 2003 F.A. Davis Company CHAPTER 1—Hematology Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). WHITE BLOOD CELL ENZYMES LEUKOCYTE ALKALINE PHOSPHATASE WBCs in peripheral blood samples retain enzymatic activity and can alter substrates added in the labora- • 37 tory. The presence of enzymatic activity is useful in studying cells that are so morphologically abnormal on stained smear that it is difficult to determine their cell line of origin (see Fig. 1–2). The two most common WBC enzyme tests are the test for leukocyte alkaline phosphatase, an enzyme found in neutrophils, and the periodic acid–Schiff stain, which tests for enzymes found in granulocytes and erythrocytes. Both tests are used to diagnose hematologic disorders, especially leukemias. Specific causes of alterations in WBC enzymes are presented in Table 1–12. Another WBC enzyme test, tartrateresistant acid phosphatase (TRAP), is performed to diagnose hairy cell leukemia, because this enzyme activity is present in the lymphocytic cells of this type of leukemia. Additional details for each test are briefly discussed subsequently. NURSING CARE BEFORE THE PROCEDURE TABLE 1–12 and Tests of Hematopoietic Function Leukocyte alkaline phosphatase (LAP) is an enzyme Causes of Alterations in White Blood Cell Enzymes Causes of Alterations Enzyme Leukocyte alkaline phosphatase (LAP) Elevated Levels Decreased Levels Chronic myelocytic leukemia Acute myelocytic leukemia Polycythemia vera Acute monocytic leukemia Myelofibrosis Chronic granulocytic leukemia Leukemoid reactions Anemias (aplastic, pernicious) Oral contraceptives Thrombocytopenia Pregnancy Infectious mononucleosis Adrenocorticotropic hormone (ACTH) excess Paroxysmal nocturnal hemoglobinuria Cushing’s syndrome Hereditary hypophosphatasia Down syndrome Collagen diseases Multiple myeloma Lymphomas Positive Periodic acid–Schiff (PAS) stain Negative Acute granulocytic leukemia Early granulocyte precursors Acute lymphoblastic leukemia Severe iron-deficiency anemia Erythroleukemia Normal erythrocyte precursors Amyloidosis Mature RBCs Thalassemia Lymphomas Copyright © 2003 F.A. Davis Company 38 SECTION I—Laboratory Tests Reference Values Leukocyte alkaline phosphatase 13–130 U Periodic acid–Schiff stain Granulocytes—positive Agranulocytes—negative Granulocytic precursors—negative Erythrocytes—negative Erythrocytic precursors—negative Tartrate-resistant acid phosphatase found in neutrophils. This enzyme is completely independent of serum alkaline phosphatase, which reflects osteoblastic activity and hepatic function. The LAP content of neutrophils increases as the cells mature; therefore, the LAP study is useful in assessing cellular maturation and in evaluating departures from normal differentiation. The LAP study is used to distinguish among various hematologic disorders. For example, LAP increases in polycythemia vera, myelofibrosis, and leukemoid reactions to infections, but decreases in chronic granulocytic leukemia. Because all of these conditions have increased numbers of immature circulating neutrophils, LAP scores can be helpful in differentiating among them. PERIODIC ACID–SCHIFF STAIN In the periodic acid–Schiff (PAS) stain, compounds that can be oxidized to aldehydes are localized by brilliant fuschia staining. Many elements in many tissues are PAS-positive, but in blood cells the PASpositive material of diagnostic importance is cytoplasmic glycogen. Early granulocytic precursors and normal erythrocytic precursors are PAS-negative. Mature RBCs remain PAS-negative, but granulocytes acquire increasing PAS positivity as they mature.37 INDICATIONS FOR WHITE BLOOD CELL ENZYMES STUDY Identification of morphologically abnormal WBCs on stained smear Suspected leukemia or other hematologic disorders (see Table 1–12, p. 37) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A capillary sample is generally preferred for these Activity absent tests. The sample is spread on a slide, fixed, and stained. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample (see Appendix I). REFERENCES 1. Porth, CM: Pathophysiology: Concepts of Altered States, ed 5. JB Lippincott, Philadelphia, 1998, p 113. 2. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 21. 3. Ibid, p 21. 4. Ibid, p 21. 5. Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia,1996, p 2. 6. Price, S, and Wilson, L: Pathophysiology, ed 3. McGraw-Hill, New York, 1986, p 180. 7. Porth, op cit, p 114. 8. Sacher and McPherson, op cit, p 30. 9. Fischbach, FT: A Manual of Laboratory and Diagnostic Tests, ed 4. JB Lippincott, Philadelphia, 1992, pp 89–91. 10. Hillman and Finch, op cit, pp 4–5. 11. Sacher and McPherson, op cit, p 32. 12. Hillman and Finch, op cit, pp 6–7. 13. Sacher and McPherson, op cit, p 32. 14. Ibid, p 41. 15. Ibid, p 41. 16. Ibid, p 43. 17. Ibid, p 32. 18. Hillman and Finch, op cit, pp 95–96. 19. Fischbach, op cit, p 88. 20. Hillman and Finch, op cit, p 42. 21. Sacher and McPherson, op cit, p 45. 22. Hillman and Finch, op cit, p 12. 23. Fischbach, op cit, p 43. 24. Sacher and McPherson, op cit, p 46. 25. Hillman and Finch, op cit, p 43. 26. Hole, JW: Human Anatomy and Physiology, ed 4. Wm C Brown, Dubuque, Iowa, p 603. 27. Hillman and Finch, op cit, p 43. 28. Sacher and McPherson, op cit, p 44. 29. Hillman and Finch, op cit, pp 10–11. 30. Ibid, pp 87, 110. 31. Fischbach, op cit, p 82. 32. Sacher and McPherson, op cit, pp 99–100. 33. Ibid, pp 67–68. 34. Boggs, DR, and Winkelstein, A: White Cell Manual, ed 4. FA Davis, Philadelphia, 1983, p 1. 35. Hole, op cit, pp 625–627. 36. Boggs and Winkelstein, op cit, pp 63–65. 37. Sacher and McPherson, op cit, pp 70–71. Copyright © 2003 F.A. Davis Company CHAPTER Hemostasis and Tests of Hemostatic Functions TESTS COVERED Platelet Count, 42 Bleeding Time, 44 Platelet Aggregation Test, 46 Clot Retraction Test, 47 Rumple-Leeds Capillary Fragility Test (Tourniquet Test), 48 Prothrombin Time, 49 Partial Thromboplastin Time/Activated Partial Thromboplastin Time, 51 Whole Blood Clotting Time (Coagulation Time, Lee-White Coagulation Time), 52 Thrombin Clotting Time, 53 Prothrombin Consumption Time, 54 Factor Assays, 55 Plasma Fibrinogen, 57 Fibrin Split Products, 58 Euglobulin Lysis Time, 58 INTRODUCTION Hemostasis is the collective term for all the mechanisms the body uses to protect itself from blood loss. In other words, failure of hemostasis leads to hemorrhage. Hemostatic mechanisms are organized into three categories: (1) vascular activity, (2) platelet function, and (3) coagulation. VASCULAR ACTIVITY Vascular activity consists of constriction of muscles within the walls of the blood vessels in response to vascular damage. This vasoconstriction narrows the path through which the blood flows and may sometimes entirely halt blood flow. The vascular phase of hemostasis affects only arterioles and their dependent capillaries; large vessels cannot constrict sufficiently to prevent blood loss. Even in small vessels, vasoconstriction provides only a brief hemostasis. PLATELET FUNCTION Platelets serve two main functions: (1) to protect intact blood vessels from endothelial damage provoked by the countless microtraumas of day-today existence and (2) to initiate repair through the formation of platelet plugs when blood vessel walls are damaged. When overt trauma or microtrauma damages blood vessels, platelets adhere to the altered surface. Adherence requires the presence of ionized calcium (coagulation factor IV), fibrinogen (coagulation factor I), and a protein associated with coagulation factor VIII, called von Willebrand’s factor (vWF). The process of adherence involves reversible changes in platelet shape and, usually, the release of adenosine diphosphate (ADP), adenosine triphosphate (ATP), calcium, and serotonin. With a strong enough stimulus, the next phase of platelet activity, platelet aggregation, occurs and results in the formation of a loose plug in the damaged endothelium. The platelet plug aids in controlling bleeding until a blood clot has had time to form.1 39 Copyright © 2003 F.A. Davis Company 40 SECTION I—Laboratory Tests Platelets generate prostaglandins that ultimately promote platelet adherence, whereas the endothelial cells lining the blood vessels produce a different prostaglandin that inhibits platelet aggregation. Ingestion of aspirin inhibits the actions of the prostaglandins released by platelets, an effect that may persist for many days after a person takes even a small amount of aspirin. Aspirin also may affect the actions of the prostaglandins produced by endothelial cells, but not to the extent that it affects platelet prostaglandins.2 Thus, the net effect of aspirin is to inhibit hemostasis. Thrombin, which is generated by the coagulation sequence (see the next section), independently promotes the release of substances from the platelets. Release of platelet factor 3 enhances coagulation mechanisms, thereby increasing thrombin generation. Platelet factor 4, also released by platelets, reinforces the interactions between coagulation and platelet aggregation by neutralizing the naturally generated anticoagulant, endogenous heparin.3 COAGULATION Coagulation is a complex process by which plasma proteins interact to form a stable fibrin gel.4 The fibrin strands thus formed create a meshwork that cements blood components together, a process known as syneresis. Ultimately, a blood clot is formed.5,6 Normal coagulation depends on the presence of all clotting factors and follows specific sequences known as pathways or cascades. At least 30 substances are believed to be involved in the clotting process. The most significant ones are shown in Table 2–1. Note that clotting factors are now designated by Roman numerals. The “a” indicates an activated clotting factor.7 There is no factor VI because that number was originally assigned to what is now known to be activated factor V.8 Each of the clotting factors is involved at a specific step in the coagulation process, with one clotting factor leading to activation of the next factor in the sequence. Three major clotting sequences have been identified: (1) the intrinsic pathway, (2) the extrinsic pathway, and (3) the common final pathway. The intrinsic pathway is activated when blood comes in contact with the injured vessel wall; the extrinsic pathway is activated when blood is exposed to damaged tissues. Both pathways are needed for normal hemostasis, and both lead to the common final pathway.9 A schematic representation of the intrinsic, extrinsic, and common pathways is shown in Figure 2–1. TABLE 2–1 • Clotting Factors I Fibrinogen Ia Fibrin II Prothrombin IIa Thrombin III Thromboplastin, tissue thromboplastin IV Calcium, ionized calcium V Accelerator globulin (AcG), proaccelerin, labile factor VII Proconvertin, autoprothrombin I, serum prothrombin conversion accelerator (SPCA) VIIa Convertin VIII Antihemophilic factor (AHF), antihemophilic globulin (AHG) IX Christmas factor, antihemophilic factor B, plasma thromboplastin component (PTC), autoprothrombin II X Stuart factor, Stuart-Prower factor, autoprothrombin III XI Plasma thromboplastin antecedent (PTA) XII Hageman factor XIII Fibrin-stabilizing factor The common final pathway is initiated with the activation of factor X. Factors X and V, along with platelet phospholipid and calcium, combine to form prothrombin activator, which converts prothrombin to thrombin. Thrombin subsequently converts fibrinogen to fibrin gel. Thrombin also enhances platelet release reactions, augments the activation of factors V and VIII, and activates factor XIII.10 Stable (insoluble) fibrin is formed in the presence of activated factor XIII. Calcium plays an important role throughout the coagulation process. It is necessary for the activation of factors VII, IX, X, and XI; for the conversion of prothrombin (factor II) to thrombin; and for the formation of fibrin. However, hypocalcemia does not usually cause bleeding difficulties because cardiac arrest occurs before levels are low enough to precipitate abnormal hemostasis. Citrate, oxalate, and ethylenediaminetetra-acetic acid (EDTA) are anticoagulants because they bind calcium and prevent it from participating in the clotting process. Any one of these substances may be added to the vacuum tubes used to collect peripheral blood Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis and Tests of Hemostatic Functions 41 Image/Text rights unavailable samples when an uncoagulated specimen is needed (see Appendix I, Table A–1).11 ANTAGONISTS TO HEMOSTASIS Both platelet activation and coagulation are selfperpetuating processes that could potentially continue until an injured vessel is completely occluded. Coagulation inhibitors are present to prevent excessive clotting and to dissolve the clot as tissue repair occurs. Maintaining adequate blood flow aids in diluting and removing clotting factors and in dispersing aggregated platelets. Partially activated coagulation factors are carried to the liver and the reticuloendothelial system, where they are degraded.12 Two specific anticoagulation mechanisms also help to prevent excessive clotting: (1) the fibrinolytic system and (2) the antithrombin system. In the fibrinolytic system, fibrin strands are broken down into progressively smaller fragments by a proteolytic enzyme, plasmin. Although plasmin does not circulate in active form, its precursor, plas- minogen, does. Plasminogen is converted into plasmin by several plasminogen activators, among them factor XII, urokinase, and streptokinase. Once activated, plasmin digests fibrin, splits fibrinogen into peptide fragments (fibrin split products [FSP]), and degrades factors V, VIII, and XIII. In addition, the FSP interfere with platelet aggregation, reduce prothrombin, and interfere with conversion of soluble fibrin to insoluble fibrin. Plasma also contains agents that neutralize plasmin itself. Among these are antiplasmin and 1-antitrypsin. A balance between proplasmin and antiplasmin substances aids in maintaining normal coagulation.13 The antithrombin system protects the body from excessive clotting by neutralizing the clotting capability of thrombin.14 Although various substances inhibit thrombin, the most important one is antithrombin III (AT III), a substance that abolishes the activity of thrombin (activated factor II); activated factors X, XI, and XII; and plasmin. Another name for AT III is heparin cofactor. Heparin augments by approximately 100 times the affinity of AT III and the activated clotting factors on which it Copyright © 2003 F.A. Davis Company 42 SECTION I—Laboratory Tests acts. A deficiency of AT III, which can be congenital or acquired, makes an individual prone to excessive clotting. Platelet factor 4, which is released when platelets are broken down, inhibits AT III activity.15 • Overview of Causes of Altered Platelet Function TABLE 2–2 Increased Function Decreased Function PLATELET STUDIES Trauma Circulating platelets (thrombocytes) are anuclear, cytoplasmic disks that bud off from megakaryocytes, large multinucleated cells found in the bone marrow16,17 (see Fig. 1–2). Platelets survive in the circulation for about 10 days. Regulation of platelet production is ascribed to thrombopoietin by analogy to erythropoietin (see Chapter 1), although no single substance has been specifically identified. With pronounced hemostatic stress or marrow stimulation, platelet production can increase to seven to eight times that of normal production. Newly generated platelets are larger and have greater hemostatic capacity than mature circulating platelets.18 Two thirds of the total number of platelets are in the systemic circulation, and the remaining third exists as a pool of platelets in the spleen. The pool exchanges freely with the general circulation.19 The spleen also aids in removing old or damaged platelets from the circulation. In disorders involving exaggerated splenic activity (hypersplenism), 90 percent of the body’s platelets may be trapped in the enlarged spleen, and the client is predisposed to excessive bleeding. Hypersplenism is seen in certain acute infections (e.g., infectious mononucleosis, miliary tuberculosis), connective tissue diseases (e.g., rheumatoid arthritis, lupus erythematosus), myeloproliferative diseases (e.g., leukemias, lymphomas, hemolytic anemias), and chronic liver diseases (e.g., cirrhosis).20 The functions of platelets are discussed in the introduction to this chapter. In general, individuals with too few platelets or with platelets that function poorly experience numerous pinpoint-sized hemorrhages (petechiae) and multiple small, superficial bruises (ecchymoses). Frequently, there is generalized oozing from mucosal surfaces and from venipuncture sites or other small, localized injuries. Large, deep hematomas and bleeding into joints are not characteristic of platelet deficiency (thrombocytopenia).21 Platelet studies involve evaluating the number and function of circulating platelets. Platelet numbers are assessed by the platelet count (see the next section). Disorders of platelet function (thrombopathies) are less common than disorders of platelet number. An overview of the causes of altered platelet function is provided in Table 2–2. Surgery Uremia Fractures Myeloproliferative disorders Strenuous exercise Dysproteinemias Severe liver disease Glanzmann’s thrombasthenia Pregnancy Bernard-Soulier syndrome (hereditary giant platelet syndrome) Idiopathic thrombocytopenic purpura Infectious mononucleosis von Willebrand’s disease Drugs such as aspirin and other anti-inflammatory agents, antihistamines, antidepressants, alcohol, methylxanthines PLATELET COUNT Platelets may be counted manually or with electronic counting devices. Although larger numbers of platelets are capable of being examined with electronic counting, the procedure is subject to error if (1) the white blood cell (WBC) count is greater than 10,000 cells per cubic millimeter, (2) there is severe red blood cell fragmentation, (3) the diluting fluid contains extraneous particles, (4) the plasma sample settles too long during processing, or (5) platelets adhere to one another. Causes of increased numbers of platelets (thrombocytosis, thrombocythemia) and decreased numbers of platelets (thrombocytopenia) are presented in Table 2–3. Mean platelet volume can also be determined by the electronic automated method. The test reveals the size of platelets important in the diagnosis of disorders affecting the hematologic system. An increased volume of platelets that are larger than normal in diameter is found in lupus erythematosus, thrombocytopenic purpura, B12-deficiency anemia, hyperthyroidism, and myelogenic and other myeloproliferative diseases. A decreased volume of the larger sized platelets is found in Wiskott-Aldrich syndrome.22 Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis TABLE 2–3 • and Tests of Hemostatic Functions 43 Causes of Altered Platelet Levels Decreased Levels (Thrombocytopenia) Increased Levels (Thrombocytosis) Decreased Production Increased Destruction Leukemias (chronic) Vitamin B12/folic acid deficiencies Idiopathic thrombocytopenic purpura Polycythemia vera Radiation Splenomegaly caused by liver disease Anemias (posthemorrhagic and iron-deficiency) Viral infections Lymphomas Splenectomy Leukemias (acute) Hemolytic anemias Tuberculosis and other acute infections Histiocytosis Rocky Mountain spotted fever Hemorrhage Bone marrow malignancies Sarcoidosis Carcinomatosis Fanconi’s syndrome Meningococcemia Trauma Wiskott-Aldrich syndrome Antibody/HLA-antigen reactions Surgery Uremia Hemolytic disease of the newborn Chronic heart disease Drugs such as anticancer drugs, anticonvulsants, alcohol, carbamates, chloramphenicol, chlorothiazides, isoniazid, pyrazolones, streptomycin, sulfonamides, sulfonylureas Congenital infections (cytomegalovirus [CMV], herpes, syphilis, toxoplasmosis) Cirrhosis Chronic pancreatitis Childbirth Drugs such as epinephrine Disseminated intravascular coagulation (DIC) Immune complex formation Chronic cor pulmonale Miliary tuberculosis Burns Drugs and chemicals such as aspirin, benzenes, DDT, digitoxin, gold salts, heparin, quinidine, quinine, thiazides Reference Values Values vary slightly across the life cycle, with lower platelet counts seen in newborns (see Table 1–4). 150,000 to 450,000 per cubic millimeter (average 250,000 per cubic millimeter) Mean platelet volume 25 m diameter Critical values: 20,000 U/L or 1,000,000 U/L INTERFERING FACTORS Altered test results may occur if: The WBC count is greater than 100,000 per cubic millimeter. There is severe red blood cell fragmentation. The fluid used to dilute the sample contains extraneous particles. The plasma sample settles too long during processing. Platelets adhere to one another. The client is receiving drugs that alter platelet functions and numbers (see Tables 2–2 and 2–3). Traumatic venipunctures may lead to erroneous results as a result of activation of the coagulation sequence. Excessive agitation of the sample may cause the platelets to clump together and adhere to the walls of the test tube, thus altering test results. INDICATIONS FOR PLATELET COUNT Family history of bleeding disorder Copyright © 2003 F.A. Davis Company 44 SECTION I—Laboratory Tests Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia Determination of effects of diseases and drugs known to alter platelet levels (see Table 2–3) Identification of individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures, as indicated by a platelet count of approximately 50,000 to 100,000 per cubic millimeter Identification of individuals who may be prone to spontaneous bleeding, as indicated by a platelet count of less than 15,000 to 20,000 per cubic millimeter Differentiation between decreased platelet production and decreased platelet function: Platelet dysfunction is defined as a long bleeding time with a platelet count of greater than 100,000/mm3.23 NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a lavender-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a platelet deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Also, inspect the site for excessive bruising after the procedure. Abnormal increase (thrombocytosis): Note and report signs of dehydration and input and output (I&O) ratio that can contribute to venous stasis, possible thrombosis, or bleeding tendency if the coagulation process is affected. Administer ordered aspirin and antacid, and observe for bleeding tendency if prothrombin time is increased. Abnormal decrease (thrombocytopenia): Note and report petechiae, bruising, or hematoma. Administer ordered corticosteroids. Protect children from trauma, advise adults to use soft toothbrushes and electric razors, and prevent other trauma by padding side rails and avoiding intramuscular and subcutaneous injections. Assess bleeding from skin and mucous membranes (petechiae, ecchymoses, epistaxis, feces, urine, emesis, sputum). Administer platelet transfusion and assess for any allergic responses, sepsis, or hypervolemia. Critical values: Notify the physician immediately if the platelet count is less than 20,000/mL or greater than 1 million/mL. Prepare for transfusion of platelets by intravenous drip or bolus infusion. BLEEDING TIME One of the best indicators of platelet deficiency is prolonged bleeding after a controlled superficial injury; that is, capillaries subjected to a small, clean incision bleed until the defect is plugged by aggregating platelets. When platelets are inadequate in number or if their function is impaired, bleeding time is prolonged. If the platelet count falls below 10,000/mm3, bleeding time is prolonged. Prolonged bleeding time with a platelet count of greater than 100,000/mm3 indicates platelet dysfunction. Bleeding time is prolonged in von Willebrand’s disease, an inherited deficiency of vWF, a protein associated with clotting factor VIII that is necessary for normal platelet adherence. Aspirin ingestion also prevents platelet aggregation and may prolong bleeding time for as long as 5 days after a single 300-mg dose.24 Other causes of prolonged bleeding times are listed in Table 2–4. Reference Values Method Normal Values Duke 1–3 min Ivy 3–6 min Template 3–6 min Values vary according to the method used to perform the test (see the section on procedure). When the platelet count is low, bleeding time may be calculated from platelet numbers using the following formula. The result should be evaluated in relation to the normal values for the Ivy and template methods. Bleeding time 30.5 – platelet count/mm3 3850 The calculated value also may be compared with the actual results of bleeding time obtained by the Ivy and template methods. An actual bleeding time Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis TABLE 2–4 • and Tests of Hemostatic Functions 45 Causes of Prolonged Bleeding Time Drugs Diseases Alcohol Aplastic anemia Anticoagulants Bernard-Soulier syndrome (hereditary giant plate syndrome) Aspirin and other salicylates (OTC cold remedies, analgesics) Connective tissue diseases Chlorothiazides Glanzmann’s thrombasthenia High-molecular-weight dextran Hepatic cirrhosis Mithramycin Hypersplenism Streptokinase Hypothyroidism Sulfonamides Leukemias Thiazide diuretics Malignancies such as Hodgkin’s disease and multiple myeloma Disseminated intravascular coagulation (DIC) Measles Mumps Scurvy von Willebrand’s disease longer than the calculated result suggests defective platelet function in addition to reduced numbers. It is also possible to detect above-normal hemostatic capacity in cases in which active young platelets compose the entire population of circulating platelets, because young platelets have enhanced hemostatic capabilities.25 This phenomenon may be seen in disorders involving increased platelet destruction (see Table 2–3). INTERFERING FACTORS Ingestion of aspirin and aspirin-containing medications within 5 days of the test may prolong the bleeding time. Other drugs that may prolong bleeding time are listed in Table 2–4. INDICATIONS FOR BLEEDING TIME TEST Family history of bleeding disorders, especially von Willebrand’s disease (Tests of platelet adhesiveness and levels of factor VIII also are necessary to confirm the diagnosis of von Willebrand’s disease.) Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia Thrombocytopenia as indicated by platelet count Identification of individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures Determination of platelet dysfunction as indicated by a prolonged bleeding time with a platelet count of greater than 100,000 per cubic millimeter Determination of effects of diseases and drugs known to affect bleeding time (see Table 2–4) NURSING CARE BEFORE THE PROCEDURE Explain to the client: That the test will be performed by a laboratory technician and requires approximately 15 minutes The procedure, including the momentary discomfort to be expected when the skin is incised Aspirin and aspirin-containing medications should be withheld for at least 5 days before the test. Other drugs that may prolong bleeding time (see Table 2–4) should also be withheld. THE PROCEDURE The test may be performed using the Duke, Ivy, or template method. All three methods involve piercing the skin and observing the duration of bleeding time from the puncture site. Welling blood must be removed, but gently so as not to disrupt the fragile platelet plug. After the skin is pierced, oozing blood Copyright © 2003 F.A. Davis Company 46 SECTION I—Laboratory Tests is removed at 15-second intervals by touching filter paper to the drop of blood without touching the wound itself. As platelets accumulate, bleeding slows and the oozing drop of blood gets smaller. The end point occurs when there is no fluid blood left to produce a spot on the filter paper.26 The test is timed with a stopwatch. For all methods, the site to be used is cleansed with antiseptic and allowed to dry. In the Duke method, the earlobe is incised 3 mm deep with a sterile lancet. For the Ivy and template methods, the volar surface of the forearm is used. A blood pressure cuff is applied above the elbow and inflated to 40 mm Hg; the pressure is maintained throughout the test. In the Ivy method, two incisions 3 mm deep are made freehand with sterile lancets. In the template method, two incisions, each 1 mm deep and 9 mm long, are made with a standardized template. The advantage of the template method is the fact that it provides the ability to achieve a reproducible, precise incision every time. The elapsed time at the point when bleeding ceases is recorded. If bleeding persists beyond 10 minutes, the test is discontinued and a pressure dressing is applied to the puncture site(s). NURSING CARE AFTER THE PROCEDURE When the test is completed, a sterile dressing or Band-Aid is applied to the site. For persistent bleeding, ice may be applied to the site in addition to the pressure dressing. Observe the puncture site(s) every 5 minutes for bleeding. Clients with clotting factor disorders may rebleed after initial bleeding has stopped. This may occur approximately 20 to 30 minutes after the initial procedure. Check the puncture site(s) at least twice daily for infection or failure to heal. For the Ivy and template methods, assess for excessive bruising at the blood pressure cuff application site. • Drugs That Impair Platelet Aggregation TABLE 2–5 Aminophylline Phenothiazines Antihistamines Phenylbutazone Anti-inflammatory drugs, both steroids and nonsteroidal types Salicylates Sulfinpyrazone Caffeine Tricyclic antidepressants Dipyridamole of a test tube. Normally, platelet aggregates should be visible in less than 5 minutes. Platelet aggregation in response to specific inducing agents is diagnostic for specific disorders. Aspirin, other anti-inflammatory agents, and many phenothiazines markedly inhibit the aggregating effect of collagen and epinephrine but do not interfere with the direct action of added ADP. Also, conditions that depress the release-inducing effects of collagen and epinephrine and of directly added ADP affect platelet aggregation. Individuals with von Willebrand’s disease have platelets that respond normally to epinephrine, collagen, and ADP. Without vWF in their plasma, however, the platelets will not be aggregated by ristocetin.28 Other disorders that may impair platelet aggregation include Glanzmann’s thrombasthenia, BernardSoulier syndrome (hereditary giant platelet syndrome), idiopathic thrombocytopenic purpura, and infectious mononucleosis. Drugs that interfere with platelet aggregation are listed in Table 2–5. Reference Values Platelet aggregates should be visible in less than 5 minutes. PLATELET AGGREGATION TEST Platelet aggregation can be measured by bringing platelet-rich plasma into contact with known inducers of platelet aggregation. Most inducers, such as collagen, epinephrine, and thrombin, act through the effects of ADP, which is released by the platelets themselves. Adding exogenous ADP causes platelet aggregation directly. Ristocetin, an antibiotic, may also be used for this test.27 Platelet aggregation is quantified by determining whether platelet-rich plasma becomes clear as evenly suspended platelets aggregate and fall to the bottom INTERFERING FACTORS Ingestion of aspirin and other drugs known to interfere with platelet aggregation within 5 to 7 days of the test (see Table 2–5). Delay in processing the sample or excessive agitation of the sample may alter test results. INDICATIONS FOR PLATELET AGGREGATION TEST Suspected von Willebrand’s disease or other inherited platelet disorder Evaluation of platelet aggregation in clients with Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis disorders known to cause alterations (e.g., uremia, severe liver disease, myeloproliferative disorders, dysproteinemias) Therapy with drugs known to alter platelet aggregation (see Table 2–5) NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is generally recommended that the person abstain from food for 8 hours before the test and, if possible, from drugs that may impair platelet aggregation for 5 to 7 days before the test. THE PROCEDURE and Tests of Hemostatic Functions If fibrinogen levels are low, the initial clot is so fragile that the fibrin strands rupture, and red blood cells spill into serum when retraction begins. If there is excessive fibrinolysis, as often happens with reduced fibrinogen levels, the incubated tube may contain only cells and fibrin with no fibrin clot at all. Low fibrinogen levels and excessive fibrinolysis are seen in disseminated intravascular coagulation (DIC).29 The clot retraction test also can be modified to demonstrate the inhibitory effect of antiplatelet antibodies, especially those associated with drugs. Clot retraction is abolished if more than 90 percent of platelet activity is neutralized. Serum suspected of containing antibodies can be added to normal blood to see if retraction is inhibited.30 A venipuncture is performed and the sample collected in a light-blue-topped tube. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have platelet deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Also, inspect the site for excessive bruising after the procedure. Complications and precautions: Note and report drugs that alter platelet aggregation and discontinue if test results indicate prolonged aggregation. Report any abnormal test results to the physician. CLOT RETRACTION TEST When blood collected in a test tube first clots, the entire column of blood solidifies. As time passes, the clot diminishes in size. Serum (the fluid remaining after blood coagulates) is expressed, and only the red blood cells remain in the shrunken fibrin clot. Because platelets are necessary for this process, the speed and extent of clot retraction roughly reflect the adequacy of platelet function. Individuals with thrombocytopenia or platelet dysfunction, for example, have samples with scant serum and a soft, plump, poorly demarcated clot. The results of the clot retraction test should be evaluated in relation to other hematologic, platelet, and coagulation studies. If the client has a low hematocrit, for example, the clot is small and the volume of serum is great. In contrast, individuals with polycythemia or hemoconcentration have poor clot retraction because the numerous red blood cells contained in the clot separate the fibrin strands and interfere with normal retraction. 47 Reference Values A normal clot, gently separated from the side of the test tube and incubated at 98.6F (37C), shrinks to about half its original size within 1 hour. The result is a firm, cylindrical fibrin clot that contains all of the red blood cells and is sharply demarcated from the clear serum. INTERFERING FACTORS Rough handling of the sample alters clot formation. INDICATIONS FOR CLOT RETRACTION TEST Evaluation of adequacy of platelet function Evaluation of thrombocytopenia of unknown etiology Suspected antiplatelet antibodies resulting from immune disorders or drug-antibody reactions Suspected abnormalities of fibrinogen or fibrinolytic activity Monitoring of response to conditions that predispose to DIC NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and approximately 5 mL of blood is collected in a red-topped tube. The sample is promptly sent to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essen- Copyright © 2003 F.A. Davis Company 48 SECTION I—Laboratory TABLE 2–6 • Tests Causes of Positive Rumple-Leeds Capillary Fragility Test Strongly positive (grade 4) Aplastic anemia Chronic renal disease Glanzmann’s thrombasthenia Idiopathic thrombocytopenic purpura (ITP) Leukemia Thrombocytopenia caused by acute infectious disease (measles, influenza, scarlet fever) Moderately positive (grade 3) Hepatic cirrhosis Slightly positive (grade 2) Allergic and senile purpuras Decreased estrogen levels Deficiency of vitamin K, factor VII, fibrinogen, or prothrombin Dysproteinemia Polycythemia vera von Willebrand’s disease tially the same as for any study involving the collection of a peripheral blood sample. Because the client may have platelet dysfunction or deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. RUMPLE-LEEDS CAPILLARY FRAGILITY TEST (TOURNIQUET TEST) The capillary fragility test indicates the ability of capillaries to resist rupturing under pressure. Excessive capillary fragility may be caused by either abnormalities of capillary walls or thrombocytopenia. The causes of positive test results are listed in Table 2–6. The test is performed by applying a blood pressure cuff inflated to 100 mm Hg to the client’s arm for 5 minutes. The resulting petechiae in a circumscribed area are then counted. This test is unnecessary in the presence of obvious petechiae or large ecchymoses. It also should not be performed on clients known to have or suspected of having DIC. INTERFERING FACTORS Repetition of the test on the same extremity within 1 week will yield inaccurate results. INDICATIONS FOR RUMPLE-LEEDS CAPILLARY FRAGILITY TEST (TOURNIQUET TEST) History of “easy bruising” or production of Reference Values Fewer than 10 petechiae (excluding those that may have been present before the test) in a 2inch circle is considered normal. Results may also be reported according to the following scale, with grade 1 indicating a normal or negative result. Causes of positive results are listed in Table 2–6. Grade Petechiae per 2-Inch Circle 1 0–10 2 10–20 3 20–50 4 50 petechiae by the application of a tourniquet for venipuncture Verification of increased capillary fragility, although the test itself is not specific for any particular bleeding disorder (see Table 2–6) NURSING CARE BEFORE THE PROCEDURE Explain to the client: The procedure, including the degree of discomfort to be expected from the inflated blood pressure cuff Inspect the client’s forearms and select a site that is as free as possible of petechiae. Measure an area 2 inches in diameter; the site may be circled lightly with a felt-tipped marker if necessary for reference. Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis If petechiae are present in the site to be measured, note and record the number. THE PROCEDURE A blood pressure cuff is applied to the arm and inflated to 100 mm Hg. The pressure is maintained for 5 minutes. The blood pressure cuff is then removed and the petechiae counted and the number recorded. NURSING CARE AFTER THE PROCEDURE There is no specific aftercare. If the arm feels “tense” or “full,” it may be elevated for a few minutes to hasten venous drainage. Complications and precautions: Note and report tendency for easy bruising or presence of petechiae. Take measures to prevent trauma to the skin and mucous membranes if results are above the normal values. COAGULATION STUDIES Coagulation studies are performed to evaluate the components and pathways of the coagulation sequence. Innumerable tests have been devised to diagnose inherited, acquired, and iatrogenic deficiencies of coagulation. Some of these require specialized techniques or rare reagents available only in laboratories that perform many such tests. Other tests are less precisely diagnostic but more available and more readily applicable to immediate clinical situations. The tests included here are widely available. Screening tests of hemostatic function include the platelet count, bleeding time, prothrombin time, and partial thromboplastin time. When a “coagulation profile” or “coagulogram” is ordered, it includes the four screening tests plus clotting time and activated partial thromboplastin time. PROTHROMBIN TIME The prothrombin time (PT, pro time) test is used to evaluate the extrinsic pathway of the coagulation sequence. It represents the time required for a firm fibrin clot to form after tissue thromboplastin (coagulation factor III) and calcium are added to the sample. These added substances directly activate factor X, the key factor in all three coagulation pathways (see Fig. 2–1). Neither platelets nor the factors involved in the intrinsic pathway are necessary for the clot to form. To give a normal PT result, plasma must have at least 100 mg/dL of fibrinogen (normal: 150 to 400 mg/dL) and adequate levels of factors X, VII, V, and II (prothrombin). Because the test bypasses the clot- and Tests of Hemostatic Functions 49 ting factors of the intrinsic pathway, the PT cannot detect the two most common congenital coagulation disorders: (1) deficiency of factor VIII (hemophilia A, or “classic” hemophilia) and (2) deficiency of factor IX (hemophilia B, or Christmas disease). Also, thrombocytopenia does not prolong the PT. PT measurements are reported as time in seconds or as a percentage of normal activity, or both. Time in seconds indicates the length of time for the blood to clot when chemicals are added in comparison to normal blood with the same chemicals added (control value). A value that is higher than the control sample is considered to be deficient in prothrombin. Some laboratories report the results in percentages that are derived from a plotted graph based on dilutions of the control samples and the time in seconds it takes for the sample to clot; the seconds are then converted to percentages. The time then reflects the percentage of normal clotting time by comparing the client’s clotting time to its intersection point with the percentage on the graph. Usually an increase in time for clotting equals a decrease in the percentage of activity, although different laboratories can obtain different results when determining the percentages. This difference is because of the different thromboplastins used as reagents in the testing procedure. Because the variability in responsiveness to the different thromboplastins has resulted in dosing differences, a thromboplastin has been developed by the first International Reference Preparation. This reagent is used to monitor the therapeutic levels for coagulation during coumarin-type therapy. A standardization of reporting the PT assay test results developed by the World Health Organization has been adopted for this reagent. It is known as the International Normalized Ratio (INR). The INR is calculated with the use of a nomogram developed to demonstrate the relationship between the INR and the prothrombin ratios with the International Sensitivity Index range (values associated with the available thromboplastin reagents from the various companies that develop them). PT evaluation can now be based on the INR and both are reported as PT and its equivalent INR for evaluation and decisions in oral anticoagulation therapy as endorsed by the Committee on Antithrombotic Therapy of the American College of Chest Physicians, the Committee for Thrombosis and Hemostasis, and the International Committee for Standardization in Hematology. The recommended INR therapeutic range for oral anticoagulant therapy is 2.0 to 3.0 in the treatment of venous thrombosis, pulmonary embolism, and the prevention or treatment of systemic embolism. A pro time test system is now Copyright © 2003 F.A. Davis Company 50 SECTION I—Laboratory Tests Reference Values Conventional Units Newborns SI Units 12–21 sec 12–21 s Men 9.6–11.8 sec 9.6–11.8 s Women 9.5–11.3 sec 9.5–11.3 s 2.0–3.0 sec for anticoagulation, higher (3.0–4.5 sec) for recurrent systemic embolization 2.0–3.0 s 3.0–4.5 s for recurrent systemic embolization Adults INR Critical values 8–9 sec below control or 40 sec available to perform immediate measurement of PT at the bedside using a fresh whole blood sample, reagent cartridges, and a monitor that operates on rechargeable batteries. Prothrombin is a vitamin K–dependent protein produced by the liver. Thus, any disorder that impairs the liver’s ability to use vitamin K or to form proteins (e.g., the various types of cirrhosis) prolongs the PT. Anticoagulants of the coumarin family act by inhibiting hepatic synthesis of the vitamin K–dependent factors II, VII, IX, and X. A natural anticoagulant system dependent on the action of vitamin K on the proteins C and S is different from the activity of this vitamin on coagulation factors II, VII, IX, and X. Protein C acts to neutralize the activity of factors VIIIa and Va, and protein S increases the inactivation of VIIIa and Va by the protein C. Any deficiency of the various factors can alter the balance between the two proteins and result in thrombotic disorders. The tests are performed to determine their functional activity and reveal a tendency toward hypercoagulation and thrombosis or to diagnose a hereditary deficiency. Because values may vary according to the source of the substances added to the sample and the type of laboratory equipment used, the result is usually evaluated in relation to a control sample obtained from an individual with normal hemostatic function. Test results are sometimes given as a percentage of normal activity, comparing the client’s results against a curve that shows the normal clotting rate of diluted plasma. The normal value in this case is 100 percent; however, the method itself is thought to be inaccurate because dilution affects the clotting process. 8–9 s below control or 40 s INTERFERING FACTORS Numerous drugs may alter the PT results, including the following: Drugs that prolong the PT, such as coumarin derivatives, quinidine, quinine, thyroid hormones, adrenocorticotropic hormone, steroids, alcohol, phenytoin, indomethacin, and salicylates Drugs that may shorten the PT, such as barbiturates (especially chloral hydrate), oral contraceptives, and vitamin K31 Traumatic venipuncture may lead to erroneous results because of activation of the coagulation sequence. Excessive agitation of the sample may erroneously prolong the PT. A fibrinogen level of less than 100 mg/dL (SI units, 1.00 g/L) (normal: 150 to 400 mg/dL [SI units, 1.50–4.00 g/L]) may prolong the PT. INDICATIONS FOR PROTHROMBIN TIME Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia Identification of individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures Evaluation of response to anticoagulant therapy with coumarin derivatives and determination of dosage required to achieve therapeutic results Differentiation of clotting factor deficiencies of V, VII, and X, which prolong the PT, from congenital coagulation disorders such as hemophilia A (factor VIII) and hemophilia B (factor IX), which do not alter the PT Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis Monitoring of effects on hemostasis of conditions such as liver disease, protein deficiency, and fat malabsorption NURSING CARE BEFORE THE PROCEDURE In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may affect the PT result, all medications taken by the client should be noted. If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a light-blue-topped tube. Traumatic venipunctures and excessive agitation of the sample should be avoided. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. Bleeding episode: Note and report increase in PT, medications taken that affect the PT and expected test values, symptoms such as bleeding from any area (blood in sputum, feces, urine; bleeding from nose, skin), headache, increased pulse, or pain in the abdomen or back. Report changes related to administration of coumarintype medication and adjust drug dosage as ordered until desired INR is reached. Protect skin, mucous membranes, and organs from trauma (shaving, brushing teeth, suctioning, intramuscular [IM], subcutaneous [SC], and intravenous [IV] injections, falls, activities that are strenuous, straining). Test for occult blood in body secretions and excretions. Inform client to avoid drugs that potentiate the effect of coumarin-type drugs. Instruct client in importance and frequency of PT laboratory testing. Venous thrombosis: Note and report decreases in PT or other factors predisposing to formation of venous thrombi. Provide leg exercises and adequate fluid intake. Advise client to avoid crossing legs, wearing constrictive clothing, or participating in other activities that impair and Tests of Hemostatic Functions 51 circulation. Inform client of importance and frequency of PT testing. Critical values: Notify the physician immediately of an increase of greater than 40 seconds or 15 seconds above the control time. Prepare the client for administration of IM vitamin K or IV frozen plasma. Notify the physician immediately of an increase of greater than 24 seconds in individuals with a liver disease if they are experiencing hypoprothrombinemia from vitamin K deficiency. Notify the physician immediately if there is a decrease of less than 8 to 9 seconds or 11 to 12 seconds below the control time. Prepare the client for possible SC administrations of heparin. PARTIAL THROMBOPLASTIN TIME/ACTIVATED PARTIAL THROMBOPLASTIN TIME The partial thromboplastin time (PTT) test is used to evaluate the intrinsic and common pathways of the coagulation sequence. It represents the time required for a firm fibrin clot to form after phospholipid reagents similar to thromboplastin reagent are added to the specimen. Because coagulation factor VII is not required for the PTT, the test bypasses the extrinsic pathway (see Fig. 2–1). To give a normal PTT result, factors XII, XI, IX, VIII, X, V, II (prothrombin), and I (fibrinogen) must be present in the plasma. The PTT is more sensitive than the PT in detecting minor deficiencies of clotting factors because factor levels below 30 percent of normal prolong the PTT. The activated partial thromboplastin time (aPTT) is essentially the same as the PTT but is faster and more reliably reproducible. In this test, the thromboplastin reagent may be kaolin, celite, or ellagic acid, all of which more rapidly activate factor XII. It is possible to infer which factors are deficient by comparing the results of the PTT with those of the PT. A prolonged PTT with a normal PT points to a deficiency of factors XII, XI, IX, and VIII and to von Willebrand’s disease. In contrast, a normal PTT with a prolonged PT occurs only in factor VII deficiency.32 In addition to heparin therapy and coagulation factor deficiencies, the following also prolong the PTT: circulating products of fibrin and fibrinogen degradation, polycythemia, severe liver disease, vitamin K deficiency, DIC, and established therapy with coumarin anticoagulants. INTERFERING FACTORS Heparin and established therapy with coumarin derivatives alter the PTT. Copyright © 2003 F.A. Davis Company 52 SECTION I—Laboratory Tests Reference Values Newborns Time in seconds is higher up to 3 mo of age than for adults Adults PTT 30–45 sec aPTT 35–45 sec* Critical values >20 sec more than control if not receiving heparin therapy 53 sec or >2.5 times control if receiving heparin therapy * Values can vary among laboratories. Traumatic venipunctures may lead to erroneous results because of activation of the coagulation sequence. Excessive agitation of the sample may prolong the PTT. INDICATIONS FOR PTT/APTT TEST Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia Identification of individuals who may be prone to bleeding during surgical, obstetric, dental, or invasive diagnostic procedures Evaluation of responses to anticoagulant therapy with heparin or established therapy, or both, with coumarin derivatives and determination of dosage required to achieve therapeutic results Detection of congenital deficiencies in clotting factors such as hemophilia A (factor VIII) and hemophilia B (factor IX), which alter the PTT Monitoring of effects on hemostasis of conditions such as liver disease, protein deficiency, and fat malabsorption NURSING CARE BEFORE THE PROCEDURE In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a light-blue-topped tube. Traumatic venipunctures and excessive agitation of the sample should be avoided. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. Bleeding episode: Report increase in PTT or aPTT during heparin therapy; note that a therapeutic range is maintained (usually 1.5 to 2.5 times the control). Note also (1) drugs taken that can interfere with the action of heparin therapy, (2) the administration of prophylactic low-dose heparin that does not require PTT testing, and (3) symptoms such as bleeding from any area (blood in sputum, urine, feces; bleeding from nose, skin, mucous membranes). Adjust dosage according to physician order. Protect from trauma to skin, mucous membranes, organs, and joints (falls; rough handling of extremities; shaving; brushing teeth; IM, SC, and IV injections; suctioning). Test for occult blood in body secretions and excretions. Inform client to avoid drugs that affect the PTT. Provide special considerations to allay anxiety related to possible bleeding tendencies. Critical values: Notify the physician at once of an increase of greater than 20 seconds above the control if the individual is not receiving heparin therapy. If heparin therapy is administered, a PTT level of less than 53 seconds indicates an inadequate anticoagulation effect; the physician should be told immediately if a level is greater than 2.5 times the control time level. WHOLE BLOOD CLOTTING TIME (COAGULATION TIME, LEE-WHITE COAGULATION TIME) Whole blood clotting time, also known as coagulation time (CT) or Lee-White coagulation time, is the Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis oldest but least accurate of the coagulation tests. It measures the time it takes blood to clot in a test tube. Because the sensitivity of the test is low, coagulation problems of mild to moderate severity are not apparent. Heparin prolongs clotting time; therefore, the test was once used to monitor heparin therapy. PTT or aPTT is currently used to evaluate such therapy. Reference Values 4 to 8 minutes Because this test is relatively insensitive and difficult to standardize, a normal result does not rule out a coagulation defect. INTERFERING FACTORS Heparin prolongs the whole blood clotting time. Traumatic venipuncture may lead to erroneous results. INDICATIONS FOR WHOLE BLOOD CLOTTING TIME TEST Evaluation of response to heparin therapy Adequate anticoagulation is indicated by a clotting time of about 20 minutes. Signs of abnormal bleeding such as epistaxis, easy bruising, bleeding gums, hematuria, and menorrhagia Suspected congenital coagulation defect that involves the intrinsic coagulation pathway (e.g., deficiencies of factors VIII, IX, XI, and XII) NURSING CARE BEFORE THE PROCEDURE In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving heparin anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and 3 mL of blood collected in a syringe and then discarded. A new syringe, glass or plastic, is attached to the venipuncture needle, and an additional 3 mL of blood is withdrawn. Traumatic venipunctures and excessive movement of the needle in the vein must be avoided if accurate results are to be obtained. As the second sample is withdrawn, timing is begun with a stopwatch. The sample is immediately and gently transferred into three glass tubes (1 mL in each). The test tubes are placed in a water bath at and Tests of Hemostatic Functions 53 98.6F (37C) and are tilted gently every 30 seconds until a firm clot has formed in each tube. Timing is completed when all tubes contain firm clots, and the interval is recorded as the clotting time. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Also, inspect the site for excessive bleeding after the procedure. Bleeding tendency: If anticoagulant therapy is administered, note and report bleeding from any area (skin, nose, mucous membranes; blood in urine, feces; excessive menses). Note results of the coagulation factor screen for deficiencies. Protect the skin, mucous membranes, and other organs from trauma. Test for occult blood in body secretions and excretions. THROMBIN CLOTTING TIME The thrombin clotting time (TCT, plasma thrombin time) test is used to evaluate the common final pathway of the coagulation sequence. Preformed thrombin (coagulation factor IIa), usually of bovine origin, can be added to the blood sample to convert fibrinogen (factor I) directly to a fibrin clot. Because the test bypasses the intrinsic and extrinsic pathways, deficiencies in either one do not affect the TCT (see Fig. 2–1). Thrombin-induced clotting is very rapid, and the test result can be standardized to any desired normal value (usually 10 to 15 seconds). The TCT is prolonged if fibrinogen levels are below 100 mg/dL (normal: 150 to 400 mg/dL), if the fibrinogen present is functioning abnormally, or if fibrinogen inhibitors (e.g., streptokinase, urokinase) are present (see below). In all of these conditions, the PT and PTT also are prolonged.33 Reference Values 10 to 15 seconds (Values vary among laboratories.) INTERFERING FACTORS A fibrinogen level of less than 100 mg/dL (SI units, 1.00 g/L) (normal: 150 to 400 mg/dL [SI units, 1.50 to 4.00 g/L) prolongs the TCT. Copyright © 2003 F.A. Davis Company 54 SECTION I—Laboratory Tests Abnormally functioning fibrinogen prolongs the TCT. Fibrinogen inhibitors such as streptokinase and urokinase prolong the TCT. Traumatic venipunctures and excessive agitation of the sample may alter results. therapy or in those with DIC, hypoprothrombinemia, and cirrhosis. Abnormal PCT results must be evaluated in relation to coagulation studies such as PT, PTT, and factor assays, to differentiate platelet factor deficiencies from clotting factor deficiencies. INDICATIONS FOR THROMBIN CLOTTING TIME TEST Confirmation of suspected DIC as indicated by a prolonged TCT Detection of hypofibrinogenemia or defective fibrinogen Monitoring of effects of heparin or fibrinolytic therapy (e.g., with streptokinase) NURSING CARE BEFORE THE PROCEDURE In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a light-blue-topped tube. Traumatic venipunctures and excessive agitation of the sample should be avoided. Reference Values Fifteen to 20 seconds with more than 80 percent of the prothrombin consumed INTERFERING FACTORS Traumatic venipunctures and excessive agitation of the sample may alter test results. Therapy with anticoagulants may shorten the PCT. INDICATIONS FOR PROTHROMBIN CONSUMPTION TIME TEST Suspected deficiency of platelet factor 3 or of the clotting factors involved in the intrinsic coagulation pathway (i.e., factors VIII, IX, XI, and XII), as indicated by a shortened PCT Suspected DIC, as indicated by a shortened PCT Monitoring of effects on hemostasis of conditions such as liver disease and protein deficiency NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. PROTHROMBIN CONSUMPTION TIME The prothrombin consumption time (PCT, serum prothrombin time) test measures utilization of prothrombin when a blood clot forms. Normally, the formation of a clot “consumes” prothrombin by converting it to thrombin. Individuals with deficiencies in platelets, platelet factor 3, or factors involved in the intrinsic coagulation pathway (see Fig. 2–1) are not able to convert as much prothrombin to thrombin. In such cases, excess prothrombin remains in the serum after the clot is formed, thus shortening the PCT. The PCT also may be shortened in persons receiving anticoagulant NURSING CARE BEFORE THE PROCEDURE In general, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the client is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. As with other coagulation studies, traumatic venipunctures and excessive agitation of the sample should be avoided. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis FACTOR ASSAYS If the PT or PTT/aPTT is abnormal, but the nature of the factor deficiency is unknown, specific coagulation factors may be measured. Factor assays require specialized techniques not available in many laboratories. Factor assays are used to discriminate among mild, moderate, and severe deficiencies and TABLE 2–7 • and Tests of Hemostatic Functions 55 to follow the course of acquired factor inhibitors. States associated with particular factor deficiencies are presented in Table 2–7. Factors of the extrinsic (II, V, VII, X) and intrinsic (VIII, IX, XI, XII) coagulation pathways are usually measured separately. The factor XIII assay is a separate test in which a blood clot is observed for 24 hours. Clot dissolution within this time indicates States Associated with Coagulation Factor Deficiencies States Associated with Deficiency Factor Synonym(s) Congenital Acquired EXTRINSIC PATHWAY II Prothrombin Hypoprothrombinemia Vitamin K deficiency Liver disease V Accelerator globulin (AcG), proaccelerin, labile factor Parahemophilia Liver disease Acute leukemia Surgery VII Proconvertin, autoprothrombin I, serum prothrombin conversion accelerator (SPCA) Factor VII deficiency Liver disease Vitamin K deficiency Antibiotic therapy X Stuart factor, Stuart-Prower factor, autoprothrombin III Stuart factor deficiency Liver disease Vitamin K deficiency Anticoagulants Normal pregnancy Disseminated intravascular coagulation (DIC) Hemorrhagic disease of the newborn INTRINSIC PATHWAY VIII* IX Antihemophilic factor (AHF), antihemophilic globulin (AHG) Christmas factor, antihemophilic factor B, plasma thromboplastin component (PTC), autoprothrombin II Hemophilia A (classic hemophilia) Disseminated intravascular coagulation (DIC) von Willebrand’s disease Fibrinolysis Hemophilia B (Christmas disease) Liver disease Vitamin K deficiency Anticoagulants Nephrotic syndrome XI Plasma thromboplastin antecedent (PTA) Factor XI deficiency Liver disease (Continued on following page) Copyright © 2003 F.A. Davis Company 56 SECTION I—Laboratory TABLE 2–7 Tests • States Associated with Coagulation Factor Deficiencies (Continued) States Associated with Deficiency Factor Synonym(s) Congenital Acquired Vitamin K deficiency Anticoagulants Congenital heart disease XII Hageman factor Hageman trait Normal pregnancy Nephrotic syndrome COMMON PATHWAY XIII Fibrin-stabilizing factor Factor XIII deficiency Liver disease Lead poisoning Multiple myeloma Agammaglobulinemia Elevated fibrinogen levels Postoperatively * Factor VIII is increased in normal pregnancy (as is factor X) and in states of inflammation and other physiologic stress. severe factor XIII deficiency. The test for fibrinogen (factor I) is discussed later. INTERFERING FACTORS Traumatic venipunctures and excessive agitation of the sample may alter test results INDICATIONS FOR FACTOR ASSAYS Therapy with anticoagulants and other drugs known to alter hemostasis Prolonged PT or PTT of unknown etiology: If the PT is prolonged but the PTT is normal, Reference Values Conventional Units SI Units Extrinsic Pathway Factor II 70–130 mg/100 mL 0.7–1.3 U Factor V 70–130 mg/100 mL 0.7–1.3 U Factor VII 70–150 mg/100 mL 0.7–1.5 U Factor X 70–130 mg/100 mL 0.7–1.3 U Factor VIII 50–200 mg/100 mL 0.5–2.0 U Factor IX 70–130 mg/100 mL 0.7–1.3 U Factor XI 70–130 mg/100 mL 0.7–1.3 U Factor XII 30–225 mg/100 mL 0.3–2.2 U Intrinsic Pathway Common Pathway Factor XIII Dissolution of a formed clot within 24 hr Note: Normal values vary among laboratories. Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis factors of the extrinsic pathway are evaluated (i.e., factors, II, V, VII, and X). If the PTT is prolonged but the PT is normal, factors of the intrinsic pathway are evaluated (i.e., factors VIII, IX, XI, XII). Monitoring of effects of disorders and drugs known to lead to deficiencies in clotting factors (see Table 2–7, p. 55) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE For assays of the factors involved in the intrinsic and extrinsic coagulation pathways, a venipuncture is performed and the sample collected in a light-bluetopped tube. For factor XIII assays, the sample is collected in a red-topped tube. As with other coagulation studies, traumatic venipunctures and excessive agitation of the sample should be avoided. The samples should be sent to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. and Tests of Hemostatic Functions 57 fibrinogen present is then extrapolated from this value. In the immunologic technique, the degree of reactivity between the plasma sample and antifibrinogen antibodies is measured. The assumption underlying this method is that any plasma constituent that reacts with antifibrinogen antibodies is, indeed, fibrinogen. Heat-precipitation tests are based on a similar assumption that all of the material responsive to the precipitation technique is really fibrinogen.34 Reference Values 150–450 mg/dL INTERFERING FACTORS Transfusions of whole blood, plasma, or fractions within 4 weeks of the test may lead to erroneous results. Traumatic venipuncture and excessive agitation of the sample may alter test results. INDICATIONS FOR PLASMA FIBRINOGEN TEST Confirmation of suspected DIC, as indicated by decreased fibrinogen levels Evaluation of congenital or acquired dysfibrinogenemias Monitoring of hemostasis in disorders associated with low fibrinogen levels (e.g., severe liver diseases and cancer of the prostate, lung, or pancreas) Detection of elevated fibrinogen levels, which may predispose to excessive thrombosis in various situations (e.g., immune disorders of connective tissue; glomerulonephritis; oral contraceptive use; cancer of the breast, stomach, or kidney) NURSING CARE BEFORE THE PROCEDURE PLASMA FIBRINOGEN In the common final pathway, fibrinogen (factor I) is converted to fibrin by thrombin (see Fig. 2–1). Plasma fibrinogen studies are based on the fact that, in normal healthy individuals, the serum should contain no residual fibrinogen after clotting has occurred. Three different techniques can be used to perform the test: (1) standard assay (classical procedure), (2) immunologic technique, and (3) heat-precipitation tests. In the standard assay, thrombin is added to the blood sample to induce clotting. Because fibrinogen is a plasma protein, the amount of protein in the resulting clot is measured. The quantity of precursor Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a light-blue-topped tube. As with other coagulation studies, traumatic venipunctures and excessive agitation of the sample should be avoided. The sample should be sent to the laboratory immediately. Copyright © 2003 F.A. Davis Company 58 SECTION I—Laboratory Tests NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. FIBRIN SPLIT PRODUCTS After a fibrin clot has formed, the fibrinolytic system acts to prevent excessive clotting. In this system, plasmin digests fibrin. Fibrinogen also may be degraded if there is a disproportion among plasmin, fibrin, and fibrinogen. The substances that result from this degradation—fibrin split products (FSP) or fibrinogen degradation products (FDP)—interfere with normal coagulation and with formation of the hemostatic platelet plug. Normally, FSP are removed from the circulation by the liver and the reticuloendothelial system. In situations such as widespread bleeding or DIC, however, FSP are found in the serum. Tests for FSP are performed on serum using immunologic techniques. Because FSP do not coagulate, they remain in the serum after fibrinogen is removed through clot formation. Antifibrinogen antibodies are added to the serum to detect the presence of FSP. Because normal serum contains neither FSP nor fibrinogen, there should be nothing present to react with the antibodies. If a reaction occurs, FSP are present.35 Reference Values 2 to 10 mg/mL INTERFERING FACTORS Heparin, fibrinolytic drugs such as streptokinase and urokinase, and large doses of barbiturates may produce elevated levels of FSP. Traumatic venipunctures and excessive agitation of the sample may alter test results. INDICATIONS FOR FIBRIN SPLIT PRODUCTS TEST Confirmation of suspected DIC, as indicated by elevated FSP levels Evaluation of response to therapy with fibrinolytic drugs Monitoring of effects on hemostasis of trauma, extensive surgery, obstetric complications, and disorders such as liver disease NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or in a special tube provided for the FSP test by the laboratory. As with other coagulation studies, traumatic venipunctures and excessive agitation of the sample should be avoided. The sample should be sent to the laboratory promptly. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. Inspect the site for excessive bruising after the procedure. EUGLOBULIN LYSIS TIME The euglobulin lysis time test is used to document excessive fibrinolytic activity. Euglobulins are proteins that precipitate from acidified dilute plasma; these include fibrinogen, plasminogen, and plasminogen activator but very little antiplasmin activity. In euglobulins prepared from normal blood, the initial clot dissolves in 2 to 6 hours. With excessive fibrinolytic activity, a clot forms if thrombin is added to the sample. Shortened euglobulin lysis times are seen in fibrinolytic therapy with streptokinase or urokinase, prostatic cancer, severe liver disease, extensive vascular trauma or surgery, and shock. Reference Values Lysis in 2 to 6 hours INTERFERING FACTORS Decreased fibrinogen levels may lead to falsely Copyright © 2003 F.A. Davis Company CHAPTER 2—Hemostasis shortened lysis time because of the reduced amount of fibrin to be lysed.36 Traumatic venipunctures and excessive agitation of the sample may alter results. INDICATIONS FOR EUGLOBULIN LYSIS TIME TEST Suspected abnormal fibrinolytic activity as indicated by lysis of the clot within about 1 hour Differentiation of primary fibrinolysis from DIC, which usually presents with a normal euglobulin lysis time Monitoring of effects of fibrinolytic therapy on normal coagulation NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If the individual is receiving anticoagulant therapy, the time and the amount of the last dose should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a light-blue-topped tube. As with other coagulation studies, traumatic venipuncture and excessive agitation of the sample should be avoided. The sample should be sent to the laboratory promptly. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for any study involving the collection of a peripheral blood sample. Because the client may have a coagulation deficiency, maintain digital pressure directly on the puncture site for 3 to 5 minutes after the needle is withdrawn. and Tests of Hemostatic Functions 59 Inspect the site for excessive bruising after the procedure. Clot lysis: Note and report decreases in lysis level during fibrinolytic therapy. Monitor client response and effect of therapy on coagulation. REFERENCES 1. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, pp 182–183. 2. Ibid, p 185. 3. Ibid, p 185. 4. Ibid, p 190. 5. Porth, CM: Pathophysiology: Concepts of Altered Health States, ed 5. JB Lippincott, Philadelphia,1998, p 122. 6. Fischbach, FT: A Manual of Laboratory and Diagnostic Tests, ed 4. JB Lippincott, Philadelphia, 1992, p 95. 7. Ibid, p 118. 8. Porth, op cit. 9. Ibid, p 121. 10. Sacher and McPherson, op cit, pp 192–193. 11. Ibid, p 195. 12. Ibid, p 195. 13. Ibid, p 196. 14. Fischbach, op cit, p 98. 15. Sacher and McPherson, op cit, p 197. 16. Porth, op cit, p 121. 17. Sacher and McPherson, op cit, p 182. 18. Ibid, p 182. 19. Porth, op cit, p 121. 20. Porth, op cit, p 126. 21. Sacher and McPherson, op cit, p 187. 22. Fischbach, op cit, pp 125–126. 23. Porth, op cit, p 126. 24. Sacher and McPherson, op cit, p 190. 25. Ibid, p 190. 26. Ibid, p 190. 27. Ibid, pp 188–189. 28. Ibid, p 189. 29. Ibid, p 187. 30. Ibid, pp 187–188. 31. Ibid, p 193. 32. Ibid, p 201. 33. Ibid, p 200. 34. Ibid, p 200. 35. Ibid, pp 139–140. 36. Ibid, p 203. Copyright © 2003 F.A. Davis Company CHAPTER Immunology and Immunologic Testing TESTS COVERED T- and B-Lymphocyte Assays, 62 Immunoblast Transformation Tests, 66 Immunoglobulin Assays, 68 Serum Complement Assays, 71 Immune Complex Assays, 73 Radioallergosorbent Test for IgE, 73 Autoantibody Tests, 74 Fungal Infection Antibody Tests, 78 Staphylococcal Tests, 80 Streptococcal Tests, 81 Febrile/Cold Agglutinin Tests, 82 Fluorescent Treponemal AntibodyAbsorption Test, 83 INTRODUCTION Venereal Disease Research Laboratory and Rapid Plasma Reagin Tests, 84 Viral Infection Antibody Tests, 85 Infectious Mononucleosis Tests, 85 Hepatitis Tests, 87 Acquired Immunodeficiency Syndrome Tests, 88 Serum -Fetoprotein Test, 90 Carcinoembryonic Antigen Test, 92 CA 15-3, CA 19-9, CA 50, and CA 125 Antigen Tests, 93 The immune system protects the body from invasion by foreign elements ranging from microorganisms and pollens to transplanted organs and subtly altered autologous proteins. An antigen is any substance that elicits an immune response in an immunocompetent host to whom that substance is foreign. The cells responsible for immune reactivity are lymphocytes and macrophages. The primary function of the lymphocytes is to react with antigens and thus initiate immune responses. There are two main categories of immune response: (1) the cell-mediated response, produced by locally active T lymphocytes present at the same time and place as the specific antigen, and (2) the humoral response, the manufacture by B lymphocytes of antibody proteins that enter body fluids for widespread distribution throughout the body.1 The immune system also removes damaged or worn-out cells and destroys abnormal cells as they develop in the body. The cells responsible for these functions are the macrophages, which engulf particulate debris (phagocytosis) and also secrete a vast array of enzymes, enzyme inhibitors, oxidizing agents, chemotactic agents, bioactive lipids (prostaglandins and related substances), complement components, and products that stimulate or inhibit multiplication of other cells. These phagocytic and secretory activities help mediate responses to immune stimulation. Macrophages also are critically important in the induction of immunity. Only after macrophages process antigen and present it to lymphocytes can immunologic reactivity develop. 60 Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology and Immunologic Testing 61 Laboratory tests can demonstrate with remarkable sensitivity many of the body’s immune activities. In general, quantification of cellular components, the presence and activities of antibodies and antigens, and measurement of biologically active secretions constitute the laboratory tests of immune functions. TESTS OF LYMPHOCYTE FUNCTIONS Lymphocytes, the second most numerous of the several types of white cells in the peripheral blood (see Table 1–4), are essential components of the immune system. Diseases affecting lymphocytes frequently manifest as an inability to protect the individual against environmental pathogens (immune deficiency disorders) or as the development of immune reactions to the individual’s own cells.2 The lymphocytes in the circulation represent only a small fraction of the total body pool of these cells. The majority are located in the spleen, lymph nodes, and other organized lymphatic tissues. The lymphocytes in the blood are able to enter and leave the circulation freely. Thus, the movement of cells from one area or compartment to another is continuous. Despite this process, the number of lymphocytes in the blood and tissues is kept quite constant. Lymphocytes have been divided into two major categories based on their immunologic activity: T lymphocytes and B lymphocytes. There also is a third group of lymphocytes that lack the characteristics of either T or B cells; they are called null cells.3 T lymphocytes are primarily responsible for cellmediated immunity, which requires direct cell contact between the antigen and the lymphocyte. This immune reaction occurs at the local site and generally develops slowly. Examples of cell-mediated immune responses include reactions against intracellular pathogens such as bacteria, viruses, fungi, and protozoa; positive tuberculin skin test results; contact dermatitis; transplant rejection (acute and chronic reactions); and tumor immunity. As with other blood cells, T lymphocytes develop from stem cells (see Fig. 1–2) and then migrate to the thymus, where they proliferate and mature. Thymopoiesis is, however, an ineffective process, and many T lymphocytes die either within the thymus or shortly after leaving it. Only a small portion of the T lymphocytes reaches the peripheral tissues as mature T cells capable of effecting cell-mediated immunity.4 Note that the thymus functions primarily during fetal life. The peripheral T-lymphoid system is fully developed at birth and normally does not require a constant input of new cells for maintenance after birth. Thus, it is possible to surgically remove the thymus (e.g., as is done to treat myasthenia gravis) without impairing the individual’s cell-mediated immune system. In contrast, failure of the thymus to develop during fetal life leads to a severe defect in cellular immunity (Di George’s syndrome), usually resulting in death during infancy as a consequence of repeated infections.5 Two subsets of T lymphocytes have been identified: helper T cells and suppressor T cells. Helper T cells promote the proliferation of T lymphocytes, stimulate B-lymphocyte reactivity, and activate macrophages, thereby increasing their bactericidal and cytotoxic functions. Suppressor T cells limit the magnitude of the immune response. In normal individuals, there is a balance between helper and suppressor activities. Many immune diseases are associated with deficiencies or excesses of the Tlymphocyte subtypes (Fig. 3–1).6 The B lymphocytes are responsible for humoral immunity through the production of circulating antibodies. Examples of humoral immunity include elimination of encapsulated bacteria, neutralization of soluble toxins, protection against viruses, transplant rejection (hyperacute reaction), and possible Figure 3–1. In normal, healthy individuals, there is a balance between helper and suppressor activities. Many immunodeficiency syndromes appear to be caused by a disturbance of this balance such that a state of unresponsiveness is created. This could result from either a lack of helper activity or an excess of suppressor activity. Conversely, autoimmunity, which results from aberrant responses directed at the host’s own antigens, could result from abnormal immunoregulation from either excessive helper or reduced suppressor activities. (From Boggs, DR, and Winkelstein, A: White Cell Manual, ed 4. FA Davis, Philadelphia, 1983, p 71, with permission.) Copyright © 2003 F.A. Davis Company 62 SECTION I—Laboratory Tests tumor immunity. Pathological alterations in antibody production are responsible for disorders such as autoimmune hemolytic anemia, immune thrombocytopenia, allergic responses, some forms of glomerulonephritis and vasculitis, and transfusion reactions.7 Actual production of antibodies (immunoglobulins) occurs in plasma cells, the most differentiated form of B lymphocyte. All B lymphocytes have immunoglobulins (Ig) on their surfaces. These serve as receptors for specific antibodies. Five classes of immunoglobulins are currently identified: IgG, IgM, IgA, IgD, and IgE. Immune activation requires interaction not only of surface Ig with the specific antigen but also of B lymphocytes with the helper T cells. The activated B lymphocytes undergo transformation into immunoblasts that replicate and then differentiate into either plasma cells, which produce antibodies, or memory cells (“small lymphocytes”), which retain the ability to recognize the antigen. Similar memory cells have been found in the Tlymphocyte system.8 The relationships between the T-lymphocyte and B-lymphocyte systems are diagrammed in Figure 3–2. In both cellular and humoral immune responses, initial exposure to specific antigens initiates the primary immune response. Depending on the nature and quantity of the antigen, it may take days, weeks, or months for the cells to recognize and respond to the antigen. Subsequent exposure to the same antigen, however, elicits the secondary (anamnestic) response much more rapidly than the primary response.9 Tests of lymphocyte functions include T- and B- lymphocyte assays, immunoblast transformation tests, and immunoglobulin assays. T- AND B-LYMPHOCYTE ASSAYS T- and B-lymphocyte assays are used to diagnose a number of immunologic disorders (Tables 3–1 and 3–2). A variety of methods are used. The most common way to assess T-cell activity is to measure the individual’s response to delayed hypersensitivity skin tests. This involves intradermal injection of minute amounts of several antigens to which the individual has previously been sensitized (e.g., tuberculin, mumps, Candida). Erythema and induration should occur at the site within 24 to 48 hours. Absence of response is termed anergy and, thus, the test is frequently called an anergy panel. Anergy to skin tests reflects either a temporary or a permanent failure of cell-mediated immunity.10 Other measures of T and B lymphocytes involve determination of the number of cell types present. T lymphocytes are recognized by their ability to form rosettes with sheep erythrocytes (i.e., the sheep red cells surround the T lymphocyte). Although the sheep erythrocytes adhere to the cell membranes of the T lymphocytes, they react to neither B lymphocytes nor null cells.11 T lymphocytes and their subsets also can be distinguished by their ability to react with various monoclonal antibodies. Monoclonal antibodies constitute a single species of immunoglobulins with specificity for a single antigen and are produced by immunizing mice with specific antigens. The most commonly used monoclonal antibodies to T Figure 3–2. The relationship between the T-lymphocyte and B-lymphocyte systems. (From Winkelstein, A, et al: White Cell Manual, ed 5. FA Davis, Philadelphia,1998, with permission.) Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology • TABLE 3–1 and Immunologic Testing Causes of Altered Levels of T and B Lymphocytes Increased Levels Decreased Levels T LYMPHOCYTES Acute lymphocytic leukemia Di George’s syndrome Multiple myeloma Chronic lymphocytic leukemia Infectious mononucleosis Acquired immunodeficiency syndrome (AIDS) Graves’ disease Hodgkin’s disease Nezelof syndrome Wiskott-Aldrich syndrome Waldenström’s macroglobulinemia Severe combined immunodeficiency disease (SCID) Long-term therapy with immunosuppressive drugs B LYMPHOCYTES Chronic lymphocytic leukemia Acute lymphocytic leukemia Multiple myeloma X-linked agammaglobulinemia Di George’s syndrome SCID Waldenström’s macroglobulinemia Acute lupus erythematosus TABLE 3–2 • Disorders Associated with Abnormal T-Cell Subsets IMMUNE DEFICIENCY DISEASES (HELPER AND/OR SUPPRESSOR ACTIVITY) Common variable hypogammaglobulinemia Acute viral infections (infectious mononucleosis, cytomegalic inclusion disease) Chronic graft-versus-host disease Multiple myeloma Chronic lymphomocytic leukemia Primary biliary cirrhosis Sarcoidosis Immunosuppressive drugs (azathioprine, corticosteroids, cyclosporin A) Acquired immunodeficiency syndrome (AIDS) AUTOIMMUNITY (HELPER AND/OR SUPPRESSOR ACTIVITY) Connective tissue diseases (e.g., systemic lupus erythematosus) Acute graft-versus-host disease Autoimmune hemolytic anemia Multiple sclerosis Myasthenia gravis Inflammatory bowel diseases Atopic eczema Adapted from Boggs, DR, and Winkelstein, A: White Cell Manual, ed 4. FA Davis, Philadelphia, 1983, p 72. 63 Copyright © 2003 F.A. Davis Company 64 SECTION I—Laboratory Tests lymphocytes are designated T3, T4, and T8. T3 is a pan-T-cell antibody that reacts with a determinant that is present on all mature peripheral T lymphocytes and can, therefore, be used to enumerate the total number of T cells present. T4 antibodies identify helper T cells, and T8 antibodies identify suppressor T cells.12 Other monoclonal antibodies include T10, T9, and T6. T10 and T9 antibodies react with very immature T lymphocytes (thymocytes) that are found in the thymus gland but not in the peripheral circulation. T10 antigen also is seen in mature thymocytes that are localized primarily in the medullary regions of the thymus. T6 antibodies also react with certain immature thymocytes. As T lymphocytes mature, reactivity to T6 antibodies is lost. Tests involving reactivity to immature T lymphocytes are useful in diagnosing T-cell leukemias and lymphomas.13 B lymphocytes are detected by immunofluorescent techniques. Such techniques involve mixing lymphocyte suspensions with heterologous antisera to immunoglobulins that have been labeled with a dye such as fluorescein. The antisera combine with B lymphocytes and when the suspension is examined by fluorescent microscopy, only B lymphocytes appear.14 T and B lymphocytes can be differentiated by electron microscopy, because T cells are smooth and B cells have surface projections. This technique is not, however, available in many laboratories. INDICATIONS FOR T- AND B-LYMPHOCYTE ASSAYS Diagnosis of disorders associated with abnormal levels of T and B lymphocytes (see Table 3–1) Diagnosis of disorders associated with abnormal T-cell subtypes (see Table 3–2) Support for diagnosing acquired immunodeficiency syndrome (AIDS), as indicated by decreased helper T cells, normal or increased suppressor T cells, and a decreased ratio of helper to suppressor T cells Diagnosis of severe combined immunodeficiency disease (SCID), an inherited disorder characterized by failure of the stem cell to differentiate into T and B lymphocytes (Fig. 3–3) Diagnosis of Di George’s syndrome, characterized by failure of the thymus (and parathyroids) to develop, with a resulting decrease in T lymphocytes (see Fig. 3–3) Diagnosis of X-linked agammaglobulinemia, characterized by severe B-lymphocyte deficiency (see Fig. 3–3) Diagnosis of common variable hypogammaglobulinemia (CVH), characterized by absent, decreased, or defective B cells and most commonly caused by either lack of helper T lymphocytes or abnormal suppressor T cells (see Fig. 3–3) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube or other type of blood collection tube, depending on laboratory preference. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Because the client may be immunosuppressed, assess the site for signs of infection. Complications and precautions for compromised immune status: Note and report helper Tcell level and relation to suppressor T-cell level or decreased B cells. Administer chemotherapy or Reference Values T lymphocytes 60–80% of circulating lymphocytes* B lymphocytes 10–20% of circulating lymphocytes Null cells 5–20% of circulating lymphocytes Helper T lymphocytes 50–65% of circulating T lymphocytes Suppressor T lymphocytes 20–35% of circulating T lymphocytes Ratio of helper to suppressor T lymphocytes 2:1 * A decreased lymphocyte count (lymphopenia) usually indicates a decrease in the number of circulating T lymphocytes. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology TABLE 3–3 • and Immunologic Testing 65 Immunoglobulins Causes of Altered Levels Class IgG Locations Functions Increased Decreased Plasma Produces antibodies against bacteria, viruses, and toxins Infections—all types, acute and chronic Lymphocytic leukemia Interstitial fluid Protects neonate Starvation Agammaglobulinemia Placenta Activates the complement system Liver disease Amyloidosis Is a major factor in secondary (anamnestic) response Rheumatic fever Toxemia of pregnancy Sarcoidosis IgG myelomas IgA Respiratory tract Protects mucous membranes from viruses and bacteria Autoimmune disease Lymphocytic leukemia Gastrointestinal tract Includes antitoxins, antibacterial agglutinins, antinuclear antibodies, and allergic reagins Chronic infections Agammaglobulinemia Liver disease Malignancies Activates complement through the alternative pathway Wiskott-Aldrich syndrome Hereditary ataxia-telangiectasia IgA myeloma Hypogammaglobulinemia Genitourinary tract Tears Saliva Milk, colostrum Malabsorption syndromes Exocrine secretions IgM — Primary responder to antigens Lymphosarcoma Lymphocytic leukemia Produces antibody against rheumatoid factors, gram-negative organisms, and the ABO blood group Brucellosis, actinomycosis Agammaglobulinemia Trypanosomiasis Amyloidosis Relapsing fever IgG and IgA myeloma Activates the complement system Malaria Dysgammaglobulinemia Infectious mononucleosis Rubella virus in newborn Waldenström’s macroglobulinemia IgD Serum Cord blood Unknown Chronic infections — IgD myelomas (Continued on following page) Copyright © 2003 F.A. Davis Company 66 SECTION I—Laboratory Tests TABLE 3–3 • Immunoglobulins (Continued) Causes of Altered Levels Class IgE Locations Functions Increased Decreased Congenital agammaglobulinemia Serum Allergic reactions Atopic skin disorders Interstitial fluid Anaphylaxis Hay fever Protects against parasitic worm infestations Asthma Anaphylaxis IgE myeloma other ordered medications. Provide reverse protective precautions to prevent infection. IMMUNOBLAST TRANSFORMATION TESTS When responding to a specific antigen, mature lymphocytes undergo a series of morphological and biochemical changes that enable them to become actively proliferating cells (immunoblasts). The lymphocytes enlarge, synthesize new nucleic acids and proteins, and undergo a series of mitoses. This proliferative expansion increases the pool of anti- gen-responsive cells (Fig. 3–4).15 Immunoblast transformation tests evaluate the capability of lymphocytes to change to proliferative cells and, thus, to respond normally to antigenic challenge. Several methods of performing immunoblast transformation tests can be used. Nonimmune transformation tests involve exposing a sample of the client’s lymphocytes to mitogens, agents that cause normally responsive lymphocytes to become immunoblasts independent of any antigenic effect. Effective mitogens include plant extracts such as phytohemagglutinin (PHA), concanavalin A (conA), and pokeweed mitogen. PHA and conA stimulate Figure 3–3. Several immunodeficiency diseases can be viewed as cellular blocks in the normal maturation of lymphocytes. (From Winkelstein, A, et al: White Cell Manual, ed 5. FA Davis, Philadelphia, 1998, p 103, with permission.) Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology and Immunologic Testing 67 Figure 3–4. Responses of mature lymphocytes to antigens. In both the T- and B-cell systems, stimulated cells undergo a redifferentiation process leading to immature-appearing lymphoblasts. (From Winkelstein, A, et al: White Cell Manual, ed 5. FA Davis, Philadelphia, 1998, p 83, with permission.) Reference Values Nonimmune transformation tests A stimulation index of greater than 10 indicates immunocompetence. Antigen-specific transformation tests A stimulation index of greater than 3 indicates prior exposure to the antigen. Mixed lymphocyte culture Nonresponsiveness indicates good histocompatibility. primarily T lymphocytes; pokeweed stimulates both T and B lymphocytes, although the effect on B lymphocytes is greater. Approximately 72 hours after the lymphocytes have been incubated with the mitogens, radiolabeled thymidine is added and then incorporated into the deoxyribonucleic acid (DNA) of the proliferating cells. The rate of uptake of radioactive thymidine indicates the extent of lymphocyte proliferation.16 After immune capability has been established, antigen-specific transformation tests can demonstrate whether the person’s T cells have encountered specific antigens; that is, an individual’s cellmediated immunities can be documented by observing the way T cells respond to a battery of known antigens (e.g., soluble viral or bacterial antigens or tissue antigens of human white cells from organ donors). The mixed lymphocyte culture (MLC) technique is widely used in testing before organ transplantation. This test is based on the fact that cultured lymphocytes can recognize and respond to foreign antigens that have not previously sensitized the host. Immunologically responsive lymphocytes cultured together with cells possessing unfamiliar or unknown surface antigens gradually develop sensitivity; after a lag period of 48 to 72 hours, the responding cells undergo immunoblast transformation if the stimulating cells possess antigens different from those of the host.17 INTERFERING FACTORS Radioisotope studies performed within 1 week of the test may alter test results. Pregnancy or oral contraceptive use may lead to a decreased response to PHA in nonimmune transformation tests. INDICATIONS FOR IMMUNOBLAST TRANSFORMATION TESTS Support for diagnosing immunodeficiency disorders as indicated by a decreased response to nonimmune transformation tests Identification of microorganisms to which the individual was previously exposed as indicated by an increased response to antigen-specific transformation tests Support for identifying compatible organ donors Copyright © 2003 F.A. Davis Company 68 SECTION I—Laboratory Tests and recipients as indicated by nonresponsiveness on mixed lymphocyte culture NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). All clients should be interviewed to determine whether they have undergone any radioisotope tests within the past week; if the client is a woman, it should be determined whether she is pregnant or using oral contraceptives. THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube or other type of blood collection tube, depending on laboratory preference. The sample should be transported to the laboratory promptly. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Because the client may be immunosuppressed, assess the site for signs of infection. Complications and precautions: Note and report the lymphocyte response to an antigenic challenge in relation to signs and symptoms of tissue rejection or allergic condition. IMMUNOGLOBULIN ASSAYS Immunoglobulins are serum antibodies produced by the plasma cells of the B lymphocytes. Immunoglobulins (Ig) have been subdivided into the five classes: IgG, IgA, IgM, IgD, and IgE. Their functions are listed in Table 3–3. IgG, IgA, and IgM have been further divided into subclasses: IgG1, IgG2, IgG3, and IgG4. Four techniques can be used to assess Ig: (1) serum protein electrophoresis, (2) immunoelectrophoresis, (3) radial immunodiffusion, and (4) radioimmunoassay. Serum protein electrophoresis, although not specific to the immunoglobulins, may indicate the presence of immunologic disorders such that additional testing may not be needed. Electrophoresis separates the serum proteins into albumin and globulin components, with the latter being further broken down into 1, 2, , and fractions. Most of the fraction derives from IgG molecules, whereas IgM contributes to the portion.18 Three types of alterations in immunoglobulins can be identified by serum protein electrophoresis: (1) hypogammaglobulinemia, a reduction in the total quantity of immunoglobulins; (2) monoclonal gammopathy, excessive amounts of single immunoglobulins or proteins related to immunoglobulins (seen in multiple myeloma and macroglobulinemia); and (3) polyclonal gammopathy, excessive amounts of several different immunoglobulins (seen in many infections and diffuse inflammatory conditions).19,20 Examples of these serum protein electrophoretic patterns are diagrammed in Figure 3–5. Additional examples of disorders associated with monoclonal and polyclonal gammopathies are listed in Table 3–4. Immunoelectrophoresis is not a quantitative technique, but it provides such detailed separation of the individual immunoglobulins that modest deficiencies are readily detected. It identifies the presence of monoclonal protein and its type. Radial immunodiffusion allows measurement of the quantity of individual immunoglobulins to concentrations as low as 10 to 20 mg/dL. Radioimmunoassay provides better results when immunoglobulin levels are below 20 mg/dL. Serum IgD and IgE are normally well below this level, as are immunoglobulin levels in most body fluids other than serum. Cryoglobulin is an immunoglobulin that precipitates in the cold and, in those who develop high concentrations, causes the blockage of small capillaries in fingers, ears, and toes exposed to cold temperatures. The test is performed by first cooling the blood serum in a refrigerator to note whether a precipitate forms in 2 to 7 days and then measuring the volume in relation to the percentage of the total serum to obtain a numerical value analogous to a hematocrit. Three positive types of cryoglobulins can be identified by immunoelectrophoresis. Pyroglobulin is a protein identified by heating the blood serum to obtain a precipitate, indicating an abnormality. The test is performed to determine cold sensitivity as well as to assist in the diagnosis of collagen disorders, malignancies, or infections.21 INTERFERING FACTORS Immunizations within 6 months before the test may alter test results. Transfusions of either whole blood or fractions within 2 months may alter test results. INDICATIONS FOR IMMUNOGLOBULIN ASSAYS Suspected immunodeficiency, either congenital or acquired Suspected immunoproliferative disorders such as Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology and Immunologic Testing 69 Figure 3–5. Serum protein electrophoretic patterns. (From Winkelstein, A, et al: White Cell Manual, ed 5. FA Davis, Philadelphia, 1998, p 95, with permission.) multiple myeloma or Waldenström’s macroglobulinemia Suspected autoimmune disorder Suspected malignancy involving the lymphoreticular system Monitoring of effects of chemotherapy or radiation therapy, or both, which may suppress the immune system Identification of hypogammaglobulinemia, monoclonal gammopathy, and polyclonal Image/Text rights unavailable Copyright © 2003 F.A. Davis Company 70 SECTION I—Laboratory Tests Reference Values Percentage of Total Protein Serum Protein Electrophoresis Conventional Units SI Units Constituent Albumin 52–68 0.520–0.680 Globulin 32–48 0.320–0.480 1-Globulin 2.4–5.3 0.024–0.053 2-Globulin 6.6–13.5 0.066–0.135 -Globulin 8.5–14.5 0.085–0.145 -Globulin 10.7–21.0 0.107–0.210 Immunoglobulins Neonates SI Units 6 mo SI Units 1 yr SI Units 6 yr SI Units 12 yr SI Units 16 yr SI Units Adults SI Units Percentage of total immunoglobulins in adults IgG, mg/dL IgA, mg/dL IgM, mg/dL IgD, mg/dL IgE, mg/dL 650–1250 0–12 5–30 — — 6.5–12.5 g/L 0.00–0.12 g/L 0.05–0.30 g/L 200–1100 10–90 10–80 — — 2.0–11.0 g/L 0.10–0.90 g/L 0.10–0.80 g/L 300–1400 20–150 20–100 — — 3.0–14.0 g/L 0.20–1.50 g/L 0.20–1.0 g/L 550–1500 50–175 22–100 — — 5.50–15.0 g/L 0.50–1.75 g/L 0.22–1.0 g/L 660–1450 50–200 30–120 — — 6.60–14.5 g/L 0.50–2.0 g/L 0.30–1.20 g/L 700–1050 7–225 35–75 — — 7.0–10.5 g/L 0.70–2.25 g/L 0.35–0.75 g/L 800–1800 100–400 55–150 0.5–3 0.01–0.04 8.0–18.0 g/L 1.0–4.0 g/L 0.55–1.50 g/L 0.005–0.03 g/L 0–430 mg/L 75–80% 15% 10% 0.2% 0.0002% gammopathy by serum protein electrophoresis (see Fig. 3–5 and Table 3–4) Support for diagnosing a variety of disorders associated with altered immunoglobulin levels (see Table 3–3) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should be interviewed to determine whether he or she has received immunizations within 6 months before the test or transfusions of whole blood or fractions within 2 months before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The sample should be transported to the laboratory promptly. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Because the client may be immunosuppressed, assess the site for signs of infection. Complications and precautions: Note and report abnormal levels in relation to immunodeficiency, malignant, or autoimmune disorders. TESTS OF THE COMPLEMENT SYSTEM Complement is a system of protein molecules, the sequential interactions of which produce biologic effects on surface membranes, on cellular behavior, and on the interactions of other proteins. Each of the proteins of the complement system is inactive by itself. Activation occurs through a cascadelike sequence after contact with substances such as IgG or IgM antigen-antibody complexes, aggregated IgA, certain naturally occurring polysaccharides and lipopolysaccharides, activation products of the coagulation system, and bacterial endotoxins. Activation of the complement system results in an inflammatory response that destroys or damages cells. Complement proteins are identified by letters and numbers and are listed here in order of activation in the “classical pathway” of the complement cascade: C1q, C1r, C1s, C4, C2, C3, and then C5 through C9. The “alternate pathway” bypasses C1, C4, and C2 activation and begins directly with C3. The key step in the alternate pathway is activation of properdin, a serum protein without biologic effects in its inactive form. Contact with aggregated IgA, with bacterial endotoxins, or with complex molecules such as dextran, agar, and zymosan alters properdin and initiates the sequence at C3.22 Complete activation to C9 leads to membrane disruption and irreversible cell damage. Along the way to complete activation, the following activities occur: C2 releases a low-molecular-weight peptide with kinin activity. Activation of products of C3 and C5 affects mast cells, smooth muscle, and leukocytes to produce an anaphylactic effect; other elements of C3 and C5 bind to cell membranes and render them more susceptible to phagocytosis, a process called opsonization. Fragments of C3 and C4 cause immune adherence, in which complement-coated particles bind to cells with surface membranes that have complement receptors; activated C3 and C4 are also capable of virus neutralization. C3 and C5 exert chemotactic activity on neutrophils, and the C5 to C9 complex influences the procoagulant activity of and Immunologic Testing 71 platelets. Conversely, procoagulant factor XII can initiate C1 activation, and plasmin (the substance that dissolves fibrin) and thrombin (which converts fibrinogen to fibrin) can cleave C3 into its active form.23 SERUM COMPLEMENT ASSAYS Radioimmunoassay and immunodiffusion techniques have made it possible to quantify each of the complement components. For clinical purposes, however, only total complement, C3, and C4 are measured. Total complement (CH50), also known as a hemolytic assay, is measured by exposing a sample of human serum to sheep red cells coated with complement-requiring antibody. Results are expressed as CH50 units, reflecting the dilution at which adequate complement exists to lyse one-half of the test cells. C3 and C4 levels are measured individually by radial immunodiffusion. These latter tests take 24 to 36 hours to complete, and results are easily affected by improper handling of the specimen.24 The causes of alterations in C3 and C4 levels are presented in Table 3–5. INTERFERING FACTORS Failure to transport the sample to the laboratory immediately may alter test results because complement deteriorates rapidly at room temperature. Hemolysis of the sample may alter test results. INDICATIONS FOR SERUM COMPLEMENT ASSAYS Suspected acute inflammatory disorder as generally indicated by elevated total complement levels Suspected immune or infectious disorder (e.g., acute glomerulonephritis, systemic lupus erythematosus [SLE], rheumatoid arthritis, hepatitis, subacute bacterial endocarditis, gram-negative sepsis) or both, as indicated by decreased total complement levels Support for diagnosing hereditary deficiencies of complement components as indicated by decreased levels of total complement or of specific components such as C3 and C4, or of both (see Table 3–5) Support for diagnosing cancer, especially that of the breast, lung, digestive system, cervix, ovary, and bladder, as indicated by increased levels of C3 and C4 (see Table 3–5) Monitoring for the progression of malignant disease as indicated by declining complement levels as the disease progresses Support for diagnosing a variety of immune and Copyright © 2003 F.A. Davis Company 72 SECTION I—Laboratory TABLE 3–5 Component Tests • Causes of Alterations in C3 and C4 Levels Increased Levels C3 Decreased Levels Acute rheumatic fever Advanced systemic lupus erythematosus (SLE) Rheumatoid arthritis Glomerulonephritis Early SLE Renal transplant rejection Most cancers Chronic active hepatitis Cirrhosis Multiple sclerosis Anemias Gram-negative septicemia Subacute bacterial endocarditis Inborn C3 deficiency Serum sickness Immune complex disease C4 Rheumatoid spondylitis SLE Juvenile rheumatoid arthritis Lupus nephritis Most cancers Acute poststreptococcal glomerulonephritis Chronic active hepatitis Cirrhosis Subacute bacterial endocarditis Inborn C4 deficiency Serum sickness Immune complex disease Reference Values Conventional Units Total complement (CH50) C3 C4 40–90 U/mL SI Units 0.4–0.9 g/L Men 80–180 mg/dL 0.80–1.80 g/L Women 76–120 mg/dL 0.76–1.20 g/L Men 15–60 mg/dL 0.15–0.60 g/L Women 15–52 mg/dL 0.15–0.52 g/L Note: Values for total complement, C3, and C4 may vary according to laboratory methods and the reference range established by the laboratory performing the test. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology inflammatory disorders as indicated by altered C3 and C4 levels (see Table 3–5) Monitoring of progress after various immune and inflammatory disorders as indicated by levels approaching or within the reference ranges NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The sample must be handled gently to avoid hemolysis and transported to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Note and report types and deficiencies of complement components and their relation to an inflammatory or infectious disorder. and Immunologic Testing 73 Reference Values Immune complexes are not normally found in the serum. INTERFERING FACTORS Rough handling of the sample and failure to transport the sample promptly to the laboratory may cause deterioration of any immune complexes present. INDICATIONS FOR IMMUNE COMPLEX ASSAYS Suspected immune disorders such as SLE, scleroderma, dermatomyositis, polymyositis, glomerulonephritis, and rheumatic fever as indicated by the presence of immune complexes Monitoring of the effects of therapy for various immune disorders Suspected serum sickness or allergic reactions to drugs as indicated by the presence of immune complexes NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). IMMUNE COMPLEX ASSAYS Immune complexes are combinations of antigen and antibody that are capable of activating the complement cascade. Although the activated agent is directed against the immune complex, tissues that are “innocent bystanders” may also be severely damaged, especially when immune complexes are produced too rapidly for adequate clearance by the body. Immune complexes are commonly present in autoimmune disorders and also are found in immune hypersensitivities that do not involve autoimmunity. Two methods can be used to determine the circulating immune complexes (CIC) in the blood in the diagnosis of autoimmune and infectious diseases. One involves screening for large amounts of precipitate in serum that has been refrigerated. The other is the Raji cell assay, in which these specially prepared cells that bind complement (C3) are combined with the serum sample and then incubated. Further incubation with a radiolabeled antihuman immunoglobulin allows for binding of the CIC on the surface of the Raji cells. This is followed by washing of the cells and measurement of the radioactivity to determine the CIC in the blood.25 THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The sample must be handled gently and transported to the laboratory promptly. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Note and report the presence of complexes in relation to signs and symptoms of an existing or suspected autoimmune disease. RADIOALLERGOSORBENT TEST FOR IgE IgE antibodies are responsible for hypersensitivity reactions described as atopic (allergic) or anaphylactic. Examples of IgE-mediated diseases include hay fever, asthma, certain types of eczema, and idiosyncratic, potentially fatal reactions to insect venoms, penicillin, and other drugs or chemicals. Copyright © 2003 F.A. Davis Company 74 SECTION I—Laboratory Tests Almost all of the body’s active IgE is bound to tissue cells, with only small amounts in the blood. Thus, IgE antibodies cannot circulate in search of antigen but must wait for antigens to appear in their area. Once this happens, the interaction of IgE antibodies with specific antigens causes mast cells (tissue basophils) to release histamine and other substances that promote vascular permeability.26 The radioallergosorbent test (RAST) for IgE measures the quantity of IgE antibodies in the serum after exposure to specific antigens selected on the basis of the person’s history. RAST has replaced skin tests and provocation procedures, which were inconvenient, painful, and hazardous to the client. Reference Values If the client is not allergic to the antigen, IgE antibody is not detected. A positive test result in relation to a specific antigen is more than 400 percent of control. Results of the test may vary depending on the reference serum used for the control. INTERFERING FACTORS Radioisotope tests within 1 week before the test may alter results. INDICATIONS FOR RADIOALLERGOSORBENT TEST FOR IgE Onset of asthma, hay fever, dermatitis Systemic reaction to insect venom, drugs, or chemicals Identification of the specific antigen(s) to which the client reacts Monitoring of response to desensitization procedures NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). All clients should be interviewed to determine whether they have undergone any radioisotope tests within the past week. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The allergy panel desired should be indicated on the laboratory request form. Each panel usually consists of six antigens. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Instruct client to avoid contact with substances, ingestion of drugs, or exposure to insects that cause reactions. AUTOANTIBODY TESTS Antibodies directed against “self ” components are believed to be responsible for the pathogenesis of many diseases. Some show widespread systemic involvement (Table 3–6), whereas others are confined to a specific organ system (Table 3–7). INTERFERING FACTORS Many drugs may cause false-positive results in certain autoantibody tests (Table 3–8). INDICATIONS FOR AUTOANTIBODY TESTS Signs and symptoms of the disorder for which each test is pathognomonic or for which the test provides confirming data (see Tables 3–6 and 3–7) Monitoring of response to treatment for autoimmune disorders NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Food and fluids are not restricted, except for the cryoglobulin test, which requires a 4-hour fast from food. THE PROCEDURE The procedure is the same for all autoantibody tests, except cryoglobulins. A venipuncture is performed and the sample collected in a red-topped tube. For cryoglobulins, the sample is collected in a prewarmed red-topped tube. The sample must be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food withheld before the test. Complications and precautions: Note and report the presence of cell-specific or tissue-specific antibodies in relation to a suspected disease and the presenting signs and symptoms. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology TABLE 3–6 • and Immunologic Testing 75 Summary of Autoantibody-Related Disorders and Tests Used in Diagnosis Incidence Antibody C-reactive protein (CRP) Present in 90% or More of Cases Present in 50–90% of Cases Present in 50% of Cases Rheumatic fever Active tuberculosis Multiple sclerosis Rheumatoid arthritis Gout Guillain-Barré syndrome Acute bacterial infections Advanced cancers Scarlet fever Viral hepatitis Leprosy Varicella Cirrhosis Surgery Burns Intrauterine contraceptive devices Peritonitis Rheumatoid factor (RF) Antinuclear antibodies (ANA) Rheumatoid arthritis Systemic lupus erythematosus (SLE) Early rheumatoid arthritis Advanced age SLE Juvenile rheumatoid arthritis (20%) Scleroderma Infectious diseases Dermatomyositis Healthy adults (5%) Sjögren’s syndrome Burns Scleroderma Asbestosis Drug-induced SLE-like syndrome Juvenile chronic polyarthritis Chronic active hepatitis Rheumatoid arthritis Heart disease, with longterm procainamide therapy Rheumatic fever Myasthenia gravis Advanced age Dermatomyositis Polyarteritis nodosa Primary biliary cirrhosis Anti-DNA Active SLE SLE in remission Juvenile rheumatoid arthritis Progressive systemic sclerosis Drug-induced SLE-like syndrome Uveitis Cold agglutinins Atypical pneumonia Viral infections Congenital syphilis Influenza Infectious mononucleosis Malaria Pulmonary embolus Lymphoreticular malignancy Anemia Cirrhosis (Continued on following page) Copyright © 2003 F.A. Davis Company 76 SECTION I—Laboratory TABLE 3–6 • Tests Summary of Autoantibody-Related Disorders and Tests Used in Diagnosis (Continued) Incidence Present in 90% or More of Cases Antibody Present in 50% of Cases Present in 50–90% of Cases Lupus erythematosus (LE) cell preparation SLE — — Cryoglobulins Raynaud’s syndrome — — Cryoglobulinemia Reference Values Conventional Units C-reactive protein (CRP) Antinuclear antibodies (ANA) Rheumatoid factor (RF) Anti-DNA antibodies Negative to trace Negative Negative (1:20) 1 mg/mL Antimitochondrial antibodies Negative Antiskin antibodies Negative Antiadrenal cortex antibodies Negative Antithyroglobulin, antithyroid microsome antibodies 1:100 Antismooth muscle antibodies Negative Antiparietal cell, anti-intrinsic factor antibodies Negative Antistriated muscle antibodies Negative Antimyocardial antibodies Negative Antiglomerular basement membrane antibodies Negative Anti-insulin antibodies Negative Acetylcholine receptor antibodies Negative Anti-SS-A and anti-SS-B antibodies Negative Lupus erythematosus cell test (LE prep) Negative Cold agglutinins Cryoglobulins 1:16 Negative Antiglobulin tests (Coombs’ tests)* Direct Negative Indirect Negative * See also Chapter 4. SI Units 2.0 kU/L Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology TABLE 3–7 Antibody Target Cell/Tissue • and Immunologic Testing 77 Cell- and Tissue-Specific Antibodies Diseases for Which the Test Is Usually Diagnostic Other Diseases in Which This Antibody May Also Be Present Skeletal muscle Myasthenia gravis Cardiac muscle Myocardial infarction Acute rheumatic fever Smooth muscle Chronic active hepatitis Biliary cirrhosis Viral hepatitis Infectious mononucleosis Systemic lupus erythematosus (SLE) (10%) Mitochondria Primary biliary cirrhosis Chronic active hepatitis Drug-induced jaundice Viral hepatitis SLE (20%) Skin Pemphigus — Altered IgG Rheumatoid arthritis — Adrenal cells Addison’s disease — Intrinsic factor, parietal cells Pernicious anemia SLE (5%) Long-acting thyroid stimulator Graves’ disease — Hashimoto’s thyroiditis Long-acting thyroid microsomes Primary myxedema SLE (5%) Juvenile lymphocytic thyroiditis Pernicious anemia (25%) Graves’ disease Allergies Healthy adults Hashimoto’s thyroiditis Pernicious anemia Primary myxedema Allergies Graves’ disease Healthy adults (5–10%) Salivary ducts Sjögren’s syndrome Rheumatoid arthritis Red blood cell membrane Autoimmune hemolytic anemia Transfusion reaction Platelet cell membrane Idiopathic thrombocytopenic purpura — Basement membranes of lungs, renal glomeruli Goodpasture’s syndrome — Thyroglobulin Glomerulonephritis IMMUNOLOGIC ANTIBODY TESTS Exposure to bacteria, fungi, viruses, and parasites induces production of antibodies that either can be identified only during acute disease or can remain identifiable for many years. Exposure can be through immunization, from previous infection so minimal that it passed unrecognized, or from current symptomatic or prepathogenic infection. Detection and identification of specific antibodies in the blood by assays performed in the serology laboratory are preferred for obtaining diagnostic information. This is especially true when the antigen assays or culture techniques performed in the microbiology labora- Copyright © 2003 F.A. Davis Company 78 SECTION I—Laboratory Tests • Drugs that May Cause False-Positive Reactions in Autoantibody Tests* TABLE 3–8 Antibiotics Para-aminosalicylic acid Anti-DNA Penicillin Chlorpromazine Phenylbutazone Clofibrate Phenytoin Ethosuximide Procainamide Griseofulvin Propylthiouracil Hydralazine Quinidine Isoniazid Radioactive diagnostics Mephenytoin Streptomycin Methyldopa Sulfonamides Methysergide Tetracyclines Oral contraceptives Trimethadione * The drugs listed here may cause false-positive reactions in the following tests: antinuclear antibodies, lupus erythematosus cell test, and antiglobulin (Coombs’) tests. Various methods for detection of antibodies are used. They include immunoprecipitation, complement fixation, neutralization assay, particle agglutination/agglutination inhibition, immunofluorescence assay, enzyme immunoassay, and radioimmunoassay. The concentrations of antibody are referred to as the titer, and their predictable patterns are useful in both diagnosing a disease and monitoring its course. Fungal Infection Antibody Tests Most pathogenic fungi elicit antibodies in immunocompetent hosts. Assays for fungal antibodies are used to diagnose invasive deep-seated recent or current infections. Serologic testing for parasitic organisms or antibodies in the blood sample is also used in the diagnosis of infections. Depending on the antibody to be identified, testing uses the various assay techniques mentioned in the introduction of this chapter. Table 3–9 indicates the fungal and parasitic infections for which tests are available and the causes of alteration in the test results. INTERFERING FACTORS tory are ineffective in producing a causative agent or in clients who cannot tolerate the invasive procedure necessary to collect a specimen for culture. TABLE 3–9 Organism • Recent fungal skin tests may alter results. Obtaining the sample near fungal skin lesions may contaminate the specimen and alter test results. Fungal and Parasitic Immunologic Tests Tests Available Causes of Alterations Fungi Histoplasma capsulatum CF, I, LA Prior exposure to organism or cross-reactive agent, recent skin test Blastomyces dermatitidis EIA Blastomycosis Coccidioides immitis CF, I, LA Acute or chronic infection, repeated skin testing with coccidioidin Aspergillus fumigatus CF, I Pulmonary aspergillosis, aspergillosis allergy Cryptococcus neoformans A Test demonstrates antigen, not antibodies, in infection Sporotrichum schenckii A Deep tissue infection Candida albicans LA Systemic infection, vaginal infection Toxoplasma gondii IFA, EIA Acute or chronic toxoplasmosis Entamoeba histolytica A, IFA Amebic dysentery Parasites Aagglutination, CFcomplement fixation, Iimmunodiffusion, IFAindirect fluorescent antibody tests, LAlatex agglutination, EIAenzyme immunoassay. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology and Immunologic Testing 79 Reference Values Organism Complement Immunodiffusion Fixation Titers Test Agglutination Other Tests Fungi Histoplasma capsulatum 1:8 Negative — — Blastomyces dermatitidis 1:8 Negative — — Coccidioides immitis 1:2 Negative — — Aspergillus fumigatus 1:8 Negative — — Cryptococcus neoformans — — Negative — Sporotrichum schenckii — — 1:40 — Candida albicans — — — Latex agglutination (LA) test 1:8 Toxoplasma gondii — — — Indirect fluorescent antibody tests 1:16 Entamoeba histolytica — — — Indirect hemagglutination test 1:32 Parasites INDICATIONS FOR FUNGAL INFECTION ANTIBODY TESTS Suspected infection with the fungus for which the test is performed Persistent pulmonary symptoms after pneumonia Acute meningitis of unknown etiology Identification of the state of infection by rising or falling titers Confirmation of previous exposure to the fungus despite absence of clinical signs of illness NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should be interviewed to determine if he or she has undergone any recent fungal skin tests that may alter test results. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. Venipuncture should not be performed on or near any fungal skin lesions. The sample must be handled gently and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Note and report signs and symptoms of fungal infection, superficial or deep-seated presence, and rise of serum antibodies to a specific fungal or parasitic microorganism or culture identification of the microorganism. Assess factors that can cause infection such as travel or residence in areas where infection is endemic; antibiotic or corticosteroid therapy; chemotherapy; presence of an intravenous (IV) line to administer fluids, medications, or parenteral nutrition; or invasive procedures such as surgery. Note symptoms of vaginitis such as itching and foul-smelling, white, cheeselike secretion. Administer ordered antifungals via oral, IV, or vaginal routes. Monitor Copyright © 2003 F.A. Davis Company 80 SECTION I—Laboratory TABLE 3–10 • Tests Commonly Performed Serologic Tests for Diagnosis of Recent Bacterial Infections Organism Clinically Significant Result* Test Staphylococcus aureus Immunodiffusion for teichoic acid antibodies 1:4 Streptococcus pyogenes Antistreptolysin O (ASO) 1:240 Anti-DNAase B 1:240 Antihyaluronidase 4x titer rise Salmonella typhi (typhoid fever) Widal test 4x titer rise Legionella pneumophila (Legionnaires’ disease) Indirect immunofluorescence 1:256 Treponema pallidum Rapid plasma reagin (RPR) 1:8 Venereal Disease Research Laboratory (VDRL) 1:8 Fluorescent treponemal antibodyabsorption (FTA-ABS) (IgM) Positive Borrelia burgdorferi (Lyme disease) Indirect immunofluorescence 1:128 Mycoplasma pneumoniae (atypical pneumonia) Cold agglutinins Complement fixation 1:128 1:32 Rickettsia rickettsii (spotted and typhus fevers) Weil-Felix (OX-19) 1:320 * Titers greater than or equal to those displayed in the table or fourfold or greater rises in titer between acute and convalescent sera are only suggestive of recent infection by all of the agents listed. Titers less than those displayed in the table do not rule out infection. Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia 2000, p 709. respiratory status for changes in rate, ease, depth, and breath sounds and place on respiratory precautions according to universal standards, if appropriate. Prepare client for skin tests if ordered. bacterial antibody detection of recent or existing infectious diseases are individually outlined and discussed. They include staphylococcal, streptococcal, and febrile/cold agglutinin tests. STAPHYLOCOCCAL TESTS Bacterial Infection Antibody Tests Although most bacterial infections are successfully diagnosed by culture, serologic testing is performed for antibodies to screen for past, recent, or existing infection in those with negative cultures. Clients in whom these tests are performed usually have sustained a fever of unknown origin or have been treated with antimicrobials. Table 3–10 indicates the commonly performed tests for recent bacterial infections for identification and titers that are suggestive of recent infection. Also, specific individual serologic tests that have special applications in The teichoic acid antibody is measured to diagnose infections caused by Staphylococcus aureus. Teichoic acid attaches to the organism’s cell wall. High titers are associated with invasive infections such as bacterial endocarditis and osteomyelitis. Reference Values Teichoic acid antibody titer <1:2 INTERFERING FACTORS Improper technique in testing Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology INDICATIONS FOR STAPHYLOCOCCAL TESTS Suspected infection caused by S. aureus Diagnosis of osteomyelitis or endocarditis caused by a bacterial infection Monitoring of ongoing therapy administered for gram-positive bacterial infections NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Inform the client that repeat or serial blood sampling and testing can be performed. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The tube should be labeled as an acute or convalescent sample, whichever applies. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Inform the client of the time to return for a repeat test, usually in 2 weeks, to determine the change in titers between the acute and convalescent stages. Abnormal values: Note and report increases in titers. Assess for signs and symptoms associated with staphylococcal infections such as temperature elevation, bone pain in osteomyelitis, and changes in heart sounds in endocarditis. Administer ordered analgesic and antibiotic therapy and instruct in preventive antibiotic therapy in those at risk. STREPTOCOCCAL TESTS Group A -hemolytic streptococci produce a variety of extracellular products capable of stimulating antibody production. Such antibodies do not act on the bacteria and have no protective effect, but their existence indicates recent active streptococci. Antibody production is most reliably noted in response to streptolysin O, and the test for this antibody is termed an antistreptolysin O (ASO) titer. Antibodies in response to hyaluronidase (AH), streptokinase (anti-SK), deoxyribonuclease B (ADN-B), and nicotinamide (anti-NADase) also can be produced. When ASO titers are low, tests for these latter antibodies can be produced to substantiate the diagnosis, because they are more sensitive tests. Elevated antistreptococcal antibody titers can occur in healthy carriers of -hemolytic strepto- and Immunologic Testing 81 cocci. Elevated levels also are seen in those with rheumatic fever, glomerulonephritis, bacterial endocarditis, scarlet fever, otitis media, and streptococcal pharyngitis. Reference Values ASO titer Preschool children 85 Todd units/mL School-age children 170 Todd units/mL Adults 85 Todd units/mL ADN-B titer Preschool children 60 Todd units/mL School-age children 170 Todd units/mL Adults 85 Todd units/mL AH titer 128 Todd units/mL Anti-SK titer 128 Todd units/mL INTERFERING FACTORS Therapy with antibiotics and adrenal corticosteroids may result in falsely decreased levels. Elevated blood -lipoproteins may result in falsely elevated levels. INDICATIONS FOR STREPTOCOCCAL TESTS Suspected streptococcal infection, to confirm the diagnosis Detection and monitoring of response to therapy for poststreptococcal illnesses such as rheumatic fever and glomerulonephritis Differentiation of rheumatic fever from rheumatoid arthritis, with the former indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Medications that the client is currently taking or has recently taken should be noted, because therapy with antibiotics and adrenal corticosteroids may alter test results. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. A capillary sample may be obtained in infants and children as well as in adults for whom a venipuncture may not be feasible. The sample must be handled gently and sent promptly to the laboratory. Copyright © 2003 F.A. Davis Company 82 SECTION I—Laboratory Tests Reference Values Weil-Felix reaction (Proteus antigen test) 1:80 Widal’s test (O and H antigen tests) 1:160 Brucella agglutination test (slide agglutination test) 1:80 Tularemia agglutination test (tube dilution test) 1:40 M. pneumoniae (cold agglutinin test) 1:32 NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report increased levels of specific tests in relation to signs and symptoms of joint or renal disease. Assess for joint pain, elevated temperature, sore throat, and history of a recent infection. Administer ordered antipyretics, analgesics, and antibiotic therapy. Prepare for additional tests if more specificity is needed. FEBRILE/COLD AGGLUTININ TESTS Febrile agglutinin tests are performed concurrently with blood culture for microorganism identification to diagnose the infectious cause of a febrile condition. The test is performed with the use of antigens to specific organisms and their reaction (agglutination) with antibodies in the client’s blood serum. Diseases that can be diagnosed using these tests, along with the type of febrile agglutinin test used, are listed in Table 3–11. The cold agglutinin test is performed to identify TABLE 3–11 • cold agglutinins, antibodies that result from Mycoplasma pneumoniae infection. This infection is caused by a nonbacterial agent, but it still manifests a febrile condition. The antibodies cause agglutination of red blood cells at temperature ranges of 35.6 to 46.4F (2 to 8C), with a positive titer resulting in those with atypical pneumonia or cold agglutination disorders, depending on the severity of the disease. INTERFERING FACTORS Vaccination, chronic exposure to infected animals, and cross-reactions with other antibodies may result in falsely elevated titers. Individuals who are immunosuppressed or are receiving antibiotic therapy may have false-negative results. INDICATIONS FOR FEBRILE/COLD AGGLUTININ TESTS Determination of possible cause of fever of unknown origin (FUO) Suspected typhus, Rocky Mountain spotted fever, or other disorder for which selected tests are specific Febrile Agglutinin Tests Diseases Test Rickettsial Infections Rocky Mountain spotted fever, typhus (murine, scrub, epidemic, and recrudescent) Weil-Felix reaction (Proteus antigen test) Salmonella Infections Typhoid and paratyphoid fevers Widal’s test (O and H antigen tests) Brucella Infections Cattle, hog, goat (Hosts may transmit infections to humans.) Brucella agglutination test (slide agglutination test) Tularemia Rabbit fever and deer fly fever Tularemia agglutination test (tube dilution test) Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and transported immediately to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report increased titers in cold agglutinin test in relation to specific signs and symptoms of the disease such as fever, change in respiratory status, and nonproductive cough; also note increased titers in febrile disorders in relation to specific infectious processes. Assess for culture results or need to obtain culture for organism identification; place on enteric precautions as appropriate. Administer ordered antimicrobial therapy. Inform client of the need for serial testing during acute and convalescent stages. • Infection with Treponema pallidum provides two distinct categories of antibodies: (1) reagin (a nonspecific antibacterial antibody) and (2) antitreponemal antibody. Reagin tests, by their nature nonspecific, include the Wassermann and Reiter complement fixation tests, now seldom used. Reagin tests currently used for screening are the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) flocculation tests. Because reagin screening tests often yield false-positive reactions (Table 3–12), positive test results are confirmed by means of treponemal antibody tests. The best of these is the fluorescent treponemal antibodyabsorption test with absorbed serum.27 FLUORESCENT TREPONEMAL ANTIBODY-ABSORPTION TEST The fluorescent treponemal antibody-absorption (FTA-ABS) test is conducted on a sample of the client’s serum that is layered onto a slide fixed with T. pallidum organisms. If the antibody is present, it will attach to the organisms and can subsequently be demonstrated by its reaction with fluoresceinlabeled antiglobulin serum. The FTA-ABS test rarely gives false-positive results, except sporadically in clients with SLE; the Causes of False-Positive Reactions to Reagin Tests Transiently Positive Persistently Positive OCCURRING IN 10% OF CLIENTS WITH THE FOLLOWING: Infectious mononucleosis Systemic lupus erythematosus Malaria Rheumatoid arthritis Brucellosis Illicit drug use Typhus Hepatitis Lymphogranuloma venereum Leprosy Subacute bacterial endocarditis Malaria Advanced age Nonsyphilitic treponemal disease (pints, yaws, bejel) OCCURRING RARELY IN CLIENTS WITH THE FOLLOWING: Hepatitis Tuberculosis Measles Scleroderma Chickenpox Mycoplasma pneumonia After smallpox vaccination 83 Syphilis Tests Suspected “carrier” state for typhoid Positive blood or stool culture for Salmonella TABLE 3–12 and Immunologic Testing Copyright © 2003 F.A. Davis Company 84 SECTION I—Laboratory Tests pattern of fluorescence may have an atypical beaded appearance in these cases. Elderly individuals and clients with immune complex diseases occasionally also have false-positive results.28 Note that these tests are not specific for antibodies to T. pallidum, and many factors, including laboratory procedures, may cause false-positive results (see Table 3–12). Reference Values Reference Values Negative INTERFERING FACTORS False-positive results may occasionally occur in elderly individuals and in clients with SLE or other immune complex diseases. INDICATIONS FOR FLUORESCENT TREPONEMAL ANTIBODY-ABSORPTION TEST Confirmation of the presence of treponemal antibodies in the serum (Note: The test also may be applied to cerebrospinal fluid [CSF] to diagnose tertiary syphilis.) Verification of syphilis as the cause of positive VDRL and RPR test results NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client’s history should be reviewed for possible sources of false-positive results. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and must be transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. VENEREAL DISEASE RESEARCH LABORATORY AND RAPID PLASMA REAGIN TESTS The VDRL and RPR tests are flocculation tests for reagin and are used in screening for syphilis. The VDRL test uses heat-inactivated serum and can be made on slides or in tubes. The RPR test uses unheated serum or plasma, which is added to a reagent-treated plasma card. Automated procedures have been adapted for multichannel analyzers.29 Results are reported qualitatively as strongly reactive, reactive, weakly reactive, or negative. A degree of quantification is possible by diluting the serum and reporting the highest titer that remains positive. Positive results must be further evaluated either by repeat testing or with tests specific for antitreponemal antibodies.30 INTERFERING FACTORS Many factors, including laboratory procedures, may cause false-positive results (see Table 3–12). INDICATIONS FOR VENEREAL DISEASE RESEARCH LABORATORY AND RAPID PLASMA REAGIN TESTS Routine screening for possible syphilis Known or suspected exposure to syphilis, including congenital syphilis Verification of an antigen-antibody reaction to reagin, although a positive result is not necessarily diagnostic for syphilis Monitoring of response to treatment for syphilis, with effective treatment indicated by decreasing titers NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). A thorough history should be obtained to identify possible causes of false-positive results (see Table 3–12). It is recommended that alcohol ingestion be avoided for 24 hours before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and transported promptly to the laboratory. For neonates, a sample of cord blood may be obtained at delivery. Subsequent samples of venous blood from the infant may be required if the mother’s titer is lower than that of the infant, indicating active syphilis in the infant despite successful treatment of the mother. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report a positive result and degree of reactivity. Assess for pregnancy and sexual contacts. Ensure that positive results are reported to the health department for follow-up and treatment of sexual contacts. Administer ordered antibiotic medication regimen. Instruct in importance of preventive measures to take during sexual activity, especially if pregnant, and the screening and treatment of sexual partner. Inform that the test should be repeated every 3 months for at least 1 year or until the reaction becomes negative. Provide a sensitive, nonjudgmental environment for the client. Viral Infection Antibody Tests Viral cultures either are not available or can be disproportionately expensive in relation to the potential benefit, because effective antiviral treatment is not available for most organisms. For these reasons, viral antibody tests are used to determine exposure to and existing infections with certain viruses that are difficult to culture, or they are used to screen donors before blood donation or organ transplantation (Table 3–13). Because many types of tests can be performed, requests for viral antibody tests must be specific and include enough clinical information to permit selection of the appropriate study. A request for “viral studies” is meaningless. Antibody assays for detection of some specific disease entities, although included in Table 3–13, are outlined and discussed in the next section. They include infectious mononucleosis, hepatitis, and AIDS tests. Reference Values In general, lack of exposure to the virus yields a negative test result. Reference values vary with the type of viral antibody test. The laboratory performing the test should be consulted. INDICATIONS FOR VIRAL INFECTION ANTIBODY TESTS Suspected AIDS or exposure to human immunodeficiency virus (HIV) Retrospective confirmation of viral infection Determination of immunity to rubella in women of childbearing age and Immunologic Testing 85 Confirmation of exposure to rubella in early pregnancy Suspected herpes encephalitis Determination of immunity to chickenpox in children with leukemia, because this infection may be fatal in such children Identification of asymptomatic carriers of cytomegalovirus (CMV) Monitoring of the course of prolonged viral disease Monitoring of mothers and neonates for exposure to viral infections that may cause congenital disease in the newborn infant (usually done by the toxoplasmosis, other infections, rubella, CMV infection, and herpes simplex [TORCH] test; see Table 3–13) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Women of childbearing age with low rubella titers should be appropriately immunized. Abnormal test results, complications, and precautions: Response is dependent on the type of viral antibody test and the specific infectious process identified in Table 3–13. See the specific tests that follow for nursing implications related to aftercare and observations. INFECTIOUS MONONUCLEOSIS TESTS Diagnosis of infectious mononucleosis, caused by Epstein-Barr virus (EBV), depends on serologic (antigen-antibody) confirmation of clinical manifestations of the disease that include fever, sore throat, and lymphadenopathy. EBV stimulates the formation of new antigens that, in turn, stimulate a humoral and cellular immune response. The humoral response is characterized by an increased titer of the antibodies IgG and IgM early in the disease. The cellular response is characterized by the activation of T cells later in the illness in response to the EBV-induced infection. Copyright © 2003 F.A. Davis Company 86 SECTION I—Laboratory Tests TABLE 3–13 • Tests for Viral Diseases Virus/Disease Serologic Tests Respiratory syndromes Influenza CF, HI Parainfluenza Adenoviruses CF, HI, NT Chlamydia CF, IFA Respiratory syncytial virus Arbovirus CF, HI, NT Colorado tick fever Yellow fever Meningoencephalitis Antibodies to echo, herpes, polio, and coxsackie viruses by neutralization tests Herpes viruses Fluorescein-tagged antibodies in cells, EIA, indirect HI Herpes simplex* Varicella zoster Cytomegalovirus* Epstein-Barr virus Heterophile antibody (Monotest), agglutination test, IFA Rubella* IgM titers, CF, HI Mumps Measles Infectious hepatitis IgM titers, IgG titers, hepatitis A virus antibodies (anti-Ha), CF, RIA Serum hepatitis Antibodies to hepatitis B virus surface antigen (HBsAb) (HBsAg) Cytomegalic inclusion disease CF, HI, EIA Acquired immunodeficiency syndrome (AIDS) Human immunodeficiency virus (HIV-1) antibodies, IFA, EIA, WIB Leukemia and tropical spastic paraparesis HTLV-1 and HTLV-II antibodies, ETA, WIB * In the TORCH test, antibodies to Toxoplasma gondii (see Table 3–9), rubella virus, cytomegalovirus, and herpesvirus are measured. CFcomplement fixation, EIAenzyme immunoassay, HIhemagglutination inhibition, IFAimmunofluorescent antibody, NTneutralization test, RIAradioimmunoassay, WIBWestern immunoblot assay. The hallmark of EBV infection is the heterophil antibody, also called the Paul-Bunnell antibody, the formation of which is stimulated by the virus. The heterophil antibody is an IgM that agglutinates sheep or horse red cells. Forssman antibody, which can be present in the serum of normal people as well as in that of individuals with serum sickness, also agglutinates with sheep erythrocytes. The Davidsohn differential absorption test can be used to distinguish between the Paul-Bunnell antibody and the Forssman antibody. Currently, more rapid and sensitive tests are available that use red blood cells from horses in a single-step agglutination test.31 These tests (e.g., Monospot, Monoscreen) are used as screening tests for infectious mononucleosis and are gradually replacing the more traditional techniques. Reference Values Negative, or a titer of less than 1:56 heterophile antibodies Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology INTERFERING FACTORS False-positive results may occur in the presence of narcotic addiction, serum sickness, lymphomas, hepatitis, leukemia, cancer of the pancreas, and phenytoin therapy. INDICATION FOR INFECTIOUS MONONUCLEOSIS TESTS Suspected infectious mononucleosis (Of individuals with EBV infectious mononucleosis, 95 percent will have a positive result, 86 percent in the first week of illness.) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). A thorough history should be obtained to identify possible sources of false-positive results. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. For screening tests, the directions accompanying the test kit are followed. For traditional tests, the sample should be sent to the laboratory promptly. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report increased heterophile titer or titers against EBV. Assess signs and symptoms of infection such as fever, chills, malaise, sore throat, anorexia, enlarged lymph nodes, and fatigue. Provide rest, adequate nutritional and fluid intake, and activities that do not cause fatigue or stress. HEPATITIS TESTS Hepatitis tests include measurements of serologic markers that appear during the course of the disease caused by the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus. Laboratory methods used in the detection of specific antigens or antibodies include radioimmunoassay (RIA) and enzyme immunoassay (EIA). Hepatitis A is a self-limiting disease that does not usually cause liver damage or a chronic infectious state. It occurs as the result of oral ingestion of the virus and is characterized by malaise, anorexia, fever, and nausea. The virus is present in the feces, but and Immunologic Testing 87 diagnosis is based on serologic markers (anti-HAV, IgM, IgG) identified in the laboratory. The diagnosis is made for hepatitis A if anti-HAV antibodies can be demonstrated in the early acute stage of the disease or if there is a high level of IgM anti-HAV compared to the level of the IgG antibody to HAV. IgM antibodies appear in the early stages, and IgG antibodies indicate past infection and immunity to reinfection. Hepatitis B, also known as the Australian antigen, is a more serious, prolonged disease that can result in liver damage and chronic active hepatitis. HBV can be found in the blood, feces, saliva, semen, sweat, urine, or any body fluid of infected individuals and can be transmitted by exposure to blood products or parenteral contact with articles contaminated with material containing the virus. Diagnosis is made by identification of the hepatitis B surface antigen (HBsAg) circulating in the blood before and during the acute early stage before enzyme elevations or in chronic carriers after an acute illness. It is the first indicator of acute hepatitis infection. The recovery from and immunity to HBV as late as 6 to 10 months after an active infection are identified by the detection of anti-HBs. The presence of hepatitis B antibody (anti-HBe, HBeAb) indicates the resolution of acute infection or, along with positive HBsAg, indicates an asymptomatic, healthy carrier. The presence of hepatitis B e antigen (HBeAg) is an early indicator of hepatitis B infection. If HBeAg persists for more than 3 months, it is indicative of chronic infection. Delta hepatitis coinfects with HBV, and diagnosis is made by detection of the antibodies (anti-D) in the blood. Hepatitis C is a parenterally acquired disease usually caused by blood transfusion but also by IV drug abuse. The disease can lead to chronic hepatitis and cirrhosis of the liver. The test is performed to detect the antibodies to HCV in the blood of those at risk for the infection and transmission of the virus as a blood donor. Antibody formation can take as long as a year after exposure to the virus. Hepatitis D is caused by a “defective” virus that can produce infection only when HBV is present. HDV antigens do not circulate and are found only in hepatocytes. Hepatitis D occurs with HBV and can result in more serious disease in individuals with chronic HBV infection. Hepatitis D is also known as delta agent hepatitis. Hepatitis E is similar in presentation and disease course to hepatitis A. It occurs primarily in Asia, Africa, and South America.32 INTERFERING FACTORS The administration of radionuclides within 1 Copyright © 2003 F.A. Davis Company 88 SECTION I—Laboratory Tests body fluids, personal contact through sexual activity, or presence of pregnancy (the infection could be transmitted to the infant).33 Reference Values Hepatitis A Anti-HAV Negative THE PROCEDURE IgM Negative IgG Negative A venipuncture is performed and the sample collected in a red-topped tube. For screening tests, the directions accompanying the test kit are followed. For traditional testing, the sample should be sent to the laboratory promptly, with the test performed within 7 days or frozen for future analysis. Hepatitis B Surface antigen (HBsAg) Negative Surface antibody (HBsAb) Negative B antigen (HBeAg) Negative B antibody (HBeAb) Negative Core antibody (anti-HBcAb) Negative Hepatitis C C antibody (anti-HCV) Negative Hepatitis D Delta antibody (anti-HDV) Negative week of testing using the RIA technique can cause inaccurate results. Rheumatoid factor and competing IgG-specific antibody can cause inaccurate positive and negative results. INDICATIONS FOR HEPATITIS TESTS Detection of the presence of antigen or antibody to a specific type of hepatitis depending on symptoms and stage of the disease in the diagnosis of the condition Determination of possible hepatitis carrier status Determination of past exposure or immunity status in those with a history of hepatitis Screening of pretransfusion donors for a history or presence of hepatitis, especially if asymptomatic and information source questionable Determination of progression to chronic hepatitis or persistent signs and symptoms of liver dysfunction NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Obtain a thorough history regarding possible ingestion of contaminated water or foods, environmental sanitation factors conducive to occurrence, recent blood transfusion, parenteral exposure to materials contaminated by blood or NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report presence of antigen or antibody to a specific type of hepatitis. Provide rest and energy-saving assistance as needed, skin care for jaundice and pruritus, and adequate nutritional and fluid intake. Disease transmission: Note and report type of hepatitis. If hepatitis A, place client on enteric precautions. If hepatitis B, C, or D, observe standard precautions for blood-borne pathogens (see Appendix III for hand protection, personal protection, and needles and sharps), and instruct in precautions against transmission via sharing of needles by IV drug abusers and sexual contact. Disease prevention: Hepatitis A and B vaccines for active immunity. Instruct client to avoid donating blood for 6 months if a transfusion has been received and to never donate blood if diagnosis of hepatitis B has been made. ACQUIRED IMMUNODEFICIENCY SYNDROME TESTS AIDS and the early stages of HIV infection are diseases of the immune system caused by the human immunodeficiency virus or HIV-2. This virus is responsible for infecting and destroying the T-helper lymphocytes (CD4 cells). This destruction, in turn, affects the ability of the body to produce antibodies and suppresses cellular immune responses, leading to disorders and infections by many opportunistic infectious agents. The average time from HIV infection to development of full-blown AIDS is approximately 10 years. The clinical manifestations of the infection also can vary from an initially mild illness to an acute state. Those at high risk for the disease include male homosexuals, hemophiliacs, recipients of blood or blood products before 1985, and IV drug Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology users who share needles. Heterosexual transmission of the virus is on the rise.34 After the virus has been acquired, antigens are detectable in the blood serum as early as 2 weeks, and they remain for 2 to 4 months. At this time, antibodies appear. Late in the disease, antigens reappear and antibodies decrease, indicating a poor prognosis. The most common tests to screen for HIV-1 virus antibodies are the EIA, also known as the enzyme-linked immunosorbent assay (ELISA), and the immunofluorescence assay. The test is repeated if the results are positive or borderline. Repeat testing after a positive value requires confirmation by the Western immunoblot (WIB) assay, which has the ability to identify antibodies to at least nine different epitopes of HIV-1. Antigen testing in the early stages of HIV-1 infections before antibodies are detected can be undertaken to monitor clients for progression of the disease and response to therapy. It is also useful to diagnose HIV-1 infection in infants when maternal antibodies are passively transferred and diagnosis based on serologic testing is difficult.35 Reference Values Negative for HIV antigen by antigen capture assay during initial infectious state and in advanced state of the disease Negative for HIV antibodies by antibody detection methods, EIA, and immunofluorescence assay Negative for confirmation test for HIV antibodies by WIB and Immunologic Testing 89 INDICATIONS FOR ACQUIRED IMMUNODEFICIENCY SYNDROME TESTS Detection of the core p24 protein and antibodies to the identified protein in the diagnosis and staging or progression of infections in AIDS Confirmation of positive test results obtained by EIA to ensure accurate results Determination of the extent of CD4 (T-helper lymphocytes) cell decreases in relation to normal or increased levels of CD8 (T-suppressor) cells to predict immunodeficiency state Prediction of exacerbation of the disease by increased protein 2-microglobulin, indicating destruction of lymphocytes and macrophages Assistance in the diagnosis of AIDS in the presence of opportunistic infections determined by culture and microorganism identification Screening of those in high-risk groups for the development of AIDS Screening of blood donors by blood banks before obtaining blood donations Screening of blood before using for transfusion or preparation of blood products NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Obtain a history regarding possible contact with the virus such as sexual practices, drug abuse with needle sharing, transfusion with contaminated blood products, or presence of pregnancy (virus could be transmitted to the infant). Inform the client of confidentiality and legal requirements regarding the test performance and test results. INTERFERING FACTORS Negative results can occur in infected individuals because of lack of antibody formation early in the disease and in late stages because of loss of ability to produce antibodies. Inaccurate results can occur with the use of test kits that contain proteins if an individual has been exposed to the media used in the kits. Cross-reactive antibodies directed to antigenic determinants found in nonpathogenic retroviruses can result in inaccurate positive results.36 Children who become infected before birth through an infected mother can have inaccurate negative results. Corticosteroids can affect lymphocyte subset test results. Protease inhibitors can inhibit replication of infected cells and cell-to-cell spread of HIV. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped (antigen or antibody) or lavender-topped (lymphocyte or microglobulin) tube, depending on the tests to be performed. Appropriate apparel (gloves and mask) and precautions for blood-borne pathogens are carried out when obtaining and caring for the blood samples (see Appendix III). NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report positive test results. Inform client of the most current information regarding medications, economic and Copyright © 2003 F.A. Davis Company 90 SECTION I—Laboratory Tests social assistance, and possible psychological counseling services. Instruct client in adequate nutritional and fluid intake. Provide a sensitive, nonjudgmental, and caring environment for the client. Disease transmission: Instruct client in precautions to take during sexual activity; advise to avoid sharing needles during drug use and to avoid donating blood. Provide care using standard precautions and observing transmission-based isolation procedures for blood-borne pathogens. Medicolegal aspects: Observe regulations for confidentiality in reporting test results, such as use of computer or telephone. Maintain confidentiality of records containing test results. Carry out state regulation regarding the reporting of positive results. Provide a form for physician to sign regarding any risks associated with testing and obtain a signed informed permission request before the test. Contact Centers for Disease Control and Prevention (CDC) for the latest guidelines on reporting HIV status and appropriate follow-up and counseling. IMMUNOLOGIC TESTS RELATED TO CANCER Tumor markers are defined as substances produced by malignant or benign cells in response to the presence of cancer. They are detected by the examination of body fluids and tissue specimens. Their use includes tumor prediction, detection, and identification; monitoring of the course and prognosis; and evaluation of therapy protocols. The most desirable markers are those that can detect malignancy in a remote area by the analysis of body fluids (serum, urine, fluid from effusion, and CSF) rather than by invasive procedures to obtain a tissue sample. The markers are classified as endocrine (hormones), metabolic consequences associated with tumor (albumin, blood cells, lipids), enzymes and isozymes, oncofetal antigens or glycoproteins, and gene alteration or oncogenes. Current tumor markers and some clinical associations in use at this time are listed in Table 3–14.37,38 Panels of tumor markers to assist in the identification or confirmation of a malignancy in relation to tissue site and to assist in monitoring the course and prognosis of the malignancy are also performed. Malignancies or cancer can invade organ tissues, access vascular channels, and metastasize to other body sites. They are characterized by an abnormal number of cells that grow without the normal control and immune abilities of the body. There is no single molecular or morphologic characteristic specific to malignancies.39 This allows for the presence of abnormal reference values associated with benign cells and conditions other than cancer. Complete specific test information regarding the blood cells, enzyme, hormone, endocrine, and metabolic markers listed in Table 3–14 is included in the respective chapters. These tests are commonly performed to obtain information about many other disorders, and differentiation is made when analyzing the results in the diagnosis of malignancy. Antigens and globulins, used in the diagnosis and treatment of cancer and commonly found in fetal life, are considered individually in this section. These substances are considered abnormal in adults if present in excessive amounts. SERUM -FETOPROTEIN TEST During the first 10 weeks of life, the major serum protein is not albumin, but -fetoprotein (AFP). Fetal liver synthesizes huge quantities of AFP until about the 32nd week of gestation. Thereafter, synthesis declines until, at 1 year of age, the serum normally contains no more than 30 ng/mL. Resting liver cells (hepatocytes) normally manufacture very little AFP, but rapidly multiplying hepatocytes resume synthesis of large amounts.40 Thus, the test’s greatest usefulness is in monitoring for recurrence of hepatic carcinoma or metastatic lesions involving the liver. Note that 30 to 50 percent of Americans with liver cancer do not have elevated AFP levels. More consistent elevations are seen in those Asian and African populations with a very high incidence of hepatocellular carcinoma.41 Measurement of AFP levels in maternal blood and amniotic fluid is used to detect certain fetal abnormalities, especially neural tube defects such as anencephaly, spina bifida, and myelomeningocele (see Chapter 10). Routine prenatal screening includes determination of the mother’s serum AFP level at 13 to16 weeks of pregnancy. If maternal blood levels are elevated on two samples obtained 1 week apart, an ultrasound may be performed, and AFP levels in amniotic fluid may be analyzed. Other possible causes of elevated AFP levels during pregnancy include multiple pregnancy and fetal demise. INDICATIONS FOR SERUM -FETOPROTEIN TEST Monitoring for hepatic carcinoma or metastatic lesions involving the liver, as indicated by highly elevated levels (e.g., 10,000 to 100,000 ng/mL) Monitoring for response to treatment for hepatic carcinoma, with successful treatment indicated by an immediate drop in levels Monitoring for recurrence of hepatic carcinoma, Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology TABLE 3–14 • and Immunologic Testing 91 Cancer Tests and Tumor Markers Marker Clinical Association Alkaline phosphatase (ALP) (enzyme isozyme) Osteogenic sarcoma, osteoblastic carcinoma metastasis -Fetoprotein (AFP) (oncofetal antigen) Testicular, hepatic carcinoma CA 15-3 antigen (oncofetal antigen) Breast malignancy CA 19-9 antigen (oncofetal antigen) Stomach, colon, pancreatic carcinoma CA 50 antigen (oncofetal antigen) Stomach, colon, pancreatic carcinoma CA 125 antigen (oncofetal antigen) Ovarian, fallopian tube carcinoma Calcitonin (polypeptide hormone) Thyroid medullary carcinoma Carcinoembryonic antigen (CEA) (oncofetal antigen) Breast, colon, lung carcinoma Catecholamines (vanillylmandelic acid metabolite) Neuroblastoma and pheochromocytoma Creatine kinase isoenzyme (CK-BB) (enzyme isoenzyme) Breast, pulmonary carcinoma DU-PAN-2 (glycoprotein antigen) Pancreatic carcinoma Galactosyltransferase (GT II) (enzyme isoenzyme) Pancreatic carcinoma Genetic mutation (DNA, oncogenes) Predisposition to development of carcinoma, leukemia, lymphoma Human chorionic gonadotropin (hCG) (glycoprotein hormone) Testicular carcinoma 5-Hydroxyindoleacetic acid (5-HIAA) (serotonin metabolite) Carcinoid tumor Immunoglobulins produced by B lymphocytes Multiple myeloma, lymphomas Lactate dehydrogenase (LD) (enzyme isoenzyme LD1) Renal carcinoma, leukemia, lymphoma Lymphocyte B- and T-cell surface antigens (blood cell) Lymphomas, lymphoblastic leukemia Neuron-specific enolase (NSE) (enolase isoenzyme) Neuroblastoma, lung carcinoma Prostate-specific antigen (PSA) (serine protease) Prostatic carcinoma Prostatic acid phosphatase (PAP) (enzyme isozyme) Prostatic carcinoma Tissue polypeptide antigen (TPA) (oncofetal antigen) Breast, lung, liver, pancreas, colorectal, stomach, ovary, prostate, bladder, head and neck, thyroid carcinoma Squamous cell carcinoma (SCC) antigen (protein antigen) Cervical, lung, esophageal, head and neck carcinoma Vasoactive intestinal peptide (VIP) Intestinal tumor Reference Values Neonates 1 yr old to adults Conventional Units SI Units 600,000 ng/mL 600,000 g/L 30 ng/mL 30 g/L Copyright © 2003 F.A. Davis Company 92 SECTION I—Laboratory Tests with elevated levels occurring 1 to 6 months before the client becomes symptomatic Suspected hepatitis or cirrhosis, as indicated by slightly to moderately elevated levels (e.g., 500 ng/mL) Routine prenatal screening for fetal neural tube defects and other disorders, as indicated by elevated levels Suspected intrauterine fetal death, as indicated by elevated levels Support for diagnosing embryonal gonadal teratoblastoma, hepatoblastoma, and ataxia-telangiectasia diseases and in smokers (Table 3–15). Although the test is not diagnostic for any specific disease, it is used primarily when various types of carcinomas are suspected. Reference Values Less than 2.5 ng/mL INTERFERING FACTORS Levels may be elevated in smokers who do not have malignancies. NURSING CARE BEFORE THE PROCEDURE For serum studies, client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). For amniotic fluid studies, the client is prepared for amniocentesis, as described in Chapter 10. THE PROCEDURE For serum studies, a venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and transported promptly to the laboratory. For amniotic fluid studies, amniocentesis is performed (see Chapter 10). NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedures are the same as for any study involving collection of a peripheral blood sample or amniocentesis (see Chapter 10). Abnormal adult values: Note and report increased levels and relate to tissue healing or regeneration. Assess history for presence or treatment of malignancy; assist in coping with need for additional treatments. Abnormal fetal values: Note and report increased levels in amniotic fluid analysis results or pregnant woman’s serum test results. Assess for fear and anxiety levels while waiting for test results. Provide information about genetic counseling, termination of pregnancy, or both. CARCINOEMBRYONIC ANTIGEN TEST Carcinoembryonic antigen (CEA) is a glycoprotein normally produced only during early fetal life and during rapid multiplication of epithelial cells, especially those of the digestive system. Elevations of CEA occur with many cancers, primary and recurrent, as well as with a number of nonmalignant INDICATIONS FOR CARCINOEMBRYONIC ANTIGEN TEST Monitoring of clients with inflammatory intestinal disorders with a high risk of malignancy Suspected carcinoma of the colon, pancreas, or lung, because these cancers produce the highest CEA levels Monitoring of response to therapy for cancer, with effective treatment indicated by normal levels within 4 to 6 weeks Monitoring for recurrence of carcinoma, with elevated levels occurring several months before the client becomes symptomatic Suspected leukemia, gammopathy, or other disorder associated with elevated CEA levels (see Table 3–15) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample must be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Abnormal values: Note and report increased values or return of increased values. Assess history for presence of malignancy and site or treatment of malignancy. Assist client and family in coping with need for additional treatments or poor prognosis. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology TABLE 3–15 • and Immunologic Testing 93 Causes of Alterations in CEA Levels Percentage with CEA Levels, ng/mL 2.5 2.6–5 5.1–10 10 Nonsmokers 97 3 0 0 Smokers 81 15 3 1 Ex-smokers 93 5 1 1 Colorectal 28 23 14 34 Pulmonary 24 25 25 25 Gastric 39 32 10 19 9 31 26 35 Breast 53 21 13 14 Head/neck 48 32 14 5 Cause of Alteration Carcinomas Pancreatic Other 53 27 12 9 Leukemias 63 25 8 5 Lymphoma 65 24 11 0 Sarcoma 68 26 5 0 Benign tumors 82 12 6 1 Benign breast disease 85 11 4 0 Pulmonary emphysema 43 37 16 4 Alcoholic cirrhosis 29 44 24 2 Ulcerative colitis 69 18 8 5 Regional ileitis 60 27 11 2 Gastric ulcer 55 29 15 1 Colorectal polyps 81 14 3 1 Diverticulitis 73 20 5 2 CA 15-3, CA 19-9, CA 50, AND CA 125 ANTIGEN TESTS Cancer antigens are substances detected in serum or tissue and are defined by one or two monoclonal antibodies. Immunologic methods are used to detect the substances in serum and immunohistochemical methods in tissue. Assay kits for these markers are available to ensure consistent values among agencies performing the tests. These tumor markers are not used for screening malignancy in asymptomatic populations. CA 15-3 is a serum antigen defined by two monoclonal antibodies found in breast cancer and breast cancer metastasis to the liver as well as in benign diseases of the breast. CA 19-9 is a serum antigen defined by a monoclonal antibody found in malignancies of the pancreas, gallbladder, salivary glands, and endocervix as well as in benign disorders such as acute pancreatitis, inflammatory bowel disease, and hepatobiliary disease. The test is commonly performed to monitor the course of a malignancy that is known to produce the antigen. CA 50 is a serum antigen defined by a monoclonal antibody found in pancreatic, colorectal, and gastrointestinal malignancies. Besides its diagnostic value, CA 50 is used to monitor the course of a tumor that produces the antigen. Copyright © 2003 F.A. Davis Company 94 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units CA 15-3 35 U/ml 35 kU/L CA 19-9 37 U/ml 37 kU/L CA 50 37 U/ml 37 kU/L CA 125 35 U/ml 35 kU/L CA 125 is a serum antigen defined by a monoclonal antibody found in ovarian and pelvic organ malignancies as well as in breast and pancreatic malignancies. Nonmalignant conditions such as ascites of benign cause, pregnancy, menstruation, endometriosis, and pelvic inflammatory disease also cause increases in this antigen. The test is undertaken to monitor surgical removal of malignant ovarian tumor for recurrence and metastasis. Another test, tissue polypeptide antigen (TPA), is a marker identified in serum and tissue in those with a variety of malignancies in relation to the extent of the disease and subsequent recurrence or regression after surgical removal of the tumor.42 INTERFERING FACTORS Chemotherapeutic agents administered to treat tumor. Levels can be increased in the absence of disease or in benign disorders and can affect diagnostic findings for malignancy. INDICATIONS FOR CA 15-3, CA 19-9, CA 50, AND CA 125 ANTIGEN TESTS Diagnosis and confirmation of presence of local and metastatic malignancy, suggested by an increased level or a gradual rise in levels of the specific cancer antigen Determination of residual tumor after surgical intervention to remove the malignancy Monitoring of course of the malignancy and effectiveness of therapeutic regimen to determine progression, prognosis, or recurrence Differentiation between malignant and benign disorders of specific organ tissues NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Obtain a history regarding the presence of other acute or chronic diseases and the assessment data that support the diagnoses. Ensure that neoplastic medication protocols are administered. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be transported promptly to the laboratory for analysis by immunoassay methods. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report increased values or return of increased values. Assess for presence of malignancy site or metastasis or both, past or ongoing treatments, and procedures for malignancy. Assist client and family to reduce anxiety and to cope with need for additional treatments or poor prognosis. REFERENCES 1. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 63. 2. Winkelstein, A, et al: White Cell Manual, ed 5. FA Davis, Philadelphia, 1998, p 61. 3. Ibid, pp 61–62. 4. Ibid, p 63. 5. Ibid, pp 63–64. 6. Ibid, pp 68–71. 7. Ibid, p 74. 8. Sacher and McPherson, op cit, pp 242–243. 9. Ibid, p 244. 10. Winkelstein et al, op cit, p 69. 11. Ibid, p 69. 12. Ibid, pp 69–73. 13. Ibid, pp 72–73. 14. Ibid, p 74. 15. Ibid, p 65. 16. Sacher and McPherson, op cit, p 256. 17. Ibid, p 256. 18. Ibid, pp 252–253. 19. Ibid, pp 252–254. 20. Winkelstein et al, op cit, pp 83–84. 21. Sacher and McPherson, op cit, p 253. 22. Ibid, p 246. 23. Ibid, p 246. 24. Ibid, pp 254–255. 25. Ibid, p 255. 26. Ibid, p 262. Copyright © 2003 F.A. Davis Company CHAPTER 3—Immunology 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. Ibid, pp 531–532. Ibid, p 531. Ibid, p 531. Ibid, p 532. Ibid, p 542. Centers for Disease Control and Prevention, Hepatitis Branch: Epidemiology and prevention of viral hepatitis A to E: An overview. CDC, Atlanta, Ga, 1998. Sacher and McPherson, op cit, pp 441–442. Ray, CG, and Minnich, LL: Viruses, rickettsia, and chlamydia. In James, JB: Clinical Diagnosis and Management by Laboratory Methods, ed 18. WB Saunders, Philadelphia, 1991, p 1249. Ibid, pp 1249–1250. Stevens, RW, and McQuillan, GM: Serodiagnosis of human 37. 38. 39. 40. 41. 42. and Immunologic Testing 95 immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. In James, JB: Clinical Diagnosis and Management by Laboratory Methods, ed 18. WB Saunders, Philadelphia, 1991, pp 913–914. Rooney, MT, and Henry, JB: Molecular markers of malignant neoplasms. In James, JB: Clinical Diagnosis and Management by Laboratory Methods, ed 18. WB Saunders, Philadelphia, 1991, pp 285–286. Sacher and McPherson, op cit, p 779. Rooney and Henry, op cit, p 286. Sacher and McPherson, op cit, pp 437–438. Ibid, p 438. Rooney and Henry, op cit, pp 297–298. Copyright © 2003 F.A. Davis Company CHAPTER Immunohematology and Blood Banking TESTS COVERED ABO Blood Typing, 96 Rh Typing, 98 Direct Antiglobulin Test, 99 Indirect Antiglobulin Test, 100 Human Leukocyte Antigen Test, 101 INTRODUCTION Immunohematology is the study of the antigens present on blood cell membranes and the antibodies stimulated by their presence. For red cells, more than 300 antigenic configurations have been discovered and classified. A specific biologic role has been identified for only a few of these (e.g., ABO and Rh typing for blood transfusions). One commonality is that blood cell antigens are inherited, and the genes that determine them follow the laws of mendelian genetics.1 Thus, the greatest usefulness for many of the blood cell antigens that have been identified to date is in genetic studies. The focus of this chapter is on tests of blood cell antigens and related antibodies that are used in determining the compatibility of blood and blood products for transfusions. ABO BLOOD TYPING The major antigens in the ABO system are A and B. An individual with A antigens has type A blood; an individual with B antigens has type B blood. A person with both A and B antigens has type AB blood, and one having neither A nor B antigens has type O blood. The genes determining the presence or absence of A or B antigens reside on chromosome number 9.2 Immunologically competent individuals more than 6 months of age have serum antibodies that react with the A and B antigens absent from their own red cells (Table 4–1). Thus, a person with type A blood has anti-B antibodies, whereas one with type B blood has anti-A antibodies. Individuals with type AB blood have neither of these antibodies, whereas those with type O blood 96 have both. These antibodies are not inherited, but develop after exposure to environmental antigens that are chemically similar to red cell antigens (e.g., pollens and bacteria). Individuals do not, however, develop antibodies to their own red cell antigens.3,4 Anti-A and anti-B antibodies are strong agglutinins and cause rapid, complement-mediated destruction (see Chapter 3) of any incompatible cells encountered. Although most of the anti-A and anti-B activity resides in the IgM class of immunoglobulins (see Chapter 3), some activity rests with IgG. Anti-A and anti-B antibodies of the IgG class coat the red cells without immediately affecting their viability and can readily cross the placenta, resulting in hemolytic disease of the newborn. Persons with type O blood frequently have more IgG anti-A and anti-B antibodies than do Copyright © 2003 F.A. Davis Company CHAPTER 4—Immunohematology TABLE 4–1 • and Blood Banking 97 Antigens and Antibodies in ABO Blood Groups Frequency, % in US Populations Blood Group Antigens on Red Cells Antibodies in Serum Whites American Blacks Native Americans Asians A A Anti-B 40 27 16 28 B B Anti-A 11 20 4 27 O Neither Anti-A 45 49 79 40 AB A and B Neither 4 4 1 5 Anti-B From Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 268, with permission. individuals with type A or B blood. Thus, ABO hemolytic disease of the newborn (erythroblastosis fetalis) affects infants of type O mothers almost exclusively.5 When blood transfusions are required, the client is normally given blood of his or her own type to prevent adverse antigen-antibody reactions. In emergency situations, however, some individuals may be given blood of other ABO types. For example, because type O blood has neither A nor B antigens, it may be given to individuals with types A, B, and AB blood. Thus, a person with type O blood is called a universal donor. With the advent of colloid expanders (e.g., dextran), untyped blood is not given even in cases of hemorrhage. Further, because persons with type O blood have both anti-A and anti-B antibodies, they can receive only type O blood. The situation is reversed for those with type AB blood. Because these individuals lack anti-A and anti-B antibodies, they may receive transfusions of types A, B, and O blood in emergencies when type AB blood is not available. Thus, a person with type AB blood is called a universal recipient. ABO blood typing is an agglutination test in which the client’s red cells are mixed with anti-A and anti-B sera, a process known as forward grouping. The procedure is then reversed, and the person’s serum is mixed with known type A and type B cells (i.e., reverse grouping). When a transfusion is to be administered, cross-matching of blood from the donor and the recipient is performed along with typing. Cross-matching detects antibodies in the sera of the donor and the recipient that could lead to a transfusion reaction as a result of red cell destruction. Other pretransfusion or post-transfusion tests can be performed to determine the cause of transfusion reactions. The leukoagglutinins are antibodies in the donor blood that react with white blood cells in the recipient’s blood, producing fever, cough, dyspnea, and other lung complications, depending on the severity of the reaction after the transfusion. Such a reaction requires that leukocyte-poor blood be used to transfuse these clients. Platelet antibody tests are performed to detect specific antibodies that cause post-transfusion purpuric reactions. Assays as well as platelet typing can be performed to support a diagnosis of post-transfusion purpura and thrombocytopenic purpura.6 Reference Values The normal distribution of the four ABO blood groups in the United States is shown in Table 4–1. Discrepancies in the results of forward and reverse grouping may occur in infants, elderly persons, and persons who are immunosuppressed or who have a variety of immunologic disorders.7 INDICATIONS FOR ABO BLOOD TYPING Identification of the client’s ABO blood type, especially before surgery or other procedures in which blood loss is a threat or for which replacement may be needed, or both Identification of donor ABO blood type for stored blood Determination of ABO compatibility of donor’s and recipient’s blood types Identification of maternal and infant ABO blood types to predict potential hemolytic disease of the newborn NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Immunosuppressive drugs taken by the client or Copyright © 2003 F.A. Davis Company 98 SECTION I—Laboratory Tests the presence of an immunologic disorder should be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The sample must be handled gently to avoid hemolysis and sent promptly to the laboratory. Although correct client identification is important for all laboratory and diagnostic procedures, it is crucial when blood is collected for ABO typing. One of the most common sources of error in ABO typing is incorrect identification of the client and the specimens.8 NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. The client should be informed of his or her blood type, and the information should be recorded on a card or other document (e.g., driver’s license) that the client normally carries in the event of an emergency requiring a blood transfusion. Circulatory overload: Report increased blood pressure; bounding pulse; and signs of pulmonary edema such as dyspnea, rapid and labored breathing, cough producing blood-stained sputum, and cyanosis. Blood transfusion reaction: Note and report reduced blood pressure, elevated temperature, chills, palpitations, substernal or flank pain, warmth at the infusion site, or anxiety. Discontinue transfusion and infuse saline. Send the leftover unit of blood and a blood and urine specimen to the laboratory. Critical values: Notify physician immediately if an incompatible cross-match occurs. Rh TYPING After the ABO system, the Rh system is the group of red cell antigens with the greatest importance.9 The antigen was called the Rh factor because it was produced by immunizing guinea pigs and rabbits with red cells of rhesus monkeys. Researchers found that the serum from the immunized animals agglutinated not only the rhesus monkey red cells but also the red cells of approximately 85 percent of humans. Thus, human red cells could be classified into two new blood types: Rh-positive and Rh-negative. This discovery was a great breakthrough in explaining transfusion reactions to blood that had been tested for ABO compatibility as well as in explaining hemolytic disease of the newborn not caused by ABO incompatibility between mother and fetus.10 We now know that the Rh system includes many different antigens. The major antigen is termed Rho or D. Persons whose red cells possess D are called Rh-positive; those who lack D are called Rh-negative, no matter what other Rh antigens are present, because the D antigen is more likely to provoke an antibody response than any other red cell antigen, including those of the ABO system. The other major antigens of the Rh system are C, E, c, and e.11 Among blacks, there are many quantitative and qualitative variants of the Rh antigens that do not always fit into the generally accepted classifications.12 Rh-negative individuals may produce anti-D antibodies if exposed to Rh-positive cells through either blood transfusions or pregnancy. Although 50 to 70 percent of Rh-negative individuals develop antibodies if transfused with Rh-positive blood, only 20 percent of Rh-negative mothers develop anti-D antibodies after carrying an Rh-positive fetus. This difference occurs because a greater number of cells are involved in a blood transfusion than are involved in pregnancy. When Rh antibodies develop, they are predominantly IgG. Thus, they coat the red cells and set them up for destruction in the reticuloendothelial system. The antibodies seldom activate the complement system (see Chapter 3). Anti-D antibodies readily cross the placenta from mother to fetus and are the most common cause of severe hemolytic disease of the newborn. Immunosuppressive therapy (e.g., with Rho[D] immune globulin [RhoGAM]) successfully prevents antibody formation when given to an unimmunized Rh-negative mother just after delivery or abortion of an Rh-positive fetus.13 Rh typing involves an agglutination test in which the client’s red cells are mixed with serum containing anti-D antibodies. Agglutination indicates that the D antigen is present, and the person is termed Rh-positive. Reference Values The D antigen is present on the red cells of 85 percent of whites and a higher percentage of blacks, Native-Americans, and Asians. INDICATIONS FOR RH TYPING Identification of the client’s Rh type, especially before surgery or other procedures in which blood loss is a threat or for which replacement may be needed, or for both Copyright © 2003 F.A. Davis Company CHAPTER 4—Immunohematology Identification of donor Rh type for stored blood Determination of Rh compatibility of donor’s and recipient’s blood Identification of maternal and infant Rh types to predict potential hemolytic disease of the newborn Determination of anti-D antibody titer after sensitization by pregnancy with an Rh-positive fetus Determination of the need for immunosuppressive therapy (e.g., with RhoGAM) when an Rhnegative woman has delivered or aborted an Rh-positive fetus NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. The sample must be handled gently to avoid hemolysis and sent promptly to the laboratory. As with ABO typing, correct client and sample identifications are crucial in avoiding erroneous results. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as that for any study involving the collection of a peripheral blood sample. As with ABO typing, the client should be informed of his or her Rh type. Women of childbearing age who are Rh-negative should be informed of the need for follow-up should pregnancy occur. Rh incompatibility: Note and report Rh factors of mother and father, number of pregnancies, and past transfusions of Rh-positive blood given to an Rh-negative mother. Communicate incompatible test results to the physician. Inform client and prepare client for administration of Rh immunoglobulins (RhoGAM). ANTIGLOBULIN TESTS (COOMBS’ TESTS) Antiglobulin (Coombs’) tests are used to detect nonagglutinating antibodies or complement molecules on red cell surfaces. They are used most commonly in immunohematology laboratories and and Blood Banking 99 blood banks for routine cross-matching, antibody screening tests, and preliminary investigations of hemolytic anemias.14,15 The tests are based on the principle that immunoglobulins (i.e., antibodies) act as antigens when injected into a nonhuman host. This principle was originally published by Moreschi in 1908, but his findings drew little notice. In 1945, Coombs independently rediscovered the principle when he prepared antihuman serum by injecting human serum into rabbits. The rabbit antibody produced against the human globulin was then collected and purified. This antihuman globulin was used to demonstrate incomplete human antibodies that were adsorbed to red cells and did not cause visually apparent agglutination unless Coombs’ rabbit serum was used. The two applications of the test currently used are (1) the direct antiglobulin test (direct Coombs’) and (2) the indirect antiglobulin test (indirect Coombs’).16 DIRECT ANTIGLOBULIN TEST It is never normal for circulating red cells to be coated with antibody. The direct antiglobulin test (DAT, direct Coombs’) is used to detect abnormal in vivo coating of red cells with antibody globulin (IgG) or complement, or both. When this test is performed, the red cells are taken directly from the sample, washed with saline (to remove residual globulins left in the client’s serum surrounding the red cells but not actually attached to them), and mixed with antihuman globulin (AHG). If the AHG causes agglutination of the client’s red cells, specific antiglobulins can be used to determine if the red cells are coated with IgG, complement, or both. The most common cause of a positive DAT is autoimmune hemolytic anemia, in which affected individuals have antibodies against their own red cells. Other causes of positive results include hemolytic disease of the newborn, transfusion of incompatible blood, and red cell–sensitizing reactions caused by drugs. In the latter, the red cells may be coated with the drug or with immune complexes composed of drugs and antibodies that activate the complement system.17,18 Drugs associated with such reactions are listed in Table 4–2. Positive DAT results may also be seen in individuals with Mycoplasma pneumonia, leukemias, lymphomas, infectious mononucleosis, lupus erythematosus and other immune disorders of connective tissue, and metastatic carcinoma. Other conditions, such as the aftermath of cardiac vascular surgery, are associated with production of autoantibodies. Copyright © 2003 F.A. Davis Company 100 SECTION I—Laboratory Tests • Drugs That May Cause Positive Results in Direct Antiglobulin Tests TABLE 4–2 Cephaloridine (Loridine) Penicillin Cephalothin (Keflin) Phenytoin (Dilantin) Chlorpromazine (Thorazine) Procainamide (Pronestyl) Hydralazine (Apresoline) Quinidine Isoniazid Rifampin Levodopa Streptomycin Melphalan (Alkeran) Sulfonamides Methyldopa (Aldomet) Tetracycline Reference Values Negative (no agglutination) INTERFERING FACTORS Many drugs may cause positive reactions (see Table 4–2). INDICATIONS FOR DIRECT ANTIGLOBULIN TEST Suspected hemolytic anemia or hemolytic disease of the newborn as indicated by a positive reaction Suspected transfusion reaction as indicated by a positive result Suspected drug sensitivity reaction as indicated by a positive result NURSING CARE BEFORE THE PROCEDURE For samples collected by venipuncture, client preparation is the same as that for any study involving the collection of a peripheral or cord blood sample (see Appendix I). Drugs currently taken by the client should be noted. If the test is to be performed on the newborn, the parent(s) should be informed that a sample of umbilical cord blood will be obtained at delivery and will not result in blood loss to the infant. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other type of blood collection tube, depending on laboratory preference. For cord blood, the sample is collected in a red- or lavender-topped tube (depending on the laboratory) from the maternal segment of the cord after it has been cut and before the placenta has been delivered. NURSING CARE AFTER THE PROCEDURE For venipunctures, care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Note and report a positive value in cord blood of a neonate with possible erythroblastosis fetalis for direct Coombs’ because this test result indicates that antibodies are attached to the circulating erythrocytes. Assess associated bilirubin and hemoglobin levels. Prepare the infant for exchange transfusion of fresh whole blood that has been typed and cross-matched with the mother’s serum. INDIRECT ANTIGLOBULIN TEST The indirect antiglobulin test (IAT, indirect Coombs’, antibody screening test) is used primarily to screen blood samples for unexpected circulating antibodies that may be reactive against transfused red blood cells. In this test, the client’s serum serves as the source of antibody, and the red cells to be transfused serve as the antigen. The test is performed by incubating the serum and red cells in the laboratory (in vitro) to allow any antibodies that are present every opportunity to attach to the red cells. The cells are then washed with saline to remove any unattached serum globulins, and AHG is added. If the client’s serum contains an antibody that reacts with and attaches to the donor red cells, the AHG will cause the antibody-coated cells to agglutinate. If no agglutination occurs after addition of AHG, then no antigen-antibody reaction has occurred. The serum may contain an antibody, but the red cells against which it is tested do not have the relevant antigen. Thus, the reaction is negative.19 Reference Values Negative (no agglutination) INTERFERING FACTORS Recent administration of dextran, whole blood or fractions, or intravenous contrast media may result in a false-positive reaction. Drugs that may cause false-positive reactions are cephalosporins, insulin, isoniazid, levodopa, mefenamic acid, methyldopa, methyldopa hydrochloride, penicillins, procainamide hydrochloride, Copyright © 2003 F.A. Davis Company CHAPTER 4—Immunohematology quinidine, rifampin, sulfonamides, and tetracyclines. INDICATIONS FOR INDIRECT ANTIGLOBULIN TEST Antibody screening and cross-matching before blood transfusions, especially to detect antibodies whose presence may not be elicited by other methods such as ABO and Rh typing Determination of antibody titers in Rh-negative women sensitized by an Rh-positive fetus Testing for the weak Rh variant antigen D Detection of other antibodies in maternal blood that may be potentially harmful to the fetus NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Exposure to substances that may cause false-positive reactions should be noted. The medication history should also be noted. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube or other blood collection tube, depending on laboratory preference. The sample must be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Note and report a positive value for antibody detection, especially in a pregnant woman. Inform the client that further testing will be undertaken to identify the antibodies. HUMAN LEUKOCYTE ANTIGEN TEST All nucleated cells have human leukocyte antigens (HLA) on their surface membranes. Although sometimes described as “white cell antigens,” HLA characterize virtually all cell types except red blood cells. HLA consist of a glycoprotein chain and a globulin chain. They are classified into five series designated A, B, C, D, and DR (D-related), each series containing 10 to 20 distinct antigens. A, B, C, and D antigens characterize the membranes of virtually all cells except mature red blood cells; DR antigens seem to reside only on B lymphocytes and macrophages (see Chapter 3). Some antigens have been identified with specific and Blood Banking 101 • Diseases Associated with Human Leukocyte Antigens TABLE 4–3 Disease Associated Antigen Ankylosing spondylitis B27 Reiter’s syndrome B27 Diabetes mellitus (juvenile, or insulin-dependent) Multiple sclerosis B8, Bw15 A3, B7, B18 Acute anterior uveitis B27 Graves’ disease B8 Juvenile rheumatoid arthritis B27 Celiac disease B8 Psoriasis vulgaris B13, Bw17 Myasthenia gravis B8 Dermatitis herpetiformis B8 Autoimmune chronic active hepatitis B8 diseases (Table 4–3). Arthritic disorders, for example, have been closely linked to HLA-B27. In addition, HLA typing is valuable in determining parentage. If the HLA phenotypes of a child and one parent are known, it is possible to assess fairly accurately whether a given individual is the other parent.20 Reference Values HLA combinations vary according to certain races and populations. The most common B antigens in American whites, for example, are B7, B8, and B12. In American blacks, the most common of the B series are Bw17, Bw35, and a specificity characterized as 1AG. This combination is in contrast to that of African blacks, whose most common B antigens are B7, Bw17, and 1AG. Similar variations among the A antigens also have been found among various races and populations. INDICATIONS FOR HUMAN LEUKOCYTE ANTIGEN TESTS Determination of donor and recipient compatibility for tissue transplantation, especially when they are blood relatives21 Copyright © 2003 F.A. Davis Company 102 SECTION I—Laboratory Tests Determination of compatibility of donor platelets in individuals who will receive multiple transfusions over a long period of time Support for diagnosing HLA-associated diseases (see Table 4–3), especially when signs and symptoms are inconclusive Determination of biologic parentage NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube or other blood collection device, depending on laboratory preference. The sample is sent promptly to the laboratory performing the test (not all laboratories are equipped to do so). NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Medicolegal implications: HLA testing results for biologic parentage exclusion are not allowed as evidence in all jurisdictions. REFERENCES 1. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 265. 2. Ibid, p 266. 3. Harmening, D: Modern Blood Banking and Transfusion Practices, ed 4. FA Davis, Philadelphia, 2001, p 79. 4. Sacher and McPherson, op cit, pp 268–269. 5. Ibid, p 269. 6. Fischbach, FT: A Manual of Laboratory and Diagnostic Tests, ed 4. JB Lippincott, Philadelphia, 1992, pp 556–558. 7. Harmening, op cit, p 89. 8. Ibid, p 80. 9. Sacher and McPherson, op cit, p 269. 10. Harmening, op cit, p 105. 11. Sacher and McPherson, op cit, p 271. 12. Harmening, op cit, p 110. 13. Sacher and McPherson, op cit, pp 272–273. 14. Ibid, p 275. 15. Harmening, op cit, pp 65–66. 16. Ibid, pp 65–66. 17. Ibid, p 66. 18. Sacher and McPherson, op cit, p 276. 19. Ibid, p 279. 20. Harmening, op cit, p 374. 21. Ibid, p 369. Copyright © 2003 F.A. Davis Company CHAPTER Blood Chemistry TESTS COVERED Blood Glucose (Serum Glucose, Plasma Glucose), 105 Two-Hour Postprandial Blood Glucose (Postprandial Blood Sugar), 108 Oral Glucose Tolerance Test, 109 Intravenous Glucose Tolerance Test, 111 Cortisone Glucose Tolerance Test, 111 Glycosylated Hemoglobin, 112 Tolbutamide Tolerance Test, 113 Serum Proteins, 114 1-Antitrypsin Test, 116 Haptoglobin, 118 Ceruloplasmin, 119 Urea Nitrogen, 120 Serum Creatinine, 122 Ammonia, 123 Serum Creatine, 123 Uric Acid, 124 Free Fatty Acids, 127 Triglycerides, 128 Total Cholesterol, 130 Phospholipids, 131 Lipoprotein and Cholesterol Fractionation, 133 Lipoprotein Phenotyping, 135 Bilirubin, 137 Alanine Aminotransferase, 140 Aspartate Aminotransferase, 141 Alkaline Phosphatase, 142 5′-Nucleotidase, 144 Leucine Aminopeptidase, 144 -Glutamyl Transpeptidase, 145 Isocitrate Dehydrogenase, 146 Ornithine Carbamoyltransferase, 146 Serum Amylase, 147 Serum Lipase, 148 Acid Phosphatase, 149 Prostate-Specific Antigen, 150 Aldolase, 150 Creatine Phosphokinase and Isoenzymes, 151 Troponin Levels, 154 Lactic Dehydrogenase and Isoenzymes, 155 Hexosaminidase, 156 -Hydroxybutyric Dehydrogenase, 157 Cholinesterases, 157 Renin, 158 Growth Hormone, 161 Growth Hormone Stimulation Tests, 162 Growth Hormone Suppression Test, 163 Prolactin, 163 Adrenocorticotropic Hormone, 164 Thyroid-Stimulating Hormone, 165 TSH Stimulation Test, 166 FSH/LH Challenge Tests, 168 Luteinizing Hormone, 169 Antidiuretic Hormone, 170 Thyroxine, 172 Triiodothyronine, 173 T3 Uptake, 174 Thyroxine-Binding Globulin, 175 Thyroid-Stimulating Immunoglobulins, 175 Calcitonin, 176 Parathyroid Hormone, 176 Cortisol/ACTH Challenge Tests, 178 Aldosterone Challenge Tests, 180 Catecholamines, 181 Estrogens, 182 Progesterone, 183 Testosterone, 184 Human Chorionic Gonadotropin, 185 103 Copyright © 2003 F.A. Davis Company 104 SECTION I—Laboratory Tests Human Placental Lactogen, 186 Insulin, 188 C-Peptide, 189 Glucagon, 189 Gastrin, 190 Serum Sodium, 191 Serum Potassium, 192 Serum Chloride, 196 Serum Bicarbonate, 198 Serum Calcium, 200 Serum Phosphorus/Phosphate, 202 Serum Magnesium, 204 Serum Osmolality, 206 Arterial Blood Gases, 207 Vitamin A, 210 Vitamin C, 211 Vitamin D, 212 Trace Minerals, 212 Drugs and Toxic Substances, 213 INTRODUCTION The blood transports innumerable substances that participate in and reflect ongoing metabolic processes. Relatively few of these substances are routinely measured. Some materials are analyzed to provide information about specific organs and processes; other substances reflect the summed effects of numerous metabolic events.1 “Chemistry” includes the measurement of glucose, proteins, lipids, enzymes, electrolytes, hormones, vitamins, toxins, and other substances that may indicate derangement of normal physiological processes. In recent years, the diagnosis of many disorders associated with abnormal blood chemistries has become more rapid and accurate with the use of automated analyzers that can measure multiple chemistry components in a single blood sample. CARBOHYDRATES The body acquires most of its energy from the oxidative metabolism of glucose. Glucose, a simple six-carbon sugar, enters the diet as part of the sugars called sucrose, lactose, and maltose and as the major constituent of the complex polysaccharides called dietary starch. Complete oxidation of glucose yields carbon dioxide (CO2), water, and energy that is stored as adenosine triphosphate (ATP). If glucose is not immediately metabolized, it can be stored in the liver or muscle as glycogen. Unused glucose can also be converted by the liver into fatty acids, which are stored as triglycerides, or into amino acids, which can be used for protein synthesis. The liver is pivotal in distributing glucose as needed for immediate fuel or as indicated for storage or for structural purposes. If available glucose or glycogen is insufficient for energy needs, the liver can synthesize glucose from fatty acids or even from protein-derived amino acids.2 Glucose fuels most cell and tissue functions. Thus, adequate glucose is a critical requirement for homeostasis. Many cells can derive some energy from burning fatty acids, but this energy pathway is less efficient than burning glucose and generates acid metabolites (e.g., ketones) that are harmful if they accumulate in the body. Many hormones (Table 5–1) participate in maintaining blood glucose levels in steady-state conditions or in response to stress. Measures of blood glucose indicate whether the regulation is successful. Pronounced departure from normal, either too high or too low, indicates abnormal homeostasis and should initiate a search for the etiology.3 The causes of abnormal blood glucose levels are summarized in Table 5–2. Two major methods are used to measure blood glucose: chemical and enzymatic. Chemical methods use the nonspecific reducing properties of the glucose molecule. In enzymatic methods, glucose oxidase reacts with its specific substrate, glucose, liberating hydrogen peroxide, the effects of which are then measured. Values are 5 to 15 mg/dL higher for the reducing (chemical) methods than for enzymatic techniques because blood contains other reducing substances in addition to glucose. Urea, for example, can contribute up to 10 mg/dL in normal serum and even more when uremia exists. Several different indicator systems are used for automated enzymatic methods, yielding somewhat different normal values.4 Note also that, in the past, blood glucose values were given in terms of whole blood. Today, most laboratories measure serum or plasma glucose levels. Because of its higher water content, serum contains more dissolved glucose, and the resultant values are 1.15 times higher than are those for whole blood. Serum or plasma should be separated Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–1 Hormone Insulin • Chemistry 105 Hormones That Influence Blood Glucose Levels Tissue of Origin Pancreatic cells Metabolic Effect 1. Enhances entry of glucose into cells Effect on Blood Glucose Lowers 2. Enhances storage of glucose as glycogen, or conversion to fatty acids 3. Enhances synthesis of proteins and fatty acids 4. Suppresses breakdown of protein into amino acids; of adipose tissue, into free fatty acids Somatostatin Pancreatic D cells 1. Suppresses glucagon release from cells (acts locally) Lowers 2. Suppresses release of insulin, pituitary tropic hormones, gastrin, and secretin Glucagon Pancreatic cells 1. Enhances release of glucose from glycogen Raises 2. Enhances synthesis of glucose from amino acids or fatty acids Epinephrine Adrenal medulla 1. Enhances release of glucose from glycogen Raises 2. Enhances release of fatty acids from adipose tissue Cortisol Adrenal cortex 1. Enhances synthesis of glucose from amino acids or fatty acids Raises 2. Antagonizes insulin Adrenocorticotropic hormone (ACTH) Anterior pituitary 1. Enhances release of cortisol Raises 2. Enhances release of fatty acids from adipose tissue Growth hormone Anterior pituitary 1. Antagonizes insulin Raises Thyroxine Thyroid 1. Enhances release of glucose from glycogen Raises 2. Enhances absorption of sugars from intestine From Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 448, with permission. promptly because red and white blood cells continue to metabolize glucose. In blood with very high white blood cell levels, excessive glycolysis may actually lower glucose results. Arterial, capillary, and venous blood samples have comparable glucose levels in a fasting individual. After meals, venous levels are lower than those in arterial or capillary blood.5 Blood Glucose (Serum Glucose, Plasma Glucose) Blood glucose (serum glucose, plasma glucose) is measured in a variety of situations. In the fasting state, the serum glucose level gives the best indication of overall glucose homeostasis.6 Blood glucose levels also can be measured at regular intervals throughout the day to monitor responses to diet and medications in persons with a diagnosis of abnormalities of glucose metabolism. Such monitoring may take place in a hospital setting or in the home with kits specially designed for selfmonitoring of blood glucose. Serial blood glucose levels also are used to determine insulin requirements in clients with uncontrolled diabetes mellitus and for individuals receiving total parenteral or enteral nutritional support. Copyright © 2003 F.A. Davis Company 106 SECTION I—Laboratory Tests TABLE 5–2 • Causes of Altered Blood Glucose Levels Hyperglycemia Hypoglycemia PERSISTENT CAUSES Diabetes mellitus Insulinoma Hemochromatosis Addison’s disease Cushing’s syndrome Hypopituitarism Hyperthyroidism Galactosemia Acromegaly, gigantism Ectopic insulin production from tumors (adrenal carcinoma, retroperitoneal sarcomas, pleural fibrous mesotheliomas) Obesity Chronic pancreatitis Pancreatic adenoma Starvation TRANSIENT CAUSES Pheochromocytoma Acute alcohol ingestion Pregnancy (gestational diabetes) Severe liver disease Severe liver disease Severe glycogen storage diseases Acute stress reaction Stress-related catecholamine excess (“functional” hypoglycemia) Shock, trauma Convulsions, eclampsia Hereditary fructose intolerance Malabsorption syndrome Myxedema Postgastrectomy “dumping syndrome” DRUGS Glucagon Clonidine Adrenocorticosteroids Dextrothyroxine Oral contraceptives Niacin Estrogens Salicylates Thyroid hormones Antituberculosis agents Anabolic steroids Sulfonylureas Thiazide diuretics Sulfonamides Loop diuretics Insulin Propranolol Ethanol Antipsychotic drugs Clofibrate Hydantoins MAO inhibitors In addition to situations characterized by actual or potential elevations in blood sugar, glucose levels are evaluated in individuals suspected or known to have hypoglycemia. INTERFERING FACTORS Elevated urea levels and uremia may lead to falsely elevated levels. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 107 Reference Values Newborns Conventional Units Children Adults SI Units Conventional Units SI Units Conventional Units SI Units Whole blood 25–51 mg/dL 1.4–2.8 mmol/L 50–90 mg/dL 2.8–5.0 mmol/L 60–100 mg/dL 3.3–5.6 mmol/L Serum/ plasma 30–60 mg/dL 1.7–3.3 mmol/L 60–105 mg/dL 3.3–5.8 mmol/L 70–110 mg/dL 3.9–6.1 mmol/L Critical values 30 mg/dL or 300 mg/dL 1.6 mmol/L or 16.5 mmol/L 40 mg/dL or 700 mg/dL 2.2 mmol/L or 38.6 mmol/L 40 mg/dL or 700 mg/dL 2.2 mmol/L or 38.6 mmol/L Note: Values may vary depending on the laboratory method used. Extremely elevated white blood cell counts may lead to falsely decreased values. Failure to follow dietary restrictions before a fasting blood glucose may lead to falsely elevated values. Administration of insulin or oral hypoglycemic agents within 8 hours of a fasting blood glucose may lead to falsely decreased values. INDICATIONS FOR BLOOD GLUCOSE TEST Routine screening for diabetes mellitus: Fasting blood glucose levels greater than 126 mg/dL on two or more occasions may be considered diagnostic of diabetes mellitus if other possible causes of hyperglycemia are eliminated as sources of elevation (see Table 5–2). Random (nonfasting) blood glucose levels of greater than 200 mg/dL may be pathognomonic of diabetes mellitus.7 Clinical symptoms of hypoglycemia or hyperglycemia Known or suspected disorder associated with abnormal glucose metabolism (see Table 5–2) Identification of abnormal hypoglycemia as indicated by a fasting blood sugar as low as 50 mg/dL in men or 35 mg/dL in women8 Monitoring of response to therapy for abnormal glucose metabolism Determination of insulin requirements (i.e., “insulin coverage”) Monitoring of metabolic response to drugs known to alter blood glucose levels (see Table 5–2) Monitoring of metabolic response to parenteral or enteral nutritional support to determine insulin requirements NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). If a fasting sample is to be drawn, food and insulin or any oral hypoglycemic agent should be withheld for approximately 8 hours before the test (i.e., the client usually takes only water from midnight until the sample is drawn in the morning). For home glucose monitoring, the client should be instructed in the correct use of the testing equipment and in the method used to obtain the blood sample. THE PROCEDURE A venipuncture is performed and the sample is obtained in either a gray- or a red-topped tube, depending on the laboratory performing the test. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. A capillary sample may be obtained in infants and children as well as in adults for whom venipuncture may not be feasible. Capillary samples also are used for self-monitoring of blood glucose. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Resume food and medications withheld before the test after the sample is drawn. Abnormal values: Note and report increased levels. Assess for symptoms associated with hyperglycemia such as polyuria and possible dehydra- Copyright © 2003 F.A. Davis Company 108 SECTION I—Laboratory Tests Reference Values Children Adults Elderly Persons Conventional Units SI Units Conventional Units SI Units Conventional Units SI Units Blood 120 mg/dL 6.6 mmol/L 120 mg/dL 6.6 mmol/L 140 mg/dL 7.7 mmol/L Serum/ plasma 150 mg/dL 8.3 mmol/L 140 mg/dL 7.7 mmol/L 160 mg/dL 8.8 mmol/L Note: Values may vary, depending on the laboratory method used. tion, polydipsia, or weight loss. Prepare for additional glucose tests for diabetes mellitus. Monitor intake and output (I&O). Prepare to administer ordered medications (insulin or oral hypoglycemic) to treat known diabetic condition. Instruct client on diabetic diet in relation to medications, activities, and blood and urine test results. Note and report decreased levels. Assess for symptoms associated with hypoglycemia such as weakness, sweating, nervousness, hunger, confusion, or palpitations. Prepare to administer sucrose or glucose orally or intravenously (IV). Instruct client to keep readily absorbed carbohydrates on hand. Instruct client on diet and its relation to medications, activities, and blood and urine test results. Critical values: Notify the physician immediately of a blood glucose level of less than 30 mg/dL in infants or less than 40 mg/dL in adults or a blood glucose level of greater than 300 mg/dL in infants or greater than 700 mg/dL in adults. Two-Hour Postprandial Blood Glucose (Postprandial Blood Sugar) The 2-hour postprandial blood glucose (postprandial blood sugar, PPBS) test reflects the metabolic response to a carbohydrate challenge.9 In normal individuals, the blood sugar returns to the fasting level within 2 hours. In contrast, postprandial hypoglycemia appears to result from delayed or exaggerated response to the insulin secreted in relation to dietary blood sugar rise. It may occur as an early event in individuals with non-insulin-dependent diabetes mellitus (NIDDM, type II diabetes mellitus) or in individuals with gastrointestinal malfunction. Frequently, no cause is demonstrated and the hypoglycemia is considered “functional.” Postprandial hypoglycemia differs from fasting hypoglycemia (i.e., hypoglycemia that occurs after 10 or more hours without food) in that the latter nearly always has pathologi- cal significance. It results from either overproduction of insulin or undermobilization of glucose and is most commonly seen in clients with tumors of the pancreatic cells (insulinoma), liver disease, and chronic alcohol ingestion.10 With advancing age, the speed of glucose clearance declines. Two-hour levels in persons who do not have diabetes and in those with negative family histories may increase an average of 6 mg/dL for each decade over age 30 years.11 INTERFERING FACTORS Failing to follow dietary instructions may alter test results. Smoking and drinking coffee during the 2-hour test period may lead to falsely elevated values. Strenuous exercising during the 2-hour test period may lead to falsely decreased values. INDICATIONS FOR 2-HOUR POSTPRANDIAL BLOOD GLUCOSE (POSTPRANDIAL BLOOD SUGAR) TEST Abnormal fasting blood sugar Routine screening for diabetes mellitus, as indicated by a blood glucose level greater than the fasting level and especially by a 2-hour level greater than 200 mg/mL Identification of postprandial hypoglycemia and differentiation of this state from fasting hypoglycemia, with fasting hypoglycemia almost always indicative of a pathological state Known or suspected disorder associated with abnormal glucose metabolism (see Table 5–2) Monitoring of metabolic response to drugs known to alter blood glucose levels (see Table 5–2) NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any test involving collection of a peripheral blood sample. Specific preparation includes ingesting a meal (usually breakfast) containing at least 100 g of carbohydrate 2 hours before the test. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood The American Diabetes Association recommends a 300-g carbohydrate diet for 2 to 3 days before the test, but this recommendation is not universally followed. The time of the last meal before the test should be noted. The client should then fast from food and avoid coffee, smoking, and strenuous exercise until the sample is obtained. Although medications are not withheld for this test, those taken should be noted. THE PROCEDURE Two hours after the carbohydrate challenge is ingested, a venipuncture is performed and the sample is collected in either a gray- or a red-topped tube, depending on the laboratory performing the test. A capillary sample may be obtained in children and in adults for whom venipuncture may not be feasible. Capillary samples are also used when the test is performed for mass screenings. Note that in some instances a fasting blood sugar level may be obtained before the carbohydrate challenge. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Resume usual diet and activities. Complications and precautions: Abnormal increased or decreased values are treated in the same way as for blood glucose testing. If the glucose level does not return to a fasting state in 2 hours, an additional glucose tolerance test is required, and there are no critical values to report. Glucose Tolerance Tests Glucose tolerance tests (GTTs) are used to evaluate the response to a carbohydrate challenge throughout a 3- to 5-hour period. When a glucose load is presented, the normal individual’s blood insulin level rises in response to it, with peak levels occurring 30 to 60 minutes after the carbohydrate challenge. Blood glucose levels, although elevated immediately after the carbohydrate challenge, return to normal fasting levels 2 to 3 hours later. For individuals in whom abnormal hypoglycemia or gastrointestinal malabsorption is suspected, the test may be extended to a 5-hour period.12–14 Several methods can be used to perform a glucose tolerance test. The oral, IV, and cortisone glucose tolerance tests are discussed in this section. Tolerance tests also may be performed for pentose, lactose, galactose, and D-xylose. Chemistry 109 ORAL GLUCOSE TOLERANCE TEST The oral glucose tolerance test (OGTT) is used for individuals who are able to eat and who are not known to have problems with gastrointestinal malabsorption. The client should be in a normal nutritional state and should be capable of normal physical activity (i.e., not immobilized or on bed rest), because carbohydrate depletion and inactivity may impair glucose tolerance. In addition, drugs that affect blood glucose levels (see Table 5–2) should not be taken for several days before the test. Because oral glucose tolerance testing is affected by so many variables, the results are subject to many diagnostic interpretations.15 The OGTT may be performed using blood samples only or using urine samples as well. The urine is normally negative for sugar throughout the test; that is, because the average renal threshold for glucose is 180 mg/dL, the plasma glucose level must be approximately 180 mg/dL before sugar appears in the urine. Renal threshold levels vary, however, and urine testing during an OGTT may show how much glucose the individual spills, if any, at various blood glucose levels. As long as the renal threshold is not surpassed by the blood glucose levels, all of the glucose presented to the kidneys is reabsorbed from the glomerular filtrate by the renal tubules, provided that renal function is normal. INTERFERING FACTORS Failure to ingest a diet with sufficient carbohydrate content (e.g., 150 g/day) for at least 3 days before the test may result in falsely decreased values. Impaired physical activity may lead to falsely increased values. Excessive physical activity before or during the test may lead to falsely decreased values. Smoking before or during the test may lead to falsely increased values. Ingestion of drugs known to alter blood glucose levels may lead to falsely increased or decreased values (see Table 5–2). INDICATIONS FOR ORAL GLUCOSE TOLERANCE TEST Abnormal fasting or postprandial blood glucose levels that are not clearly indicative of diabetes mellitus Identification of impaired glucose metabolism without overt diabetes mellitus, which is characterized by a modest elevation in blood glucose after 2 hours and a normal level after 3 hours Evaluation of glucose metabolism in women of childbearing age, especially those who are preg- Copyright © 2003 F.A. Davis Company 110 SECTION I—Laboratory Tests Reference Values Time After Carbohydrate Challenge 1 Hr 2 Hr 30 min Conventional Units SI Units Conventional Units SI Units Conventional Units SI Units 3 Hr ConvenSI tional Units Units Whole blood glucose 150 mg/dL 8.3 160 mmol/L mg/dL 8.8 115 mmol/L mg/dL Same as 6.6 fastmmol/L ing Same as fasting Serum/ plasma 160 mg/dL 8.8 170 mmol/L mg/dL 9.4 125 mmol/L mg/dL Same as 7.1 fastmmol/L ing Same as fasting Urine Negative throughout test glucose Note: Values for children over age 6 years are the same as those for adults. Values for elderly individuals are 10 to 30 mg/dL higher at each interval because of the age-related decline in glucose clearance. nant and have a history of previous fetal loss, birth of babies weighing 9 pounds or more, or positive family history for diabetes mellitus Support for diagnosing hyperthyroidism and alcoholic liver disease, which are characterized by a sharp rise in blood glucose followed by a decline to subnormal levels Identification of true postprandial hypoglycemia (5-hour GTT) caused by excessive insulin response to a glucose load Support for diagnosing gastrointestinal malabsorption, which is characterized by peak glucose levels lower than that normally expected and hypoglycemia in the latter hours of the test (5hour GTT) Identification of abnormal renal tubular function, if glycosuria occurs without hyperglycemia Nursing Alert Individuals with fasting blood sugars of greater than 150 mg/dL or postprandial blood glucose levels greater than 200 mg/dL should not receive the glucose load required for this test. If the client vomits the oral glucose preparation, notify the laboratory and physician immediately, and implement any treatment ordered. If signs and symptoms of hypoglycemia are observed or reported, obtain a blood sugar immediately and administer orange juice with 1 tsp of sugar or other beverage containing sugar; notify the physician that the test has been terminated. NURSING CARE BEFORE THE PROCEDURE Explain to the client: The general procedure for the test, including the administration of glucose and the frequency of collection of blood and urine samples The importance of eating a diet containing at least 150 g carbohydrate per day for 3 days before the test (Provide sample menus or lists of foods that demonstrate how this may be accomplished.) Which medications, if any, are to be withheld before the test That no food may be eaten after midnight before the test but that water is not restricted The importance of not smoking or performing strenuous exercise after midnight before the test and until the test is completed The symptoms of hypoglycemia and the necessity of reporting such symptoms immediately Provide containers for collection of urine samples. THE PROCEDURE A venipuncture is performed and a sample is obtained for a fasting blood sugar. At the same time, a second voided (double-voided) urine sample is collected and tested for glucose. To collect a secondvoided specimen, have the client void 30 minutes before the required specimen is due. Discard this urine, then collect the second voided specimen at the designated time. The glucose load is administered orally. This is a calculated dose, either 1.75 g/kg body weight or 50 g/m2 body surface. Several commercial preparations are available that are flavored for palatability. Blood Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood and urine samples are obtained at 1/2-hour, 1-hour, 2-hour, and 3-hour intervals. The second voided urine specimen is necessary only at the beginning of the test. The client should drink one glass of water each time a urine sample is collected to ensure adequate urinary output for remaining specimens. If the test is extended to 5 hours, additional samples are collected at 4- and 5-hour intervals. The test may be performed with blood samples only, depending on the desired information to be obtained from the test. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as those for any test involving the collection of peripheral blood samples. Resume food and medications withheld before the test, as well as usual activities. Complications and precautions: Same as for blood glucose. Closely monitor those clients whose pretest levels are greater than 200 mg/dL for possible reactions to the additional glucose intake required for the test. INTRAVENOUS GLUCOSE TOLERANCE TEST The intravenous glucose tolerance test (IVGTT) is essentially the same as the OGTT, except that the carbohydrate challenge is administered IV instead of orally. Because the results are somewhat difficult to interpret, the IVGTT is used only in certain clinical situations or for research purposes. Reference Values The reference values are the same as those for the OGTT, except that the blood glucose level at the 1/2-hour interval may be 300 to 400 mg/dL because of the direct IV administration of the glucose load. INTERFERING FACTORS Those factors that may alter the results of an OGTT may also alter the results of an IVGTT. Infusions of total parenteral nutrition (TPN, hyperalimentation) during the test may lead to falsely elevated values; alternative solutions with less glucose should be infused for at least 3 hours before and during the test. INDICATIONS FOR INTRAVENOUS GLUCOSE TOLERANCE TEST Inability to take or tolerate oral glucose preparations used for the OGTT Chemistry 111 Suspected gastrointestinal malabsorption problems that interfere with accurate performance of the OGTT Evaluation of blood glucose control without the effects of gastrin, secretin, cholecystokinin, and gastric inhibitory peptide, all of which stimulate insulin production after oral ingestion of glucose NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for the OGTT. If the person is receiving TPN, an alternative solution with less glucose should be prescribed and infused for at least 3 hours before and during the test. THE PROCEDURE The procedure is essentially the same as that for the OGTT except that an intermittent venous access device (e.g., heparin lock) may be inserted to administer the glucose load and to obtain blood samples. Existing IV lines also may be used to administer the carbohydrate challenge, which is usually 50 percent glucose, with the amount to be given determined by the client’s weight or body surface. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as those for the OGTT. If an intermittent venous access device was inserted for the procedure, remove it after completion of the test and apply a pressure bandage to the site. Resume food and medications withheld before the test, as well as usual activities. Resume infusions of TPN as ordered. CORTISONE GLUCOSE TOLERANCE TEST The cortisone glucose tolerance test (cortisone GTT) combines administration of a carbohydrate challenge with a cortisone challenge. Cortisone enhances the synthesis of glucose from amino acids and fatty acids (gluconeogenesis) and, when administered with a glucose load, may produce an abnormal GTT that would not otherwise be evident. The cortisone GTT is used only in certain clinical situations and for research purposes. Reference Values The reference values are similar to those for the OGTT except that the blood glucose level at the 2-hour interval may be 20 mg/dL higher than the client’s fasting level. Copyright © 2003 F.A. Davis Company 112 SECTION I—Laboratory Tests INTERFERING FACTORS Those factors that may alter the results of an OGTT may also alter the results of a cortisone GTT. Failure to administer or take the oral cortisone as prescribed for the test will alter results. INDICATIONS FOR CORTISONE GLUCOSE TOLERANCE TEST Inconclusive results of OGTT when prediabetes or “borderline” diabetes is suspected, with a 2hour level of greater than 165 mg/dL considered indicative of diabetes NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for the OGTT. In addition, the client should be instructed on the purpose and administration of the oral cortisone acetate. THE PROCEDURE The procedure is the same as that for the OGTT except that cortisone acetate is administered orally 8 hours and again 2 hours before the standard GTT is begun. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for the OGTT. Glycosylated Hemoglobin Throughout the red blood cell’s life span, the hemoglobin molecule incorporates glucose onto its chain. Glycosylation is irreversible and occurs at a stable rate. The amount of glucose permanently bound to hemoglobin depends on the blood sugar level. Thus, the level of glycosylated hemoglobin, designated Hgb A1c, reflects the average blood sugar over a period of several weeks. The test is used to evaluate the overall adequacy of diabetic control and provides information that may be missed by individual blood and urine glucose tests. Insulin-dependent diabetics, for example, may have undetected periods of hyperglycemia alternating with postinsulin periods of normoglycemia or even hypoglycemia. High Hgb A1c levels reflect inadequate diabetic control in the preceding 3 to 5 weeks. In addition to providing a more accurate assessment of overall blood glucose control, the test is more convenient for diabetic clients because it is performed only every 5 to 6 weeks and because there are no dietary or medication restrictions before the test. Reference Values Hgb A1c is 3 to 6 percent of hemoglobin. Hgb A1c is 7 to 11 percent in diabetes under control. INTERFERING FACTORS Individuals with hemolytic anemia and high levels of young red blood cells may have spuriously low levels. Individuals with elevated hemoglobin levels or on heparin therapy may have falsely elevated levels. INDICATIONS FOR GLYCOSYLATED HEMOGLOBIN TEST Monitoring overall blood glucose control in clients with known diabetes, because the test aids in assessing blood glucose levels over a period of several weeks and provides data that may be missed by random blood or urine glucose tests: With prolonged hyperglycemia, levels of Hgb A1c may rise to as high as 18 to 20 percent. After normoglycemic levels are stabilized, Hgb A1c levels return to normal in about 3 weeks.16 Monitoring adequacy of insulin dosage for blood glucose control, especially that administered by automatic insulin pumps Evaluating the diabetic client’s degree of compliance with the prescribed therapeutic regimen, because fasting or adjusting medications shortly before the test will not significantly alter results NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). The client should be informed that fasting or adjusting medications for diabetes shortly before the test will not significantly alter results. THE PROCEDURE A venipuncture is performed and the sample obtained in a lavender-topped tube. The sample must be mixed adequately with the anticoagulant contained in the tube and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Complications and precautions: A value of greater than 15 percent of total Hgb A1c indicates that the diabetes is out of control. Notify the physician at once. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 113 Tolbutamide Tolerance Test NURSING CARE BEFORE THE PROCEDURE Tolbutamide (Orinase) is a hypoglycemic agent that produces hypoglycemia by stimulating the cells of the pancreas to secrete and release insulin. An IV infusion of tolbutamide raises the serum insulin and causes a rapid decrease in the blood glucose level. Thus, the test demonstrates the pancreatic -cell response to drug-induced stimulation. Note that the test can be performed with glucagon or leucine instead of tolbutamide for clients who are sensitive to sulfonylureas or sulfonamides. Client preparation is essentially the same as that for an OGTT. The individual should be informed that venous access will be established with either a continuous infusion or an intermittent device and that a medication that lowers blood sugar will be administered. The client should be questioned regarding allergies to sulfonylureas or sulfonamides. Clients with a history of abnormal hypoglycemia will need reassurance that they will be monitored closely during the test. Reference Values A decrease in serum glucose levels is evident within 5 to 10 minutes of administration of the drug. The lowest glucose levels occur in about 20 to 30 minutes and are generally about half of the client’s usual fasting level. The glucose level returns to pretest values in 1 to 3 hours. INTERFERING FACTORS The factors that may alter the results of an OGTT may also alter the results of a tolbutamide tolerance test. INDICATIONS FOR TOLBUTAMIDE TOLERANCE TEST Evaluation of fasting or postprandial hypoglycemia by assessing the degree of pancreatic cell response to drug-induced stimulation Suspected insulinoma (insulin-producing tumor of the pancreatic cells) as indicated by glucose levels that drop markedly in response to tolbutamide and take 3 or more hours to return to normal levels Suspected prediabetic state that may be characterized by excessive insulin release, as indicated by glucose levels that are lower than expected but that follow the overall pattern of a normal response to the test Nursing Alert Because of the expected drop in blood sugar levels, the test should be performed with extreme caution, if at all, on individuals with fasting blood sugars of 50 mg/dL or less. If the client is allergic to sulfonylureas or sulfonamides, the test should be performed using glucagon or leucine instead of tolbutamide. THE PROCEDURE Venous access is established and a sample is obtained for a fasting blood sugar (FBS). The IV catheter is then connected to an intermittent device (e.g., heparin lock) or to a continuous IV infusion of normal saline at a keep-vein-open (KVO) rate. Tolbutamide 1.0 g mixed in 20 mL sterile water is administered IV. Blood glucose samples are obtained via the IV catheter at 15-minute intervals for the first hour and then at 11/2-, 2-, and 3-hour intervals. Observe the client closely for signs and symptoms of hypoglycemia. If hypoglycemia occurs, obtain a stat FBS, notify the physician, and initiate an IV infusion of 5 percent glucose and water, if ordered. Note any signs or symptoms of sensitivity reaction to tolbutamide. If a reaction occurs, notify the physician and administer drugs as ordered. Maintain an open IV line until there is no further danger of adverse drug reaction. NURSING CARE AFTER THE PROCEDURE The venous access device is left in place until any danger of hypoglycemia is past. It is then removed and a pressure bandage applied to the site. Food and medications withheld before the test, as well as usual activities, should be resumed on its completion. Continue to observe for signs and symptoms of hypoglycemia for 2 hours or more, depending on results of the 3-hour interval blood sugar. Assess the venipuncture site for signs of hematoma or phlebitis. Observe for adequate intake when foods are resumed. PROTEINS Proteins, also called polypeptides, consist of amino acids linked by peptide bonds. Although all human proteins are constructed from a mere 20 amino acids, variations in chain length, amino acid Copyright © 2003 F.A. Davis Company 114 SECTION I—Laboratory Tests sequence, and incorporated constituents combine to make possible an almost infinite number of protein molecules. All cells manufacture proteins, with different proteins characterizing different cell types. The amino acids needed for these processes enter the body from dietary sources. These amino acids are rapidly distributed to tissue cells, which promptly incorporate them into proteins. Three-fourths of the body’s solid matter is protein and, except for hemoglobin, relatively little circulates in whole blood. The major plasma proteins are albumin, the globulins, and fibrinogen. Fibrinogen evolves into insoluble fibrin when blood coagulates. The fluid that remains after coagulation is called serum. Serum and plasma have the same protein composition except that serum lacks fibrinogen and several other coagulation factors (prothrombin, factor VIII, factor V, and factor XIII). The proteins in circulating blood transport amino acids from one site to another, providing raw materials for synthesis, degradation, and metabolic interconversion. Circulating proteins also function as buffers in acid–base balance, contribute to the maintenance of colloidal osmotic pressure, and aid in transporting lipids, enzymes, hormones, vitamins, and certain minerals. Most plasma proteins originate in the liver. Hepatocytes synthesize fibrinogen, albumin, and TABLE 5–3 • 60 to 80 percent of the globulins. The remaining globulins are immunoglobulins (antibodies), which are manufactured by the lymphoreticular system. Immunoglobulins are studied as part of the immune system (see Chapter 3), whereas fibrinogen is usually studied as part of a coagulation workup (see Chapter 2). The focus of this section is on the major serum proteins (albumin and nonantibody globulins), binding proteins, and protein metabolites.17 Serum Proteins General assessment of the serum proteins includes measurement of total protein, albumin, globulin, and the albumin-to-globulin (A-G) ratio. Although these tests are being replaced by serum protein electrophoresis (see Chapter 3), they may still be ordered for screening purposes or as components of multitest chemistry profiles, because they provide an overall picture of protein homeostasis. Several disorders can cause alterations in serum proteins. Those affecting total protein levels are listed in Table 5–3. Albumin levels show less variation. Except for dehydration, exercise, and effects of certain drugs (e.g., gallamine triethiodide [Flaxedil]), elevated albumin levels do not occur. Albumin may be decreased in a number of situations Causes of Altered Total Serum Proteins Increased Levels Decreased Levels Kala-azar Renal disease Dehydration Ulcerative colitis Macroglobulinemias Water intoxication Sarcoidosis Cirrhosis Severe burns Drugs Scleroderma Adrenocorticotropic hormone, corticosteroids Malnutrition Clofibrate Hodgkin’s disease Dextran Hemorrhage Growth hormone Heparin Drugs Insulin Ammonium ion Sulfobromophthalein (Bromsulphalein, BSP) Dextran Thyroid preparations Oral contraceptives Tolbutamide Pyrazinamide X-ray contrast media Salicylates Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood caused, in general, by (1) decreased hepatic synthesis, (2) excessive renal excretion, (3) increased metabolic degradation, and (4) complex combined disorders. Specific problems associated with hypoalbuminemia are listed in Table 5–4. Globulin levels show more variation than do albumin levels, probably because of the multiple production sites for this protein. Causes of altered globulin levels are listed in Table 5–5 according to the type of globulin affected. The A-G ratio indicates the balance between total albumin and total globulin and is usually evaluated in relation to the total protein level. A low protein level and a reversed A-G ratio (i.e., decreased albumin and elevated globulins) suggest chronic liver disease. A normal total protein level with a reversed A-G ratio suggests myeloproliferative disease (e.g., leukemia, Hodgkin’s disease) or certain chronic infectious diseases (e.g., tuberculosis, chronic hepatitis). INTERFERING FACTORS High serum lipid levels may interfere with accurate testing. Numerous drugs may alter protein levels (see Tables 5–3 and 5–4). INDICATIONS FOR SERUM PROTEINS TEST Routine screening as part of a complete physical examination, with normal results indicating satisfactory overall protein homeostasis Clinical signs of diseases associated with altered serum proteins (see Tables 5–3, 5–4, and 5–5) Monitoring of response to therapy with drugs that may alter serum protein levels Chemistry • Causes of Hypoalbuminemia TABLE 5–4 Decreased Synthesis of Albumin Malnutrition (starvation, malabsorption iron deficiency) Chronic diseases (tuberculosis) Acute infections (hepatitis, brucellosis) Chronic liver disease Collagen disorders (scleroderma, systemic lupus erythematosus) Drugs Acetaminophen (Tylenol) Azathioprine (Imuran) Conjugated estrogens (Premarin) Cyclophosphamide (Cytoxan) Dextran Ethinyl estradiol (Estinyl) Heroin Mestranol/norethynodrel (Enovid) Niacin Nicotinyl alcohol (Roniacol) Increased Loss of Albumin Ascites Burns (severe) Nephrotic syndrome Chronic renal failure NURSING CARE BEFORE THE PROCEDURE Increased Catabolism of Albumin Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Some laboratories require an 8-hour fast before the test, as well as a low-fat diet for several days before the test, because high serum lipid levels may interfere with accurate testing. Malignancies (leukemias, advanced tumors) THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently and sent promptly to the laboratory. Trauma Multifactorial Causes Cirrhosis Congestive heart failure Pregnancy Toxemia of pregnancy Diabetes mellitus Myxedema Rheumatic fever NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a 115 Rheumatoid arthritis Hypocalcemia Copyright © 2003 F.A. Davis Company 116 SECTION I—Laboratory TABLE 5–5 Globulin 1 Tests • Causes of Altered Serum Globulin Levels Increased Levels Decreased Levels Pregnancy Genetic deficiency of 1-antitrypsin Malignancies Acute infections Tissue necrosis 2 Acute infections Hemolytic anemia Trauma, burns Severe liver disease Advanced malignancies Rheumatic fever Rheumatoid arthritis Acute myocardial infarction Nephrotic syndrome Hypothyroidism Hypocholesterolemia Biliary cirrhosis Nephrotic syndrome Diabetes mellitus Cushing’s syndrome Malignant hypertension Connective tissue diseases (such as systemic lupus erythematosus and rheumatoid arthritis) Nephrotic syndrome Hodgkin’s disease Lymphosarcoma Chronic active liver disease Drugs Drugs Lymphocytic leukemia Bacille Calmetté-Guérin vaccine Tolazamide (Tolinase) Tubocurarine Methotrexate Anticonvulsants peripheral blood sample. Resume any foods withheld before the test. Abnormal values: Note and report increased levels. Assess for symptoms of dehydration that can cause hyperproteinemia such as thirst, dry skin and mucous membranes, or poor skin turgor. Assess fluid loss resulting from vomiting, diarrhea, or renal dysfunction. Note and report decreased levels. Assess in relation to hypoalbuminuria and for edema in serum albumin levels as low as 2.0 to 2.5 g/dL. Assess for causes of hypoalbuminemia such as acute or chronic liver disease or renal dysfunction. Assess for stress, injury, or infection that requires increased protein intake. Prepare for IV administration of albumin replace- ment in severe conditions. Monitor I&O. Encourage and instruct in increased dietary protein intake. 1-Antitrypsin Test 1-Antitrypsin (1-AT) is an 1-globulin produced by the liver. Its function is inhibition of the proteolytic enzymes trypsin and plasmin, which are released by alveolar macrophages and by bacteria in the lungs. As with many other proteins, the 1-AT molecule has several structural variants. Some of these variant molecules have different electrophoretic mobility and reduced ability to inhibit proteolytic enzymes. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 117 Reference Values The reference values for total protein, albumin, and globulin vary slightly across the life cycle and are listed accordingly. Values for -globulins are provided for comparison purposes. Total Protein Albumin -Globulins Globulins Conventional Units SI Units Conventional Units SI Units Newborns 5.0–7.1 g/dL 50–70 g/L 2.5–5.0 g/dL 25–50 g/L 1.2–4.0 g/dL 12–40 g/dL 0.7–0.9 g/dL 7–9 g/L 3 mo 4.7–7.4 g/dL 47–74 g/L 3.0–4.2 g/dL 30–42 g/L 1.0–3.3 g/dL 10–33 g/L 0.1–0.5 g/dL 1–5 g/L 1 yr 5.0–7.5 g/dL 50–75 g/L 2.7–5.0 g/dL 27–50 g/L 2.0–3.8 g/dL 20–38 g/L 0.4–1.2 g/dL 4–12 g/L 15 yr 6.5–8.6 g/dL 65–86 g/L 3.2–5.0 g/dL 32–50 g/L 2.0–4.0 g/dL 20–40 g/L 0.6–1.2 g/dL 6–12 g/L Adults 6.6–7.9 g/dL 66–79 g/L 3.3–4.5 g/dL 33–45 g/L 2.0–4.2 g/dL 20–42 g/L 0.5–1.6 g/dL 5–16 g/L Age ConvenSI Conventional Units Units tional Units SI Units A-G ratio 1.5:1–2.5:1 Although discussed in Chapter 3, the normal values for serum protein electrophoresis are repeated next for reference purposes. Values are reported as percentage of total proteins. Total Globulins Conventional Units 52–68 SI Units 0.520– 1 Albumin Conventional Units 32–48 0.680 SI Units 0.320– 0.480 Conventional Units 10.7– 21.0 2 SI Units 0.107– 0.210 Inherited deficiencies in normal 1-AT activity are associated with the development, early in life, of lung and liver disorders in which functional tissue is destroyed and replaced with excessive connective tissue; that is, emphysema and cirrhosis may develop in children and young adults who are deficient in 1AT, without the usual predisposing factors associated with onset of these disorders. Such deficiencies are seen on serum protein electrophoresis as a flat area where the normal 1-globulin hump should be. More detailed physiochemical analysis can demonstrate which variant form is present. Decreased levels of 1-AT also are seen in nephrotic syndrome and malnutrition. Reference Values 80 to 213 mg/dL INTERFERING FACTORS Pregnancy Conventional Units 8.5– SI Units 0.085– 14.5 0.145 Conventional Units 6.6– 13.5 SI Units 0.066– Conventional Units 2.4–5.3 0.135 SI Units 0.024– 0.053 Oral contraceptive and steroid administration Extreme physical stress caused by trauma or surgery INDICATIONS FOR 1-ANTITRYPSIN TEST Genetic absence or deficiency of 1-AT, indicated by decreased levels of the protease Suspected inflammation, infection, and necrosis processes, indicated by increased levels of the protease Family history of 1-AT deficiency NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). The client should fast for 8 hours before the test. Water is not restricted. Oral contraceptives and steroids should be withheld 24 hours before the study, although this practice should be confirmed with the person ordering the test. Copyright © 2003 F.A. Davis Company 118 SECTION I—Laboratory Tests THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and frozen if not tested immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume meals or medications withheld before the test. Abnormal values: Note and report decreased levels. Assess for pulmonary or liver disorders and associated signs and symptoms, smoking history, and pollution in the home or work environment. Inform client of stop-smoking clinics and resources for genetic counseling. Instruct client in ways to protect pulmonary system from irritants. Inform client of the importance of medical follow-up. Suggest ongoing support resources to assist client in coping with illness and possible early death. Binding Proteins HAPTOGLOBIN Haptoglobin, an 2-globulin produced in the liver, binds free hemoglobin released by the hemolysis of red blood cells in the bloodstream. Most red blood cells are normally removed in the reticuloendothelial system (e.g., liver, spleen) by a process known as extravascular destruction. Approximately 10 percent of red blood cells are, however, broken down in the circulation (intravascular destruction). This percentage may increase in situations caused by excessive red blood cell hemolysis (e.g., transfusion reaction, hemolytic anemia). The free hemoglobin released from intravascular red blood cell destruction is unstable in plasma and dissociates into components (- dimers) that are quickly bound to haptoglobin. Formation of the haptoglobin–hemoglobin complex prevents the renal excretion of plasma hemoglobin and stabilizes the heme-globin bond. The haptoglobin–hemoglobin complex is removed from the circulation by the liver. There is a limit to the capacity of the haptoglobinbinding mechanism, and a sudden intravascular release of several grams of hemoglobin can exceed binding capacity. Furthermore, because haptoglobin itself is removed from the circulation as a haptoglobin–hemoglobin complex and is catabolized by the liver, a decrease in or absence of haptoglobin may be used to indicate increased intravascular red blood cell hemolysis. Because haptoglobin is formed in the liver, chronic liver disease with impaired protein synthesis also may result in decreased haptoglobin levels. Although haptoglobin is absent in most newborns, congenital absence of haptoglobin (congenital ahaptoglobinemia) can occur in a very small percentage of the population. If haptoglobin is deficient or its binding capacity overwhelmed, unbound hemoglobin dimers are free to be filtered by the renal glomerulus, after which they are reabsorbed by the renal tubules and converted into hemosiderin (a storage form of iron). If renal tubular uptake capacity is exceeded, either free hemoglobin or methemoglobin (a type of hemoglobin with iron in the ferric, instead of the ferrous, form) is excreted in the urine. Note that reabsorption of free hemoglobin may damage the renal tubules because of excessive deposition of hemosiderin.18 Elevated haptoglobin levels are seen in inflammatory diseases (e.g., ulcerative colitis, arthritis, pyelonephritis) and in disorders involving tissue destruction (e.g., malignancies, burns, acute myocardial infarction). Steroid therapy may also elevate haptoglobin levels. Elevated levels are not of major clinical significance except to indicate that additional testing may be necessary to determine the source of the elevation. Reference Values Conventional Units SI Units Newborns 0–10 mg/dL 0–0.1 g/L Adults 30–160 mg/dL 0.3–1.6 g/L INTERFERING FACTORS Steroid therapy may result in elevated levels. INDICATIONS FOR HAPTOGLOBIN TEST Known or suspected disorder characterized by excessive red blood cell hemolysis, as indicated by decreased levels Known or suspected chronic liver disease, as indicated by decreased levels Suspected congenital ahaptoglobinemia, as indicated by decreased levels Known or suspected disorders involving a diffuse inflammatory process or tissue destruction, as indicated by elevated levels Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–6 • Chemistry 119 Causes of Altered Levels of Ceruloplasmin Increased Levels Acute infections Decreased Levels Wilson’s disease Hepatitis Malabsorption syndromes Hodgkin’s disease Long-term total parenteral nutrition Hyperthyroidism Menkes’ kinky hair syndrome Pregnancy Nephrosis Malignancies of bone, lung, stomach Severe liver disease Myocardial infarction Early infancy Rheumatoid arthritis Drugs Oral contraceptives Estrogens Methadone Phenytoin (Dilantin) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. Some laboratories require that the sample be placed in ice immediately upon collection. The sample should be handled gently to avoid hemolysis, which may alter test results, and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. CERULOPLASMIN Ceruloplasmin (Cp) is an 2-globulin that binds copper for transport within the circulation after it is absorbed from the gastrointestinal tract. Among the disorders associated with abnormal ceruloplasmin levels is Wilson’s disease (hepatolenticular degeneration), an inherited disorder characterized by excessive absorption of copper from the gastrointestinal tract, decreased ceruloplasmin, and deposition of copper in the liver, brain, corneas (Kayser-Fleischer rings), and kidneys. In addition to low ceruloplasmin levels, serum copper levels are decreased because of excessive excretion of unbound copper in the kidneys and deposition of copper in the body tissues. The disorder manifests during the first three decades of life and is fatal unless treatment is instituted. Other causes of abnormal ceruloplasmin levels are listed in Table 5–6. Reference Values Conventional Units SI Units Newborns 2–13 mg/dL 20–130 mol/L Adults 23–50 mg/dL 230–500 mol/L INDICATIONS FOR CERULOPLASMIN TEST Family history of Wilson’s disease (hepatolenticular degeneration) Signs of liver disease combined with neurological changes, especially in a young person, with Wilson’s disease indicated by decreased levels Monitoring of ceruloplasmin levels in disorders associated with abnormal values (see Table 5–6) Monitoring of response to TPN (hyperalimentation), which may lead to decreased levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company 120 SECTION I—Laboratory Tests THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. Some laboratories require that the sample be placed in ice immediately on collection. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. nitrogen; the result is expressed as urea nitrogen. Nitrogen contributes 46.7 percent of the total weight of urea. The concentration of urea can be calculated by multiplying the urea nitrogen result by 2.14.19 INTERFERING FACTORS Therapy with drugs known to alter urea nitrogen levels (see Table 5–7) NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal values: Note and report decreased levels. Assess for hepatic or neurological or psychiatric manifestations of Wilson’s disease. Assess for history of ceruloplasmin deficiency by Kayser-Fleischer rings determined by slit-lamp examination. Inform of need for follow-up medical care and genetic counseling. INDICATIONS FOR UREA NITROGEN TEST Known or suspected disorder associated with impaired renal function, as indicated by increased levels: Obstructive, inflammatory, or toxic damage to the kidneys, nephron loss caused by aging, or extrarenal conditions that reduce the glomerular filtration rate (GFR) increase retention of urea. Monitoring for the effects of disorders associated with altered fluid balance: Dehydration or hypovolemia caused by vomiting, diarrhea, hemorrhage, or inadequate fluid intake raises the urea nitrogen. Fluid overload decreases the urea nitrogen if renal function is adequate. Known or suspected liver disease as indicated by decreased levels caused by the liver’s inability to convert ammonia to urea (80 percent of liver function may be lost before this is evident) Monitoring for effects of drugs known to be nephrotoxic or hepatotoxic Monitoring of response to various disorders known to result in altered urea nitrogen levels (see Table 5–7) Protein Metabolites Most nitrogen in the blood resides in proteins, and the amount of nitrogen contained in proteins is high in relation to amino acid content. When proteins are metabolized, the nitrogen-containing components are removed from the amino acids, a process known as deamination. The resulting protein metabolites include urea, creatinine, ammonia, creatine, and uric acid. Levels of these nonprotein nitrogenous compounds reflect various aspects of protein balance and metabolism. UREA NITROGEN Urea is a nonprotein nitrogenous compound that is formed in the liver from ammonia. Although urea diffuses freely into both extracellular and intracellular fluid, it is ultimately excreted by the kidneys. Blood urea levels reflect the balance between production and excretion of urea. Changes in protein intake, fluid balance, liver function, and renal excretion affect blood urea levels. Specific causes of alterations are listed in Table 5–7. Blood urea analysis involves measurement of NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Some laboratories require an 8-hour fast before the test. THE PROCEDURE A venipuncture is performed and the sample is obtained in either a gray-topped or red-topped tube, Reference Values Conventional Units [Urea Nitrogen] SI Units [Urea] Newborns 4–18 mg/dL 1.4–6.4 mmol/L Children 7–18 mg/dL 2.5–6.4 mmol/L Adults 5–20 mg/dL 1.8–7.1 mmol/L Critical values 100 mg/dL 35.7 mmol/L Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–7 • Chemistry Causes of Altered Urea Levels Increased Levels Decreased Levels Congestive heart failure Inadequate dietary protein Shock Severe liver disease Hypovolemia Water overload Urinary tract obstruction Nephrotic syndrome Renal diseases Pregnancy Starvation Amyloidosis Infection Malabsorption syndromes Myocardial infarction Drugs Diabetes mellitus IV dextrose Burns Phenothiazines Gastrointestinal bleeding Thymol Advanced pregnancy Nephrotoxic agents Excessive protein ingestion Malignancies Addison’s disease Gout Pancreatitis Tissue necrosis Advanced age Drugs Aspirin Acetaminophen Cancer chemotherapeutic agents Antibiotics (amphotericin B, cephalosporins, aminoglycosides) Thiazide diuretics Indomethacin (Indocin) Morphine Codeine Sulfonamides Methyldopa (Aldomet) Propranolol (Inderal) Guanethidine (Ismelin) Pargyline (Eutonyl) Lithium carbonate Dextran Sulfonylureas 121 Copyright © 2003 F.A. Davis Company 122 SECTION I—Laboratory Tests depending on the laboratory performing the test. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. If the client’s diet was restricted before the test, the usual diet may be resumed. Abnormal levels: Note and report decreased levels. Assess hydration status for overhydration, I&O, osmolality, and sodium levels. Note and report increased levels and assess in relation to creatinine level. Assess electrolyte panel and for signs and symptoms of anemia, gastrointestinal bleeding, oliguria, confusion, and level of consciousness if urea nitrogen rises to greater than 20 to 50 mg/dL. Monitor urinary output every hour. Provide safety measures if consciousness is altered. Instruct as to restriction in fluid and dietary intake of protein (meat, fish, poultry). Daily generation of creatinine remains fairly constant unless crushing injury or degenerative diseases cause massive muscle damage. The kidneys excrete creatinine very efficiently. Levels of blood and urine flow affect creatinine excretion much less than they influence urea excretion because temporary alterations in renal blood flow and glomerular function can be compensated by increased tubular secretion of creatinine. Thus, serum creatinine is a more sensitive indicator of renal function than is urea nitrogen.20 INDICATIONS FOR SERUM CREATININE TEST Critical values: Notify the physician immediately if levels are greater than 100 mg/dL. SERUM CREATININE Creatinine is the end product of creatine metabolism. Creatine, although synthesized largely in the liver, resides almost exclusively in skeletal muscle, where it reversibly combines with phosphate to form the energy storage compound phosphocreatine. This reaction (creatine phosphate ← → phosphocreatine) repeats as energy is released and regenerated, but in the process small amounts of creatine are irreversibly converted to creatinine, which serves no useful function and circulates only for transportation to the kidneys. The amount of creatinine generated in an individual is proportional to the mass of skeletal muscle present; level of muscular activity is not a critical determinant. Known or suspected impairment of renal function, including therapy with nephrotoxic drugs: In the absence of disorders affecting muscle mass, elevated creatinine levels indicate decreased renal function. Creatinine levels may be normal in situations in which a slow decline in renal function occurs simultaneously with a slow decline in muscle mass, as may occur in elderly individuals (in such situations, a 24-hour urine collection yields lower than normal excretion levels). Along with a urea nitrogen, to provide additional client information: An elevated urea nitrogen with a normal creatinine usually indicates a nonrenal cause for the excessive urea. The urea nitrogen rises more steeply than creatinine as renal function declines, and it falls more rapidly with dialysis. With severe, permanent renal impairment, urea levels continue to climb, but creatinine values tend to plateau (at very high circulating creatinine levels, some is excreted through the gastrointestinal tract). Known or suspected disorder involving muscles, including crushing injury to muscles: In the absence of renal disease, elevated serum creatinine levels are associated with trauma or Reference Values Conventional Units SI Units Children 6 yr 0.3–0.6 mg/dL 24–54 mol/L Children 6–18 yr 0.4–1.2 mg/dL 36–106 mol/L Men 0.6–1.3 mg/dL 53–115 mol/L Women 0.5–1.0 mg/dL 44–88 mol/L Critical values 10 mg/dL 880 mol/L Adults Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood disorders causing excessive muscle mass (gigantism, acromegaly). Decreased levels are associated with muscular dystrophy. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Some laboratories require an 8-hour fast before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Increased levels should be assessed in relation to the urea nitrogen; notify the physician immediately if levels are greater than 10 mg/dL unless the client is on dialysis. AMMONIA Blood ammonia comes from two sources: (1) deamination of amino acids during protein metabolism and (2) degradation of proteins by colon bacteria. The liver converts ammonia to urea, generating glutamine as an intermediary. The kidneys then use glutamine as a source for synthesizing ammonia for renal regulation of electrolyte and acid–base balance. Serum ammonia levels have little effect on renal excretion of ammonia. Circulating blood normally contains very little ammonia because the liver converts ammonia in the portal blood to urea. When liver function is severely compromised, especially in situations when decreased hepatocellular function is combined with impaired portal blood flow, ammonia levels rise. Both elevated serum ammonia and abnormal glutamine metabolism have been implicated as etiologic factors in hepatic encephalopathy (hepatic coma).21 Additional causes of altered serum ammonia levels are listed in Table 5–8. Reference Values Conventional Units Chemistry 123 INDICATIONS FOR SERUM AMMONIA TEST Evaluation of advanced liver disease or other disorders associated with altered serum ammonia levels (see Table 5–8) Identification of impending hepatic encephalopathy in clients with known liver diseases (e.g., after bleeding from esophageal varices or other gastrointestinal sources, or after excessive ingestion of protein) as indicated by rising levels Monitoring for the effectiveness of treatment for hepatic encephalopathy as indicated by declining levels NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). An 8-hour fast from food is required before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube. Some laboratories require that the sample be placed in ice immediately on collection. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods withheld before the test. SERUM CREATINE Creatine is a nitrogen-containing compound found largely in skeletal muscle, where it functions as an energy source. Its use by muscles results in loss proportionate to the muscle mass and level of muscular activity. Measurement of serum creatine reflects this loss, which is fairly constant under normal conditions. Reference Values Conventional Units SI Units Men 0.1–0.4 mg/dL 9–35 mol/L Women 0.2–0.7 mg/dL 18–62 mol/L SI Units Newborns 90–150 g/dL 64–107 mol/L Children 40–80 g/dL 23–47 mol/L Adults 15–45 g/dL 11–32 mol/L INTERFERING FACTORS Failure to follow dietary restrictions and vigorous exercise within 8 hours of the test may alter results. Copyright © 2003 F.A. Davis Company 124 SECTION I—Laboratory TABLE 5–8 Tests • Causes of Altered Blood Ammonia Levels Increased Levels Decreased Levels Liver failure, late cirrhosis Renal failure GI hemorrhage Hypertension Late congestive heart failure Drugs Azotemia Arginine (R-Gene) Hemolytic disease of the newborn Benadryl Chronic obstructive pulmonary disease Sodium salts Leukemias Glutamic acid (Acidulin) Reye’s syndrome MAO inhibitors Inborn enzyme deficiency Antibiotics (tetracycline [Achromycin], kanamycin [Kantrex], neomycin) Excessive protein ingestion Potassium salts Alkalosis Drugs Acetazolamide (Diamox) Ammonium salts Barbiturates Colistin (Coly-Mycin S) Diuretics Ethanol Heparin Isoniazid Methicillin Morphine Tetracycline INDICATIONS FOR SERUM CREATINE TEST Signs and symptoms of muscular disease (e.g., muscle injury, muscular dystrophies, dermatomyositis), as indicated by elevated levels Monitoring for the progression of muscle-wasting diseases with serial measurements indicating the rate of muscle deterioration Evaluation of the effects of hyperthyroidism and rheumatoid arthritis on muscle tissue NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Food, fluids, and vigorous exercise are not permitted for at least 8 hours before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Resume foods and fluids withheld before the test, as well as usual activities. URIC ACID Uric acid (urate) is the end product of purine metabolism. Purines are important constituents of Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 125 Reference Values Conventional Units SI Units Children 2.5–5.5 mg/dL 0.15–0.33 mmol/L Men 4.0–8.5 mg/dL 0.24–0.51 mmol/L Women 2.7–7.3 mg/dL 0.16–0.43 mmol/L Critical values 12 mg/dL 0.71 mmol/L nucleic acids; purine turnover occurs continuously in the body, producing substantial amounts of uric acid even in the absence of dietary purine (e.g., meats, legumes, yeasts) intake. Most uric acid is synthesized in the liver and excreted by the kidneys. Serum urate levels are affected by the amount of uric acid produced as well as by the efficiency of renal excretion. Both gout and urate renal calculi (kidney stones) are associated with elevated uric acid levels. Other disorders and drugs associated with altered uric acid levels are listed in Table 5–9. INTERFERING FACTORS Therapy with drugs known to alter uric acid levels (see Table 5–9), unless the test is being conducted to monitor such drug effects INDICATIONS FOR URIC ACID TEST Family history of gout (autosomal dominant genetic disorder) or signs and symptoms of gout, or both, with the disorder indicated by elevated levels Known or suspected renal calculi, to determine the cause Signs and symptoms of disorders associated with altered uric acid levels (see Table 5–9) Monitoring for the effects of drugs known to alter uric acid levels (see Table 5–9), either as a side effect or as a therapeutic effect Evaluation of the extent of tissue destruction in infection, starvation, excessive exercise, malignancies, chemotherapy, or radiation therapy Evaluation of possible liver damage in eclampsia, as indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Some laboratories require an 8-hour fast from food before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods withheld before the test. Abnormal values: Note and report increased level. Assess for symptoms associated with renal stones and joint pain. Prepare to administer ordered medications (allopurinol, probenecid, nonsteroidal anti-inflammatory analgesics). Increase fluid intake. Instruct client to avoid highpurine fluids and foods (sardines, organ meats, legumes, alcohol, caffeine-containing beverages). Critical values: Notify the physician immediately if levels are greater than 12 mg/dL. LIPIDS Lipids are carbon- and hydrogen-containing compounds that are insoluble in water but soluble in organic solvents. Biologically important categories of lipids are the neutral fats (e.g., triglycerides), the conjugated lipids (e.g., phospholipids), and the sterols (e.g., cholesterol). Lipids function in the body as sources of energy for various metabolic processes. Other functions include contributing to the formation of cell membranes, bile acids, and various hormones. Lipids are derived from both dietary sources and internal body processes. Almost the entire fat portion of the diet consists of triglycerides, which are combinations of three fatty acids and one glycerol molecule. Triglycerides are found in foods of both animal and plant origin. The usual diet also includes small quantities of phospholipids, cholesterol, and cholesterol esters. Phospholipids and cholesterol esters contain fatty acids. In contrast, cholesterol does not contain fatty acids, but its sterol nucleus is synthesized from their degradation products. Because cholesterol has many of the physical and chemical properties of other lipids, it is included as a dietary fat. Note that cholesterol occurs only in foods of animal origin, including eggs and cheese. Copyright © 2003 F.A. Davis Company 126 SECTION I—Laboratory Tests TABLE 5–9 • Causes of Altered Uric Acid Levels Increased Levels Decreased Levels Excessive dietary purines Fanconi’s syndrome Polycythemia Wilson’s disease Gout Yellow atrophy of the liver Psoriasis Drugs Type III hyperlipidemia Probenecid Chemotherapy, radiation therapy for malignancies Sulfinpyrazone von Gierke’s disease Aspirin (4 g/day) Sickle cell anemia Adrenocorticotropic hormone, corticosteroids Pernicious anemia Coumarin Acute tissue destruction (infection, starvation, exercise) Estrogens Eclampsia, hypertension Allopurinol Hyperparathyroidism Acetohexamide (Dymelor) Decreased excretion from lactic acidosis, ketoacidosis, renal failure, congestive heart failure Azathioprine (Imuran) Drugs Clofibrate Alcohol 2-Phenylcinchoninic acid (Cinchophen) Aspirin (2 g/day) Chlorprothixene (Taractan) Thiazide diuretics Mannitol Diazoxide (Hyperstat) Marijuana Epinephrine Ethacrynic acid (Edecrin) Furosemide Phenothiazines Dextran Methyldopa Ascorbic acid Aminophylline Antibiotics (gentamicin) Griseofulvin Rifampin Triamterene (Dyrenium) Nearly all dietary fats are absorbed into the lymph. Ingested triglycerides are emulsified by bile and then broken down into fatty acids and glycerol by pancreatic and enteric lipases. The fatty acids and glycerol then pass through the intestinal mucosa and are resynthesized into triglycerides that aggregate and enter the lymph as minute droplets called chylomicrons. Although chylomicrons are composed primarily of triglycerides, cholesterol and phospholipids absorbed from the gastrointestinal tract also contribute to their composition (Table 5–10). In addition to dietary sources of lipids, the body itself is able to produce various fats. Unused glucose Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–10 Triglyceride % • Chemistry 127 Lipoprotein Composition Cholesterol Phospholipid % % Protein % Electrophoretic Mobility Chylomicrons 85–95 3–5 5–10 1–2 Remain at origin Very-low-density lipoproteins 60–70 10–15 10–15 10 2-Lipoprotein, pre--lipoprotein Low-density lipoproteins 5–10 45 20–30 15–25 -Lipoprotein High-density lipoproteins Very little 20 30 50 1-Lipoprotein From Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 473, with permission. and amino acids, for example, may be converted into fatty acids by the liver. Similarly, nearly all body cells are capable of forming phospholipids and cholesterol, although most of the endogenous production of these lipids occurs in the liver or intestinal mucosa. Because lipids are insoluble in water, special transport mechanisms are required for circulation in the blood. Free fatty acids travel through blood combined with albumin and in this form are called nonesterified fatty acids. Very little free fatty acid is normally present in the blood; therefore, the major lipid components found in serum are triglycerides, cholesterol, and phospholipids. These lipids exist in blood as macromolecules complexed with specialized proteins (apoproteins) to form lipoproteins. Lipoproteins are classified according to their density, which results from the amounts of the various lipids they contain (see Table 5–10). The least dense lipoproteins are those with the highest triglyceride levels. Lipoprotein densities also are reflected in the electrophoretic mobility of the various types. As with the formation of other endogenous lipids, most lipoproteins are formed in the liver.22,23 FREE FATTY ACIDS Free fatty acids (FFA) travel through the blood combined with albumin and in this form are called nonesterified fatty acids (NEFA). Normally, approximately three fatty acid molecules are combined with each molecule of albumin. If, however, the need for fatty acid transport is great (e.g., when needed carbohydrates are not available or cannot be used for energy), as many as 30 fatty acids can combine with one albumin molecule. Thus, although blood levels of FFA are never very high, they rise impressively after stimuli to release fat. The same stimuli that elevate FFA will, in most cases, also elevate serum triglycerides and may produce alterations in lipoprotein levels. Specific causes of both elevated and decreased FFA, including drugs, are listed in Table 5–11. Reference Values Conventional Units Free fatty acids 8–25 mg/dL SI Units 0.30–0.90 mmol/L INTERFERING FACTORS Ingestion of alcohol within 24 hours before the test may result in falsely elevated values. Failure to follow dietary restrictions before the test may alter values. Drugs known to alter FFA levels should not be ingested unless the test is being performed to evaluate such effects (see Table 5–11). INDICATIONS FOR FREE FATTY ACIDS TEST Support for diagnosing uncontrolled or untreated diabetes mellitus, as indicated by elevated levels Evaluation of response to treatment for diabetes, as indicated by declining levels Suspected malnutrition, as indicated by elevated levels Known or suspected disorder associated with excessive hormone production (see Table 5–11), as indicated by elevated levels Evaluation of response to therapy with drugs known to alter FFA levels (see Table 5–11) NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should abstain from alcohol for 24 hours and from food for at least 8 hours before the test. Water is not restricted. Copyright © 2003 F.A. Davis Company 128 SECTION I—Laboratory Tests • Factors Associated with Altered Free Fatty Acid Levels TABLE 5–11 Increased Levels Decreased Levels Diabetes mellitus Drugs Starvation Aspirin Pheochromocytoma Clofibrate Acute alcohol intoxication Glucose Chronic hepatitis Insulin Acute renal failure Neomycin Glycogen storage disease Streptozocin Hypoglycemia Hypothermia Hormones Adrenocorticotropic hormone Cortisone Epinephrine, norepinephrine Growth hormone Thyroid-stimulating hormone Thyroxine Drugs Abnormal values: Note and report any increased level. Assess in relation to glucose and ketone and to lipid and lipoprotein electrophoresis levels. Assess for recent weight gain or loss. Instruct in appropriate fat and carbohydrate intake in the diet. TRIGLYCERIDES Triglycerides, which are combinations of three fatty acids and one glycerol molecule, are used in the body to provide energy for various metabolic processes, with excess amounts stored in adipose tissue. Fatty acids readily enter and leave the triglycerides of adipose tissue, providing raw materials needed for conversion to glucose (gluconeogenesis) or for direct combustion as an energy source. Although fatty acids originate in the diet, many also derive from unused glucose and amino acids that the liver and, to a smaller extent, the adipose tissue convert into storage energy. Altered triglyceride levels are associated with a variety of disorders and also are affected by hormones and certain drugs, including alcohol (Table 5–12). Diets high in calories, fats, or carbohydrates will elevate serum triglyceride levels, which is considered a risk factor for atherosclerotic cardiovascular disease. Reference Values Amphetamines Caffeine Conventional Units SI Units Chlorpromazine 2 yr 5–40 mg/dL 0.06–0.45 mmol/L Isoproterenol 2–20 yr 10–140 mg/dL 0.11–1.58 mmol/L Nicotine 20–40 yr Men 10–140 mg/dL 0.11–1.58 mmol/L Women 10–150 mg/dL 0.11–1.68 mmol/L Men 10–180 mg/dL 0.11–2.01 mmol/L Women 10–190 mg/dL 0.11–2.21 mmol/L Reserpine Tolbutamide 40–60 yr Drugs known to affect FFA levels (see Table 5–11) may be withheld before the test, although this may not always be done if the therapeutic effect on FFA levels is being evaluated. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent immediately to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods and any drugs withheld before the test. Note: Values for serum triglycerides may vary according to the laboratory performing the test. In addition, values have been found to vary in relation to race, income level, level of physical activity, dietary habits, and geographic location as well as in relation to age and gender, as shown here. INTERFERING FACTORS Failure to follow the usual diet for 2 weeks before the test may yield results that do not accurately reflect client status. Ingestion of alcohol 24 hours before and food 12 hours before the test may falsely elevate levels. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–12 • Chemistry 129 Disorders and Drugs Associated with Altered Triglyceride Levels Elevated Levels Decreased Levels DISORDERS Primary hyperlipoproteinemia Acanthocytosis Atherosclerosis Cirrhosis Hypertension Inadequate dietary protein Myocardial infarction Hyperthyroidism Diabetes mellitus Hyperparathyroidism Obstructive jaundice Hypothyroidism (primary) Hypoparathyroidism Nephrotic syndrome Chronic obstructive pulmonary disease Down syndrome von Gierke’s disease DRUGS Alcohol Clofibrate Cholestyramine Dextrothyroxine Corticosteroids Heparin Colestipol Menotropins (Pergonal) Oral contraceptives Sulfonylureas Thyroid preparations Norethindrone Estrogen Androgens Furosemide Niacin Miconazole Anabolic steroids Ascorbic acid Drugs known to alter triglyceride levels should not be ingested within 24 hours before the test unless the test is being conducted to evaluate such effects (see Table 5–12). INDICATIONS FOR SERUM TRIGLYCERIDES TEST As a component of a complete physical examination, especially for individuals over age 40 years or who are obese, or both, to estimate the degree of risk for atherosclerotic cardiovascular disease Family history of hyperlipoproteinemia (hyperlipidemia) Known or suspected disorders associated with altered triglyceride levels (see Table 5–12) Monitoring of response to drugs known to alter triglyceride levels or lipid-lowering agents NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any procedure involving collection of a peripheral blood sample (see Appendix I). For this test, the client should ingest a normal diet, so that no weight gain or loss will occur for 2 weeks before the study, and should abstain from alcohol for 24 hours and from food for 12 hours before the test. Water is not restricted. It is also recommended that drugs that may alter triglyceride levels be withheld for 24 hours before Copyright © 2003 F.A. Davis Company 130 SECTION I—Laboratory Tests the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent promptly to the laboratory. INTERFERING FACTORS Ingestion of alcohol 24 hours before and food 12 hours before the test may falsely elevate levels. Ingestion of drugs known to alter cholesterol levels within 12 hours of the test may alter results, unless the test is being conducted to evaluate such effects (see Table 5–13). NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods and any drugs withheld before the test. Abnormal values: Note and report increased level. Assess in relation to cholesterol and lipoprotein electrophoresis. Instruct in low-fat diet and weight reduction caloric intake as appropriate. TOTAL CHOLESTEROL Cholesterol is necessary for the formation of cell membranes and is a component of the materials that render the skin waterproof. Cholesterol also contributes to the formation of bile salts, adrenocorticosteroids, estrogens, and androgens. Cholesterol has two sources: (1) that obtained from the diet (exogenous cholesterol) and (2) that which is synthesized in the body (endogenous cholesterol). Although most body cells can form some cholesterol, most is produced by the liver and the intestinal mucosa. Because cholesterol is continuously synthesized, degraded, and recycled, it is probable that very little dietary cholesterol enters directly into metabolic reactions. Altered cholesterol levels are associated with a variety of disorders and also are affected by hormones and certain drugs (Table 5–13). Reference Values INDICATIONS FOR TOTAL CHOLESTEROL TEST As a component of a complete physical examination, especially for individuals over age 40 years or those who are obese, or both, to estimate the degree of risk for atherosclerotic cardiovascular disease: In general, the desirable blood cholesterol level is less than 200 mg/dL. Cholesterol levels of 200 to 240 mg/dL are considered borderline, and the person is considered at high risk if other factors such as obesity and smoking are present; for the latter individuals, additional tests such as lipoprotein and cholesterol fractionation should be performed. Cholesterol levels of greater than 250 mg/dL place the person at definite high risk for cardiovascular disease and require treatment; additional tests such as lipoprotein and cholesterol fractionation should be performed. Family history of hypercholesterolemia or cardiovascular disease or both Known or suspected disorders associated with altered cholesterol levels (see Table 5–13) Monitoring of response to dietary treatment of hypercholesterolemia and support for decisions regarding need for drug therapy (Cholesterol levels may fall with diet modification alone over a period of 6 months, only to return gradually to previous levels.) Monitoring for response to drugs known to alter cholesterol levels (see Table 5–13) or lipid-lowering agents Conventional Units SI Units 25 yr 125–200 mg/dL 3.27–5.20 mmol/L NURSING CARE BEFORE THE PROCEDURE 25–40 yr 140–225 mg/dL 3.69–5.85 mmol/L 40–50 yr 160–245 mg/dL 4.37–6.35 mmol/L 50–65 yr 170–265 mg/dL 4.71–6.85 mmol/L 65 yr 175–265 mg/dL 4.71–6.85 mmol/L General client preparation is the same as that for any procedure involving collection of a peripheral blood sample (see Appendix I). For this test, the client should abstain from alcohol for 24 hours and from food for 12 hours before the study. Water is not restricted. It also is recommended that drugs that may alter cholesterol levels be withheld for 12 hours before the test, although this practice should be confirmed with the person ordering the study. Note: Values for total cholesterol may vary according to the laboratory performing the test. In addition, values have been found to vary according to gender, race, income level, level of physical activity, dietary habits, and geographic location as well as in relation to age, as shown here. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–13 • Chemistry 131 Disorders and Drugs Associated with Altered Cholesterol Levels Elevated Levels Decreased Levels DISORDERS Familial hyperlipoproteinemia Malabsorption syndromes Atherosclerosis Liver disease Hypertension Hyperthyroidism Myocardial infarction Cushing’s syndrome Obstructive jaundice Pernicious anemia Hypothyroidism (primary) Carcinomatosis Nephrosis Xanthomatosis Pregnancy Oophorectomy DRUGS Adrenocorticotropic hormone Antidiabetic agents Androgens Cholestyramine Bile salts Clofibrate Catecholamines Colchicine Corticosteroids Colestipol Oral contraceptives Dextrothyroxine Phenothiazines Estrogen Salicylates Glucagon Thiouracils Haloperidol (Haldol) Vitamins A and D (excessive) Heparin Kanamycin Neomycin Nitrates, nitrites Para-aminosalicylate Phenytoin (Dilantin) THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any drugs withheld before the test. PHOSPHOLIPIDS Phospholipids consist of one or more fatty acid molecules and one phosphoric acid radical, and they usually have a nitrogenous base. The three major types of body phospholipids are the lecithins, the Copyright © 2003 F.A. Davis Company 132 SECTION I—Laboratory Tests cephalins, and the sphingomyelins. In addition to diet as a source of phospholipids, nearly all body cells are capable of forming these lipids. Most endogenous phospholipids are formed, however, in the liver and intestinal mucosa. The phospholipids are transported together in circulating blood in the form of lipoproteins. Phospholipids are important for the formation of cell membranes and for the transportation of fatty acids through the intestinal mucosa into lymph. Phospholipids also serve as donors of phosphate groups for intracellular metabolic processes and may act as carriers in active transport systems. Saturated lecithins are essential for pulmonary gas exchange, whereas the cephalins are major constituents of thromboplastin, which is necessary to initiate the clotting process. Sphingomyelin is present in large quantities in the nervous system and acts as an insulator around nerve fibers.24 Phospholipids may be measured as part of an overall lipid evaluation, but the significance of altered levels is not completely understood. A direct relationship between elevated phospholipids and atherosclerotic cardiovascular disease has not been demonstrated. Alterations in phospholipid levels may be seen in situations similar to those in which serum triglycerides and cholesterol also are abnormal. For example, elevated levels are associated with diabetes mellitus, nephrotic syndrome, chronic pancreatitis, obstructive jaundice, and early starvation. Decreased levels are seen in clients with primary hypolipoproteinemia, severe malnutrition and malabsorption syndromes, and cirrhosis. Antilipemic drugs (e.g., clofibrate) may lower phospholipid levels, and epinephrine, estrogens, and chlorpromazine tend to elevate them. Another clinical application of phospholipid data is the use of the lecithin:sphingomyelin (L:S) ratio in estimating fetal lung maturity, with adequate lung maturity indicated by lecithin levels greater than those for sphingomyelin by a ratio of 2:1 or greater (see Chapter 10). Reference Values Conventional Units SI Units Infants 100–275 mg/dL 1.00–2.75 g/L Children 180–295 mg/dL 1.80–2.95 g/L Adults 150–380 mg/dL 1.50–3.80 g/L Note: Values may vary, depending on the laboratory performing the test and the age of the client. INTERFERING FACTORS Ingestion of alcohol 24 hours before and food 12 hours before the test may falsely elevate levels. Ingestion of drugs known to alter phospholipid levels within 12 hours before the test may alter results unless the test is being conducted to evaluate such effects. Antilipemic drugs (e.g., clofibrate) may lower phospholipid levels. Epinephrine, estrogens, and chlorpromazine tend to elevate phospholipid levels. INDICATIONS FOR SERUM PHOSPHOLIPIDS TEST Known or suspected disorders that cause or are associated with altered lipid metabolism: Altered phospholipid levels are seen in situations similar to those in which serum triglycerides and cholesterol also are altered (see Tables 5–12 and 5–13). Elevated levels are associated with diabetes mellitus, nephrotic syndrome, chronic pancreatitis, obstructive jaundice, and early starvation. Decreased levels are seen in primary hypolipoproteinemia, severe malnutrition, malabsorption syndromes, and cirrhosis. Support for identifying problems related to fat metabolism and transport: Phospholipid formation parallels deposition of triglycerides in the liver, and severely decreased levels result in low levels of lipoproteins that are essential for fat transport. Abnormal bleeding of unknown origin, with decreased cephalin (a type of phospholipid), a possible contributor to low levels of thromboplastin Suspected neurological disorder, which may be associated with decreased levels of sphingomyelin (a type of phospholipid) NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any procedure involving collection of a peripheral blood sample (see Appendix I). For this test, the client should abstain from alcohol for 24 hours and from food for 12 hours before the study. Water is not restricted. It also is recommended that drugs that may alter phospholipid levels be withheld for 12 hours before the test, although this practice should be confirmed with the person ordering the study. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods and any drugs withheld before the test. LIPOPROTEIN AND CHOLESTEROL FRACTIONATION Lipids are transported in the blood as lipoproteins— complex molecules consisting of triglycerides, cholesterol, phospholipids, and proteins. Lipoproteins exist in several forms that reflect the different concentrations of their constituents. These forms, or fractions, are classified according to either their densities or their electrophoretic mobility. The lipoprotein fractions in relation to density are (1) chylomicrons, (2) very-low-density lipoproteins (VLDL), (3) low-density lipoproteins (LDL), and (4) high-density lipoproteins (HDL). The least dense lipoproteins—chylomicrons and VLDL—contain the highest levels of triglycerides and lower amounts of cholesterol and protein. LDL and HDL contain Chemistry 133 the lowest amounts of triglycerides and relatively higher amounts of cholesterol and protein (see Table 5–10). Lipoprotein densities correspond to the electrophoretic mobility patterns of the several lipoprotein fractions. The two main fractions of lipoproteins, as identified by electrophoresis, are and . -Lipoproteins, which approximate the HDL (1), migrate with the -globulins. The -lipoproteins, which reflect the VLDL (pre-) and the LDL (), migrate with the -globulins. Chylomicrons remain at the origin. The cholesterol content of the HDL and LDL fractions also can be determined by measuring total cholesterol remaining after one fraction has been removed. Note, however, that HDL cholesterol does not correlate well with the total cholesterol concentration, is higher in women than in men, and tends to be inversely proportional to triglyceride levels. High HDL cholesterol and low LDL cholesterol levels are predictive of a reduced risk of cardiovascular disease, whereas high LDL cholesterol and low HDL cholesterol levels are considered risk factors for atherosclerotic cardiovascular disease. Further, many health-care providers believe that an adequate lipid assessment need include only (1) total cholesterol, (2) HDL cholesterol, (3) serum triglycerides, and (4) estimate of chylomicron concentration. Specific conditions associated with altered levels of lipoprotein fractions are listed in Table 5–14. Reference Values Conventional Units SI Units Total lipoproteins 400–800 mg/dL — Chylomicrons — — VLDL or pre- 3–32 mg/dL — LDL or 38–40 mg/dL 0.98–1.04 mmol/L HDL or 1 20–48 mg/dL 0.51–1.24 mmol/L LDL Cholesterol Age HDL Cholesterol Conventional Units SI Units Conventional Units SI Units 25 yr 73–138 mg/dL 1.87–3.53 mmol/L 32–57 mg/dL 0.82–1.46 mmol/L 25–40 yr 90–180 mg/dL 2.30–4.60 mmol/L 32–60 mg/dL 0.82–1.54 mmol/L 40–50 yr 100–185 mg/dL 2.56–4.74 mmol/L 33–60 mg/dL 0.84–1.54 mmol/L 50–65 yr 105–190 mg/dL 2.69–4.96 mmol/L 34–70 mg/dL 0.87–1.79 mmol/L 65 yr 105–200 mg/dL 2.69–5.12 mmol/L 35–75 mg/dL 0.90–1.92 mmol/L Note: HDL cholesterol values are normally lower in men than in women, with an average range of 22 to 68 mg/dL. Copyright © 2003 F.A. Davis Company 134 SECTION I—Laboratory TABLE 5–14 • Lipoprotein Chylomicrons Tests Conditions Associated with Altered Levels of Lipoprotein Fractions Increased Level Decreased Level Ingested fat Not applicable—normal value is zero Ingested alcohol Types I and V hyperlipoproteinemia VLDL Ingested fat Abetalipoproteinemia Ingested carbohydrate Cirrhosis Ingested alcohol Hypobetalipoproteinemia All types of hyperlipoproteinemia Exogenous estrogens Diabetes mellitus Hypothyroidism (primary) Nephrotic syndrome Alcoholism Pancreatitis Pregnancy LDL cholesterol Ingested cholesterol Types I and V hyperlipoproteinemia Ingested saturated fatty acids Hypobetalipoproteinemia Types II and III hyperlipoproteinemia Abetalipoproteinemia Hypothyroidism (primary) Hyperthyroidism Biliary obstruction Cirrhosis Nephrotic syndrome HDL cholesterol Ingested alcohol (moderate amounts) All types of hyperlipoproteinemia Chronic hepatitis Exogenous estrogens Hypothyroidism (primary) Hyperthyroidism Early biliary cirrhosis Cirrhosis Biliary obstruction Tangier disease INTERFERING FACTORS Failure to follow usual diet for 2 weeks before the test may yield results that do not accurately reflect client status. Ingestion of alcohol 24 hours before and food 12 hours before the test may alter results. Excessive exercise 12 hours before the test may alter results (regular exercise has been found to lower HDL cholesterol levels). Numerous drugs may alter results, including those that are known to alter lipoprotein components (see Tables 5–12 and 5–13). INDICATIONS FOR LIPOPROTEIN AND CHOLESTEROL FRACTIONATION Serum cholesterol levels of greater than 250 mg/dL, which indicate high risk for cardiovascular disease and the need for further evaluation and possible treatment Estimation of the degree of risk for cardiovascular disease: Individuals with LDL cholesterol levels greater than 160 mg/dL are considered to be at high risk. Individuals at or above the upper reference Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood range for HDL cholesterol have half the average risk, whereas those at or near the bottom have two, three, or more times the average risk. Known or suspected disorders associated with altered lipoprotein levels (see Table 5–14) Evaluation of response to treatment for altered levels and support for decisions regarding the need for drug therapy (LDL cholesterol levels may decrease with dietary modification alone; if not, drug treatment is recommended.) NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any procedure involving collection of a peripheral blood sample (see Appendix I). For this test, the client should ingest a normal diet, such that no weight gain or loss will occur for 2 weeks before the study, and should abstain from alcohol for 24 hours and from food for 12 hours before the test. Water is not restricted. The client also should avoid excessive exercise for at least 12 hours before the test. It also is recommended that drugs that may alter lipoprotein components be withheld for 24 to 48 hours before the test (see Tables 5–12 and 5–13), although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any drugs withheld before the test, as well as usual activities. Abnormal values: Note and report increased or decreased levels indicating atherosclerosis and high risk for heart disease. Administer ordered medications. Provide information about a lowfat, low-cholesterol, and low-calorie diet, if needed. LIPOPROTEIN PHENOTYPING Lipoprotein phenotyping is an extension of the information obtained through lipoprotein fractionation and provides another approach to correlating laboratory findings with disease. Six different lipoprotein distribution patterns (phenotypes) are seen in serums with high levels of Chemistry 135 cholesterol or triglycerides or both. These phenotypes, which are referred to by their assigned numbers, have been correlated with genetically determined abnormalities (familial or primary hyperlipoproteinemias) and with a variety of acquired conditions (secondary hyperlipoproteinemias). Phenotype descriptions have proved useful in classifying diagnoses and in evaluating treatment and preventive regimens. Most hyperlipemic serums can be categorized into lipoprotein phenotypes without performing electrophoresis if the following are known: (1) chylomicron status, (2) serum triglyceride level, (3) total cholesterol, and (4) HDL cholesterol. Table 5–15 shows the clinical significance of each of the lipoprotein phenotypes as primary familial syndromes and as secondary occurrences caused by disorders that alter lipid metabolism. INTERFERING FACTORS Failure to follow usual diet for 2 weeks before the test may yield results that do not accurately reflect client status. Ingestion of alcohol 24 hours before and food 12 hours before the test may alter results. Excessive exercise 12 hours before the test may alter results. Numerous drugs, including those that are known to alter lipoprotein components (see Tables 5–12, 5–13, and 5–15) may alter results. INDICATIONS FOR LIPOPROTEIN PHENOTYPING Further evaluation of elevated serum cholesterol levels and results of lipoprotein and cholesterol fractionation Family history of primary hyperlipoproteinemia (hyperlipidemia) Identification of the client’s specific lipoprotein phenotype Known or suspected disorders associated with the several lipoprotein phenotypes (see Table 5–15) NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For this test, the client should ingest a normal diet, so that no weight gain or loss will occur for 2 weeks before the study, and should abstain from alcohol for 24 hours and from food for 12 hours before the test. Water is not restricted. The client also should avoid excessive exercise for at least 12 hours before the test. Copyright © 2003 F.A. Davis Company 136 SECTION I—Laboratory TABLE 5–15 Phenotype I II • Tests Clinicopathological Significance of Lipoprotein Phenotypes May Occur Secondary to Familial Syndrome Abdominal pain Insulin-dependent diabetes Eruptive xanthomas Lupus erythematosus Lipemia retinalis Dysglobulinemias Early vascular disease absent Pancreatitis Early, severe vascular disease High-cholesterol diet Prominent xanthomas Nephrotic syndrome Porphyria Remarks Lipoprotein lipase is deficient. Familial trait is autosomal dominant; homozygotes are especially severely affected. Hypothyroidism Dysglobulinemias Obstructive liver diseases III Accelerated vascular disease, onset in adulthood Hypothyroidism Xanthomas, palmar yellowing Dysglobulinemias Abnormal glucose tolerance Uncontrolled diabetes Diet, lipid-lowering drugs are very effective. Hyperuricemia IV Accelerated vascular disease, onset in adulthood Obesity Weight loss lowers VLDL. Abnormal glucose tolerance High alcohol intake High-fat diet may convert to type V. Hyperuricemia Oral contraceptives Diabetes Nephrotic syndrome Glycogen storage disease V Abdominal pain High alcohol intake Pancreatitis Diabetes Eruptive xanthomas Nephrotic syndrome Abnormal glucose tolerance Pancreatitis Vascular disease not associated Hypercalcemia Weight loss does not lower VLDL. From Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 477, with permission. It also is recommended that drugs that may alter lipoprotein components be withheld for 24 to 48 hours or longer before the test (see Tables 5–12, 5–13, and 5–15), although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in either a red- or lavender-topped tube, depending on the laboratory’s procedure for determining lipoprotein phenotypes. The sample should be sent to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 137 Reference Values Phenotype I IIa IIb III IV V Frequency Very rare Common Common Uncommon Very common Rare Chylomicrons ↑↑↑ Normal Normal Normal or ↑ Normal ↑↑ Pre--lipoproteins (approximates VLDL) ↑ ↑↑ ↑ (these two bands merge) ↑↑↑ ↑↑ -Lipoproteins (approximates LDL) ↓ ↑↑ ↑↑ Normal or ↑ Normal or ↓ 1-Lipoproteins (approximates HDL) ↓ Normal Normal Normal Normal or ↓ Normal or ↓ Total cholesterol Normal or ↑ ↑↑ ↑↑ ↑↑ Normal or ↑ ↑↑ Total triglycerides ↑↑↑ Normal ↑ ↑↑ or ↑↑↑ ↑↑ or ↑↑↑ ↑↑↑ Refrigerated serum or plasma “Cream”/ clear or turbid Clear or turbid turbid turbid “Cream”/ turbid From Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 476, with permission. Resume food and any drugs withheld before the test, as well as usual activities. BILIRUBIN Bilirubin is a degradation product of the pigmented heme portion of hemoglobin. Old, damaged, and abnormal erythrocytes are removed from the circulation by the spleen and to some extent by the liver and bone marrow. The heme component of the red blood cells is oxidized to bilirubin by the reticuloendothelial cells and released into the blood. In the blood, the fat-soluble bilirubin binds to albumin as unconjugated (prehepatic) bilirubin for transport to the liver. In the liver, hepatocytes detach bilirubin from albumin and conjugate it with glucuronic acid, which renders the bilirubin water soluble. Most of the conjugated (posthepatic) bilirubin is excreted into the hepatic ducts and then into bile. Only small amounts of conjugated bilirubin diffuse from the liver back into the blood. Thus, most circulating bilirubin is normally in the unconjugated form. Bilirubin is an excretory product that serves no physiological function in bile or blood. Once the conjugated bilirubin in bile enters the intestine, most is converted to a series of urobilinogen compounds and excreted into the stool as stercobilinogen after oxidation. A lesser amount is recycled to the liver and either returned to bile or excreted in urine as urobilinogen, which is oxidized to urobilin. Bilirubin and its degradation products are pigments and provide the yellow tinge in normal serum, the yellow-green hue in bile, the brown in stools, and the yellow in urine. Abnormally elevated serum bilirubin levels produce jaundice; obstruction to biliary excretion of bilirubin may produce lightcolored stools and dark urine. The terms indirect and direct, which are used to describe unconjugated (prehepatic) and conjugated (posthepatic) bilirubin, respectively, derive from the methods of testing for their presence in serum. Conjugated bilirubin is described as direct (direct reacting) because it is water soluble and can be measured without modification. Unconjugated bilirubin must be rendered soluble with alcohol or Copyright © 2003 F.A. Davis Company 138 SECTION I—Laboratory TABLE 5–16 • Tests Causes of Elevations in Indirect and Direct Bilirubin Levels Increased Indirect (Unconjugated) Bilirubin Increased Direct (Conjugated) Bilirubin Hemolysis: hemoglobinopathies, spherocytosis, G-6-PD deficiency, autoimmunity, transfusion reaction Intrahepatic disruption: viral hepatitis, alcoholic hepatitis, chlorpromazine, cirrhosis Red blood cell degradation: hemorrhage into soft tissues or body cavities, inefficient erythropoiesis, pernicious anemia Extrahepatic bile duct obstruction: gallstones; carcinoma of gallbladder, bile ducts, or head of pancreas; bile duct stricture from inflammation or surgical misadventure Bile duct disease: biliary cirrhosis, cholangitis (idiopathic, infectious), biliary atresiaa Defective hepatocellular uptake or conjugation: viral hepatitis, hereditary enzyme deficiencies (Gilbert, Crigler-Najjar syndromes), hepatic immaturity in newborns other solvents before the test can be performed and is thus referred to as indirect (indirect reacting). Impaired liver function causes dramatic increases in serum bilirubin levels (hyperbilirubinemia). Bilirubin must be in the conjugated form for normal excretion via bile, stools, and urine. When the liver is unable to conjugate bilirubin adequately, serum levels of unconjugated bilirubin rise. Disorders in which excessive hemolysis of red blood cells is combined with impaired liver function also produce hyperbilirubinemia. An example is physiological jaundice of the newborn, in which the increased destruction of red blood cells, common after birth, is combined with the immature liver’s inability to conjugate sufficient bilirubin. Kernicterus, a complication of newborn hyperbilirubinemia, occurs when unconjugated bilirubin is deposited in brain tissue. Impaired excretion of conjugated (posthepatic, direct) bilirubin from the liver into the bile ducts or from the biliary tract itself causes this form of bilirubin to be reabsorbed from the liver into the blood, with resultant elevated serum levels. Because conjugated bilirubin is water soluble and readily crosses the renal glomerulus, excessive amounts may be excreted in the urine. The stools, however, are lighter in color because of diminished amounts of conjugated bilirubin in the gut. Serum bilirubin levels are measured as total bilirubin, indirect bilirubin, and direct bilirubin. Total bilirubin reflects the combination of unconjugated and conjugated bilirubin in the serum and can be used to screen clients for possible disorders involving bilirubin production and excretion. If total bilirubin is normal, the levels of indirect (unconjugated) and direct (conjugated) bilirubin also are assumed to be normal in most cases. When total bilirubin levels are elevated, indirect and direct bilirubin levels are measured to determine the source of the overall elevation. Specific causes of elevations in indirect and direct bilirubin are shown in Table 5–16. Numerous drugs also may alter bilirubin levels. Reference Values Conventional Units SI Units Total bilirubin Newborns 2.0–6.0 mg/dL 34.0–102.0 mol/L 48 hr 6.0–7.0 mg/dL 102.0–120.0 mol/L 5 day 4.0–12.0 mg/dL 68.0–205.0 mol/L 1 mo–adults 0.3–1.2 mg/dL 5.0–20.0 mol/L Indirect bilirubin (unconjugated, prehepatic) 1 mo–adults 0.3–1.1 mg/dL 5.0–19.0 mol/L 0.1–0.4 mg/dL 1.7–6.8 mol/L Direct bilirubin 1 mo–adults Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood INTERFERING FACTORS Prolonged exposure of the client, as well as of the blood sample, to sunlight and ultraviolet light reduces serum bilirubin levels. Failure of the client to follow dietary restrictions before the test. Fasting normally lowers indirect bilirubin levels. In Gilbert’s syndrome, a congenital defect in bilirubin degradation, chronically elevated levels of indirect bilirubin increase dramatically in the fasting state. Numerous drugs may elevate bilirubin levels (e.g., steroids, sulfonamides, sulfonylureas, barbiturates, antineoplastic agents, propylthiouracil, allopurinol, antibiotics, gallbladder dyes, caffeine, theophylline, indomethacin, and any drugs that are considered hepatotoxic); it is recommended that such drugs be withheld for 24 hours before the test, if possible. INDICATIONS FOR BILIRUBIN TEST Known or suspected hemolytic disorders, including transfusion reactions, as indicated by elevated total and indirect bilirubin levels (see also Table 5–16): Hemolysis alone rarely causes indirect bilirubin levels higher than 4 or 5 mg/dL. If hemolysis is combined with impaired or immature liver function, levels may rise more dramatically. Confirmation of observed jaundice: Jaundice manifests when serum levels of indirect or direct bilirubin reach 2 to 4 mg/dL. Determination of the cause of jaundice (e.g., liver dysfunction, hepatitis, biliary obstruction, carcinoma) Support for diagnosing liver dysfunction as evidenced by elevated direct and total bilirubin levels or by elevation of all three levels if bile duct drainage also is impaired Support for diagnosing biliary tract obstruction as evidenced by elevated direct and total bilirubin levels or by elevation of all three levels if liver function is impaired25 NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For these tests, the client should fast from foods for at least 4 hours before the test. Water is not restricted. Because many drugs may alter bilirubin levels (see section titled “Interfering Factors”), a medication history should be obtained. Chemistry 139 It is recommended that those drugs that may alter test results be withheld for 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample obtained in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent immediately to the laboratory. The sample should not be exposed for prolonged periods to sunlight (i.e., more than 1 hour), ultraviolet light, or fluorescent lights. In infants, a capillary sample is obtained by heelstick. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any drugs withheld before the test. Abnormal values: Note and report increased levels. Assess for associated signs and symptoms of hyperbilirubinemia such as jaundice, pruritus, pain caused by liver disease, biliary obstruction, or food intolerances. Administer phenobarbital if levels are greater than 12 mg/dL in newborns, because this can lead to central nervous system damage. Prepare for exchange transfusion if level is greater than 15 mg/dL. ENZYMES Enzymes are catalysts that enhance reactions without directly participating in them. Individual enzymes, each of which has its own substrate and product specificity, exist for nearly all of the metabolic reactions that maintain body functions. Enzymes are normally intracellular molecules. Because certain metabolic reactions occur in many tissues, the involved enzymes exist in many cell types. Enzymes with more restricted metabolic functions are found in only one of several specialized cell types. The presence of enzymes in circulating blood indicates cellular changes that have permitted their escape into extracellular fluid. The continuous synthesis and destruction of the cells of the enzymes’ origins, for example, allow small amounts of enzymes to appear in the blood. Cellular disruption caused by damage by disease, toxins, or trauma, as well as increased cell wall permeability, also elevates serum enzyme levels. Additional causes of elevated enzyme levels are an increase in the number or activity of enzyme-containing cells and decreases in normal excretory or degradation mechanisms. Copyright © 2003 F.A. Davis Company 140 SECTION I—Laboratory Tests Decreased serum enzyme levels rarely have diagnostic significance because so few enzymes are present in substantial quantity. Enzyme levels may decline if the number of synthesizing cells declines, if generalized or specific restriction in protein synthesis occurs (enzymes are proteins), or if excretion or degradation increases. Very few enzymes are studied routinely. Although highly specialized enzyme analysis is applied to the study of many genetically determined diseases, most diagnostic enzyme studies involve only those enzymes with changing values in serum, providing inferential or confirmatory evidence of various pathological processes. A major goal of enzyme analysis is to localize disease processes to specific organs, preferably to specific functional subdivisions or even to specific cellular activities. Enzymes unique to a single cell type or found in only a few sites are particularly useful in this regard. The source of elevations of those enzymes with widespread distribution also can be determined by partitioning total activity into isoenzyme fractions. Isoenzymes are different forms of a single enzyme with immunologic, physical, or chemical characteristics distinctive for their tissue of origin. Efforts to standardize the study of enzymes (enzymology) have led to new terminology for naming and measuring enzymes. The Commission on Enzymes of the International Union of Biochemistry (IUB) has classified enzymes according to their biochemical functions, assigning to each a numerical designation that embodies class, subclass, and specification number. The IUB has also assigned descriptive names according to the specific reaction catalyzed and, in many cases, a practical name useful for common reference. One result of this standardization is that enzymes that have been studied for years have been renamed according to the new terminology. For example, the liver enzyme that was formerly called glutamic-oxaloacetic transaminase (GOT) is now named aspartate aminotransferase (AST). Another attempt to standardize enzymology is the introduction of international units (IU) for reporting enzyme activity. One IU of an enzyme is the amount that catalyzes transformation of 1 mol of substrate per minute under defined conditions. The actual amounts vary among enzymes, and the IU is not a single universally applicable value that can be used to compare enzymes of different characteristics.26 In this section, enzymes associated with organs and tissues such as the liver, pancreas, bone, heart, and muscle are discussed. Enzymes specific to red and white blood cells are included in Chapter 1. Alanine Aminotransferase Alanine aminotransferase (ALT), formerly known as glutamic-pyruvic transaminase (GPT), catalyzes the reversible transfer of an amino group between the amino acid, alanine, and -ketoglutamic acid. Hepatocytes are virtually the only cells with high ALT concentrations, although the heart, kidneys, and skeletal muscles contain moderate amounts. Elevated serum ALT levels are considered a sensitive index of liver damage resulting from a variety of disorders and numerous drugs, including alcohol. Elevations also may be seen in nonhepatic disorders such as muscular dystrophy, extensive muscular trauma, myocardial infarction, congestive heart failure (CHF), and renal failure, although the increase in ALT produced by these disorders is not as great as that produced by conditions affecting the liver. This test was formerly known as the serum glutamic-pyruvic transaminase (SGPT) test. Reference Values Conventional Units SI Units 10–30 U/L 0.17–0.51 kat/L 1–36 U/L 0.02–0.61 kat/L 5–35 U/L 0.08–0.60 kat/L 5–25 U/L 0.08–0.43 kat/L 8–50 U/L 0.14–0.85 kat/L 4–36 U/L 0.07–0.61 kat/L Note: Reference values vary among laboratories and according to the method used for reporting results. INTERFERING FACTORS Numerous drugs, including alcohol, may falsely elevate levels. INDICATIONS FOR ALANINE AMINOTRANSFERASE TEST Known liver disease or liver damage caused by hepatotoxic drugs: Markedly elevated levels (sometimes as high as 20 times normal) are considered confirmatory of liver disease. A sudden drop in serum ALT levels in the presence of acute illness after extreme elevation of blood levels (e.g., as seen in severe viral or toxic hepatitis) is an ominous sign and indicates that so many cells have been damaged that no additional source of enzyme remains. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Monitoring for response to treatment for liver disease, with tissue repair indicated by gradually declining levels NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For this test, the client should abstain from alcohol for at least 24 hours before the study. Because many drugs may alter ALT levels, a medication history should be obtained. It is recommended that drugs that may alter test results be withheld for 12 hours before the test, although this practice should be confirmed with the person ordering the study. Chemistry 141 hours, and lactic dehydrogenase, which begins rising 12 hours or more after infarction and remains elevated for a week or more. Elevation of AST cannot be used as the single enzyme indicator for myocardial infarction, because it also rises in several other conditions included in the differential diagnosis of heart attack. Other disorders associated with elevated AST, and the magnitude of those elevations, are listed in Table 5–17. Note also that numerous drugs, especially those known to be hepatotoxic or nephrotoxic, may elevate AST levels.27 The test for AST was formerly known as serum glutamic-oxaloacetic transaminase (SGOT). INTERFERING FACTORS Numerous drugs may falsely elevate levels. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. TABLE 5–17 • Conditions Affecting Serum Aspartate Aminotransferase Levels NURSING CARE AFTER THE PROCEDURE Pronounced Elevation (5 or more times normal) Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test. Abnormal levels: Note and report increased levels. Assess symptoms of liver dysfunction associated with increases such as jaundice, anorexia, and fatigue. Relate increases to other liver function tests. Provide rest and interventions to conserve energy. Tell client which drugs to avoid and encourage client to eat a healthy diet. Aspartate Aminotransferase Aspartate aminotransferase (AST), formerly known as glutamic-oxaloacetic transaminase (GOT), catalyzes the reversible transfer of an amino between the amino acid, aspartate, and -ketoglutamic acid. ALT exists in large amounts in both liver and myocardial cells and in smaller but significant amounts in skeletal muscles, kidneys, pancreas, and brain. Serum AST rises when cellular damage occurs to the tissues in which the enzyme is found. When heart muscle suffers ischemic damage, serum AST rises within 6 to 8 hours; peak values occur at 24 to 48 hours and decline to normal within 72 to 96 hours. Elevation of AST occurs midway in the time sequence between that of creatine phosphokinase (CPK), which rises very early and falls within 48 Acute hepatocellular damage Myocardial infarction Shock Acute pancreatitis Infectious mononucleosis Moderate Elevation (3–5 times normal) Biliary tract obstruction Cardiac arrhythmias Congestive heart failure Liver tumors Chronic hepatitis Muscular dystrophy Dermatomyositis Slight Elevation (up to 3 times normal) Pericarditis Cirrhosis, fatty liver Pulmonary infarction Delirium tremens Cerebrovascular accident Hemolytic anemia Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 415, with permission. Copyright © 2003 F.A. Davis Company 142 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units Newborns 16–72 U/L 0.27–1.22 kat/L 6 mo 20–43 U/L 0.34–0.73 kat/L 1 yr 16–35 U/L 0.27–0.60 kat/L 5 yr 19–28 U/L 0.32–0.48 kat/L Men 8–46 U/L 0.14–0.78 kat/L Women 7–34 U/L 0.12–0.58 kat/L Adults INDICATIONS FOR ASPARTATE AMINOTRANSFERASE TEST Suspected disorders or injuries involving the liver, myocardium, kidneys, pancreas, or brain, with elevated levels indicating cellular damage to tissues in which AST is normally found (see Table 5–17): In myocardial infarction, AST rises within 6 to 8 hours, peaks at 24 to 48 hours, and declines to normal within 72 to 96 hours. Monitoring of response to therapy with potentially hepatotoxic or nephrotoxic drugs Monitoring of response to treatment for various disorders in which AST may be elevated, with tissue repair indicated by declining levels NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs alter AST levels, a medication history should be obtained. It is recommended that any drugs that may alter test results be withheld for 12 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test, pending test results. Complications and precautions: Increases in this enzyme level in relation to ALT and other assessment data may indicate a cardiac disorder. Monitor vital signs and cardiac activity by electrocardiogram (ECG). Alkaline Phosphatase Phosphatases are enzymes that cleave phosphate from compounds with a single phosphate group. Those that are optimally active at pH 9 are grouped under the name alkaline phosphatase (ALP). ALP is elaborated by a number of tissues. Liver, bone, and intestine are the major isoenzyme sources. During pregnancy, the placenta also is an abundant source of ALP, and certain cancers elaborate small amounts of a distinctive form of ALP called the Regan enzyme. Additional sources of ALP are the proximal tubules of the kidneys, the lactating mammary glands, and the granulocytes of circulating blood (see Chapter 1 section titled “Leukocyte Alkaline Phosphatase”). Bone ALP predominates in normal serum, along with a modest amount of hepatic isoenzyme, which is believed to derive largely from the epithelium of the intrahepatic biliary ducts rather than from the hepatocytes themselves. Levels of intestinal ALP vary; most people have relatively little, but isolated elevations of this enzyme have been observed. Intestinal ALP enters the blood very briefly while fats are being digested and absorbed, but intestinal disease rarely affects serum ALP levels. Conditions associated with elevated serum ALP levels, and the magnitude of those elevations, are listed in Table 5–18.28 Numerous drugs also may elevate serum ALP levels. Decreased levels are seen in cretinism, secondary growth retardation, scurvy, achondroplasia, and, rarely, hypophosphatasia. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 143 Reference Values General Reference Levels Bessey-Lowry Method Bodansky Method King-Armstrong Method Newborns 50–65 U/L — — — Children 20–150 U/L 3.4–9.0 U/L 5–14 U/L 15–30 U/L Adults 20–90 U/L 0.8–2.3 U/L 1.5–4.5 U/L 4–13 U/L INTERFERING FACTORS Numerous drugs, including IV albumin, may falsely elevate levels. • Conditions Associated with Elevated Serum Alkaline Phosphatase Levels TABLE 5–18 Pronounced Elevation (5 or more times normal) Advanced pregnancy Biliary obstruction Biliary atresia Cirrhosis Osteitis deformans Osteogenic sarcoma Hyperparathyroidism (primary, or secondary to chronic renal disease) Paget’s disease Clofibrate, azathioprine (Imuran), and fluorides may falsely decrease levels. INDICATIONS FOR SERUM ALKALINE PHOSPHATASE TEST Signs and symptoms of disorders associated with elevated ALP levels (e.g., biliary obstruction, hepatobiliary disease, bone disease including malignant processes) (see also Table 5–18) Differentiation of obstructive biliary disorders from hepatocellular disease, with greater elevations of ALP seen in obstructive biliary disorders Known renal disease to determine effects on bone metabolism Signs of growth retardation in children NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter ALP levels, a medication history should be obtained. Infusion of albumin of placental origin THE PROCEDURE Moderate Elevation (3–5 times normal) Infectious mononucleosis A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Metastatic tumors in bone NURSING CARE AFTER THE PROCEDURE Granulomatous or infiltrative liver diseases Metabolic bone diseases (rickets, osteomalacia) Extrahepatic duct obstruction Mild Elevation (up to 3 times normal) Viral hepatitis Chronic active hepatitis Cirrhosis (alcoholic) Healing fractures Early pregnancy Growing children Large doses of vitamin D Congestive heart failure Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Abnormal levels: Note and report increased levels. Correlate with serum calcium and phosphorus, serum bilirubin, and isoenzymes to determine reason for treatments, progress, and prognosis in diseases of the bone or liver. Assess for jaundice and pathological fracture. If client is pregnant, handle extremities carefully and protect from trauma. Administer ordered vitamin D. Provide comfort measures (soothing bath for pruritus, pain control, support for body image changes) to treat jaundice, if it is present. Advise client to restrict dietary fat. Copyright © 2003 F.A. Davis Company 144 SECTION I—Laboratory Tests Alkaline Phosphatase Isoenzymes THE PROCEDURE If serum alkaline phosphatase (ALP) levels are elevated but the clinical picture does not provide enough information to determine the origin of the excess, ALP isoenzymes are evaluated. The major ALP isoenzymes derive from liver, bone, intestine, and placenta. ALP isoenzymes may be partitioned by electrophoresis or by exploitation of differences in physical properties on optimal substrates. Electrophoresis has been applied with only modest success. Hepatic and intestinal isoenzymes are easier to differentiate with this method than are hepatic and bone enzymes. Because hepatic ALP is more heat resistant than bone ALP, the most common way to differentiate between these two isoenzymes is by heating the serum to 132.8 F (56 C). Evaluation of ALP isoenzymes usually focuses on measuring those of hepatic origin not affected by bone growth or pregnancy. These are 5′-nucleotidase, leucine aminopeptidase, and -glutamyl transpeptidase. A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. LEUCINE AMINOPEPTIDASE Leucine aminopeptidase (LAP), an isoenzyme of alkaline phosphatase, is widely distributed in body tissues, with greatest concentrations found in hepatobiliary tissues, pancreas, and small intestine. Elevated levels are associated with biliary obstruction resulting from gallstones and tumors, including those of the head of the pancreas, strictures, and atresia. Advanced pregnancy and therapy with drugs containing estrogen and progesterone also may raise LAP levels. 5′-NUCLEOTIDASE Reference Values 5′-Nucleotidase (5′-N), an isoenzyme of ALP, is a specific phosphomonoesterase formed in the hepatobiliary tissues. Elevated serum 5′-N levels are associated with biliary cirrhosis, carcinoma of the liver and biliary structures, and choledocholithiasis or other biliary obstruction. Leucine Conventional Units SI Units Men 0.80–2.00 mg/dL 61.0–152.0 mol/L Women 0.75–1.85 mg/dL 57.0–141.0 mol/L Note: Values may vary depending on the units of measure used by the laboratory performing the test. Reference Values Conventional Units 0–1.6 U SI Units 27–233 nmol/s/L 0.3–3.2 U (Bodansky) INDICATIONS FOR 5′-NUCLEOTIDASE TEST Elevated alkaline phosphatase of uncertain etiology: Elevated 5′-N levels support the diagnosis of hepatobiliary disorders as the source of the elevated alkaline phosphatase. Normal levels support the diagnosis of bone disease as the source of the elevated alkaline phosphatase. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). INTERFERING FACTORS Advanced pregnancy and therapy with drugs containing estrogen and progesterone may falsely elevate levels. INDICATIONS FOR LEUCINE AMINOPEPTIDASE TEST Elevated ALP of uncertain etiology: Elevated levels support the diagnosis of hepatobiliary or pancreatic disease or both as the source of the elevated ALP. Normal levels support the diagnosis of bone disease as the source of the elevated ALP. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). Some laboratories require the client to fast from food for 8 hours before the test. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any food withheld before the test. -GLUTAMYL TRANSPEPTIDASE -Glutamyl transpeptidase (GGT), an isoenzyme of ALP, catalyzes the transfer of glutamyl groups among peptides and amino acids. Hepatobiliary tissues and renal tubular and pancreatic epithelia contain large amounts of GGT. Other sources include the prostate gland, brain, and heart. Most GGT in serum derives from hepatobiliary sources, and elevated levels point to hepatobiliary disease. INTERFERING FACTORS Alcohol, barbiturates, and phenytoin may elevate GGT levels. Late pregnancy and oral contraceptives may produce lower than normal values. INDICATIONS FOR -GLUTAMYL TRANSPEPTIDASE TEST Elevated alkaline phosphatase of uncertain etiology: Pronounced elevations are seen in clients with obstructive disorders of the hepatobiliary tract and hepatocellular carcinoma. 145 Modest elevations occur with hepatocellular degeneration (e.g., cirrhosis) and with pancreatic or renal cell damage or neoplasms. Other disorders associated with elevated GGT levels include CHF, acute myocardial infarction (after 4 to 10 days), hyperlipoproteinemia (type IV), diabetes mellitus with hypertension, and epilepsy. Normal levels in the presence of elevated ALP support the diagnosis of bone disease. Known or suspected alcohol abuse, including monitoring of individuals participating in alcohol abstinence programs About 60 to 80 percent of individuals considered to have alcohol abuse problems have elevated GGT levels, whether or not other signs of liver damage are present. Moderate increases in GGT levels occur with low alcohol intake. A significant sustained rise occurs with ingestion of six or more drinks per day. Normal levels return within 2 to 6 weeks of abstinence from alcohol. NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Some laboratories require the client to fast from food for 8 hours before the test. When the test is conducted to determine whether the liver is the source of elevated ALP, the client should abstain from alcohol for 2 to 3 weeks before the test. This restriction may not apply when the test is used to monitor compliance with alcohol abstinence programs. The client’s reported intake (or nonintake) of alcohol should, however, be noted. Reference Values Conventional Units Newborns Chemistry SI Units 5 times children’s (1–2 yr) values Children 1–2 yr 3–30 U/L 0.05–0.51 kat/L 5–15 yr 5–27 U/L 0.08–0.46 kat/L Men 6–37 U/L 0.10–0.63 kat/L Women 45 yr 5–27 U/L 0.08–0.46 kat/L Women 45 yr 6–37 U/L 0.10–0.63 kat/L Adults Copyright © 2003 F.A. Davis Company 146 SECTION I—Laboratory Tests THE PROCEDURE THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any food withheld before the test. Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test, pending test results. Isocitrate Dehydrogenase Isocitrate dehydrogenase (ICD) catalyzes the decarboxylation of isocitrate in the Krebs cycle. This enzyme is important in controlling the rate of the cycle, which must be precisely adjusted to meet the energy needs of cells. ICD is found in the liver, heart, skeletal muscle, placenta, platelets, and erythrocytes. Reference Values Conventional Units SI Units Newborns 4.0–28.0 U/L 0.06–0.48 kat/L Adults 1.27–7.0 U/L 0.02–0.12 kat/L Ornithine Carbamoyltransferase Ornithine carbamoyltransferase (OCT), formerly known as ornithine transcarbamoylase, catalyzes ornithine to citrulline in the urea cycle before its link with the citric acid cycle. Its importance stems from its role in the conversion of ammonia to urea by the liver. Decreased levels may be seen in inherited disorders associated with a partial block in the urea cycle. Reference Values Conventional Units SI Units 8–20 mIU/mL INTERFERING FACTORS Numerous drugs, including those that are hepatotoxic, may cause elevated levels. INDICATIONS FOR ISOCITRATE DEHYDROGENASE TEST Elevated serum aspartate aminotransferase (ALT, SGOT) or ALP of uncertain etiology, or both: Elevated ICD levels are seen in early viral hepatitis, cancer of the liver, intrahepatic and extrahepatic obstruction, biliary atresia, cirrhosis, and preeclampsia. Therapy with potentially hepatotoxic drugs that may lead to elevated ICD levels early in the course of treatment NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter ICD levels, a medication history should be obtained. It is recommended that any drugs that may alter test results be withheld for 24 hours before the test, although this practice should be confirmed with the person ordering the study. 8–20 U/L 0.02–0.34 kat/L INTERFERING FACTORS Hepatotoxic drugs and chemicals may produce elevated levels. INDICATIONS FOR ORNITHINE CARBAMOYLTRANSFERASE TEST Elevated serum ALP of uncertain etiology: Elevated OCT levels are seen in viral hepatitis, cholecystitis, cirrhosis, cancer of the liver, and obstructive jaundice. Therapy with hepatotoxic drugs or exposure to hepatotoxic chemicals, with early effects indicated by elevated OCT levels Suspected mushroom poisoning as indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter OCT levels, a medication history should be obtained. It is recommended that any drugs that may alter test Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood results be withheld for 24 hours before the test, although this practice should be confirmed with the person ordering the study. Chemistry 147 • Causes of Elevated Serum Amylase TABLE 5–19 THE PROCEDURE Pronounced Elevation (5 or more times normal) A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Acute pancreatitis Pancreatic pseudocyst Morphine administration Moderate Elevation (3–5 times normal) NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test, pending test results. Advanced carcinoma of the pancreatic head Mumps Parotitis Perforated peptic ulcer (sometimes) Duodenal obstruction Mild Elevation (up to 3 times normal) Serum Amylase Amylase is a digestive enzyme that splits starch into disaccharides such as maltose. Although many cells have amylase activity (e.g., liver, small intestine, skeletal muscle, fallopian tubes), amylase circulating in normal serum derives from the parotid glands and the pancreas. Unlike many other enzymes, amylase activity is primarily extracellular; it is secreted into saliva and the duodenum, where it splits large carbohydrate molecules into smaller units for further digestive action by intestinal enzymes. Elevations in serum amylase are generally seen in pancreatic inflammations, which cause disruption of pancreatic cells and absorption of the extracellular enzyme from the intestine and peritoneal lymphatics. Serum amylase levels also rise sharply after administration of drugs that constrict pancreatic duct sphincters. The most common offender is morphine, and this drug is never indicated for individuals with abdominal pain that could be of pancreatic or biliary tract origin. Other drugs that may produce elevated serum amylase levels are codeine, chlorothiazides, aspirin, pentazocine, corticosteroids, oral contraceptives, pancreozymin, and secretin. Specific causes of elevated serum amylase, Chronic pancreatitis (nonadvanced) Renal failure Common bile duct obstruction Gastric resection Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 554, with permission. and the magnitude of the elevations produced, are listed in Table 5–19. INTERFERING FACTORS A number of drugs may produce elevated levels (e.g., morphine, codeine, chlorothiazides, aspirin, pentazocine, corticosteroids, oral contraceptives, pancreozymin, and secretin). High blood glucose levels, which may be a result of diabetes mellitus or IV glucose solutions, can lead to decreased levels. INDICATIONS FOR SERUM AMYLASE TEST Diagnosis of early acute pancreatitis: Serum amylase begins rising within 6 to 24 Reference Values Conventional Units SI Units Children 60–160 U/dL 1.88–5.03 kat/L Adults 80–180 U/dL (Somogyi) 1.36–3.0 kat/L 45–200 U/dL (dye) Note: Values may vary according to the laboratory performing the test. Copyright © 2003 F.A. Davis Company 148 SECTION I—Laboratory Tests hours after onset and returns to normal in 2 to 7 days. Urine amylase levels may remain elevated for several days after serum amylase levels return to normal. Detection of blunt trauma or inadvertent surgical trauma to the pancreas as indicated by elevated levels Diagnosis of macroamylasemia, a disorder seen in alcoholism, malabsorption syndrome, and other digestive problems with circulating complexes of amylase and high-molecular-weight dextran (findings include high serum amylase and negative urine amylase) Support for diagnosing other disorders associated with elevated serum amylase levels (see Table 5–19) Support for diagnosing disorders associated with decreased amylase levels, such as advanced chronic pancreatitis, advanced cystic fibrosis, liver disease, liver abscess, toxemia of pregnancy, severe burns, and cholecystitis fluids, nasogastric tube (NG) insertion, and bowel decompression to decrease pancreatic stimulation. Instruct client to avoid alcohol intake and to reduce carbohydrate intake if absorption problem exists. Serum Lipase Lipases split triglycerides into fatty acids and glycerol. Different lipolytic enzymes have different specific substrates, but overall activity is collectively described as lipase. Serum lipase derives primarily from pancreatic lipase, which is secreted into the duodenum and participates in fat digestion. Pancreatic lipase is quite distinct from lipoprotein lipases, which clear the blood of chylomicrons after fats are absorbed. Viral hepatitis and disorders in which bile salts are decreased may produce low serum lipase levels, as will protamine and IV infusions of saline. Reference Values NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum amylase levels, a medication history should be obtained. It is recommended that any drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test, pending test results. Abnormal values: Note and report increased levels. Correlate with urine amylase, hypocalcemia, hypokalemia, hyperglycemia, and bilirubin in relation to pancreatic diseases. Assess for fluid deficit if pancreatic hemorrhage is present, severity of abdominal pain if acute inflammation is present, jaundice if common bile duct is obstructed, and bowel sounds. Maintain nothing by mouth (NPO) status and prepare client for IV All groups Conventional Units SI Units 0–160 U/L 0–2.72 kat/L INTERFERING FACTORS Morphine, cholinergic drugs, and heparin may lead to elevated levels. Protamine and IV infusions of saline may lead to decreased levels. INDICATIONS FOR SERUM LIPASE TEST Diagnosis of acute pancreatitis, especially if the client has been ill for more than 3 days: Serum amylase levels may return to normal after 3 days, but serum lipase remains elevated for approximately 10 days after onset. Support for diagnosing pancreatic carcinoma, especially if there is a sustained moderate elevation in serum lipase levels Support for diagnosing other disorders associated with elevated serum lipase levels (e.g., peptic ulcer, acute cholecystitis, and early renal failure) Support for diagnosing disorders associated with decreased serum lipase levels (e.g., advanced chronic pancreatitis, cystic fibrosis, advanced carcinoma of the pancreas, and viral hepatitis) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 149 Reference Values Conventional Units Newborns 10.4–16.4 U/L 1 mo–13 yr 0.5–11.0 U/L (King-Armstrong) Adults SI Units 6.4–15.2 U/L 108.0–258.0 kat/L 0–0.8 U/L 0.0–14.0 kat/L 0.1–2.0 U/L (Gutman) 0.5–2.0 U/L (Bodansky) 0.1–5.0 U/L (King-Armstrong) 0.1–0.8 U/L (Bessey-Lowry) 0–0.56 U/L (Roy) The client should fast from food for at least 8 hours before the test. It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any drugs withheld before the test. Acid Phosphatase Phosphatases are enzymes that cleave phosphate from compounds with a single phosphate group. Those that are optimally active at pH 5 are grouped under the name acid phosphatase (ACP). Many tissues (kidneys, spleen, liver, bone) contain ACP, but the prostate gland, red blood cells (RBCs), and platelets are especially rich in this activity. Two isoenzymes, prostatic fraction and RBC/platelet fraction, are diagnostically significant. These isoenzymes differ from one another in preferred substrate and in the degree to which they are inhibited by various additives during laboratory testing. Normal serum contains more RBC/platelet than prostatic ACP, and small changes in prostatic fraction may be difficult to detect. Tartaric acid inhibits prostatic ACP. Thus, many laboratories report tartrateinhibitable ACP as well as total ACP in an effort to focus more specifically on the prostatic fraction. Decreased levels of prostatic ACP are seen after estrogen therapy for prostatic carcinoma and in clients with Down syndrome. Decreased levels are associated with ingestion of alcohol, fluorides, oxalates, and phosphates. Administration of androgens in women and of clofibrate in both genders produces elevated levels. INTERFERING FACTORS Prostatic massage or rectal examination within 48 hours of the test may cause elevated levels. Administration of androgens in females and of clofibrate in either gender may produce elevated levels. Ingestion of alcohol, fluorides, oxalates, and phosphates may result in decreased levels. INDICATIONS FOR SERUM ACID PHOSPHATASE TEST Enlarged prostate gland, especially if prostatic carcinoma is suspected: Prostatic ACP is elevated in 50 to 75 percent of individuals with prostatic carcinoma that has extended beyond the gland. Cancers that remain within the gland cause ACP elevation in only 10 to 25 percent of those affected. Benign hyperplasia, inflammation, or ischemic damage to the prostate rarely causes elevated ACP levels. Evaluation of the effectiveness of treatment of prostatic carcinoma: ACP levels fall to normal within 3 to 4 days of successful estrogen therapy. Copyright © 2003 F.A. Davis Company 150 SECTION I—Laboratory Tests Recurrent elevation strongly suggests that bone metastases are active. Support for diagnosing other disorders associated with elevated prostatic ACP levels (e.g., metastatic bone cancer, Paget’s disease, osteogenesis imperfecta, hyperparathyroidism, and multiple myeloma) Known or suspected hematologic disorder: Elevated RBC/platelet ACP is seen in hemolytic anemia, sickle cell crisis, thrombocytosis, and acute leukemia. Support for diagnosing other disorders associated with increased RBC/platelet ACP (e.g., renal insufficiency, liver disease, Gaucher’s disease, and Niemann-Pick disease) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). It is recommended that any drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. If the test cannot be performed within a few hours, the serum should be frozen. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test. Abnormal values: Note and report increased levels or associated levels of prostate-specific antigen. Provide support in coping with a life-threatening disease, hormonal therapy, and possible surgical procedure. Prostate-Specific Antigen Prostate-specific antigen (PSA) is a glycoprotein found in the prostate tissues. Its presence is tested by immunoassay techniques to assist in the detection of prostatic carcinoma. It is considered to be a more specific immunohistochemical marker for metastatic tumor of prostate origin than is ACP. ACP is a test also performed to diagnose prostatic carcinoma, but it is not entirely specific for this disease, because increased values have been noted in bladder as well as in prostatic carcinoma. Increased levels of PSA correlate with the amount of prostatic tissue, both malignant and benign. Reference Values Conventional Units SI Units Men 40 yr 2.0 ng/mL 2.0 g/L Men 40 yr 2.8 ng/mL 2.8 g/L INTERFERING FACTORS Prostatic massage or rectal examination within 48 hours of the test can cause elevated levels. INDICATIONS FOR PROSTATE-SPECIFIC ANTIGEN TEST Screening for early detection of prostate carcinoma and evaluating those who are at risk for this disease, primarily men over 40 years of age Diagnosing a malignant tumor of the prostate gland, revealed by increased levels, depending on the volume of the tumor Determining chemotherapeutic regimen protocol or radiation therapy and monitoring and evaluating the response to therapy, revealed by a decrease in the PSA level Evaluating progression or recurrence of the tumor, revealed by a rise in the PSA level NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The age of the client should be noted on the laboratory form. The sample should be refrigerated if the test is not performed within 24 hours. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Aldolase Aldolase (ALS) is a glycolytic enzyme that catalyzes the breakdown of 1,6-diphosphate into triose phosphate. It is found in many body tissues but is most diagnostically significant in disorders of skeletal and cardiac muscle, liver, and pancreas. Three isoen- Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 151 Reference Values Conventional Units SI Units Newborns 5.2–32.8 U/L (Sibley-Lehninger) 0.09–0.54 kat/L Children 2.6–16.4 U/L (Sibley-Lehninger) 0.04–0.27 kat/L Adults 1.3–8.2 U/L (Sibley-Lehninger) 0.02–0.14 kat/L Men 3.1–7.5 U/L at 98.6 F (37 C) 0.05–0.13 kat/L Women 2.7–5.3 U/L at 98.6 F (37 C) 0.04–0.09 kat/L zymes have been identified: A, originating in skeletal and cardiac muscle; B, originating in liver, kidneys, and white blood cells; and C, originating in brain tissue. Isoenzyme C probably lacks diagnostic capability because it does not cross the blood–brain barrier. involving collection of a peripheral blood sample (see Appendix I). It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. INTERFERING FACTORS THE PROCEDURE Hepatotoxic drugs, insecticides, and anthelminthics may cause elevated levels. Phenothiazines may cause decreased levels. INDICATIONS FOR ALDOLASE TEST Family history of Duchenne’s muscular dystrophy: ALS levels rise before clinical signs appear, thus permitting early diagnosis. Signs and symptoms of neuromuscular disorders, to differentiate muscular disorders from neurological disorders: Pronounced elevations are seen in clients having Duchenne’s muscular dystrophy, polymyositis, dermatomyositis, trichinosis, and severe crush injuries. Decreased aldolase levels are seen in those with late muscular dystrophy, because of loss of muscle cells, or with use of phenothiazines. ALS is not elevated in those with multiple sclerosis or myasthenia gravis, both of which are of neural origin. Support for diagnosing other disorders associated with elevated ALS levels: Moderate increases are associated with acute hepatitis, neoplasms, and leukemia. Mild elevations are seen in acute myocardial infarction (peak elevation occurs in 24 hours, with gradual return to normal within 1 week). Evaluation of response to exposure to hepatotoxic drugs or chemicals, with liver damage indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test. Abnormal values: Note and report increased levels related to skeletal muscular disorders. Assess for muscle fatigue and strength related to an acute or chronic disorder. Provide energy-saving care to conserve the client’s energy while still maintaining as much independence as possible. Instruct in a planned rest and exercise program. Creatine Phosphokinase and Isoenzymes Creatine phosphokinase (CPK), also called creatine kinase (CK), catalyzes the reversible exchange of phosphate between creatine and adenotriphosphate (ATP). Important in intracellular storage and release of energy, CPK exists almost exclusively in skeletal muscle, heart muscle, and, to a lesser extent, brain. No CPK is found in the liver. Anything that damages skeletal or cardiac muscle elevates serum CPK levels. Brain injury affects serum CPK levels much less, probably because relatively little enzyme crosses the blood–brain barrier. Spectacular CPK elevations occur in the early phases of muscular dystrophy, but CPK elevation diminishes as the disease progresses and muscle Copyright © 2003 F.A. Davis Company 152 SECTION I—Laboratory Tests • Causes of Elevated Creatine Phosphokinase TABLE 5–20 Pronounced Elevation (5 or more times normal) Early muscular dystrophy (CPK-MM, CPK3) Acute myocardial infarction (CPK-MB, CPK2) Severe angina (CPK-MB, CPK2) Polymyositis (CPK-MM, CPK3) Cardiac surgery Moderate Elevation (2–4 times normal) Vigorous exercise Deep intramuscular injections Surgical procedures affecting skeletal muscles Delirium tremens Convulsive seizures Dermatomyositis Alcoholic myopathy Hypothyroidism Pulmonary infarction Acute agitated psychosis Mild Elevation (up to 2 times normal) Late pregnancy Women heterozygous for the gene causing Duchenne’s muscular dystrophy (CPK-MM, CPK3) Brain injury (CPK-BB, CPK1) Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 536, with permission. mass decreases. Levels of CPK may be normal to low in late, severe cases. Additional causes of elevated CPK, and the magnitude of those elevations, are listed in Table 5–20. The CPK molecule consists of two parts, which may be identical or dissimilar. These two constituent chains are called M (muscle) and B (brain). Three diagnostically significant isoenzymes have been identified in relation to the two main components of CPK. Brain CPK (CPK-BB, CPK1) is almost entirely BB, cardiac CPK (CPK-MB, CPK2) contains 60 percent MM and 40 percent MB, and skeletal muscle CPK (CPK-MM, CPK3) contains about 90 percent MM and 10 percent MB. The isoenzyme normally present in serum is almost entirely MM, and only CPK-MM (CPK3) rises when skeletal muscle is damaged. In contrast, serum CPK-MB (CPK2) rises only when heart muscle is damaged. Drugs that may produce elevated CPK levels include anticoagulants, morphine, alcohol, salicylates in high doses, amphotericin-B, clofibrate, and certain anesthetics. Any medication administered intramuscularly (IM) also elevates CPK. In addition to late muscular dystrophy, decreased levels are seen in early pregnancy. Myoglobin is an oxygen-carrying protein normally found in cardiac and skeletal muscle. In acute myocardial infarction (AMI), myoglobin levels rise within 1 hour. Although myoglobin alone is not particularly sensitive to cardiac damage, in conjunction with CPK-MB it has a diagnostic capability approaching 100 percent in correctly identifying AMI.29 See Table 5–21. INTERFERING FACTORS Vigorous exercise, deep intramuscular (IM) injections, delirium tremens, and surgical procedures in which muscle is transected or compressed may produce elevated levels. Drugs that may produce elevated CPK levels include anticoagulants, morphine, alcohol, salicylates in high doses, amphotericin-B, clofibrate, and certain anesthetics. Early pregnancy may produce decreased levels. INDICATIONS FOR CREATINE PHOSPHOKINASE AND ISOENZYMES TEST Signs and symptoms of acute myocardial infarction: Acute myocardial infarction releases CPK into the serum within the first 48 hours, and values return to normal in about 3 days. CPK levels rise before aspartate aminotransferase and lactic dehydrogenase levels rise. The isoenzyme CPK-MB (CPK2) rises only when the heart muscle is damaged; it appears in the first 6 to 24 hours and is usually gone in 72 hours. Both total CPK and MB fraction may rise in severe angina or extensive reversible ischemic damage.30 Recurrent elevation of CPK suggests reinfarction or extension of ischemic damage. An elevated CPK level helps to differentiate myocardial infarction from CHF and conditions associated with liver damage. Family history of Duchenne’s muscular dystrophy: Spectacular CPK elevations occur in the early phases of muscular dystrophy, even before clinical signs or symptoms appear. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 153 Reference Values Conventional Units SI Units Total CPK Newborns 30–100 U/L 0.51–1.70 kat/L Children 15–50 U/L 0.26–0.85 kat/L 5–55 U/L — 55–170 U/L 0.94–2.89 kat/L 5–35 g/mL — 5–25 U/L — 30–135 U/L 0.51–2.30 kat/L 5–25 g/mL — CPK-BB (CPK1) 0% of total CK — CPK-MB (CPK2) 0–7% of total CK — CPK-MM (CPK3) 5–70% of total CK — Myoglobin 100 ng/mL 100 nmol/L Adults Men Women Isoenzymes Image/Text rights unavailable Copyright © 2003 F.A. Davis Company 154 SECTION I—Laboratory Tests Image/Text rights unavailable CPK elevation diminishes as the disease progresses and muscle mass decreases. Signs and symptoms of other disorders associated with elevated CPK levels (see Table 5–20) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). It is recommended that any drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. Vigorous exercise and IM injections also should be avoided for 24 hours before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Troponin Levels Differential diagnosis of chest pain remains problematic. It is estimated that 12 percent of patients with AMI are sent home from the emergency department.31 Traditional measures to diagnose AMI include an ECG and measurement of cardiac enzymes, particularly creatine kinase CK-MB.32 In recent years, troponin levels have been studied to determine the efficacy of this laboratory test in diagnosis of AMI. Troponin is a protein found in striated muscle. There are three specific types: troponin-C (TnC), troponin-I (TnI), and troponin-T (TnT). TnT and TnI are specific for cardiac disease, and several studies have concluded that elevated levels of these enzymes result in greater sensitivity in diagnosing AMI and determining comprehensive risk stratification of patients with unstable angina.31,33,34 TnT and TnI will be elevated within 4 hours after myocardial damage and remain elevated for 10 to 14 days. Reference Values NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as those for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test, as well as usual activities. Abnormal values: Note and report increased levels of CPK, CPK-MB, lactic dehydrogenase (in relation to myocardial infarction), and CPK-MM (in relation to muscular dystrophy). Monitor vital signs. Monitor ECG for dysrhythmias. Monitor for fluid overload (distended neck veins, dyspnea, crackles on auscultation). Repeat ordered CPK and lactic dehydrogenase enzyme and isoenzyme tests. Presence of cardiac enzyme marker INTERFERING FACTORS TnT may be present in renal failure. INDICATIONS FOR TROPONIN LEVELS TEST Diagnosis and risk stratification for unstable angina Diagnosis of AMI NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 155 Reference Values Conventional Units Total LDH SI Units 80–120 U (Wacker) @ 636 F (300 C) 150–450 U (Wroblewski) 1.21–3.52 kat/L 71–207 U/L LDH Isoenzymes Percentage of Total Fraction of Total LDH1 29–37% 0.29–0.37 LDH2 42–48% 0.42–0.48 LDH3 16–20% 0.16–0.20 LDH4 2–4% 0.02–0.04 LDH5 0.5–1.5% 0.005–0.015 Note: Values may vary according to the laboratory performing the test. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Lactic Dehydrogenase and Isoenzymes Lactic dehydrogenase (LDH) catalyzes the reversible conversion of lactic acid to pyruvic acid within cells. Because many tissues contain LDH, elevated total LDH is considered a nonspecific indication of cellular damage unless other clinical data make the tissue origin obvious. Pronounced elevations in total LDH are seen in clients with megaloblastic anemia, metastatic cancer (especially if the liver is involved), shock, hypoxia, hepatitis, and renal infarction. Moderate elevations occur in those with myocardial and pulmonary infarctions, hemolytic conditions, leukemias, infectious mononucleosis, delirium tremens, and muscular dystrophy. Mild elevations are associated with most liver diseases, nephrotic syndrome, hypothyroidism, and cholangitis. The most useful diagnostic information is obtained by analyzing the five isoenzymes of LDH through electrophoresis. These isoenzymes are specific to certain tissues. The heart and erythrocytes are rich sources of LDH1 and LDH2; however, the brain is a source of LDH1, LDH2, and LDH3. The kidneys contain LDH3 and LDH4; the liver and skeletal muscle contain LDH4 and LDH5. Certain glands (thyroid, adrenal, and thymus), pancreas, spleen, lungs, lymph nodes, and white blood cells contain LDH3, whereas the ileum is an additional source of LDH5. Situations in which isoenzyme analysis is most useful include distinguishing myocardial infarction from lung or liver problems, diagnosing myocardial infarction in ambiguous settings such as the postoperative period or during severe shock and in hemolysis at a time of bone marrow hypoplasia. Normally, serum contains more LDH2 than LDH1. Damage to tissues rich in LDH1, however, will cause this ratio to reverse. The reversed ratio (i.e., LDH2 greater than LDH2) is an important diagnostic finding that occurs whether or not total LDH is elevated. The reversal is short lived. In myocardial infarction, for example, the LDH1:LDH2 ratio returns to normal within a week of the infarction even though total LDH may remain elevated.35 The tissue sources of LDH isoenzymes and common causes of elevations are summarized in Table 5–21. Numerous drugs may elevate LDH levels: anabolic steroids, anesthetics, aspirin, alcohol, fluorides, narcotics, clofibrate, mithramycin, and procainamide. INTERFERING FACTORS Numerous drugs may produce elevated LDH levels (e.g., anabolic steroids, anesthetics, aspirin, alcohol, fluorides, narcotics, clofibrate, mithramycin, and procainamide). Copyright © 2003 F.A. Davis Company 156 SECTION I—Laboratory Tests INDICATIONS FOR LACTIC DEHYDROGENASE AND ISOENZYMES TEST Confirmation of AMI or extension thereof, as indicated by elevation (usually) of total LDH, elevation of LDH1 and LDH2, and reversal of the LDH1:LDH2 ratio within 48 hours of the infarction Differentiation of acute myocardial infarction from pulmonary infarction and liver problems, which elevate LDH4 and LDH5 Confirmation of red blood cell hemolysis or renal infarction, especially as indicated by reversal of the LDH1:LDH2 ratio Confirmation of chronicity in liver, lung, and kidney disorders, as evidenced by LDH levels that remain persistently high Evaluation of the effectiveness of cancer chemotherapy (LDH levels should fall with successful treatment.) Evaluation of the degree of muscle wasting in muscular dystrophy (LDH levels rise early in this disorder and approach normal as muscle mass is reduced by atrophy.) Signs and symptoms of other disorders associated with elevation of the several LDH isoenzymes (see Table 5–21) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. mental and physical development of the infant, with death resulting by the third or fourth year of life. The deficiency of this enzyme is most common in families of Eastern-European Jewish and FrenchCanadian origin. Because of this deficiency, gangliosides or complex sphingolipids are not metabolized and accumulate in the brain, causing the paralysis, blindness, dementia, and mental retardation that develop in the children who have this disorder.36 Reference Values 56–80 percent of a total normal level (10.4–23.8 U/L) INTERFERING FACTORS Pregnancy decreases the level of hexosaminidase in relation to the total, resulting in an inaccurate false positive. Oral contraceptives can decrease the level. INDICATIONS FOR HEXOSAMINIDASE TEST Screening young adults for asymptomatic possession of this gene with or without a family history of Tay-Sachs disease Identifying carriers in high-risk clients during prenatal examination, revealed by a lowered enzyme activity Diagnosing Tay-Sachs in infants, revealed by a very low level or absence of enzyme activity In utero prenatal diagnosis of amniotic fluid or cells obtained from chorionic villi NURSING CARE BEFORE THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). Food and fluids should be avoided for 8 hours before the test, and oral contraceptives should be withheld. NURSING CARE AFTER THE PROCEDURE THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test. A venipuncture is performed and the sample collected in a red-topped tube. Refer to the procedures to obtain prenatal samples via chorionic villus biopsy or amniocentesis (see Chapters 10 and 14). THE PROCEDURE NURSING CARE AFTER THE PROCEDURE Hexosaminidase Hexosaminidase A is a test performed to determine the presence of the lysosomal disease known as TaySachs, a genetic autosomal recessive condition characterized by early and progressive retardation in the Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any drugs withheld before the test. Complications and precautions: Recommend Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood special genetic counseling for those with a family history of the disease or with abnormal test results. -Hydroxybutyric Dehydrogenase -Hydroxybutyric dehydrogenase (-HBD, HBD) is an enzyme similar to two isoenzymes of lactic dehydrogenase: LDH1 and LDH2. The -HBD test, however, is cheaper and easier to perform than LDH isoenzyme electrophoresis. Moreover, HBD levels remain elevated for 18 days after acute myocardial infarction, providing a diagnosis when the client has delayed seeking treatment or has not had classic signs and symptoms. Reference Values Conventional Units 70–300 U/L 140–350 U/L Note: Values may vary according to the laboratory performing the test. INDICATIONS FOR -HYDROXYBUTYRIC DEHYDROGENASE TEST Suspected “silent” myocardial infarction or otherwise atypical myocardial infarction in which the client delayed seeking care: HBD levels remain elevated for 18 days after acute myocardial infarction (i.e., when other cardiac enzymes have returned to normal levels). Support for diagnosing other disorders associated with elevated HBD levels (e.g., megaloblastic and hemolytic anemias, leukemias, lymphomas, melanomas, muscular dystrophy, nephrotic syndrome, and acute hepatocellular disease) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test Chemistry 157 involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Cholinesterases Cholinesterases hydrolyze concentrated acetylcholine and also cleave other choline esters. Two types of cholinesterase are measured: (1) acetylcholinesterase (“true” cholinesterase) and (2) pseudocholinesterase. Acetylcholinesterase (AcCHS) is found at nerve endings and in erythrocytes; very little is found in serum. Its substrate specificity is limited to acetylcholine, and it is optimally active against very low acetylcholine concentrations. Pseudocholinesterase (PCE) derives from the liver and is normally found in the serum in substantial amounts. It is active against acetylcholine and other choline esters. PCE is unusual in that the diagnostically significant change is depression, not elevation. An important application of information about PCE is in evaluating individuals for genetic variations of the enzyme before surgery in which succinylcholine, an inhibitor of acetylcholine, is to be used to induce anesthesia. Persons homozygous for the abnormal form of PCE have depressed total serum activity and their enzyme does not inactivate succinylcholine; persons who receive the drug during surgery may experience prolonged respiratory depression. Presence of the abnormal form of PCE is determined by exposing the enzyme to dibucaine. Normal PCE is inhibited by dibucaine, Reference Values Conventional Units SI Units Acetylcholinesterase (AcCHS) 0.5–1.0 pH units Pseudocholinesterase (PCE) 0.5–1.3 pH units Men 274–532 IU/dL 2.74–5.32 kU/L Women 204–500 IU/dL 2.04–5.00 kU/L Copyright © 2003 F.A. Davis Company 158 SECTION I—Laboratory Tests whereas abnormal PCE is found to be “dibucaine resistant.”37 INTERFERING FACTORS Numerous drugs may falsely decrease cholinesterase levels (e.g., caffeine, theophylline, quinidine, quinine, barbiturates, morphine, codeine, atropine, epinephrine, phenothiazines, folic acid, and vitamin K). INDICATIONS FOR CHOLINESTERASE DETERMINATIONS collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Renin Suspected exposure to organic phosphate insecticides: Red blood cell AcCHS levels decline with severe exposure; serum PCE decreases occur earlier. When exposure ceases, serum PCE rises before red blood cell AcCHS returns to normal. Red blood cell AcCHS levels are more useful than are serum PCE levels in determining prior exposure. Impending use of succinylcholine during anesthesia: Persons homozygous for the abnormal form of PCE have depressed total serum activity, and their enzyme does not inactivate succinylcholine, with the abnormal PCE indicated as “dibucaine resistant.” NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter cholinesterase levels and activity, a medication history should be obtained. It is recommended that those drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. Renin is an enzyme released by the juxtaglomerular apparatus of the kidney in response to decreased extracellular fluid volume, serum sodium, and renal perfusion pressure. It catalyzes the conversion of angiotensinogen, produced by the liver, to angiotensin I. Angiotensin I is then converted to angiotensin II in the lungs. Angiotensin II elevates systemic blood pressure by causing vasoconstriction and by stimulating the release of aldosterone. Renin released by the kidneys is found initially in the renal veins. Thus, the output of renin by each kidney may be determined by obtaining samples directly from the right and left renal veins and comparing the results with those obtained from an inferior vena cava sample. This test is indicated when renal artery stenosis is suspected, because the kidney affected by decreased perfusion releases higher amounts of renin. Renal vein assay for renin is performed using fluoroscopy and involves cannulation of the femoral vein and injection of dye to aid in visualizing the renal veins. Because this is an invasive procedure, a signed consent is required. INTERFERING FACTORS THE PROCEDURE A venipuncture is performed and the sample Failure to follow dietary restrictions, if ordered, before the test may affect the test results. Failure to take prescribed diuretics, if ordered, before the test may affect the test results. Failure to maintain required positioning (e.g., upright versus recumbent) for at least 2 hours before the test may affect the test results. Reference Values Peripheral vein Conventional Units SI Units 0.4–4.5 (ng/hr)/mL (normal salt intake, standing position) 0.4–4.5 gh–1 L–1 1.5–1.6 (ng/hr)/mL or more (normal salt intake, supine position) 1.5–1.6 gh–1 L–1 Renal vein assay Difference between each renal sample and the vena cava sample should be 1.4–1.0 Note: Values for peripheral vein samples should be substantially higher (e.g., 2.9–24 [ng/hr]/mL) in clients who are sodium depleted and in the upright position. These values also may vary according to the laboratory performing the test. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood High-dose adrenocorticosteroid therapy, excessive salt intake, and excessive licorice ingestion may produce decreased levels. INDICATIONS FOR RENIN TEST Assessment of renin production by the kidneys when client has hypertension of unknown etiology or when other disorders associated with altered renin levels are suspected: Elevated renin levels are seen in renovascular and malignant hypertension, adrenal hypofunction (Addison’s disease), salt-wasting disorders, end-stage renal disease, reninproducing renal tumors, and secondary hyperaldosteronism. Decreased levels are associated with primary hyperaldosteronism, hypervolemia, excessive salt ingestion or retention, excessive adrenocorticosteroid levels resulting from either disease or drug therapy, and excessive licorice ingestion. Renin levels may be high, low, or normal in essential hypertension. In primary hyperaldosteronism, plasma renin levels are decreased, even with salt depletion before the test (results should be evaluated in relation to the serum aldosterone level, which is elevated in primary hyperaldosteronism). Suspected renal artery stenosis as the cause of hypertension, as indicated by renal vein output of renin by the affected kidney more than 1.4 times that of the vena cava sample Nursing Alert The renal vein assay for renin should be performed with extreme caution, if at all, in clients with allergies or previous exposure to radiographic dyes. NURSING CARE BEFORE THE PROCEDURE Client preparation varies according to the method for obtaining the sample and the factors to be controlled (e.g., salt depletion). 1. Peripheral vein, normal salt intake. Client preparation is essentially the same as that for any test involving collection of a peripheral blood sample. The client should follow a normal diet with adequate salt and potassium intake. Licorice intake and certain medications may be restricted for 2 weeks or more before the test, although this practice should be confirmed with the person ordering the study. The position relevant to the type of Chemistry 159 sample (e.g., upright versus recumbent) should be maintained for 2 hours before the test. 2. Peripheral vein, sodium depleted. Client preparation is the same as just described, except that a diuretic is administered for 3 days before the study and dietary sodium is limited to “no added salt” (approximately 3 g/day). Sample menus should be provided. The purpose of the diuretic therapy and sodium restriction should be explained, and client understanding and ability to follow pretest preparation should be ascertained. Explain to the client: The purpose of the study That a “no added salt” diet must be followed for 3 days before the study That prescribed diuretics must be taken for 3 days before the study Other restrictions in diet (e.g., licorice) or drugs necessary before the study That the test will be performed in the radiology department by a physician and will take about 30 minutes The general procedure, including the sensations to expect (momentary discomfort as the local anesthetic is injected, sensation of warmth as the dye is injected) Whether premedications will be given After-procedure assessment routines (e.g., frequent vital signs) and activity restrictions Encourage questions and verbalization of concerns appropriate to the client’s age and mental status. Then: Question the client about possible allergies to radiographic dyes. Ensure that signed consent has been obtained. To the extent possible, ensure that the dietary and medication regimens and restrictions are followed. Assist the client in maintaining the upright position (standing or sitting) for 2 hours before the test, if ordered, to stimulate renin secretion. Take and record vital signs and have the client void; provide a hospital gown. Administer premedication, if ordered. Obtain a stretcher for client transport. THE PROCEDURE The procedure varies with the method for obtaining the sample. 1. Peripheral vein. A venipuncture is performed and the sample collected in a chilled lavendertopped tube. The tube should be inverted gently several times to promote adequate Copyright © 2003 F.A. Davis Company 160 SECTION I—Laboratory Tests mixing with the anticoagulant, placed in ice, and sent to the laboratory immediately. 2. Renal vein. The client is assisted to the supine position on the fluoroscopy table, and a site is selected for femoral vein catheterization. The skin may be shaved (if necessary), cleansed with an antiseptic, draped with sterile covers, and injected with a local anesthetic. A catheter is inserted into the femoral vein and advanced to the renal veins under fluoroscopic observation. Radiographic dye may be injected into the inferior vena cava at this point to aid in identification of the renal veins. A renal vein is entered and a blood sample obtained. The other renal vein is then entered and a second blood sample obtained. The catheter is then retracted into the inferior vena cava and a third sample obtained. The samples are placed in chilled lavender-topped tubes that are labeled to identify collection sites. The tubes should be inverted gently several times to promote adequate mixing with the anticoagulant, placed in ice, and sent to the laboratory immediately. The femoral catheter is removed after the third sample is obtained, and pressure is applied to the site for 10 minutes. A pressure dressing is then applied. NURSING CARE AFTER THE PROCEDURE 1. Peripheral vein. Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Pretest diet and medications, which may have been modified or restricted before the study, should be resumed. 2. Renal vein. Maintain the client on bed rest for 8 hours after the procedure. Monitor vital signs and record according to the following schedule: every 15 minutes for 1 hour, every 30 minutes for 1 hour, and every hour for 4 hours. Monitor the catheterization site for bleeding or hematoma each time vital signs are checked. Resume previous diet and medications. Abnormal values: Note and report results and correlate with urinary sodium, serum, and urinary aldosterone. Monitor blood pressure, especially if antihypertensive medications have been withheld. Monitor I&O for fluid deficit or excess. Allergic response (renal vein): Note and report allergic response to dye injection and assess for rash, urticaria, dyspnea, and tachycardia. Administer ordered antihistamine or steroids and oxygen. Have emergency equipment and supplies on hand. Vein thrombosis (renal vein): Note and report any flank or back pain, hematuria, or abnormal renal test results (blood urea nitrogen, creatinine). HORMONES Hormones are chemicals that control the activities of responsive tissues. Some hormones exert their effects in the vicinity of their release; others are released into the extracellular fluids of the body and affect distant tissues. Similarly, some hormones affect only specific tissues (target tissues), whereas others affect nearly all cells of the body. Chemically, hormones are classified as polypeptides, amines, and steroids. Hormones act on responsive tissues by (1) altering the rate of synthesis and secretion of enzymes or other hormones, (2) affecting the rate of enzymatic catalysis, and (3) altering the permeability of cell membranes. Once the hormone has accomplished its function, its rate of secretion normally decreases. This is known as negative feedback. After sufficient reduction in hormonal effects, negative feedback decreases, and the hormone is again secreted. Hypophyseal Hormones The hypophysis, also known as the pituitary gland, lies at the base of the brain in the sella turcica and is connected to the hypothalamus by the hypophyseal stalk. The hypophysis has two distinct portions: (1) the adenohypophysis (anterior pituitary) and (2) the neurohypophysis (posterior pituitary). The adenohypophysis arises from upward growth of pharyngeal epithelium in the embryo, whereas the neurohypophysis arises from the downward growth of the hypothalamus in the embryo. Almost all hormonal secretion from the hypophysis is controlled by the hypothalamus. Neurohypophyseal hormones are formed in the hypothalamus and travel down nerve fibers to the neurohypophysis, where they are stored and then released into the circulation in response to feedback mechanisms. Adenohypophyseal hormone secretion is controlled by releasing and inhibiting factors that are secreted by the hypothalamus and carried to the adenohypophysis by the hypothalamic–hypophyseal portal vessels. Hypothalamic releasing and inhibiting factors identified thus far include (1) thyrotropin-releasing hormone (TRH); (2) corticotropin-releasing hormone (CRH); (3) gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone–releasing hormone (LHRH) and follicle-stimulating hormone–releasing factor; (4) growth hormone–releasing hormone (GHRH); (5) growth hormone–inhibiting hormone Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood (GHIH); and (6) prolactin inhibitory hormone (PIH). A releasing factor for melanocyte-stimulating hormone also is believed to exist. The releasing factors either stimulate or inhibit the adenohypophysis in the release of its hormones. The adenohypophysis consists of three major cell types: (1) acidophils, (2) basophils, and (3) chromophobes. The acidophils secrete growth hormone (GH), also called somatotropic hormone (STH, SH) or somatotropin, and prolactin (HPRL), also known as luteotropic hormone (LTH), lactogenic hormone, or lactogen. The basophils secrete adrenocorticotropic hormone (ACTH), also known as adrenocorticotropin and corticotropin; thyroid-stimulating hormone (TSH), also known as thyrotropin; folliclestimulating hormone (FSH); luteinizing hormone (LH), also known as interstitial cell–stimulating hormone (ICSH); and melanocyte-stimulating hormone (MSH). The chromophobes, which constitute about half of the adenohypophyseal cells, are resting cells capable of transformation to either acidophils or basophils. The hormones stored and released by the neurohypophysis include antidiuretic hormone (ADH), also known as vasopressin, and oxytocin. Radioimmunoassays are used to determine the blood levels of the hypophyseal hormones. GROWTH HORMONE Growth hormone (GH, STH, SH) is secreted in episodic bursts, usually during early sleep. The effects of GH occur throughout the body. GH promotes skeletal growth by stimulating hepatic production of proteins. It also affects lipid and glucose metabolism. Under the influence of growth hormone, free fatty acids enter the circulation for use by muscle; hepatic glucose production (gluconeogenesis) also rises. Growth hormone also increases blood flow to the renal cortex and the glomerular filtration rate; the kidney excretes more calcium and less phosphate than usual. GH is believed to antagonize insulin. Deficiencies in GH are apparent only in childhood. Children with GH deficiency have very small statures but normal body proportions. The child also may be deficient in other hypophyseal hormones, and this disorder is known as pituitary dwarfism. Excessive levels of GH are apparent in all ages. Excess GH in children causes the long bones of the skeleton to enlarge and produces gigantism. In adults, the bones of the skull, hands, and feet thicken to produce the physical appearance of acromegaly. In this disorder, the internal organs, skeletal muscle, Chemistry 161 and heart muscle hypertrophy. Nerves and cartilage also enlarge and may produce nerve compression and joint disorders. Reference Values Conventional Units SI Units Newborns 15–40 ng/mL 15–40 g/L Children 0–10 ng/mL 0–10 g/L Adults 0–10 ng/mL 0–10 g/L Note: Values may vary according to the laboratory performing the test. INTERFERING FACTORS Hyperglycemia and therapy with drugs such as adrenocorticosteroids and chlorpromazine may cause falsely decreased levels. Hypoglycemia, physical activity, stress, and a variety of drugs (e.g., amphetamines, arginine, dopamine, levodopa, methyldopa, beta blockers, histamine, nicotinic acid, estrogens) may cause falsely elevated levels.38 INDICATIONS FOR GROWTH HORMONE TEST Growth retardation in children with decreased levels indicative of pituitary etiology Monitoring for response to treatment of growth retardation caused by GH deficiency Suspected disorder associated with decreased GH (e.g., pituitary tumors, craniopharyngiomas, tuberculosis meningitis, and pituitary damage or trauma) Gigantism in children with increased levels indicative of pituitary etiology Support for diagnosing acromegaly in adults as indicated by elevated levels; acidophil or chromophobe tumors of the adenohypophysis may account for these elevated levels39 NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should be informed that the test will be performed on 2 consecutive days, between the hours of 6 and 8 AM. The client should fast from food and avoid strenuous exercise for 12 hours before each sample is drawn. Additionally, it is recommended by some that the client be maintained on bed rest for 1 hour before each sample is obtained. Copyright © 2003 F.A. Davis Company 162 SECTION I—Laboratory Tests Because many drugs may affect serum GH levels, a medication history should be obtained. It is recommended that those drugs that alter test results be withheld for 12 hours before the study, although this practice should be confirmed with the person ordering the test. Reference Values Conventional Units SI Units Arginine Men 10 ng/mL 10 g/L THE PROCEDURE Women 15 ng/mL 15 g/L The test is performed on 2 consecutive days, between the hours of 6 and 8 AM. A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent immediately to the laboratory. L-Dopa 7 ng/mL above baseline level 7 g/L NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any medications withheld before the test, as well as usual activities. Abnormal values: Note and report increased levels. Assess for signs and symptoms of hyperglycemia and abnormal (increased) growth pattern. Prepare client for possible surgery or radiation therapy. Note and report decreased levels in association with GH stimulation tests. Assess growth pattern abnormalities for age and gender. Instruct caretaker in availability of replacement therapy and follow-up, if appropriate. GROWTH HORMONE STIMULATION TESTS Baseline levels of GH are affected by many factors and may be misleading at times. Stimulation tests are performed to determine responsiveness to substances that normally stimulate GH secretion, such as arginine and L-dopa. Insulin also may be given to induce hypoglycemia, which in turn stimulates GH secretion. It has been found that blood sugar levels of less than 50 mg/dL cause GH levels to rise 10 times or more in normal individuals. Idiosyncratic responses to the different stimulants may occur. Thus, it may be necessary to perform two or three different stimulation tests before arriving at diagnostic conclusions.40 INTERFERING FACTORS Factors that may affect serum GH determinations also may alter results of GH stimulation tests. INDICATIONS FOR GROWTH HORMONE STIMULATION TESTS Low or undetectable serum GH levels, with GH deficiency or adult panhypopituitarism or insulin confirmed by no increase after administration of the stimulant Confirmation of the diagnosis of acromegaly as evidenced by reduced GH output after L-dopa is administered as a stimulant (i.e., an idiosyncratic response is seen in acromegaly) Nursing Alert If insulin is used as the stimulant, the client should be observed carefully during and after the test for signs and symptoms of extreme hypoglycemia. NURSING CARE BEFORE THE PROCEDURE Initial client preparation is the same as that for serum GH determinations. The client should be weighed on the day of the test because dosage of the stimulant is determined by weight. Because several blood samples will be obtained and because certain of the stimulants (i.e., insulin and arginine) are administered IV, the client should be informed that an intermittent venous access device (e.g., heparin lock) will be inserted. THE PROCEDURE An intermittent venous access device is inserted, usually at about 8 AM, and a venous sample is obtained and placed in a red-topped tube. The sample is handled gently to avoid hemolysis and sent to the laboratory immediately. The stimulant is then administered. L-Dopa is administered orally; arginine and insulin are administered IV in a saline infusion. If insulin is used to lower blood sugar, an ampule of 50 percent glucose should be on hand in the event that severe hypoglycemia occurs. After the stimulant is administered, three blood samples are obtained via the venous access device at 30-minute intervals. The samples are placed in redtopped tubes and sent to the laboratory immediately upon collection. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 163 NURSING CARE AFTER THE PROCEDURE THE PROCEDURE Care and assessment after the procedure are essentially the same as for serum GH determinations. If an intermittent venous access device was inserted for the procedure, remove after completion of the test and apply a pressure bandage to the site. If insulin was used as the stimulant, resume dietary intake as soon as possible after the test is completed and observe for signs of hypoglycemia. Complications and precautions: If insulin is used, note and report signs and symptoms of hypoglycemia such as sweating, tachycardia, tremors, irritability, or confusion. Prepare client for IV glucose administration. A venipuncture is performed and a sample collected in a red-topped tube. The sample is handled gently to avoid hemolysis and sent to the laboratory immediately. The glucose solution (usually 100 g) is administered orally. If the client is unable to drink or retain the glucose solution, the physician is notified. IV glucose may be administered, if necessary, to perform the test. After 1 to 2 hours, depending on laboratory procedures, a second blood sample is collected in a red-topped tube and sent to the laboratory immediately. GROWTH HORMONE SUPPRESSION TEST Care and assessment after the procedure are the same as for serum GH determinations. Complications and precautions: Monitor for hyperglycemia after ingestion of the glucose solution. Hyperglycemia suppresses GH secretion in normal individuals. This principle is used in evaluating individuals with abnormally elevated levels and those who are believed to be hypersecreting GH but who show normal levels on routine serum GH determinations. Administration of a glucose load that produces hyperglycemia should decrease serum GH levels within 1 to 2 hours. In individuals who are hypersecreting GH, a decrease in serum GH will not occur in response to hyperglycemia. Note that the test may require repetition to confirm results. Reference Values Conventional Units 3 ng/dL SI Units 3 g/L INTERFERING FACTORS Factors that may affect serum GH determinations may also alter results of GH suppression tests. INDICATIONS FOR GROWTH HORMONE SUPPRESSION TEST Elevated serum GH levels Signs of GH hypersecretion with serum GH levels within normal limits Confirmation of GH hypersecretion as indicated by decreased response to GH suppression NURSING CARE BEFORE THE PROCEDURE Initial client preparation is the same as that for serum GH determinations. The client should be informed that it will be necessary to drink an oral glucose solution and that two blood samples will be obtained. NURSING CARE AFTER THE PROCEDURE PROLACTIN Prolactin (hPRL, LTH) is secreted by the acidophil cells of the adenohypophysis. It is unique among hormones in that it responds to inhibition via the hypothalamus rather than to stimulation; that is, prolactin is secreted except when influenced by the hypothalamic inhibiting factor, which is believed to be the neurotransmitter dopamine. The only known function of hPRL is to induce milk production in a female breast already stimulated by high estrogen levels. Once milk production is established, lactation can continue without elevated prolactin levels. Levels of hPRL rise late in pregnancy, peak with the initiation of lactation, and surge each time a woman breast-feeds. The function of hPRL in men is not known. Excessive circulating hPRL disturbs sexual function in both men and women. Women experience amenorrhea and anovulation, and they may have inappropriate milk secretion (galactorrhea). Men experience impotence, which occurs even when testosterone levels are normal, and sometimes gynecomastia.41 INTERFERING FACTORS Therapy with drugs such as estrogens, oral contraceptives, reserpine, -methyldopa, phenothiazines, haloperidol, tricyclic antidepressants, and procainamide derivatives may produce elevated levels. Episodic elevations may occur in response to sleep, stress, exercise, and hypoglycemia. Copyright © 2003 F.A. Davis Company 164 SECTION I—Laboratory Tests be handled gently to avoid hemolysis and transported promptly to the laboratory. Reference Values Conventional Units SI Units Children 1–20 ng/mL 1–20 g/L Men 1–20 ng/mL 1–20 g/L Nonlactating 1–25 ng/mL 1–25 g/L Menopausal 1–20 ng/mL 1–20 g/L Women Therapy with dopamine, apomorphine, and ergot alkaloids may produce decreased levels. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Assess for signs and symptoms of pituitary conditions such as mood changes; body image changes; sexual dysfunction in men; and menstrual, milk secretion, and weight gain abnormalities in women. ADRENOCORTICOTROPIC HORMONE INDICATIONS FOR SERUM PROLACTIN TEST Sexual dysfunction of unknown etiology in men and women, because excessive circulating hPRL may indicate the source of the problem (e.g., damage to the hypothalamus, pituitary adenoma) Failure of lactation in the postpartum period or suspected postpartum hypophyseal infarction (Sheehan’s syndrome), or both, as indicated by decreased levels Suspected tumor involving the lungs or kidneys, with elevated levels indicating ectopic hPRL production Support for diagnosing primary hypothyroidism as indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum hPRL levels, a medication history should be obtained. It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should Adrenocorticotropic hormone (ACTH) is secreted by the basophils of the adenohypophysis. ACTH stimulates the adrenal cortex to secrete (1) glucocorticoids, of which cortisol predominates; (2) adrenal androgens, which are converted by the liver to testosterone; and, to a lesser degree, (3) mineralocorticoids, of which aldosterone predominates. ACTH secretion is closely linked to melanocytestimulating hormone; it also is thought to stimulate pancreatic cells and the release of GH. ACTH release, which is stimulated by its corresponding hypothalamic releasing factor, occurs episodically in relation to decreased circulating levels of glucocorticoid, increased stress, and hypoglycemia. ACTH levels also vary diurnally; the highest levels occur on awakening, decrease throughout the day, and then begin to rise again a few hours before awakening. Circulating aldosterone levels may influence ACTH secretion to some extent; however, androgens are believed to have no effect on ACTH levels. ACTH assays are expensive to perform and are not universally available. INTERFERING FACTORS ACTH levels vary diurnally; highest levels occur upon awakening, decrease throughout the day, and then begin to rise again a few hours before awakening. Reference Values Conventional Units SI Units BioScience Laboratories 80 pg/mL at 8 AM 17.6 pmol/L Mayo Clinic 120 pg/mL at 6 to 8 AM 26.4 pmol/L Note: Normal values vary according to the laboratory performing the test. Results are usually evaluated in relation to other tests of adrenal-hypophyseal function (e.g., plasma cortisol). Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Numerous drugs may lead to decreased ACTH levels (e.g., adrenocorticosteroids, estrogens, calcium gluconate, amphetamines, spironolactone, and ethanol). Stress, exercise, and blood glucose levels may affect results. INDICATIONS FOR PLASMA ADRENOCORTICOTROPIC HORMONE TEST Signs and symptoms of adrenocortical dysfunction: Elevated ACTH levels with low cortisol levels indicate adrenocortical hypoactivity (Addison’s disease). Low ACTH levels with high cortisol levels indicate adrenocortical hyperactivity (Cushing’s syndrome) caused by benign or malignant adrenal tumors. High ACTH levels, without diurnal variation, combined with high cortisol levels indicate adrenocortical hyperfunction caused by excessive ACTH production (e.g., resulting from pituitary adenoma and nonendocrine malignant tumors in which there is ectopic ACTH production). Decreased ACTH levels are associated with panhypopituitarism, hypothalamic dysfunction, and long-term adrenocorticosteroid therapy. NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). For this test, the client should follow a low-carbohydrate diet for 48 hours and fast from food for 12 hours before the test. In addition, strenuous exercise should be avoided for 12 hours before the test, and 1 hour of bed rest is necessary immediately before the test. Medications that may alter test results should be withheld for at least 24 to 48 hours or longer before the study, although this practice should be confirmed with the person ordering the test. The client should be informed that it may be necessary to obtain more than one sample and that samples must be obtained at specific times to detect peak and trough levels of ACTH. THE PROCEDURE Between 6 and 8 AM (peak ACTH secretion time), a venipuncture is performed and the sample collected in a green-topped tube. The sample must be placed in a container of ice and sent to the laboratory immediately. When ACTH hypersecretion is Chemistry 165 suspected, a second sample may be obtained between 8 and 10 PM to determine whether diurnal variation in ACTH levels is occurring. The ACTH stimulation test can be conducted by the timed serial laboratory analysis of blood plasma samples for cortisol levels after the administration of metyrapone. The ACTH suppression test can be conducted by the laboratory analysis of blood plasma samples for cortisol levels after the administration of dexamethasone. The tests are performed to assist in the diagnosis of Addison’s disease or Cushing’s syndrome. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods and any medications withheld before the test, as well as usual activities. Complications and precautions: Note cortisol level and its relation to increases in ACTH production by the pituitary gland. THYROID-STIMULATING HORMONE Thyroid-stimulating hormone (TSH) is produced by the basophil cells of the adenohypophysis in response to stimulation by its hypothalamic releasing factor, thyrotropin-releasing hormone (TRH). TRH responds to decreased circulating levels of thyroid hormones, as well as to intense cold, psychological tension, and increased metabolic need, and it stimulates the adenohypophysis to secrete TSH. TSH accelerates all aspects of hormone production by the thyroid gland and enhances hPRL release. Measuring TSH provides useful information about both hypophyseal and thyroid gland function. Hypersecretion of TSH by the adenohypophysis (e.g., because of TSH-secreting pituitary tumors) causes hyperthyroidism as a result of excessive stimulation of the thyroid gland. Elevated TSH levels are also seen with prolonged emotional stress and are more common in colder climates. Primary hypothyroidism (i.e., hypothyroidism caused by disorders involving the thyroid gland itself) leads to elevated TSH levels because of normal feedback mechanisms. TSH levels are normally elevated at birth. Note that increased TSH secretion is associated with excess secretion of exophthalmos-producing substance, which also originates in the adenohypophysis. This substance promotes water storage in the retro-orbital fat pads and causes the eyes to protrude, a common sign of hyperthyroidism. Exophthalmos sometimes persists after the hyper- Copyright © 2003 F.A. Davis Company 166 SECTION I—Laboratory Tests thyroidism is corrected and also may occur in persons with normal thyroid function. TSH levels are normal in situations in which the functional ability of the thyroid gland is normal but the thyroid hormone levels are low, a phenomenon that is seen in clients with severe illnesses with protein deficiency (thyroid hormones are proteins) such as neoplastic disease, severe burns, trauma, liver disease, renal failure, and cardiovascular problems. Deficiency of thyroid hormone produces a hypometabolic state. Excess TSH production is not stimulated, however, because circulating thyroid levels are appropriate to the client’s metabolic needs (i.e., the person is metabolically euthyroid). Treatment involves correcting the underlying causes. The apparent hypothyroidism is not treated, however, because such treatment could be devastating to a severely debilitated person. TSH is measured by radioimmunoassay. Immunologic cross-reactivity occurs with glycoprotein hormones such as human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Reference Values Conventional Units Newborns Children and adults SI Units 25 IU/mL by day 3 25 mU/L 10 IU/mL 10 mU/L INTERFERING FACTORS Aspirin, adrenocorticosteroids, and heparin may produce decreased TSH levels. Lithium carbonate and potassium iodide may produce elevated TSH levels. Falsely increased levels may occur in hydatidiform mole, choriocarcinoma, embryonal carcinoma of the testes, pregnancy, and postmenopausal states characterized by high FSH and LH levels.42 INDICATIONS FOR THYROID-STIMULATING HORMONE TEST Signs and symptoms of hypothyroidism, hyperthyroidism, or suspected pituitary or hypothalamic dysfunction, or hypothyroidism or hyperthyroidism combined with suspected pituitary or hypothalamic dysfunction: Elevated levels are seen with primary hypothyroidism. Decreased or undetectable levels are associated with secondary hypothyroidism caused by pituitary or hypothalamic hypofunction. Decreased levels are seen with primary hyperthyroidism. Elevated levels may indicate secondary hyperthyroidism resulting from pituitary hyperactivity (e.g., caused by tumor). Differentiation of functional euthyroidism from true hypothyroidism in debilitated individuals, with the former indicated by normal levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). It is recommended that drugs known to alter TSH levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. The test for TSH is used on newborns to screen for congenital hypothyroidism. It is performed by obtaining a sample of blood from a heelstick and saturating a spot on a special filter paper with the blood. A kit is available for this test; it contains a comparison chart to identify elevations. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Note the relation of TSH to levels of other thyroid tests indicating hypothyroidism as opposed to other thyroid disorders. TSH STIMULATION TEST The TSH stimulation test is used to evaluate the thyroid–pituitary–hypothalamic feedback loop. In this test, a purified form of hypothalamic thyrotropin-releasing hormone (TRH) is administered IV. Normally, TRH stimulates the adenohypophysis to release TSH, which, in turn, causes hormonal release from the thyroid gland. A normal response (e.g., elevated TSH levels) indicates that the adenohypophysis is capable of responding to TRH stimulation. If thyroid hormones also are measured as part of the test, elevated levels indicate that the thyroid gland is capable of responding to TSH stimulation. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Reference Values TSH levels rise within 15 to 30 minutes of TRH administration, peak at 2.5 to 4 times normal, and return to baseline levels within 2 to 4 hours. Thyroid hormone secretion (e.g., T3 and T4), which should be increased by 50 to 75 percent, occurs in 1 to 4 hours. INDICATIONS FOR TSH STIMULATION TEST Low or undetectable serum TSH levels, hypothyroidism, or hyperthyroidism of unknown etiology or type, or low serum TSH levels combined with hypothyroidism or hyperthyroidism: A normal or delayed TSH response in persons with low baseline TSH levels and signs of hypothyroidism indicates hypothalamic dysfunction or disruption of the hypothalamic–hypophyseal portal circulation and confirms the diagnosis of tertiary hypothyroidism. A decreased or absent TSH response in persons with low baseline TSH levels and signs of hypothyroidism indicates hypopituitarism and confirms the diagnosis of secondary hypothyroidism. A normal or increased TSH response in clients with elevated baseline TSH levels and signs of hypothyroidism, with persistently decreased thyroid gland hormone levels, confirms the diagnosis of primary hypothyroidism. A decreased or absent TSH response in persons with low baseline TSH levels and signs of hyperthyroidism, with persistently elevated thyroid gland hormone levels, indicates that thyroid hormone production is occurring autonomously and confirms the diagnosis of primary hyperthyroidism. NURSING CARE BEFORE THE PROCEDURE Initial client preparation is the same as that for serum determinations of TSH. Because several blood samples will be obtained and because the TRH will be administered IV, the client should be informed that an intermittent venous access device (e.g., heparin lock) may be inserted. THE PROCEDURE The procedure varies somewhat according to the laboratory performing the test. One example of the procedure is described subsequently. An intermittent venous access device is inserted and a venous sample is obtained and placed in a red- Chemistry 167 topped tube. The sample is handled gently to avoid hemolysis and sent promptly to the laboratory. The sample should be labeled either with the time drawn or as the baseline sample. A bolus of TRH is then administered IV through the access device. Additional blood samples are obtained via the access device 1/2, 1, 2, 3, and 4 hours after administration of the TRH. Each sample is placed in a red-topped tube, labeled, and sent to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are essentially the same as for serum TSH determinations. If an intermittent venous access device was inserted for the procedure, remove after completion of the test and apply a pressure bandage to the site. Complications and precautions: Note increased levels in relation to other thyroid tests and prepare client for a nuclear scan laboratory study using the iodine 131 (131I) radionuclide (see Chapter 20). FOLLICLE-STIMULATING HORMONE Follicle-stimulating hormone (FSH) is secreted by the basophil cells of the adenohypophysis in response to stimulation by hypothalamic gonadotropin-releasing hormone (GnRH), which also is called luteinizing hormone–releasing hormone (LHRH) and follicle-stimulating hormone–releasing factor. FSH affects gonadal function in both men and women. In women, FSH promotes maturation of the graafian (germinal) follicle, causing estrogen secretion and allowing the ovum to mature. In men, FSH partially controls spermatogenesis, but the presence of testosterone also is necessary. GnRH secretion, which in turn stimulates FSH secretion, is stimulated by decreased estrogen and testosterone levels. Isolated FSH elevation also may occur when there is failure to produce spermatozoa, even though testosterone production is normal. FSH production is inhibited by rising estrogen and testosterone levels. FSH levels are normally low during childhood but begin to rise as puberty approaches. Surges of FSH occur initially during sleep but, as puberty advances, daytime levels also rise. During childbearing years, FSH levels in women vary according to the menstrual cycle. Decreased FSH levels after puberty are associated with male and female infertility. After the reproductive years, estrogen and testosterone levels decline, causing FSH levels to rise in response to normal feedback mechanisms. A 24- Copyright © 2003 F.A. Davis Company 168 SECTION I—Laboratory Tests hour urine specimen also can be collected and tested for FSH. FSH/LH CHALLENGE TESTS The hypothalamic–hypophyseal–gonadal axis can be evaluated by administering drugs and hormones known to affect specific hormonal interactions. These include clomiphene, GnRH, hCG, and progesterone. Clomiphene, a drug used to treat infertility, prevents the hypothalamus from recognizing normally inhibitory levels of estrogen and testosterone. Consequently, the hypothalamus continues to secrete GnRH, which, in turn, continues to stimulate the adenohypophysis to secrete FSH and LH. After 5 days of clomiphene, both FSH and LH levels rise, usually 50 to 100 percent above baseline levels. In anovulatory women whose ovaries are normal, clomiphene often enhances FSH and LH levels so that ovulation is induced. If FSH and LH levels do not rise with clomiphene administration, either hypothalamic or hypophyseal dysfunction is indicated. The source of the dysfunction may be identified by administering purified GnRH. If FSH and LH levels rise, the pituitary gland is normal but hypothalamic function is impaired. FSH and LH levels that do not rise indicate hypophyseal dysfunction. Human chorionic gonadotropin (hCG), a placental hormone with effects similar to those of LH, is used to evaluate testicular activity in men with low testosterone levels. Elevated testosterone levels after hCG administration indicate that testicular function is normal but that hypothalamic–pituitary activity is impaired. Failure of testosterone levels to rise suggests primary testicular dysfunction. Progesterone, a hormone secreted by the ovary, is used to evaluate amenorrhea. In the normal menstrual cycle, the progesterone surge that follows ovulation inhibits GnRH secretion, and hormonal levels decline. Menstrual bleeding, also called withdrawal bleeding, occurs when the estrogen-stimulated endometrium experiences a drop in hormonal stimulation. This normal situation can be simulated by administering oral or IM progesterone to amenorrheic women already exposed to adequate estrogen levels. If menstrual bleeding occurs, the underlying cause of the amenorrhea is failure to ovulate. Lack of bleeding in response to progesterone administration indicates (1) inadequate estrogen production, resulting from either primary ovarian failure or inadequate pituitary secretion of FSH; (2) hypothalamic dysfunction with defective GnRH secretion; (3) impaired hypophyseal response to GnRH; or (4) abnormal uterine response to hormonal stimulation. These possibilities can be distinguished by administering estrogen to stimulate the endometrium and then repeating the progesterone challenge. If bleeding occurs, then either ovarian failure or inadequately responsive hypothalamic–hypophyseal activity is the underlying cause of the amenorrhea. Measuring FSH, LH, and estrogen levels helps further to diagnose the problem.43 INTERFERING FACTORS In menstruating women, values vary in relation to the phase of the menstrual cycle. Values are higher in postmenopausal women. Administration of the drug clomiphene may result in elevated FSH levels. Therapy with estrogens, progesterone, and phenothiazines may result in decreased FSH levels.44 Reference Values Conventional Units SI Units Children 5–10 mIU/mL 5–10 IU/L Men 10–15 mIU/mL 10–15 IU/L Early in cycle 5–25 mIU/mL 5–25 IU/L Midcycle 20–30 mIU/mL 20–30 IU/L Luteal phase 5–25 mIU/mL 5–25 IU/L Women (menopausal) 40–250 mIU/mL 40–250 IU/L Women (menstruating) Note: Results should be evaluated in relation to other tests of gonadal function. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood INDICATIONS FOR FOLLICLE-STIMULATING HORMONE TEST Evaluation of ambiguous sexual differentiation in infants Evaluation of early sexual development in girls under age 9 years or boys under age 10 years, with precocious puberty associated with elevated levels Evaluation of failure of sexual maturation in adolescence Evaluation of sexual dysfunction or changes in secondary sexual characteristics in men and women: Elevated levels are associated with ovarian or testicular failure, with polycystic ovary disease, after viral orchitis, and with Turner’s syndrome in women and Klinefelter’s syndrome in men. Decreased levels may be seen with neoplasms of the testes, ovaries, and adrenal glands, resulting in excessive production of sex hormones. Suspected pituitary or hypothalamic dysfunction: Elevated levels may be seen in pituitary tumors. Decreased levels are associated with hypothalamic lesions and panhypopituitarism. Suspected early acromegaly as indicated by elevated levels Suspected disorders associated with decreased FSH levels, such as anorexia nervosa and renal disease NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is recommended that drugs known to alter FSH levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. In women, the phase of the menstrual cycle should be ascertained, if possible. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Note levels in relation to 24-hour urinary FSH and LH results. Prepare client for serial samples for testing. Chemistry 169 LUTEINIZING HORMONE Luteinizing hormone is secreted by the basophil cells of the adenohypophysis in response to stimulation by GnRH, the same hypothalamic releasing factor that stimulates FSH release. LH affects gonadal function in both men and women. In women, a surge of LH occurs at the midpoint of the menstrual cycle and is believed to be induced by high estrogen levels. LH causes the ovum to be expelled from the ovary and stimulates development of the corpus luteum and production of progesterone. As progesterone levels rise, LH production decreases. In men, LH stimulates the interstitial Leydig cells, located in the testes, to produce testosterone. During childhood, LH levels decrease and are lower than those of FSH. Similarly, LH levels rise after those of FSH as puberty approaches. During the childbearing years, LH levels in women vary according to the menstrual cycle but remain fairly constant in men. Decreased LH levels after puberty are associated with male and female infertility. After the reproductive years, as gonadal hormones decline, LH levels rise in response to normal feedback mechanisms. The rise in LH levels, however, is not as marked as that for FSH levels. A 24-hour urine specimen also can be collected and tested for LH. INTERFERING FACTORS In menstruating women, values vary in relation to the phase of the menstrual cycle. Values are higher in postmenopausal women. Drugs containing estrogen tend to cause elevated LH levels. Drugs containing progesterone and testosterone may lead to decreased levels. INDICATIONS FOR SERUM LUTEINIZING HORMONE TEST Evaluation of male and female infertility, as indicated by decreased levels Support for diagnosing infertility caused by anovulation as evidenced by lack of the midcycle LH surge Evaluation of response to therapy to induce ovulation Suspected pituitary or hypothalamic dysfunction: Elevated levels may be seen in pituitary tumors. Decreased levels are associated with hypothalamic lesions and panhypopituitarism. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company 170 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units Children 5–10 mIU/mL 5–10 IU/L Men 5–20 mIU/mL 5–20 IU/L Early in cycle 5–25 mIU/mL 5–25 IU/L Midcycle 40–80 mIU/mL 40–80 IU/L Luteal phase 5–25 mIU/mL 5–25 IU/L Women (menopausal) 75 mIU/mL 75 IU/L Women (menstruating) Note: Results should be evaluated in relation to other tests of gonadal function. It is recommended that any drugs known to alter LH levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. In women, the phase of the menstrual cycle should be ascertained, if possible. If the test is being performed to detect ovulation, the client should be informed that it may be necessary to obtain a series of samples over a period of several days to detect peak LH levels. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Psychogenic stimuli (e.g., stress, pain, anxiety) also may stimulate ADH release, but the mechanism by which this occurs is unclear. ADH acts on the epithelial cells of the distal convoluted tubules and the collecting ducts of the kidneys, making them permeable to water. Thus, with ADH, more water is absorbed from the glomerular filtrate into the bloodstream. Without ADH, water remains in the filtrate and is excreted, producing very dilute urine. In contrast, maximal ADH secretion produces very concentrated urine. ADH also is believed to stimulate mild contractions in the pregnant uterus and to aid in promoting milk ejection in lactation, functions similar to those of oxytocin, which also is secreted by the hypothalamus and released by the neurohypophysis. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Abnormal test results, complications, and precautions: Respond as for FSH testing, because LH is usually performed on the same blood sample. ANTIDIURETIC HORMONE Antidiuretic hormone (ADH) is formed by the hypothalamus but is stored in the neurohypophysis (posterior pituitary gland). ADH is released in response to increased serum osmolality or decreased blood volume. Although as little as a 1 percent change in serum osmolality will stimulate ADH secretion, blood volume must decrease by approximately 10 percent for ADH secretion to be induced. Reference Values Conventional Units 2.3–3.1 pg/mL SI Units 2.3–3.1 ng/L INTERFERING FACTORS Alcohol, phenytoin drugs, -adrenergic drugs, and morphine antagonists may lead to decreased ADH secretion. Acetaminophen, barbiturates, cholinergic agents, clofibrate, estrogens, nicotine, oral hypoglycemic agents, cytotoxic agents (e.g., vincristine), tricyclic antidepressants, oxytocin, carbamazepine (Tegretol), and thiazide diuretics may lead to increased ADH secretion.45 Pain, stress, and anxiety may lead to increased ADH secretion. Failure to follow dietary and exercise restrictions before the test may alter results. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood INDICATIONS FOR SERUM ANTIDIURETIC HORMONE TEST Polyuria or altered serum osmolality of unknown etiology, or both, to identify possible alterations in ADH secretion as the cause Central nervous system trauma, surgery, or disease that may lead to impaired secretion of ADH Differentiation of neurogenic (central) diabetes insipidus from nephrogenic diabetes insipidus: Neurogenic diabetes insipidus is characterized by decreased ADH levels. ADH levels may be elevated in nephrogenic diabetes insipidus if normal feedback mechanisms are intact. Known or suspected malignancy associated with syndrome of inappropriate ADH (SIADH) secretion (e.g., oat cell lung cancer, thymoma, lymphoma, leukemia, and carcinoma of the pancreas, prostate gland, and intestine), with the disorder indicated by elevated ADH levels Known or suspected pulmonary conditions associated with SIADH secretion (e.g., tuberculosis, pneumonia, and positive pressure mechanical ventilation), with the disorder indicated by elevated ADH levels NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving collection of a peripheral blood sample (see Appendix I). The client should fast from food and avoid strenuous exercise for 12 hours before the sample is obtained. It is recommended that drugs that may alter ADH levels be withheld for 12 to 24 hours before the study, although this practice should be confirmed with the person ordering the test. THE PROCEDURE A venipuncture is performed and the sample collected in a plastic red-topped tube. Plastic is used because contact with glass causes degradation of ADH. The sample should be handled gently to avoid hemolysis and sent to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Resume food and any medications withheld before the test, as well as usual activities. Abnormal levels: Note and report increased levels in relation to renin level. Assess for fluid volume excess resulting from sodium and water retention. Chemistry 171 Monitor I&O, weight gain, edema, and increases in blood pressure. Instruct in diuretic therapy regimen. Note and report decreased levels in relation to sodium level. Assess for fluid volume deficit. Monitor I&O and weight loss. Instruct in long-term fluid, sodium, and corticosteroid therapy regimen. Thyroid and Parathyroid Hormones The thyroid gland synthesizes and releases thyroxine (T4) and triiodothyronine (T3) in response to stimulation by TSH, which is secreted by the adenohypophysis. The thyroid gland synthesizes its hormones from iodine and the essential amino acid tyrosine. Most of the body’s iodine is ingested as iodide through dietary intake and is absorbed into the bloodstream from the gastrointestinal tract. One-third of the absorbed iodide enters the thyroid gland; the remaining two-thirds is excreted in the urine. In the thyroid gland, enzymes oxidize iodide to iodine. The thyroid gland secretes a protein, thyroglobulin, into its follicles. Thyroglobulin has special properties that allow the tyrosine contained in its molecules to react with iodine to form thyroid hormones. The thyroid hormones thus formed are stored in the follicles of the gland as the thyroglobulin–thyroid hormone complex called colloid. When thyroid hormones are released into the bloodstream, they are split from thyroglobulin as a result of the action of proteases, which are secreted by thyroid cells in response to stimulation by TSH. Much more T4 than T3 is secreted into the bloodstream. Upon entering the bloodstream, both immediately combine with plasma proteins, mainly thyroxine-binding globulin (TBG), but also with albumin and prealbumin. Although more than 99 percent of both T4 and T3 are bound to TBG, physiological activity of both hormones results from only the unbound (“free”) molecules. Note also that TBG has greater affinity for T4 than for T3, which allows for more rapid release of T3 from TBG for entry into body cells. T3 is thought to exert at least 65 to 75 percent of thyroidal hormone effects, and it is believed by some that T4 has no endocrine activity at all until it is converted to T3, which occurs when one iodine molecule is removed from T4.46 The main function of thyroid hormones is to increase the metabolic activities of most tissues by increasing the oxidative enzymes in the cells. This increase, in turn, causes increased oxygen consumption and increased utilization of carbohydrates, Copyright © 2003 F.A. Davis Company 172 SECTION I—Laboratory Tests proteins, fats, and vitamins. Thyroid hormones also mobilize electrolytes and are necessary for the conversion of carotene to vitamin A. Although the mechanism is not known, thyroid hormones are essential for the development of the central nervous system. Thyroid-deficient infants may suffer irreversible brain damage (cretinism). Thyroid deficiency in adults (myxedema) produces diffuse psychomotor retardation, which is reversible with hormone replacement. Thyroid hormones also are thought to increase the rate of parathyroid hormone secretion. Alterations in thyroid hormone production may be caused by disorders affecting the hypothalamus, which secretes thyrotropin-releasing hormone in response to circulating T4 and T3 levels; the pituitary gland; or the thyroid gland itself. Such alterations may affect all body systems. Hypothyroidism is the general term for the hypometabolic state induced by deficient thyroid hormone secretion, whereas hyperthyroidism indicates excessive production of thyroid hormones. An additional hormone produced by the thyroid gland is calcitonin, which is secreted in response to high serum calcium levels. Calcitonin causes an increase in calcium reabsorption by bone, thus lowering serum calcium.47 A number of tests pertaining to thyroid hormones may be performed, some of which may be grouped as a “thyroid screen” (e.g., T4, T3, and TSH). A “T7” is sometimes ordered. This is interpreted as a T4 plus a T3, because there is no such substance as T7. Before it was possible to measure thyroid hormones directly, serum iodine measurements (e.g., proteinbound iodine) were used as indicators of thyroid function. These tests were severely affected by organic and inorganic iodine contaminants and are no longer used to any great extent. Similarly, measurement of thyroidal uptake of radioactive iodine (131I) has been replaced by direct measurements of T4 and TSH.48 THYROXINE Thyroxine (T4) is measured by competitive protein binding or by radioimmunoassay. In competitive protein binding, the affinity between T4 and TBG is exploited. Reagent TBG fully saturated with radiolabeled T4 is incubated with T4 extracted from the client’s serum. TheT4 from the test serum displaces the radiolabeled T4 in the amount present. This procedure is known as T4 by displacement (T4 D), T4 by competitive binding (T4 CPB), and T4 MurphyPattee (T4 MP). T4 measured by radioimmunoassay (T4 RIA) is the preferred method to measure T4 because it is not affected by circulating iodinated substances. Most T4 (99.97 percent) in the serum is bound to TBG. The remainder circulates as unbound (“free”) T4 (FT4) and is responsible for all of the physiological activity of thyroxine. Because FT4 is not dependent on normal levels of TBG, as is the case with total serum thyroxine, FT4 levels are considered the most accurate indicator of thyroxine and its thyrometabolic activity. It is difficult, however, to measure FT4 directly because quantities are so small and the interference from bound T4 is great. Free hormone levels are, therefore, usually calculated by multiplying the values for total T4 by the T3 uptake ratio. The result is expressed as the free thyroxine index (FT4 I). The free hormone index varies directly with the amount of circulating hormone and inversely with the amount of unsaturated TBG present in the serum.49 Reference Values Conventional Units SI Units T4 D Newborns 11.0–23.0 g/dL 140–230 nmol/L 1–4 mo 7.5–16.5 g/dL 95–200 nmol/L 4–12 mo 5.5–14.5 g/dL 70–185 nmol/L Children 5.0–13.5 g/dL 65–170 nmol/L Adults 4.5–13.0 g/dL 60–165 nmol/L T4 RIA 4.0–12.0 g/dL 50–150 nmol/L FT4 0.9–2.3 ng/dL 10–30 nmol/L Note: Values may vary according to the laboratory performing the test. Results should be evaluated in relation to other tests of thyroid function. INTERFERING FACTORS Results of T4 D may be altered by circulating iodinated substances; T4 RIA is not similarly affected. Pregnancy, estrogen therapy, or estrogen-secreting tumors may produce elevated T4 levels. Ingestion of thyroxine will elevate T4 levels. Heroin and methadone may produce elevated T4 levels. Androgens, glucocorticoids, heparin, salicylates, phenytoin anticonvulsants, sulfonamides, and antithyroid drugs such as propylthiouracil may lead to decreased T4 levels. INDICATIONS FOR THYROXINE TEST Signs of hypothyroidism, hyperthyroidism, or neonatal screening for congenital hypothyroidism Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood (required in many states), or hypothyroidism or hyperthyroidism combined with neonatal screening: Decreased T4 and FT4 levels indicate hypothyroid states and also may be seen in early thyroiditis. Elevated T4 and FT4 levels indicate hyperthyroid states. Normal T4 and FT4 levels in clients with signs of hyperthyroidism may indicate T3 thyrotoxicosis. Normal FT4 levels are seen in pregnancy, whereas T4 and TBG are usually elevated. Monitoring of response to therapy for hypothyroidism or hyperthyroidism: Elevated T4 and FT4 levels indicate response to treatment for hypothyroidism. Decreased T4 and FT4 levels indicate response to treatment for hyperthyroidism. Evaluation of thyroid response to protein deficiency associated with severe illnesses (e.g., metastatic cancer, liver disease, renal disease, diabetes mellitus, cardiovascular disorders, burns, and trauma): T4 is decreased in such disorders because of a deficiency of TBG, a protein. FT4 index is normal, if thyroid function is normal, because FT4 index is not dependent on TBG levels. Chemistry 173 NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels and relation to other thyroid tests and procedures performed. Assess for signs and symptoms of hyperthyroidism such as tachycardia, increased appetite, diaphoresis, elevated temperature, exophthalmos, weight loss, insomnia, hyperactivity, or inability to handle stress. Prepare for possible radionuclide therapy or surgical intervention. Administer ordered medications to reduce levels. Instruct in adequate fluid and nutritional dietary intake and eye care for exophthalmos. Instruct client to avoid stressful situations. Decreased levels: Note and report decreased levels and relation to other thyroid tests and proce-dures. Assess for cold intolerance, weight gain, skin changes, constipation, lethargy, or fatigue. Administer ordered replacement therapy. Instruct client in appropriate fluid and low caloric nutritional dietary intake, long-term thyroid medication regimen, control of environment for relaxation and warmth, and care of skin and hair. Instruct client to avoid sedatives to promote sleep. NURSING CARE BEFORE THE PROCEDURE TRIIODOTHYRONINE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is usually recommended that thyroid medications be withheld for 1 month before the test and that other drugs that may alter thyroxine levels be withheld for at least 24 hours before the study. This practice should be confirmed, however, with the person ordering the test. For infants, explain to the parent(s) the purpose of the test and that it may require repetition in 3 to 6 weeks because of normal changes in infant thyroid hormone levels. Although produced in smaller quantities than T4, triiodothyronine (T3) is physiologically more significant. The competitive protein-binding techniques that are useful in measuring T4 are not used to measure T3 because it is present in smaller amounts and has less affinity for TBG than for T4. Thus, T3 is measured only by radioimmunoassay (T3 RIA). As with T4, most T3 (99.7 percent) in the serum is bound to TBG. The remainder circulates as unbound (“free”) T3 (FT3) and is responsible for all of the physiological activity of T3. Because FT3 is not dependent on normal levels of TBG, as is the case with total T3, FT3 levels are the most accurate indicators of thyrometabolic activity. FT3 levels may be calculated by multiplying total T3 levels by the T3 uptake ratio. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. For neonatal screening, the sample is obtained by heelstick. A multiple neonatal screening kit is usually used; the directions provided with the kit must be followed carefully. INDICATIONS FOR TRIIODOTHYRONINE TEST Support for diagnosing hyperthyroidism in clients with normal T4 levels, with early hyperthyroidism and T3 thyrotoxicosis indicated by elevated T3 levels in the presence of normal T4 levels Copyright © 2003 F.A. Davis Company 174 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units T3 RIA Newborns 90–170 ng/dL 1.3–2.6 nmol/L Adults 80–200 ng/dL 1.2–3.0 nmol/L FT3 0.2–0.6 ng/dL 0.003–0.009 nmol/L Reverse triiodothyronine (rT3) 38–44 ng/dL 0.58–0.67 nmol/L Support for diagnosing “euthyroid sick” syndrome in severely ill clients with protein deficiency, as indicated by low T3 levels, normal FT3 levels, and elevated rT3 levels50 the RT3 U level determined from a pool of normal serum Reference Values Conventional Units SI Units T3 resin uptake 25–35% 0.25–0.35 T3 uptake ratio 0.1–1.35 0.1–0.35 NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. T3 UPTAKE The T3 uptake (RT3 U) test evaluates the quantity of TBG in the serum and the quantity of thyroxine (T4) bound to it. In the T3 uptake procedure, a known amount of resin containing radiolabeled T3 is added to a sample of the client’s serum. Normally, TBG in the serum is not fully saturated with thyroid hormones; the saturation level varies in relation to the amounts of TBG and thyroid hormones present. In the T3 uptake test, the radiolabeled T3 binds with available TBG sites. Results of the test are determined by measuring the percentage of labeled T3 that remains bound to the resin after all available sites on TBG have been filled. Note that the percentage of T3 bound to the resin is inversely proportional to the percentage of TBG saturation in the serum. Results of the T3 uptake test are evaluated in relation to serum levels of total T4 and T3 and also are used in calculating FT3 and FT4 indices. For these calculations, the T3 uptake ratio (RT3 UR) is used, a ratio obtained by dividing the client’s RT3 U level by INTERFERING FACTORS Drugs that alter TBG levels or that compete for TBG-binding sites may affect test results. Estrogens may lead to increased TBG levels. Androgens and glucocorticoids may lead to decreased TBG levels. Salicylates and phenytoin anticonvulsants compete with T4 for TBG-binding sites. Results may vary during pregnancy when TBG levels are usually elevated. INDICATIONS FOR T3 UPTAKE TEST Signs of hypothyroidism or hyperthyroidism: Decreased levels (indicating a low percentage of radiolabeled T3 remaining) indicate low serum T4 levels and hypothyroidism. Elevated levels (indicating a high percentage of radiolabeled T3 remaining) indicate high serum T4 levels and hyperthyroidism. Known or suspected problems associated with altered TBG levels (e.g., hereditary abnormality of TBG synthesis, drug therapy, pregnancy, and disorders associated with decreased serum proteins): Elevated levels may indicate low TBG levels. Decreased levels may indicate elevated TBG levels. Monitoring for response to therapy with drugs that compete with T4 for TBG-binding sites: Elevated levels may indicate that TBG-binding sites are saturated with competing drugs. Calculation of free T3 and T4 indices Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is recommended that drugs that alter TBG levels or compete for TBG-binding sites be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Chemistry Diagnosis of hereditary abnormality of globulin synthesis, indicated by decreased levels NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is recommended that drugs that may alter TBG levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. NURSING CARE AFTER THE PROCEDURE THYROXINE-BINDING GLOBULIN THYROID-STIMULATING IMMUNOGLOBULINS Thyroxine-binding globulin (TBG) may be measured directly by radioimmunoassay. Estrogens elevate serum TBG levels; thus, women who are pregnant, who are receiving estrogen therapy or oral contraceptives, or who have estrogen-secreting tumors have higher TBG levels. Reference Values Conventional Units 16–32 g/dL SI Units 120–180 mg/mL INTERFERING FACTORS Estrogens elevate serum TBG levels and, thus, women who are pregnant, who are receiving estrogen therapy or oral contraceptives, or who have estrogen-secreting tumors have higher TBG levels. Androgens and corticosteriods decrease serum TBG levels. INDICATIONS FOR THYROXINE-BINDING GLOBULIN TEST Signs and symptoms of hypothyroidism or hyperthyroidism in conditions associated with altered TBG levels (e.g., pregnancy), to differentiate true thyroid disorders from problems related to altered TBG levels 175 Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Resume any medications withheld before the test. The globulin formerly known as long-acting thyroid stimulator (LATS) is one of the biologically unique autoantibodies with the effect of stimulating the target cell. Now called thyroid-stimulating immunoglobulins (TSI, TSIg), these antibodies react with the cell surface receptor that usually combines with TSH. The TSI reacts with the receptors, activates intracellular enzymes, and promotes epithelial cell activity that operates outside the feedback regulation for TSH. Reference Values TSI is not normally detected in the serum, although it may be found in the serum of about 5 percent of people without apparent hyperthyroidism or exophthalmos. INTERFERING FACTORS Administration of radioactive iodine preparations within 24 hours of the test may alter results. INDICATIONS FOR THYROID-STIMULATING IMMUNOGLOBULINS TEST Known or suspected thyrotoxicosis with elevated levels found in 50 to 80 percent of affected individuals Copyright © 2003 F.A. Davis Company 176 SECTION I—Laboratory Tests Determination of possible etiology of exophthalmos as indicated by elevated levels Monitoring of response to treatment for thyrotoxicosis with possible relapse indicated by elevated levels NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should not have received any radioactive iodine preparations within 24 hours of the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. CALCITONIN Calcitonin, also called thyrocalcitonin, is secreted by the parafollicular or C cells of the thyroid gland in response to elevated serum calcium levels. Its role is not completely understood, but the following functions are known: (1) It antagonizes the effects of parathyroid hormone and vitamin D, (2) it inhibits osteoclasts that reabsorb bone so that calcium continues to be laid down and not reabsorbed into the blood, and (3) it increases renal clearance of magnesium and inhibits tubular reabsorption of phosphates. The net result is that calcitonin decreases serum calcium levels. tonin levels, when serum calcium levels are normal. (Further verification may require raising the serum calcium level by IV infusion of calcium or pentagastrin and measuring the level to which plasma calcitonin rises in response; a rise of 0.105 to 0.11 ng/mL is to be expected.) Altered serum calcium levels of unknown etiology may be caused by a disorder associated with altered calcitonin levels. Elevated calcitonin levels are seen in cancers involving the breast, lung, and pancreas as a result of ectopic calcitonin production by tumor cells. Elevated calcitonin levels also are seen in primary hyperparathyroidism and in secondary hyperparathyroidism resulting from chronic renal failure. NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). For this test, the client should fast from food for at least 8 hours before collection of the sample. THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving collection of a peripheral blood sample. Resume foods withheld before the test. Complications and precautions: Note increased levels. Assess in relation to calcium and parathyroid hormone levels. Prepare the client for subsequent treatment decisions (medication protocol, surgery). Reference Values Conventional Units SI Units Men 0.155 ng/mL 0.155 g/L Women 0.105 ng/mL 0.105 g/L INTERFERING FACTORS Failure to fast from food for 8 hours before the test may alter results. INDICATIONS FOR CALCITONIN TEST Support for diagnosing medullary carcinoma of the thyroid gland is indicated by elevated calci- PARATHYROID HORMONE Parathyroid hormone (PTH, parathormone) is secreted by the parathyroid glands in response to decreased levels of circulating calcium. Actions of PTH include (1) mobilizing calcium from bone into the bloodstream, along with phosphates and protein matrix; (2) promoting renal tubular reabsorption of calcium and depression of phosphate reabsorption, thereby reducing calcium excretion and increasing phosphate excretion by the kidneys; (3) decreasing renal secretion of hydrogen ions, which leads to increased renal excretion of bicarbonate and chloride; and (4) enhancing renal production of active Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 177 vitamin D metabolites, causing increased calcium absorption in the small intestine. The net result of PTH action is maintenance of adequate serum calcium levels. calcium also may be obtained. The sample(s) should be handled gently to avoid hemolysis and transported promptly to the laboratory. Reference Values Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume foods withheld before the test. Increased levels: Note and report increased levels in relation to calcium and phosphate levels. Assess for signs and symptoms of hypercalcemia (greater than 10.5 mg/dL) leading to renal calculi formation, susceptibility to fractures, sluggishness, lethargy, anorexia, and constipation. Instruct in dietary restriction of calcium, medication regimen (corticosteroids, antineoplastics, phosphates), or signs and symptoms of hypophosphatemia (less than 3 mg/dL) such as irritability, confusion, and functional deficits. Instruct in dietary intake of foods rich in phosphorus and medication replacement regimen. Decreased levels: Note and report decreased levels in relation to calcium levels. Assess for signs and symptoms of hypocalcemia (less than 8.5 mg/dL), such as muscle cramping and spasms of hands and feet. In mild cases, instruct in dietary intake of calcium and vitamin D supplements; in severe states, prepare for IV administration of calcium. Conventional Units 2.3–2.8 pmol/L SI Units 23–28 g/mL Note: PTH is measured by radioimmunoassay. Because the antibody used for the assay directly affects the results, values vary according to the laboratory performing the test. INTERFERING FACTORS Failure to fast from food for 8 hours before the test may alter results. INDICATIONS FOR PARATHYROID HORMONE TEST Suspected hyperparathyroidism: Elevated levels occur in primary hyperparathyroidism as a result of hyperplasia or tumor of the parathyroid glands. Elevated levels also may occur in secondary hyperparathyroidism (usually as a result of chronic renal failure, malignant tumors that produce ectopic PTH, and malabsorption syndromes). Suspected surgical removal of the parathyroid glands or incidental damage to them during thyroid or neck surgery, as indicated by decreased levels Evaluation of parathyroid response to altered serum calcium levels, with elevated serum calcium levels, especially those resulting from malignant processes, leading to decreased PTH production Evaluation of parathyroid response to other disorders that may lead to decreased PTH production (e.g., hypomagnesemia, autoimmune destruction of the parathyroid glands)51 NURSING CARE BEFORE THE PROCEDURE Client preparation is essentially the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For this test, the client should fast from food for at least 8 hours before collection of the sample. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. A sample for serum NURSING CARE AFTER THE PROCEDURE Adrenal Hormones Adrenal hormones are secreted by two functionally and embryologically distinct portions of the adrenal gland. The adrenal cortex, which is of mesodermal origin, secretes three types of steroids: (1) glucocorticoids, which affect carbohydrate metabolism; (2) mineralocorticoids, which promote potassium excretion and sodium retention by the kidneys; and (3) adrenal androgens, which the liver converts to testosterone. Cortisol is the predominant glucocorticoid, whereas aldosterone is the predominant mineralocorticoid. Production and secretion of cortisol and adrenal androgens are stimulated by ACTH. Although ACTH also may enhance aldosterone production, the usual stimulants are either increased serum potassium or decreased serum sodium. The adrenal medulla, which constitutes only about one-tenth of the volume of the adrenal glands, derives from the ectoderm and physiologically belongs to the sympathetic nervous system. The hormones secreted by the adrenal medulla are epinephrine and norepinephrine, which are collectively known as the catecholamines. Epinephrine is Copyright © 2003 F.A. Davis Company 178 SECTION I—Laboratory Tests secreted in response to sympathetic stimulation, hypoglycemia, or hypotension. Most norepinephrine is manufactured by and secreted from sympathetic nerve endings; only a small amount is normally secreted by the adrenal medulla.52 CORTISOL Cortisol (hydrocortisone), the predominant glucocorticoid, is secreted in response to stimulation by ACTH. Ninety percent of cortisol is bound to cortisol-binding globulin (CBG) and albumin; the free portion is responsible for its physiological effects. Cortisol stimulates gluconeogenesis, mobilizes fats and proteins, antagonizes insulin, and suppresses inflammation. Cortisol secretion varies diurnally, with the highest levels seen upon awakening and the lowest levels occurring late in the day. Bursts of cortisol excretion also may occur at night. Elevated cortisol levels occur in Cushing’s syndrome, in which there is excessive production of adrenocorticosteroids. Cushing’s syndrome may be caused by pituitary adenoma, adrenal hyperplasia, benign or malignant adrenal tumors, and nonendocrine malignant tumors that secrete ectopic ACTH. Therapy with adrenocorticosteroids also may produce cushingoid signs and symptoms. Elevated cortisol levels are additionally associated with stress, hyperthyroidism, obesity, and diabetic ketoacidosis. Decreased cortisol levels occur with Addison’s disease, in which there is deficient production of adrenocorticosteroids. Addison’s disease is usually caused by idiopathic adrenal hypofunction, although it may also be seen in pituitary hypofunction, hypothyroidism, tuberculosis, metastatic cancer involving the adrenal glands, amyloidosis, and hemochromatosis. Addison’s disease may occur after withdrawal of corticosteroid therapy because of drug-induced atrophy of the adrenal glands. CORTISOL/ACTH CHALLENGE TESTS A variety of tests that stimulate or suppress cortisol/ACTH levels can be used further to evaluate individuals with signs and symptoms of adrenal hypofunction or hyperfunction or abnormal cortisol levels. Dexamethasone is a potent glucocorticoid that suppresses ACTH and cortisol production. In the rapid dexamethasone test, 1 mg of oral dexamethasone is given at midnight; cortisol levels are then measured at 8 AM. Normally, plasma cortisol should be no more than 5 to 10 mg/dL after dexamethasone administration. A 5-hour urine collection test for 17-hydroxycorticoids (17-OHCS), metabolites of glucocorticoids, also may be collected as part of the test. Elevated plasma cortisol levels in response to dexamethasone administration are associated with Cushing’s syndrome. Metyrapone is a drug that inhibits certain enzymes required to convert precursor substances into cortisol. When the drug is administered, plasma cortisol levels decrease and ACTH levels subsequently increase in response. The test involves mainly measurement of urinary excretion of 17OHCS, which should rise if the adenohypophysis is normally responsive to decreased cortisol levels. Plasma cortisol levels are measured to ensure that sufficient suppression has been induced by the metyrapone such that test results will be valid. Insulin-induced hypoglycemia (serum glucose of 50 mg/dL or less) also stimulates ACTH production. Adenohypophyseal response to hypoglycemia is usually measured indirectly by plasma cortisol levels because the test is more universally available. A normal response is an increase of 6 g/dL or more over baseline cortisol levels. Lack of response to hypoglycemic stimulation indicates either pituitary or adrenal hypofunction. They can be differentiated either by directly measuring plasma ACTH levels or by administering ACTH preparations and observing cortisol response. Purified exogenous ACTH or synthetic ACTH preparations (e.g., cosyntropin) may be used diagnostically to stimulate cortisol secretion. The usual response is an increase in plasma cortisol levels of 7 to 18 g/dL over baseline levels within 1 hour of ACTH administration. Lack of response indicates adrenal insufficiency.53 Reference Values 8 AM Conventional Units 4 PM SI Units Conventional Units SI Units Children 15–25 g /dL 410–690 nmol/L 5–10 g/dL 140–280 nmol/L Adults 9–24 g /dL 250–690 nmol/L 3–12 g/dL 80–330 nmol/L Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood INTERFERING FACTORS The time of day when the test is performed may alter results because cortisol levels vary diurnally, with highest levels being seen on awakening and lowest levels occurring late in the day. Stress and excessive physical activity may produce elevated levels. Pregnancy, therapy with estrogen-containing drugs, lithium carbonate, methadone, and ethyl alcohol may lead to elevated cortisol levels. Therapy with levodopa, barbiturates, phenytoin (Dilantin), and androgens may produce decreased levels. Failure to follow dietary restrictions, if ordered, may alter test results. INDICATIONS FOR CORTISOL ASSAY Suspected adrenal hyperfunction (Cushing’s syndrome) from a variety of causes, as indicated by elevated levels that do not vary diurnally Evaluation of effects of disorders associated with elevated cortisol levels (e.g., hyperthyroidism, obesity, and diabetic ketoacidosis) Suspected adrenal hypofunction (Addison’s disease) from a variety of causes, as indicated by decreased levels Monitoring for response to therapy with adrenocorticosteroids: Elevated levels are seen in clients receiving adrenocorticosteroid therapy. Decreased levels may occur for months after therapy is discontinued, resulting from druginduced atrophy of the adrenal glands. NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Some laboratories require an 8-hour fast and activity restriction before the test. Medications that may alter cortisol levels should be withheld for 12 to 24 hours before the study, although this practice should be confirmed with the person ordering the test. The client should be informed that it may be necessary to obtain more than one sample and that samples must be obtained at specific times to detect peak and trough levels of cortisol. THE PROCEDURE At approximately 8 AM, a venipuncture is performed and the sample is collected in a green-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. If cortisol hypersecretion is suspected, then a second Chemistry 179 sample may be obtained at approximately 4 PM to determine whether diurnal variation in cortisol levels is occurring. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume food and any medications withheld before the test, as well as usual activities. Increased levels: Note and report increased levels in relation to urinary cortisol, serum glucose, and calcium. Assess potential for infection, fluid volume excess (weight gain, edema, increased blood pressure), hyperglycemia (thirst, polyuria, polydipsia), mood changes (euphoria, psychosis), poor body image (moon face, buffalo hump on the back, acne, hair growth in undesirable areas in women, obese trunk, and thin extremities), and bone or joint pain. Monitor I&O. Provide support for psychophysiological changes. Help client to develop coping skills. Instruct client to increase dietary protein; decrease sodium, calories, and carbohydrates; and avoid infections. Decreased levels: Note and report decreased levels in relation to electrolyte panel (hyponatremia, hyperkalemia) and serum glucose for hypoglycemia. Assess for fluid volume deficit, long-term administration of corticosteroid therapy, and changes in body image (pigmentation of the skin, masculinization in women). Monitor I&O. Administer ordered corticosteroid regimen. Provide support for physical changes affecting body image. Advise client to avoid situations that cause stress or anxiety. Instruct client in longterm supplemental or replacement cortisone regimen. ALDOSTERONE Aldosterone, the predominant mineralocorticoid, is secreted by the zona glomerulosa of the adrenal cortex in response to decreased serum sodium, decreased blood volume, and increased serum potassium. It is thought that altered serum sodium and potassium levels directly stimulate the adrenal cortex to release aldosterone. In addition, decreased blood volume and altered sodium and potassium levels stimulate the juxtaglomerular apparatus of the kidney to secrete renin. Renin is subsequently converted to angiotensin II, which then stimulates the adrenal cortex to secrete aldosterone. In normal states, ACTH does not play a major role in aldosterone secretion. In disease or stress states, however, ACTH may also enhance aldosterone secretion. Copyright © 2003 F.A. Davis Company 180 SECTION I—Laboratory Tests Aldosterone increases sodium reabsorption in the renal tubules, gastrointestinal tract, salivary glands, and sweat glands. This subsequently results in increased water retention, blood volume, and blood pressure. Aldosterone also increases potassium excretion by the kidneys in exchange for the sodium ions that are retained. ALDOSTERONE CHALLENGE TESTS In normal individuals, increased serum sodium levels and blood volume suppress aldosterone secretion. In primary aldosteronism, however, this response is not seen. Serum sodium levels may be elevated through ingestion of a high-sodium diet for approximately 4 days or by infusing 2 L of normal saline intravenously. If appropriate control of aldosterone levels is managed through negative feedback systems and the renin–angiotensin system, plasma aldosterone levels will be low normal or decreased in response to the increased sodium load. Fludrocortisone acetate (Florinef), a synthetic mineralocorticoid, produces the same effect after 3 days of administration. Aldosterone challenges are used to differentiate between primary and secondary hyperaldosteronism.54 Reference Values Conventional Units SI Units Supine 3–9 ng/dL 0.08–0.30 nmol/L Standing 5–30 ng/dL 0.14–0.80 nmol/L INTERFERING FACTORS Upright body posture (see “Nursing Care Before the Procedure” section), stress, and late pregnancy may lead to increased levels. Therapy with diuretics, hydralazine (Apresoline), diazoxide (Hyperstat), and nitroprusside may lead to elevated levels. Excessive licorice ingestion may produce decreased levels, as may therapy with propranolol and fludrocortisone (Florinef). Altered serum electrolyte levels affect aldosterone secretion. Decreased serum sodium and elevated serum potassium increase aldosterone secretion. Elevated serum sodium and decreased serum potassium suppress aldosterone secretion. INDICATIONS FOR PLASMA ALDOSTERONE TEST Suspected hyperaldosteronism as indicated by elevated levels: Primary aldosteronism (e.g., resulting from benign adenomas or bilateral hyperplasia of the aldosterone-secreting zona glomerulosa cells) is indicated by elevated aldosterone and low plasma renin levels. Secondary hyperaldosteronism (e.g., resulting from changes in blood volume and serum electrolytes, CHF, cirrhosis, nephrotic syndrome, chronic obstructive pulmonary disease [COPD], and renal artery stenosis) is indicated by elevated aldosterone and plasma renin levels. Suspected hypoaldosteronism (e.g., as seen in diabetes mellitus and toxemia of pregnancy) as indicated by decreased levels Evaluation of hypertension of unknown etiology NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The client should not have ingested licorice for 2 weeks before the test. Medications that alter plasma aldosterone levels also may be withheld for up to 2 weeks before the test, although this practice should be confirmed with the person ordering the study. If hospitalized, the client should be told not to get out of bed in the morning until the sample has been obtained and that it may be necessary to obtain a second sample after he or she has been up for about 2 to 4 hours. Nonhospitalized individuals should be instructed on when to report to the laboratory in relation to the length of time to be upright before the test. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-, green-, or lavender-topped tube, depending on laboratory procedures. The client’s position and length of time the position was held should be noted on the laboratory request form. The sample(s) should be handled gently to avoid hemolysis and sent to the laboratory immediately. A sample for plasma renin also may be obtained in conjunction with the test. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels related to urinary aldosterone levels. Assess for fluid volume excess caused by sodium and fluid retention, and administer ordered diuretics. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 181 Reference Values Conventional Units Epinephrine and norepinephrine SI Units 100–500 ng/L Epinephrine Supine 0–110 pg/mL 0–600 pmol/L Standing 0–140 pg/mL 0–764 pmol/L Supine 70–750 pg/mL 413–4432 pmol/L Standing 200–1700 pg/mL 1,182–10,047 pmol/L Norepinephrine Note: Results are usually evaluated in relation to urinary measurements of catecholamine metabolites. Several measurements of plasma levels may also be indicated. Decreased levels: Note and report decreased levels related to sodium levels. Assess for fluid volume deficit. Instruct in sodium and corticosteroid replacement regimen. CATECHOLAMINES The adrenal medulla, a component of the sympathetic nervous system, secretes epinephrine and norepinephrine, which are collectively known as the catecholamines. A third catecholamine, dopamine, is secreted in the brain, where it functions as a neurotransmitter. Epinephrine (adrenalin) is secreted in response to generalized sympathetic stimulation, hypoglycemia, or arterial hypotension. It increases the metabolic rate of all cells, heart rate, arterial blood pressure, and levels of blood glucose and free fatty acids, and it decreases peripheral resistance and blood flow to the skin and kidneys. Norepinephrine is secreted by sympathetic nerve endings, as well as by the adrenal medulla, in response to sympathetic stimulation and the presence of tyramine. It decreases the heart rate, while increasing peripheral vascular resistance and arterial blood pressure. Normally, norepinephrine is the predominant catecholamine. The only clinically significant disorder involving the adrenal medulla is the catecholamine-secreting tumor, pheochromocytoma. Catecholamineproducing tumors also can originate along sympathetic paraganglia; these tumors are known as functional paragangliomas. Pheochromocytomas may release catecholamines, primarily epinephrine, continuously or intermittently. Because the most common sign of pheochromocytoma is arterial hypertension, measurement of plasma catecholamines (or the urinary metabolites thereof) is indicated in evaluating new-onset hypertension.55 INTERFERING FACTORS Catecholamine levels vary diurnally and with postural changes. Shock, stress, hyperthyroidism, strenuous exercise, and smoking may produce elevated plasma catecholamines. Dopamine, norepinephrine (Levophed), sympathomimetic drugs, tricyclic antidepressants, methyldopa, hydralazine, quinidine, and isoproterenol (Isuprel) may produce elevated levels. A diet high in amines (e.g., bananas, nuts, cereal grains, tea, coffee, cocoa, aged cheese, beer, ale, certain wines, avocados, and fava beans) may produce elevated plasma catecholamine levels, although this effect is more likely to be seen in relation to certain urinary metabolites. INDICATIONS FOR PLASMA CATECHOLAMINES TEST Hypertension of unknown etiology or suspected pheochromocytoma or paragangliomas or both Identification of pheochromocytoma as the cause of hypertension as indicated by elevated combined catecholamine and epinephrine levels Support for diagnosing paragangliomas as indicated by elevated combined catecholamine and norepinephrine levels NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). For this test, the client should fast for 12 hours and abstain from smoking for 24 hours before the test. Vigorous exercise should be avoided, with provision made for rest in a recumbent position for at least 1 hour before the study. Copyright © 2003 F.A. Davis Company 182 SECTION I—Laboratory Tests Medications that may alter test results, especially over-the-counter cold preparations containing sympathomimetics, may be withheld for up to 2 weeks before the test, although this practice should be confirmed with the person ordering the study. The need for dietary restriction of amine-rich foods for 48 hours before the test should be confirmed with the laboratory performing the test or the person ordering it. If samples are to be obtained via an intermittent venous access device (e.g., heparin lock), the client should be informed of its purpose and that it may be inserted as long as 24 hours before the test. steroids, and their molecular structures and those of the adrenocorticosteroids are quite similar. Moreover, small amounts of the gonadal hormones or precursors thereof are secreted by the adrenal glands in both men and women. Secretion of gonadal hormones is regulated via the hypothalamic–hypophyseal system. When blood levels of gonadal hormones decline, the hypothalamus is stimulated to release gonadotropin-releasing hormone, which then stimulates the adenohypophysis to release its gonadotropic hormones. These tropic hormones are called, in both men and women, follicle-stimulating hormone and luteinizing hormone, even though the ovarian follicle and corpus luteum are unique to women. THE PROCEDURE If more than one sample is to be obtained, a heparin lock should be inserted 12 to 24 hours before the test; the stress of repeated venipunctures could falsely elevate levels. For hospitalized individuals, a sample of venous blood should be collected in a chilled lavendertopped tube between 6 and 8 AM. For nonhospitalized clients, the first sample should be obtained after approximately 1 hour of rest in a recumbent position. The sample is handled gently to avoid hemolysis, packed in ice, and sent to the laboratory immediately. The client should then be helped to stand for 10 minutes, after which a second sample is obtained. The time(s) of collection and the position of the client should be noted on the laboratory request form. NURSING CARE AFTER THE PROCEDURE If an intermittent venous access device was inserted, remove after completion of the test and apply a pressure bandage to the site. Resume foods and any medications withheld before the test, as well as usual activities. Abnormal levels: Note increased levels in relation to 24-hour urinary vanillylmandelic acid (VMA) and metanephrine levels. Assess for pulse and blood pressure increases, hyperglycemia, shakiness, and palpitations associated with increased values. Gonadal Hormones The gonadal hormones, secreted primarily by the ovaries and testes, include estrogens, progesterone, and testosterone. These hormones are essential for normal sexual development and reproductive function in men and women. All gonadal hormones are ESTROGENS Estrogens are secreted in large amounts by the ovaries and, during pregnancy, by the placenta. Minute amounts are secreted by the adrenal glands and, possibly, by the testes. Estrogens induce and maintain the female secondary sex characteristics, promote growth and maturation of the female reproductive organs, influence the pattern of fat deposition that characterizes the female form, and cause early epiphyseal closure. They also promote retention of sodium and water by the kidneys and sensitize the myometrium to oxytocin. Elevated estrogen levels are associated with ovarian and adrenal tumors as well as estrogen-producing tumors of the testes. Decreased levels are associated with primary and secondary ovarian failure, Turner’s syndrome, hypopituitarism, adrenogenital syndrome, Stein-Leventhal syndrome, anorexia nervosa, and menopause. Estrogen levels vary in relation to the menstrual cycle. Many different types of estrogens have been identified, but only three are present in the blood in measurable amounts: estrone, estradiol, and estriol. Estrone (E1) is the immediate precursor of estradiol (E2), which is the most biologically potent of the three. In addition to ovarian sources, estriol (E3) is secreted in large amounts by the placenta during pregnancy from precursors produced by the fetal liver. Through radioimmunoassay, plasma levels of E2 and E3 can be determined. Total plasma estrogen levels are difficult to measure and are not routinely performed. INTERFERING FACTORS In menstruating women, estrogen levels vary in relation to the menstrual cycle. Therapy with estrogen-containing drugs and Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 183 Reference Values Conventional Units SI Units Estradiol (E2) Children under 6 yr 3–10 pg/mL 10–36 pmol/L 12–34 pg/mL 40–125 pmol/L Early cycle 24–68 pg/mL 90–250 pmol/L Midcycle 50–186 pg/mL 200–700 pmol/L Late cycle 73–149 pg/mL 250–550 pmol/L 30–32 2–12 ng/mL 7–40 nmol/L 33–35 3–19 ng/mL 10–65 nmol/L 36–38 5–27 ng/mL 15–95 nmol/L 39–40 10–30 ng/mL 35–105 nmol/L Adults Men Women (menstruating) Estriol (E3) Weeks of pregnancy adrenocorticosteroids will elevate levels, whereas clomiphene will decrease them. INDICATIONS FOR ESTROGENS TEST Infertility or amenorrhea of unknown etiology, with primary or secondary ovarian failure indicated by low estradiol (E2) levels Establishment of the time of ovulation Evaluation of response to therapy for infertility Suspected precocious puberty with the disorder indicated by elevated estradiol (E2) levels Suspected estrogen-producing tumors, as indicated by consistently high estradiol (E2) levels without normal cyclic variations High-risk pregnancy with suspicion of fetal growth retardation, placental dysfunction, or impending fetal jeopardy, as indicated by decreased estriol (E3) levels relative to the stage of pregnancy NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). It is recommended that drugs known to alter estrogen levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. In menstruating women, the phase of the menstrual cycle should be ascertained, if possible. If the test is being conducted to detect ovulation, the client should be informed that it may be necessary to obtain a series of samples over a period of several days to detect the normal variation in estrogen levels. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Assess increased or decreased levels in relation to age, gender, pregnancy, and menopausal status and in relation to associated levels of 24-hour urinary analysis and serum estradiol and estriol levels. PROGESTERONE Progesterone is secreted in nonpregnant women during the latter half of the menstrual cycle by the corpus luteum and in large amounts by the placenta during pregnancy. It also is secreted in minute amounts by the adrenal cortex in both men and Copyright © 2003 F.A. Davis Company 184 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units 100 ng/dL 3 nmol/L Follicular phase 150 ng/dL 5 nmol/L Luteal phase 300–1200 ng/dL 10–40 nmol/L First trimester 1500–5000 ng/dL 50–160 nmol/L Second and third trimesters 8,000–20,000 ng/dL 250–650 nmol/L Women (menopausal) 10–22 ng/dL 2 nmol/L Men Women (menstruating) Women (pregnant) women. Progesterone prepares the endometrium for implantation of the fertilized ovum, decreases myometrial excitability, stimulates proliferation of the vaginal epithelium, and stimulates growth of the breasts during pregnancy. Although progesterone may promote sodium and water retention, its effect is weaker than that of aldosterone, which it directly antagonizes. The net effect is loss of sodium and water from the body. INTERFERING FACTORS In menstruating women, progesterone levels vary in relation to the menstrual cycle. Therapy with estrogen, progesterone, or adrenocorticosteroids may produce elevated levels. INDICATIONS FOR PLASMA PROGESTERONE TEST Infertility of unknown etiology with failure to ovulate, indicated by low levels throughout the menstrual cycle Evaluation of response to therapy for infertility Support for diagnosing disorders associated with elevated progesterone levels (e.g., precocious puberty, ovarian tumors or cysts, and adrenocortical hyperplasia and tumors) High-risk pregnancy with suspicion of placental dysfunction, fetal abnormality, impending fetal jeopardy, threatened abortion, or toxemia of pregnancy, as indicated by lower than expected levels for the stage of pregnancy Support for diagnosing disorders associated with decreased progesterone levels (e.g., panhypopituitarism, Turner’s syndrome, adrenogenital syndrome, and Stein-Leventhal syndrome) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is recommended that any drugs that may alter progesterone levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. In menstruating women, the phase of the menstrual cycle should be ascertained, if possible. If the test is being performed to detect ovulation, the client should be informed that it may be necessary to obtain a series of samples over a period of several days to detect the normal variation in progesterone levels. THE PROCEDURE A venipuncture is performed and the sample collected in a green-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Assess increased or decreased levels in relation to age, menstrual or pregnancy status, and 24-hour urinary pregnanediol level. TESTOSTERONE Testosterone is produced in men by the Leydig cells of the testes. Minute amounts also are secreted by the adrenal glands in men and women and by the ovaries in women. In the male fetus, testosterone is secreted by the genital ridges and fetal testes. Testosterone is produced in response to stimulation by luteinizing hormone, which is secreted by the adenohypophysis in response to stimulation by gonadotropin-releasing hormone. Testosterone Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 185 Reference Values Conventional Units SI Units 0.12–0.16 ng/mL 0.41–0.55 nmol/L 60 yr 3.9–7.9 ng/mL 13.59–27.41 nmol/L 60 yr 1.5–3.1 ng/dL 5.20–10.75 nmol/L Menstruating 0.25–0.67 ng/mL 0.87–2.32 nmol/L Menopausal 0.21–0.37 ng/mL 0.72–1.28 nmol/L Children Men Women promotes development of the male sex organs and testicular descent in the fetus, induces and maintains secondary sexual characteristics in men, promotes protein anabolism and bone growth, and enhances sodium and water retention to some degree. INTERFERING FACTORS Testosterone levels vary diurnally, with highest levels occurring in the early morning. Administration of testosterone, thyroid and growth hormones, clomiphene, and barbiturates may lead to elevated levels. Therapy with estrogens and spironolactone (Aldactone) may produce decreased levels. INDICATIONS FOR TESTOSTERONE TEST In men, support for diagnosing precocious puberty, testicular tumors, and benign prostatic hypertrophy, as indicated by elevated levels In women, support for diagnosing adrenogenital syndrome, adrenal tumors or hyperplasia, SteinLeventhal syndrome, ovarian tumors or hyperplasia, and luteomas of pregnancy, as indicated by elevated levels In men and women, support for diagnosing nonendocrine tumors that produce ACTH ectopically, as indicated by elevated levels without diurnal variation In men, support for diagnosing infertility, with testicular failure indicated by decreased levels Support for diagnosing other disorders associated with decreased testosterone levels (e.g., hypopituitarism, Klinefelter’s syndrome, cryptorchidism [failure of testicular descent], and cirrhosis) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). It is recommended that drugs that may alter testosterone levels be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in either a red- or a green-topped tube, depending on the laboratory performing the test. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Complications and precautions: Assess increased or decreased levels in relation to age, gender, menstrual or menopausal status, as well as possible sexual dysfunction and medicolegal aspects of the abuse of anabolic steroids related to athletic ability. Placental Hormones During pregnancy, the placenta secretes estrogens, progesterone, human chorionic gonadotropin (hCG), and human placental lactogen (hPL). Estrogens and progesterone, which are not specific to pregnancy, are discussed in the preceding sections. In contrast, hCG and hPL are fairly specific to pregnancy, but levels may also be altered in individuals with trophoblastic tumors (e.g., hydatidiform mole, choriocarcinoma) and tumors that ectopically secrete placental hormones. HUMAN CHORIONIC GONADOTROPIN Human chorionic gonadotropin (hCG) is a glycoprotein that is unique to the developing placenta. Its Copyright © 2003 F.A. Davis Company 186 SECTION I—Laboratory Tests presence in blood and urine has been used for decades to detect pregnancy. Tests using rabbits, frogs, and rats, however, have now been replaced by immunologic tests that use antibodies to hCG. Earlier immunologic tests were not always reliable, because the antibody used could cross-react with other glycoprotein hormones such as luteinizing hormone. Furthermore, it was sometimes not possible to obtain reliable results until 4 to 8 weeks after the first missed period. Currently, more sensitive and specific tests use antibody that reacts only with the subunit of hCG, not with other hormones. The most sensitive of the radioimmunoassays for hCG can detect elevated levels within 8 to 10 days after conception, even before the first missed period. Because hCG is associated with the developing placenta, it is secreted at increasingly higher levels during the first 2 months of pregnancy, declines during the third and fourth months, and then remains relatively stable until term. Levels return to normal within 1 to 2 weeks of termination of pregnancy. Human chorionic gonadotropin prevents the normal involution of the corpus luteum at the end of the menstrual cycle and stimulates it to double in size and produce large quantities of estrogen and progesterone. It is also thought to stimulate the testes of the male fetus to produce testosterone and to induce descent of the testicles into the scrotum. INDICATIONS FOR HUMAN CHORIONIC GONADOTROPIN TEST Suspected testicular tumor as indicated by elevated levels Support for diagnosing nonendocrine tumors that produce hCG ectopically (e.g., carcinoma of the stomach, liver, pancreas, and breast; multiple myeloma; and malignant melanoma), as indicated by elevated levels Monitoring for the effectiveness of treatment for malignancies associated with ectopic hCG production, as indicated by decreasing levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Complications and precautions: Relate age, gender, and time of gestation to the test results. HUMAN PLACENTAL LACTOGEN Early detection of pregnancy (i.e., within 8 to 10 days of conception), especially in women with a history of infertility or habitual abortion Prediction of outcome in threatened abortion (levels below 10,000 mIU/mL are highly predictive that abortion will occur) Suspected intrauterine fetal demise or incomplete abortion as indicated by decreased levels56 Suspected hydatidiform mole or choriocarcinoma as indicated by elevated levels Human placental lactogen (hPL), also known as human chorionic somatotropin (hCS), is produced by the placenta but exerts its known effect on the mother. Human placental lactogen causes decreased maternal sensitivity to insulin and causes utilization of glucose, thus increasing the glucose available to the fetus. It also promotes release of maternal free fatty acids for utilization by the fetus. It is also thought that hPL stimulates the action of growth hormone in protein deposition, promotes breast Reference Values Conventional Units SI Units 3 mIU/mL 3 IU/L 8–10 days 5–40 mIU/mL 5–40 IU/L 1 mo 100 mIU/mL 100 IU/L 2 mo 100,000 mIU/mL 100,000 IU/L 4 mo–term 50,000 mIU/mL 50,000 IU/L Nonpregnant women Pregnant women Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 187 Reference Values Conventional Units SI Units 0.5 g/mL Not detected 0.5 g/mL Not detected 5–27 weeks 4.6 g/mL 4.6 mg/L 28–31 weeks 2.4–6.1 g/mL 2.4–6.1 mg/L 32–35 weeks 3.7–7.7 g/mL 3.7–7.7 mg/L 36 weeks–term 5.0–8.6 g/mL 5.0–8.6 mg/L Diabetic at term 10–12 g/mL 10.0–12.0 mg/L Men Women Nonpregnant Pregnant growth and preparation for lactation, and maintains the pregnancy by altering the endometrium. Human placental lactogen rises steadily through pregnancy, maintaining a high plateau during the last trimester. Blood levels of hPL correlate with placental weight and tend to be high in diabetic mothers. Levels also may be elevated in multiple pregnancy and Rh isoimmunization, as well as in nonendocrine tumors that secrete ectopic hPL. During pregnancy, hPL levels vary greatly with the individual as well as on a day-to-day basis. Thus, serial determinations may be necessary with the client serving as her own control.57 INTERFERING FACTORS During pregnancy, hPL levels vary greatly with the individual as well as on a day-to-day basis. Levels tend to be higher in diabetic mothers, multiple gestation, and Rh isoimmunization. INDICATIONS FOR HUMAN PLACENTAL LACTOGEN TEST Detection of placental insufficiency as evidenced by low hPL levels in relation to gestational age Support for diagnosing intrauterine growth retardation caused by placental insufficiency, as indicated by hPL levels of less than 4 g/mL, especially when blood estrogen levels are low Prediction of outcome in threatened abortion as indicated by lower than expected levels for the stage of pregnancy Support for diagnosing hydatidiform mole and choriocarcinoma as indicated by decreased levels Support for diagnosing malignancies associated with elevated levels (e.g., nonendocrine tumors that secrete ectopic hPL) Monitoring for the effectiveness of treatment for malignancies associated with ectopic hPL production as indicated by decreasing levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). The pregnant client should be informed that several determinations may be necessary throughout the pregnancy. THE PROCEDURE A venipuncture is performed and the sample is collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Pancreatic Hormones The islets of Langerhans, the endocrine cells of the pancreas, produce at least three glucose-related hormones: (1) insulin, which is produced by the beta cells; (2) glucagon, which is produced by the alpha cells; and (3) somatostatin, which is produced by the delta cells. The overall effect of insulin is to promote glucose utilization and energy storage. It accomplishes this by enhancing glucose and potassium entry into most body cells, stimulating glycogen synthesis in liver and muscle, promoting the conversion of glucose to Copyright © 2003 F.A. Davis Company 188 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units 8.0–15.0 U/mL or 0.3–0.6 ng/mL 55–104 pmol/L 25–231 U/mL 173–1604 pmol/L 1 hr 18–276 U/mL 125–1916 pmol/L 2 hr 16–166 U/mL 111–1152 pmol/L 3 hr 4–38 U/mL 27–263 pmol/L Insulin-to-glucose ratio 0.3:1 Fasting After 100 g glucose 1 /2 hr fatty acids and triglycerides, and enhancing protein synthesis. It exerts its effects by interacting with cell surface receptors. In contrast to insulin, glucagon increases blood glucose levels by stimulating the breakdown of glycogen and the release of glucose stored in the liver. Somatostatin inhibits secretion of both insulin and glucagon. It also inhibits release of growth hormone, thyroid-stimulating hormone, and adrenocorticotropic hormone by the adenohypophysis and may decrease production of parathormone, calcitonin, and renin. In addition, it is thought to inhibit secretion of gastric acid and gastrin. The exact physiological roles of glucagon and somatostatin are unknown. Blood levels of insulin are measured by radioimmunoassay and can be determined in most laboratories. Samples for blood glucagon levels require special handling, and tests for its presence may not be routinely available in all laboratories. Somatostatin may be measured but this test is not routinely performed. C-peptide, a metabolically inactive peptide chain formed during the conversion of proinsulin to insulin, may be measured to provide an index of -cell activity not affected by exogenous insulin. INSULIN Insulin is secreted by the cells in response to elevated blood glucose, certain amino acids, ketones, fatty acids, cortisol, growth hormone, glucagon, gastrin, secretin, cholecystokinin, gastric inhibitory peptide, estrogen, and progesterone. Because of normal feedback mechanisms, high insulin levels inhibit secretion of insulin. Elevated blood levels of somatostatin, epinephrine, and norepinephrine also inhibit insulin secretion. Abnormally elevated serum insulin levels are seen with insulin- and proinsulin-secreting tumors (insulinomas), with reactive hypoglycemia in developing diabetes mellitus, and with excessive administration of exogenous insulin. A blood glucose level is usually obtained with the serum insulin determination. Serum insulin levels may also be measured when glucose tolerance tests are performed. INTERFERING FACTORS Administration of insulin or oral hypoglycemic agents within 8 hours of the test may lead to falsely elevated levels. Failure to follow dietary restrictions before the test may lead to falsely elevated levels. Therapy with drugs containing estrogen and progesterone may produce elevated levels. INDICATIONS FOR SERUM INSULIN TEST Evaluation of postprandial (“reactive”) hypoglycemia of unknown etiology Support for diagnosing early or developing noninsulin-dependent diabetes mellitus as indicated by excessive production of insulin in relation to blood glucose levels (best demonstrated with glucose tolerance tests or 2-hour postprandial tests) Confirmation of functional hypoglycemia (i.e., no known physiological cause for the hypoglycemia) as indicated by circulating insulin levels appropriate to changing blood glucose levels Evaluation of fasting hypoglycemia of unknown etiology Support for diagnosing insulinoma as indicated by sustained high levels of insulin and absence of blood glucose-related variations Evaluation of uncontrolled insulin-dependent diabetes mellitus Differentiation between insulin-resistant diabetes, in which insulin levels are high, and non-insulinresistant diabetes, in which insulin levels are low Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Support for diagnosing pheochromocytoma as indicated by decreased levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for the related blood glucose test (e.g., fasting blood glucose, glucose tolerance test) with which the serum insulin determination is performed. THE PROCEDURE The general procedure is the same as that for the related blood glucose test. Blood samples for serum insulin determinations are obtained in red-topped tubes and then packed in ice. The samples should be handled gently to avoid hemolysis and sent immediately to the laboratory. Chemistry 189 INDICATIONS FOR C-PEPTIDE TEST Suspected excessive insulin administration in either diabetic or nondiabetic individuals, as indicated by low C-peptide and elevated serum insulin levels Determination of -cell function when insulin antibodies preclude accurate measurement of serum insulin production (Insulin antibodies are most common in diabetic clients receiving exogenous insulin prepared from animal extracts.) Support for diagnosing insulinoma, especially when the tumor secretes more proinsulin than active hormone, because the normal correlation between insulin and C-peptide will be altered NURSING CARE AFTER THE PROCEDURE NURSING CARE BEFORE THE PROCEDURE Care and assessment after the procedure are the same as for the related blood glucose test. Assess the client for signs of hypoglycemia, which may occur in response to fasting or excessive blood glucose load. Resume foods and any medications withheld before the test. Abnormal values: Note and report decreased or increased levels and relation to type I or II diabetes mellitus, respectively, and response to glucose intake. Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). Some laboratories may require that the client fast from food for 8 hours before the test. Critical values: Notify the physician at once if fasting level is greater than 30 U/mL. Prepare client for glucose administration. C-PEPTIDE Measurement of C-peptide, which is accomplished through radioimmunoassay techniques, provides an index of -cell activity that is unaffected by the administration of exogenous insulin. As the cells release insulin, they also release equimolar amounts of metabolically inactive C-peptide. Injectable insulin preparations are purified to remove Cpeptide. Furthermore, injected insulin elevates immunoreactive serum insulin levels and suppresses pancreatic secretion of endogenous insulin and Cpeptide. That is, although exogenous insulin elevates serum insulin levels, C-peptide levels are either unaffected or decreased. C-peptide determinations may be carried out to augment or confirm results of serum insulin measurements.59 THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. The sample also can be tested for insulin measurement. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume usual diet. GLUCAGON Glucagon is secreted by the cells of the islets of Langerhans in response to decreased blood glucose levels. Its actions are opposed by insulin. Elevated glucagon levels are associated with conditions that produce actual hypoglycemia or a physiological need for greater blood glucose (e.g., trauma, infection, starvation, excessive exercise) and with insulin lack. Thus, elevated glucagon levels may be found in severe or uncontrolled diabetes mellitus, despite hyperglycemia. Reference Values Reference Values Conventional Units 0.9–4.2 ng/mL SI Units 0.30–1.39 nmol/L Conventional Units 50–200 pg/mL SI Units 50–200 ng/L Copyright © 2003 F.A. Davis Company 190 SECTION I—Laboratory Tests INTERFERING FACTORS Trauma, infection, starvation, and excessive exercise may lead to elevated levels, as will acute pancreatitis, pheochromocytoma, uncontrolled diabetes mellitus, and uremia. Failure to follow dietary restrictions before the test may lead to falsely decreased levels. INDICATIONS FOR GLUCAGON DETERMINATION Suspected glucagonoma as indicated by elevated levels (as high as 1000 pg/mL) in the absence of diabetic ketoacidosis, uremia, pheochromocytoma, or acute pancreatitis Confirmation of glucagon deficiency related to loss of pancreatic tissue as a result of chronic pancreatitis, pancreatic neoplasm, or surgical resection (Arginine infusion, which normally leads to elevated glucagon levels, may be used for further confirmation of the deficiency state.) Suspected renal transplant rejection, as indicated by rising plasma glucagon levels (Glucagon levels may rise markedly several days before serum creatinine begins to rise.) NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). For this test, the client should fast from foods for 8 hours before the study. Water is permitted. THE PROCEDURE A venipuncture is performed and the sample is collected in either a green- or a lavender-topped tube, depending on the laboratory performing the test. The sample should be handled gently to avoid hemolysis and sent to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Resume usual diet as soon as possible after the sample has been obtained. Complications and precautions: Assess the test results in relation to insulin and glucose levels. Gastric and Intestinal Hormones The stomach and intestine secrete various enzymes and hormones that aid in the digestive process. The hormones secreted include gastrin, cholecystokinin, secretin, and gastric inhibitory peptide (GIP). Of these, only gastrin is currently of diagnostic significance. Gastrin is secreted by the gastrin cells (G cells) of the gastric antrum, the pylorus, and the proximal duodenum in response to vagal stimulation and the presence of food (especially protein) in the stomach. Gastrin stimulates the secretion of acidic gastric juice and pepsin and the release of pancreatic enzymes. It also stimulates motor activities of the stomach and intestine, increases pyloric relaxation, constricts the gastroesophageal sphincter, and promotes the release of insulin. Cholecystokinin is secreted by the duodenal mucosa in response to the presence of fats. It opposes the actions of gastrin, stimulates contraction of the gallbladder, relaxes the sphincter of Oddi, and with secretin, controls pancreatic secretions. Secretin is secreted by the duodenal mucosa in response to the presence of peptides and acids in the duodenum. It also opposes the actions of gastrin, and with cholecystokinin, controls pancreatic secretions. GIP inhibits gastric motility and secretion and stimulates secretion of insulin. GASTRIN Measurement of serum gastrin levels, which is accomplished through radioimmunoassay techniques, is indicated when disorders producing elevated levels are suspected. Excessive gastrin secretion occurs because of normal feedback mechanisms in disorders associated with decreased gastric acid production as a result of cellular destruction or atrophy (e.g., gastric carcinoma and age-related changes in gastric acid secretion). Elevated levels also may be seen in gastric and duodenal ulcers, in which gastric acid secretion is actually normal or low; pernicious anemia; uremia; and chronic gastritis. Decreased gastrin levels are associated with true gastric hyperacidity as may occur with stress ulcers. Both protein ingestion and calcium infusions elevate serum gastrin levels in certain situations. Thus, these substances can be used to provoke gastrin secretion when a single serum determination is inconclusive. In the secretagogue provocation test, a fasting serum gastrin sample is drawn and the client is then given a high-protein test meal. A postprandial blood sample is then obtained. In individuals with duodenal or gastric ulcers, gastrin levels will be markedly higher than in normal persons after protein-stimulated gastrin secretion. Likewise, an infusion of calcium gluconate produces elevated serum gastrin levels in a person with gastrinoma caused by gastrin production by tumor cells. This effect is not seen in individuals with peptic ulcer disease. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 191 ELECTROLYTES Reference Values Conventional Units SI Units Fasting 50–150 pg/mL 50–150 ng/L Postprandial 80–170 pg/mL 80–170 ng/L Note: Postprandial values may vary according to the test method used. INTERFERING FACTORS Protein ingestion and calcium infusions will elevate serum gastrin levels in some situations; these substances may be used for “challenge tests” of gastrin secretion. INDICATIONS FOR SERUM GASTRIN TEST Suspected gastrinoma (Zollinger-Ellison syndrome) as indicated by markedly elevated levels (e.g., greater than 1000 pg/mL) and by marked response to calcium challenge Support for diagnosing gastric carcinoma, pernicious anemia, or G-cell hyperplasia as indicated by elevated levels Differential diagnosis of peptic ulcer disease from other disorders, because gastrin levels may be normal but will rise in response to protein challenge NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any test involving collection of a peripheral blood sample (see Appendix I). For this test, the client should fast from food for 12 hours before the study. Water is not restricted. It also is recommended that medications be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be packed in ice, handled gently to avoid hemolysis, and transported immediately to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Resume usual diet and medications. Complications and precautions: Assess bowel sounds if levels are increased to 100 to 500 pg/mL, which indicates Zollinger-Ellison syndrome associated with peptic ulcer disease. Electrolytes are substances that dissociate into electrically charged ions when dissolved. Cations carry positive charges and anions carry negative charges. Both affect the electrical and osmolal (i.e., the number of particles dissolved in a fluid) functioning of the body. Body fluids always contain equal numbers of positive and negative charges, but the nature of the ions, the number of charges present on a single molecule, and the nature and mobility of the charged molecules differ enormously among body fluid compartments (e.g., intracellular versus extracellular). Not all charged particles are ions. Proteins, for example, carry a net negative charge. Whenever fluid contains protein, there must be accompanying cations. Similarly, not all solutes found in plasma are ions. Urea and glucose, for example, do not dissociate; they do not contribute to electrical activity of fluids and membranes, and they contribute only moderately to plasma osmolality. Electrolyte quantities and the balance among them in the body fluid compartments are controlled by (1) oxygen and carbon dioxide exchange in the lungs; (2) absorption, secretion, and excretion of many substances by the kidneys; and (3) secretion of regulatory hormones by the endocrine glands. Quantitatively, the most important body fluid ions are sodium, potassium, chloride, and bicarbonate. These ions are measured in routine serum electrolyte determinations. Other serum ions that may be measured include calcium, magnesium, and phosphorus.60 SERUM SODIUM Sodium (Na, Na ) is the most abundant cation in extracellular fluid and, along with its accompanying chloride and bicarbonate anions, accounts for 92 percent of serum osmolality. Sodium plays a major role in maintaining homeostasis through a variety of functions, which include (1) maintenance of osmotic pressure of extracellular fluid, (2) regulation of renal retention and excretion of water, (3) maintenance of acid–base balance, (4) regulation of potassium and chloride levels, (5) stimulation of neuromuscular reactions, and (6) maintenance of systemic blood pressure. Serum sodium levels may be affected by a variety of disorders and drugs (Table 5–22) and are evaluated in relation to other serum electrolyte and blood chemistry results. Tests of urinary sodium and osmolality also may be necessary for complete interpretation. Note that falsely decreased serum sodium levels may occur with Copyright © 2003 F.A. Davis Company 192 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units Infants 134–150 mEq/L 134–150 mmol/L Children 135–145 mEq/L 135–145 mmol/L Adults 135–145 mEq/L 135–145 mmol/L Critical values 120 mEq/L or 160 mEq/L 120 mmol/L or 160 mmol/L elevated serum triglyceride levels and myeloma proteins. INTERFERING FACTORS Elevated serum triglyceride levels and myeloma proteins may lead to falsely decreased levels. Adrenocorticosteroids, methyldopa, hydralazine, reserpine, and cough medicines may lead to increased levels. Lithium, vasopressin, and diuretics may lead to decreased levels. INDICATIONS FOR SERUM SODIUM TEST Routine electrolyte screening in acute and critical illness Determination of whole body stores of sodium, because the ion is predominantly extracellular Known or suspected disorder associated with altered fluid and electrolyte balance (see Table 5–22) Estimation of serum osmolality, which is normally 285 to 310 mOsm/kg, by using the following formula, where BUN stands for blood urea nitrogen: Serum osmolality 2(Na ) glucose 20 BUN 3 Note: If the value for serum osmolality is greater than 2.0 to 2.3 times the value for serum sodium, then hyperglycemia, uremia, or metabolic acidosis should be suspected. Evaluation of the effects of drug therapy on serum sodium levels (e.g., diuretic therapy) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum sodium levels, a medication history should be obtained. It is recommended that any drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels. Assess for symptoms associated with hypernatremia, such as fluid deficit with thirst; dry mucous membranes and skin; poor skin turgor; or fluid excess with edema, weight gain, or elevated blood pressure. Administer fluid replacement at an ordered rate and time if the client is dehydrated or if diuretics are administered for fluid excess. Instruct client in a low-sodium diet. Decreased levels: Note and report decreased levels. Assess for symptoms associated with hyponatremia, such as oliguria, rapid pulse, abdominal cramping, fluid retention, weight gain, edema, or elevated blood pressure. Administer ordered sodium replacement via IV or dietary intake. Instruct client in sodium intake (food, salt tablets) to replace and maintain sodium, especially if this electrolyte is lost because of vomiting, diarrhea, perspiration, or use of diuretics. Critical values: Notify the physician at once of levels less than 120 mEq/L or greater than 160 mEq/L. SERUM POTASSIUM Potassium (K, K ) is the most abundant intracellular cation; much smaller amounts are found in the blood. Potassium is essential for the transmission of electrical impulses in cardiac and skeletal muscle. In addition, it helps to maintain the osmolality and electroneutrality of cells, functions in enzyme reactions that transform glucose into energy and amino Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–22 • Chemistry 193 Disorders and Drugs Associated with Altered Serum Sodium and Extracellular Fluid Levels Increased Serum Sodium (Hypernatremia) Decreased Serum Sodium (Hyponatremia) Total Body Sodium Normal, ECF Volume Low Total Body Sodium and ECF Volume Low, but Total Body Sodium Proportionately Lower Hypovolemia Addison’s disease Dehydration Salt-losing renal disorders Fever Gastrointestinal fluid loss (nasogastric suction, vomiting, diarrhea, fistula, paralytic ileus) Thyrotoxicosis Diaphoresis Hyperglycemic hyperosmolar nonketotic syndrome Diuresis Diabetes insipidus Burns Hyperventilation Ascites Mechanical ventilation without humidification Massive pleural effusion Diabetes ketoacidosis Total Body Sodium Increased Proportionately More Than ECF Volume Total Body Sodium Normal and ECF Volume Normal to High Excessive salt ingestion Acute water intoxication Inappropriate or incorrect intravenous therapy with fluids containing sodium Syndrome of inappropriate antidiuretic hormone secretion Cushing’s syndrome Glucocorticoid deficiency Hyperaldosteronism Severe total body potassium depletion Total Body Sodium Low with ECF Volume Proportionately Lower Total Body Sodium and ECF Volume Increased, but ECF Proportionately Greater Gastroenteritis Acute renal failure with water overload Osmotic diuresis Congestive heart failure Diaphoresis Cirrhosis Nephrotic syndrome Drugs Drugs Adrenocorticosteroids Lithium carbonate Methyldopa (Aldomet) Vasopressin Hydralazine (Apresoline) Diuretics (thiazides, mannitol, ethacrynic acid, furosemide) Reserpine (Serpasil) Cough medicines Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 401, with permission. acids into proteins, and participates in the maintenance of acid–base balance. Numerous disorders and drugs can affect serum potassium levels. As shown in Table 5–23, the clinical problems associated with altered serum potas- sium levels may be categorized as (1) inappropriate cellular metabolism, (2) altered renal excretion, and (3) altered potassium intake. False elevations in serum potassium can occur with vigorous pumping of the hand after tourniquet application for Copyright © 2003 F.A. Davis Company 194 SECTION I—Laboratory Tests venipuncture, in hemolyzed samples, or with high platelet counts during clotting. Falsely decreased levels are seen in anticoagulated samples left at room temperature. Altered serum potassium levels are of particular concern because of their effects on cardiac impulse conduction, especially when the client also is taking medications that affect cardiac conduction. The combination of low serum potassium (hypokalemia) and therapy with digitalis preparations, for example, can produce serious consequences because of increased ventricular irritability. Note also that potassium is a very changeable ion, moving easily between intracellular and extracellular TABLE 5–23 • fluids. An example is seen in states of acidosis and alkalosis. In acidosis (decreased serum pH), potassium moves from the cells into the blood; in alkalosis (increased serum pH), the reverse occurs. INTERFERING FACTORS False elevations may occur with vigorous pumping of the hand after tourniquet application for venipuncture, in hemolyzed samples, or with high platelet counts during clotting. Falsely decreased levels are seen in anticoagulated samples left at room temperature. Numerous drugs may produce elevated and decreased levels (see Table 5–23). Disorders and Drugs Associated with Altered Serum Potassium Levels Increased Serum Potassium (Hyperkalemia) Decreased Serum Potassium (Hypokalemia) Inappropriate Cellular Metabolism Inappropriate Cellular Metabolism Acidosis Alkalosis Insulin deficiency Insulin excess Hypoaldosteronism Familial periodic paralysis Cell necrosis (trauma, burns, hemolysis, antineoplastic therapy) Rapid cell generation (leukemia, treated megaloblastic anemia) Addison’s disease Chronic excessive licorice ingestion Decreased Renal Excretion Increased Excretion Acute renal failure Gastrointestinal loss (vomiting, diarrhea, nasogastric suction, fistula) Chronic interstitial nephritis Excessive diuresis Tubular unresponsiveness to aldosterone Hyperaldosteronism Hypoaldosteronism Laxative abuse Hypomagnesemia Renal tubular acidosis Diaphoresis Thyrotoxicosis Cushing’s syndrome Increased Potassium Intake Decreased Potassium Intake Salt substitutes Anorexia nervosa Potassium supplements (oral or IV) Diet deficient in meat and vegetables Potassium salts of antibiotics Clay eating (binds potassium and prevents absorption) Transfusion of old banked blood IV therapy with inadequate potassium supplementation Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–23 • Chemistry 195 Disorders and Drugs Associated with Altered Serum Potassium Levels Increased Serum Potassium (Hyperkalemia) Decreased Serum Potassium (Hypokalemia) Drugs Drugs Aldosterone antagonists Furosemide Potassium preparations of antibiotics Ethacrynic acid Amphotericin B Thiazide diuretics Tetracycline Insulin Heparin Aspirin Epinephrine Prednisone Marijuana Cortisone Isoniazid Gentamicin Polymyxin B Lithium carbonate Sodium polystyrene sulfonate (Kayexalate) Ammonium chloride Aldosterone Laxatives Adapted from Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p. 402, with Permission. Reference Values Conventional Units SI Units Infants 4.1–5.3 mEq/L 4.1–5.3 mmol/L Children 3.4–4.7 mEq/L 3.4–4.7 mmol/L Adults 3.5–5.0 mEq/L 3.5–5.0 mmol/L Critical values 2.5 mEq/L or 6.5 mEq/L 2.5 mmol/L or 6.5 mmol/L INDICATIONS FOR SERUM POTASSIUM TEST Routine electrolyte screening in acute and critical illness Known or suspected disorder associated with altered fluid and electrolyte balance, especially renal disease, disorders of glucose metabolism, trauma, and burns (see Table 5–23) Known or suspected acidosis of any etiology, because potassium moves from the cells into the blood in acidotic states Evaluation of cardiac dysrhythmias to determine whether altered serum potassium level is contributing to the problem (e.g., the combination of low serum potassium and therapy with digitalis preparations may lead to ventricular irritability) Evaluation of the effects of drug therapy (e.g., diuretics) on serum potassium levels Evaluation of response to treatment for abnormal serum potassium levels Nursing Alert Because of the effects of serum potassium levels on cardiac impulse conduction, abnormal values should be reported to the physician immediately so that treatment may be instituted. Copyright © 2003 F.A. Davis Company 196 SECTION I—Laboratory Tests NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum potassium levels, a medication history should be obtained. It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. Vigorous pumping of the hand after tourniquet application should be avoided, because it may lead to falsely elevated results. The sample should be handled gently to avoid hemolysis, which may also falsely elevate results, and transported immediately to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels. Assess for symptoms associated with hyperkalemia such as oliguria, irritability, diarrhea, and ECG tracings for peaked T waves. Assess results of arterial blood gases (ABGs). Prepare client for IV administration of medications (sodium bicarbonate for acidosis, calcium gluconate if calcium level is low) or oral or enema administration of sodium polystyrene sulfonate. Instruct client in low potassium dietary intake and food restrictions (citrus juices, bananas, dried fruits, potatoes, and tomatoes). Decreased levels: Note and report decreased levels. Assess for symptoms of hypokalemia such as thirst, vomiting, anorexia, weak pulse, decreased blood pressure, ECG tracings for depressed T waves, or prominent U waves. Administer oral or IV potassium replacement. Instruct client in foods high in potassium, as already listed. Critical values: Notify the physician at once of levels less than 2.5 mEq/L or greater than 6.5 mEq/L (greater than 8.1 mEq/L in infants). SERUM CHLORIDE Chloride (Cl, Cl2) is the most abundant anion in extracellular fluid. It participates with sodium in the maintenance of water balance and aids in the regulation of osmotic pressure. It also contributes to gastric acid (HCl) for digestion and for activation of enzymes. Its most important function is in the maintenance of acid–base balance. In certain forms of metabolic acidosis, for example, serum chloride levels may rise in response to decreased serum bicarbonate levels; this condition is known as hyperchloremic acidosis. If bicarbonate levels fall and serum chloride concentration remains relatively normal, however, a gap between measured cations (i.e., sodium and potassium) and measured anions (i.e., chloride and bicarbonate) occurs. This condition often is called anion gap acidosis (see also section titled “Anion Gap,” which follows). Chloride also helps to maintain acid–base balance through the chloride-bicarbonate shift mechanism, in which chloride ions enter red blood cells in exchange for bicarbonate. Bicarbonate leaves the red blood cells in response to carbon dioxide, which is released from the tissues into venous blood and absorbed into the red blood cells. The carbon dioxide is subsequently converted into carbonic acid, which dissociates into bicarbonate and hydrogen ions. When the bicarbonate concentration in the red blood cells exceeds that of the plasma, bicarbonate diffuses into the blood, and chloride enters the red blood cells to supply the anions necessary for electroneutrality. For this reason, the chloride content of red blood cells in venous blood is slightly higher than that of arterial red blood cells. Numerous disorders and drugs may alter serum chloride levels (Table 5–24). INTERFERING FACTORS Drugs such as potassium chloride, ammonium chloride, acetazolamide (Diamox), methyldopa (Aldomet), diazoxide (Hyperstat), and guanethidine (Ismelin) may lead to elevated levels. Drugs such as ethacrynic acid (Edecrin), furosemide (Lasix), thiazide diuretics, and bicarbonate may lead to decreased levels. INDICATIONS FOR SERUM CHLORIDE TEST Routine electrolyte screening in acute and critical illness Known or suspected disorder associated with altered acid–base or fluid and electrolyte balance, or both conditions Support for diagnosing disorders associated with altered serum chloride levels (see Table 5–24) Differentiation of the type of acidosis (hyperchloremic versus anion gap acidosis), with serum chloride levels remaining relatively normal in anion gap acidosis Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–24 • Chemistry 197 Disorders and Drugs Associated with Altered Serum Chloride Levels Increased Serum Chloride (Hyperchloremia) Decreased Serum Chloride (Hypochloremia) DISORDERS Acidosis Alkalosis Hyperkalemia Hypokalemia Hypernatremia Hyponatremia Dehydration Gastrointestinal loss (vomiting, diarrhea, nasogastric suction, fistula) Eclampsia Renal failure (severe) Diuresis Congestive heart failure Hypoventilation (especially due to chronic obstructive pulmonary disease) Hyperventilation (especially due to neurogenic hyperventilation related to head injury) Acute infections Cushing’s syndrome Burns Hyperaldosteronism Heat stroke Anemia Fever Hypoproteinemia Diabetic ketoacidosis Serum sickness Pyelonephritis Hyperparathyroidism Addisonian crisis Excessive dietary salt Starvation Jejunoileal bypass Inadequate chloride intake Gastric carcinoma DRUGS Potassium chloride Ethacrynic acid (Edecrin) Ammonium chloride Furosemide (Lasix) Acetazolamide (Diamox) Thiazide diuretics Methyldopa (Aldomet) Bicarbonate Diazoxide (Hyperstat) Guanethidine (Ismelin) Reference Values Conventional Units SI Units Newborns 94–112 mEq/L 94–112 mmol/L Infants 95–110 mEq/L 95–110 mmol/L Children 98–105 mEq/L 98–105 mmol/L Adults 95–105 mEq/L 95–105 mmol/L Critical values 80 mEq/L or 115 mEq/L 80 mmol/L or 115 mmol/L Copyright © 2003 F.A. Davis Company 198 SECTION I—Laboratory Tests Evaluation of the effects of drug therapy on serum chloride levels (see Table 5–24) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum chloride levels, a medication history should be obtained. It is recommended that those drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. kidneys regulate both the generation of bicarbonate ions and their rate of urinary excretion. Bicarbonate also participates with chloride in the bicarbonatechloride shift mechanism involving red blood cells. Measurement of serum bicarbonate ion concentration may be made directly or indirectly by means of total CO2 content, because more than 90 percent of blood CO2 exists in the ionized bicarbonate form. Bicarbonate also is measured as part of blood gas determinations. Numerous disorders, especially those involving acid–base imbalance, and drugs are associated with altered serum bicarbonate levels (Table 5–25). THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels (hyperchloremia) in relation to increased sodium and decreased bicarbonate, and assess for changes in chloride caused by or resulting in metabolic acidosis. Decreased levels: Note and report decreased levels (hypochloremia). Assess for possible cause (vomiting, gastric suction, diarrhea, diuretic medication regimen, chronic lung disease, increased bicarbonate and decreased potassium resulting in metabolic alkalosis). Critical values: Notify the physician at once of levels less than 80 mEq/L or greater than 115 mEq/L. SERUM BICARBONATE Bicarbonate (HCO3, HCO3–) is the major extracellular buffer in the blood; it functions with carbonic acid (H2CO3) in maintaining acid–base balance. Normally, the ratio of bicarbonate to dissolved carbon dioxide (CO2), which derives from H2CO3, is 20:1. If this ratio is altered, acid–base imbalance occurs. Additional CO2, for example, causes increased acidity (falling pH), whereas loss of CO2 produces alkalinity (rising pH). Similarly, additional bicarbonate leads to alkalosis, whereas loss of bicarbonate produces acidosis. The lungs control regulation of CO2 levels. Bicarbonate levels are under renal control; the ANION GAP The results of serum levels of sodium, potassium, chloride, and bicarbonate may be used to calculate the anion gap. The anion gap refers to the normal discrepancy between unmeasured (i.e., those not routinely measured) cations and anions in the blood. Unmeasured anions include the negative charges contributed by serum proteins and those of phosphates, sulfates, and other metabolites. Unmeasured anions normally total about 24 mEq/L. Cations not routinely measured include calcium and magnesium, and together they account for about 7 mEq/L. Because there are normally more unmeasured anions than cations, the difference between the two is called the anion gap. This is normally 12 to 18 mEq/L. The anion gap can be determined by subtracting the sum of routinely measured anions, chloride and bicarbonate, from the sum of routinely measured cations, sodium and potassium (i.e., [Na K] – [Cl HCO3]). The concept of anion gap allows consideration of metabolic derangements without measuring specific metabolites. An increase in the anion gap is seen in acidotic states in which there is no compensatory rise in chloride levels. Examples of anion gap acidosis include diabetic ketoacidosis, lactic acidosis caused by either tissue hypoxia (type A) or renal or hepatic metabolic defect (type B), and excessive alcohol ingestion.61 INTERFERING FACTORS Numerous drugs may alter serum bicarbonate levels (see Table 5–25). INDICATIONS FOR SERUM BICARBONATE TEST Routine electrolyte screening in acute and critical illness Known or suspected disorder associated with altered acid–base or fluid and electrolyte balance, or both Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–25 • Chemistry 199 Disorders and Drugs Associated with Altered Serum Bicarbonate Levels Increased Serum Bicarbonate Decreased Serum Bicarbonate DISORDERS Metabolic alkalosis Metabolic acidosis Compensated metabolic alkalosis Compensated metabolic acidosis Respiratory acidosis (slightly elevated or normal) Respiratory alkalosis (slightly low or normal) Compensated respiratory acidosis Compensated respiratory alkalosis Hypoventilation Hyperventilation Chronic obstructive pulmonary disease Diarrhea Vomiting Dehydration Nasogastric suction Severe malnutrition Diuresis Burns Aldosteronism Myocardial infarction Congestive heart failure Acute ethanol intoxication Hypokalemia Shock Cushing’s syndrome Renal disease Pulmonary edema Hyperthyroidism Milk-alkali syndrome DRUGS Aldosterone Triamterene (Dyrenium) Adrenocorticotropic hormone Acetazolamide (Diamox) Sodium bicarbonate abuse Calcium chloride Adrenocorticosteroids Ammonium chloride Viomycin Salicylate toxicity Thiazide diuretics Paraldehyde Sodium citrate Reference Values Conventional Units SI Units Peripheral vein 19–25 mEq/L 19–25 mmol/L Arterial sample 22–26 mEq/L 22–26 mmol/L Critical values 15 mEq/L or 35 mEq/L 15 mmol/L or 35 mmol/L Support for diagnosing disorders associated with altered serum bicarbonate levels (see Table 5–25) Determination of the degree of compensation in acidotic and alkalotic states (Table 5–26) Evaluation of the effects of drug therapy on serum bicarbonate levels NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum bicarbonate Copyright © 2003 F.A. Davis Company 200 SECTION I—Laboratory Tests TABLE 5–26 • Blood Gases in Acid–Base Imbalance pH pCO2 HCO3 Base Excess (BE) ↓ ↑ Normal Normal Sl ↓ or normal ↑ ↑ ↑ Normal Normal ↓ ↓ Normal ↓ ↓ Sl ↓ or normal ↓ ↓ ↓ ↑ Normal ↑ ↑ Sl ↑ or normal ↑ ↑ ↑ ↓ ↑ ↓ ↓ Respiratory acidosis with compensation ↑ Respiratory alkalosis with compensation Sl ↑ or normal ↓ ↓ ↓ Metabolic acidosis with compensation Metabolic alkalosis with compensation Mixed respiratory and metabolic acidosis Sl slightly. levels, a medication history should be obtained. It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels or base excess in relation to hypokalemia and hypochloremia. Assess for vomiting, presence of gastric suctioning, diuretic therapy, or excessive intake of oral bicarbonate (baking soda, antacids). Assess for respiratory changes, tingling in fingers, or more severe muscular irritability symptoms. Assess for cardiac dysrhythmias if hypokalemia is present. Administer ordered oral or IV electrolyte replacement (potassium, chloride). Administer fluids (juices, broth) to replace electrolytes if decreases are not extreme. Decreased levels: Note and report decreased levels or base deficit in relation to other electrolytes. Assess gastrointestinal losses such as vomiting leading to acidosis and diarrhea leading to alkalosis, I&O, metabolic acidosis with change in respirations (Kussmaul’s breathing), confusion, or lethargy. Prepare for IV sodium bicarbonate. Monitor I&O closely to prevent fluid and electrolyte imbalance. Critical values: Notify the physician at once of levels less than 15 mEq/L or greater than 35 mEq/L. SERUM CALCIUM Calcium (Ca, Ca ) is the most abundant cation in the body and participates in virtually all vital processes. About half the total amount of calcium circulates as free ions that participate in blood coagulation, neuromuscular conduction, intracellular regulation, glandular secretion, and control of skeletal and cardiac muscle contractility. The remaining calcium is bound to circulating proteins and plays no physiological role. Serum calcium measurement includes both ionized and protein-bound calcium. Calcium ions undergo continuous turnover, with bone serving as the major reservoir. Serum contains only a small amount at any one time, but the serum level reflects overall calcium metabolism. Calcium levels are largely regulated by the parathyroid glands and vitamin D. Other substances affecting calcium levels include estrogens and androgens, calcitonin, and ingested carbohydrates. Increased or decreased serum proteins also may affect levels of proteinbound calcium.62 Table 5–27 shows the various disorders and drugs associated with altered calcium levels. Abnormal serum calcium may produce cardiac dysrhythmias. Furthermore, serum calcium levels have a reciprocal relationship with serum phosphate levels; if one rises, the other tends to fall. Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–27 • Chemistry 201 Disorders and Drugs Associated with Altered Serum Calcium Levels Increased Levels (Hypercalcemia) Decreased Levels (Hypocalcemia) DISORDERS Acidosis Alkalosis Hyperparathyroidism Hypoparathyroidism Cancers involving bone Pseudohypoparathyroidism Paget’s disease of bone Inadequate dietary intake of calcium and/or vitamin D Prolonged immobility Vitamin D–resistant rickets Leukemia Malabsorption syndromes Multiple myeloma Hypoproteinemia Lymphomas Laxative abuse Hyperproteinemia Acute pancreatitis Polycythemia vera Burns Bone growth or active bone formation Osteomalacia Vitamin D intoxication Peritonitis Hyperthyroidism (severe) Pregnancy Milk-alkali syndrome Overwhelming infections Hypomagnesemia Renal failure Phosphate excess DRUGS Thiazide diuretics Barbiturates Hormones (androgens, progestins, estrogens) Anticonvulsants Vitamin D Acetazolamide (Diamox) Calcium supplements Adrenocorticosteroids Cytotoxic drugs INTERFERING FACTORS Values are higher in children because of growth and active bone formation. Numerous drugs may alter serum calcium levels (see Table 5–27). Increased or decreased serum protein levels may alter results. INDICATIONS FOR SERUM CALCIUM TEST Evaluation of the effects of various disorders on overall calcium metabolism, especially diseases involving bone (see Table 5–27) Detection of parathyroid gland loss after thyroid or other neck surgery, as indicated by decreased levels Monitoring of the effects of renal failure on calcium levels, which are usually decreased in the disorder Evaluation of cardiac dysrhythmias to determine whether altered serum calcium level is contributing to the problem Evaluation of coagulation disorders to determine whether altered serum calcium level is contributing to the problem Monitoring for the effects of various drugs on serum calcium levels (see Table 5–27) Evaluation of the effectiveness of treatment for Copyright © 2003 F.A. Davis Company 202 SECTION I—Laboratory Tests Reference Values Conventional Units Newborns SI Units 7.0–11.5 mg/dL 1.75–2.90 mmol/L 3.7–7.0 mEq/L Infants 8.6–11.2 mg/dL 2.15–2.80 mmol/L 5.0–6.0 mEq/L Children 12.0 mg/dL 3 mmol/L 6.0 mEq/L Adults 9–11 mg/dL 2.25–2.75 mmol/L 4.5–5.5 mEq/L Critical values 6 mg/dL or 13 mg/dL abnormal calcium levels, especially in deficiency states Nursing Alert Because altered serum calcium levels may produce cardiac dysrhythmias, abnormal values should be reported to the physician immediately so that treatment may be instituted. NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum calcium levels, a medication history should be obtained. It is recommended that drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels. Assess for symptoms associated with hypercalcemia such as muscle relaxation, bone pain, 1.5 mmol/L or 3.25 mmol/L nausea and vomiting, or increased intake of dietary calcium. Encourage fluid intake. Instruct client to restrict foods and medications high in calcium (milk and other dairy foods, eggs, some antacids). Decreased levels: Note and report decreased levels. Assess for symptoms associated with hypocalcemia such as muscular irritability (tingling in fingers and around mouth, muscle cramping or twitching, facial spasm or Chvostek’s sign, carpopedal spasm or Trousseau’s sign, and tetany). Instruct client to eat foods and fluids high in calcium. Administer oral calcium supplement or replacement; prepare for IV calcium replacement in more severe cases. Critical values: Notify the physician at once of levels less than 6 mg/dL or greater than 13 mg/dL. SERUM PHOSPHORUS/PHOSPHATE Phosphorus (P), the dominant intracellular anion, is measured in serum as phosphate (HPO4– –, H2PO4–). Results are reported as inorganic phosphorus (Pi). Phosphates are vital constituents of nucleic acids, intracellular energy storage compounds, intermediary compounds in carbohydrate metabolism, and various regulatory compounds, including that which modulates dissociation of oxygen from hemoglobin. Phosphorus also aids in regulation of calcium levels and functions as a buffer in the maintenance of acid–base balance. It contributes to the mineralization of bones and teeth, promotes renal tubular reabsorption of glucose, and, as a component of phospholipids, aids in fat transport. As with calcium, phosphorus ions undergo continuous turnover, with bone serving as the major Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–28 • Chemistry 203 Disorders and Drugs Associated with Altered Serum Phosphorus/Phosphate Increased Levels (Hyperphosphatemia) Decreased Levels (Hypophosphatemia) DISORDERS Diabetic ketoacidosis Recovery phase of diabetic ketoacidosis Renal failure Renal tubular acidosis Vitamin D intoxication Hypocalcemia Hypercalcemia Vitamin D deficiency Prolonged immobilization Hyperparathyroidism Hypoparathyroidism Carbohydrate ingestion Pseudohypoparathyroidism Malnutrition Bone growth or active bone formation Malabsorption syndromes Hyperthyroidism Hypothyroidism Acromegaly Hypopituitarism Sarcoidosis Alcoholism Pyloric obstruction Prolonged vomiting and diarrhea Milk-alkali syndrome DRUGS Sodium phosphate Acetazolamide (Diamox) Heparin Aluminum hydroxide Phenytoin (Dilantin) Insulin Posterior pituitary injection (Pituitrin) Epinephrine Androgens Reference Values Conventional Units SI Units Infants 4.5–6.7 mg/dL 1.45–2.16 mmol/L Children 4.5–5.5 mg/dL 1.45–1.78 mmol/L Adults 2.4–4.7 mg/dL 0.78–1.50 mmol/L Critical values 1 mg/dL 0.32 mmol/L Note: Phosphorus is measured in terms of phosphate; the results cannot be expressed in milliequivalents because different phosphate groups have different valences. reservoir. Serum contains a relatively small amount of phosphorus at any given time. Phosphorus levels are largely regulated by the parathyroid glands and vitamin D, and they are normally reciprocal to those of serum calcium. The equilibrium between serum phosphate levels and intracellular stores is affected by carbohydrate metabolism and blood pH. When persons with diabetic ketoacidosis are treated with insulin, for example, phosphate enters the cells along with glucose and potassium. Phosphate excretion is controlled by the kidneys. Disorders and drugs associated with altered phosphorus levels are listed in Table 5–28. Note that several disorders associated with decreased phosphorus levels are the same as those causing elevated serum calcium levels (e.g., hyperparathyroidism). Copyright © 2003 F.A. Davis Company 204 SECTION I—Laboratory Tests INTERFERING FACTORS Phosphate levels are higher in children because of bone growth and active bone formation. Values vary diurnally, being higher at night than in the morning. A number of drugs may alter serum phosphate levels (see Table 5–28). Hemolysis of the sample may cause falsely elevated values resulting from release of phosphate from red blood cells. INDICATIONS FOR SERUM PHOSPHORUS/PHOSPHATE TEST Support for diagnosing disorders associated with altered phosphorus/phosphate levels, especially bone disorders, parathyroid disorders, renal disease, and alcoholism (see Table 5–28) Monitoring of the effects of renal failure on phosphorus levels, which are usually increased in the disorder Support for identification of the cause of growth abnormalities in children Monitoring for the effects of various drugs on serum phosphate levels (see Table 5–28) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Because many drugs may alter serum phosphorus/phosphate levels, a medication history should be obtained. It is recommended that any drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis, which may falsely elevate levels, and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels (hyperphosphatemia) and associated calcium levels. Instruct client to avoid foods high in phosphorus (milk and dairy products, poultry, fish, grain cereals). Decreased levels: Note and report decreased levels (hypophosphatemia) in relation to calcium levels. Instruct client to include foods and fluids high in phosphorus, as already listed. Critical values: Notify the physician at once of levels less than 1 mg/dL. SERUM MAGNESIUM Magnesium (Mg, Mg ) is an essential nutrient found in bone and muscle. In the blood, magnesium is most abundant in the red blood cells, with relatively little found in the serum. Magnesium functions in (1) control of sodium, potassium, calcium, and phosphorus; (2) utilization of carbohydrates, lipids, and proteins; and (3) activation of enzyme systems that enable B vitamins to function. Magnesium also increases intestinal absorption of calcium and is required for bone and cartilage formation. It is essential for oxidative phosphorylation, nucleic acid synthesis, and blood clotting. Magnesium is so abundant in foods that dietary deficiency is rare. Decreased serum magnesium levels are seen, however, in chronic alcoholism. Elevated levels most commonly occur in renal failure. A variety of other disorders and drugs also are associated with altered magnesium levels (Table 5–29). Altered magnesium levels are associated with cardiac dysrhythmias, especially decreased levels, which may lead to excessive ventricular irritability. INTERFERING FACTORS A number of drugs may alter serum magnesium levels (see Table 5–29). Because magnesium is found in red blood cells, hemolysis of the sample may lead to falsely elevated values. INDICATIONS FOR SERUM MAGNESIUM TEST Determination of magnesium balance in renal failure and chronic alcoholism Evaluation of known or suspected disorders associated with altered magnesium levels (see Table 5–29) Evaluation of cardiac dysrhythmias to determine whether altered serum magnesium level is contributing to the problem (i.e., decreased magnesium levels may lead to excessive ventricular irritability) Monitoring of the effects of various drugs on serum magnesium levels (see Table 5–29) NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–29 • Chemistry Disorders and Drugs Associated with Altered Serum Magnesium Levels Increased Levels (Hypermagnesemia) Decreased Levels (Hypomagnesemia) DISORDERS Addison’s disease Hyperaldosteronism Adrenalectomy Hypokalemia Renal failure Hypocalcemia Diabetic ketoacidosis Diabetic ketoacidosis (resolving) Dehydration Alcoholism, cirrhosis Hypothyroidism Hyperthyroidism Hyperparathyroidism Hypoparathyroidism Acute pancreatitis Gastrointestinal loss (vomiting, diarrhea, nasogastric suction, fistula) Malabsorption syndromes Malnutrition Nephrotic syndrome Toxemia of pregnancy High-phosphate diet DRUGS Antacids and laxatives containing magnesium Thiazide diuretics Salicylates Ethacrynic acid (Edecrin) Lithium carbonate Calcium gluconate Amphotericin B Neomycin Insulin Aldosterone Ethanol Reference Values Conventional Units SI Units Newborns 1.4–2.9 mEq/L 0.58–1.19 mmol/L Children 1.6–2.6 mEq/L 0.65–1.07 mmol/L Adults 1.5–2.5 mEq/L 0.61–1.03 mmol/L 1.8–3.0 mg/dL 0.74–1.23 mmol/L 1 mg/dL or 4.9 mg/dL 0.41 or 2.02 mmol/L Critical values 205 Copyright © 2003 F.A. Davis Company 206 SECTION I—Laboratory Tests Because many drugs may alter serum magnesium levels, a medication history should be obtained. It is recommended that those drugs that may alter test results be withheld for 12 to 24 hours before the test, although this practice should be confirmed with the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis, which may falsely elevate levels, and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels. Assess for symptoms associated with hypermagnesemia, such as a decrease in muscle activity, which can affect respiration and lead to respiratory arrest and coma. Instruct client to avoid foods high in magnesium (meats, fish, whole grains, green vegetables) and medications containing magnesium (antacids or laxatives). Decreased levels: Note and report decreased levels. Assess for symptoms of hypomagnesemia, such as weakness, tremors, paresthesia, and tetany, which can lead to convulsions. Assess for decreases in potassium, sodium, and calcium. Administer ordered magnesium replacement. Instruct client to eat foods high in magnesium, as already listed. Critical values: Notify the physician at once of levels less than 1.0 mg/dL or greater than 4.9 mg/dL. SERUM OSMOLALITY Osmolality refers to the concentration of solutes in plasma or serum (particle number) or in urine (number of particles). Osmolality affects the movement of fluids across body membranes and the kidney’s ability to concentrate or dilute the urine. Dehydration causes an increase in osmolality, and overhydration causes a decrease. Increased osmolality causes an increase in antidiuretic hormone (ADH) secretion, which results in increased reabsorption of water by the kidneys, increased concentration in urine, and decreased concentration in serum. This lower concentration in serum osmolality normally reduces ADH secretion, which then decreases water reabsorption by the kidneys and excretion of diluted urine. Urine is normally more concentrated than plasma; the ratio of urine to serum osmolality ranges from 1:1 to 3:1 in normal states. A decrease in the 1:1 ratio is seen in fluid overload or in diabetes insipidus, and a ratio that does not rise above 1.2:1.0 indicates a loss of renal concentration function.63 Serum osmolality is mostly used to monitor fluid and electrolyte balance; urine osmolality is used to monitor the concentrating ability of the kidneys and fluid and electrolyte balance. Decreased levels in serum osmolality are seen in fluid excess or overhydration, hyponatremia, and syndrome of inappropriate ADH (SIADH) secretion. Decreased levels in urine osmolality are seen in diabetes insipidus, excess fluid intake or overhydration, hypokalemia, hypercalcemia, and severe renal disease. Increased levels in serum osmolality are seen in dehydration, hypercalcemia, hypernatremia, hyperglycemia, diabetes insipidus, ketosis, severe renal disease, alcohol ingestion, and mannitol therapy. Increased levels in urine osmolality are seen in Addison’s disease, SIADH, hypernatremia, shock or acidotic states, and CHF. INTERFERING FACTORS A delay of longer than 10 hours in testing the specimen can affect test results. Osmotic diuretics and mineralocorticoids can affect test results. Improper technique such as tourniquet in place for an extended time can cause hemostasis. INDICATIONS FOR SERUM OSMOLALITY TEST Screening for alcohol ingestion revealed by increase in osmolality level as the alcohol level in the blood is increased Reference Values Conventional Units SI Units Children 270–290 mOsm/kg 270–290 mmol/kg Adults 280–300 mOsm/kg 280–300 mmol/kg Critical values 240 mOsm or 360 mOsm 240 or 360 mmol/kg Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Monitoring fluid and electrolyte balance (especially sodium) and determining a state of dehydration or overhydration Evaluating ADH secretion or suppression Monitoring IV fluid replacement therapy to prevent fluid excess or overload Evaluating the effect of renal dialysis therapy and course of renal failure NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample (see Appendix I). Obtain a history of conditions affecting renal function, a medication regimen, and the results of an electrolyte panel. Any medications that may affect test results should be withheld, although this practice should be confirmed with the person ordering the study. Inform the client that a urine specimen can be collected, tested, and compared with the results of the blood test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis or hemostasis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume any medications withheld before the test. Increased levels: Note and report increased levels. Assess for symptoms associated with dehydration, such as thirst, dry skin and mucous membranes, and poor skin turgor. Assess relationship to urine osmolality and electrolyte panel. Prepare to increase fluid intake orally or IV. Decreased levels: Note and report decreased levels. Assess for symptoms associated with overhydration such as edema, weight gain, dyspnea, cough, and venous distention. Assess relationship to urine osmolality and electrolyte panel. Administer ordered medications such as diuretic therapy. Critical values: Notify physician at once of levels less than 240 mOsm or greater than 360 mOsm. ARTERIAL BLOOD GASES Arterial blood gas (ABG) determinations are made not only to determine levels of actual blood gases (i.e., oxygen and carbon dioxide) but also to assess Chemistry 207 the client’s overall acid–base balance. Thus, ABG levels may indicate hypoxia, hypercapnia or hypocapnia, acidosis, alkalosis, and physiological compensation for acid–base imbalance. The components of an ABG determination are as follows: 1. pH reflects the number of hydrogen ions in the body and is influenced primarily by the ratio of bicarbonate ions (HCO3–) to carbonic acid (H2CO3), which is essentially carbon dioxide (CO2), in the blood. The normal HCO3–-toCO2 ratio is 20:1. When the hydrogen ion concentration increases (acidosis), the pH falls; when the hydrogen ion concentration decreases (alkalosis), the pH rises. Bicarbonate levels are regulated by the kidneys, whereas carbon dioxide levels are controlled by the lungs. Both the lungs and the kidneys respond to alterations in pH levels by either retaining or excreting carbon dioxide and bicarbonate, respectively. 2. pO2 indicates the partial pressure of oxygen in the blood. When oxygen levels are lower than normal, the client is hypoxic. Hypoxemia may be caused by either low cardiac output or impaired lung function. 3. pCO2 indicates the partial pressure of carbon dioxide in the blood, which is regulated by the lungs. Except in cases of compensation for metabolic acid–base imbalances, elevated levels (hypercapnia, hypercarbia) indicate impaired gas exchange in the lungs so that excess CO2 is not eliminated. Decreased levels (hypocapnia, hypocarbia) indicate increased loss of CO2 through the lungs (hyperventilation). 4. HCO3– indicates the bicarbonate ion concentration in the blood, which is regulated by the kidneys. Altered levels are associated with metabolic acid–base imbalances or reflect response to respiratory alterations in CO2 levels. 5. O2 saturation (O2 Sat, SaO2) indicates the oxygen content of the blood expressed as percent of oxygen capacity (the amount of oxygen the blood could carry if all of the hemoglobin were fully saturated with oxygen). If the blood is 50 percent saturated, for example, the oxygen content is one-half of the oxygen capacity. 6. Base excess (BE) usually indicates the difference between the normal serum bicarbonate (HCO3–) level and the client’s bicarbonate level. Positive values indicate excess bicarbonate relative to normal values, whereas negative values indicate decreased HCO3– levels. Copyright © 2003 F.A. Davis Company 208 SECTION I—Laboratory Tests Reference Values Conventional Units SI Units pH Newborns 7.32–7.49 Adults 7.35–7.45 pO2 Newborns 60–70 mm Hg Adults 75–100 mm Hg pCO2 35–45 mm Hg HCO3 – Newborns 20–26 mEq/L 20–26 mmol/L Adults 22–26 mEq/L 22–26 mmol/L O2 saturation 96–100% Base excess Critical values pH pO2 Infants Adults pCO2 HCO3– O2 saturation 1 to –2 7.2 or 7.6 37 mm Hg or 92 mm Hg 40 mm Hg 20 mm Hg or 70 mm Hg 10 mEq/L or 40 mEq/L 60% INTERFERING FACTORS Fever may falsely elevate pO2 and pCO2; hypothermia may lower them. Suctioning of respiratory passages within 20 to 30 minutes of the test may alter results. Excessive heparin in the sample will lower pH and pCO2. Exposure of the sample to atmospheric air (e.g., air bubbles in the sample) may alter results. Exposure of the sample to room temperature for more than 2 minutes may alter test results. INDICATIONS FOR ARTERIAL BLOOD GASES TEST Evaluation of the effectiveness of pulmonary ventilation in maintaining adequate oxygenation and in removing carbon dioxide, especially in disorders such as chronic pulmonary disease, neurological insults, and drug intoxication Evaluation of the effectiveness of cardiac output in maintaining adequate oxygenation, especially in shock and acute myocardial infarction Determination of the need for oxygen therapy (Oxygen is generally indicated if the pO2 is 70 mm Hg or less, except in pulmonary disorders charac- 10 mmol or 40 mmol/L terized by chronic hypoxemia in which lower oxygen levels may be tolerated by the client without supplemental oxygen.) Determination of respiratory failure, which is defined as a pO2 of 50 mm Hg or less with a pCO2 of 50 mm Hg or more Determination of acid–base balance, type of imbalance, and degree of compensation (see Table 5–26) Determination of need for mechanical ventilation (For example, elevated or rising pCO2 levels may indicate the need for mechanical ventilation, especially when pO2 is decreased.) Evaluation of effectiveness of mechanical ventilation and indication for modification of ventilator settings Evaluation of response to weaning from mechanical ventilation NURSING CARE BEFORE THE PROCEDURE Explain to the client: That repeat determinations may be necessary until cardiopulmonary function or acid–base balance, or both, are stabilized Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood The method and site for obtaining the sample (e.g., arterial puncture or arterial line sample) Any anticipated discomforts (Arterial punctures cause a brief, sharp pain unless a local anesthetic is used.) That if an arterial puncture is performed, it will be necessary to maintain digital pressure on the puncture site for 5 minutes or more, after which a pressure dressing will be applied Prepare the client for the procedure: Take the client’s temperature. Fever may falsely elevate pO2 and pCO2; hypothermia may lower them. The client should not have had a respiratory therapy treatment, been suctioned, or had ventilator settings changed less than 20 to 30 minutes before the sample is obtained. If the test is being conducted to determine the need for oxygen therapy or response to weaning from mechanical ventilation, the client should be off oxygen, off mechanical ventilation, or on a weaning mode for a preset time, which is specified by the person ordering the test. If the sample is to be obtained by radial artery puncture, the Allen test should be performed to assess patency of the ulnar artery; in the event that thrombosis involving the radial artery occurs after the puncture: Extend the client’s wrist over a rolled towel or similar support. Ask the client to clench the fist; if the client cannot clench the fist, elevate the hand above heart level. Apply digital pressure over both radial and ulnar arteries. Ask the client to unclench the fist while pressure is maintained on the arteries. Observe the palm for blanching, which is the expected response. Release pressure on the ulnar artery while continuing to maintain pressure on the radial artery. Observe the palm for returning pinkness, which is a positive result. If the palm remains blanched or if return of pinkness takes longer than approximately 5 seconds (a negative result), do not use the wrist for arterial punctures. Inform the client’s physician of a negative response to the Allen test. THE PROCEDURE The procedure varies slightly with the method for obtaining the sample. Chemistry 209 Arterial Puncture. A blood gas collection kit is obtained. If prepackaged kits are not available, obtain a 3-mL syringe, heparin (usually in the concentration of 100 U/mL), 20-gauge or 21-gauge needles, povidone-iodine or alcohol swabs or sponges, gauze pads, and tape. Fill a plastic or paper cup or a small plastic bag about halfway with ice. If the syringe is not preheparinized, draw approximately 1 mL of heparin into the syringe, pull the plunger back to about the 3-mL line, and rotate the barrel. Then expel all except approximately 0.1 mL of heparin and change the needle. Excess heparin in the syringe will lower the pH and pCO2 of the sample. Palpate the artery to be used. The radial artery is usually the most accessible, but the brachial or the femoral artery also may be used. If the radial artery is to be used, extend the client’s wrist over a rolled towel or similar support. Cleanse the site with povidone-iodine and allow to dry. It is recommended by some that the iodine solution be removed with an alcohol swab before arterial puncture. If the client is allergic to iodine, use only alcohol to prepare the site. Some authorities also advocate anesthetizing the puncture site with a small amount of 1 percent lidocaine (Xylocaine). Using the heparinized syringe with needle attached, puncture the artery. A 45-degree angle is used for radial artery punctures; a 60- to 90-degree angle is used for brachial arteries. A 90-degree angle is generally used for femoral artery punctures. Advance the needle until blood begins to enter the syringe; it should not be necessary to pull back on the plunger. After 2 to 3 mL of blood have been obtained, withdraw the needle and immediately apply firm pressure to the puncture site with a sterile gauze pad. Inform the client that the discomfort felt after the puncture will disappear in a few minutes. Meanwhile, expel any air or air bubbles from the syringe, because mixing with atmospheric air may alter test results. The needle may be plugged by inserting it into a rubber cap, or it may be removed and the rubber cap supplied in the blood gas collection kit placed on the hub of the syringe. The sample is then placed in ice to inhibit metabolic blood activity; failure to do this within 2 minutes of collecting the sample will alter test results. The sample is sent immediately for analysis. On the ABG request form or sample label, note the time the sample was collected, the client’s temperature, and whether the client was breathing room air, receiving oxygen, or using mechanical ventilation. Copyright © 2003 F.A. Davis Company 210 SECTION I—Laboratory Tests Arterial Line Sample. See Appendix I, the section titled “Indwelling Devices and Atrial Venous Catheters.” NURSING CARE AFTER THE PROCEDURE For arterial punctures, maintain digital pressure on the site for 5 minutes and then apply a sterile pressure dressing. If the client is receiving anticoagulants or has bleeding tendencies, apply digital pressure for 10 to 15 minutes. Observe the arterial puncture site for bleeding or hematoma formation every 5 to 10 minutes for one-half hour after the pressure dressing is applied. Check for presence of pulses distal to the site when performing site observations, if the brachial or the femoral artery was used. Check for signs of nerve impairment distal to the site. Provide support when test findings are revealed and if repeated or serial testing is necessary in acute conditions. Evaluate the results of pH with electrolytes (particularly hypokalemia or hyperkalemia) and oxygen, carbon dioxide, and bicarbonate associated with respiratory or metabolic acidosis or alkalosis. Assess respiratory pattern, level of consciousness, neuromuscular irritability, fluid and electrolyte imbalances, and symptoms of impaired tissue perfusion as a result of hypoxia, any of which can be associated with abnormal ABGs. Notify physician at once of critical lab values. VITAMINS AND TRACE MINERALS Vitamins are essential organic substances that perform various metabolic functions. Vitamins cannot be synthesized in adequate amounts by the body and, therefore, inadequate dietary intake causes deficiency diseases. Vitamins are classified as fat soluble and water soluble. The fat-soluble vitamins are vitamins A, D, E, and K. Because they are stored in the body, excessive ingestion of exogenous fat-soluble vitamins may cause abnormally elevated levels. Vitamin C and the B-complex vitamins are water soluble and are not stored in the body. The Bcomplex vitamins include B1 (thiamine), which is involved in carbohydrate metabolism; B2 (riboflavin), which is involved in the transport of oxidative metabolism and fatty acids; B3 (niacin), which is involved in the transport of cellular respiration; and B6 (pyridoxine), which is involved as a cofactor of enzymes and in the conversion of trypto- phan to nicotinic acid. A vitamin B6 deficiency causes beriberi, and a vitamin B3 deficiency causes pellagra. For diagnostic purposes, blood levels of vitamins A and C and a metabolite of vitamin D are measured. Vitamin B12 and folic acid also are measured in studies pertaining to hematologic function (see Chapter 1). VITAMIN A Vitamin A is obtained from foods of animal origin, such as eggs, milk, butter, and liver. Its precursor, carotene, a yellowish pigment, is obtained from yellow or orange vegetables and fruits and from leafy green vegetables. Vitamin A promotes normal vision by permitting visual adaptation to light and dark, and it prevents night blindness (xerophthalmia). It also contributes to the growth of bone, teeth, and soft tissues; supports the formation of thyroxine; maintains epithelial cellular membranes; aids in spermatogenesis; and maintains the integrity of skin and mucous membranes as barriers to infection. Reference Values Conventional Units Vitamin A 65–275 IU/dL SI Units — 0.15–0.60 mg/mL 0.52–2.09 mol/L Carotene Infants 0–40 g/dL 0–0.7 mol/L Children 40–130 g/dL 0.7–2.4 mol/L Adults 50–300 g/dL 0.9–5.5 mol/L INTERFERING FACTORS Pregnancy and oral contraceptive use can lead to falsely elevated levels, as can hyperlipidemia, hypercholesterolemia of diabetes, myxedema, and nephritis. Excessive ingestion of mineral oil, low-fat diets, and liver disease may lead to decreased levels. Failure to follow dietary and drug restrictions before the test may alter results. Excessive exposure of the sample to light may alter results. INDICATIONS FOR VITAMIN A AND CAROTENE TEST Evaluation of skin disorders, with vitamin A deficiency a possible cause Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Support for diagnosing xerophthalmia (night blindness) as indicated by decreased levels Suspected vitamin A deficiency caused by fat malabsorption or biliary tract disease Support for diagnosing excessive vitamin A or carotene ingestion, or both, as indicated by elevated blood levels NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For this test, the client should fast for 8 hours before the study. Water is not restricted. Vitamin supplements containing vitamin A should be withheld for at least 24 hours before the test. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be covered to protect it from light, which may alter test results; handled gently to avoid hemolysis; and sent promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Resume usual diet. Vitamin supplements may be resumed pending test results. Decreased level: Note and report symptoms of deficiency or decreased level. Administer ordered vitamin A supplement orally, and instruct client to eat foods high in vitamin A to correct deficiency. Increased level: Note and report symptoms of excesses or increased level. Discontinue the oral or topical medication administered for acne or other skin conditions. VITAMIN C Vitamin C (ascorbic acid) functions in many metabolic processes, especially in those related to collagen formation and the stress response. In addition, vitamin C helps to maintain capillary strength, facilitates the release of iron from ferritin for hemoglobin formation and red blood cell maturation, and may maintain the integrity of the amniotic sac. Elevated vitamin C levels are associated with excessive intake of the vitamin within 24 hours of the test. Decreased intake produces scurvy with low vitamin C levels. Chemistry 211 Reference Values Conventional Units SI Units Children 0.6–1.6 mg/dL 34–91 mol/L Adults 0.2–2.0 mg/dL 11–113 mol/L INTERFERING FACTORS Excessive intake of vitamin C within 24 hours of the test will produce elevated levels. Failure to follow dietary restrictions before the test may alter results. INDICATIONS FOR VITAMIN C TEST Evaluation of the effects of major stressors (e.g., pregnancy, major surgery, burns, infections, malignancies) on vitamin C levels Evaluation of the effects of malabsorption syndromes on vitamin C levels Evaluation of the effectiveness of therapy with vitamin C in treating deficiency states NURSING CARE BEFORE THE PROCEDURE General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I). For this test, the client should fast from food for 8 hours beforehand. Vitamin C preparations also should be withheld for 24 hours before the study. THE PROCEDURE A venipuncture is performed and the sample collected in a black-topped tube. The sample is handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Resume usual diet. Vitamin C preparations may be resumed pending test results. Decreased level: Note and report symptoms of deficiency or decreased level such as bleeding and poor wound healing. Instruct client to eat foods high in vitamin C to correct deficiency. Administer oral vitamin C supplement in ordered dosage. Increased level: Note and report symptoms of excesses or increased level. Discontinue the oral intake to prevent overdose; high doses taken as a preventive treatment can cause renal calculi. Copyright © 2003 F.A. Davis Company 212 SECTION I—Laboratory Tests VITAMIN D The form of vitamin D most easily and accurately measured is 25-hydroxy-cholecalciferol [vitamin D3, 25(OH)D3, cholecalciferol], a monohydroxylated form that leaves the liver for subsequent dihydroxylation by the kidney. Indirect measurement of vitamin D by serum alkaline phosphatase, calcium, and phosphorus determinations preceded 25(OH)D3 assays and may still be used in the diagnosis of disorders of calcium metabolism. Vitamin D aids in the maintenance of calcium–phosphorus balance and in the deposition of calcium and phosphorus in the bone. It also facilitates absorption of calcium and phosphorus from the small intestine and aids in the renal excretion of phosphorus. Reference Values Conventional Units SI Units 25(OH)D3 0.7–3.3 IU/mL 10–55 ng/mL 25–100 pmol/L INTERFERING FACTORS Excessive ingestion of vitamin D leads to elevated levels. Therapy with anticonvulsants and glucocorticoids may produce decreased levels. INDICATIONS FOR VITAMIN D TEST Differential diagnosis of hypercalcemia caused by parathyroid adenoma or vitamin D toxicity Confirmation of vitamin D deficiency as the cause of bone disease Confirmation of vitamin D deficiency caused by malabsorption syndromes, hepatobiliary disease, and chronic renal failure Evidence of interference with vitamin D levels as a result of anticonvulsant or steroid therapy NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any study involving the collection of a peripheral blood sample. It is recommended that anticonvulsant and steroid medications be withheld for 24 hours before the test, although this practice should be confirmed by the person ordering the study. THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported promptly to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample. Resume medications withheld before the test. Decreased level: Note and report symptoms of deficiency or decreased level such as bone deformities. Instruct client to eat foods that are enriched with vitamin D. Administer ordered oral supplement. Increased level: Note and report symptoms of excesses or increased levels taken in medications or vitamin supplements, or both (intoxication, renal calculi, gastrointestinal intolerance). Discontinue the oral intake of vitamin D, and instruct client to avoid foods high in vitamin D. TRACE MINERALS Seven trace minerals are known to be essential to human function even though they are present in minute quantities in the body. These essential minerals are cobalt, copper, iodine, iron, manganese, molybdenum, and zinc. Cobalt is a constituent of vitamin B12 and is essential to the formation of red blood cells. Copper participates in cytochrome oxidation of tissue cells for energy production, promotes absorption of iron from the intestines and transfer from tissues to plasma, and is essential to hemoglobin formation. It also promotes bone and brain tissue formation and supports the maintenance of myelin. Iodine is an essential component for the synthesis of thyroid hormones. Iron, which is discussed in Chapter 1, is an essential component of hemoglobin. Manganese functions as a coenzyme in urea formation and in the metabolism of proteins, fats, and carbohydrates. Molybdenum facilitates the enzymatic action of xanthine oxidase and liver aldehyde oxidase in purine catabolism and functions in the formation of carboxylic acid. Zinc is an essential component of cellular enzymes such as alkaline phosphatase, carbonic anhydrase, lactic dehydrogenase, and carboxypeptidase, which function in protein and carbohydrate metabolism. It also aids in the storage of insulin, functions in deoxyribonucleic acid (DNA) replication, assists in carbon dioxide exchange, promotes body growth and sexual maturation, and may affect lymphocyte formation and cellular immunity. Other trace minerals are found in the body, but Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood Chemistry 213 Reference Values Conventional Units SI Units Cobalt 1 g/dL 1.7 nmol/L Copper 130–230 g/dL 20.41–36.11 mol/L Iodine (protein-bound) 4–8 g/dL Manganese 4–20 mg/dL Zinc 50–150 g/dL 7.6–23.0 mol/L Chromium 0.3–0.85 g/L 5.7–16.3 nmol/L their functions remain unclear. These minerals include chromium, fluorine, lithium, arsenic, cadmium, nickel, silicon, tin, and vanadium. Deficiencies of trace minerals are likely only in individuals dependent on parenteral nutrition, because the normal diet provides adequate intake. Elevated blood levels are usually caused by environmental contamination, either in industrial settings or through water pollution. INDICATIONS FOR TRACE MINERALS TEST Monitoring of response to parenteral nutrition, which may lead to deficiencies of trace minerals Suspected exposure to environmental toxins, which may be indicated by elevated levels of trace minerals NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). THE PROCEDURE A venipuncture is performed and the sample collected in a metal-free tube. The sample is handled gently to avoid hemolysis and transported immediately to the laboratory. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. Abnormal values: Note and report deficiency or decreased levels associated with anemia, poor wound healing, reduced sexual maturation, growth retardation, and the administration of total parenteral nutrition that can eliminate some trace minerals. Instruct client to eat foods high in trace minerals. Administer oral supplements as ordered. DRUGS AND TOXIC SUBSTANCES Blood levels of drugs are used to monitor attainment of therapeutic drug levels, compliance with therapeutic regimens, and potential excess dosing. They are also used in situations when accidental or deliberate drug overdose is suspected. In therapeutic situations, serial samples may be drawn to determine peak (highest) and trough (lowest) blood levels of drugs. Samples for peak drug levels are generally drawn within 30 to 60 minutes of drug administration. Trough levels are drawn immediately before the next dose of the drug is to be given. It is necessary to know as exactly as possible the time the drug was administered or ingested for accurate interpretation of test results. Many potential toxins are present in the household and in industrial settings. Data regarding circulating levels of toxic substances may be used to diagnose either acute or chronic poisoning with metals or common commercial substances. Reference Values Therapeutic and toxic levels of various drugs are shown in Table 5–30. Toxic doses and effects of industrial and household toxins are listed in Table 5–31. For child values, refer to agency laboratory information. INDICATIONS FOR BLOOD LEVELS OF DRUGS AND TOXIC SUBSTANCES TEST Determination of therapeutic levels of prescribed drugs, especially those with narrow therapeutic ranges or serious toxic effects, or both Evaluation of the degree of compliance with the therapeutic regimen Known or suspected drug overdose Known or suspected exposure to environmental toxins Copyright © 2003 F.A. Davis Company 214 SECTION I—Laboratory Tests TABLE 5–30 Drug Peak Time • Blood Levels of Drugs Duration of Action Therapeutic Level Toxic Level 2 days 20–25 g/mL 35 g/mL 34–43 mol/L 60 mol/L 4–8 g/mL 12 g/mL 8.4–16.8 mol/L 25.1 mol/L 35 g/mL Antibiotics Amikacin IM: 1/2 hr IV: 15 min SI units Gentamicin 1 IM: /2 hr 2 days IV: 15 min SI units Kanamycin 1/2 hr 2 days 20–25 g/mL 42–52 mol/L 73 mol/L 1 /2–11/2 hr 5 days 25–30 g/mL 30 g/mL IV: 15 min 2 days 2–8 g/mL 12 g/mL 4–17 mol/L 25 mol/L SI units Streptomycin SI units Tobramycin SI units Anticonvulsants Barbiturates and barbiturate-related Amobarbital IV: 30 sec 10–20 hr 7 g/mL 30 g/mL 30 mol/L 132 mol/L IV: 30 sec 15 hr 4 g/mL 15 g/mL 18 mol/L 66 mol/L 55 g/mL SI units Pentobarbital SI units Phenobarbital 15 min 80 hr 10 g/mL 43 mol/L 230 mol/L PO: 3 hr 7–14 hr 1 g/mL 10 g/mL 4 mol/L 45 mol/L SI units Primidone SI units Benzodiazepines Clonazepam (Klonopin) 1–4 hr 60 hr SI units Diazepam (Valium) 1–4 hr 1–2 days SI units 5–70 ng/ml 70 ng/mL 55–222 mol/L 222 mol/L 5–70 ng/mL 70 ng/mL 0.01–0.25 mol/L 0.25 mol/L 10–20 g/mL 20 g/mL 40–80 mol/L 80 mol/L Hydantoins Phenytoin (Dilantin) 3–12 hr 7–42 hr SI units Succinimides Ethosuximide (Zarontin) SI units 1 hr 8 days 40–80 g/mL 100 g/mL 283–566 mol/L 708 mol/L Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–30 Drug • Duration Peak Time Chemistry 215 Blood Levels of Drugs Therapeutic of Action Level Toxic Level Miscellaneous Carbamazepine (Tegretol) 4 hr 2 days SI units Valproic acid (Depakene) 1–4 hr 2–10 g/mL 12 g/mL 8–42 mol/L 50 mol/L 50–100 g/mL 100 g/mL 350–700 mol/L 700 mol/L 8–9 hr 10–18 g/mL 20 g/mL 25–30 hr 2–4.5 g/mL 9 g/mL 5.9–13 mol/L 26 mol/L 2.4–5 g/mL 6 g/mL 7–15 mol/L 18 mol/L 4–8 g/mL 12 g/mL 17–35 mol/L 50 mol/L 2–8 g/mL 30 g/mL 24 hr SI units Bronchodilators Aminophylline/theophylline PO: 2 hr IV: 15 min Cardiac Drugs Disopyramide (Norpace) PO: 2 hr SI units Quinidine PO: 1 hr 20–30 hr IV: immediate SI units Procainamide (Pronestyl) PO: 1 hr 10–20 hr 1 IV: /2 hr SI units NAPA (N-acetyl procainamide, a procainamide metabolite) — — IV: immediate 5–10 hr 7–29 mol/L 108 mol/L 2–6 g/mL 9 g/mL 8–25 mol/L 38 mol/L 6–8 hr 5–10 g/kg 30 g/kg 5–10 g/kg 15 g/kg SI units Lidocaine SI units Bretylium Verapamil 15–30 min PO: 5 hr 8–10 hr IV: 3–5 min IV: 1/2–1 hr Diltiazem PO: 2–3 hr 3–4 hr 50–200 ng/mL 200 ng/mL Nifedipine 1–3 hr 3–4 hr 5–10 mg 90 mg Digitoxin 4 hr 30 days 10–25 ng/mL 30 ng/mL 13–33 nmol/L 39 nmol/L 0.5–2 ng/mL 2.5 ng/mL 0.6–2.5 nmol/L 3.0 nmol/L 10–18 g/mL 20 g/mL 40–71 mol/L 80 mol/L 2.3–5 g/mL 5 g/mL 7–15 mol/L 15 mol/L SI units Digoxin 2 hr 7 days SI units Phenytoin (Dilantin) PO: 2 hr 96 hr SI units Quinidine IV: 1 hr — SI units — (Continued on the following page) Copyright © 2003 F.A. Davis Company 216 SECTION I—Laboratory Tests Evaluation of chronic exposure to industrial products known to be toxic NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a peripheral blood sample (see Appendix I). TABLE 5–30 Drug • THE PROCEDURE A venipuncture is performed and the sample collected in a red-topped tube. The sample should be handled gently to avoid hemolysis and transported to the laboratory immediately. For drug levels, the name of the drug, dosage, and time Blood Levels of Drugs (Continued) Duration Peak Time Therapeutic of Action Level Toxic Level Salicylates 2–20 mg/dL 30 mg/dL SI units 0.1–1.4 mmol/L 2.1 mmol/L 2–30 mg/dL 40 mg/dL SI units 0.1–2.1 mmol/L 2.8 mmol/L 0.005 mg/dL Aspirin 15 min 12–30 hr Narcotics Codeine — — — — — — 17 nmol/L SI units Hydromorphone (Dilaudid) 0.1 mg/dL 350 nmol/L SI units Methadone — — — — — — 0.2 mg/dL 6.46 mol/L SI units Meperidine (Demerol) 0.5 mg/dL 20 mol/L SI units Morphine — — — 0.005 mg/dL — — 10 g/mL 55 g/mL 43 mol/L 230 mol/L 30 g/mL Barbiturates Phenobarbital SI units Amobarbital — — 7 g/mL 30 mol/L 130 mol/L — — 4 g/mL 15 g/mL 17 mol/L 66 mol/L 3 g/mL 10 g/mL 12 mol/L 42 mol/L 0.1 g/dL 100 mg/dL SI units Pentobarbital SI units Secobarbital — — SI units Alcohols Ethanol — — (legal level for intoxication) Methanol — — — 20 mg/dL Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–30 Drug • Chemistry 217 Blood Levels of Drugs Duration Peak Time Therapeutic of Action — — Level Toxic Level Psychiatric Drugs Amitriptyline (Elavil) SI units Imipramine (Tofranil) — — SI units Lithium (Lithonate) 1–4 hr — SI units 100–250 ng/mL 300 ng/mL 361–902 nmol/L 1083 nmol/L 100–250 ng/mL 300 ng/mL 357–898 nmol/L 1071 nmol/L 0.8–1.4 mEq/L 1.5 mEq/L 0.8–1.4 mol/L 1.5 mol/L 0–25 g/mL 150 g/mL 0–170 mol/L 1000 mol/L 4 hr after ingestion Miscellaneous Acetaminophen — — SI units Prochlorperazine — — 0.5 g/mL 1.0 g/mL Bromides — — 75–150 mg/dL 150 mg/dL 7–15 mmol/L 15 mmol/L SI units administered or ingested should be noted on the laboratory request form. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a peripheral blood sample. It may be necessary to withhold subsequent doses of drugs administered for therapeutic reasons until test results are available, but this practice should be confirmed with the person prescribing the medication. Abnormal values: Note and report both therapeutic and toxic values for the drug test performed. Notify the physician at once if any value is at a critical level. Prepare for immediate interventions to prevent cardiac arrest or other manifestations of toxicity, such as ECG monitor- ing, oxygen, or intubation and ventilation. Administer ordered antidote or other medications. Long-term drug therapy: Support client and instruct in long-term medication regimen, which symptoms to note and report, and when to discontinue the medication. Medicolegal aspects: Collection, delivery, possession, and transportation of the specimen should be witnessed by a legally responsible person, and the possession of it must remain unbroken from the time of collection to the completion of any legal court action (chain of evidence). Seal specimen to prevent tampering and label “Medicolegal Case.” In some cases a number is used instead of a name for identification. Toxicology tests to determine abuse, suicide, intentional overdose, or suspected murder or attempted murder require these considerations. Copyright © 2003 F.A. Davis Company 218 SECTION I—Laboratory TABLE 5–31 • Tests Toxic Doses and Effects of Industrial and Household Toxins Substance Toxic Dose Toxic Effects Aniline 50 mg/kg Methemoglobinemia, hepatotoxicity, nephrotoxicity Arsenic/antimony 5 mg/kg Gastric hemorrhage, shock Barium salts — Bloody diarrhea, cardiac depression, muscle spasms, respiratory failure, renal failure Benzene products 50 mg/kg CNS depression, respiratory failure, cardiac arrest, bone marrow depression, liver damage Bismuth 0.1–3.5 g/L Weakness, fever, anorexia, black gum line, renal damage Cadmium 41 ng/mL Severe gastroenteritis, liver damage, acute renal failure; if inhaled as dust or fumes, pulmonary edema Carbon tetrachloride 5–10 mL (total) CNS depression, liver and kidney failure Chlorate or bromate salts 50 mg/kg Methemoglobinemia, intravascular hemolysis, acute renal failure Cobalt 0.11–0.45 g/L Nerve damage, thyroid dysfunction Copper salts 50 mg/kg Generalized capillary damage, kidney and liver damage Cyanide 5 mg total (0.5 mg/100 mL of blood) Confusion, dyspnea, convulsions, death from respiratory failure DDT 50 mg/kg Fatigue, confusion, ataxia, convulsions, death from respiratory failure 2.4-D — Lethargy, diarrhea, cardiac arrest, hyperpyrexia, convulsion, coma Ergot 5 mg/kg Gastrointestinal inflammation, renal damage, gangrene of fingers and toes caused by persistent peripheral vascoconstriction Ethylene glycol 5 mg/kg CNS depression, death from renal failure or respiratory paralysis Iron salts 500 mg/kg Bloody diarrhea, shock, liver damage Fluoride 50 mg/kg (0.2–0.3 mg/dL of blood) Hemorrhagic gastroenteritis, tremors, hypocalcemia, shock Formaldehyde 500 mg/kg Hemorrhagic gastroenteritis, renal failure, circulatory collapse Hydrogen sulfide 0.1–0.2% in air Death from respiratory paralysis Sodium hypochlorite Several ounces of household bleach Edema of pharynx, glottis, larynx; perforation of esophagus or stomach, pulmonary edema from fumes Iodine 5 mg/kg Bloody diarrhea, renal damage, death from asphyxia or circulatory collapse Copyright © 2003 F.A. Davis Company CHAPTER 5—Blood TABLE 5–31 • Chemistry 219 Toxic Doses and Effects of Industrial and Household Toxins Substance Toxic Dose Toxic Effects Ipecac, syrup or fluid extract 1–2 oz fluid extract (14 times more concentrated than syrup) Shock caused by intractable vomiting and diarrhea, death from cardiac depression Isopropyl alcohol 500 mg/kg Severe CNS depression, death from respiratory failure or circulatory collapse Kerosene 500 mg/kg if swallowed; few mL lethal if aspirated Severe chemical pneumonitis, coma Lead 30 g/kg (120 g/L blood level) Gastrointestinal inflammation, liver and kidney damage, encephalopathy in children, paralysis of extremities, death from encephalopathy or peripheral vascular collapse Lye, sodium and potassium hydroxide 10 g total dose may be fatal Laryngeal or glottic edema, perforation of esophagus or stomach, severe diarrhea, shock, death Mercury salts 5 mg/kg Acute: Death from acute renal failure or peripheral vascular collapse Chronic: Progressive peripheral neuritis, death from renal failure Naphthalene (mothballs) 5 g/kg CNS excitement or depression, acute hemolytic anemia, convulsions Nicotine 5 mg/kg CNS stimulation followed by depression; vomiting, diarrhea, dyspnea, death from respiratory paralysis Oxalic acid 50 mg/kg Shock caused by severe gastroenteritis, hypocalcemia, convulsions, renal damage, coma, death Parathion/organophosphorus insecticides 5 mg/kg Vomiting, diarrhea, generalized muscle weakness, convulsions, coma, death, all caused by inhibition of acetylcholinesterase and accumulation of cholinesterase at myoneural junctions Phosphorus 5 mg/kg Penetrating burns; liver, kidney, and cardiac damage Quaternary ammonium germicides 5 mg/kg CNS depression, dyspnea, death from asphyxia Rotenone 50 mg/kg Severe hypoglycemia, tremors, convulsions, respiratory stimulation followed by depression, death from respiratory arrest Selenium 58–234 g/L Metallic taste, nausea, vomiting, headache, pulmonary disorders Silver salts 3.5–35 g total dose Bloody diarrhea, severe corrosion of the gastrointestinal tract, coma, convulsions, death (Continued on the following page) Copyright © 2003 F.A. Davis Company 220 SECTION I—Laboratory TABLE 5–31 Substance • Tests Toxic Doses and Effects of Industrial and Household Toxins (Continued) Toxic Dose Toxic Effects Strychnine 5 mg/kg Stimulation of spinal cord, tetanic convulsions, death in 1–3 hr (with the face fixed in a grin and the body arched in hyperextension) from anoxia Thallium salts 5 mg/kg (50 g/L blood level) Hemorrhagic gastroenteritis, encephalopathy (delirium, convulsions, coma), death Turpentine 500 mg/kg Aspiration pneumonitis, vomiting, diarrhea, CNS excitement (delirium), stupor, convulsions, coma, death from respiratory failure Zinc 70–50 g/L Hypertension, tachycardia nausea, vomiting, diarrhea, cough, metallic taste REFERENCES 1. Sacher, RA, and McPherson, RA: Widmann’s Clinical Inter-pretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 321. 2. Ibid, pp 322–323. 3. Ibid, p 323. 4. Ibid, p 324. 5. Ibid, p 323. 6. Ibid, p 325. 7. Ibid, p 605. 8. Ibid, p 611. 9. Ibid, p 326. 10. Ibid, pp 610–611. 11. Ibid, p 606. 12. Ibid, p 326. 13. Springhouse Corporation: Nurse’s Reference Library, Diagnostics, ed 2. Springhouse, Springhouse, PA, 1986, p 242. 14. Fischbach, FT: A Manual of Laboratory Diagnostic Tests, ed 4. JB Lippincott, Philadelphia, 1992, p 303. 15. Sacher and McPherson, op cit, p 606. 16. Ibid, p 607. 17. Ibid, p 433. 18. Hillman, RS, and Finch, CA: Red Cell Manual, ed 7. FA Davis, Philadelphia, 1996, p 23. 19. Sacher and McPherson, op cit, p 328. 20. Ibid, p 329. 21. Ibid, pp 433–434. 22. Ibid, p 338. 23. Guyton, AC: Textbook of Medical Physiology, ed 6. WB Saunders, Philadelphia, 1981, pp 849–850. 24. Ibid, pp 856–857. 25. Sacher and McPherson, op cit, pp 332, 425. 26. Ibid, pp 397–398. 27. Ibid, pp 402–403. 28. Ibid, pp 400–401, 427–428. 29. Kontos, MC, et al: Use of the combination of myoglobin and CKMB mass for rapid diagnosis of acute myocardial infarction. Am J Emerg Med, 15(1):14–19, 1997. 30. Sacher and McPherson, op cit, pp 406–409. 31. Collinson, PO: Troponin T or troponin I or CK-MB (or none?). Eur Heart J, 19(Suppl N):N16–24, 1998. 32. Sommers, M, and Johnson, S: Davis’s Manual of Nursing Therapeutics for Diseases and Disorders. FA Davis, Philadelphia, 1997. 33. Kost, GJ, Kirk, JD, and Omand, K: A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction. Arch Pathol Lab Med, 122(3):245–251, 1998. 34. Lindahl, B, Venge, P, and Wallentin, L: The FRISC experience with troponin T. Use as decision tool and comparison with other prognostic markers. Eur Heart J, 19(Suppl N):N51–58, 1998. 35. Sacher and MacPherson, op cit, pp 411–412. 36. Berkow, R (ed): The Merck Manual, ed 16. Merck Research Laboratories, Rahway, NJ, 1992, p 1839. 37. Sacher and McPherson, op cit, pp 405–406. 38. Ibid, pp 555–556. 39. Ibid. 40. Ibid, p 557. 41. Ibid, pp 557, 634. 42. Ibid, pp 583, 587, 590–591. 43. Ibid, pp 621–623. 44. Ibid, pp 617–627. 45. Ibid, pp 559–562. 46. Ibid, pp 582–583. 47. Guyton, op cit, pp 931–937, 984. 48. Sacher and McPherson, op cit, pp 585–586, 588. 49. Ibid, pp 586–587. 50. Ibid, pp 582–583, 590–592. 51. Ibid, pp 594, 598–601. 52. Ibid, pp 562, 577. 53. Ibid, pp 565–568. 54. Ibid, pp 572–573. 55. Ibid, pp 577–579. 56. Ibid, pp 631–632. 57. Ibid, pp 633–634. 58. Ibid, pp 603–604. 59. Ibid, pp 604, 611. 60. Ibid, pp 367–368. 61. Ibid, pp 379, 383. 62. Ibid, pp 357, 596. 63. Ibid, pp 380–381. Copyright © 2003 F.A. Davis Company CHAPTER Studies of Urine TESTS COVERED Routine Urinalysis, 222 Clearance Tests and Creatinine Clearance, 239 Tubular Function Tests and Phenolsulfonphthalein Test, 240 Concentration Tests and Dilution Tests, 241 Electrolytes, 244 Pigments, 247 Enzymes, 250 Hormones and Their Metabolites, 252 Proteins and Their Metabolites, 261 Vitamins and Minerals, 263 Microbiologic Examination of Urine, 264 Cytologic Examination of Urine, 265 Drug Screening Tests of Urine, 265 OVERVIEW OF URINE FORMATION AND ANALYSIS Because urine results from filtration of blood, many of the substances carried in the blood are also found in the urine. The nature and amount of the substances present in urine reflect ongoing physiological processes in health and disease states. The comparative ease of obtaining urine samples ensures the continued use of urine studies as an aid to diagnosis.1 Urine is an ultrafiltrate of plasma from which substances essential to the body are reabsorbed and through which substances that are not needed are excreted. Normally, 25 percent of the cardiac output perfuses the kidneys each minute. This perfusion results in the production of 180 L of glomerular filtrate per day, 90 percent of which is reabsorbed. In addition to water, substances reabsorbed include glucose, amino acids, and electrolytes. Substances excreted from the body include urea, uric acid, creatinine, and ammonia. The major electrolytes lost are chloride, sodium, and potassium. Other substances found in urine include pigments, enzymes, hormones and their metabolites, vitamins, minerals, and drugs. Red blood cells, white blood cells, epithelial cells, crystals, mucus, and bacteria may also be found in urine.2,3 In general, the concentration of most substances normally found in the urine reflects the plasma levels of the substances. If the plasma concentration of a substance is high, more of it is lost in the urine in the presence of normal renal function. Conversely, if the plasma concentration is abnormally low, the substance is reabsorbed. The concentration of substances found in the urine is also affected by factors such as dietary intake, body metabolism, endocrine function, physical activity, body position, and time of day.4 For these reasons, results of urine tests must be evaluated in relation to the client’s history and current health status. For some studies, urine specimens are collected at certain times of day or over 24-hour periods. Dietary intake may also be modified for certain studies. Commercially prepared reagent dipsticks are available to perform simple and quick testing in hospitals, clinics, physicians’ offices, and homes. They are used for routine screening of single or multiple urinary evaluations of protein, glucose, ketones, hemoglobin, urobilinogen, and nitrites as well as pH. The strips contain reagents that react with specific substances by changing color. Color change is observed and compared to a color chart for the presence of abnor221 Copyright © 2003 F.A. Davis Company 222 SECTION I—Laboratory Tests mal levels of substances. Special care in their use is required to prevent inaccurate results, and confirmation of quantitative tests is appropriate if results from the dipstick testing reveal abnormalities. Urine samples for more exhaustive laboratory testing may be obtained through a variety of methods. These are described in Appendix II. Urine studies include routine urinalysis, clearance tests, tubular function tests, concentration tests, and analyses for specific substances such as electrolytes, pigments, enzymes, hormones and their metabolites, proteins, and vitamins and minerals. Microbiologic and cytologic examination of urine may also be performed. ROUTINE URINALYSIS A routine urinalysis (UA) has two major components: (1) macroscopic analysis and (2) microscopic analysis. Macroscopic analysis includes examining the urine for overall physical and chemical characteristics. The microscopic component of a UA involves examining the sample for formed elements, also termed urinary sediment. Urine samples for routine analysis are best collected first thing in the morning. Urine that has accumulated in the bladder overnight is more concentrated, thus allowing detection of substances that may not be present in more dilute random samples.5 The sample should be examined within 1 hour of collection. If this is not possible, the sample may be refrigerated until it can be examined. Failure to observe these precautions may lead to invalid results. If, for example, the sample is allowed to stand for long periods without refrigeration, the glucose level may drop and the ketones may dissipate. The color of the urine may also deepen. Similarly, urinary sediment begins deteriorating within 2 hours of sample collection. If bacteria are present, they may multiply if the sample is neither examined promptly nor refrigerated. Also, the pH of the sample may be altered, rendering it more alkaline. If the sample is exposed to light for long periods of time, bilirubin and urobilinogen may be oxidized.6 MACROSCOPIC ANALYSIS COLOR The color of urine is mainly a result of the presence of the pigment urochrome, which is produced through endogenous metabolic processes. Because urochrome is normally produced at a fairly constant rate, the intensity of the yellow color may indirectly indicate urine concentration and the client’s state of hydration.7,8 Pale urine with a low specific gravity may occur, for example, in a normal person after high fluid intake. Note, however, that an individual with uncontrolled or untreated diabetes may also produce pale urine. The pale urine in this case is caused by osmotic diuresis resulting from the excessive glucose load. The client actually may be dehydrated. Further, the specific gravity of the urine from such an individual could be high because of the presence of excessive glucose.9 Similarly, deeper colored urine may not always indicate concentrated urine. The presence of bilirubin may produce darker urine in normally hydrated individuals. Urine color may be described as pale yellow, straw, light yellow, yellow, dark yellow, and amber. For the most accurate appraisal of urine color, the sample should be examined in good light against a white background. If the sample is allowed to stand at room temperature for any length of time, the urochrome will increase and the color of the sample may deepen.10 Numerous factors that affect the color of urine are listed in Table 6–1. APPEARANCE (CLARITY) The term appearance generally refers to the clarity of the urine sample. Urine is normally clear or slightly cloudy. In alkaline urine, cloudiness may be caused by precipitation of phosphates and carbonates. In acidic urine, cloudiness may be caused by precipitation of urates, uric acid, or calcium oxalate. The accumulation of uroerythrin, a pink pigment normally present in urine, may produce a pinkish or reddish haze in acidic urine. The most common substances that may cause cloudy urine are white blood cells, red blood cells, bacteria, and epithelial cells. Presence of these substances may indicate inflammation or infection of the urinary and genital tracts and must be confirmed through microscopic examination. Other substances that may produce cloudy urine are mucus, yeasts, sperm, prostatic fluid, menstrual and vaginal discharges, fecal material, and external substances such as talcum powder and antiseptics.11 Proper client instruction and specimen collection may aid in reducing the presence of such substances in the urine. Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies • TABLE 6–1 Urine Color Very pale yellow Factors Affecting the Color of Urine Cause Excessive fluid intake Urine Color Green Diabetes insipidus Vitamins Nephrotic syndrome Psychoactive drugs Alcohol Proprietary diuretics Blue Nitrofurans Anxiety Proprietary diuretics Underhydration Methylene blue Brown Acid hematin Urobilin Myoglobin Carrots Bile pigments Phenacetin Levodopa Cascara Nitrofurans Nitrofurantoin Some sulfa drugs Chlorpromazine Quinacrine Riboflavin Sulfasalazine Bilirubin Phenazopyridine (Pyridium) Red Biliverdin Pseudomonas Bilirubin Orange Cause Diabetes mellitus Diuretics Dark yellow, amber of Urine Rhubarb Black, brownish black Melanin Homogentisic acid Indicans Urobilin Azo drugs Red blood cells oxidized to methemoglobin Phenothiazine Levodopa Oral anticoagulants Cascara Red blood cells Iron complexes Hemoglobin Phenols Myoglobin Porphyrins Porphobilinogen Many drugs and dyes Rifampin Phenolsulfonphthalein Fuscin Beets Rhubarb Senna 223 Copyright © 2003 F.A. Davis Company 224 SECTION I—Laboratory Tests Lymph and fat globules in urine can also yield cloudy specimens. The presence of lymph in the urine is most often associated with obstruction of abdominal lymph flow and rupture of lymphatic vessels into portions of the urinary tract. Fat globules in the urine are most commonly associated with nephrotic syndrome but may also be seen in clients with fractures of the long bones or pelvis.12 ODOR Normally, a fresh urine specimen has a faintly aromatic odor. As the specimen stands, the odor of ammonia predominates because of the breakdown of urea. Ingestion of certain foods and drugs impart characteristic odors to urine; this is especially true of asparagus. Some unusual odors are indicative of certain disease states. Urine with a fruity odor, for example, may indicate ketonuria resulting from uncontrolled diabetes mellitus or starvation. Other abnormal odors are associated with amino acid disorders. Urine with a “mousy” smell is associated with phenylketonuria (PKU), whereas urine that smells like maple syrup is associated with maple syrup urine disease. Urine with a “fishy” or fetid odor is generally associated with bacterial infection. This odor is especially noticeable when urine is allowed to stand for some time. Occasionally, urine may lack an odor. This characteristic is seen in acute renal failure because of acute tubular necrosis and failure of normal mechanisms of ammonium secretion.13,14 SPECIFIC GRAVITY The specific gravity of urine is an indication of the kidney’s ability to reabsorb water and chemicals from the glomerular filtrate. It also aids in evaluating hydration status and in detecting problems related to secretion of antidiuretic hormone. By definition, specific gravity is the density of a liquid compared with that of a similar volume of distilled water when both solutions are at the same or similar temperatures. The normal specific gravity of distilled water is 1.000. The specific gravity of urine is greater than 1.000 and reflects the density of the substances dissolved in the urine. Both the number of particles present and their size influence the specific gravity of urine. Large urea molecules, for example, influence the specific gravity more than do small sodium and chloride molecules. Similarly, if large amounts of glucose or protein are present in the sample, the specific gravity will be higher.15 The specific gravity of the glomerular filtrate is normally 1.010 as it enters Bowman’s capsule. A consistent urinary specific gravity of 1.010 usually indicates damage to the renal tubules such that concentrating ability is lost. Urine with a low specific gravity may be seen in clients with overhydration and diabetes insipidus. Urine with a high specific gravity is associated with dehydration, uncontrolled diabetes mellitus, and nephrosis. High specific gravities may also be seen in clients who are receiving intravenous (IV) solutions of dextran or other highmolecular-weight fluids and in those who have received radiologic contrast media. The specific gravity of urine provides preliminary information. For a more thorough evaluation of renal concentrating ability, urine osmolality may be determined, and concentration tests may be performed.16 PH The pH of urine reflects the kidney’s ability to regulate the acid–base balance of the body. In general, when too much acid is present in the body (i.e., respiratory or metabolic acidosis), acidic urine (low pH) is excreted. Conversely, alkaline urine (high pH) is excreted in states of respiratory or metabolic alkalosis. Various foods and drugs also affect urinary pH. The kidney controls the acid–base balance of the body through regulation of hydrogen ion excretion. Various acids are excreted via the glomerulus along with sodium ions. In the renal tubules, bicarbonate ions are reabsorbed and hydrogen ions are secreted in exchange for sodium ions. Additional hydrogen ions are excreted as ammonium. Disorders involving the renal tubules affect regulation of pH. In renal tubular acidosis, for example, the ability of the distal tubules to secrete hydrogen ions and form ammonia is impaired. Metabolic acidosis results. Similarly, in proximal tubular acidosis, bicarbonate is wasted. As noted previously, the acidity or alkalinity of the urine generally reflects that of the body. A paradoxic situation can occur, however, in clients with hypokalemic alkalosis, which can occur with prolonged vomiting or excessive use of diuretics. In this situation, an acidic urine may be produced when hydrogen ions are secreted instead of potassium ions (which are deficient) to maintain electrochemical neutrality in the renal tubules.17 The pH or urine samples must be evaluated in relation to the client’s dietary and drug intake. A diet high in meat and certain fruits such as cranberries produces acidic urine. A diet high in vegetables and citrus fruits produces an alkaline urine. Drugs such as ammonium chloride and methenamine mandelate produce an acid urine, whereas sodium bicarbonate, potassium citrate, and acetazolamide result in alkaline urine. The changes in urinary pH that occur in relation Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies to ingestion of certain foods and drugs are applied to the treatment of certain urinary tract disorders. Maintenance of an acidic urine may be used in the treatment of urinary tract infections (UTIs) because urea-splitting organisms do not multiply as rapidly in an acidic environment. These same organisms cause the pH of a urine specimen to rise if it is allowed to stand for a period of time.18 Acidic urine also helps to prevent the formation of ammonium magnesium kidney stones, which are more likely to form in alkaline urine. Other types of kidney stones are more likely to be prevented if the urine is alkaline. The induction of alkaline urine may also be used in the treatment of UTIs with drugs such as kanamycin, in sulfonamide therapy, and in the treatment of salicylate poisoning.19 Urine is generally less acidic after a meal (the “alkaline tide”) because of secretion of acids into the stomach. Urine tends to be more acidic in the morning as a result of the mild respiratory acidosis that normally occurs during sleep.20 Thus, the time of day at which the sample is collected may influence evaluation of urinary pH. PROTEIN Urine normally contains only a scant amount of protein, which derives from both the blood and the urinary tract itself. The proteins normally filtered through the glomerulus include small amounts of low-molecular-weight serum proteins such as albumin. Most of these filtered proteins are reabsorbed by the proximal renal tubules. The distal renal tubules secrete a protein (Tamm-Horsfall mucoprotein) into the urine. Other normal proteins in urine include microglobulin, immunoglobulin light chains, enzymes and proteins from tubular epithelial cells, leukocytes, and other cells shed by the urinary tract. More than 200 urinary proteins have been identified.21 Normal protein excretion must be differentiated from that which is caused by disease states. Persons who do not have renal disease may have proteinuria after strenuous exercise or during dehydration. Functional (nonrenal) proteinuria may also be seen in congestive heart failure (CHF), cold exposure, and fever.22 Postural (orthostatic) proteinuria may also occur in a small percentage of normal individuals. In this situation, the client spills protein while in an upright posture but not when recumbent. Postural proteinuria is evaluated by having the client collect a urine sample on first arising and then approximately 2 hours later after having been up and about. The second sample should be positive for protein; the first should be negative. Orthostatic proteinuria is of Urine 225 generally a benign condition, although the client should be reevaluated periodically for persistent, nonpostural proteinuria. Persistent proteinuria is generally indicative of renal disease or of systemic disorders leading to increased serum levels of low-molecular-weight proteins. Renal disease resulting in proteinuria may be a result of damage to the glomerulus or to the renal tubules. When the glomerular membrane is damaged, greater amounts of albumin pass into the glomerular filtrate. If damage is more extensive, large globulin molecules are also excreted. Nephrotic syndrome is an example of renal disease primarily associated with glomerular damage. In this disorder there is heavy proteinuria accompanied by decreased serum albumin. In contrast, renal disease resulting from tubular damage is characterized by loss of proteins that are normally reabsorbed by the tubules (i.e., low-molecular-weight proteins). An example of renal disease primarily associated with tubular damage is pyelonephritis. The proteinuria that occurs in disorders involving the renal tubules is generally not as profound as that associated with glomerular damage.23,24 Systemic disorders that result in excessive production or release of hemoglobin, myoglobin, or immunoglobulins may lead to proteinuria and may, in addition, lead to actual renal disease. Myoglobinemia, for example, which may occur with extensive destruction of muscle fibers, leads to excretion of myoglobin in the urine and may lead to acute renal tubular necrosis.25 Multiple myeloma, a neoplastic disorder of plasma cells, is another example of a systemic disorder that may cause proteinuria. In this disorder, the blood contains excessive levels of monoclonal immunoglobulin light chains (Bence Jones protein).26 This protein overflows through the glomerulus in quantities greater than the renal tubules can absorb. Thus, large amounts of Bence Jones protein appear in the urine. As with myoglobinuria, the excessive amounts of protein can ultimately damage the kidney itself. Because proteinuria may indicate serious renal or systemic disease, its detection on UA must always be further evaluated for possible cause. Proteinuria occurring in the latter months of pregnancy also must be carefully evaluated because it may indicate serious complications of pregnancy. GLUCOSE Normally, glucose is virtually absent from the urine. Although nearly all glucose passes into the glomerular filtrate, most of it is reabsorbed by the proximal renal tubules through active transport mechanisms. In active transport, carrier molecules attach to mole- Copyright © 2003 F.A. Davis Company 226 SECTION I—Laboratory Tests cules of other substances (e.g., glucose) and transport them across cell membranes. Usually there are enough carrier molecules to transport all of the glucose from the renal tubules back to the blood. If plasma glucose levels are very high, however, such that carrier mechanisms are overwhelmed, glucose will appear in the urine. The point at which a substance appears in the urine is called its renal threshold.27 The renal threshold for glucose ranges from 160 to 200 mg/dL, depending on the individual. That is, the blood sugar must rise to its renal threshold level before glucose appears in the urine. The most common cause of glycosuria is uncontrolled diabetes mellitus. Because even a normal person may have elevated blood glucose levels immediately after a meal, urine samples for glucose are best collected immediately before meals, when the blood sugar should be at its lowest point. Similarly, urine that has been accumulating in the bladder overnight may contain excessive amounts of glucose resulting from increased concentration of urine and perhaps also from something eaten the previous evening. Because a negative test result for urinary sugar may not necessarily indicate a normal blood sugar level and because there is a great deal of variation in individual renal thresholds for glucose, recent trends for diabetes control have moved away from urinary glucose monitoring to blood glucose monitoring. Evaluation of glucose in routine urine specimens, however, remains a useful screening technique. In addition to diabetes mellitus, many other disorders can result in glycosuria. In general, these disorders fall into two general categories: (1) those in which the blood sugar is elevated and (2) those in which the blood sugar is not elevated but in which renal tubular absorption of glucose is impaired. Disorders that may lead to elevated blood glucose levels and, thus, to glycosuria are listed in Table 6–2. In addition, several drugs are known to elevate the blood sugar enough to produce glycosuria. These also are listed in Table 6–2. When renal tubular reabsorption of glucose is impaired, glucose may appear in the urine without actual hyperglycemia. In disorders involving the renal tubules, glycosuria is one of many abnormal findings. Reabsorption of amino acids, bicarbonate, phosphate, sodium, and water may also be impaired. Disorders associated with altered renal tubular function and glycosuria are listed in Table 6–2. Pregnancy represents a special case in which glycosuria may be present without hyperglycemia. During pregnancy, the glomerular filtration rate (GFR) is increased so that it may not be possible for the renal tubules to reabsorb all of the glucose presented. Glucose may appear in the urine even though blood glucose levels are within normal limits. This situation must be distinguished from actual diabetes with elevated blood sugar levels, a serious complication of pregnancy.28 Certain drugs are known to produce false-positive results when testing for glucose in urine, especially when copper sulfate reduction testing methods (e.g., Clinitest tablets, Benedict’s solution) are used. These drugs are listed in Table 6–3. Allowing urine specimens to remain at room temperature for long periods may produce false-positive results. The presence of nonglucose sugars in the urine may also produce false-positive results in tests for glycosuria. These sugars include lactose, fructose, galactose, pentose, and sucrose. Lactose may appear in the urine during normal pregnancy and lactation, in lactase deficiency states, and in certain disorders affecting the intestines (e.g., celiac disease, tropical sprue, and kwashiorkor). Fructose may appear in the urine after parenteral feedings with fructose and in clients with inherited enzyme deficiencies, which are generally benign in nature. Galactose in the urine also is associated with certain inherited enzyme deficiencies. Pentose may appear in the urine after ingestion of excessive amounts of fruits. Similarly, sucrose may be found if large amounts of sucrose are ingested, but it may also be found in clients with intestinal disorders associated with sucrase deficiency (e.g., sprue).29 Glycosuria may, therefore, indicate a number of pathological states or may result from drug and food ingestion. A thorough history and further evaluation through additional laboratory tests are indicated whenever glycosuria occurs. KETONES The term ketones refers to three intermediate products of fat metabolism: acetone, acetoacetic acid, and -hydroxybutyric acid. Measurable amounts of ketones are not normally present in urine. With excessive fat metabolism, however, ketones may be found. Excessive fat metabolism can occur in several situations: (1) impaired ability to metabolize carbohydrates, (2) inadequate carbohydrate intake, (3) excessive carbohydrate loss, and (4) increased metabolic demand.30 The disorder most commonly associated with impaired ability to metabolize carbohydrates is diabetes mellitus. Because carbohydrates cannot be used to meet the body’s energy needs, fats are burned, leading to the presence of ketones in the urine. A similar situation occurs when carbohydrate intake is inadequate to the body’s needs. This is seen in weight-reduction diets and starvation. Excessive loss of carbohydrates (e.g., caused by vomiting and diarrhea) and increased metabolic demand (e.g., acute febrile conditions and Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies TABLE 6–2 • of Urine Disorders and Drugs That May Result in Glycosuria Glycosuria with High Blood Sugar Diabetes mellitus Glucosuria without High Blood Sugar Renal tubular dysfunction Gestational diabetes Fanconi’s syndrome Acromegaly Galactosemia Cushing’s syndrome Cystinosis Hyperthyroidism Lead poisoning Pheochromocytoma Multiple myeloma Advanced cystic fibrosis Pregnancy (must be distinguished from gestational diabetes) Hemochromatosis Severe chronic pancreatitis Carcinoma of the pancreas Hypothalamic dysfunction Brain tumor or hemorrhage Massive metabolic derangement Severe burns Uremia Advanced liver disease Sepsis Cardiogenic shock Glycogen storage disease Obesity Medication-induced hyperglycemia Adrenal corticosteroids Adrenocorticotropic hormone Thiazides Oral contraceptives Excessive IV glucose Dextrothyroxine TABLE 6–3 227 • Drugs That May Produce False-Positive Glycosuria Results Ascorbic acid Oxytetracycline (Terramycin) Cephalosporins Para-aminobenzoic acid (PABA) Chloral hydrate Paraldehyde Levodopa Penicillins Metaxalone (Skelaxin) Salicylates Morphine Streptomycin Nalidixic acid (NegGram) Radiographic contrast media Copyright © 2003 F.A. Davis Company 228 SECTION I—Laboratory Tests toxic states, especially in infants and children) can also produce ketonuria. Other disorders in which ketones may be found in the urine include lactic acidosis and salicylate toxicity. Ketonuria also has been found after anesthesia and is believed to be a result of both decreased food intake before surgery and increased metabolic demand in relation to physiological stressors. As with glucose, ketones in the urine are associated with elevated blood ketone levels. Because ketone bodies are acids, ketonuria may indicate systemic acidosis. Ketones in urine are measured most frequently in clients with diabetes mellitus and in those on weight-reduction diets. The finding of ketones on UA requires further follow-up through history and laboratory tests to determine the source. Individuals receiving levodopa, paraldehyde, phenazopyridine (Pyridium), and phthalein compounds may produce false-positive results when tested for ketonuria. BLOOD Blood can be present in the urine as either red blood cells or hemoglobin. If enough blood is present, the color of the sample can range from pink-tinged to red to brownish-black. Very small amounts of blood, although clinically significant, may not be detected unless the sample is tested with reagent strips (“dipsticks”) or by microscopic examination. The dipstick approach for macroscopic UA provides a useful screening approach. Positive results require further evaluation to determine the nature and source of the blood.31,32 The presence of red blood cells in urine (hematuria) is relatively common, whereas the presence of hemoglobin in urine (hemoglobinuria) is seen much less frequently. Hematuria is usually associated with disease of or damage to the genitourinary tract. When hematuria is accompanied by significant proteinuria, kidney disease is generally indicated (e.g., acute glomerulonephritis). In contrast, hematuria with only small amounts of protein is associated with inflammation and bleeding of the lower urinary tract (e.g., cystitis).33 Other disorders commonly associated with hematuria include pyelonephritis, tumors of the genitourinary tract, kidney stones, lupus nephritis, and trauma to the genitourinary tract. Nonrenal causes of hematuria include bleeding disorders and anticoagulant therapy. Hematuria may also occur in healthy individuals after excessive strenuous exercise because of damage to the mucosa of the urinary bladder.34 Free hemoglobin is not normally found in the urine. Instead, any hemoglobin that could be presented to the glomerulus combines with haptoglobin. The resultant hemoglobin–haptoglobin complex is too large to pass through the glomerular membrane. If the amount of free hemoglobin exceeds the amount of haptoglobin, however, the hemoglobin will pass through the glomerulus and ultimately be excreted into the urine.35 Any disorder associated with hemolysis of red blood cells and resultant release of hemoglobin can lead to the appearance of hemoglobin in the urine. Common causes of hemoglobinuria include hemolytic anemias, transfusion reactions, trauma to red blood cells by prosthetic cardiac valves, extensive burns, trauma to muscles and blood vessels, and severe infections. Hemoglobinuria may also occur in healthy individuals and is thought to be caused by trauma to small blood vessels.36 Note that hemoglobin is broken down in the renal tubular cells into ferritin and hemosiderin. Hemosiderin may, therefore, be found in urine a few days after an episode of acute red cell hemolysis. Hemosiderin also is found in the urine of individuals with hemochromatosis, a disorder of iron metabolism.37 BILIRUBIN AND UROBILINOGEN If the urine sample for UA appears dark or if the client is experiencing jaundice, the specimen can be tested for the presence of bilirubin and excessive urobilinogen. Both of these substances are bile pigments that result from the breakdown of hemoglobin (Fig. 6–1). The average life span of red blood cells is 120 days. Old and damaged cells are broken down primarily in the spleen and to some extent in the liver. The breakdown products are iron, protein, and protoporphyrin. The body reuses the iron and protein; the protoporphyrin is converted into bilirubin and is released into the circulation, where it combines with albumin. This form of bilirubin is called unconjugated or prehepatic bilirubin. It does not pass into the urine because the complex is insoluble in water and is too large to pass through the glomerular membrane. When circulating unconjugated bilirubin reaches the liver, it is conjugated with glucuronic acid. The conjugated (posthepatic) bilirubin is normally absorbed into the bile ducts, stored in the gallbladder, and ultimately excreted via the intestine.38 In the intestine, bilirubin is converted into urobilinogen by bacteria. Approximately half of the urobilinogen is excreted in the stools, where it is converted into urobilin; the remaining half is reabsorbed from the intestine back into the bloodstream. From the bloodstream, urobilinogen is either recir- Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 229 Figure 6–1. Hemoglobin degradation. (From Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 56, with permission.) culated to the liver and excreted with bile or excreted via the kidneys. Normally, only a small amount of urobilinogen is found in the urine.39 Bilirubin may be found in the urine in liver disease and is usually found in clients who have biliary tract obstructions. Excessive urobilinogen may also be found in the urine of those with liver disease or hemolytic disorders. Urobilinogen is absent from the urine in disorders that cause complete obstruction of the bile ducts (Table 6–4). Bilirubinuria can occur in clients with liver disease when the integrity of liver cells is disrupted and conjugated bilirubin leaks into the circulation; this leakage may be seen in hepatitis and cirrhosis. In fact, in these disorders, bilirubin may appear in the urine before the client actually becomes jaundiced. If liver function is impaired such that the liver cannot conjugate bilirubin, excessive bilirubin will not be found in the urine. Similarly, excessive bilirubin is not seen in the urine of clients with hemolytic disorders. These disorders have marked destruction of red blood cells with resultant high levels of unconjugated bilirubin. The normally functioning liver is unable to conjugate the excessive load, and although serum levels of unconjugated bilirubin rise, urinary bilirubin excretion remains relatively unchanged. TABLE 6–4 • This condition, again, is a result of the kidney’s inability to excrete unconjugated bilirubin. If bile duct obstruction occurs, the conjugated bilirubin cannot pass from the biliary tract into the intestine. Instead, excess amounts are absorbed into the bloodstream and excreted via the kidneys. Also, because little or no bilirubin passes into the intestine, where urobilinogen is formed, the urine will be negative for urobilinogen. Absence of urobilinogen in urine is associated with complete obstruction of the common bile duct. When absence of urobilinogen is combined with the presence of blood in the stool, carcinoma involving the head of the pancreas may be indicated.40 As noted previously, approximately half of the urobilinogen formed in the intestines is reabsorbed into the bloodstream. Normally, most of this urobilinogen is circulated to the liver, where it is processed and excreted via bile. A smaller amount is excreted in the urine. When liver cells are damaged, excretion of urobilinogen in bile is decreased, whereas its urinary excretion is increased. This condition may be seen in clients with cirrhosis, hepatitis, and CHF with congestion of the liver. Excessive urobilinogen also appears in the urine in persons with hemolytic disorders. As noted, in Urine Bilirubin and Urobilinogen in Jaundice Urine Bilirubin Bile duct obstruction Urine Urobilinogen Normal Liver damage or Hemolytic disease Negative From Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 57, with permission. Copyright © 2003 F.A. Davis Company 230 SECTION I—Laboratory Tests such disorders the amount of unconjugated bilirubin produced is more than the liver can handle, but the liver attempts to compensate, and increased amounts of urobilinogen are ultimately formed. When this urobilinogen is recirculated back to the liver, however, the liver is unable to process it further and additional amounts are excreted in the urine. A number of factors can cause spurious results when urine is tested for bilirubin and urobilinogen. Because excessive exposure of a urine sample to light and room air may lead to false-negative results for bilirubin, only fresh urine specimens should be used. Large amounts of ascorbic acid and nitrates in the urine also cause false-negative results. Note that bilirubin excretion is enhanced in alkalotic states. This also is true of urobilinogen and is a result of decreased tubular reabsorption from alkaline urine. Similarly, acidic urine results in decreased urinary levels of urobilinogen. As noted, urobilinogen is formed by bacterial action in the intestine. Broadspectrum antibiotics impair this process and result in decreased urobilinogen production. As with bilirubin, high levels of nitrates in the urine may also cause false-negative results in tests for urobilinogen.41,42 NITRITE Testing urine samples for nitrite is a rapid screening method for determining the presence of bacteria in the specimen. This test is based on the fact that nitrate, which is normally present in urine, is converted to nitrite in the presence of bacteria. The test is performed by the dipstick method and, if positive, indicates that clinically significant bacteriuria is present. Positive test results should always be followed by a regular urine culture. Several factors can interfere with the accuracy of tests for nitrite. First, not all bacteria reduce nitrate to nitrite. Those that do so include the gram-negative bacteria, the organisms most frequently involved in UTIs. Because yeasts and gram-positive bacteria may not convert nitrate to nitrite, the presence of these organisms can cause a false-negative test result. For bacteria to convert nitrate to nitrite, the organisms must be in contact with urinary nitrate for some period of time. Thus, freshly voided random samples or urine that is withdrawn from a Foley catheter may produce false-negative results. The best urine samples for nitrite testing are first morning samples from urine that has been in the bladder overnight. Other causes of false-negative results include inadequate amounts of nitrate in the urine for conversion (may occur in individuals who do not eat enough green vegetables), large amounts of ascorbic acid in the urine, antibiotic therapy, and excessive bacteria in the urine so that nitrite is further reduced to nitrogen, which is not detected by the test. False-positive reactions will occur if the container in which the sample is collected is contaminated with gram-negative bacteria.43,44 LEUKOCYTE ESTERASE Testing urine samples for the presence of leukocyte esterase is a rapid screening method for determining the presence of certain white blood cells (i.e., neutrophils) in the sample and, thus, the possibility of a UTI. This test is performed by the dipstick method and is based on the fact that the esterases present in neutrophils will convert the indoxyl carboxylic acid ester on the dipstick to indoxyl, which is converted to indigo blue by room air. Approximately 15 minutes are needed for this reaction to take place if neutrophils are present. If positive, the test should be followed by a regular urine culture.45 Some factors can interfere with the accuracy of tests for leukocyte esterases. False-positive results can occur if the sample is contaminated with vaginal secretions.46 False-negative results can occur if high levels of protein and ascorbic acid are present in the urine. If the urine contains excessive amounts of yellow pigment, a positive reaction will be indicated by a change to green instead of blue.47 MICROSCOPIC ANALYSIS The microscopic component of a UA involves examining the sample for formed elements, or urinary sediment, such as red and white blood cells, epithelial cells, casts, crystals, bacteria, and mucus. Microscopic analysis is performed by centrifuging approximately 10 to 15 mL of urine for about 5 minutes. The resulting sediment is then examined under the microscope. Microscopic analysis is the most time-consuming component of the UA. It involves both identifying and quantifying the formed elements present.48 Note that the Addis count is a variation of the microscopic urinalysis. For an Addis count, all urine is collected for 12 hours and then the nature and quantity of formed elements are determined. This test, which was once used to follow the progress of acute renal disease, is seldom used today, because microscopic analysis of a single random sample usually is sufficient.49 RED BLOOD CELLS Red blood cells are too large to pass through the glomerulus; thus, the finding of red blood cells in the urine (hematuria) is considered abnormal. If red Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies blood cells are present, damage to the glomerular membrane or to the genitourinary tract is indicated. For this test, the number of red blood cells is counted. The result may indicate the nature and severity of the disorder causing the hematuria. Renal and genitourinary disorders associated with the presence of red blood cells in the urine include glomerulonephritis, lupus nephritis, nephritis associated with drug reactions, tumors of the kidney, kidney stones, infections, trauma to the kidney, renal vein thrombosis, hydronephrosis, polycystic kidney disease, acute tubular necrosis (occasionally), and malignant nephrosclerosis (occasionally).50 Red blood cells may also be seen with some nonrenal disorders: acute appendicitis; salpingitis; diverticulitis; tumors involving the colon, rectum, and pelvis; acute systemic febrile and infectious diseases; polyarteritis nodosa; malignant hypertension; and blood dyscrasias. Drugs that may lead to hematuria include salicylates, anticoagulants, sulfonamides, and cyclophosphamide. Strenuous exercise can also cause red blood cells to appear in the urine because of damage to the mucosa of the bladder.51 Contamination of the sample with menstrual blood may lead to false-positive results. WHITE BLOOD CELLS Normally, only a few white blood cells are found in urine. Increased numbers of leukocytes in the urine generally indicate either renal or genitourinary tract disease. As with red blood cells, white blood cells may enter the urine either through the glomerulus or through damaged genitourinary tissues. In addition, white blood cells may migrate through undamaged tissues to sites of infection or inflammation. An excessive amount of white blood cells in the urine is termed pyuria.52 The most frequent cause of pyuria is bacterial infection anywhere in the renal or genitourinary system (e.g., pyelonephritis, cystitis). Noninfectious inflammatory disorders, however, may also lead to pyuria. Such disorders include glomerulonephritis and lupus nephritis. In addition, tumors and renal calculi may cause pyuria because of the resultant inflammatory response. A higher than normal number of leukocytes may be seen if the sample is contaminated with genital secretions. This finding is especially true in women. White blood cells disintegrate in dilute, alkaline urine and in samples that are allowed to stand at room temperature for more than 1 to 2 hours.53 EPITHELIAL CELLS Epithelial cells found in urine samples are derived from three major sources: (1) the linings of the male of Urine 231 and female lower urethras and the vagina (squamous epithelial cells); (2) the linings of the renal pelvis, bladder, and upper urethra (transitional epithelial cells); and (3) the renal tubules themselves. Because it is normal for old epithelial cells to slough from their respective areas, finding a few epithelial cells in a urine sample is not necessarily abnormal. Presence of a large numbers of cells, especially those of renal tubular origin, is considered a pathological situation. When large numbers of renal tubular cells are shed, tubular necrosis is indicated. In addition to acute tubular necrosis (ATN), excessive numbers of tubular epithelial cells may be seen in renal transplant rejection, any ischemic injury to the kidney, glomerulonephritis, pyelonephritis, and damage to the kidney by drugs and toxins.54 Renal tubular epithelial cells may contain certain lipids and pigments. Cells that contain lipoproteins, triglycerides, and cholesterol are called oval fat bodies. Presence of oval fat bodies occurs in lipid nephrosis and results from lipids leaked through nephrotic glomeruli. Histiocytes are fat-containing cells that are larger than oval fat bodies and that usually can be distinguished from the latter on microscopic examination. Histiocytes may be seen in nephrotic syndrome and in lipid-storage diseases.55 Pigments that may be absorbed into renal tubular epithelial cells include hemoglobin that is converted to hemosiderin, melanin, and bilirubin. Hemoglobin and bilirubin have been discussed previously. Melanin may be found in tubular epithelial cells in the presence of malignant melanoma that has metastasized to the genitourinary tract. Finding increased epithelial cells from the lower genitourinary tract is generally not of major clinical significance, with one exception. If excessive numbers of transitional epithelial cells are found in large clumps, or sheets, carcinoma involving any portion of the area from the renal pelvis to the bladder may be indicated.56 CASTS Casts are gel-like substances that form in the renal tubules and collecting ducts. They are termed casts because they take the shape of the area of the tubule or collecting duct in which they form. TammHorsfall protein, a mucoprotein secreted by the distal renal tubular cells, is the major constituent of casts. This protein forms a framework in which other elements may be trapped (e.g., red and white blood cells, bacteria, fats, urates). Healthy individuals may normally excrete a few casts, especially if there is a low urinary pH, increased protein in the urine, increased excretion of solutes, and decreased Copyright © 2003 F.A. Davis Company 232 SECTION I—Laboratory Tests rate of urine flow.57 As noted previously, proteinuria may occur after strenuous exercise. This may lead to the formation and excretion of an increased number of casts in healthy individuals. Red blood cells may also be found in casts excreted in response to such exercise. Otherwise, excretion of an excessive number of casts is usually associated with widespread kidney disease that involves the renal tubules.58 Casts are classified according to the nature of the substances present in them (Table 6–5). As can be seen in the table, the finding of excessive numbers of casts requires further diagnostic follow-up, because such a condition may indicate serious renal disease. CRYSTALS Crystals form in urine because of the presence of the salts from which they are precipitated. Of the numerous types of crystals (Table 6–6), many are not of major clinical significance. Also, several factors affect the formation of urinary crystals: (1) pH of the urine, (2) temperature of the urine, and (3) concentration of the substances from which the crystals are formed. Table 6–6 shows the pH of the urine at which the several types of crystals are most likely to be formed. In terms of the temperature of the sample, crystals are most likely to be seen in samples that have stood at room temperature for several hours or have been refrigerated, depending on the type of crystal. The concentration of various substances that lead to the formation of crystals is important in that the greater the concentration, the greater the likelihood of precipitation of the substance into the urine in crystal formation. In analyzing crystals on microscopic examination, it is important to determine the type of crystal present. The presence of certain crystals may indicate disease states (e.g., liver disease, cystinuria). In addition, drug therapy or use of radiographic dyes can cause precipitation of crystals that may portend renal damage by blocking the tubules.59 OTHER SUBSTANCES A number of other substances may be found on microscopic urinalysis: bacteria, yeast, mucus, spermatozoa, and parasites. Bacteria are not normally present but may be seen if UTI is present or if the sample was contaminated externally. The number of bacteria will increase if the specimen is allowed to stand at room temperature for several hours. Bacteria in the urine are generally not of major significance unless accompanied by excessive numbers of white blood cells, which may indicate an infectious or inflammatory process. Yeast in the urine usually indicates contamination of the sample with vaginal secretions in women with yeast infections such as Candida albicans. Yeasts may also be seen in the urine of clients with diabetes. Mucus in urine generally reflects secretions from the genitourinary tract and is usually associated with contamination of the sample with vaginal secretions. Spermatozoa may be found in urine after sexual intercourse or nocturnal emissions. Parasites are frequently of vaginal origin and may indicate vaginitis caused by Trichomonas vaginalis. A true urinary parasite is Schistosoma haematobium, seen in the urine of individuals with schistosomiasis, an uncommon disorder in the United States. If pinworms and other intestinal parasites are found, contamination of the sample with fecal material is indicated.60 SUMMARY The UA, which consists of macroscopic and microscopic components, yields a great deal of information about the client. All the tests may be performed separately, especially those associated with macroscopic analysis. The most complete picture, however, is obtained by synthesizing the data obtained from the various tests. Although a variety of disorders may be indicated by abnormal results on a UA test, the most common disorders indicated are the several types of renal disease. Table 6–7 shows ways in which the results of macroscopic and microscopic analyses are combined to indicate certain types of renal disease. Other types of disorders associated with abnormal urinalysis results are listed in the indications for the UA test. INTERFERING FACTORS Improper specimen collection so that the sample is contaminated with vaginal secretions or feces Use of collection containers contaminated with bacteria Therapy with medications or ingestion of foods that may alter the color, odor, or pH of the sample Delay in sending unrefrigerated samples to the laboratory within 1 hour of collection, which may lead to: Deepening of the color of the sample Increased alkalinity of the sample Increased concentration of glucose, if already present Oxidation of bilirubin, if present, and urobilinogen Deterioration of urinary sediment Multiplication of bacteria, if present Failure to time properly those tests done by the dipstick method (e.g., glucose and ketones) Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies TABLE 6–5 • Type Hyaline of Urine 233 Summary of Urine Casts Origin Tubular secretion of Tamm-Horsfall protein Clinical Significance Glomerulonephritis Pyelonephritis Chronic renal disease Congestive heart failure Stress and exercise Red blood cell Attachment of red blood cells to Tamm-Horsfall protein matrix Glomerulonephritis Strenuous exercise Lupus nephritis Subacute bacterial endocarditis Renal infarction Malignant hypertension White blood cell Attachment of white blood cells to Tamm-Horsfall protein matrix Inflammation or infection involving the glomerulus Pyelonephritis Lupus nephritis Epithelial cell Tubular cells remaining attached to Tamm-Horsfall protein fibrils Renal tubular damage Granular Disintegration of white cell casts Stasis of urine flow Bacteria Urinary tract infection Urates Stress and exercise Tubular cell lysosomes Acute glomerulonephritis Protein aggregates Renal transplant rejection Pyelonephritis Lead poisoning Waxy Hyaline casts in an advanced stage of development Stasis of urine flow Renal transplant rejection Renal tubular inflammation and degeneration Chronic renal failure End-stage renal disease Fatty Renal tubular cells Nephrotic syndrome Broad casts Oval fat bodies Nephrotic syndrome Formation in collecting ducts (i.e., casts are larger than those formed in the tubules) Extreme stasis of urine flow Renal failure (severe) Chronic glomerulonephritis Adapted from Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 93. Copyright © 2003 F.A. Davis Company 234 SECTION I—Laboratory TABLE 6–6 Crystal • Tests Major Characteristics and Clinical Significance of Urinary Crystals pH Color Clinical Significance NORMAL Uric acid Acid Yellow-brown Gout Leukemias and lymphomas, especially if client is receiving chemotherapy Amorphous urates Acid Brick dust or yellow-brown Not of major clinical significance Calcium oxalate Acid/neutral (alkaline) Colorless (envelopes) High doses of ascorbic acid Severe chronic renal disease Ethylene glycol toxicity Crohn’s disease, hypercalcemia Amorphous phosphates Alkaline, neutral White colorless May be found in urine that has stood at room temperature for several hours Calcium phosphate Alkaline, neutral Colorless Not of major clinical significance Ammonium biurate Alkaline Yellow-brown (thorny apples) Not of major clinical significance Calcium carbonate Alkaline Colorless (dumb-bells) Not of major clinical significance Triple phosphate Alkaline Colorless (coffin lids) Not of major clinical significance Cystine Acid Colorless Cystinuria (inherited metabolic defect that prevents reabsorption of cystine by the proximal tubules) Cholesterol Acid Colorless (notched plates) High serum cholesterol More likely to be seen in refrigerated specimens Leucine Acid/neutral Yellow Severe liver disease ABNORMAL Tyrosine Acid/neutral Colorless, yellow Severe liver disease Sulfonamides Acid/neutral Green Therapy with sulfonamides Radiographic dye Acid Colorless Dye excretion Ampicillin Acid/neutral Colorless Therapy with ampicillin Adapted from Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001. pp 115–116. INDICATIONS FOR ROUTINE URINALYSIS The routine urinalysis is a screening technique that is an essential component of a complete physical examination, especially when performed on admission to a health-care facility or before surgery. It may also be performed when renal or systemic disease is suspected. Note that the components of a UA may be performed separately, if necessary. This may be done to monitor previously identified conditions. Other indications or purposes for a UA include the following: Detection of infection involving the urinary tract as indicated by urine with a “fishy” or fetid odor and presence of nitrite, leukocyte esterase, white blood cells, red blood cells (possibly), and bacteria Copyright © 2003 F.A. Davis Company TABLE 6–7 • Laboratory Correlations in Renal Diseases Disease Macroscopic Examination Acute glomerulonephritis Macroscopic hematuria RBCs ASO titer ↑ Specific gravity ↑ RBC casts GFR ↓ Protein 5 g/day Granular casts Sed rate ↑ Microscopic Examination Remarks Other Laboratory Findings Microscopic hematuria remains longer than proteinuria WBCs Macroscopic hematuria Protein RBCs WBCs Granular casts BUN ↑ Creatinine ↑ FDP ↑ GFR ↓ Cryoglobulins ↑ Oliguria Chronic glomerulonephritis Macroscopic hematuria RBCs BUN ↑ Oliguria or anuria Specific gravity 1.010 WBCs Creatinine ↑ Nocturia Protein All types of casts Broad casts Serum phosphorus ↑ Serum calcium ↓ Anemia Membranous glomerulonephritis Blood Protein RBCs Hyaline casts Positive ANA Positive HBsAg Microscopic hematuria Membranoproliferative (mesangioproliferative) glomerulonephritis Macroscopic hematuria Protein RBCs RBC casts BUN ↑ Creatinine ↑ ASO titer ↑ Complement ↓ Hematuria may be microscopic Focal glomerulonephritis Blood Protein RBCs Fat droplets IgA deposits on membrane Macroscopic or microscopic hematuria of Urine (Continued on the following page ) CHAPTER 6—Studies “Smoky” turbidity Rapidly progressive (crescentic) glomerulonephritis 235 Copyright © 2003 F.A. Davis Company 236 • Laboratory Correlations in Renal Diseases (Continued) Disease Macroscopic Examination Minimal change disease Blood Microscopic Examination Other Laboratory Findings Serum protein ↓ Oval fat bodies Serum albumin ↓ Hematuria may be absent Tests RBCs Remarks Fat droplets Hyaline casts Fatty casts Nephrotic syndrome Protein Oval fat bodies Serum lipids ↑ Fat droplets Serum protein ↓ Generalized casts Serum albumin ↓ Heavy proteinuria 5 g/day Waxy casts Fatty casts Pyelonephritis Cloudy WBCs Protein WBC casts Nitrite Bacteria Leukocytes RBCs SECTION I—Laboratory TABLE 6–7 Concentrating ability decreased in chronic cases Adapted from Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, pp 124–130. ANAantinuclear antibody, ASOantistreptolysin O, BUNblood urea nitrogen, FDPfibrin degradation products, GFRglomerular filtration rate, HbsAghepatitis B surface antigen, IgAimmunoglobulin A. Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 237 Reference Values Macroscopic Analysis Color Pale yellow to amber Appearance Clear to slightly cloudy Odor Mildly aromatic Specific gravity 1.001–1.035 (usual range 1.010–1.025) pH 4.5–8.0 Protein Negative Glucose Negative Other sugars Negative Ketones Negative Blood Negative Bilirubin Negative Urobilinogen 0.1–1.0 Ehrlich units/dL (1–4 mg/24 hr) Nitrate Negative Leukocyte esterase Negative Microscopic Analysis Red blood cells (RBCs) 0–3 per high-power field (HPF) White blood cells (WBCs) 0–4 per HPF Epithelial cells Few Casts Occasional (hyaline or granular) Crystals Occasional (uric acid, urate, phosphate, or calcium oxalate) Critical values: RBC 0.50, WBC, or pathological crystals, as well as grossly bloody urine, and 3 to 41 glucose or ketones, or both Detection of uncontrolled diabetes mellitus as indicated by the presence of glucose and ketones (seen primarily in insulin-dependent diabetes mellitus) and by urine with low specific gravity Detection of gestational diabetes during pregnancy Detection of possible complications of pregnancy as indicated by proteinuria Detection of bleeding within the urinary system, as indicated by positive dipstick test for blood and detection of red blood cells on microscopic examination Detection of various types of renal disease (see Table 6–7) Detection of liver disease as indicated by the presence of bilirubin (possibly), excessive urobilinogen, and leucine or tyrosine crystals, or both Detection of obstruction within the biliary tree as indicated by presence of bilirubin and absence of urobilinogen Detection of multiple myeloma as indicated by the presence of Bence Jones protein Monitoring of the effectiveness of weight-reduction diets as indicated by the presence of ketones in the urine Detection of excessive red blood cell hemolysis within the systemic circulation as indicated by the presence of free hemoglobin and elevated urobilinogen levels Detection of extensive injury to muscles as indicated by the presence of myoglobin in the urine NURSING CARE BEFORE THE PROCEDURE Explain to the client: That results are most reliable if the specimen is obtained upon arising in the morning, after urine has accumulated overnight in the bladder (Exception: Serial urine samples for glucose should consist of fresh urine.) Copyright © 2003 F.A. Davis Company 238 SECTION I—Laboratory Tests Nursing Alert Improper collection and disposition of sample for UA may lead to spurious results (see “Interfering Factors” section). The best samples, in general, are those that are collected first thing in the morning after urine has collected in the bladder overnight. The sample should be received in the laboratory within 1 hour of collection. If this is not possible, the sample can be refrigerated. The time of collection and the source of the sample must be noted, because this information is important in evaluating the results and in distinguishing normal from abnormal results. Because many drugs and foods may alter results, a thorough medication and diet history is necessary for evaluating the data obtained. The proper way to collect the sample, if the client is to do this independently (see Appendix II) The importance of the sample being received in the laboratory within 1 hour of collection Prepare for the procedure: The client should be provided with the proper specimen container. For women, a clean-catch midstream kit should be provided. Techniques for collecting samples from children are described in Appendix II. For catheterized specimens, a catheterization tray is needed if an indwelling catheter is not already present. THE PROCEDURE A voided or catheterized sample of approximately 15 mL is collected (see Appendix II). NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include observing the color, clarity, and odor of the sample when it is obtained. Perform dipstick tests for glucose, ketones, protein, and blood on separate portions of the sample, if desired. Hydration state: Note and report intake and output (I&O) ratio and adequacy, changes in urinary pattern and diuresis, and dehydration and fluid shifts. Monitor I&O and effect on specimen collection and testing, urinary sample characteristics and amount, and urinary pattern changes. Correct techniques: Store dipsticks in a dry, cool, dark place. Immerse dipstick in the urine for an appropriate time and examine in a well-lit place after an appropriate time interval. Confirm all abnormal test results. Specific gravity: Note and report increases over 1.020. Monitor I&O. Assess for dehydration. Administer additional fluids, if allowed. Note decreases below 1.009. Monitor I&O and weight for fluid overload. Assess for renal dysfunction. Inform and instruct client in fluid intake necessary to maintain adequate hydration. pH: Note and report increases over 6 (alkaline urine). Assess for risk of or presence of UTI or renal calculi. Increase fluid intake and restrict foods that leave an alkaline ash (milk, citrus fruits). Administer ordered vitamin C. Note decreases below 6 (acid urine). Administer medications to promote an alkaline urine. Assess for possible metabolic or respiratory acidotic states. Protein: Note and report any trace or range of protein from 0 to 41 or 10 to 1000 mg/dL. Collect another specimen and test or prepare the client for an ordered 24-hour urine analysis. Glucose: Note and report any trace or range of glucose from 0 to 41. Assess blood glucose level. Also assess for drugs that cause elevations, increased urinary output and thirst, or possible dehydration state. Prepare for further testing for glucose levels in the blood and urine. Ketones: Note and report moderate acetone level and blood level over 50 mg/dL. Assess weight, dietary regimen, diarrhea, presence of diabetes mellitus, or possible ketoacidotic state. Administer ordered insulin or other medications. Blood: Note and report microscopic or macroscopic amounts of blood. Assess for anticoagulant therapy, urinary tract or renal disorders, or toxic response to drug therapy. Bilirubin: Note and report presence of bilirubin. Assess for jaundice of mucous membranes and sclera and for clay color of stool. Also assess for liver or biliary tract disorders and drug regimens that cause liver damage. Nitrite: Note and report positive result. Obtain a clean-catch urine specimen for culture tests. Leukocyte esterase: Note and report positive results with a positive nitrite test. Obtain a cleancatch urine specimen for culture tests. Critical values: Physician should be notified immediately of a positive microscopic result of high levels of red blood cells, greater than 50 white blood cells, or pathological crystals, as well as grossly bloody urine, and 3 to 41 or 1 to Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies 2 percent of glucose or ketones, or both, by dipstick testing. TESTS OF RENAL FUNCTION Renal function tests are used to evaluate the excretory, secretory, and osmolar regulation dynamics of the kidney. Broad categories of such tests include (1) clearance tests, (2) tubular function tests, and (3) concentration tests. CLEARANCE TESTS AND CREATININE CLEARANCE The term clearance refers to the relationship between the renal excretory mechanisms and the circulating blood levels of the materials to be excreted. Clearance reflects the overall efficiency of glomerular functioning. Substances filtered through the glomerulus are (1) excreted into the urine unaltered by the renal tubules, (2) reabsorbed partially or entirely by the renal tubules, or (3) added to by the renal tubules. For the purpose of clearance tests, substances that pass through the glomerulus and are not altered by the renal tubules are analyzed. The assumption is that all of the substance is cleared from the plasma via the glomerulus and is excreted unchanged into the urine. Substances that may be measured in clearance tests include inulin, urea, para-aminohippuric acid (PAH), and creatinine.61 Inulin is an inert sugar that is not metabolized, absorbed, or secreted by the body. To determine renal clearance, inulin must be infused IV at a constant rate throughout the testing period. Renal clearance is then calculated by measuring the urinary excretion of inulin in relation to plasma concentration. Because this test involves administration of an exogenous substance, it is not used frequently.62 PAH is similar to inulin in that it also must be administered IV for clearance tests. Urea, an end product of protein metabolism, is formed in the liver and excreted relatively unchanged by the kidneys. Blood urea levels are affected by a variety of factors, and, therefore, it is not the ideal substance for renal clearance tests. Blood urea levels may be elevated if shock, trauma, sepsis, or tumors cause increased protein metabolism. A high-protein diet or state of dehydration will also cause elevated blood urea levels. High blood urea levels could result in normal clearance test values even though renal function is depressed. Creatinine is the ideal substance for determining renal clearance because a fairly constant quantity is produced within the body. As discussed in Chapter of Urine 239 5, creatinine is the end product of creatine metabolism. Creatine resides almost exclusively in skeletal muscle, where it participates in energy-requiring metabolic reactions. In these processes, a small amount of creatine is irreversibly converted to creatinine, which then circulates to the kidneys and is excreted. The amount of creatinine generated in an individual is proportional to the mass of skeletal muscle present and remains fairly constant unless there is massive muscle damage caused by crushing injury or degenerative muscle disease.63 Because muscle mass is usually greater in men than in women, the quantity of creatinine excreted is usually greater in men. Creatinine clearance is a sensitive indicator of glomerular function because those factors affecting creatinine clearance are primarily caused by alterations in renal function. These factors include the number of functioning nephrons, the efficiency with which they function (i.e., if there is decreased functioning of some nephrons, others may function more efficiently to compensate), and the amount of blood entering the nephrons. In general, a 50 percent reduction in functioning nephrons causes creatinine clearance to be slightly decreased. Loss of two-thirds of the nephrons, however, produces a sharp decrease. Note that creatinine clearance tends to decline with normal aging. Thus, it is important to know the client’s age when interpreting test results.64 Renal disease is the major cause of reduced creatinine clearance. Other disorders that can result in decreased creatinine clearance include shock, hypovolemia, and exposure to nephrotoxic drugs and chemicals. The creatinine clearance test is performed by collecting all urine for 24 hours, measuring the creatinine present, and calculating clearance according to the basic formula shown here. As indicated by the formula, it is necessary to determine the plasma level of creatinine at some point during the test. C UV P where C creatinine clearance U amount of creatinine in urine V volume of urine excreted per 24 hours P plasma creatinine level INTERFERING FACTORS Incomplete urine collection may yield a falsely lowered value. Excessive ketones in urine and presence of substances such as barbiturates, phenolsulfon- Copyright © 2003 F.A. Davis Company 240 SECTION I—Laboratory Tests Reference Values Creatinine Clearance Conventional Units SI Units Men 85–125 mL/min 1.41–2.08 mL/s/1.73 m2 Women 75–115 mL/min 1.21–1.91 mL/s/1.73 m2 phthalein, and sulfobromophthalein (Bromsulphalein [BSP]) may cause falsely lowered values. INDICATIONS FOR CLEARANCE TESTS AND CREATININE CLEARANCE Determination of the extent of nephron damage in known renal disease (i.e., at least 50 percent of functioning nephrons must be lost before values will be decreased) Monitoring for the effectiveness of treatment in renal disease Determination of renal function before administering nephrotoxic drugs or drugs that may build up if glomerular filtration is reduced NURSING CARE BEFORE THE PROCEDURE Explain to the client: The necessity of collecting all urine for 24 hours How to maintain the sample (e.g., on ice, refrigerated) if being collected at home That a blood sample also will be collected once during the test Prepare for the procedure: Provide the proper collection container. Provide for proper preservation of the sample. Use the techniques for collecting a 24-hour sample as described in Appendix II. THE PROCEDURE Creatinine Clearance. A 24-hour urine sample is collected (see Appendix II). A preservative may be added to the collection container by the laboratory to prevent degradation of the creatinine. If a preservative is not available, the urine should be kept on ice or refrigerated throughout the collection period. A blood sample is obtained at some point during the urine collection to determine plasma creatinine level. NURSING CARE AFTER THE PROCEDURE Special aftercare interventions are not required for this test. Compromised renal function: Note and report creatinine clearance that has decreased in comparison to an increased serum creatinine and estimated GFR. Monitor I&O and fluid and protein restrictions. Instruct client in dietary, fluid, and medication inclusions and exclusions. TUBULAR FUNCTION TESTS AND PHENOLSULFONPHTHALEIN TEST Tubular function tests assess the ability of the renal tubules to remove waste products and other substances (e.g., drugs) from the blood and secrete them into the urine. Normal tubular function is dependent on two main factors: (1) adequate renal blood flow and (2) effective tubular function. According to Sacher and McPherson,65 although tests of tubular function may provide valuable physiological insight, they provide little diagnostic information in individual clinical situations. More appropriate information may be obtained by measuring blood and urine levels of substances such as glucose and electrolytes and comparing the results. Elevated serum potassium levels, for example, combined with decreased potassium in the urine indicate impaired tubular secretion of potassium. Failure to excrete an appropriate acidic or alkaline urine in relation to blood pH levels also indicates disruption of normal tubular secreting mechanisms. If tubular function tests are to be performed, they are usually carried out by injecting phenolsulfonphthalein (PSP) IV and then measuring its excretion in serial urine samples. PSP is a dye that binds to albumin in the bloodstream and, therefore, cannot be excreted through the glomerulus. To be excreted, the dye must be secreted by renal tubular cells. In the proximal renal tubules, the dye has greater affinity for the cells lining the tubules than it does for the protein. When it dissociates from the protein, it can be secreted by the tubules.66 Because it is a dye, PSP imparts a pinkish color to alkaline urine upon excretion. Within 2 hours of injection, 75 percent of the dose is excreted if renal blood flow and tubular function are normal. Measurement of the dye that is present is accomplished with a spectrophotometer. Thus, any substances that alter the color of urine (see Table 6–1) may also alter test results. The client must be well hydrated so that renal perfusion is adequate and urine flow is brisk. If the urine lacks sufficient alkalinity, substances such as sodium hydroxide may be added to the sample in the laboratory to produce the necessary pH for testing. Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 241 Reference Values Adults After 15 min, 25% of the dose is excreted After 30 min, 50–60% of the dose is excreted After 60 min, 60–70% of the dose is excreted After 2 hr, 70–80% of the dose is excreted Children Amounts excreted are 5–10% higher at the preceding time intervals INTERFERING FACTORS Failure to collect the urine samples at the required times (Reference Values are based on these times.) Failure to completely empty the bladder each time a specimen is collected Presence in the urine of any substance that alters the color of urine (see Table 6–1), because results are based on dye excretion Inadequately hydrated client such that the kidneys are inadequately perfused or urine flow is decreased Presence in the blood of radiographic dye, salicylates, sulfonamides, and penicillin that may lead to decreased excretion of the dye High serum protein levels, which may lead to decreased excretion of the dye Severe hypoalbuminemia, excessive albuminuria, or severe liver disease, which may lead to increased excretion of the dye INDICATIONS FOR TUBULAR FUNCTION TESTS AND PHENOLSULFONPHTHALEIN TEST Assessment of renal blood flow and tubular secreting ability (The PSP test is of limited clinical usefulness.) Nursing Alert The PSP excretion test should not be performed on clients who have demonstrated previous allergy to the dye. NURSING CARE BEFORE THE PROCEDURE Explain to the client: The importance of increased fluid intake before the test That foods and drugs that impart color to the urine (e.g., carrots, beets, rhubarb, azo drugs) should be avoided for 24 hours before the test That a dye that circulates through the blood and then is excreted by the kidneys will be injected IV That four urine specimens will be obtained at timed intervals (i.e., 15 minutes, 30 minutes, 1 hour, and 2 hours) after injection of the dye The importance of completely emptying the bladder each time a urine sample is obtained Obtain a signed permission consent form. Then: Ensure to the extent possible that dietary and medication restrictions are followed. Provide sufficient fluids to promote adequate hydration. Obtain four containers for the urine samples. THE PROCEDURE PSP Excretion Test. PSP dye is injected IV, after which a pressure dressing is applied to the injection site. Urine samples are then collected at 15-minute, 30-minute, 1-hour, and 2-hour intervals. Each specimen should consist of at least 50 mL. If the client cannot void at the required time, a Foley catheter may be inserted and the specimen obtained. The catheter is then clamped until the next specimen is due. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming any withheld foods and medications. Monitor the dye injection site for inflammation and hematoma formation. Remove a catheter if one has been inserted for the test, and assess voiding pattern. Allergic response: Note and report skin rash, urticaria, and change in pulse and respirations. Administer ordered antihistamine and steroid therapy. Have resuscitation equipment and oxygen on hand. Urinary infection: Note and report urinary pattern changes and characteristics (cloudy, foul smelling). Obtain urine specimen for culture. Monitor I&O. Administer antimicrobial therapy as ordered. CONCENTRATION TESTS AND DILUTION TESTS Concentration tests assess the ability of the renal tubules to appropriately absorb water and essential salts such that the urine is properly concentrated. The glomerular filtrate entering the renal tubules Copyright © 2003 F.A. Davis Company 242 SECTION I—Laboratory Tests normally has a specific gravity of 1.010. If the renal tubules are damaged such that they cannot effectively reabsorb water and salt, the specific gravity of the excreted urine will remain at 1.010. Loss of tubular concentrating ability is one of the earliest indicators of renal disease and may occur before blood levels of urea and creatinine rise. In addition to the various forms of renal disease, other situations in which renal concentrating ability may be impaired include failure to secrete antidiuretic hormone (central diabetes insipidus), lack of renal response to antidiuretic hormone (nephrogenic diabetes insipidus), prolonged overhydration, osmotic diuresis (especially that caused by uncontrolled diabetes mellitus), hypokalemia, hypocalcemia, lithium and ethanol use, severe hypoproteinemia, multiple myeloma, amyloidosis, sickle cell disease or trait, and psychogenic polydipsia. The concentration of urine may be determined by measuring either the specific gravity or the osmolality of the sample. In some cases, a single early-morning specimen will suffice. In other situations, timed tests conducted over 12 to 24 hours may be necessary. Another approach is to measure both the serum and the urine osmolality and to compare the results. Measuring the osmolality of urine is considered more accurate than determining the specific gravity. As noted previously, both the number and the size of particles present influence the specific gravity of urine. In contrast, osmolality is affected only by the number of particles present. Thus, smaller molecules such as sodium and chloride, which are of interest in renal concentration tests, contribute more to urine osmolality measures than they do to specific gravity determinations. In the laboratory, osmolality is reported as milliosmols (mOsm). Normally, the kidneys can concentrate urine to an osmolality of about three to four times that of plasma (normal plasma osmolality is 275 to 300 mOsm). If the client is overhydrated, the kidneys will excrete the excess water and produce urine with an osmolality as low as one-fourth or less that of plasma.67 Because factors such as fluid intake, diet (especially protein and salt intake), and exercise influence urine osmolality, it has been difficult to establish exact reference values. It is considered more reliable to measure serum and urine osmolalities and compare the two in terms of a ratio relationship (see Chapter 5). Timed concentration tests are performed if earlymorning samples indicate inadequate overnight urine concentrating ability. In the Fishberg test, an attempt is made to maximally concentrate urine through fluid restriction. In the standard version of this test, the client consumes no fluid for 24 hours (from breakfast one day to breakfast the next). In the simplified version, fluids are restricted from the evening meal until breakfast the next morning (see “The Procedure” later in this section).68 The 24hour fluid restriction should produce the maximum concentration possible. The 12-hour overnight restriction will increase the concentration to about 75 percent of maximum, partly because of the normal increase in urine concentration that occurs at night.69 The Mosenthal test also derives from the principle of increased urine concentration at night. In this test, two consecutive 12-hour urine specimens are collected, one from approximately 8 AM to 8 PM and one from 8 PM to 8 AM. If kidney function is normal, the specific gravity of the nighttime collection should be greater than that of the daytime collection.70 Note that tests of the kidney’s ability to produce dilute urine are rarely performed. These tests involve overhydrating the client and then observing for the appearance of dilute urine with low specific gravity and osmolality. The danger is that not all clients can tolerate the fluid load needed to produce the desired results. INTERFERING FACTORS Concentration Tests Failure of the client to follow the fluid restrictions necessary for the Fishberg test Ingestion of a diet with an excessive or inadequate amount of protein, sodium, or both Presence of disorders that alter serum protein or sodium levels Dilution Tests Inability of the client to ingest the required fluids for the test Inability of the client to tolerate the fluid load required for the test INDICATIONS FOR CONCENTRATION TESTS AND DILUTION TESTS Concentration Tests Early detection of renal tubular damage (i.e., before serum levels of urea and creatinine are elevated) as indicated by loss of tubular concentrating ability Detection of disorders that impair renal concentrating ability (e.g., diabetes insipidus) Differentiation of psychogenic polydipsia from organic disease as indicated by a normal response to timed concentration tests (e.g., Fishberg test) Detection of excessive or prolonged overhydration Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 243 Reference Values Concentration Tests Specific gravity 1.001–1.035 (usual range 1.010–1.025) Osmolality 50–1400 mOsm (usual range 300–900 mOsm; average 850 mOsm) Ratio of urine to serum osmolality 1.2:1 to 3:1 Fishberg test (standard) Specific gravity 1.026 or higher on at least one sample Fishberg test (simplified) Specific gravity 1.022 or higher on at least one sample Mosenthal test Specific gravity 1.020 or higher with at least a 7-point difference between the specific gravities of the daytime and nighttime samples Dilution Tests Specific gravity 1.003 Osmolality 100 mOsm Determination of decreased osmolality (overhydration) and increased osmolality (dehydration) Dilution Tests Evaluation of renal tubular response to high fluid volume as indicated by production of urine with low specific gravity and osmolality Nursing Alert Dilution tests should not be performed on clients who may have difficulty tolerating an increased fluid load (e.g., clients with CHF). NURSING CARE BEFORE THE PROCEDURE Urine Osmolality There is no specific preparation other than reviewing with the client when the specimen is to be obtained (e.g., first-voided morning urine) and providing a collection container. Fishberg Test (Standard Version) Explain to the client: That no fluids are to be taken after breakfast the initial morning of the test until the test is completed the next morning That solid (dry) foods are not restricted That client should completely empty the bladder at approximately 10 PM before retiring That client should remain in bed during the night (i.e., during the usual hours of sleep) That a urine specimen will be obtained at 8 AM after 24 hours without fluids That client should return to bed for 1 hour after the first specimen is collected That a second specimen will be collected at 9 AM That client should resume normal activity for 1 hour after the second specimen is collected That a third specimen will be collected at 10 AM Prepare for the procedure: Ensure to the extent possible that fluid restrictions are followed. Provide the proper specimen containers. Fishberg Test (Simplified Version) Explain to the client: That no fluids should be taken from the time of the evening meal until the test is completed That client should completely empty the bladder at approximately 10 PM before retiring That urine samples will be collected at 7 AM, 8 AM, and 9 AM, after approximately 12 hours without fluids Note: Some laboratories require that the evening meal consist of a high-protein, low-salt diet with no more than 200 mL fluid. If this is the case, the client should be so informed. Then: Ensure to the extent possible that fluid restrictions are followed. Provide the proper specimen containers. Mosenthal Test Explain to the client: That two consecutive 12-hour urine collections will be obtained: one from 8 AM to 8 PM in one container and one from 8 PM to 8 AM in another container Copyright © 2003 F.A. Davis Company 244 SECTION I—Laboratory Tests The importance of collecting all urine voided during the time period That there are no diet or fluid restrictions Prepare for the procedure: Provide the proper specimen containers. Dilution Tests Explain to the client: That it will be necessary to drink approximately 3 pt (1500 mL) of water in a 1/2-hour period That hourly urine specimens will be obtained for 4 hours after ingestion of the water That any symptoms of fluid excess (e.g., palpitations, shortness of breath) should be reported immediately Ensure to the extent possible that the client consumes or receives the required fluids. Then: Provide the proper specimen containers. THE PROCEDURE Specific Gravity and Urine Osmolality. A random urine specimen of at least 15 mL is collected, preferably first thing in the morning. NURSING CARE AFTER THE PROCEDURE Specific Gravity and Urine Osmolality. There are no special aftercare interventions. Fishberg Tests. Resume normal fluid intake and diet. Mosenthal Test. There are no special aftercare interventions. Dilution Tests. Monitor response to the fluid load. Note especially increased pulse rate or difficulty breathing. Hydration state: Note and report I&O ratio and adequacy, changes in urinary pattern, and diuresis. Assess for dehydration signs and symptoms. Monitor I&O and effect on specimen collection and testing. Also monitor urinary amounts and characteristics. Critical values: Notify physician immediately if the osmolality result is less than 100 mOsm (overhydration) or greater than 800 mOsm (dehydration). Fishberg Test (Standard Version). The client eats his or her usual breakfast, after which no further fluids are ingested until the test is completed the next morning. Solid (dry) foods are allowed. The client voids at approximately 10 PM or before retiring. Urine specimens are collected the next morning at 8 AM, 9 AM, and 10 AM. The client is to remain in bed between the 8 AM and 9 AM specimens and to resume normal activities between the 9 AM and 10 AM specimens. MEASUREMENT OF OTHER SUBSTANCES Fishberg Test (Simplified Version). The client eats his or her evening meal, after which no fluids are ingested until the test is completed the next morning. Some laboratories require that the evening meal consist of a high-protein, low-salt diet with no more than 200 mL of fluid. The client voids at approximately 10 PM or before retiring. Urine samples are collected the next morning at 7 AM, 8 AM, and 9 AM. One of the major functions of the kidney is the regulation of electrolyte balance. Electrolytes are filtered through the glomerulus and reabsorbed in the renal tubules. Those electrolytes most commonly measured in urine are sodium, chloride, potassium, calcium, phosphorus, and magnesium. Tests for electrolytes in urine usually involve 24-hour urine collections. Serum determinations of electrolyte levels are, therefore, preferred to the more cumbersome urinary determinations (see Chapter 5). An exception is magnesium, which indicates deficiency earlier than does serum assay. Mosenthal Test. Two separate but consecutive 12hour urine collections are obtained, one from 8 AM to 8 PM and one from 8 PM to 8 AM the next day. Dilution Tests. These tests, although rarely conducted, may be performed upon completion of the Fishberg tests. The client ingests 1500 mL of water over a 1/2-hour period. An alternative approach is to administer IV fluids, with the type and amount determined by the physician ordering the test. Urine samples are collected every hour for 4 hours after ingestion or administration of the fluid. A variety of substances can be measured in urine to detect alterations in physiological function. Among these are electrolytes, pigments, enzymes, hormones and their metabolites, proteins and their metabolites, and vitamins and minerals. ELECTROLYTES SODIUM Most of the sodium filtered through the glomerulus is reabsorbed in the proximal renal tubule. Additional amounts may be reabsorbed in the distal tubule under the influence of aldosterone, a hormone (mineralocorticoid) released by the adrenal cortex. Aldosterone is released in response to decreased serum sodium, decreased blood volume, Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies and increased serum potassium. Enhanced sodium reabsorption is reflected in decreased amounts being excreted in the urine. This may be seen in situations such as hyperaldosteronism, hemorrhage, shock, CHF with inadequate renal perfusion, and therapy with adrenal corticosteroids. Increased loss of sodium into the urine is associated with excessive salt intake, diuretic therapy, diabetic ketoacidosis, adrenocortical hypofunction, toxemia of pregnancy, hypokalemia, and excessive licorice ingestion. Renal failure may cause either retention or loss of sodium. In acute renal disease involving the renal tubules (e.g., ATN), excessive loss of sodium into the urine may occur, because the tubules are too impaired to reabsorb sodium normally. CHLORIDES Chlorides are generally reabsorbed passively along with sodium. The kidney may also secrete either chloride or bicarbonate, depending on the acid–base balance of the body. Chloride excretion is directly influenced by chloride intake. It is also influenced by factors that affect sodium excretion. Chloride excretion may be impaired in certain types of renal disease.71 POTASSIUM Like sodium, potassium is filtered through the glomerulus and reabsorbed through the tubules. Adequate excretion of potassium from the body also requires that the distal tubules and collecting ducts secrete potassium into the urine. Aldosterone also influences potassium excretion in that potassium is excreted in exchange for the sodium that is reabsorbed. Urinary excretion also varies in relation to dietary intake. Causes of excessive potassium loss in the urine include diabetic ketoacidosis, therapy with diuretics, and consumption of large amounts of licorice. The most common cause of decreased potassium in the urine is chronic renal failure, in which tubular secretory activity is impaired. CALCIUM Calcium is the most abundant cation in the body, with bone its major reservoir. Only a small amount of calcium circulates in the blood, and most calcium excretion takes place via the stools. Serum calcium levels are largely regulated by the parathyroid glands and vitamin D. Urinary calcium excretion varies directly with the serum calcium level. If blood levels are high, more calcium is excreted. Blood levels of calcium vary with dietary intake, although they are more influenced by increased intake than by decreased intake. Calcium excretion is highest just after a meal and lowest at night.72 Although many of Urine 245 disorders may alter calcium excretion, determination of urinary calcium is made primarily to evaluate individuals with kidney stones or with suspected parathyroid disorders. Seventy-five percent of all kidney stones contain calcium compounds. Contrary to popular belief, the most common cause of calcium-containing kidney stones is not excessive calcium intake. The hypercalcemia and increased calcium excretion associated with calcium kidney stones are the result of lack of appropriate renal tubular reabsorption of calcium, increased calcium reabsorption in the intestines, loss of calcium from bone, or low serum phosphorus levels. A variety of disorders can cause these basic defects,73 among them hyperparathyroidism; sarcoidosis; renal tubular acidosis; cancers of the lung, breast, and bone; multiple myeloma; and metastatic cancer. Drugs that may lead to excessive calcium excretion include toxic doses of vitamin D, adrenocorticosteroids, and calcitonin. Decreased calcium in the urine is related to hypoparathyroidism, nephrosis, acute nephritis, chronic renal failure, osteomalacia, steatorrhea, and vitamin D deficiency. Drugs associated with decreased calcium in the urine are thiazides and viomycin. As noted, a 24-hour urine collection is made to determine the quantity of calcium lost in the urine. Sulkowitch’s test, a qualitative measure, can be used to determine the presence of calcium in random urine specimens. If necessary, clients may be taught to perform this test at home. PHOSPHORUS As with calcium, serum contains relatively small amounts of phosphorus, with bone serving as the major reservoir. Phosphorus levels also are regulated by the parathyroid glands and vitamin D, with excretion controlled primarily by the kidneys. Causes of increased loss of phosphorus in the urine include hyperparathyroidism and renal tubular acidosis. Causes of decreased loss in the urine are hypoparathyroidism, nephrosis, nephritis, and chronic renal failure. Toxic doses of vitamin D may also result in decreased urinary excretion of phosphorus. Dietary intake of phosphates also influences urinary excretion. MAGNESIUM Magnesium is an essential nutrient found in bone, muscle, and red blood cells. Relatively little is found in serum. Magnesium participates in the control of serum electrolyte levels and increases intestinal absorption of calcium. Signs and symptoms of magnesium imbalance are manifested primarily in Copyright © 2003 F.A. Davis Company 246 SECTION I—Laboratory Tests the central nervous and neuromuscular systems. Urinary measures of magnesium may be used instead of serum measures because changes in magnesium levels are reflected more quickly in the urine than in the blood and may facilitate prompt diagnosis of the client’s problem. Causes of increased magnesium excretion include alcoholism, adrenocortical insufficiency, renal insufficiency, hypothyroidism, hyperparathyroidism, and excessive ingestion of magnesium-containing antacids. Thiazide diuretics and ethacrynic acid may also produce excessive urinary excretion of magnesium. Decreased urinary excretion is associated with malabsorption syndromes, dehydration, hyperaldosteronism, diabetic acidosis, pancreatitis, and advanced chronic renal disease. Increased calcium intake also results in decreased urinary excretion of magnesium. INTERFERING FACTORS antacids may lead to increased excretion of magnesium. INDICATIONS FOR MEASUREMENT OF URINARY ELECTROLYTES With the exception of magnesium, electrolytes are more likely to be measured by serum determinations than by urinary measures of the substances. General reasons for analyzing electrolytes in urine are as follows: Suspected renal disease Suspected endocrine disorder History of kidney stones Suspected malabsorption problem Central nervous system (CNS) signs and symptoms of unknown etiology, especially if thought to be a result of magnesium imbalance, which is detected earlier in urine than in blood NURSING CARE BEFORE THE PROCEDURE Dietary deficiency or excess of the electrolyte to be measured may lead to spurious results. Increased calcium intake may result in decreased magnesium excretion. Increased sodium and magnesium intake may cause increased calcium excretion. Diuretic therapy with excessive loss of electrolytes into the urine may falsely elevate results. Therapy with adrenocorticosteroids may lead to decreased sodium loss and increased calcium loss. Excessive ingestion of magnesium-containing For quantitative studies (i.e., studies to determine the amount of the electrolyte present), client preparation is the same as that for any test involving the collection of a 24-hour urine sample (see Appendix II). For calcium studies, some laboratories require that the client be on a diet with a set amount of calcium for at least 3 days before beginning the urine collection. If this is the case, the client should be instructed about the diet. Medications are not usually withheld, but the laboratory should be informed about those taken. Reference Values Conventional Units SI Units Sodium 30–280 mEq/24 hr 30–280 mmol/day Chloride 110–250 mEq/24 hr 110–250 mmol/day Potassium 40–80 mEq/24 hr 40–80 mmol/day Men 275 mg/24 hr 6.8 mmol/day Women 250 mg/24 hr 6.2 mmol/day Calcium Quantitative Qualitative Sulkowitch’s test 0 to 2 turbidity Phosphorus 0.9–1.3 g/24 hr Magnesium 150 mg/24 hr 6.0–8.5 mEq/24 hr 3.0–4.3 mmol/day 29–42.0 mmol/day Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies If the Sulkowitch test, a qualitative study, is used for home monitoring of urinary calcium, the client should be instructed in the procedure. THE PROCEDURE Quantitative Tests. A 24-hour urine collection is obtained (see Appendix II). Check with the laboratory or individual ordering the test to see whether the diet is to be modified for calcium studies. The laboratory should be informed of any medications taken by the client that may alter test results (see “Interfering Factors” section). Qualitative Tests (Sulkowitch’s Test). A random urine specimen is obtained, 5 mL of which is poured into a test tube. Acetic acid (5 mL of a 10 percent solution) is added to the sample and the mixture is boiled to remove protein. Distilled water is then added to the sample until the original volume is restored. Sulkowitch’s reagent (5 mL), which contains oxalic acid and ammonium oxalate, is then added. This reagent reacts with the calcium in the sample and produces turbidity (cloudiness) in the sample. Turbidity is graded on a scale of 0 to 14.74.74,75 NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming the client’s diet after the specimen collection is completed. PIGMENTS Pigments that may be found in urine consist primarily of those substances involved in the synthesis and breakdown of hemoglobin. These substances consist of hemoglobin, hemosiderin, bilirubin, urobilinogen, and porphyrins. Myoglobin, which is related to hemoglobin but found primarily in skeletal muscle, is another type of pigment, as is melanin, which is found in hair and skin. With the exceptions of urobilinogen and porphyrins, these substances are not normally found in urine. Hemoglobin, hemosiderin, bilirubin, and urobilinogen were previously discussed, as was myoglobin. The presence of myoglobin is associated with extensive damage to skeletal muscles. Melanin, which may be incorporated into tubular epithelial cells, is seen in malignant melanoma. The focus of this section, therefore, is on the porphyrins. PORPHYRINS Porphyrins are produced during the synthesis of heme (Fig. 6–2). If heme synthesis is deranged, these precursors accumulate and are excreted in the urine of Urine 247 in excessive amounts. Conditions producing increased levels of heme precursors are called porphyrias. The two main categories of genetically determined porphyrias are erythropoietic porphyrias, in which major diagnostic abnormalities occur in red cell chemistry, and hepatic porphyrias, in which heme precursors are found in urine and feces. Erythropoietic and hepatic porphyrias are very rare. Acquired porphyrias are characterized by greater accumulation of precursors in urine and feces than in red blood cells. Lead poisoning is the most common cause of acquired porphyria. Those porphyrins for which urine may be tested include aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrin, and coproporphyrin. Knowing the type of porphyrin excreted in excess aids in diagnosing specific disorders. Tests for porphyrins usually involve collection of 24-hour urine samples to determine the quantity of the specific substance present. Screening tests on random specimens to determine the presence of excessive amounts of porphyrins (i.e., qualitative studies) also are available. The presence of ALA in the urine is associated with lead poisoning. It is also found in liver disease (e.g., hepatic carcinoma and hepatitis) and in acute intermittent and variegate porphyria. PBG is found in the same disorders and may also be seen in clients taking griseofulvin. Rifampin, elevated urobilinogen, and light exposure can falsely elevate values. Uroporphyrin and coproporphyrin also are seen in clients with lead poisoning and liver disease as well as in those with uroporphyria and porphyria cutanea tarda. Uroporphyrin may be found in hemochromatosis, a disorder of iron metabolism that affects the liver and certain other body organs. Coproporphyrin is associated with obstructive jaundice and exposure to toxic chemicals. Porphyrins are reddish fluorescent compounds. Depending on the type of porphyrin present, therefore, the urine may be reddish or the color of port wine (see Table 6–1). The presence of congenital porphyria may be suspected when an infant’s wet diaper shows a red discoloration. PBG is excreted as a colorless compound. If a sample containing PBG is acidic and is exposed to air for several hours, however, a color change may occur.76 INTERFERING FACTORS For random samples, delay in sending the specimen to the laboratory within 1 hour of collection may lead to oxidation of bilirubin, if present, and of urobilinogen; random samples for porphyrin tests must be fresh and, thus, must be sent to the laboratory immediately upon collection. Copyright © 2003 F.A. Davis Company 248 SECTION I—Laboratory Tests Figure 6–2. Pathway of heme formation, including stages affected by the major disorders of porphyrin metabolism. (From Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 142, with permission.) For 24-hour samples, failure to collect the specimen in a dark container or in a container covered with aluminum foil or a dark plastic bag can result in invalid results. The specimen must also be refrigerated or kept on ice throughout the collection period unless a preservative has been added to the container by the laboratory. (If the client has a Foley catheter, the drainage bag must be covered with a dark plastic bag and placed in a basin of ice.) Therapy with griseofulvin, rifampin, and barbiturates may falsely elevate values in tests for porphyrins. INDICATIONS FOR ANALYSIS OF URINARY PIGMENTS Detection of liver disease as indicated by the presence of bilirubin (possible), excessive urobilinogen, and elevated porphyrins Diagnosis of the source of obstructive jaundice (i.e., obstruction in the biliary tree) as indicated by the presence of bilirubin, absence of urobilinogen, and elevated coproporphyrins Detection of suspected lead poisoning as indicated by elevated porphyrins, especially ALA and PBG Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 249 Reference Values Conventional Units SI Units Hemoglobin Negative Negative Hemosiderin Negative Negative Bilirubin Negative Negative Urobilinogen Random specimen 24-hr urine 0.1–1.0 Ehrlich U/dL Negative 1–4 mg/24 hr Myoglobin Negative Negative Melanin Negative Negative Porphyrins Aminolevulinic acid 38.1 mol/L Random specimen Children 0.5 mg/dL Adults 0.1–0.6 mg/dL 24-hr urine 7.6–45.8 mol/L 1.5–7.5 mg/dL/24 hr 11.15–57.2 mol/day Porphobilinogen Random specimen 24-hr urine Negative Negative 0–66 mol/day 0–1.5 mg/24 hr Uroporphyrin Random specimen Negative Negative 24-hr urine 10–30 g/24 hr (Values may be slightly higher in men than in women.) 12–37 nmol/day Coproporphyrin Random specimen Adults 0.045–0.30 mol/L 24-hr urine Children Adults 0–80 g/24 hr 0–0.12 mol/day 50–160 g/24 hr (Values may be slightly higher in men than in women.) Detection of excessive red blood cell hemolysis within the systemic circulation as indicated by the presence of free hemoglobin, elevated urobilinogen levels, and presence of hemosiderin a few days after the acute hemolytic episode Detection of extensive injury to muscles as indicated by the presence of myoglobin in the urine Detection of malignant melanoma as indicated by the presence of melanin in the urine 0.075–0.24 mol/day NURSING CARE BEFORE THE PROCEDURE For quantitative studies, client preparation is the same as that for any test involving collection of a 24hour urine sample (see Appendix II). The client should receive the proper container and instructions for maintaining the collection (e.g., refrigerated, protected from light). For studies involving the porphyrins, medications Copyright © 2003 F.A. Davis Company 250 SECTION I—Laboratory Tests such as griseofulvin, rifampin, and barbiturates may be withheld. This practice should be confirmed with the person ordering the test. For random samples, there is no specific preparation other than informing the client that the sample must be protected from light and sent to the laboratory within 1 hour of collection. The proper container should be provided to the client. THE PROCEDURE Quantitative Tests. A 24-hour urine collection is obtained in a dark container or in one covered with aluminum foil or a dark plastic bag. The sample must be kept refrigerated or on ice throughout the collection period unless a preservative has been added to the container by the laboratory. If the client has a Foley catheter, the drainage bag must be covered with a dark plastic bag and placed in a basin of ice. Random Specimens (Qualitative Tests). A random sample is collected and sent promptly (within 1 hour) to the laboratory. The specimen must be protected from excessive exposure to light. NURSING CARE AFTER THE PROCEDURE Care and assessment after the tests include resuming any withheld medications after the specimen collection has been completed. ENZYMES As noted in Chapter 5, enzymes are catalysts that enhance reactions without directly participating in them. Enzymes are normally intracellular molecules. When the cells and tissues in which these molecules are found are damaged, enzymes are released and increased levels are found in the blood and the urine. Because some enzymes are specific to only certain tissues, elevated levels may aid in pinpointing the source of pathophysiological problems. Although many enzymes can be measured in blood, only a few are analyzed in urine, including amylase, arylsulfatase A, lysozyme (muramidase), and leucine aminopeptidase. All studies of urinary enzymes involve the collection of 24-hour urine samples, with the exception of amylase, which may be evaluated in timed specimens over shorter periods of time (e.g.,1 or 2 hours). AMYLASE Amylase is a digestive enzyme that splits starch into disaccharides such as maltose. Although many cells have amylase activity, amylase circulating in serum (and ultimately excreted in urine) derives from the parotid glands and the pancreas. Unlike many other enzymes, amylase activity is primarily extracellular; it is secreted into saliva and the duodenum, where it splits large carbohydrate molecules into smaller units for further digestive action by intestinal enzymes. Urinary amylase levels generally parallel the levels found in blood. There is, however, a lag time between the rise of blood levels and urinary levels. Elevated urine levels also return to normal more slowly than blood levels. This difference between blood and urinary levels of amylase aids in diagnosing and monitoring disorders associated with elevated amylase levels. ARYLSULFATASE A Arylsulfatase A (ARS A) is a lysosomal enzyme found in all body cells except mature red blood cells. Its main sites of activity are in the liver, pancreas, and kidney. LYSOZYME (MURAMIDASE) Lysozyme is a bactericidal enzyme present in tears, saliva, mucus, and phagocytic cells. Lysozyme is produced in granulocytes and monocytes. LEUCINE AMINOPEPTIDASE Leucine aminopeptidase (LAP) is an isoenzyme of alkaline phosphatase, an enzyme that cleaves phosphate from compounds and is optimally active at a pH of 9. Although widely distributed in body tissues, LAP is most abundant in hepatobiliary tissues, pancreas, and small intestine. INTERFERING FACTORS Incomplete specimen collection and improper specimen maintenance may lead to spurious results. Amylase Ingestion of drugs that may falsely elevate values (morphine, codeine, meperidine, pentazocine, chlorothiazides, aspirin, corticosteroids, oral contraceptives, alcohol, indomethacin, bethanechol [Urecholine], secretin, and pancreozymin) Inadvertent addition of salivary amylase to the sample because of coughing or talking over it may falsely elevate values. Arylsulfatase A Contamination of the sample with blood, mucus, and feces may falsely elevate levels. Abdominal surgery within 1 week of the collection may falsely elevate levels. Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 251 Reference Values Amylase Conventional Units SI Units 10–80 amylase U/hr (Mayo Clinic) 265–680 U/day* 35–260 Somogyi U/hr SI U/hr 6.5–48.1* Arylsulfatase A Children 1 U/L Men 1.4–19.3 U/L Women 1.4–11 U/L Lysozyme (muramidase) 1.3–3.6 mg/24 hr Leucine aminopeptidase 2–28 U/24 hr * These values reflect routine testing methods used in many laboratories, not those under the Conventional Units heading. Lysozyme (Muramidase) Presence of bacteria in the sample, which will falsely decrease levels Presence of blood and saliva in the sample, which will falsely elevate levels Leucine Aminopeptidase Advanced pregnancy and therapy with drugs containing estrogen and progesterone may falsely elevate levels. INDICATIONS FOR URINARY ENZYME TESTS Amylase Retrospective diagnosis of acute pancreatitis when serum amylase levels have returned to normal but urine levels remain elevated for 7 to 10 days77 Diagnosis of chronic pancreatitis revealed by persistently elevated urinary amylase levels Monitoring for response to treatment for pancreatitis Assistance in identifying the cause of “acute abdomen” Differentiation between acute pancreatitis and perforated peptic ulcer (Urinary amylase levels are higher in pancreatitis.) Diagnosis of macroamylasemia, a disorder seen in alcoholism and malabsorption syndromes, as revealed by elevated serum amylase and normal urinary amylase Confirmation of the diagnosis of salivary gland inflammation Arylsulfatase A Suspected malignancy involving the bladder, colon, or rectum as indicated by elevated levels Suspected granulocytic leukemia as indicated by elevated levels Family history of lipid storage diseases (e.g., mucolipidoses II and III), with support for the diagnosis indicated by elevated levels Suspected metachromatic leukodystrophy as indicated by decreased levels Lysozyme (Muramidase) Suspected acute granulocytic or monocytic leukemia as indicated by elevated levels Monitoring for the extent of destruction of monocytes and granulocytes in known leukemias Suspected renal tubular damage as indicated by elevated levels Monitoring of response to renal transplant with rejection indicated by elevated levels78 Leucine Aminopeptidase Elevated serum alkaline phosphatase or LAP levels of unknown etiology Suspected liver (cirrhosis, hepatitis, cancer), pancreatic (pancreatitis, cancer), and biliary diseases (obstruction caused by gallstones, strictures, atresia), especially when serum LAP levels are normal (Urinary elevations lag behind serum elevations.) NURSING CARE BEFORE THE PROCEDURE Amylase. Client preparation is the same as that for any study involving a 24-hour or timed urine collection (see Appendix II). The proper container and instructions for maintaining the collection (e.g., Copyright © 2003 F.A. Davis Company 252 SECTION I—Laboratory Tests refrigerated, protected from exposure to salivary secretions) should be provided. Drugs that may alter test results (see “Interfering Factors” section) may be withheld during the test, although this practice should be confirmed with the person ordering the study. Arylsulfatase A. Client preparation is the same as that for any study involving a 24-hour urine collection. The proper container and instructions for maintaining the collection (e.g., refrigerated, placed on ice) should be provided. Lysozyme (Muramidase). Client preparation is the same as that for any study involving a 24-hour urine collection. The proper container and instructions for maintaining the collection (e.g., refrigerated, placed on ice) should be provided. The client should be cautioned to avoid touching the inside of the collection container to avoid bacterial contamination of the sample. The client also should be cautioned to avoid contaminating the sample with saliva (e.g., coughing over the specimen) or blood. Leucine Aminopeptidase. Client preparation is the same as that for any study involving a 24-hour urine collection. The proper container and instructions for maintaining the collection (e.g., refrigerated, placed on ice) should be provided. Because drugs containing estrogens and progesterone may falsely elevate levels, a medication history regarding these types of drugs should be obtained. THE PROCEDURE Amylase. A timed urine collection is obtained. The collection may be made over 1-, 2-, 6-, 8-, and 24hour periods. The sample must be kept refrigerated or on ice throughout the collection period unless the laboratory has added a preservative to the container. If the client has a Foley catheter, the drainage bag must be placed in a basin of ice. Care must be taken to avoid adding salivary secretions to the sample by coughing or talking over the specimen. The sample should be sent promptly to the laboratory when the collection is completed. Arylsulfatase A. A 24-hour urine collection is obtained. The sample must be kept refrigerated or on ice throughout the collection period unless a preservative has been added to the container by the laboratory. If the client has a Foley catheter, the drainage bag must be placed in a basin of ice. Care must be taken not to contaminate the sample with blood, mucus, or feces. The sample should be sent promptly to the laboratory when the collection is completed. Lysozyme (Muramidase). A 24-hour urine collection is obtained. The sample must be kept refrigerated or on ice throughout the collection period unless a preservative has been added to the container by the laboratory. If the client has a Foley catheter, the drainage bag must be placed on ice. Care must be taken not to contaminate the sample with bacteria, blood, or saliva. The sample should be sent promptly to the laboratory when the collection is completed. Leucine Aminopeptidase. A 24-hour urine collection is obtained. The sample must be kept refrigerated or on ice throughout the collection period unless a preservative has been added to the container by the laboratory. If the client has a Foley catheter, the drainage bag must be placed on ice. The sample should be sent promptly to the laboratory when the collection is completed. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming any withheld medications after the specimen collection has been completed. HORMONES AND THEIR METABOLITES Hormones are chemicals that control the activities of responsive tissues. Some hormones exert their effects in the vicinity of their release; others are released into the extracellular fluids of the body and affect distant tissues. Numerous hormones can be measured in blood (see Chapter 5). Most urinary measures focus on the hormones secreted by the adrenal cortex, the adrenal medulla, the gonads, and the placenta. Either the hormone itself or the metabolites thereof can be measured. Urinary measures of hormones and their metabolites usually involve collection of 24-hour urine specimens. The advantage of such quantitative measures over single blood level determinations is that overall levels of hormone secretion are reflected. This is important because blood levels of hormones tend to vary, depending on time of day. CORTISOL The adrenal cortex secretes three types of steroids: (1) glucocorticoids, which affect carbohydrate metabolism; (2) mineralocorticoids, which promote potassium excretion and sodium retention by the kidneys; and (3) adrenal androgens, which the liver converts primarily to testosterone. Cortisol is the predominant glucocorticoid. It is produced and secreted in response to adrenocorticotropic hormone (ACTH), which is secreted by the adenohypophysis. Ninety percent of cortisol is bound to Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies cortisol-binding globulin (CBG) and albumin. The “free” (unbound) portion is responsible for its physiological activity and also is the portion excreted into the urine. Cortisol stimulates gluconeogenesis, mobilizes fats and proteins, antagonizes insulin, and suppresses inflammation. The purpose of urinary measures of cortisol is to detect elevated levels of free cortisol, which may not be apparent in random blood samples. Elevated cortisol levels occur in Cushing’s syndrome, in which there is excessive production of adrenocorticosteroids. Cushing’s syndrome may be caused by pituitary adenoma, adrenal hyperplasia, benign or malignant adrenal tumors, and nonendocrine malignant tumors that secrete ectopic ACTH. Therapy with adrenal corticosteroids may also produce cushingoid signs and symptoms. Elevated cortisol levels are additionally associated with stress, hyperthyroidism, obesity, diabetic ketoacidosis, pregnancy, and excessive exercise. Other drugs that may elevate cortisol levels include estrogens, oral contraceptives, lithium carbonate, methadone, alcohol, phenothiazines, amphetamines, morphine, and reserpine. ALDOSTERONE Aldosterone, the predominant mineralocorticoid, is secreted by the zona glomerulosa of the adrenal cortex in response to decreased serum sodium, decreased blood volume, and increased serum potassium. Aldosterone is released in response to direct stimulation by altered serum sodium and potassium levels. In addition, decreased blood volume and altered sodium and potassium levels stimulate the juxtaglomerular apparatus of the kidney to secrete renin. Renin is subsequently converted to angiotensin II, which then stimulates the adrenal cortex to secrete aldosterone. In normal states, ACTH does not play a major role in aldosterone secretion. In disease states, however, ACTH may also enhance aldosterone secretion. Aldosterone increases sodium reabsorption in the renal tubules, gastrointestinal tract, salivary glands, and sweat glands. This subsequently results in increased water retention, blood volume, and blood pressure. Aldosterone also increases potassium excretion by the kidneys in exchange for the sodium ions that are retained. Excessive aldosterone levels are categorized as primary and secondary hyperaldosteronism. Primary hyperaldosteronism represents inappropriate aldosterone secretion, which is usually caused by benign adenomas or bilateral hyperplasia of the aldosterone-secreting zona glomerulosa cells. In primary aldosteronism, aldosterone is secreted inde- of Urine 253 pendently of the renin–angiotensin system. A hallmark of primary aldosteronism is low plasma renin levels. Secondary hyperaldosteronism indicates an appropriate response to pathological changes in blood volume and electrolytes. Common causes of secondary hyperaldosteronism include CHF, cirrhosis, nephrotic syndrome, chronic obstructive pulmonary disease (COPD), and renal artery stenosis. Other causes of elevated aldosterone levels are stress, excessive exercise, pregnancy, and several drugs (diuretics, Apresoline, diazoxide, and nitroprusside). In secondary hyperaldosteronism, plasma renin levels are elevated. Decreased aldosterone levels are associated with Addison’s disease, hypernatremia, hypokalemia, diabetes mellitus, toxemia of pregnancy, excessive licorice ingestion, and certain drugs (propranolol and fludrocortisone). 17-HYDROXYCORTICOSTEROIDS All glucocorticoids are degraded by the liver to metabolites, which as a group are called 17-hydroxycorticosteroids (17-OHCS). These steroid metabolites also are called Porter-Silber chromogens because of the method used to measure them in urine. Because 80 percent of urinary 17-OHCS are metabolites of cortisol, those disorders that are associated with elevated cortisol levels also are associated with elevated 17-OHCS (e.g., Cushing’s syndrome). Decreased levels of 17-OHCS are associated with Addison’s disease, hypopituitarism, and myxedema. As with cortisol, numerous drugs may alter urinary excretion of 17-OHCS. Thus, a thorough medication history is necessary. Some medications may be withheld before and during the test. When adrenocortical hypofunctioning or hyperfunctioning is suspected, 17-OHCS may be measured in urine as part of the diagnostic process. Note, however, that measurement of urinary cortisol levels provides more accurate quantification than does measurement of 17-OHCS levels in individuals receiving drugs that alter hepatic metabolism of steroids. 17-KETOSTEROIDS 17-Ketosteroids (17-KS) are metabolized from androgenic hormones. In men, two-thirds of 17-KS originate in the adrenal cortex and one-third derive from the testes. In women, virtually all 17-KS originate in the adrenal cortex. 17-Ketosteroids do not include testosterone. Components of 17-KS, which can be measured individually, include androsterone, dehydroepiandrosterone, etiocholanolone, 11hydroxyandrosterone, 11-hydroxyetiocholanolone, Copyright © 2003 F.A. Davis Company 254 SECTION I—Laboratory Tests 11-ketoandrosterone, 11-ketoetiocholanolone, pregnanediol, pregnanetriol (see following section), 5pregnanetriol, and 11-ketopregnanetriol. Levels of 17-KS are elevated in clients having adrenogenital syndrome (congenital adrenal hyperplasia), Cushing’s syndrome, hormone-secreting tumors of the adrenal glands or gonads, adrenocortical carcinoma, hyperpituitarism, and stressful conditions. Decreased levels of 17-KS are associated with Addison’s disease, liver disease, hyopituitarism, hypothyroidism, gout, nephrotic syndrome, and starvation. As with other urinary hormones, drugs may alter the excretion of 17KS. Thus, a thorough medication history is necessary. 17-KETOGENIC STEROIDS Cortisol and its many metabolites can be manipulated in the laboratory to form 17-ketosteroids. The substances thus formed are called 17-ketogenic steroids (17-KGS) and can be studied as an index of overall glucocorticoid metabolism. Before urinary 17-KGS can be evaluated, the 17-KS of androgenic origin must be either removed or measured separately.79 Because such a large array of steroid metabolites is reflected in 17-KGS measures, this test provides for a good overall assessment of adrenal function. PREGNANETRIOL Pregnanetriol is a metabolite of the cortisone precursor 17-hydroxyprogesterone. It should not be confused with pregnanediol, which is a metabolite of the hormone progesterone, secreted by the corpus luteum and the placenta (see preceding discussion). Elevated pregnanetriol levels are associated with adrenogenital syndrome. In this disorder, cortisol synthesis is impaired at the point of 17-hydroxyprogesterone conversion. The substance accumulates and its metabolite, pregnanetriol, is excreted in the urine in increased amounts. Excessive amounts of 17-hydroxyprogesterone, and the resultant pregnanetriol, are produced in response to feedback mechanisms. Because cortisol synthesis is impaired, serum cortisol levels are low. This, in turn, stimulates the adenohypophysis to secrete ACTH, which normally causes cortisol levels to rise. Because cortisol synthesis is impaired, however, pregnanetriol accumulates instead. Furthermore, the feedback mechanism continues to stimulate ACTH production. Note that excessive 17-hydroxyprogesterone can be converted to androgens. This conversion plus excessive androgen secretion in response to ACTH may result in virilization in women and in sexual precocity in boys. CATECHOLAMINES The adrenal medulla, a component of the sympathetic nervous system, secretes epinephrine and norepinephrine, which are collectively known as the catecholamines. A third catecholamine, dopamine, is secreted in the brain, where it functions as a neurotransmitter. Dopamine is a precursor of epinephrine and norepinephrine. Serotonin, an amine related to the catecholamines, is found in the platelets and in the argentaffin cells of the intestines. Epinephrine (adrenalin) and norepinephrine are normally secreted in response to generalized sympathetic nervous system stimulation. Epinephrine increases the metabolic rate of all cells, heart rate, arterial blood pressure, blood glucose, and free fatty acids. Norepinephrine, the predominant catecholamine, decreases heart rate while increasing peripheral vascular resistance and arterial blood pressure. The most clinically significant disorder involving the adrenal medulla is the catecholamine-secreting tumor, pheochromocytoma. Pheochromocytomas may release catecholamines—primarily epinephrine—continuously or intermittently. For this reason, urinary measurements are helpful in quantifying overall excretory levels. Because the most common sign of pheochromocytoma is arterial hypertension, measurement of either plasma (see Chapter 5) or urinary catecholamines and their metabolites is indicated in new-onset hypertension of unknown etiology. Total catecholamines can be measured in either random or 24-hour urine specimens. The individual catecholamines, epinephrine and norepinephrine, can be measured in 24-hour urine collections, as can metanephrine, a metabolite of epinephrine. Numerous drugs may alter blood and urine levels of catecholamines, and stress, smoking, and strenuous exercise may produce elevated levels. Thus, a thorough health history is required before testing. VANILLYLMANDELIC ACID Vanillylmandelic acid (VMA) is the predominant catecholamine metabolite found in urine. VMA is easier to detect by laboratory methods than are the catecholamines themselves. Therefore, this test is frequently used when pheochromocytoma is suspected. A disadvantage of the test is the need for a special diet for 2 days before the study as well as on the day the 24-hour urine specimen is collected. The following foods are restricted on a “VMA diet”: bananas, nuts, cereals, grains, tea, coffee, gelatin foods, citrus fruits, chocolate, vanilla, cheese, salad dressing, jelly, Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies candy, chewing gum, cough drops, most carbonated beverages, licorice, and foods with artificial flavoring or coloring. Ingestion of such foods will falsely elevate VMA levels. Note, however, that, as laboratory methods become more precise, it may be possible to dispense with the VMA diet in urinary measures of VMA.80 HOMOVANILLIC ACID Homovanillic acid (HVA) is a metabolite of dopamine, a major catecholamine itself, as well as a precursor to the catecholamines epinephrine and norepinephrine. HVA is synthesized in the brain and is associated with disorders involving the nervous system. As with other metabolites, numerous drugs, stress, and excessive exercise may alter HVA levels. 5-HYDROXYINDOLEACETIC ACID 5-Hydroxyindoleacetic acid (5-HIAA) is a metabolite of serotonin, which is normally present only in the platelets and in the argentaffin cells of the intestines. ESTROGENS AND ESTROGEN FRACTIONS Estrogens are secreted in large amounts by the ovaries and, during pregnancy, by the placenta. Minute amounts are secreted by the adrenal glands and, possibly, by the testes. Estrogens induce and maintain the female secondary sex characteristics, promote growth and maturation of the female reproductive organs, influence the pattern of fat deposition that characterizes the female form, and cause early epiphyseal closure. They also promote retention of sodium and water by the kidneys and sensitize the myometrium to oxytocin. Total estrogens as well as the estrogen fractions (estrone, estradiol, and estriol) can be measured in urine. In blood tests, only the fractions are routinely measured (see Chapter 5). Estrone (E1) is the immediate precursor of estradiol (E2), which is the most biologically potent fraction. Estriol (E3), in addition to ovarian sources, is secreted in large amounts by the placenta during pregnancy. It is also secreted by maternal and fetal adrenal glands. Normally, estriol levels should rise steadily during pregnancy. In addition to advancing and multiple pregnancy, elevated estrogen levels are associated with ovarian and adrenal tumors as well as estrogen-producing tumors of the testes. Drugs that elevate estrogen levels include estrogen-containing drugs, adrenocorticosteroids, tetracyclines, ampicillin, and phenothiazines. Decreased estrogen levels are seen with primary and secondary ovarian failure, Turner’s syndrome, hypopituitarism, adrenogenital syndrome, Stein- of Urine 255 Leventhal syndrome, anorexia nervosa, and menopause. Low or steadily decreasing levels of estriol during pregnancy may indicate placental insufficiency, impending fetal distress, fetal anomalies (e.g., anencephaly), and Rh isoimmunization. Decreased estriol levels are also associated with diabetes, hypertensive disorders, and other maternal complications of pregnancy. Note that, in ovulating women, estrogen levels vary in relation to the menstrual cycle. Thus, the date of the last menstrual period should be noted when analysis of urinary estrogens is performed. PREGNANEDIOL Pregnanediol is the chief metabolite of progesterone, which is secreted by the corpus luteum and by the placenta during pregnancy. Progesterone also is secreted in minute amounts by the adrenal cortex in both men and women. Progesterone prepares the endometrium for implantation of the fertilized ovum, decreases myometrial excitability, stimulates proliferation of the vaginal epithelium, and stimulates growth of the breasts during pregnancy. During pregnancy, after implantation of the embryo, progesterone production increases, thus sustaining the pregnancy. This increased production continues until about the 36th week of pregnancy, after which levels begin to diminish. Although serum determination of progesterone can be made (see Chapter 5), the study of its metabolite, pregnanediol, in urine reflects overall progesterone levels, which may not be apparent in single blood measures. In addition to pregnancy, elevated pregnanediol levels may be associated with ovarian tumors and cysts, adrenocortical hyperplasia and tumors, precocious puberty, and therapy with adrenocorticosteroids. Biliary tract obstruction may also produce elevated levels. Decreased levels of pregnanediol are associated with placental insufficiency, fetal abnormalities or demise, threatened abortion, and toxemia of pregnancy. Other causes of decreased levels include panhypopituitarism, ovarian failure, Turner’s syndrome, adrenogenital syndrome, and SteinLeventhal syndrome. Therapy with drugs containing progesterone may also lead to decreased pregnanediol levels. In ovulating women, pregnanediol levels vary in relation to the menstrual cycle. Thus, the date of the last menstrual period should be noted when analysis of pregnanediol is performed. HUMAN CHORIONIC GONADOTROPIN Human chorionic gonadotropin (hCG) is produced only by the developing placenta, and its presence in Copyright © 2003 F.A. Davis Company 256 SECTION I—Laboratory Tests blood (see Chapter 5) and urine has been used for decades to detect pregnancy. Human chorionic gonadotropin is secreted at increasingly higher levels during the first 2 months of pregnancy, declining during the third and fourth months, and then remaining relatively stable until term. Qualitative screening test kits for hCG are available for home use to determine pregnancy as early as 8 to 10 days after conception. These screening kits have almost eliminated quantitative testing for hCG to confirm pregnancy. A positive result indicates that a visit to a physician is necessary to obtain confirmation tests and prenatal care, and a negative result in the presence of symptoms of pregnancy indicates that a visit to a physician is necessary for further evaluation. Elevated levels may be seen in nonendocrine tumors that produce hCG ectopically (e.g., carcinomas of the stomach, liver, pancreas, and breast; multiple myeloma; and malignant melanoma). Decreased levels of hCG are associated with ectopic pregnancy, fetal demise, threatened abortion, and incomplete abortion. Drugs that may alter test results include phenothiazines and anticonvulsants. INTERFERING FACTORS Improper specimen collection and improper specimen maintenance may lead to spurious results. Numerous drugs may alter test results. A thorough medication history should be obtained before testing. Some medications may be withheld. Cortisol Excessive exercise and stressful situations during the testing period may lead to falsely elevated levels. Aldosterone Ingestion of certain foods may lower levels (e.g., licorice and excessive sodium intake). Excessive exercise and stressful situations during the testing period may falsely elevate levels. Radioactive scans within 1 week of the study may alter results because urinary aldosterone determinations are made by radioimmunoassay method. 17-Hydroxycorticosteroids Excessive exercise and stressful situations during the testing period may falsely elevate levels. 17-Ketosteroids Blood in the specimen may alter test results; the test should be postponed if the female client is menstruating. Excessive exercise and stressful situations during the testing period may falsely elevate levels. 17-Ketogenic Steroids Excessive exercise and stressful situations during the testing period may falsely elevate levels. Pregnanetriol None, except drugs and improper specimen collection and maintenance Catecholamines Excessive exercise and stressful situations during the testing period may falsely elevate levels. Vanillylmandelic Acid Numerous foods may falsely elevate levels; the client must follow a special diet for this test. Excessive exercise and stressful situations during the testing period may falsely elevate levels. Homovanillic Acid Excessive exercise and stressful situations during the testing period may falsely elevate levels. 5-Hydroxyindoleacetic Acid Certain foods (bananas, plums, pineapples, avocados, eggplants, tomatoes, and walnuts) will falsely elevate levels and must be withheld for 4 days before the test.81 Severe gastrointestinal disturbance or diarrhea may alter test results. Estrogens and Estrogen Fractions Maternal disorders (e.g., hypertension, diabetes, anemia, malnutrition, hemoglobinopathy, liver disease, intestinal disease) may result in decreased estriol levels during pregnancy. Threatened abortion, ectopic pregnancy, and early pregnancy may result in falsely decreased estriol levels. Pregnanediol None, except drugs and improper specimen collection and maintenance Human Chorionic Gonadotropin Proteinuria and hematuria may lead to falsely elevated levels. INDICATIONS FOR MEASUREMENT OF URINARY HORMONES AND THEIR METABOLITES Cortisol Diagnostic evaluation of signs of Cushing’s syndrome without definitive elevation of plasma cortisol levels (Adrenal hyperplasia raises the urinary cortisol level more significantly than it does the plasma cortisol level.) Diagnostic evaluation of obesity of undetermined Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 257 Reference Values Conventional Units Cortisol Aldosterone 20–90 g/24 hr 2–26 g/24 hr SI Units 55–230 mol/day 5.6–72 nmol/day 17-Hydroxycorticosteroids Children 1.5–4.0 mg/24 hr (age related: the younger the child, the less hormone secreted) Men 5.5–14.4 mg/24 hr 15.2–39.7 mol/day Women 4.9–12.9 mg/24 hr 13.5–35.6 mol/day 4.1–11.0 mol/day 17-Ketosteroids Children 1–3 mg/24 hr (age related: the younger the child, the less hormone secreted) 3–10 mol/day Men 8–25 mg/24 hr 27–85 mol/day Women 5–15 mg/24 hr 17–52 mol/day Elderly persons 4–8 mg/24 hr 13.5–28 mol/day 17-Ketogenic steroids Children 2–6 mg/24 hr (age related: the younger the child, the less hormone secreted) 6–17 mol/day Men 5–23 mg/24 hr 17–80 mol/day Women 3–15 mg/24 hr 10–52 mol/day Elderly persons 3–12 mg/24 hr 10–42 mol/day Pregnanetriol Children, 6 yr Up to 0.2 mg/24 hr 0.6 mol/day Children, 7–16 yr 0.3–1.1 mg/24 hr 0.9–3.3 mol/day Adults 3.5 mg/24 hr 10.4 mol/day Catecholamines Total Random urine 0–14 g/dL 0.73 nmol/day 24-hour urine 100 g/24 hr 160 nmol/day Epinephrine 10 ng/24 hr 55 nmol/day Norepinephrine 100 ng/24 hr 591 nmol/day Metanephrine 0.1–1.6 mg/24 hr 0.5–8.7 mol/day 0.7–6.8 mg/24 hr 3–34 mol/day 0–25 mg/24 hr 1–126 mol/day Vanillylmandelic acid (VMA) Homovanillic acid (HVA) Children 1–2 yr 2–10 yr 0.5–10 mg/24 hr 3–55 mol/day 10–15 yr 0.5–12 mg/24 hr 3–66 mol/day Copyright © 2003 F.A. Davis Company 258 SECTION I—Laboratory Tests Reference Values (continued) Conventional Units Adult 5-Hydroxyindoleacetic acid 8 mg/24 hr 2–9 mg/24 hr SI Units 1–14 mol/day 10.4–46.8 mol/day Estrogens Total 4–24 g/24 hr 4–24 g/day 5–25 g/24 hr 5–25 g/day Ovulatory phase 24–100 g/24 hr 24–100 g/day Luteal phase 12–80 g/24 hr 12–80 g/day Adult men Nonpregnant women Preovulatory phase Postmenopausal women 10 mg/24 hr 10 mg/day Estrone Children 0.2–1 g/24 hr 0.7–4 nmol/day Men 3.4–8.2 g/24 hr 12–37 nmol/day Early in cycle 4–7 g/24 hr 1.6–3.5 mmol/mol Luteal phase 11–31 g/24 hr 4.6–15.7 mmol/mol Nonpregnant women Postmenopausal women 0.8–7.1 g/24 hr Estradiol Children 0–0.2 g/24 hr 0–0.69 nmol/day Men 0–0.4 g/24 hr 0–1.39 nmol/day Early in cycle 0–3 g/24 hr 0–10.4 nmol/day Luteal phase 4–14 g/24 hr Nonpregnant women Postmenopausal women 0–2.3 g/24 hr 13.9–49.6 nmol/day 0–8.0 nmol/day Estriol Children 0.3–2.4 g/24 hr 1.04–8.33 nmol/day Men 0.8–7.5 g/24 hr 2.8–26.0 nmol/day Early in cycle 0–15 g/24 hr 0–52.0 nmol/day Luteal phase 13–54 g/24 hr 6.1–187.4 nmol/day Nonpregnant women Postmenopausal women 0.6–6.8 g/24 hr 2.08–23.6 nmol/day Pregnant women Up to 28 mg/24 hr (When plotted on a graph, levels should steadily rise during pregnancy.) Up to 97 mol/day Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 259 Reference Values Conventional Units SI Units Pregnanediol Men 1.5 mg/24 hr 4.7 mol/day 0.5–1.5 mg/24 hr 1.6–4.7 mol/day 2–7 mg/24 hr 6.2–22 mol/day 0.2–1 mg/24 hr 0.6–3.1 mol/day Nonpregnant women Proliferative phase Luteal phase Postmenopausal women Pregnant women 16 wk 5–21 mg/24 hr 15–65 mol/day 20 wk 6–26 mg/24 hr 18–81 mol/day 24 wk 12–32 mg/24 hr 37–100 mol/day 28 wk 19–51 mg/24 hr 59–160 mol/day 32 wk 22–66 mg/24 hr 68–206 mol/day 36 wk 22–77 mg/24 hr 40–240 mol/day 40 wk 23–83 mg/24 hr 72–197 mol/day Human chorionic gonadotropin Random urine Negative if not pregnant Negative if not pregnant Men Not measurable Not measurable Nonpregnant women Not measurable Not measurable 1st trimester Up to 500,000 IU/24 hr Up to 500,000 IU/L6 2nd trimester 10,000–25,000 IU/24 hr 10,000–25,000 IU/L6 3rd trimester 5,000–15,000 IU/24 hr 5,000–15,000 IU/L6 24-hr urine Pregnant women etiology (Obesity may raise plasma cortisol levels but does not significantly elevate free cortisol levels in urine.) Quantification of cortisol excess, regardless of its source More accurate quantification than 17-OHCS in individuals receiving drugs that alter hepatic metabolism of steroids Aldosterone Suspected hyperaldosteronism, especially when serum aldosterone levels are not definitive for the diagnosis 17-Hydroxycorticosteroids Signs and symptoms of adrenocortical hypofunctioning or hyperfunctioning Suspected Cushing’s syndrome as indicated by elevated levels Suspected Addison’s disease as indicated by decreased levels 17-Ketosteroids Suspected adrenocortical dysfunction, especially if urinary levels of 17-OHCS are normal Suspected Cushing’s syndrome as indicated by elevated levels Suspected adrenogenital syndrome as indicated by elevated levels Monitoring of response to therapy for adrenogenital syndrome 17-Ketogenic Steroids Suspected adrenal hypofunctioning or hyperfunc- Copyright © 2003 F.A. Davis Company 260 SECTION I—Laboratory Tests tioning (The test provides a good overall assessment of adrenal function.) Suspected Cushing’s syndrome as indicated by elevated levels Suspected Addison’s disease as indicated by decreased levels Monitoring for response to therapy with corticosteroid drugs or other drugs that alter adrenal function Detection of placental and fetal problems as indicated by estriol levels that fail to show a steady increase over several days or weeks (A sharp decline over several days indicates impending fetal demise; consistently low levels may indicate fetal anomalies.) Detection of maternal disorders of pregnancy as indicated by estriol levels that fail to show a steady increase over several days or weeks Pregnanetriol Suspected adrenogenital syndrome (virilization in women, precocious sexual development in boys) as indicated by elevated levels Family history of adrenogenital syndrome Monitoring of response to cortisol therapy for adrenogenital syndrome82 Suspected testicular tumors as indicated by elevated levels Suspected Stein-Leventhal syndrome as indicated by elevated levels Pregnanediol Verification of ovulation in planning a pregnancy or in determining the cause of infertility as indicated by normal values in relation to the menstrual cycle Diagnosis of placental dysfunction, as indicated by either low levels or failure of levels to progressively increase, and identification of the need for progesterone therapy to sustain the pregnancy Detection of fetal demise as indicated by decreased levels, although levels may remain within normal limits if placental circulation is adequate Catecholamines Hypertension of unknown etiology Suspected pheochromocytoma as indicated by elevated levels Acute hypertensive episode (A random sample is collected in such cases.) Suspected neuroblastoma or ganglioneuroma as indicated by elevated levels Vanillylmandelic Acid Hypertension of unknown etiology Suspected pheochromocytoma as indicated by elevated levels Suspected neuroblastoma or ganglioneuroma as indicated by elevated levels Homovanillic Acid Suspected neuroblastoma or ganglioneuroma as indicated by elevated levels Diagnosis of benign pheochromocytoma as indicated by normal HVA levels with elevated VMA levels Diagnosis of malignant pheochromocytoma as indicated by elevated HVA and VMA levels 5-Hydroxyindoleacetic Acid Detection of early carcinoid tumors (argentaffinomas) of the intestine as indicated by elevated levels Estrogens and Estrogen Fractions Suspected tumor of the ovary, testicle, or adrenal gland as indicated by elevated total estrogens and fractions Suspected ovarian failure as indicated by decreased total estrogens and fractions Human Chorionic Gonadotropin Confirmation of pregnancy within 8 to 10 days after conception, especially in women with a history of infertility or habitual abortion or in women who may desire a therapeutic abortion Suspected hydatidiform mole as indicated by elevated levels Suspected choriocarcinoma or testicular tumor as indicated by elevated levels Suspected nonendocrine tumor that produces hCG ectopically as indicated by elevated levels Threatened abortion as indicated by decreased levels NURSING CARE BEFORE THE PROCEDURE All urine studies for hormones and their metabolites involve collecting 24-hour urine samples (see Appendix II); exceptions are catecholamines and hCG, which can also be analyzed in random samples. The client should, therefore, be instructed on how to collect the sample. The proper container and instructions for maintaining the collection (e.g., refrigerated or on ice) should be provided. Drugs that may alter test results may be withheld during the test, although this practice should be confirmed with the person ordering the study. The client should be cautioned to avoid excessive exercise and stress during the following studies: cortisol, aldosterone, 17-OHCS, 17-KS, 17-KGS, catecholamines, VMA, and HVA. The client also should be instructed on the following dietary restrictions in relation to specific tests: Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies (1) aldosterone—maintain a normal salt intake; (2) VMA—maintain a “VMA diet” (see earlier discussion) for 2 days before the test and for the day of the test; and (3) 5-HIAA—maintain a diet low in serotonin (see earlier discussion) for 4 days before the test. For gonadal and placental hormone studies, the date of the last menstrual period should be noted. of Urine 261 protein) as an indicator of the accuracy of the collection because the amount excreted in 24 hours should be fairly constant. Measurement of urinary levels of uric acid are discussed later. Amino acids are also products of protein metabolism. As discussed later, abnormal metabolism and congenital disorders (e.g., phenylketonuria) are associated with excessive levels of certain amino acids. THE PROCEDURE URIC ACID All urine studies for hormones and their metabolites involve collecting 24-hour urine specimens; exceptions are catecholamines and hCG, which can also be analyzed in random samples. For 24-hour collections, an acidifying preservative is added to the container by the laboratory. In addition, some laboratories require that the sample be refrigerated or placed on ice throughout the collection period. Special diets may be required before collection of 24-hour urines for VMA and 5-HIAA (see preceding “Nursing Care Before the Procedure” section). Random samples for catecholamines can be collected at any time but frequently are obtained after a hypertensive episode. Random samples for hCG are more reliable if collected first thing in the morning because dilute urine may lead to falsenegative results. All specimens should be sent promptly to the laboratory when the collection is completed. Uric acid is an end product of purine metabolism. Purines are constituents of nucleic acids in the body and appear in the urine in the absence of dietary sources of purines. Dietary sources of purines include organ meats, legumes, and yeasts. Uric acid is filtered, absorbed, and secreted by the kidneys and is a common constituent of urine. The amount of uric acid produced in the body and the efficiency of renal excretion affect the amount of uric acid found in urine. Excessive amounts of uric acid may be found in excessive dietary intake of purines, in massive cell turnover with degradation of nucleic acids, and in disorders of purine metabolism. The body’s ability to filter, reabsorb, and secrete uric acid affects the amount of uric acid ultimately found in urine.83 Elevated urinary uric acid is commonly associated with neoplastic disorders such as leukemia and lymphosarcoma. It may be found also in individuals with pernicious anemia, sickle cell anemia, and polycythemia. Disorders associated with impaired renal tubular absorption (e.g., Fanconi’s syndrome and Wilson’s disease) also lead to elevated uric acid levels in urine.84 Drugs used to treat elevated serum uric acid levels frequently work by increasing urinary excretion of the substance. Such drugs include probenecid and sulfinpyrazone. Allopurinol also decreases serum uric acid levels but without necessarily leading to excessive urinary levels.85 Note that colchicine, a drug frequently used to treat gout, does not alter urinary levels of uric acid. Other drugs associated with elevated urinary uric acid include aspirin (large doses), adrenocorticosteroids, coumarin anticoagulants, and estrogens. Although gout is associated with elevated serum uric acid levels (see Chapter 5), decreased amounts of uric acid are often found in urine because of impaired tubular excretion. Decreased amounts of urinary uric acid also are associated with various renal diseases for the same reason. Decreased urinary uric acid levels are associated with lactic acidosis and ketoacidosis because of impaired renal excretion and also with ingestion of alcohol, aspirin (small doses), and thiazide diuretics. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming the client’s usual diet, medications, or activities at completion of specimen collection. PROTEINS AND THEIR METABOLITES Normally, the urine contains only a scant amount of protein. Excessive amounts of protein in the urine are generally associated with renal disease. Thus, part of the screening process in a UA is to test the sample for protein. If increased amounts are found, a quantitative 24-hour urine collection is performed. The presence of certain types of proteins in urine also is diagnostic of specific disease states. The presence of Bence Jones protein in the urine, for example, is associated with multiple myeloma. Protein metabolites such as creatinine and uric acid can also be measured in urine. Creatinine, which is produced at a fairly constant rate within the body, is a sensitive indicator of glomerular function because factors affecting creatinine clearance are primarily the result of alteration in renal function. Creatinine levels can also be measured along with 24-hour measures of other substances in urine (e.g., Copyright © 2003 F.A. Davis Company 262 SECTION I—Laboratory Tests AMINO ACIDS Elevated amino acid levels in urine are associated with congenital defects and disorders of amino acid metabolism. The major inherited disorders include phenylketonuria (PKU), tyrosyluria, and alkaptonuria. PKU occurs when the normal conversion of phenylalanine to tyrosine is impaired, leading to the excretion of increased keto acids such as phenylpyruvate in the urine, which can be detected on screening tests. If undetected and untreated, PKU results in severe mental retardation. Blood tests for PKU may also be performed. Tyrosyluria occurs because of either inherited disorders or metabolic defects. It is most frequently seen in premature infants with underdeveloped liver function, but it seldom results in permanent damage. Acquired severe liver disease also leads to tyrosyluria, as well as to the appearance of tyrosine crystals in the urine. Alkaptonuria represents another defect in the phenylalanine–tyrosine conversion pathway. In this disorder, homogentisic acid accumulates in the urine. Alkaptonuria generally manifests in adulthood and leads to deposition of brown pigment in the body, arthritis, liver disease, and cardiac disorders.86 URINE HYDROXYPROLINE A special urinary test for a specific amino acid is measurement of urine hydroxyproline, a component of collagen in skin and bone. Foods such as meat, poultry, fish, and foods containing gelatin falsely elevate levels and must, therefore, be restricted for at least 24 hours before the test. Drugs such as ascorbic acid, vitamin D, glucocorticoids, aspirin, mithramycin, and calcitonin will also elevate levels, as will skin disorders such as burns and psoriasis.87 INTERFERING FACTORS Improper specimen collection and improper specimen maintenance Ingestion of foods and drugs that may alter test results or failure to ingest certain foods (e.g., a low-purine diet leads to decreased levels of urinary uric acid; lack of protein intake may lead to false-negative PKU test results in infants) Skin disorders such as psoriasis and burns that may falsely elevate urine hydroxyproline levels INDICATIONS FOR MEASUREMENT OF URINARY PROTEINS Protein Detection of various types of renal disease as indicated by elevated levels Detection of possible complications of pregnancy as indicated by elevated levels Bence Jones Protein Detection of multiple myeloma Creatinine Assessment of glomerular function with decreased levels indicating impairment (see also preceding “Reference Values” section) Assessment of the accuracy of 24-hour urine collections for other substances Uric Acid Monitoring for urinary effects of disorders that cause hyperuricemia Monitoring for response to therapy with uricosuric drugs Comparison of urine levels with serum uric acid levels to provide for an index of renal function Amino Acid Screening Tests Detection of inherited and metabolic disorders such as PKU, tyrosyluria, alkaptonuria, cystinuria, and maple syrup urine disease Urine Hydroxyproline Detection of disorders associated with increased bone reabsorption (e.g., Paget’s disease, metastatic bone tumors, and certain endocrine disorders) Monitoring of treatment for Paget’s disease NURSING CARE BEFORE THE PROCEDURE The client should be instructed in the method to be used for obtaining the sample (e.g., 24-hour urine, 2-hour urine, clean-catch midstream sample). A medication history should be obtained. Drugs that may alter test results may be withheld during the test, although this practice should be confirmed with the person ordering the study. The client also must be instructed in any dietary modifications needed for the test. Such dietary modifications may be necessary in uric acid and urine hydroxyproline tests. THE PROCEDURE Protein, Creatinine, and Uric Acid. A 24-hour urine specimen is collected. For creatinine measures, a preservative is usually added to the collection container by the laboratory. It may be necessary also to refrigerate the sample. Bence Jones Protein. An early morning sample of at least 60 mL is collected. The sample should be sent promptly to the laboratory. It is recommended that the sample be collected using the clean-catch midstream technique (see Appendix II) to avoid Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies of Urine 263 Reference Values Conventional Units Protein SI Units 0–150 mg/24 hr 0–150 mg/day Men 1–1.9 g/24 hr 8.8–17.6 mmol/day Women 0.8–1.7 g/24 hr 7–15.8 mmol/day Bence Jones protein Negative Negative Uric acid 250–750 mg/24 hr 1.5–4.5 mmol/day Negative Negative Men 0.4–5 mg/2 hr 3.1–38 mol/2 hr Women 0.4–2.9 mg/2 hr 3.1–22 mol/2 hr 14–45 mg/24 hr 0.11–0.36 mmol/day Notify physician of protein levels 4 g/24 hr Notify physician of protein levels 50 nmol/day Creatinine Amino acids Screening tests (e.g., for PKU, tyrosyluria, alkaptonuria, cystinuria, maple syrup urine disease) Urine hydroxyproline 2-hour sample 24-hour sample Adults Critical values Note: Values are higher in children and during the third trimester of pregnancy contaminating the sample with other proteins from bodily secretions. Amino Acid Screening Tests. A random urine specimen of at least 20 mL is collected. In infants, collection involves application of a urine-collecting device. The specimen should be sent immediately to the laboratory. The PKU (phenylpyruvic acid) test is performed no fewer than 3 days after birth. It is performed by pressing a Phenistix reagent strip on a wet diaper or by dipping the strip into a sample obtained with a urine-collecting device, waiting 30 seconds, and comparing it to a color chart. The chart is scaled at milligram concentrations of the substance, ranging from 0 to 100. Urine Hydroxyproline. A 2- or 24-hour urine specimen is collected in a container to which preservative has been added. It may also be necessary to refrigerate the sample. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming the any withheld or modified diet and medications. Compromised renal function: Note and report presence of or increases in proteins. Monitor I&O and fluid and protein restrictions. Instruct in dietary and fluid inclusions and exclusions. Critical values: Notify physician immediately of a protein level of greater than 4 g/24 hr. VITAMINS AND MINERALS The functions and serum assays of vitamins and minerals are discussed in Chapter 5. In general, serum assays are preferred to the more cumbersome urine level determinations, which require 24-hour urine collections. VITAMINS Fat-soluble vitamins are not readily excreted in the urine, and therefore urinary determinations focus on water-soluble vitamins B and C. Urinary determinations for vitamins B1 (thiamine), B2 (riboflavin), and C may be made in suspected defi- Copyright © 2003 F.A. Davis Company 264 SECTION I—Laboratory Tests ciency states. The Schilling test for vitamin B12 absorption is discussed in Chapter 20, because it is used to diagnose an abnormality of hematopoiesis. MINERALS Minerals are essential to normal body metabolism. In urine, three commonly measured minerals include iron (found in hemosiderin), copper, and oxalate. Copper aids in the formation of hemoglobin and is a component of certain enzymes necessary for energy production.88 Elevated urinary copper levels are associated with Wilson’s disease, an inherited disorder of copper metabolism. Oxalate is found in combination with calcium in certain kidney stones. Elevated urinary oxalate levels are seen in hyperoxaluria, a disorder in which oxalate accumulates in soft tissues, especially those of the kidney and bladder.89 Oxalate levels can also be elevated by excessive ingestion of strawberries, tomatoes, rhubarb, or spinach. INTERFERING FACTORS Improper specimen collection and maintenance may affect test results. Ingestion of strawberries, tomatoes, rhubarb, or spinach may falsely elevate oxalate levels. INDICATIONS FOR MEASUREMENT OF VITAMINS AND MINERALS IN URINE Detection of vitamin deficiency states Screening for and detection of Wilson’s disease as indicated by elevated urinary copper levels Detection of hyperoxaluria as indicated by elevated oxalate levels NURSING CARE BEFORE THE PROCEDURE The client should be instructed in the method of obtaining the sample (i.e., usually a 24-hour urine collection). THE PROCEDURE A 24-hour urine specimen is collected. Samples for oxalate should be collected in containers that have been protected from light and to which hydrochloric acid has been added. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include resuming the client’s usual diet, medications, or activities at completion of specimen collection. MICROBIOLOGIC EXAMINATION OF URINE Urine tests for culture and sensitivity (C&S) indicate the type and number of organisms present in the specimen (culture) and the antibiotics to which the organisms are susceptible (sensitivity). In urine, it is common to culture out only one organism, although polymicrobial infections may be seen in individuals with Foley catheters. Most organisms infecting the urinary tract are derived from fecal flora that have ascended the urethra. Organisms commonly found in urine include Escherichia coli, Enterococcus, Klebsiella, Proteus, and Pseudomonas.90 After treatment with the appropriate antibiotic, as indicated by sensitivity tests, follow-up urine cultures may be undertaken to determine the effectiveness of treatment. Reference Values Conventional Units SI Units Vitamins B1 (thiamine) 100–200 g/24 hr B2 (riboflavin) Men 0.51 mg/24 hr 1356 nmol/day Women 0.39 mg/24 hr 1037 nmol/day C (ascorbic acid) 30 mg/ 24 hr Minerals Copper 15–60 g/24 hr 0.24–0.94 mol/day Oxalate 40 mg/24 hr 456 mol/day Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies Reference Values Negative for pathologic organisms Critical values: Notify physician if the culture result is greater than 100,000 organisms/mL (SI 1,000,000 CFU/L). of Urine 265 to detect cancer of the bladder and cytomegalic inclusion disease.91 In these disorders, abnormal cells are shed into the urine and can be detected upon examination of the sample. Reference Values Negative for abnormal cells and inclusions INTERFERING FACTORS Improper specimen collection so that the sample is contaminated with nonurinary organisms Delay in sending the specimen to the laboratory (Bacteria may multiply in nonrefrigerated samples.) INDICATIONS FOR MICROBIOLOGIC EXAMINATION OF URINE Suspected UTI Identification of antibiotics to which the cultured organism is sensitive Monitoring for response to treatment for UTIs INTERFERING FACTORS Improper specimen collection such that the sample is contaminated with extraneous cells Delay in sending the sample to the laboratory (Cells may begin to disintegrate.) INDICATIONS FOR CYTOLOGIC EXAMINATION OF URINE Suspected cancer of the bladder or other urinary tract structure, especially in individuals exposed to environmental carcinogens Suspected infection with cytomegalovirus NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of either a clean-catch midstream urine specimen, a catheterized specimen, or a suprapubic aspiration (see Appendix II). NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of a clean-catch midstream urine specimen, a catheterized specimen, or a suprapubic aspiration (see Appendix II). THE PROCEDURE A sample of at least 5 to 10 mL is obtained either by clean-catch technique, catheterization, or suprapubic aspiration. The sample is placed in a sterile container and is transported to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the test include assessing the suprapubic site for inflammation if the specimen was obtained by aspiration. Cover the area with a sterile dressing. THE PROCEDURE A sample of at least 180 mL in adults and 10 mL in children is obtained either by the clean-catch technique, catheterization, or suprapubic aspiration. Depending on the laboratory, a special container or preservative, or both, may be needed. The sample must be transported to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Critical values: Notify physician immediately if the culture result is greater than 100,000 organisms/mL (SI 1,000,000 CFU/L). Care and assessment after the test include assessing the suprapubic site for inflammation if the specimen was obtained by aspiration. Cover the area with a sterile dressing. CYTOLOGIC EXAMINATION OF URINE DRUG SCREENING TESTS OF URINE Cytology is the study of the origin, structure, function, and pathology of cells. In clinical practice, cytologic examinations are generally performed to detect cell changes caused by malignancies or inflammatory conditions. Cytologic examination of urine is performed when cancer or inflammatory disorders of the urinary tract are suspected. It is especially indicated Toxicological analysis of urine is performed to identify drugs that have been used and abused. Urine is preferred for drug screening because most drugs are detectable in urine but not in blood. The exception is testing for alcohol concentration. The screening tests are performed in groups according to the pharmacological classification of the drugs. Commonly used substances that involve a risk for psychological, Copyright © 2003 F.A. Davis Company 266 SECTION I—Laboratory Tests physical, or both psychological and physical dependence and are tested are the following: Sedatives: benzodiazepines, methaqualone Depressants: alcohol, barbiturates, opiates (codeine, morphine, methadone) Stimulants: amphetamines, cocaine, “crack,” methylphenidate Hallucinogens: cannabinoids (marijuana, hashish), phencyclidine (PCP), lysergic acid diethylamide (LSD), mescaline92 Drug abuse includes the recreational use of drugs (illicit use); unwarranted use of drugs to relieve problems or symptoms, leading to dependence and later continued use; and therapeutic use to prevent the consequences of withdrawal. These substances act on the CNS to reduce anxiety and tension, produce euphoria and other pleasurable mood changes, increase mental and physical ability, and alter sensory perceptions and change behaviors.93 Detection of levels varies with the time of the last dose of a specific drug and can range from hours to days to weeks. Anabolic steroids (synthetic derivatives of testosterone) are used to enhance athletic performance primarily in power-related sports and, in some instances, to improve appearance. Its use (known as “sports doping”) results in a change in body bulk, strength, and energy. Psychological effects include mood swings, aggressiveness, and irrational behavior. Physical effects include liver dysfunction and cardiovascular dysfunction that result from hypertension and increased low-density lipoproteins. Anabolic steroid metabolites can be detected in the urine for up to 6 months after drug use.94 Reference Values Negative for drugs in group tested INTERFERING FACTORS High or low pH of urine (alkaline or acid levels) Blood or other abnormal constituents in the urine Urine that has a low specific gravity, causing dilution INDICATIONS FOR DRUG SCREENING TESTS OF URINE Determination of abuse of drugs before or during employment in which public welfare is at stake Identification of use of drugs to enhance athletic ability and success Detection and identification of specific drugs when use and abuse is suspected so as to differentiate it from other causes of a set of signs and symptoms Confirmation of a diagnosis of drug overdose after death Detection of drug use before prescribing a medication or treatment regimen NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as for any test involving the collection of a random urine specimen (see Appendix II). If drug abuse is suspected, the collection and delivery of the urine sample should be witnessed by a legally responsible person and labeled with a code instead of a name and other personal information. The client should be informed of the procedure to collect and test the specimen, the reporting protocol, and possible implications of the results. THE PROCEDURE A random sample of 50 to 100 mL of urine is collected in a clean container and covered with a lid and labeled with a code while a trained witness observes to ensure that the specimen has been obtained from the correct client. The specimen container is placed in a plastic bag and sealed to ensure that any tampering with the package will be revealed. The signatures of the individual who collects the specimen and anyone who handles it in any way are required on a document. The specimen is examined by enzyme immunoassay or fluorescence polarization immunoassay procedures. Confirmation tests are performed to ensure that false-positive results are resolved. Because of the legal implications, documented testing procedures for a positive, negative, or unconfirmed result with evidence to support the result should accompany the test report. After the complete testing of the specimen, the sample is resealed in the labeled bag and stored for 30 days or as long as needed.95 NURSING CARE AFTER THE PROCEDURE No specific care is needed after these tests. Inform the client of the possible economic, psychological, and legal implications of a confirmed positive test. Abnormal results: Note and report effect of results on client’s psychological and physical health, economic status (work, sports), and legal status (illicit drug use). Ensure that correct testing and confirmation were performed and reported. Advise client to consider drug abuse counseling or educational programs, or both, provided by school officials, coaches, physicians, and other health-care professionals. Copyright © 2003 F.A. Davis Company CHAPTER 6—Studies REFERENCES 1. Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 25. 2. Ibid, pp 25–26. 3. Porth, CM: Pathophysiology: Concepts of Altered Health States, ed 5. JB Lippincott, Philadelphia, 1998, p 580. 4. Strasinger, op cit, p 25. 5. Ibid, p 27. 6. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 699. 7. Ibid, p 699. 8. Strasinger, op cit, p 35. 9. Schweitzer, GB, and Schumann, GB: Examination of urine. In Henry, JB: Clinical Diagnosis and Management by Laboratory Methods, ed 18. WB Saunders, Philadelphia, 1991, p 393. 10. Strasinger, op cit, p 35. 11. Ibid, p 36. 12. Schweitzer and Schumann, op cit, p 394. 13. Ibid, p 395. 14. Strasinger, op cit, p 41. 15. Ibid, p 37. 16. Ibid, p 38. 17. Schweitzer and Schumann, op cit, p 400. 18. Strasinger, op cit, p 46. 19. Schweitzer and Schumann, op cit, p 399. 20. Ibid, p 399. 21. Ibid, p 400. 22. Ibid, p 402. 23. Ibid, p 401. 24. Strasinger, op cit, p 48. 25. Schweitzer and Schumann, op cit, p 401. 26. Strasinger, op cit, p 47. 27. Porth, op cit, p 573. 28. Schweitzer and Schumann, op cit, p 405. 29. Ibid, pp 407–408. 30. Strasinger, op cit, p 53. 31. Ibid, p 54. 32. Schweitzer and Schumann, op cit, p 409. 33. Ibid, p 410. 34. Ibid, p 410. 35. Strasinger, op cit, p 55. 36. Schweitzer and Schumann, op cit, p 410. 37. Ibid, p 410. 38. Strasinger, op cit, p 56. 39. Ibid, p 58. 40. Schweitzer and Schumann, op cit, p 415. 41. Ibid, p 415. 42. Strasinger, op cit, pp 60–61. 43. Ibid, p 61. 44. Schweitzer and Schumann, op cit, p 416. 45. Strasinger, op cit, p 62. 46. Schweitzer and Schumann, op cit, p 417. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. of Urine 267 Strasinger, op cit, p 62. Ibid, pp 68. Schweitzer and Schumann, op cit, p 421. Strasinger, op cit, p 77. Schweitzer and Schumann, op cit, p 421. Strasinger, op cit, p 79. Schweitzer and Schumann, op cit, p 423. Ibid, p 424. Ibid, p 424. Ibid, p 424. Strasinger, op cit, p 87. Schweitzer and Schumann, op cit, p 425. Strasinger, op cit, pp 95–99. Ibid, p 103. Sacher and McPherson, op cit, pp 711–712. Strasinger, op cit, p 15. Sacher and McPherson, op cit, p 711. Ibid, p 712. Ibid, p 713. Strasinger, op cit, p 20. Sacher and McPherson, op cit, p 714. Strasinger, op cit, p 18. Sacher and McPherson, op cit, p 715. Strasinger, op cit, p 37. Corbett, JV: Laboratory Tests and Diagnostic Procedures with Nursing Diagnoses, ed 3. Appleton & Lange, Norwalk, Conn, 1992, p. 127. Sacher and McPherson, op cit, p 721. Schweitzer and Schumann, op cit, p 433. Ibid, p 459. Strasinger, op cit, pp 36–37. Strasinger, op cit, pp 142–143. Springhouse Corporation: Nurse’s Reference Library: Diagnostics, ed 2. Springhouse, Springhouse, Pa, 1986, p 374. Ibid, pp 376–377. Sacher and McPherson, op cit, p 564. Ibid, p 581. Ibid, pp 403–404. Ibid, pp 394–396. Ibid, p 330. Nurse’s Reference Library, op cit, p 423. Sacher and McPherson, op cit, p 331. Strasinger, op cit, pp 138–139. Nurse’s Reference Library, op cit, pp 418–419. Ibid, p 451. Ibid, pp 464–465. Sacher and McPherson, op cit, p 499. Fischbach, FT: A Manual of Laboratory Diagnostics Tests, ed 4. JB Lippincott, Philadelphia, 1992, pp 709–710. Sacher and McPherson, op cit, pp 686–688. Berkow, R (ed): The Merck Manual, ed 16. Merck Sharp and Dohme Research Laboratory, Rahway, NJ, 1992, p 1549. Ibid, p 2277. Fischbach, op cit, p 186. Copyright © 2003 F.A. Davis Company CHAPTER Sputum Analysis TESTS COVERED Gram Stain and Other Stains, 269 Culture and Sensitivity, 271 Acid-Fast Bacillus Smear and Culture, 272 Cytologic Examination, 272 OVERVIEW OF SPUTUM PRODUCTION AND ANALYSIS Sputum is the material secreted by the tracheobronchial tree and, by definition, brought up by coughing. The submucosal glands and secretory cells of the tracheobronchial mucosa normally secrete up to 100 mL of mucus per day as part of bronchopulmonary cleansing. The secretions form a thin layer over the ciliated epithelial cells and travel upward toward the oropharynx, carrying inhaled particles away from the bronchioles. From the oropharynx the secretions are swallowed; therefore, the healthy person does not produce sputum. In addition to its mechanical cleansing action, mucus attacks inhaled bacteria directly. This antibacterial effect is primarily the result of antibodies, which are predominantly IgA, but also of lysozymes and slightly acid pH. Normally, the contents of the lower respiratory tract are sterile. Environmental factors, drugs, and respiratory tract disease alter tracheobronchial secretions and may lead to sputum production. Tobacco smoke, cold air, alcohol, and sedatives depress ciliary action and may cause stasis of secretions. Respiratory infections cause an increase in secretions and may lead to a more acidic pH and changes in the chemical composition. A pH below 6.5 inhibits ciliary action, as does increased sputum viscosity. Leukocytes present in respiratory secretions also rise during infection, and membrane permeability increases because of the normal inflammatory response. Thus, antibiotics and other elements normally found in the blood may be present in the sputum. The quantity of sputum produced in pathological states is roughly parallel to the severity of the problem. Specific characteristics and constituents of sputum help to determine the nature of the disorder.1 The most common laboratory tests performed on sputum are (1) Gram stain and other staining tests, (2) culture and sensitivity, (3) examination for acid-fast bacilli (AFB), and (4) cytologic examination. The gross appearance of the specimen should, however, be observed and documented before sending the sample to the laboratory. Respiratory secretions are normally clear, colorless, odorless, and slightly watery. Abnormal sputum can be described as mucoid (consisting of mucus), mucopurulent (consisting of mucus and pus), and purulent (consisting of pus). Expectoration of mucoid sputum is seen in chronic bronchitis and asthma. A change from mucoid to mucopurulent sputum indicates infection superimposed on the chronic inflammatory condition.2 Purulent sputum may indicate acute bacterial pneumonia, bronchiectasis, or rupture of a pulmonary abscess. Foul-smelling sputum is also associated with bronchiectasis and lung abscess, as well as with cystic fibrosis. Viscous (tenacious) secretions are seen in clients with cystic fibrosis, Klebsiella pneumonia, and dehydration.3 268 Copyright © 2003 F.A. Davis Company CHAPTER 7—Sputum Analysis 269 Purulent sputum is yellow to green. Gray sputum may indicate inhaled dust; grayish-black sputum is seen after smoke inhalation. Frothy pink or rusty-colored sputum is associated with congestive heart failure (CHF). It is abnormal to expectorate blood (hemoptysis), whether the quantity involves only a few scant streaks or a life-threatening hemorrhage. In addition to being associated with CHF, rusty-colored sputum may be seen also in pneumococcal pneumonia, whereas bright streaks of blood are associated with Klebsiella pneumonia. Dark blood in small amounts is associated with tuberculosis, tumors, and trauma caused by instrumentation. Bright blood in moderate to large amounts is associated with cavitary tuberculosis, broncholithiasis, and pulmonary thrombosis. SPUTUM TESTS GRAM STAIN AND OTHER STAINS Gram staining is one of the oldest and most useful microbiologic staining techniques. It involves smearing a small amount of sputum on a slide and then exposing it to gentian or crystal violet, iodine, alcohol, and safranine, a red dye. This technique allows for morphological examination of the cells contained in the specimen and differentiates any bacteria present into either gram-positive organisms, which retain the iodine stain, or gram-negative organisms, which do not retain the iodine stain but can be counterstained with safranine. Gram staining can be used to differentiate true sputum from saliva and upper respiratory tract secretions. True sputum contains polymorphonuclear leukocytes and alveolar macrophages. It should also contain a few squamous epithelial cells. Excessive squamous cells or the absence of polymorphonuclear leukocytes usually indicates that the specimen is not true sputum. Another stain used in sputum examinations is polychromase chain reaction, used when pulmonary alveolar proteinosis or Pneumocystis carinii pneumonia is suspected. A characteristic of pulmonary alveolar proteinosis is compacted protein, which can be found either inside mononuclear cells, free in round or laminated clumps, or in aggregates with cleftlike spaces. The round and laminated clumps may resemble the cysts of P. carinii. Reference Values Normal sputum contains polymorphonuclear leukocytes, alveolar macrophages, and a few squamous epithelial cells. INTERFERING FACTORS Improper specimen collection Delay in sending specimen to the laboratory INDICATIONS FOR GRAM STAIN AND OTHER STAIN TESTS Gram Stain Differentiation of sputum from upper respiratory tract secretions, the latter being indicated by excessive squamous cells or the absence of polymorphonuclear leukocytes Determination of types of leukocytes present in sputum (e.g., neutrophils indicating infection and eosinophils seen in asthma) Differentiation of gram-positive from gram-negative bacteria in respiratory infections Identification of Curschmann’s spirals, which are associated with asthma, acute bronchitis, bronchopneumonia, and lung cancer4 Wright’s Stain Confirmation of the types of leukocytes present in sputum Polychromase Chain Reaction Identification of compacted proteins associated with pulmonary alveolar proteinosis Identification of cysts associated with P. carinii infections Confirmation of the presence of cysts associated with P. carinii infections NURSING CARE BEFORE THE PROCEDURE Explain to the client: That results are most reliable if the specimen is obtained in the morning upon arising, after secretions have accumulated overnight That a sample of secretions from deep in the respiratory tract, not saliva or postnasal drainage, is needed The methods by which the specimen will be obtained (i.e., by coughing or by tracheal suctioning) That increasing fluid intake before retiring for the night aids in liquefying secretions and may make them easier to expectorate Copyright © 2003 F.A. Davis Company 270 SECTION I—Laboratory Tests That humidifying inspired air also helps to liquefy secretions That, if feasible, the client should brush the teeth or rinse the mouth before obtaining the specimen to avoid excessive contamination of the specimen with organisms normally found in the mouth Proper handling of the container and specimen, if the client is to obtain the specimen independently The number of samples to be obtained, because it may be necessary to analyze more than one sample for accurate diagnosis Prepare for the procedure: Assist in providing extra fluids, unless contraindicated, and proper humidification. Assist with mouth care as needed. Provide sputum collection container(s). If the specimen is to be obtained by tracheal suctioning, it is recommended that oxygen be administered for 20 to 30 minutes before the procedure. Hyperventilation with 100% O2 should be performed before and after suctioning. THE PROCEDURE The procedure varies with the method for obtaining the sputum specimen. The nurse should wear gloves, face mask, and possibly glasses or goggles when obtaining the sputum sample. Expectorated Specimen. The client should sit upright, with assistance and support (e.g., with an overbed table) as needed. The client should then take two or three deep breaths and cough deeply. Any sputum raised should be expectorated directly into a sterile container. The client should not touch the lip or the inside of the container with the hands or mouth. A 10- to 15-mL specimen is adequate. If the client is unable to produce the desired amount of sputum, several strategies may be attempted. One approach is to have the client drink two glasses of water and then assume the positions for postural drainage of the upper and middle lung segments. Support for effective coughing may be provided by placing the hands or a pillow over the diaphragmatic area and applying slight pressure. Another approach is to place a vaporizer or other humidifying device at the bedside. After sufficient exposure to adequate humidification, postural drainage of the upper and middle lung segments may be repeated before attempting to obtain the specimen. It may also be helpful to obtain an order for an expectorant and administer it along with additional water approximately 2 hours before attempting to obtain the specimen. In addition, chest percussion and postural drainage of all lung segments may be used. If the client still is unable to raise sputum, the use of an ultrasonic nebulizer (“induced sputum”) may be necessary. This is usually undertaken by a respiratory therapist. Tracheal Suctioning. Suction equipment, a suction kit, and a Lukens tube or in-line trap are obtained. The client is positioned with head elevated as high as tolerated. Sterile gloves are applied, with the dominant hand maintained as “sterile” and the nondominant hand as “clean.” The suction catheter is attached with the “sterile hand” to the rubber tubing of the Lukens tube or in-line trap. The suction tubing is then attached to the male adapter of the trap with the “clean” hand. The suction catheter is lubricated with sterile saline. Nonintubated clients should be instructed, if feasible, to protrude the tongue and take a deep breath as the suction catheter is passed through the nostril. When the catheter enters the trachea, a reflex cough is stimulated; the catheter is immediately advanced into the trachea, and suction is applied. Suction should be maintained for approximately 10 seconds and never for more than 15 seconds. The catheter is then withdrawn without applying suction. The suction catheter and suction tubing are separated from the trap, and the rubber tubing is placed over the male adapter to seal the unit. The specimen is labeled and sent to the laboratory immediately. For clients who are intubated or have a tracheostomy, the aforementioned procedure is followed, except that the suction catheter is passed through the existing endotracheal or tracheostomy tube rather than through the nostril. The client should be hyperoxygenated before and after the procedure in accordance with usual protocols for suctioning such clients. NURSING CARE AFTER THE PROCEDURE For specimens obtained by expectoration or nasotracheal suctioning, care and assessment after the procedure include mouth care offered or provided after the specimen has been obtained. Provide a cool beverage to aid in relieving throat irritation caused by coughing and suctioning. Assess the client’s color and respiratory rate, and administer supplemental oxygen as necessary. For specimens obtained by endotracheal tube or tracheostomy, hyperoxygenate the client after the procedure according to usual protocols. Additional suctioning may be necessary to clear secretions raised during suctioning to obtain the specimen. Copyright © 2003 F.A. Davis Company CHAPTER 7—Sputum The characteristics (e.g., color, consistency, volume) of the sample should be noted and documented. Infection or hypoxemia: Note and report tachypnea, dyspnea, diminished breath sounds, change in skin color (cyanosis), and elevated temperature. Administer oxygen and have emergency intubation equipment on hand. Transmission of respiratory pathogens: Place on respiratory precautions. Use mask when in contact with client. Dispose of used articles according to standard precautions and transmission-based isolation procedures. Critical values: Notify physician immediately if test result is positive. CULTURE AND SENSITIVITY Sputum tests for culture and sensitivity (C&S) indicate the type and number of organisms in the specimen (culture) and the antibiotics to which the organisms are susceptible (sensitivity). Although examination of the organisms found in sputum by microscopy or stain may lend support in the diagnosis of suspected infectious disorders, growth of a pathogen in culture is more definitively diagnostic. The pathogenic organisms most often cultured from the sputum of individuals with bacterial pneumonia are Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus, and gram-negative bacilli. Other pathogens that may be identified in sputum cultures include Klebsiella pneumoniae, Mycobacterium tuberculosis, fungi such as Candida and Aspergillus, Corynebacterium diphtheriae, and Bordetella pertussis. In contrast, other organisms that can cause pneumonia, such as mycoplasmas, respiratory viruses, and rickettsiae, are not detected on routine culture.5 Sputum collected by expectoration or suctioning with catheters and by bronchoscopy cannot be cultured for anaerobic organisms. Instead, transtracheal aspiration or lung biopsy must be used.6 Interpretation of the results of sputum cultures requires knowledge of the client’s symptomatology and the nature of the pathogen cultured. Pathogens may be identified in the sputum of individuals who do not have pneumonia or whose pneumonia is actually caused by an organism not identified on culture. Similarly, a person may be diagnosed as having pneumonia on the basis of sputum cultures, when the infection is caused by an obstruction by tumors or foreign bodies, pulmonary infarction, or pulmonary hemorrhage. If Candida or Aspergillus is found on culture, the client must be further evalu- Analysis 271 ated, because these environmental contaminants may be the cause of serious pulmonary disease.7 In legionnaires’ disease, sputum cultures and Gram staining are negative, despite clinical signs of severe pneumonia. When this disease is suspected, confirmation must be obtained through immunologic blood tests (see Chapter 3).8 Rapidity of results from sputum cultures varies according to the rate of growth of the organisms. Routine cultures of M. tuberculosis, for example, may take weeks to become positive. To provide more rapid and reliable diagnostic information, some laboratories use immunologic methods such as counterimmunoelectrophoresis (CIEP) to identify microbial pathogens. In CIEP, antibodies specific to the suspected organisms are used, and rapid confirmation of significant tissue involvement is possible.9 Reference Values Normal respiratory flora include Moraxella catarrhalis, C. albicans, diphtheroids, -hemolytic streptococci, and some staphylococci. INTERFERING FACTORS Improper specimen collection Delay in sending specimen to the laboratory C&S should be performed before antimicrobial therapy to evaluate effectiveness of therapy. INDICATIONS FOR CULTURE AND SENSITIVITY TEST Support for diagnosing the cause of respiratory infection as indicated by the presence or absence (e.g., viral infections, legionnaires’ disease) of organisms in culture Confirmatory diagnosis of tuberculosis (see also AFB smear and culture) Monitoring for response to treatment for respiratory infections, especially tuberculosis Identification of antibiotics to which the cultured organism is sensitive NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of sputum or lower respiratory secretions (see section under “Gram Stain and Other Stains”). THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the “Gram Stain and Other Stains” section. Copyright © 2003 F.A. Davis Company 272 SECTION I—Laboratory Tests NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving collection of sputum or lower respiratory secretions. Depending on the nature of the suspected or confirmed infection, respiratory isolation or drainage and secretion precautions may be used, although these infection-control protocols may have been already implemented before obtaining sputum cultures. Abnormal test results, complications, and precautions: Respond the same as for stains (see earlier section). The client should be informed that culture results for the more common pathogenic microorganisms can be obtained in 24 to 48 hours and that sensitivity results can cause a change in antimicrobial therapy. ACID-FAST BACILLUS SMEAR AND CULTURE The acid-fast staining method is used primarily to identify tubercle bacilli (M. tuberculosis). Acid-fast bacilli have a cell wall that resists decolorization by acid treatment10; that is, they retain the stain applied to the specimen, a small portion of which is smeared on a slide, even after treatment with an acid-alcohol solution. Because the tubercle bacillus is slow growing and culture results may take weeks, an acid-fast bacillus (AFB) smear aids in early detection of the organism and timely initiation of antituberculosis therapy. In addition to organisms of the Mycobacterium genus, Nocardia spp. and Actinomyces spp. can also be identified by acid-fast techniques. AFB cultures are used to confirm both positive and negative results of AFB smears. By specifying that AFB is the organism to be detected on culture, the laboratory is alerted to the fact that several weeks may be needed for conclusive results. As noted, immunologic methods may also be used in diagnosing tuberculosis by sputum analysis. Reference Values Negative for AFB Monitoring for response to treatment for pulmonary tuberculosis NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of sputum or lower respiratory secretions (see section under “Gram Stain and Other Stains”). The client should be informed that it may be several weeks before culture results are available. THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the section under “Gram Stain and Other Stains”). NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of sputum or lower respiratory secretions. If tuberculosis is suspected, the client may be placed on AFB or respiratory isolation, pending AFB smear results. CYTOLOGIC EXAMINATION Cytology is the study of the origin, structure, function, and pathology of cells. In clinical practice, cytologic examinations are generally performed to detect cell changes resulting from malignancies or inflammatory conditions. Lipid droplets contained in macrophages may be found on cytologic examination and may indicate lipoid or aspiration pneumonia.11 Sputum specimens for cytologic examination may be collected by expectoration alone, during bronchoscopy, or by expectoration after bronchoscopy. The method of reporting results of cytologic examinations varies according to the laboratory performing the test. Terms used to report results include negative (no abnormal cells), inflammatory, benign atypical, suspect for malignancy, and positive for malignancy. Reference Values Negative for abnormal cells, Curschmann’s spirals, fungi, ova, and parasites INTERFERING FACTORS Improper specimen collection Delay in sending specimen to the laboratory INDICATIONS FOR ACID-FAST BACILLUS SMEAR AND CULTURE Suspected pulmonary tuberculosis INTERFERING FACTORS Improper specimen collection Delay in sending specimen to the laboratory INDICATIONS FOR CYTOLOGIC EXAMINATION Suspected lung cancer Copyright © 2003 F.A. Davis Company CHAPTER 7—Sputum History of cigarette smoking, which may lead to metaplastic (nonmalignant) cellular changes History of acute or chronic inflammatory or infectious lung disorders, which may lead to benign atypical or metaplastic cellular changes Known or suspected viral disease involving the lung Known or suspected fungal or parasitic infection involving the lung NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of sputum or lower respiratory secretions (see section under “Gram Stain and Other Stains”). THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the “Gram Stain and Other Stains” section. It is common practice to collect three sputum specimens for cytologic examination, usually on three separate mornings. After bronchoscopy, however, serial specimens may be obtained from sputum expectorated within 12 to 24 hours of the procedure. Specimens are collected in either sterile containers or sterile containers to Analysis 273 which 50 percent alcohol has been added, depending on specific laboratory procedures. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of sputum or lower respiratory secretions. Abnormal test results, complications, and precautions: The client should be offered additional support if the diagnostic findings indicate a premalignant or malignant condition and if further diagnostic procedures or chemotherapy/ radiation therapy is advised. REFERENCES 1. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 10. FA Davis, Philadelphia, 1991, p 747. 2. Ibid, p 748. 3. Ibid, p 749. 4. Ibid, p 749. 5. Ibid, p 749. 6. Ibid, p 453. 7. Ibid, p 749. 8. Ibid, p 456. 9. Ibid, pp 460–461. 10. Ibid, pp 460-461. 11. Ibid, p 749. Copyright © 2003 F.A. Davis Company CHAPTER Cerebrospinal Fluid Analysis TESTS COVERED Routine Cerebrospinal Fluid Analysis, 275 Microbiologic Examination of Cerebrospinal Fluid, 279 Cytologic Examination of Cerebrospinal Fluid, 281 Serologic Tests for Neurosyphilis, 281 OVERVIEW OF CEREBROSPINAL FLUID FORMATION AND ANALYSIS Cerebrospinal fluid (CSF) is secreted into the ventricles of the brain by specialized capillaries called choroid plexuses. Most of the CSF arises in the lateral ventricles, although additional amounts are secreted in the third and fourth ventricles. CSF formed in the ventricles circulates into the central canal of the spinal cord and also enters the subarachnoid space through an opening in the wall of the fourth ventricle near the cerebellum, after which it circulates around the brain and spinal cord. Although 500 to 800 mL of CSF are formed daily, only 125 to 140 mL are normally present. Thus, almost all of the CSF formed is reabsorbed via arachnoid granulations, which project from the subarachnoid space into the venous sinuses, and is subsequently returned to the venous circulation. The functions of CSF include cushioning the brain against shocks and blows, maintaining a stable concentration of ions in the central nervous system (CNS), and providing for removal of wastes.1 CSF is produced by the processes of filtration, diffusion, osmosis, and active transport. Initially, sodium is actively transported into the CSF; then water follows passively by osmosis. Facilitated diffusion allows glucose to move between the blood and CSF. Although similar in composition to plasma, CSF generally contains more sodium and chloride and less potassium, calcium, and glucose. Most constituents of CSF, however, parallel those found in plasma and are found in amounts equal to or slightly less than those in the blood.2,3 In addition to entering CSF via the choroid plexuses, substances may pass into CSF from the blood through capillaries in the parenchyma and meninges of the brain and spinal cord. “Barriers” exist between the blood and the CSF and between the brain and the CSF; that is, substances do not pass as readily into the CSF as they would pass into extracellular fluid through other capillary beds. Water, carbon dioxide, oxygen, glucose, small molecules, lipidsoluble substances, nonionized substances, and some drugs (e.g., erythromycin and sulfadiazine) pass rapidly into CSF, whereas large molecules, ionized substances, various toxins, and certain other drugs (e.g., chlortetracyclines and penicillins) do not pass readily into CSF.4 Under pathological conditions, elements normally held back by the blood–brain barrier may enter CSF. Red cells and white cells can enter the CSF either from rupture of vessels or from meningeal reaction to irritation. Unconjugated (prehepatic) bilirubin may be found after intracranial hemorrhage, whereas conjugated bilirubin may be found if the circulating plasma 274 Copyright © 2003 F.A. Davis Company CHAPTER 8—Cerebrospinal Fluid Analysis 275 contains large amounts. Fibrinogen, which is normally absent from CSF, may be found along with albumin and globulins when inflammatory disorders cause increased permeability of the blood–brain barrier. Urea, lactic acid, and glutamine levels in CSF will rise if plasma levels of these or related substances are elevated. Bacteria and fungi found in CSF indicate infection with these organisms.5 As a general rule, routine CSF analysis includes a cell count and differential as well as determinations of protein and glucose levels. In addition, CSF may be analyzed for electrolytes, lactic acid, urea, glutamine, and enzymes. Microbiologic studies of CSF include culture and sensitivity (C&S), Gram stain and other stains, acid-fast bacillus (AFB) smear and culture, and the Limulus assay for gram-negative bacteria. Cytologic examination for malignant cells, as well as serologic tests for syphilis, may be performed on CSF. The gross appearance, opening pressure, and closing pressure should be noted during the procedure and documented. The pH of the sample may also be noted. CSF is normally clear, colorless, and of the consistency of water. Turbidity indicates the presence of a significant number of leukocytes (i.e., greater than 200 to 500 white cells per cubic millimeter). Yellowish discoloration of CSF (xanthochromia) usually indicates previous bleeding but may also be seen when CSF protein levels are greatly elevated. Fresh blood in the specimen may be due to traumatic spinal tap, although clearing should be noted as the second and third tubes are withdrawn in such a case. Bleeding from a traumatic tap adds approximately one to two white cells and 1 mg/dL of protein for every 1000 red cells per cubic millimeter contained in the sample. If blood does not clear as subsequent samples are obtained, bleeding due to subarachnoid hemorrhage is usually indicated. Brown CSF generally indicates a chronic subdural hematoma with CSF stained from methemalbumin.6 Because fibrinogen is normally absent from CSF, the sample should not clot. Clotting may occur, however, when the protein content of the sample is elevated. In conditions involving spinal subarachnoid block, CSF may be yellow and have a tendency toward rapid spontaneous clotting. The pH of CSF is normally slightly lower than that of blood, with a range of 7.32 to 7.35 when arterial blood pH is within normal limits.7 CSF specimens must be transported to the laboratory immediately. Within 1 hour of collection, any red cells contained in the sample begin to lyse and may cause spurious coloration of the specimen. Neutrophils and malignant cells may also disintegrate in a short time. Bacteria and other cells will continue to metabolize glucose, such that delays in analysis may alter chemical values.8 The opening CSF pressure (OP) is measured after the spinal needle is determined to be in the subarachnoid space. CSF pressure may be elevated if clients are anxious and hold their breath or tense their muscles. It may also be elevated if there is venous compression such as may occur if the client’s knees are flexed too firmly against the abdomen. Significant elevations in CSF pressure may occur with intracranial tumors and with purulent or tuberculous meningitis. Less marked increases (i.e., 250 to 500 mm of water) are associated with low-grade inflammatory processes, encephalitis, or neurosyphilis. Decreases in CSF pressure are rare but may occur with dehydration, high obstruction to CSF flow, or previous aspiration of spinal fluid.9 The closing pressure (CP) is recorded before removal of the spinal needle from the subarachnoid space. Normally, CSF pressure decreases 5 to 10 mm of water for every milliliter of CSF withdrawn. The expected decrease in CSF pressure does not occur in disorders in which the total quantity of CSF is increased (e.g., hydrocephalus). In contrast, a large drop in pressure indicates a small CSF pool and is seen in tumors or spinal block.10 CEREBROSPINAL FLUID TESTS ROUTINE CEREBROSPINAL FLUID ANALYSIS Routine CSF analysis includes a cell count and differential, as well as determinations of protein and glucose levels. CSF may also be analyzed for electrolytes, lactic acid, urea, glutamine, and enzymes. CELL COUNT AND DIFFERENTIAL Normal spinal fluid is free of cells. Note that crypto- Copyright © 2003 F.A. Davis Company 276 SECTION I—Laboratory Tests coccal organisms in the sample may be mistaken for small lymphocytes. PROTEINS CSF normally contains very little protein because most proteins cannot cross the blood–brain barrier. In addition to determining the amount of protein present in CSF, levels of certain types of protein may also be measured. Albumin, for example, is a relatively small molecule and may pass more easily into CSF. For this reason, the albumin-to-globulin (A-G) ratio is normally higher in CSF than in serum. Protein electrophoresis may also be performed on CSF samples. The protein concentration in CSF may rise as a result of increased permeability of the blood–brain barrier because of inflammation and infection. CSF protein levels may also be elevated in clients with diabetes mellitus and cardiovascular disease because of increased permeability of the blood–brain barrier.11 GLUCOSE The glucose concentration of CSF is altered by the presence of microorganisms. Because all types of organisms consume glucose, levels will be decreased if the CSF contains bacteria, fungi, protozoa, or tubercle bacilli. However, this decrease is not as pronounced or may not be seen at all in viral meningitis. Bacterial and other cells present in CSF continue to metabolize glucose even after the sample has been collected. Thus, spuriously low glucose levels may be found in CSF if analysis is delayed. OTHER SUBSTANCES Other substances for which CSF may be analyzed include electrolytes, lactic acid, urea, glutamine, and enzymes. The electrolyte levels found in CSF are similar to those of plasma, with the exceptions of sodium and chloride, which are higher, and potassium and calcium, which are lower. The significance of electrolyte levels in CSF is questionable. Some writers, for example, indicate that chlorides are decreased in tuberculosis and bacterial meningitis.12,13 Others state that chloride levels provide no specific diagnostic information.14 The calcium found in CSF is that fraction not bound by protein and is about half that of serum levels. Calcium levels rise with CSF protein levels; it is more important to determine the protein level in such cases, however, than to measure calcium.15 Lactic acid in CSF reflects local glycolytic activity and adds to diagnostic information when results of other analyses are inconclusive. Severe systemic lactic acidosis causes CSF lactate to rise accordingly. Elevated CSF lactate without a parallel elevation in serum level indicates increased CSF glucose metabolism, which is usually due to bacterial or fungal meningitis. In early or partially treated bacterial or fungal meningitis, CSF cell count and glucose levels may be similar to those found in viral meningitis or noninfectious conditions. Lactate levels above 35 mg/dL rarely occur, however, unless the client has bacterial or fungal meningitis. Lactate levels remain elevated until the individual has received effective antibiotic therapy for several days. Persistent elevation of CSF lactate levels indicates inadequate treatment of meningitis.16 Urea levels in CSF and blood are approximately equal; thus, CSF urea levels rise when blood levels are elevated, as in uremia. Urea is sometimes administered intravenously (IV) to lower intracranial pressure. In such cases, the subsequent elevation in CSF urea levels causes fluid to shift from the brain to the CSF. CSF urea levels may remain elevated for 24 to 48 hours after IV administration of urea. Glutamine is synthesized in the CNS from ammonia and glutamic acid. CSF glutamine levels rise when blood ammonia levels are high, a situation seen in cirrhosis with altered hepatic blood flow and encephalopathy. Glutamine levels in CSF have been found to correlate as well or better than blood ammonia levels with the degree of hepatic encephalopathy. Enzymes that have been measured in CSF include lactic dehydrogenase (LDH), alanine aminotransferase (ALT, SGPT), and aspartate aminotransferase (AST, SGOT). Levels of these enzymes are normally lower than those found in the blood. CSF enzymes may rise in inflammatory, hemorrhagic, or degenerative diseases of the CNS. CSF enzyme levels are not measured under routine conditions, however, and may not add to the diagnostic information obtained from more routinely available tests.17 INTERFERING FACTORS Delay in transporting sample to the laboratory (may cause spurious discoloration as a result of lysis of any red cells present, disintegration of any neutrophils present, and false decrease in glucose as a result of continued utilization by cells in the sample) Blood in the sample caused by traumatic tap (adds one to two white cells and 1 mg/dL of protein for every 1000 red cells per cubic millimeter contained in the sample) INDICATIONS FOR ROUTINE CEREBROSPINAL FLUID ANALYSIS Suspected viral meningitis, cerebral thrombosis, or brain tumor as indicated by a cell count of 10 to 200 per cubic millimeter, consisting mostly of Copyright © 2003 F.A. Davis Company CHAPTER 8—Cerebrospinal Fluid Analysis 277 Reference Values Conventional Units Color SI Units Clear Pressure Children 50–100 mm H2O Adults 75–200 mm H2O (120 mm H2O average) Cell count and differential Children Up to 20 small lymphocytes per cubic millimeter Adults Up to 5 small lymphocytes per cubic millimeter No RBC or granulocytes Protein Total proteins Infants 30–100 mg/dL 0.30–1.0 g/L Children 14–45 mg/dL 0.14–0.45 g/L Adults 15–45 mg/dL (lumbar area) or less than 1% of serum levels 0.15–0.45 g/L A-G ratio 8:1 IgG 3–12% of total protein Glucose Infants 20–40 mg/dL 1.11–2.22 mmol/L Children 35–75 mg/dL 1.94–4.16 mmol/L Adults 40–80 mg/dL or less than 50–80% of blood glucose level 30–60 min earlier 2.22–4.44 mmol/L Chloride 118–132 mEq/L 118–132 mmol/L Calcium 2.1–2.7 mEq/L 1.05–1.35 mmol/L Sodium 144–154 mEq/L 144–154 mmol/L Potassium 2.4–3.1 mEq/L 2.4–3.1 mmol/L Lactic acid (lactate) 10–20 mg/dL 1.1–2.2 mmol/L Urea 10–15 mg/dL 3.6–5.3 mmol/L Glutamine Less than 20 mg/dL 1370.0 mol/L Lactic dehydrogenase (LDH) 1/10 that of serum level Electrolytes lymphocytes, a mild elevation (to 300 mg/dL) in total proteins, and normal or slightly decreased glucose level Suspected multiple sclerosis or neurosyphilis as indicated by a normal or slightly elevated cell count, consisting mostly of lymphocytes, slightly elevated protein (less than 100 mg/dL), slightly elevated globulins, elevated IgG on protein electrophoresis, and a normal or slightly decreased glucose level Suspected acute bacterial or syphilitic meningitis, herpes infection of CNS as indicated by a cell count of greater than 500 per cubic millimeter, consisting largely of granulocytes, moderate or Copyright © 2003 F.A. Davis Company 278 SECTION I—Laboratory Tests pronounced elevation in protein (greater than 300 mg/dL), pronounced decrease in glucose, and decreased chloride18 Suspected tuberculous meningitis as indicated by a cell count of 200 to 500 per cubic millimeter, consisting of lymphocytes or mixed lymphocytes and granulocytes, moderate or pronounced elevation in proteins, pronounced reduction in glucose, and decreased chloride Suspected early bacterial or fungal meningitis as indicated by CSF lactate level above 35 mg/dL, even when cell count and glucose level are only slightly altered Evaluation of effectiveness of treatment for bacterial or fungal meningitis, with effective treatment indicated by decreasing lactate levels after several days of antimicrobial therapy Suspected CNS leukemia as indicated by a cell count of 200 to 500 per cubic millimeter, consisting mainly of blast cells and a moderate reduction in glucose Suspected spinal cord tumor as indicated by a cell count of 10 to 200 per cubic millimeter, moderate or pronounced elevation in protein, and normal or slightly decreased glucose Support for diagnosing subarachnoid hemorrhage as indicated by the presence of red blood cells, elevated proteins, and a moderate reduction in glucose Support for diagnosing hepatic encephalopathy as indicated by elevated glutamine levels Support for diagnosing Guillain-Barré syndrome (ascending polyneuritis) as indicated by pronounced elevation in proteins NURSING CARE BEFORE THE PROCEDURE Explain to the client: That the procedure will be performed by a physician and requires 20 to 30 minutes The positioning used for the procedure and the necessity of remaining still while the procedure is being performed That a local anesthetic will be injected at the needle insertion site That the needle is inserted below the end of the spinal cord (for lumbar punctures) That a sensation of pressure may be felt when the needle is inserted The necessity of remaining flat in bed for 6 to 8 hours after the procedure (for lumbar punctures) and that turning from side to side is permitted as long as the head is not raised That taking fluids after the procedure will aid in returning the CSF volume to normal (provided that this is not contraindicated for the particular client) Prepare the client for the procedure: Have the client void. Provide a hospital gown. Take and record vital signs, assess legs for neurological status (strength, movement, and sensation) for comparison with postprocedure assessment. Obtain a signed informed consent if required by the agency. THE PROCEDURE The necessary equipment is assembled (e.g., lumbar puncture tray). The client is assisted to a side-lying position, with the head flexed as far as comfortable and the knees drawn up toward, but not pressing on, the abdomen. Support in maintaining this position may be provided by placing one hand on the back of the client’s neck and the other behind the knees. Lumbar punctures may also be performed with the client seated while leaning forward with arms resting on an overbed table or other support. The lumbar area is cleansed with an antiseptic and protected with sterile drapes. The skin is infiltrated with a local anesthetic and the spinal needle with stylet is inserted into a vertebral interspace between L2 to S1, usually L3–4 or L4–5. The stylet is then removed and, if the needle is properly positioned in the subarachnoid space, spinal fluid will drip from the needle. A sterile stopcock and manometer are then attached to the needle. The opening pressure is read (see earlier discussion) and, if indicated, Queckenstedt’s test is performed. When the needle and manometer are properly positioned, the CSF level should fluctuate several millimeters with respiration.19 Queckenstedt’s test is based on the principle that a change in pressure in one area of the closed system—composed of the ventricular spaces, intracranial subarachnoid space, and vertebral subarachnoid space—will be reflected in other areas of the system as well. The test is indicated when total or partial spinal block (e.g., due to tumor) is suspected, and it is performed by compressing both jugular veins while monitoring lumbar CSF pressure. Temporary occlusion of the jugular veins impairs the absorption of intracranial fluid and produces an acute rise in CSF pressure. If CSF flow is unimpeded, the pressure elevation will be transmitted to the lumbar area, and the fluid level in the manometer will rise. Total or partial spinal block is diagnosed if the CSF pressure fails to rise or if more than 20 seconds is required for the pressure to return to the pretest level after pressure on the jugular veins is released. Queckenstedt’s test is risky in clients with increased intracranial pressure of highly reactive carotid body receptors. Radiologic examinations Copyright © 2003 F.A. Davis Company CHAPTER 8—Cerebrospinal such as myelograms and computed axial tomography (CAT) scans may give more information and carry less risk.20 The manometer is then removed and CSF is allowed to drip into three sterile test tubes, 3 to 10 mL per tube. The tubes are numbered in order of filling, labeled with the client’s name, and sent to the laboratory immediately. The manometer may then be reattached and the closing pressure recorded. The spinal needle is removed, and pressure is applied to the site. If no excessive bleeding or CSF leakage is noted, an adhesive bandage is applied to the site and the client is assisted to a recumbent position. Alternatives to the lumbar puncture include cisternal and ventricular punctures. These procedures may be used when lumbar puncture is not feasible because of bony abnormalities or infection at the lumbar area. For a cisternal puncture, the client is assisted to a side-lying position with the neck flexed and the head resting on the chest. The back of the neck may require shaving before the procedure. After the skin is infiltrated with local anesthetic, the needle is inserted at the base of the occiput, between the first cervical vertebra and the foramen magnum. CSF samples are then obtained in the same manner as for lumbar punctures. Cisternal punctures are considered somewhat hazardous, because the needle is inserted close to the brainstem; however, clients are said to be less likely to experience postprocedure headaches and may resume usual activities within a few hours of the procedure.21 Ventricular punctures are surgical procedures (i.e., usually performed in an operating room) in which CSF samples are obtained directly from one of the lateral ventricles in the brain. For this procedure, a scalp incision is made and a burr hole is drilled in the occipital area of the skull. The needle is then inserted through the hole and into the lateral ventricle, and CSF samples are obtained. This procedure is rarely performed.22 The cell count and protein content of CSF samples obtained by cisternal or ventricular punctures are normally lower than those found in lumbar samples. The higher levels of cells and protein found in CSF from lumbar punctures are thought to be caused by stagnation of CSF, which occurs in the lumbar sac.23 NURSING CARE DURING THE PROCEDURE Note any distress, especially dyspnea, that may be caused by positioning. Observe for signs of brainstem herniation such as decreased level of consciousness, irregular respirations, and a unilaterally dilating pupil (uncal herniation). Fluid Analysis 279 NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client to a recumbent position and having the client maintain a flat position for 6 to 8 hours to prevent the occurrence of headache. Remind the client that turning from side to side is permitted, as long as the head is not raised. Assist the client in taking liberal amounts of fluids to replace the CSF loss, unless otherwise contraindicated. A dressing can be applied after pressure to the puncture site. Care after cisternal and ventricular punctures is essentially the same as that for lumbar punctures. For cisternal punctures, provide bed rest for only 2 to 4 hours, after which usual activities may be resumed. For ventricular punctures, maintain bed rest for 24 hours. Take and record vital signs every hour for the first 4 hours and then every 4 hours for 24 hours (for hospitalized clients). Perform a neurological check each time vital signs are taken to determine nerve damage affecting the legs. Assess the puncture site for bleeding, CSF drainage, and inflammation each time vital signs are taken during the first 24 hours and daily thereafter for several days. (Family members or support persons should be instructed to do this for nonhospitalized clients.) Observe for signs of meningeal irritation such as fever, nuchal rigidity, and irritability indicating infection. Assess the client’s comfort level, noting presence or absence of headache. Administer an ice bag to the head and a mild analgesic if ordered. MICROBIOLOGIC EXAMINATION OF CEREBROSPINAL FLUID Microbiologic studies of CSF include C&S, Gram stain and other stains, AFB smear and culture, and the Limulus assay for gram-negative bacteria. Numerous microorganisms can cause meningitis, encephalitis, and brain abscess. Thus, whenever CNS infection is suspected, CSF should be tested for the presence of bacteria, fungi, protozoa, and tubercle bacilli, because more than one organism may be present.24 The CSF is also tested for bacterial antigens in addition to culturing for bacteria. CSF rarely contains abundant organisms, so specimens for microbiologic examination must be collected and handled with strict aseptic technique. The usual laboratory procedure is to centrifuge a few milliliters of CSF to concentrate any organisms present. After Copyright © 2003 F.A. Davis Company 280 SECTION I—Laboratory Tests culture plates with several different media are inoculated, the remaining CSF sediment is examined with Gram staining and AFB staining techniques (see Chapter 7).25 Failure to isolate organisms on stained smear does not necessarily mean that organisms are absent from the CSF sample. Reliably positive results are obtained only when at least 105 bacteria per milliliter are present. Gram stains, for example, are positive in only 80 to 90 percent of individuals with untreated meningitis. CSF is almost routinely examined and cultured for AFB when the cause of the CNS disorder is unknown, because tuberculous meningitis can develop insidiously and presents with few clear diagnostic indicators.26 When infection with the fungus Cryptococcus is suspected, the specimen may be examined by testing for cryptococcal antigen.27 The cryptococcal antigen test, in which a strong anticryptococcal antibody is used, may elicit antigenic elements even when cryptococcal organisms are undetected by other methods.28 Amebae may also cause meningitis, especially in individuals who swim in lakes or indoor swimming pools. A wet-mount preparation of CSF is examined for motile cells when such an infection is suspected.29 Spinal fluid is normally cultured on several different media to test for different organisms. The meningococcal organism (Neisseria meningitidis), for example, prefers to grow in a medium with a high carbon dioxide atmosphere. Counterimmunoelectrophoresis (CIEP) can also be used to detect bacterial antigens when usual techniques fail to demonstrate bacteria in CSF.30 The presence of gram-negative organisms in CSF can be demonstrated rapidly with the Limulus assay. This test uses the bloodlike fluid of the horseshoe crab of the genus Limulus, which is coagulated by gram-negative endotoxins. This test, therefore, provides a quick means of diagnosing gram-negative infections of the CNS and gram-negative endotoxemia. The test is more reliable when performed on CSF than when performed on blood.31 Acute bacterial meningitis occurs most commonly in children younger than age 5 years and in adults who have experienced head trauma. Gramnegative bacilli (Escherichia coli, Klebsiella, Enterobacter, Proteus) are the usual etiologic agents of meningitis in premature infants and newborns. In infants, the causative agents include Streptococcus agalactiae (group B) and Listeria monocytogenes. In young children, meningitis is most frequently caused by gram-negative bacilli (Haemophilus influenzae). In adolescents, the agent is most likely to be N. meningitidis. In adults, meningitis may also be caused by Streptococcus pneumoniae. In elderly persons, the agent is a gram-negative bacillus. Viral infections, tuberculous meningitis, and fungal and protozoal infections may occur at any age and often present as insidious or misleading syndromes.32 Reference Values Organisms are not normally present in CSF. INTERFERING FACTORS Delay in transporting the sample to the laboratory (Organisms may disintegrate if the sample is held at room temperature for more than 1 hour.) Contamination of the sample with normal skin flora or other organisms because of improper collection or handling of the sample INDICATIONS FOR MICROBIOLOGIC EXAMINATION OF CEREBROSPINAL FLUID Suspected meningitis, encephalitis, or brain abscess CNS disorder of unknown etiology without clear diagnostic indicators Head trauma with possible resultant CNS infection NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of CSF samples (see section under “Routine Cerebrospinal Fluid Analysis”). THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the “Routine Cerebrospinal Fluid Analysis” section. Extreme care must be used in obtaining and collecting the sample, so as not to contaminate the sample or introduce organisms into the CNS. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a CSF sample (see section under “Routine Cerebrospinal Fluid Analysis”). Depending on the nature of the suspected or confirmed infection, use infectious disease precautions. Complications and precautions: Note and report signs and symptoms of brain disorder such as fever, irritability, or headache. Perform neurological checks and take and record vital signs. Notify physician immediately of a positive stain result. Copyright © 2003 F.A. Davis Company CHAPTER 8—Cerebrospinal CYTOLOGIC EXAMINATION OF CEREBROSPINAL FLUID Cytologic examination of CSF is performed primarily to detect malignancies involving the CNS. Cellular changes caused by malignancies whose primary site is the CNS (e.g., brain tumors) or malignancies that have metastasized to the CNS from other sites (e.g., breast and lung) may be detected. Abnormal cells resulting from acute leukemia involving the CNS may also be seen. Reference Values Fluid Analysis 281 ment fixation tests and the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) flocculation tests. The best specific test is the fluorescent treponemal antibody (FTA) test. Nonspecific reagin tests are usually used for routine testing of CSF because they are cheaper and more readily available than the FTA test. The falsepositive results that can occur when blood is tested with reagin tests occur fairly rarely in CSF specimens. Nonspecific tests are, however, less sensitive than the FTA test. Thus, if neurosyphilis is a serious diagnostic consideration, the FTA is the test of choice.33 No abnormal cells Reference Values INTERFERING FACTORS Delay in transporting the sample to the laboratory (Cells may disintegrate if the sample is held at room temperature for more than 1 hour.) Contamination of the sample with skin cells INDICATIONS FOR CYTOLOGIC EXAMINATION OF CEREBROSPINAL FLUID Suspected malignancy with primary site in the CNS Suspected metastasis of malignancies to the CNS Suspected CNS involvement in acute leukemia NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of CSF samples (see section under “Routine Cerebrospinal Fluid Analysis”). THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the “Routine Cerebrospinal Fluid Analysis” section. Care must be taken not to contaminate the sample with skin cells. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a CSF sample (see section under “Routine Cerebrospinal Fluid Analysis”). SEROLOGIC TESTS FOR NEUROSYPHILIS When syphilis involving the CNS (neurosyphilis) is suspected, serologic tests are performed on samples of CSF. Blood tests for syphilis (see Chapter 3) consist of two main types: (1) nonspecific tests that demonstrate syphilitic reagin and (2) specific tests that demonstrate antitreponemal antibodies. Reagin tests include the Wassermann and Reiter comple- Negative INTERFERING FACTORS Delay in transporting the sample to the laboratory (Organisms may disintegrate if the sample is held at room temperature for more than 1 hour.) INDICATIONS FOR SEROLOGIC TESTS FOR NEUROSYPHILIS Suspected neurosyphilis NURSING CARE BEFORE THE PROCEDURE Client preparation is the same as that for any test involving the collection of CSF samples (see section under “Routine Cerebrospinal Fluid Analysis”). THE PROCEDURE The procedures for obtaining the specimen are the same as those described in the “Routine Cerebrospinal Fluid Analysis” section. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure are the same as for any test involving the collection of a CSF sample (see section under “Routine Cerebrospinal Fluid Analysis”). REFERENCES 1. Porth, CM. Pathophysiology: Concepts of Altered Health, ed 5. JB Lippincott, Philadelphia, 1998, pp 868–869. 2. Ibid, p 868. 3. Sacher, RA, and McPherson, RA: Widmann’s Clinical Interpretation of Laboratory Tests, ed 11. FA Davis, Philadelphia, 2000, p 537. 4. Porth, op cit, p 870. 5. Sacher and McPherson, op cit, pp 731, 735. 6. Ibid, p 729. 7. Ibid, p 732. 8. Ibid, p 733. 9. Ibid, p 730. 10. Ibid, p 731. 11. Ibid, pp 732–733. Copyright © 2003 F.A. Davis Company 282 SECTION I—Laboratory Tests 12. Fischbach, FT: A Manual of Laboratory Diagnostic Tests, ed 4. JB Lippincott, Philadelphia, 1992, p 255. 13. Springhouse Corporation: Nurse’s Reference Library: Diagnostics, ed 2. Springhouse, Springhouse, Pa, 1986, p 776. 14. Sacher and McPherson, op cit, p 735. 15. Ibid, p 735. 16. Ibid, p 733. 17. Ibid, pp 733, 735. 18. Ibid, pp 731–732. 19. Ibid, p 730. 20. Ibid, pp 730–731. 22. Nurse’s Reference Library, op cit, p 779. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. Ibid, p 779. Sacher and McPherson, op cit, p 732. Ibid, p 735. Ibid, p 495. Ibid, p 735. Ibid, p 735. Ibid, p 735. Ibid, p 735. Ibid, p 735. Ibid, p 734. Ibid, p 734 Ibid, p 736. Copyright © 2003 F.A. Davis Company CHAPTER Analysis of Effusions TESTS COVERED Pericardial Fluid Analysis, 284 Pleural Fluid Analysis, 286 Peritoneal Fluid Analysis, 289 Synovial Fluid Analysis, 292 OVERVIEW OF EFFUSIONS Effusions are excessive accumulations of fluid in body cavities lined with serous or synovial membranes. Such cavities normally contain only small amounts of fluid (i.e., less than 50 mL). Serous membranes line the closed cavities of the thorax and abdomen and cover the organs within them. Membranes lining cavities are termed parietal membranes; membranes covering organs are called visceral membranes. Serous membranes consist of a layer of simple squamous epithelium (mesothelium) that covers a thin layer of connective tissue.1 Serous membranes secrete a small amount of watery fluid into the potential space between the parietal and visceral membranes. Serous fluid serves as a lubricant, allowing the internal organs to move without excessive friction. Although there is no actual space between visceral and parietal serous membranes, the potential space between them is called a cavity. In certain disease states, these cavities may contain large amounts of fluid (i.e., effusions). Three such serous cavities are the pericardial cavity, the pleural cavity, and the peritoneal cavity. Synovial membranes line the cavities of most joints, the bursae, and the synovial tendon sheaths. These membranes consist of fibrous connective tissue, which overlies loose connective tissue and adipose tissue.2 Synovial cells are found in layers one to three cells thick; wide gaps are often found between adjacent synovial cells. Synovial membranes secrete a thick, colorless fluid with a high mucin content. As with serous fluid, synovial fluid acts as a lubricant in joint cavities. It also provides nourishment to articular cartilage.3 Serous fluid is formed by diffusion from adjacent capillaries via interstitial fluid and may be described as an ultrafiltrate of plasma. Thus, substances that normally diffuse from capillaries (e.g., water, electrolytes, glucose) diffuse into serous fluid. Similarly, substances can diffuse from serous fluid back into the capillaries. Protein may also collect in serous cavities because of capillary leakage. Protein and excess fluids are normally removed from these cavities by the surrounding lymphatics. Synovial fluid is formed in a manner similar to that of serous fluid but additionally contains a hyaluronate–protein complex (i.e., a mucopolysaccharide containing hyaluronic acid and a small amount of protein) that is secreted by the connective tissue cells of the synovial membrane.4 As with serous cavities, excess proteins and fluids are normally drained from synovial cavities by the lymphatics. Changes in fluid production and drainage can lead to the development of effusions in serous and synovial cavities. Mechanical factors that can cause effusions include increased capillary permeability, increased capillary hydrostatic pressure, decreased capillary colloidal osmotic pressure, increased venous pressure, and blockage of lymphatic vessels. Damage to the serous 283 Copyright © 2003 F.A. Davis Company 284 SECTION I—Laboratory Tests and synovial membranes (e.g., caused by inflammation or infection) can also cause excessive fluid buildup. Effusions involving serous cavities may be differentiated as transudates or exudates. Transudates occur because of abnormal mechanical factors and are generally characterized by low-protein, cell-free fluids. Exudates are caused by infection or inflammation and contain cells and excessive amounts of protein. Pleural and peritoneal effusions can be either transudates or exudates; pericardial effusions, however, are almost always exudates.5 Chylous effusions caused by the escape of chyle from the thoracic lymphatic duct may form in the pleural and peritoneal cavities. Accumulation of large amounts of fluid in the peritoneal cavity is termed ascites. Samples of effusions for laboratory analysis are obtained by needle aspiration. Centesis is a suffix denoting “puncture and aspiration of.”6 Thus, aspiration of pericardial fluid is called pericardiocentesis, aspiration of pleural fluid is called thoracentesis, aspiration of peritoneal fluid is called paracentesis, and aspiration of synovial fluid is called arthrocentesis. Serous fluids are normally clear and pale yellow, occurring in amounts of 50 mL or less in the pericardial and peritoneal cavities and 20 mL or less in the pleural cavity. Cloudy (turbid) fluid suggests an inflammatory process that may be caused by infection. Milky fluid is associated with chylous effusions or chronic serous effusions (pseudochylous effusions). Bloody fluid may indicate a hemorrhagic process or a traumatic tap. Bloody pericardial fluid is associated with a number of disorders, including hemorrhagic and bacterial pericarditis, postmyocardial infarction and postpericardiectomy syndromes, metastatic cancer, aneurysms, tuberculosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. Bloody pleural effusions are most often the result of malignancies involving the lung but may also be seen in pneumonia, pulmonary infarction, chest trauma, pancreatitis, and postmyocardial infarction syndrome. Bloody pleural transudates also have been noted in congestive heart failure (CHF) and cirrhosis of the liver. Bloody peritoneal fluid is associated primarily with malignant processes and abdominal trauma. Greenish peritoneal fluid is seen in perforated duodenal ulcers, intestines, and gallbladders, as well as with cholecystitis and acute pancreatitis.7 As with serous fluid, synovial fluid is normally clear and pale yellow, occurring in amounts of approximately 3 mL or less per joint cavity. Synovial fluid is more viscous than serous fluid because of the presence of the hyaluronate–protein complex secreted by the synovial cells. Arthritis and other inflammatory conditions involving the joints may affect the production of hyaluronate and lead to decreased viscosity of synovial fluid. The mucin clot test (Ropes test), in which synovial fluid is added to a 2 to 5 percent acetic acid solution, can be used to assess the viscosity of synovial fluid in relation to the type of clot formed (e.g., solid, soft, friable, or none).8 This test, however, is not as accurate as specific synovial fluid cell counts and other analyses.9 Cloudy synovial fluid suggests an inflammatory process. Substances such as crystals, fibrin, amyloid, and cartilage fragments can also result in cloudy synovial fluid. Milky synovial fluid is associated with various types of arthritis as well as with SLE. Purulent fluid may be seen in acute septic arthritis, whereas greenish fluid may occur in Haemophilus influenzae septic arthritis, chronic rheumatoid arthritis, and acute synovitis caused by gout. Bloody synovial fluid may be the result of a traumatic tap but is most commonly associated with fractures or tumors involving the joint and traumatic or hemophilic arthritis.10 Tests of serous and synovial effusions include cell count and differential, measurement of substances normally found in the fluid (e.g., glucose), culture and sensitivity (C&S) testing, and cytologic examination. These tests are discussed subsequently in relation to the cavity from which the fluid is obtained. TESTS OF EFFUSIONS PERICARDIAL FLUID ANALYSIS Pericardial effusions are most commonly caused by pericarditis, malignancy, or metabolic damage. As noted previously, most pericardial effusions are exudates. Tests commonly performed on pericardial fluid include red cell count, white cell count and differential, determination of glucose level, and cytologic examination. Gram stains and cultures of pericardial fluid are not routinely performed unless bacterial endocarditis is suspected.11 Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis of Effusions 285 Reference Values Red blood cells None normally present White blood cells 1000/mm3 Glucose 80–100 mg/dL or essentially the same as the blood glucose level drawn 2–4 hr earlier Cytologic examination No abnormal cells Gram stain and culture No organisms present Critical values Positive Gram stain or culture Cytologic examination of pericardial fluid is undertaken to detect malignant cells. Gram stain and culture reveal the causative agent when infection is suspected. INTERFERING FACTORS Blood in the sample because of traumatic pericardiocentesis Undetected hypoglycemia or hyperglycemia Contamination of the sample with skin cells and pathogens INDICATIONS FOR PERICARDIAL FLUID ANALYSIS Pericardial effusion of unknown etiology Suspected hemorrhagic pericarditis as indicated by the presence of red cells and an elevated white cell count Suspected bacterial pericarditis as indicated by the presence of red cells, elevated white cell count with a predominance of neutrophils, and decreased glucose Suspected postmyocardial infarction syndrome (Dressler’s syndrome) as indicated by the presence of red cells and elevated white cell count with a predominance of neutrophils Suspected tuberculous or fungal pericarditis as indicated by the presence of red cells and an elevated white cell count with a predominance of lymphocytes Suspected viral pericarditis as indicated by the presence of red cells and an elevated white cell count with neutrophils predominating Suspected rheumatoid disease or SLE as indicated by the presence of red cells, elevated white cell count, and decreased glucose levels Suspected malignancy as indicated by the presence of red cells, decreased glucose, and presence of abnormal cells on cytologic examination NURSING CARE BEFORE THE PROCEDURE Explain to the client: That the procedure will be performed by a physician and will require approximately 20 minutes Where the test will be performed (i.e., it is sometimes performed in the cardiac laboratory) Any dietary restrictions (fasting for 6 to 8 hours before the test may be required) That an intravenous (IV) infusion will be started before the procedure and discontinued afterward That a sedative may be administered before the procedure That the skin will be injected with a local anesthetic at the chest needle insertion site and that this may cause a stinging sensation That, after the skin has been anesthetized, a needle will be inserted through the chest wall below and slightly to the left of the breast bone into the fluidfilled sac around the heart That a sensation of pressure may be felt when the needle is inserted to obtain the pericardial fluid That heart rate and rhythm will be monitored during the procedure The importance of remaining still during the procedure Any activity restrictions after the test (usually a few hours of bed rest) Prepare for the procedure: Withhold anticoagulant medications and aspirin as ordered. Have the client void. Provide a hospital gown. Take and record vital signs. Administer premedication as ordered. THE PROCEDURE (PERICARDIOCENTESIS) The necessary equipment is assembled, including a pericardiocentesis tray with solution for skin preparation, local anesthetic, 50-mL syringe, needles of various sizes including a cardiac needle, sterile drapes, and sterile gloves. Sterile test tubes (same as those used for collecting blood samples) also are needed; at least one red-topped, one green-topped, and one lavender-topped tube should be available. Containers for culture and cytologic analysis of pericardial fluid samples may also be needed. Cardiac monitoring equipment should be obtained, along Copyright © 2003 F.A. Davis Company 286 SECTION I—Laboratory Tests with an alligator clip for attaching a precordial (V) lead to the cardiac needle. The client is assisted to a supine position with the head elevated 45 to 60 degrees. The limb leads for the cardiac monitor are attached to the client, and the IV infusion is started. The skin is cleansed with an antiseptic solution and protected with sterile drapes. The skin at the needle insertion site is then infiltrated with local anesthetic. Strict aseptic technique is used during the entire procedure. The precordial (V) cardiac lead wire is attached to the hub of the cardiac needle with the alligator clip. The needle is then inserted just below and slightly to the left of the xiphoid process. Gentle traction is sustained on the plunger of the 50-mL syringe until fluid appears, indicating that the needle has entered the pericardial sac. Fluid can be aspirated with ultrasound guidance. Fluid samples are then withdrawn and placed in appropriate tubes. The samples are labeled and sent promptly to the laboratory. When the desired samples have been obtained, the cardiac needle is withdrawn. Pressure is applied to the site for 5 minutes. If there is no evidence of bleeding or other drainage, a sterile bandage is applied. If the client’s cardiac rhythm is stable, cardiac monitoring is discontinued. NURSING CARE DURING THE PROCEDURE Observe the client for respiratory or cardiac distress. Possible complications of a pericardiocentesis include cardiac dysrhythmias (atrial or ventricular), laceration of the pleura, laceration of the cardiac atrium or coronary vessels, injection of air into a cardiac chamber, and contamination of pleural spaces with infected pericardial fluid. Monitor the electrocardiograph for position of the needle tip to note any puncture of the right atrium. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client to a position of comfort and reminding the client of any activity restrictions. Resume any foods or fluids withheld before the test and any medications withheld on the physician’s order. Continue IV fluids until vital signs are stable and the client is able to resume normal fluid intake. Take and record vital signs as for a postoperative client (i.e., every 15 minutes for the first hour, every 30 minutes for the second hour, every hour for the next 4 hours, and then every 4 hours for 24 hours). Assess for abnormalities in ECG patterns. Assess the puncture site for bleeding, hematoma formation, and inflammation each time vital signs are taken and daily thereafter for several days. Observe the client for any cardiac or respiratory distress. Provide support when diagnostic findings are revealed. Note relief of symptoms of cardiac tamponade or pericarditis: absence of distended neck veins; normal cardiac output, heart rate, and heart sounds; absence of chest pain and pulsus paradoxus. Administer antibiotics specific to the causative agent and anti-inflammatory drugs to reduce the inflammatory response. Notify physician immediately if the Gram stain and culture are positive. PLEURAL FLUID ANALYSIS Pleural effusions are most commonly caused by CHF, hypoalbuminemia (e.g., resulting from cirrhosis of the liver), hypoproteinemia (e.g., resulting from nephrotic syndrome), neoplasms, and pulmonary infections (e.g., pneumonia, tuberculosis). Other causes include trauma and pulmonary infarctions, both of which are associated with hemorrhagic effusions, rheumatoid disease, SLE, pancreatitis, and ruptured esophagus. Chylous pleural effusions occur when damage or obstruction to the thoracic lymphatic duct has occurred. Pleural effusions can be either transudates or exudates. Tests commonly performed on pleural fluid include red cell count, white cell count and differential, Gram stain, C&S, and cytologic examination. The pH of the sample is usually determined, and the fluid is tested for levels of glucose, protein, lactic dehydrogenase (LDH), and amylase. Triglycerides and cholesterol may also be measured when chylous effusion is suspected. Gram stain and C&S tests are generally performed to identify the causative organism when infection is suspected. Cytologic examination is undertaken to detect malignant cells. Pleural effusions may also be tested for levels of immunoglobulins, complement components, and carcinoembryonic antigen (CEA) (see Chapter 3) when disorders of immunologic and malignant origin are suspected. Elevated immunoglobulins and CEA or decreased complement levels, or both, are seen in inflammatory or neoplastic reactions involving the pleural membranes.12 INTERFERING FACTORS Blood in the sample because of traumatic thoracentesis Undetected hypoglycemia or hyperglycemia Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis of Effusions 287 Reference Values Red blood cells 0–1000/mm3 White blood cells 0–1000/mm3, consisting mainly of lymphocytes Gram stain and culture No organisms present Cytologic examination No abnormal cells pH 7.37–7.43 (usually 7.40) Glucose Parallels serum levels Protein 3.0 g/dL Pleural fluid:serum protein ratio 0.5 or less Lactic dehydrogenase 71–207 IU/L Pleural fluid:serum LDH ratio 0.6 or less Amylase 180 Somogyi U/dL or 200 dye U/dL Triglycerides Cholesterol Immunoglobulins Carcinoembryonic antigen (CEA) Complement Critical values Parallel serum levels Positive Gram stain or culture Contamination of the sample with skin cells and pathogens INDICATIONS FOR PLEURAL FLUID ANALYSIS Pleural effusion of unknown etiology Differentiation of pleural transudates from exudates (Table 9–1) Suspected traumatic hemothorax as indicated by bloody pleural fluid, elevated red cell count, and hematocrit similar to that found in whole blood Suspected pleural effusion caused by pulmonary tuberculosis as indicated by presence of red blood cells (fewer than 10,000 per cubic millimeter); white cell count of 5,000 to 10,000 per cubic millimeter, consisting mostly of lymphocytes; presence of acid-fast bacilli (AFB) on smear and culture; pH of less than 7.30, decreased glucose (sometimes); and elevated protein, pleural fluid:serum protein ratio, LDH, and pleural fluid:serum LDH ratio Suspected pleural effusion caused by pneumonia (parapneumonic effusion) as indicated by presence of red blood cells (5,000 per cubic millimeter); white cell count of 5,000 to 25,000 per cubic millimeter, consisting mainly of neutrophils and sometimes including eosinophils; pH less than 7.40; and elevated protein, pleural fluid:serum protein ratio, LDH, and pleural fluid:serum LDH ratio. (If the pneumonia is of bacterial origin, the organism may be demonstrated on culture and the pleural fluid glucose level may be decreased.) Suspected bacterial or tuberculous empyema as indicated by red cell count of less than 5,000 per cubic millimeter; white cell count of 25,000 to 100,000 per cubic millimeter, consisting mostly of neutrophils; pH less than 7.30; decreased glucose; and increased protein, LDH, and related ratios13 Suspected pleural effusion caused by carcinoma as indicated by presence of red blood cells (1,000 to more than 100,000 per cubic millimeter); white cell count of 5,000 to 10,000 per cubic millimeter, consisting mostly of lymphocytes and sometimes including eosinophils; detection of malignant cells on cytologic examination; pH less than 7.30; decreased glucose (sometimes); increased protein, LDH, and related ratios; elevated CEA and immunoglobulins; and decreased complement14 Suspected pleural effusion caused by pulmonary infarction as indicated by red cell count of 1,000 to 100,000 per cubic millimeter; white cell count of 5,000 to 15,000 per cubic millimeter, consisting mainly of neutrophils and sometimes including eosinophils; pH greater than 7.30; normal Copyright © 2003 F.A. Davis Company 288 SECTION I—Laboratory TABLE 9–1 • Tests Differentiation of Pleural Transudates From Exudates Transudates Exudates Appearance Clear Cloudy; may be bloody Red blood cells 1000/mm 1000/mm3 (usually) White blood cells 1000/mm3 1000/mm3 pH 7.40 or higher 7.40 Glucose Parallels serum level May be less than serum level Protein 3.0 g/dL 3.0 g/dL Pleural fluid:serum protein ratio 0.5 0.5 Lactic dehydrogenase 200 IU/L 200 IU/L Pleural fluid:serum LDH ratio 0.6 0.6 Common causes Congestive heart failure Pneumonia 3 Cirrhosis Tuberculosis Nephrotic syndrome Empyema Pulmonary infarction Rheumatoid disease Systemic lupus erythematosus Carcinoma Pancreatitis glucose; and elevated protein, LDH, and related ratios15 Suspected pleural effusion caused by rheumatoid disease as indicated by a normal red cell count; a white cell count of 1,000 to 20,000 per cubic millimeter with either lymphocytes or neutrophils predominating; pH less than 7.30; decreased glucose; elevated protein, LDH, and related ratios; and elevated immunoglobulins16 Suspected pleural effusion caused by SLE as indicated by findings similar to those in rheumatoid disease, except that glucose is not usually decreased Suspected pleural effusion caused by pancreatitis as indicated by red cell count of 1,000 to 10,000 per cubic millimeter; white cell count of 5,000 to 20,000 per cubic millimeter, consisting mostly of neutrophils; pH greater than 7.30; normal glucose; elevated protein, LDH, and related ratios; and elevated amylase Suspected pleural effusion caused by esophageal rupture as indicated primarily by a pH as low as 6.0 and elevated amylase17 Differentiation of chylous pleural effusions caused by thoracic lymphatic duct blockage from pseudochylous (chronic serous) effusions, with chylous effusions indicated primarily by a triglyceride level two to three times that of serum; decreased cholesterol; and markedly elevated chylomicrons NURSING CARE BEFORE THE PROCEDURE Explain to the client: That the procedure will be performed by a physician and requires approximately 20 minutes That there are no food or fluid restrictions before the test That a sedative is not usually given before the procedure, although a cough suppressant may be given to prevent coughing The positioning used for the procedure (supported sitting or side-lying) That the skin will be injected with a local anesthetic at the chest needle insertion site and that the injection may cause a stinging sensation That, after the skin has been anesthetized, a needle will be inserted through the posterior chest into the space near the lungs where excessive fluid has accumulated That a sensation of pressure may be felt when the needle is inserted The importance of remaining still during the Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis procedure and the need to control breathing, coughing, and movement Any activity restrictions after the test (usually 1 hour of bed rest) Prepare for the procedure: Withhold anticoagulant medications and aspirin as ordered. Have the client void. Provide a hospital gown. Take and record vital signs. Administer cough suppressant, if ordered. THE PROCEDURE (THORACENTESIS) The necessary equipment is assembled, including a thoracentesis tray with solution for skin preparation, local anesthetic, 50-mL syringe, needles of various sizes including a thoracentesis needle, sterile drapes, and sterile gloves. Sterile collection bottles and containers for culture and cytologic examination also are needed. The client is assisted to the position that will be used for the test. The usual position is sitting on the side of a bed or treatment table, leaning slightly forward to spread the intercostal spaces, with arms supported on an overbed table with several pillows. Alternatively, the client may sit on the bed or table with legs extended on it and arms supported as described earlier. If the client cannot assume either sitting position, the side-lying position is used. In such situations, the client lies on the unaffected side. The skin is cleansed with an antiseptic solution and protected with sterile drapes. The skin at the needle insertion site is then infiltrated with local anesthetic. The thoracentesis needle is inserted. When fluid appears, a stopcock and 50-mL syringe are attached to the needle and the fluid is aspirated. The pleural fluid samples are placed in appropriate containers, labeled, and sent promptly to the laboratory. If the thoracentesis is being performed for therapeutic as well as diagnostic reasons, additional pleural fluid may be withdrawn. When the desired amount of fluid has been removed, the needle is withdrawn, and slight pressure is applied to the site for a few minutes. If there is no evidence of bleeding or other drainage, a sterile bandage is applied to the site. NURSING CARE DURING THE PROCEDURE Observe the client for signs of respiratory distress or pneumothorax (e.g., anxiety, restlessness, dyspnea, cyanosis, tachycardia, and chest pain). Possible complications of a thoracentesis include pneumothorax, mediastinal shift, and excessive reaccumulation of pleural fluid. of Effusions 289 NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client in lying on the unaffected side and reminding the client that this position should be maintained for approximately 1 hour. Elevate the head for client comfort. Prepare for a post-thoracentesis chest x-ray examination ordered to ensure that a pneumothorax as a result of the tap has not occurred and to evaluate the amount of fluid removed. Take and record vital signs as ordered (e.g., every 15 minutes for the first half hour, every 30 minutes for the next hour, and then every 4 hours for 24 hours or until stable). Observe the client for respiratory distress or hemoptysis, diaphoresis, or skin color changes. Auscultate breath sounds. Absent or diminished breath sounds on the side used for the thoracentesis may indicate pneumothorax. Assess the puncture site for bleeding, hematoma formation, and inflammation each time vital signs are taken and daily thereafter for several days. Provide support when diagnostic findings are revealed and information is given about subsequent therapy based on the findings. Note relief of chest pain, dyspnea, or diminished breath sounds. Note response to antibiotic or cytotoxic drugs if injected into the cavity after fluid removal. Notify physician immediately if the Gram stain or culture is positive. PERITONEAL FLUID ANALYSIS Peritoneal transudates are most commonly caused by CHF, cirrhosis of the liver, and nephrotic syndrome. Peritoneal exudates occur with neoplasms including metastatic carcinoma, infections (e.g., tuberculosis, bacterial peritonitis), trauma, pancreatitis, and bile peritonitis. Chylous peritoneal effusions occur when there is damage or obstruction to the thoracic lymphatic duct. Accumulation of large amounts of fluid in the peritoneal cavity is termed ascites, and the peritoneal fluid is referred to as ascitic fluid. Peritoneal fluid is removed by paracentesis or by paracentesis and lavage with normal saline or Ringer’s lactate. Lavage involves instilling the desired solution over 15 to 20 minutes, then removing it and analyzing it for cells and other constituents. Tests commonly performed on peritoneal or ascitic fluid include red cell count, white cell count and differential, Gram stain, C&S, AFB smear and culture, and cytologic examination. The fluid may Copyright © 2003 F.A. Davis Company 290 SECTION I—Laboratory Tests also be tested for glucose, amylase, ammonia, alkaline phosphatase, and CEA. Urea and creatinine may be measured if there is suspicion of ruptured or punctured urinary bladder. Gram stain and C&S tests are generally performed to identify the causative organism when infection is suspected. If tuberculous effusion is suspected, an AFB smear and culture can be performed, although positive results are seen in only 25 to 50 percent of cases.18 Cytologic examination is used to detect malignant cells. INTERFERING FACTORS Blood in the sample as a result of traumatic paracentesis Undetected hypoglycemia or hyperglycemia Contamination of the sample with skin cells and pathogens INDICATIONS FOR PERITONEAL FLUID ANALYSIS Ascites of unknown cause Suspected peritoneal effusion caused by abdominal malignancy as indicated by elevated red cell count, decreased glucose, elevated CEA, and detection of malignant cells on cytologic examination Suspected abdominal trauma as indicated by elevated red cell count of greater than 100,000 per cubic millimeter19 Suspected ascites caused by cirrhosis of the liver as indicated by elevated white cell count, neutrophil count of greater than 25 percent but less than 50 percent, and an absolute granulocyte count of less than 250 per cubic millimeter Suspected bacterial peritonitis as indicated by elevated white cell count, neutrophil count greater than 50 percent, and an absolute granulocyte count of greater than 250 per cubic millimeter20 Suspected tuberculous peritoneal effusion as indicated by elevated lymphocyte count, positive AFB smear and culture in about 25 to 50 percent of cases, and decreased glucose Suspected peritoneal effusion caused by pancreatitis, pancreatic trauma, or pancreatic pseudocyst as indicated by elevated amylase levels Suspected peritoneal effusion caused by gastrointestinal perforation, strangulation, or necrosis as indicated by elevated amylase, ammonia, and alkaline phosphatase levels21 Suspected rupture or perforation of the urinary bladder as indicated by elevated ammonia, creatinine, and urea levels NURSING CARE BEFORE THE PROCEDURE Explain to the client: That the test will be performed by a physician and takes approximately 30 minutes Reference Values Red blood cells 100,000/mm3 White blood cells 300/mm3 (undiluted peritoneal fluid) 500/mm3 (lavage fluid) Neutrophils 25% Absolute granulocyte count 250/mm3 Gram stain and culture No organisms present AFB smear and culture No AFB present Cytologic examination Glucose Amylase Ammonia Alkaline phosphatase Creatinine Urea Carcinoembryonic antigen Critical values No abnormal cells present Parallel serum levels Positive Gram stain or culture Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis That there are no food or fluid restrictions before the test The positioning used for the procedure (seated or in high-Fowler’s position) That the skin will be injected with a local anesthetic at the abdominal needle insertion site and that this injection may cause a stinging sensation That, after the skin has been anesthetized, a large needle will be inserted through the abdominal wall That a “popping” sensation may be experienced as the needle penetrates the peritoneum The importance of remaining still during the procedure Any activity restrictions after the test (usually 1 hour or more of bed rest) Prepare for the procedure: Withhold anticoagulant medications and aspirin as ordered. Have the client void, or catheterize the client if he or she is unable to void to ensure an empty bladder that is not as likely to be punctured by the needle. Provide a hospital gown and have the client put it on with the opening in the front. Take and record vital signs. If the client has ascites, obtain weight and measure abdominal girth. If the abdomen is hirsute, it may be necessary to shave the area of the puncture site. THE PROCEDURE (PARACENTESIS) The necessary equipment is assembled, including a paracentesis tray with solution for skin preparation, local anesthetic, 50-mL syringe, needles of various sizes including large-bore paracentesis needle or trocar and cannula, sterile drapes, and sterile gloves. Specimen collection tubes and bottles for the tests to be performed also are needed. The client is assisted to the position that will be used for the test. The usual position is sitting on the side of a bed or treatment table, with the feet and back supported. An alternative approach is to place the client in bed in a high-Fowler’s position. The skin is cleansed with an antiseptic solution and protected with sterile drapes. The skin at the needle or trocar insertion site is then infiltrated with local anesthetic. The paracentesis needle is inserted approximately 1 to 2 inches below the umbilicus. If a trocar with cannula is to be used, a small skin incision may be made to facilitate insertion. The 50-mL syringe with stopcock is attached to the needle or cannula after the trocar has been removed. Gentle suction may be applied with the syringe to remove of Effusions 291 fluid. For peritoneal lavage, sterile normal saline or Ringer’s lactate may be infused via the needle or cannula over 15 to 20 minutes. The client is then turned from side to side before the lavage fluid is removed. Samples of peritoneal or ascitic fluid are obtained, placed in appropriate containers, labeled, and sent promptly to the laboratory. If the paracentesis is being performed for therapeutic as well as diagnostic reasons, additional fluid is removed. No more than 1000 to 1500 mL of fluid should be removed at any one time to avoid complications such as hypovolemia and shock resulting from abdominal pressure changes and massive fluid shifts into the space that has been drained by paracentesis. When the desired amount of fluid has been removed, the needle or cannula is withdrawn and slight pressure is applied to the site for a few minutes. If there is no evidence of bleeding or other drainage, a sterile dressing is applied to the site. NURSING CARE DURING THE PROCEDURE If feasible, check the client’s vital signs every 15 minutes during the procedure. Observe the client for pallor, diaphoresis, vertigo, hypotension, tachycardia, pain, or anxiety. Rapid removal of fluid may precipitate hypovolemia and shock. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client to a position of comfort and reminding the client of any activity restrictions. Redress the puncture site using sterile technique if excessive drainage is present. Take and record vital signs as for a postoperative client (i.e., every 15 minutes for the first hour, every 30 minutes for the next 2 hours, every hour for the next 4 hours, and then every 4 hours for 24 hours). Take temperature every 4 hours for 24 hours. Monitor intake and output for at least 24 hours. Assess the puncture site for bleeding, excessive drainage, and signs of inflammation each time the vital signs are taken and daily thereafter for several days. Continue to observe the client for pallor, vertigo, hypotension, tachycardia, pain, or anxiety for at least 24 hours after the procedure. If a large amount of fluid was removed, measure abdominal girth and weigh the client. Provide support when diagnostic findings are revealed and information is given about subsequent therapy (antibiotics) based on findings. Have IV fluids and albumin on hand if hypoten- Copyright © 2003 F.A. Davis Company 292 SECTION I—Laboratory Tests sion results from the fluid shift from the vascular space. Note severe abdominal pain. Rigid abdominal muscles indicate that peritonitis is developing from the paracentesis. Notify physician immediately of a positive Gram stain or culture. SYNOVIAL FLUID ANALYSIS Synovial fluid is a clear, pale yellow, and viscous liquid formed by plasma ultrafiltration and by secretion of a hyaluronate–protein complex by synovial cells. It is secreted in small amounts (i.e., 3 mL or less) into the cavities of most joints. Synovial effusions are associated with disorders or injuries involving the joints. Samples for analysis are obtained by aspirating joint cavities. The most commonly aspirated joint is the knee, although samples can also be obtained from the shoulder, hip, elbow, wrist, and ankle if clinically indicated. Synovial fluid analysis is used primarily to determine the type or cause of joint disorders. Joint disorders can be classified according to five categories based on synovial fluid findings: (1) noninflammatory (e.g., degenerative joint disease), (2) inflammatory (e.g., rheumatoid arthritis, SLE), (3) septic (e.g., acute bacterial or tuberculous arthritis), (4) crystal induced (e.g., gout or pseudogout), and (5) hemorrhagic (e.g., traumatic or hemophilic arthritis).22 Tests commonly performed on synovial fluid include red cell count, white cell count and differential, white cell morphology, microscopic examination for crystals, Gram stain, and C&S. Determination of protein, glucose, and uric acid levels also aids in diagnosis. Various immunologic tests such as determination of complement, rheumatoid factor, and antinuclear antibodies also have been used in synovial fluid analysis. In the recent past, the mucin clot test has been used in analyzing synovial fluid, but this test is not considered as reliable as specific cell counts and other measurements of synovial fluid constituents. Lactate and pH measurements can be used as nonspecific indicators of inflammation and to differentiate between infection and inflammation.23 Table 9–2 lists the types of white blood cells and inclusions seen in synovial fluid, along with the disorders with which the presence of such cells is associated. Examination of synovial fluid for crystals is used in diagnosing crystal-induced arthritis. The several types of crystals that can be identified are listed in Table 9–3. Monosodium urate (MSU) crystals are associated with arthritis caused by gout, whereas calcium pyrophosphate (CPP) crystals are seen in pseudogout. Cholesterol crystals are associated with chronic joint effusions, which may be caused by tuberculous or rheumatoid arthritis. Arthritis associated with the presence of apatite crystals is commonly recognized as a cause of synovitis. Corticosteroid crystals may be seen for a month or more after intra-articular injections of steroids and may induce acute synovitis. Although usually of a rhomboid shape, corticosteroid crystals are sometimes needle shaped and may be confused with MSU or CPP crystals. Not shown in Table 9–3 are talcum crystals. These crystals, which are shaped like Maltese crosses, are most commonly seen after joint surgery and reflect contamination of the joint with talcum powder from surgical gloves.24 Gram stain and C&S tests are used to identify the causative organisms when infection is suspected. AFB smear and culture can be performed when tuberculous arthritis is suspected, but results are frequently negative. When the results of microbiologic tests of synovial fluid are inconclusive, synovial biopsy may be necessary to establish the diagnosis.25 The need to perform immunologic tests of synovial fluid is indicative of the association of the immune system with inflammatory joint disorders. Substances measured include rheumatoid factor (RF), antinuclear antibodies (ANA), and complement, all of which can also be measured in serum (see Chapter 3). Determination of complement levels in synovial fluid aids in differentiating arthritis of immunologic origin from that with nonimmunologic causes. Decreased synovial fluid complement levels are seen in approximately 60 to 80 percent of individuals with rheumatoid arthritis and SLE. Decreased complement levels are occasionally seen in rheumatic fever, gout, pseudogout, and bacterial arthritis; however, synovial complement levels may be high in these disorders if serum levels also are elevated. Complement levels in synovial fluid can be measured as total complement (CH50) or as individual components (C1q, C4, C2, and C3). Because synovial fluid complement levels parallel synovial fluid protein levels, complement levels can be expressed as ratios in relation to protein levels to ensure that abnormal findings are not caused by changes in synovial fluid membrane filtration.26,27 INTERFERING FACTORS Blood in the sample caused by traumatic arthrocentesis Undetected hypoglycemia or hyperglycemia or failure to comply with dietary restrictions before the test, or both Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis TABLE 9–2 • of Effusions 293 White Blood Cells and Inclusions Seen in Synovial Fluid Cell/Inclusion Neutrophil Description Significance Polymorphonuclear leukocyte Bacterial sepsis Crystal-induced inflammation Lymphocyte Mononuclear leukocyte Nonseptic inflammation Macrophage (monocyte) Large mononuclear leukocyte; may be vacuolated Normal Viral infections Synovial lining cell Similar to macrophage but may be multinucleated, resembling a mesothelial cell Normal LE cell Neutrophil containing characteristic ingested “round body” Lupus erythematosus Reiter cell Vacuolated macrophage with ingested neutrophils Reiter’s syndrome Nonspecific inflammation RA cell (ragocyte) Neutrophil with dark cytoplasmic granules containing immune complexes Rheumatoid arthritis Immunologic inflammation Cartilage cells Large, multinucleated cells Osteoarthritis Rice bodies Macroscopically resemble polished rice Tuberculosis, septic and rheumatoid arthritis Microscopically show collagen and fibrin Fat droplets Refractile intracellular and extracellular globules Traumatic injury Stain with Sudan dyes Hemosiderin Inclusions within synovial cells Pigmented villonodular synovitis From Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, 2001, p 182, with permission. TABLE 9–3 • Synovial Fluid Crystals Crystal Shape Monosodium urate Needles Calcium pyrophosphate Rods Needles Rhombics Cholesterol Notched rhombic plates Apatite Small needles Corticosteroid Flat, variable-shaped plates Adapted from Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, 2001, p 183. Copyright © 2003 F.A. Davis Company 294 SECTION I—Laboratory Tests Reference Values Red blood cells 2000/mm3 White blood cells 200/mm3 Neutrophils 25% White cell morphology No abnormal cells or inclusions (see Table 9–2) Crystals None present (see Table 9–3) Gram stain and culture No organisms present Acid-fast bacillus smear and culture No AFB present Protein 3 g/dL Glucose Not 10 mg/dL of blood level or not 40 mg/dL Uric acid Parallels serum level Lactate 0.6–2.0 mmol/L or 5–20 mg/dL Antinuclear antibodies Rheumatoid factor Complement Critical values Contamination of the sample with pathogens Improper handling of the specimen (Refrigeration of the sample may result in an increase in MSU crystals because of decreased solubility of uric acid. Exposure of the sample to room air with a resultant loss of carbon dioxide and rise in pH encourages the formation of calcium CPP crystals.)28 INDICATIONS FOR SYNOVIAL FLUID ANALYSIS Joint effusion of unknown etiology Suspected trauma, tumors involving the joint, or hemophilic arthritis as indicated by an elevated red cell count, elevated protein level, and possibly fat droplets if trauma is involved (see Table 9–2) Suspected joint effusion caused by noninflammatory disorders (e.g., osteoarthritis, degenerative joint disease) as indicated by a white cell count of less than 5000 per cubic millimeter with a normal differential and the presence of cartilage cells (see Table 9–2) Suspected rheumatoid arthritis as indicated by a white cell count of 2,000 to 100,000 per cubic millimeter with an elevated neutrophil count (i.e., 30 to 50 percent), presence of rheumatoid arthritis cells and possibly rice bodies (see Table 9–2), cholesterol crystals if effusion is chronic, elevated protein level, decreased glucose level, moderately elevated lactate level (i.e., 2 to 7.5 mmol/L), Parallel serum levels Positive Gram stain or culture decreased pH, presence of RF (60 percent of cases), and decreased complement Suspected SLE involving the joints as indicated by a white cell count of 2,000 to 100,000 per cubic millimeter with an elevated neutrophil count (i.e., 30 to 40 percent), presence of LE cells (see Table 9–2), elevated protein level, decreased glucose level (i.e., 2 to 7.5 mmol/L), decreased pH, presence of ANA (20 percent of cases), and decreased complement Suspected acute bacterial arthritis as indicated by a white cell count of 10,000 to 200,000 per cubic millimeter with a markedly elevated neutrophil count (i.e., as high as 90 percent), positive Gram stain (50 percent of cases), positive cultures (30 to 80 percent of cases), possible presence of rice bodies (see Table 9–2), decreased glucose, lactate level greater than 7.5 mmol/L, pH less than 7.3, and complement levels paralleling those found in serum (i.e., may be elevated or decreased)29 Suspected tuberculous arthritis as indicated by a white cell count of 2,000 to 100,000 per cubic millimeter with an elevated neutrophil count (i.e., 30 to 60 percent), possible presence of rice bodies (see Table 9–2), cholesterol crystals if effusion is chronic, positive AFB smear and culture in some cases (results are frequently negative), decreased glucose, elevated lactate levels, and decreased pH Suspected joint effusion caused by gout as indi- Copyright © 2003 F.A. Davis Company CHAPTER 9—Analysis cated by a white cell count of 500 to 200,000 per cubic millimeter with an elevated neutrophil count (i.e., approximately 70 percent), presence of MSU crystals (see Table 9–3), decreased glucose, elevated uric acid levels, and complement levels paralleling those of serum (may be elevated or decreased)30,31 Differentiation of gout from pseudogout as indicated primarily by finding CPP crystals (see Table 9–3), which are associated with pseudogout (Other findings in pseudogout are similar to those of gout except that the white cell count may not be as high.) NURSING CARE BEFORE THE PROCEDURE Explain to the client: That it will be performed by a physician and requires approximately 20 minutes Any dietary restrictions (fasting for 6 to 12 hours before the test is recommended if the synovial fluid is to be tested for glucose) The positioning to be used (seated or supine for knee, shoulder, elbow, wrist, or ankle aspiration; supine for hip joint aspiration) That the skin at the site will be injected with a local anesthetic and that it may cause a stinging sensation That, after the skin has been anesthetized, a large needle will be inserted into the joint capsule That discomfort may be experienced as the joint capsule is penetrated The importance of remaining still during the procedure Any activity restrictions after the test (The client usually is advised to avoid excessive use of the joint for several days after the procedure to prevent pain and swelling.) That ice packs or analgesics or both may be prescribed after the procedure to prevent swelling and alleviate discomfort Prepare for the procedure: Withhold anticoagulant medications and aspirin as ordered. Ensure to the extent possible that any dietary restrictions are followed. Have the client void. Provide a hospital gown if necessary to allow access to the site without unduly exposing the client. Take and record vital signs. If the client is extremely hirsute, it may be necessary to shave the area of the puncture site. THE PROCEDURE (ARTHROCENTESIS) The necessary equipment is assembled, including an of Effusions 295 arthrocentesis tray with solution for skin preparation, local anesthetic, a 20-mL syringe, needles of various sizes, sterile drapes, and sterile gloves. Specimen collection tubes and containers for the tests to be performed also are obtained. For cell counts and differential, lavender-topped tubes containing ethylenediaminetetra-acetic acid (EDTA) are used. Green-topped tubes containing heparin are used for certain immunologic and chemistry tests, whereas samples for glucose are collected in either plain red-topped tubes or gray-topped tubes containing potassium oxalate. Plain sterile tubes (e.g., red-topped tubes) are recommended for microbiologic testing and crystal examination.32 The client is assisted to the position that will be used for the test (sitting or supine). The skin is cleansed with antiseptic solution, protected with sterile drapes, and infiltrated with local anesthetic. The aspirating needle is inserted into the joint space and as much fluid as possible is withdrawn. The specimen should contain at least 10 mL of synovial fluid, but more may be removed to reduce swelling. Manual pressure may be applied to facilitate fluid removal. If medication is to be injected into the joint, the syringe containing the sample is detached from the needle and replaced with the one containing the drug. The medication is injected with gentle pressure. The needle is then withdrawn and digital pressure is applied to the site for a few minutes. If there is no evidence of bleeding, a sterile dressing is applied to the site. An elastic bandage may also be applied to the joint. The samples of synovial fluid are placed in the appropriate containers, labeled, and sent to the laboratory immediately. NURSING CARE AFTER THE PROCEDURE Care and assessment after the procedure include assisting the client to a position of comfort. Apply an ice pack to the site and administer analgesics as needed. Resume any foods, fluids, or medications withheld before the test on the physician’s order. Remind the client of any activity restrictions and, if indicated, site care requirements. Apply an elastic bandage to the joint to provide support and to minimize edema formation. Take and record vital signs. Assess comfort level and response to measures such as ice packs and analgesics. Assess the puncture site for bleeding, bruising, inflammation, and excessive drainage of synovial fluid approximately every 4 hours for 24 hours and then daily thereafter for several days. Copyright © 2003 F.A. Davis Company 296 SECTION I—Laboratory Tests Provide support when diagnostic findings are revealed and information is provided about subsequent treatment based on findings (antiinflammatory drugs, immobilization of the joint, analgesics). Notify physician immediately of a positive Gram stain or culture. REFERENCES 1. Hole, JW: Human Anatomy and Physiology, ed 4. Wm C Brown, Dubuque, Iowa, p 158. 2. Ibid, p 158. 3. Kjeldsberg, CR, and Krieg, AF: Cerebrospinal fluid and other body fluids. In Henry, JB: Clinical Diagnosis and Management by Laboratory Methods, ed 18. WB Saunders, Philadelphia, 1991, p 457. 4. Strasinger, SK: Urinalysis and Body Fluids, ed 4. FA Davis, Philadelphia, 2001, p 191. 5. Kjeldsberg and Krieg, op cit, p 463. 6. Miller, BF, and Keane, CB: Encyclopedia and Dictionary of Medicine, Nursing and Allied Health, ed 4. WB Saunders, Philadelphia, 1987, p 226. 7. Kjeldsberg and Krieg, op cit, p 468. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. Strasinger, op cit, p 173. Kjeldsberg and Krieg, op cit, p 461. Ibid, p 458. Strasinger, op cit, p 182. Ibid, p 182. Ibid, p 180. Ibid, p 182. Kjeldsberg and Krieg, op cit, p 464. Strasinger, op cit, p. 183. Kjeldsberg and Krieg, op cit, p 465. Ibid, p 469. Ibid, p 468. Strasinger, op cit, p 184. Kjeldsberg and Krieg, op cit, p 469. Strasinger, op cit, pp 172–173. Kjeldsberg and Krieg, op cit, pp 461–462. Ibid, pp 459–460. Ibid, pp 462–463. Ibid, p 462. Strasinger, op cit, p 178. Ibid, p 174. Ibid, p 177. Ibid, p 174. Kjeldsberg and Krieg, op cit, p 462. Strasinger, op cit, p 172. Copyright © 2003 F.A. Davis Company CHAPTER Amniotic Fluid Analysis TESTS COVERED Tests for Genetic and Neural Tube Defects, 298 Tests for Hemolytic Disease of the Newborn, 299 Tests for Fetal Maturity, 300 OVERVIEW OF AMNIOTIC FLUID FORMATION AND ANALYSIS Amniotic fluid is produced in the membranous sac that surrounds the developing fetus. This sac appears during the second week of gestation and arises from a membrane called the amnion. Amniotic fluid is derived from the exchange of water from maternal blood across fetal membranes, from fetal cellular metabolism, and later in pregnancy from fetal urine. Amniotic fluid serves several purposes. It prevents the amniotic membranes from adhering to the embryo and protects the fetus from shocks and blows. It also aids in controlling the embryo’s body temperature and permits the fetus to move freely, thus aiding in normal growth and development.1 Amniotic fluid can be thought of as an extension of the extracellular fluid space of the fetus.2 Testing samples of amniotic fluid for various constituents and substances can, therefore, be used to assess fetal well-being and maturation. Specifically, amniotic fluid analysis is used to test for various inherited disorders, anatomic abnormalities such as neural tube defects, hemolytic disease of the newborn, and fetal maturity. Amniotic fluid is normally clear and colorless in early pregnancy. Later in pregnancy, it may appear slightly opalescent because of the presence of particles of vernix caseosa and may be pale yellow because of fetal urine. The presence of meconium in amniotic fluid is normal in breech presentations but abnormal in vertex presentations and indicates relaxation of the anal sphincter from hypoxia. Amniotic fluid stained the color of port wine generally indicates abruptio placentae. As the fetus begins to produce urine, it also swallows amniotic fluid in amounts that nearly equal urinary output (i.e., 400 to 500 mL per day).3 Failure to swallow sufficient amounts of amniotic fluid results in excessive accumulation of fluid in the amniotic sac (polyhydramnios). This occurrence is commonly associated with anencephaly and esophageal atresia but can also occur in the presence of maternal diabetes and hypertensive disorders of pregnancy. Excessive amounts of amniotic fluid also are seen with fetal edema, which is associated with fetal heart failure, hydrops fetalis, and multiple births. Excessive swallowing of amniotic fluid results in decreased volume (oligohydramnios) and is associated with chronic illness of the fetus, placental insufficiency, fetal urinary tract malformations, and multiple births.4 By the 14th to 16th weeks of pregnancy, the amniotic sac normally contains at least 50 mL of fluid; at term, the sac contains 500 to 2500 mL of amniotic fluid, with an average volume of 1000 mL. Samples of amniotic fluid are obtained by needle aspiration (Fig. 10–1). As noted in Chapter 9, centesis is a suffix denoting “puncture and aspiration of ”; thus, aspiration of fluid from the amniotic sac is called amniocentesis. For suspected genetic and neural tube defects, amniocen297 Copyright © 2003 F.A. Davis Company 298 SECTION I—Laboratory Tests tesis is generally performed early in the second trimester of pregnancy (i.e., 14th to 16th weeks), when there is sufficient amniotic fluid for sampling yet enough time for safe abortion, if desired. For hemolytic Figure 10–1. disease of the newborn, a series of amniocenteses may be performed beginning with the 26th week. Tests for fetal maturity usually are not performed until at least the 35th week of gestation. Amniocentesis with needle placement to obtain an amniotic fluid sample. TESTS OF AMNIOTIC FLUID Tests of amniotic fluid are discussed hereafter in relation to the three general purposes for which they are performed: (1) to detect genetic and neural tube defects, (2) to test for hemolytic disease of the newborn, and (3) to assess fetal maturity. TESTS FOR GENETIC AND NEURAL TUBE DEFECTS Tests for genetic and neural tube defects include gender determination, chromosome analysis, and measurement of -fetoprotein (AFP) and acetylcholinesterase levels. Determination of the gender of the fetus is indicated when sex-linked inherited disorders are suspected (e.g., hemophilia, Duchenne’s muscular dystrophy). In such disorders, the abnormal gene is carried by women, although the disorder itself is inherited only by male offspring. Although no specific tests for these disorders are currently available, knowing the gender of the fetus may aid in deciding whether to continue the preg- nancy. Some couples carrying these disorders, for example, choose to abort all male fetuses, even though some would have been normal.5 Determining the chromosomal makeup (karyotype) of the fetus may also assist in the prenatal diagnosis of disorders such as Down syndrome (trisomy 21) and Tay-Sachs disease. Karyotyping, especially when augmented by staining techniques, includes determination of the number of chromosomes as well as specific morphologic changes in the chromosomes that may indicate various genetic disorders. Karyotyping is performed by culturing fetal cells and then photographing individual chromosomes during the metaphase of mitosis.6 Among the disorders that can be detected are alterations in carbohydrate, lipid, and amino acid metabolism. Karyotyping can take from 2 to 4 weeks before results are available to the client. Specimens for chromosome analysis must be delivered promptly to the laboratory performing the test. If immediate culturing is not possible, the sample must be incubated at normal body temperature for no longer than 2 days.7 Copyright © 2003 F.A. Davis Company CHAPTER 10—Amniotic Neural tube and other anatomic defects in the fetus can be determined by measuring levels of AFP and acetylcholinesterase in amniotic fluid. In the embryo, the central nervous system develops from the neural tube, which begins to form at about 22 days of gestation. Failure of the neural tube to close properly can result in disorders such as anencephaly, spina bifida, and myelomeningocele. During gestation, the major fetal serum protein is AFP. Similar to albumin, this protein is manufactured in large quantities by the fetal liver until the 32nd week of gestation, with peak production occurring at 13 weeks (see Chapter 3). With a severe neural tube defect, higher than normal amounts of AFP escape into the amniotic fluid as well as into the maternal circulation. Routine prenatal screening includes determination of the mother’s serum AFP level at 13 to 16 weeks of pregnancy. Causes of elevated maternal AFP levels are listed in Table 10–1. If maternal levels are elevated on two samples obtained 1 week apart, an ultrasound is performed to determine gestational age and to check for twins or gross fetal anomalies. If the ultrasound is normal, amniotic fluid samples are obtained and analyzed for AFP levels.8,9 If AFP levels are elevated in amniotic fluid, the presence of acetylcholinesterase in the fluid can be determined to confirm the presence of a neural tube defect. Using electrophoretic methods, the isoenzyme of acetylcholinesterase, which originates in fetal spinal fluid, can also be demonstrated and is more specific to the diagnosis of neural tube defect.10 AFP and acetylcholinesterase may be falsely Fluid Analysis 299 elevated if the sample is contaminated with fetal blood. The level of the fetal spinal fluid isoenzyme of acetylcholinesterase is not, however, so affected. TESTS FOR HEMOLYTIC DISEASE OF THE NEWBORN One of the oldest uses of amniotic fluid analysis is in evaluating suspected hemolytic disease of the newborn, in which the mother builds antibodies against fetal red blood cell antigens (isoimmunization). The result is hemolysis of fetal erythrocytes with release of bilirubin into the amniotic fluid. The most common causes are ABO and Rh incompatibilities (e.g., an Rh-negative mother carrying an Rhpositive fetus), although other red cell antibodies may also be involved. Maternal IgG antibodies may cross the placenta to react with fetal red blood cells as early as the 16th week of pregnancy. As fetal red blood cells are broken down, bilirubin is released and can be detected in the amniotic fluid.11 Normally, the bilirubin level in amniotic fluid is highest between the 16th and 30th weeks of gestation. Much of this bilirubin is in the unconjugated form and can be excreted by the placenta. As the fetal liver matures, it begins to conjugate the bilirubin; this can occur as early as 28 weeks of gestation. The conjugated bilirubin is not, however, cleared by the placenta; instead, it is excreted by the fetal biliary tract and absorbed by the intestine. After the 30th week of gestation, the bilirubin level in amniotic fluid normally decreases as pregnancy progresses. This is partly because of dilution of any bilirubin present by the normal increase in amniotic fluid Image/Text rights unavailable Copyright © 2003 F.A. Davis Company 300 SECTION I—Laboratory Tests volume. At term, bilirubin is nearly absent from amniotic fluid.12 In hemolytic disease of the newborn, fetal red cell destruction leads to excessive bilirubin levels, which overwhelm both placental and fetal liver mechanisms for its clearance. Bilirubin levels in amniotic fluid continue to rise throughout the pregnancy and consist primarily of unconjugated bilirubin.13 The amount of bilirubin present in the amniotic fluid indicates the degree of fetal red hemolysis and, indirectly, the degree of fetal anemia. When hemolytic disease of the newborn is suspected or if maternal IgG levels are elevated, or both, serial amniocenteses for bilirubin determinations are performed beginning at approximately the 26th week of pregnancy. Bilirubin measurement in amniotic fluid is performed by spectrophotometric analysis, with the optical density (OD) of the fluid measured at wavelength intervals between 365 and 550 mm. When excessive bilirubin is present, a rise in OD at 450 mm, the wavelength of maximum bilirubin absorption, is seen.14 The results of spectrophotometric analysis can be compared with the Liley graph (Fig. 10–2) to predict fetal outcome or to plan medical management of the problem. Substances other than bilirubin may cause abnormal spectrophotometric results. Maternal hemoglobin from a traumatic amniocentesis, methemalbumin, and meconium in amniotic fluid may cause false elevations, as will fetal acidosis. Fetal hemoglobin can be differentiated from maternal hemoglobin by staining and cytologic techniques. The presence of methemalbumin indicates marked hemolysis and impending fetal demise.15 Falsely decreased bilirubin levels can occur if the amniotic fluid sample is exposed to light or if excessive amniotic fluid volume causes dilution. Other disorders that can cause elevated amniotic fluid bilirubin levels include anencephaly and intestinal obstruction.16 TESTS FOR FETAL MATURITY Tests for fetal maturity are generally performed after the 35th week of pregnancy, when preterm delivery is being considered because of fetal or maternal problems. The lungs are the last of the fetal organs to mature; therefore, the most common complication of early delivery is newborn respiratory distress syndrome (RDS). Tests of amniotic fluid for fetal maturity focus on determining fetal lung maturity and include the lecithin:sphingomyelin (L:S) ratio, as well as measures of other lung surface lipids such as phosphatidylglycerol and phosphatidylinositol. Image/Text rights unavailable Copyright © 2003 F.A. Davis Company CHAPTER 10—Amniotic If the lungs are found to be mature by these tests, the other body organs also are assumed to be mature.17,18 Tests of amniotic fluid, which can be used to indicate maturity of other fetal organ systems, include creatinine and bilirubin determinations, as well as examination of fetal cells for type and lipid content. During the last trimester of pregnancy, fetal lung enzyme systems initiate the production of surfactant by type II pneumocytes, which line the alveoli. Surfactant, a phospholipid mixture, lowers the surface tension in the alveoli and prevents them from collapsing during exhalation. The phospholipid components of surfactant are (1) lecithin (phosphatidylcholine), (2) sphingomyelin, (3) phosphatidyl glycerol (PG), (4) phosphatidylethanolamine (PE), (5) phosphatidylinositol (PI), and (6) phosphatidylserine (PS). Surfactant appears in amniotic fluid as a result of fetal respiratory movements that cause it to diffuse from fetal airways.19 L:S RATIO Lecithin constitutes about 75 percent of surfactant in mature lungs and is re